Alzheimer's Disease

Alzheimer's: Diagnosis & Assessment

Separate pages for

Early Markers

Cognitive Tests

Older news items (pre-2010) brought over from the old website

Diagnosis & assessment

Dementia often undiagnosed

A study involving 553 patients of 34 primary care physicians affiliated with three Portland-area managed health care plans has confirmed previous research finding that many older patients showing signs of dementia are not being diagnosed. The study found that only 18% of mildly impaired patients and 34.8% of moderately-to-severely impaired patients were clinically evaluated for dementia, and that none of the mildly impaired patients and just 4.3% of the more severely impaired patients were offered dementia medication.

Boise, L., Neal, M. B., & Kaye, J. (2004). Dementia Assessment in Primary Care: Results From a Study in Three Managed Care Systems. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 59(6), M621–M626. doi:10.1093/gerona/59.6.M621

http://www.eurekalert.org/pub_releases/2004-07/ohs-sdo071504.php

Life expectancy following diagnosis of Alzheimer’s depends on age at diagnosis

A new study reveals that the life span of people with Alzheimer's disease depends greatly on the age of the person when Alzheimer's disease is diagnosed. The study indicates that the median survival of patients with Alzheimer's disease could range from 8.3 years for those diagnosed at age 65 to 3.4 years for those diagnosed at age 90. There were no significant differences between men and women. The average length of time between the onset of symptoms and the diagnosis of Alzheimer's was 2.8 years.

Brookmeyer, R., Corrada, M.M., Curriero, F.C. & Kawas, C. 2002. Survival Following Diagnosis of Alzheimer Disease, Archives of Neurology, 59, 1764-1767.

http://www.eurekalert.org/pub_releases/2002-11/jhub-lef111502.php

New tests

Biomarker signatures predict conversion from MCI to Alzheimer's

Cerebrospinal fluid samples from 410 volunteers (100 with mild Alzheimer’s; 196 with MCI; 114 cognitively normal older adults) has revealed that concentrations of amyloid beta-42 peptide and tau protein successfully assessed brain status and predicted development. The test diagnosed Alzheimer’s with 96% accuracy; ruled out Alzheimer’s with 95% accuracy; and predicted the conversion from MCI to Alzheimer’s with 82% accuracy.

Shaw, L.M. et al. 2009. Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects. Annals of Neurology, Published Online March 18 2009.

http://www.eurekalert.org/pub_releases/2009-03/uops-pmp031609.php

Computers better at diagnosing Alzheimer's

A new method has been developed that allows a standard computer to spot the differences between brain scans from patients with proven Alzheimer’s disease and people with no signs of the disease at all. The accuracy is better than the 86% correct diagnostic rate of best clinical practice. The method was also better at distinguishing Alzheimer’s from fronto-temporal dementia. The findings may help ensure that patients are diagnosed earlier, increasing treatment options.

Klöppel, S. et al 2008. Automatic classification of MR scans in Alzheimer's disease. Brain, 131, 681-689.

http://www.eurekalert.org/pub_releases/2008-02/wt-ccb022108.php

Portable device quickly detects early Alzheimer's

A new device may allow patients to take a brief, inexpensive test that could be administered as part of a routine yearly checkup at a doctor’s office to detect mild cognitive impairment (MCI) — often the earliest stage of Alzheimer’s. The device, called DETECT, takes about ten minutes to run through a battery of visual and auditory stimuli such as pictures and words that assess cognitive abilities relative to age, gauging reaction time and memory capabilities. Its software can track cognitive capabilities year to year during annual appointments. Moreover, because the device blocks outside sound and light from the patient’s environment, it can be administered in virtually any setting, providing more consistent results. Preliminary analysis gives the test similar accuracy to the 90-minute “Gold Standard” pen and paper test. The device is expected to be commercialized later this year.

http://www.eurekalert.org/pub_releases/2008-01/giot-pdq011608.php

New diagnostic criteria for Alzheimer's disease

An international group of Alzheimer’s disease (AD) experts have proposed new diagnostic criteria for Alzheimer’s. The existing criteria were published in 1984. To meet the new criteria for probable AD, patients must show progressive memory loss over more than six months, plus at least one or more of the supportive biomarker criteria. These include: atrophy in a particular part of the brain shown by MRI, abnormal biomarker proteins in the cerebrospinal fluid, a specific pattern on PET of the brain, and a genetic mutation for AD within the immediate family.

Dubois, B. et al. 2007. Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS–ADRDA criteria. Lancet Neurology, 6, 734-746.

http://www.eurekalert.org/pub_releases/2007-07/l-ndc070607.php

Protein 'fingerprint' in spinal fluid could spot Alzheimer's disease early

In a pilot study, a panel of 23 protein biomarkers in cerebrospinal fluid has been found to be over 90% sensitive in identifying people with Alzheimer's disease.

Finehout, E.J. et al. 2006. Cerebrospinal fluid proteomic biomarkers for Alzheimer's disease (pNA). Annals of Neurology, published online ahead of print December 13

http://www.eurekalert.org/pub_releases/2006-12/cuns-pi120706.php

New reliable test for Alzheimer's

A new test for Alzheimer’s promises a reliable means of diagnosing Alzheimer’s in a living patient. Combined with clinical assessment, testing blood flow in a specific region of the brain may boost the degree of diagnostic certainty in difficult cases from 90% to almost 100%. The test involves use of single-photon emission computed tomography (SPECT) — a radioisotope test that produces a three-dimensional picture of the amount of blood flowing in certain regions of the brain — to identify a characteristic sign of Alzheimer's disease (reduced blood flow in the posterior cingulate cortex) and distinguish it from a group of illnesses known as frontotemporal diseases, which comprise the second-leading cause of dementia in the elderly. The test did fail to identify Alzheimer’s patients with an atypical form of Alzheimer’s known as tangle-predominant AD. This form of Alzheimer’s also appears to be resistant to drugs currently used to help treat Alzheimer’s. Evidence of shrinkage in brain structures such as the hippocampus and parietal cortex is also central to diagnosing Alzheimer's. This atrophy can be seen on a standard MRI.

Bonte, F.J., Harris, T.S., Roney, C.A. & Hynan, L.S. 2004. Differential Diagnosis Between Alzheimer's and Frontotemporal Disease by the Posterior Cingulate Sign. Journal of Nuclear Medicine, 45 (5), 771-4.

http://www.eurekalert.org/pub_releases/2004-05/uots-rin050404.php
http://www.eurekalert.org/pub_releases/2004-05/sonm-sis050504.php

New diagnostic marker for Alzheimer's disease

A mouse study has unexpectedly revealed that a protein that senses changes in calcium levels can be used to estimate the extent of cognitive deficits caused by toxic amyloid peptides found in Alzheimer brains. The discovery came about when researchers found that those mice with learning and memory deficits had not only the expected high level of amyloid peptides in their brains, but also had very low levels of a protein called calbindin that binds calcium and regulates functions in granule cells, located in the dentate gyrus (a region that plays an important role in memory formation). Examination of autopsy brain tissue from Alzheimer sufferers has confirmed this finding. It is hoped that this will prove a valuable diagnostic marker.

Palop, J.J. et al. 2003. Neuronal depletion of calcium-dependent proteins in the dentate gyrus is tightly linked to Alzheimer's disease-related cognitive deficits. PNAS, 100, 9572-9577.

http://www.eurekalert.org/pub_releases/2003-07/uoc--bcs071003.php

A new portable device might be able to screen for Alzheimer's

NeuroGraph™, a portable device that provides an almost instantaneous reading of brain activity and can swiftly detect differences from the norm, offers enormous commercial potential as a screening device for Alzheimer’s disease. It might also be useful in pharmaceutical trials, to test the efficacy of new drugs on brain activity against drugs already on the market.

http://www.eurekalert.org/pub_releases/2001-09/oonr-da091901.php

New home-safety assessment scale for people with dementia living at home

A pan-Canadian team of researchers designed, tested and validated the first "Home-safety Assessment Scale for People with Dementia Living at Home" (S.A.S.). The SAS has been tested and validated among 175 patients in English and French, in both urban and rural areas. "Thanks to the SAS, physicians, nurses, family helpers, social workers, physiotherapists and occupational therapists can now evaluate in a few minutes the risks of accidents in any particular home."

http://www.eurekalert.org/pub_releases/2001-09/mu-nha091401.php

Diagnosing Alzheimer's

It is not always easy for doctors to know whether a patient is suffering from Alzheimer's disease or some other form of dementia. A new study suggests tracking a patient's circadian rhythm (the daily cycle of body temperature change and activity) may lead not only to better diagnosis but also to better therapy for the devastating sleep disturbances that often accompany dementia. The study looked at the circadian rhythms of 38 dementia patients over six years. Some had Alzheimer's; others had what is known as fronto-temporal degeneration. Patients with Alzheimer's reached their temperature peak much later in the day than healthy people. People with fronto-temporal dementia had a normal temperature rhythm, but their activity levels peaked much earlier compared with levels of healthy people. And while people with fronto-temporal degeneration did have restful periods, these were much rarer with Alzheimer's. Their work, the researchers said, may help doctors who have tried to treat insomnia in dementia patients with melatonin and light therapy, in an effort to "reset" their biological clocks.

Harch, P. G., Kriedt, C., Van Meter, K. W., & Sutherland, R. J. (2007). Hyperbaric oxygen therapy improves spatial learning and memory in a rat model of chronic traumatic brain injury. Brain Research, 1174, 120–129. doi:10.1016/j.brainres.2007.06.105

http://www.nytimes.com/2001/04/17/health/17VITA-5.html

New guidelines for diagnosis and treatment of Alzheimer's

Experts reviewed more than a thousand studies to develop new guidelines for physicians for diagnosis and treatment of Alzheimer's. The recommendations include topics ranging from how to recognize early signs of Alzheimer's, how to diagnose, when medication is most effective and what types of support can improve the quality of life for patients and caregivers.
"It's important to remember there are choices available that can make a difference in your life or the life of your husband, grandmother, neighbor or anyone you care about who has Alzheimer's disease," said neurologist Steven DeKosky, MD, co-author of the guidelines. Early diagnosis is important because research shows current medication and care options are most effective in people with mild to moderate Alzheimer's disease. While Alzheimer's disease has no cure, medication can improve quality of life and cognitive functions–including memory, thought and reasoning– particularly among people who are mildly to moderately affected. Regular routines and activities such as mild exercise or walking can help with behavioral symptoms. In addition, education and support for caregivers can improve the well-being of both the person with Alzheimer's disease and the caregiver.
While the comprehensive guidelines were developed for physician use, a summary is available to help patients and their families better understand the options to discuss with their doctor.

Petersen, R. C., Stevens, J. C., Ganguli, M., Tangalos, E. G., Cummings, J. L., & DeKosky, S. T. (2001). Practice parameter: Early detection of dementia: Mild cognitive impairment (an evidence-based review) Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology, 56(9), 1133–1142. doi:10.1212/WNL.56.9.1133

Knopman, D. S., DeKosky, S. T., Cummings, J. L., Chui, H., Corey–Bloom, J., Relkin, N., … Stevens, J. C. (2001). Practice parameter: Diagnosis of dementia (an evidence-based review) Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology, 56(9), 1143–1153. doi:10.1212/WNL.56.9.1143

Doody, R. S., Stevens, J. C., Beck, C., Dubinsky, R. M., Kaye, J. A., Gwyther, L., … Cummings, J. L. (2001). Practice parameter: Management of dementia (an evidence-based review) Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology, 56(9), 1154–1166. doi:10.1212/WNL.56.9.1154

http://www.eurekalert.org/pub_releases/2001-05/AAoN-Ngee-0605101.php

Scans

PET scans may improve accuracy of dementia diagnosis

A study involving 66 patients with mild dementia or mild cognitive impairment, who were diagnosed with either Alzheimer's disease, frontotemporal dementia or dementia with Lewy bodies, by three specialists, had these diagnoses changed more than 25% of the time after PET imaging. The findings point to the importance of using PET scans to accurately diagnose the type of dementia.

Frey, K. et al. 2009. PET neurochemical vs. clinical phenotypes in mild-early dementia. Presented at the SNM's 56th Annual Meeting, June 13-17, 2009. Scientific Paper 251.

http://www.eurekalert.org/pub_releases/2009-06/sonm-psm061409.php

Technique shows brain aging before symptoms appear

A new chemical marker called FDDNP, which binds to plaque and tangle deposits in the brain, has enabled PET scans to reveal exactly where these abnormal protein deposits are accumulating, and has found that older age correlated with higher concentrations of FDDNP in the medial and lateral temporal regions of the brain, areas involved with memory, where plaques and tangles usually collect. Of the 76 study volunteers, 34 carried the ‘Alzheimer’s gene’. This group demonstrated higher FDDNP levels in the frontal region of the brain than those without the gene variant. Thirty-six of the volunteers had mild cognitive impairment, and these had higher measures of FDDNP in the medial temporal brain regions than normal volunteers. Those who had both MCI and the APOE-4 gene also had higher concentrations of FDDNP in the medial temporal brain regions than those who had MCI but not APOE-4. The pilot study offers hope of early diagnosis of brain impairment, before symptoms show themselves.

Small, G.W. et al. 2009. Influence of Cognitive Status, Age, and APOE-4 Genetic Risk on Brain FDDNP Positron-Emission Tomography Imaging in Persons Without Dementia. Archives of General Psychiatry, 66(1), 81-87.

http://www.eurekalert.org/pub_releases/2009-01/uoc--uat010509.php

MRI brain scans accurate in early diagnosis of Alzheimer's disease

Adding to the growing body of evidence indicating MRI brain scans provide valuable diagnostic information about Alzheimer's disease, a study in which a new visual rating system for evaluating the severity of shrinkage in the medial temporal lobe was used on brain scans of 260 people has found that scores accurately distinguished those with Alzheimer’s from those with mild cognitive impairment and those without memory problems. The test also accurately predicted those who would move from one group to another within a year or two.

Duara, R. et al. 2008. Medial temporal lobe atrophy on MRI scans and the diagnosis of Alzheimer disease. Neurology, 71, 1986-1992.

http://www.eurekalert.org/pub_releases/2008-12/uosf-mbs121808.php

Study validates Pittsburgh Compound-B in identifying Alzheimer's disease toxins

Previous research demonstrating that Pittsburgh Compound-B (PiB) binds to beta-amyloid deposits has involved only the autopsied brains of patients afflicted with Alzheimer’s. A new study correlated PiB-identified beta-amyloid deposits in a living patient with post-mortem autopsy results 10 months later, confirming that PiB allows accurate assessment of the amount of beta-amyloid plaques in brains of people afflicted with Alzheimer’s. A further study of the autopsied brains of 27 other patients with confirmed Alzheimer’s confirmed that PiB binds almost exclusively to beta-amyloid.

Ikonomovic, M.D. et al. 2008. Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer's disease. Brain Advance Access, published on March 12, 2008.
Full text at http://brain.oxfordjournals.org/cgi/content/abstract/awn016v1

http://www.eurekalert.org/pub_releases/2008-03/uops-svp032608.php

Brain scans show early Alzheimer's disease in people with memory problems

PET scans performed on the brains of 13 elderly men and women with mild cognitive impairment (MCI) and 14 elderly people without memory problems found that those with MCI had as much as 39% more PIB uptake in some parts of the brain than people without MCI, and about half of the MCI patients had PIB uptake in the Alzheimer's disease range. MCI subjects with at least one APOE 4 allele tended to have higher PIB uptake than MCI subjects without APOE 4. PIB is an imaging agent that allows amyloid plaque to be seen and measured.

Kemppainen, N.M. et al. 2007. PET amyloid ligand [11C]PIB uptake is increased in mild cognitive impairment. Neurology, 68, 1603-1606.

http://www.eurekalert.org/pub_releases/2007-05/aaon-bs050107.php

Compound shows promise for early detection of Alzheimer's disease

A new molecular marker called FDDNP has been found to track the progression of Alzheimer’s in PET scans more effectively than other markers, giving hope of earlier, more accurate diagnosis of the disease.

Small, G.W. et al. 2006. PET of Brain Amyloid and Tau in Mild Cognitive Impairment. The New England Journal of Medicine, 355 (25), 2652-63.

http://www.eurekalert.org/pub_releases/2006-12/nioa-nic121906.php
http://www.eurekalert.org/pub_releases/2006-12/uoc--nit121506.php

Non-invasive MRI technique distinguishes between Alzheimer's and frontotemporal dementia

A new study has found that a non-invasive imaging technique called arterial spin labeling is just as accurate and much faster and cheaper compared to invasive scanning techniques in distinguishing Alzheimer's disease from frontotemporal dementia (FTD). Frontotemporal dementia is the second-most common dementia after Alzheimer's disease. The present study aimed simply at differentiating the two types of dementia; further research needs to be done to confirm that the technique can be used to diagnose an individual patient.

The results were presented at the first International Conference on Prevention of Dementia, held June 18-21 in Washington, D.C.

http://www.eurekalert.org/pub_releases/2005-06/uoc--nmt061605.php

New computer program may enable early prediction of Alzheimer's risk

Researchers have developed a brain scan-based computer program that quickly and accurately measures metabolic activity in the hippocampus, a key brain region that shrinks with the development of Alzheimer’s. The study followed 53 normal subjects aged 54 to 80 for at least 9 years and in some cases for as long as 24 years, and found that hippocampal glucose metabolism was significantly reduced on the first scan of those 25 individuals who would later experience cognitive decline related to either mild cognitive impairment or to Alzheimer's. The findings bring hope of being able to predict who will develop Alzheimer’s at least 9 years ahead of symptoms.

Mosconi, L., Tsui, W-H., De Santi, S., Li, J., Rusinek, H., Convit, A., Li, Y., Boppana, M. & de Leon, M.J. 2005. Reduced hippocampal metabolism in MCI and AD: Automated FDG-PET image analysis. Neurology, 64, 1860-1867.

http://www.eurekalert.org/pub_releases/2005-06/nyum-ncp061505.php

Expert system gives non-experts diagnostic accuracy of Alzheimer's disease from PET scans

A computer program has been developed that enhances the diagnostic accuracy of PET scans with Alzheimer's patients. A PET scan is a very reliable noninvasive test, but only in the hands of an experienced investigator. The new program enables even inexperienced doctors to diagnose reliably, hopefully enabling diagnosis to occur earlier.

Siessmeier, T., Oehm, S., Drzezga, A., Fellgiebel, A., Schreckenberger, M., Uthman, T. & Bartenstein, P. 2005. Use of an Expert System for the Diagnosis of Suspected Alzheimer's Disease (AD) With FDG PET. Presented at the Society of Nuclear Medicine's 52nd Annual Meeting in Toronto; Scientific Poster Abstract 155

http://www.eurekalert.org/pub_releases/2005-06/sonm-esd061605.php

Pet scans detect brain differences in people at risk for Alzheimer's

Brain imaging of 32 participants, mostly in their 60s and 70s, has found clear differences in brain function between healthy people who carry a genetic risk factor for Alzheimer's disease and those who lack the factor. More research is needed before it's known for certain if the difference is an early sign of Alzheimer's.

Scarmeas, N., Habeck, C., Anderson, K.E., Hilton, J., Devanand, D.P., Pelton, G.H., Tabert, M.H., Flynn, J., Park, A., Ciappa, A., Tycko, B. & Stern, Y. 2004. Altered PET Functional Brain Responses in Cognitively Intact Elderly Persons at Risk for Alzheimer Disease (Carriers of the {epsilon}4 Allele). American Journal of Geriatric Psychiatry, 12, 596-605.

http://www.eurekalert.org/pub_releases/2004-11/cuco-psd111904.php

Rate of brain volume loss predicts dementia

A new study has found that rates of total brain volume loss may help identify patients with mild cognitive impairment who are at high risk of developing dementia. The study followed 55 people over 14 years, and found that loss of volume in the hippocampus predicted which mildly cognitively impaired individuals would stay stable and which would decline to Alzheimer's with 70% accuracy, while the rate of total brain volume loss was 62% accurate in predicting cognitive outcome. Combining both variables produced the strongest model: 75% accuracy. The discovery could help doctors plan early treatment strategies and prevention studies.

The study was presented at the 56th annual meeting of the American Academy of Neurology in San Francisco.

http://www.eurekalert.org/pub_releases/2004-04/ohs-osr042804.php

New PET technique improves accuracy of early diagnosis of Alzheimer's

A new study identifies a new Positron Emission Tomography (PET) scanning technique that may increase the already high accuracy of PET in diagnosing Alzheimer’s at a very early stage. Altered brain connections between the entorhinal cortex and both hemispheres of the brain can be clearly identified with 18F-FDG PET. The entorhinal cortex is a critical site for learning and memory. It now appears that most of its connections to the neocortex in both hemispheres are destroyed at a very early stage of Alzheimer’s.

Mosconi, L., Pupi, A., De Cristofaro, M.T.R., Fayyaz, M. & Herholz, K. 2004. Functional Interactions of the Entorhinal Cortex: An 18F-FDG PET Study on Normal Aging and Alzheimer's Disease. Journal of Nuclear Medicine, 45 (3), 382-392.

http://www.eurekalert.org/pub_releases/2004-03/sonm-nss031104.php

New technique allows sight of amyloid plaque in living brains

The first human study has now been completed of a compound that, through PET scanning, enables researchers to see the amyloid plaque deposits in the brains of Alzheimer’s sufferers. The compound has been dubbed Pittsburgh Compound B (PIB), and should be a very useful new tool in Alzheimer’s research.

Klunk, W.E. et al. 2004. Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound-B. Annals of Neurology, 55 (3), 306-319.

http://www.eurekalert.org/pub_releases/2004-01/uopm-uop012104.php

Hippocampal damage seen in those with alcoholic memory disorder and those with Alzheimer's

A comparison between the brains of five men with alcoholic Korsakoff's syndrome and the brains of men with Alzheimer's disease as well as the brains of healthy men, found that the brains of all Korsakoff's patients and Alzheimer's patients were comparable in significant volume loss in the hippocampus. Greater hippocampal damage (for Korsakoff's patients) and smaller hippocampal size (for Alzheimer’s) was correlated with poorer memory performance. It is suggested that, although there are of course a number of differences between these disorders, the nature of the memory impairment may be the same. Awareness of the similarities may help detection of both disorders.

Sullivan, E.V. & Marsh, L. 2003. Hippocampal volume deficits in alcoholic Korsakoff’s syndrome. Neurology, 61, 1716-1719.

http://www.eurekalert.org/pub_releases/2003-12/aaon-seu121503.php

Imaging techniques help distinguish between Alzheimer's and vascular dementia

A combination of magnetic resonance imaging (MRI) and MR spectroscopy has enabled researchers to differentiate between Alzheimer’s and dementia caused by poor blood flow (vascular dementia). Comparison of the brains of those with Alzheimer’s, those who had suffered subcortical ischemic vascular dementia (SIVD), and those belonging to cognitively normal older adults, also found significant differences in the chemical signature of various brain regions, leading researchers to suggest that in patients with SIVD, there may only be neuronal dysfunction rather than neuronal loss, offering hope for recovery of neuronal function in these areas. More research is needed to confirm these results.

Schuff, N. et al. 2003. Different patterns of N-acetylaspartate loss in subcortical ischemic vascular dementia and AD. Neurology, 61, 358-364.

Activity in the mediotemporal lobe lower in elderly with poor memory

An imaging study has revealed that, although there is no difference on standard MRI scans,scans showing the amount of oxygen (and thus activity) find that elderly persons with a poor memory have less activity in the mediotemporal lobe when storing new information than elderly persons with a normally functioning memory.This more sensitive scan may help early diagnosis of Alzheimer's.

The research was done as part of a doctoral thesis by Dr Sander Daselaar.

http://www.eurekalert.org/pub_releases/2003-03/nofs-svp032103.php

PET scans can help early diagnosis of Alzheimer's

Early diagnosis of Alzheimer’s is becoming more and more important, with the arrival of drugs and therapies which can help slow the progression of the disease, if caught early. A new study reveals that PET scans may be able to identify Alzheimer’s, and distinguish it from other dementias.

Initial results were presented recently at the International Conference on Alzheimer's Disease and Related Disorders.

http://www.eurekalert.org/pub_releases/2002-11/uomh-sit110102.php

Value of PET scans in diagnosing Alzheimer’s

A new study has measured the advantage of early diagnosis of Alzheimer’s using PET scanning. The study compared the use of two strategies for diagnosing Alzheimer's: clinical evaluation using the American Academy of Neurology (AAN) 2001 recommendations, and the same with the addition of a PET scan. They concluded that, although both approaches accurately diagnosed most Alzheimer's patients, the appropriate use of PET reduced erroneous diagnoses by half. A review of the literature suggested conventional methods would falsely attribute symptoms to early Alzheimer's in 23 cases out of 100, and overlook eight cases. Analysis suggested that incorporating PET scans would have prevented 11 of the 23 false positives and five of the eight false negatives. The researchers estimated that PET could cut unnecessary drug therapy by half (48%) and reduce months in a nursing home by 62%.

Cummings, J.L. 2002. 2-Deoxy-2-[18F]Fluoro-D-Glucose Positron Emission Tomography in Alzheimer's Diagnosis: Time for Technology Transfer, Molecular Imaging and Biology, 4 (6), 385-386.

http://www.eurekalert.org/pub_releases/2002-10/uoc--uss100402.php

MRI brain scan may detect Alzheimer's disease decades before first symptoms

MRI scans of the brain may detect Alzheimer’s disease decades before the first clinical signs of dementia occur, according to a study revealing that shrinkage of the hippocampus occurs very early in the disease process.

Gosche, K.M., Mortimer, J.A., Smith, C.D., Markesbery, W.R. & Snowdon, D.A. 2002. Hippocampal volume as an index of Alzheimer neuropathology: Findings from the Nun Study. Neurology, 58, 1476-1482.

http://www.eurekalert.org/pub_releases/2002-05/uosf-mbs052302.php

Brain scans predict cognitive impairment

A three-year study of 48 healthy people from 60 to 80 years old, by New York University School of Medicine researchers, predicted which healthy elderly men and women would develop memory impairment based on scans of their brains. At the beginning of the study, everyone scored within the normal range on a battery of tests typically used to detect early loss of memory and other mental skills. However, PET scans revealed a reduction in glucose metabolism in an area of the brain called the entorhinal cortex among 12 people. Three years later, 11 of these people had experienced mild cognitive impairment and one had developed Alzheimer's disease. "Our work extends the use of PET scanning to identifying in normal aging subjects the earliest metabolic abnormalities that may lead to the memory losses referred to as mild cognitive impairment (MCI). The diagnosis of MCI carries a high risk for future Alzheimer's disease."

Leon, M. J. de, Convit, A., Wolf, O. T., Tarshish, C. Y., DeSanti, S., Rusinek, H., … Fowler, J. (2001). Prediction of cognitive decline in normal elderly subjects with 2-[18F]fluoro-2-deoxy-d-glucose/positron-emission tomography (FDG/PET). Proceedings of the National Academy of Sciences, 98(19), 10966–10971. doi:10.1073/pnas.191044198

http://www.eurekalert.org/pub_releases/2001-09/nyum-bps090701.php

tags development: 

tags problems: 

Alzheimer's: Causes

Older news items (pre-2010) brought over from the old website

Role of fatty acids in Alzheimer's disease

Fatty acids are rapidly taken up by the brain and incorporated into phospholipids, a class of fats that form the membrane or barrier that shields the content of cells from the external environment. Now genetically engineered mice have revealed that there is a striking increase in arachidonic acid and related metabolites in the hippocampus. Removal or reduction of the enzyme that releases this acid prevented memory deficits in the Alzheimer mice. It’s thought that the acid causes too much excitation.

Sanchez-Mejia, R.O. et al. 2008. Phospholipase A2 reduction ameliorates cognitive deficits in a mouse model of Alzheimer's disease. Nature Neuroscience, 11, 1311-1318.

http://www.eurekalert.org/pub_releases/2008-10/gi-gsi101408.php

Support for view of Alzheimer's as form of diabetes

Research in the last few years has raised the possibility that Alzheimer’s memory loss could be due to a third form of diabetes. A new study clarifies the connection between insulin and Alzheimer’s. It seems that the toxic protein ADDL, found in the brains of individuals with Alzheimer’s, removes insulin receptors from nerve cells, rendering those neurons insulin resistant. The findings suggest that some existing drugs now used to treat diabetic patients may be useful for Alzheimer’s treatment.

Zhao,W-Q. et al. 2007. Amyloid beta oligomers induce impairment of neuronal insulin receptors. FASEB Journal, published online ahead of print August 24.

http://www.eurekalert.org/pub_releases/2007-09/nu-dst092607.php

Link between size of hippocampus and progression to Alzheimer's

A study of 20 older adults with mild cognitive impairment has found that the hippocampus was smaller in those who developed into Alzheimer's during the 3 year period.

Apostolova, L.G. et al. 2006. Conversion of Mild Cognitive Impairment to Alzheimer Disease Predicted by Hippocampal Atrophy Maps. Archives of Neurology, 63, 693-699.

http://www.eurekalert.org/pub_releases/2006-05/uoc--rml050406.php

Post-mortem brain studies reveal features of mild cognitive impairment

Autopsies have revealed that the brains of patients with mild cognitive impairment display pathologic features that appear to place them at an intermediate stage between normal aging and Alzheimer's disease. For instance, the patients had begun developing neurofibrillary tangles, but the number of plaques was similar to that in healthy patients. All patients with mild cognitive impairment had abnormalities in their temporal lobes, which likely caused their cognitive difficulties, and many also had abnormalities in other areas that did not relate to the features of Alzheimer's disease. In a second study, of 34 patients with mild cognitive impairment who had progressed to clinical dementia before their deaths, 24 were diagnosed (post-mortem) with Alzheimer’s, and 10 with other types of dementia. As in the other study, all patients had abnormalities in their temporal lobes.

Petersen, R.C. et al. 2006. Neuropathologic Features of Amnestic Mild Cognitive Impairment. Archives of Neurology, 63, 665-672.

Jicha, G.A. et al. 2006. Neuropathologic Outcome of Mild Cognitive Impairment Following Progression to Clinical Dementia. Archives of Neurology, 63, 674-681.

http://www.eurekalert.org/pub_releases/2006-05/jaaj-pbs050406.php

Neurons can produce apolipoprotein E

Apolipoprotein E has been known to be synthesized in the brain in support cells such as astrocytes, microglia, and ependymal layer cells. Controversial for the last decade has been the question of whether or not neurons can produce apoE. Using a unique mouse model, researchers have now demonstrated that neurons can produce apoE, but only in response to injury to the brain.

Xu, Q. et al. 2006. Profile and Regulation of Apolipoprotein E (ApoE) Expression in the CNS in Mice with Targeting of Green Fluorescent Protein Gene to the ApoE Locus. Journal of Neuroscience, 26, 4985-4994.

http://www.eurekalert.org/pub_releases/2006-05/gi-gsp051006.php

Protein identified as cause of memory loss

Researchers have identified a substance in the brain that is proven to cause memory loss, giving drug developers a target for creating drugs to treat memory loss in people with dementia. The substance is a form of the amyloid-beta protein that is distinct from plaques and has been given the name Ab*56. Ab*56 impairs memory independently of plaques or neuronal loss, and may contribute to cognitive deficits associated with Alzheimer's disease.

Lesné, S. et al. 2006. A specific amyloid-beta protein assembly in the brain impairs memory. Nature, 440, 352-357.

http://www.eurekalert.org/pub_releases/2006-03/uom-uom_1031306.php

Reduced insulin in the brain triggers Alzheimer's degeneration

By depleting insulin and its related proteins in the brain, researchers have replicated the progression of Alzheimer's disease – including plaque deposits, neurofibrillary tangles, impaired cognitive functioning, cell loss and overall brain deterioration – in an experimental animal model. Brain deterioration was not related to the pancreas, raising the possibility that Alzheimer's is a neuroendocrine disorder, or a Type 3 diabetes.

Lester-Coll, N. et al. 2006. Intracerebral streptozotocin model of type 3 diabetes: relevance to sporadic Alzheimer’s disease. Journal of Alzheimer’s Disease, 9(1)

http://www.eurekalert.org/pub_releases/2006-03/l-rii031606.php

Pin1 enzyme key in preventing onset of Alzheimer's disease

An enzyme called Pin1, previously shown to prevent the formation of the tangles characteristic of Alzheimer's brains, has now been shown to also play a pivotal role in guarding against the development of the plaques that are also characteristic of Alzheimer's. These findings establish a direct link between amyloid plaques and tau tangles, and provide further evidence that Pin1 (prolyl isomerase) is essential to protect individuals from age-related neurodegeneration.

Pastorino, L. et al. 2006. The prolyl isomerase Pin1 regulates amyloid precursor protein processing and amyloid-beta production Nature, 440, 528-534.

http://www.eurekalert.org/pub_releases/2006-03/hms-nrs032006.php

Link between APOE and memory neurotransmitter

A new link in the complex chain of Alzheimer’s development has been found. It’s been found that receptors that bind apolipoprotein E (APOE) and those that bind glutamate are in fact connected, separated only by a small protein. It may be that inefficient or high levels of APOE are clogging these binding sites, preventing glutamate from activating the processes necessary to form memories. It may also be that the APOE4 variant — associated with Alzheimer's — is less efficient at removing lipid debris in the brain than is APOE2 or APOE3.

Hoe, H-S. et al. 2006. Apolipoprotein E Receptor 2 Interactions with the N-Methyl-D-aspartate Receptor. Journal of Biological Chemistry, 281, 3425-3431.

http://www.eurekalert.org/pub_releases/2006-02/gumc-nrr020906.php

Two pathways lead to Alzheimer's disease

Mild cognitive impairment (MCI), a transitional stage between normal cognition and Alzheimer's disease, has been categorized into two sub-types on the basis of differing symptoms. Those with the amnesic subtype (MCI-A) have memory impairments only, while those with the multiple cognitive domain subtype (MCI-MCD) have other types of mild impairments, such as in judgment or language, and mild or no memory loss. Both sub-types progress to Alzheimer's disease at the same rate. A new imaging technique has now revealed that these types do in fact have different pathologies. The hippocampus of patients with MCI-A was not significantly different from that of Alzheimer's patients (who show substantial shrinkage), but the hippocampus of those with MCI-MCD was not significantly different from that of the healthy controls.

Becker, J.T., Davis, S.W., Hayashi, K.M., Meltzer, C.C., Toga, A.W., Lopez, O.L., Thompson, P.M., for the Imaging Methods and Analysis in Geriatrics Research Group. 2006. Three-dimensional Patterns of Hippocampal Atrophy in Mild Cognitive Impairment. Archives of Neurology, 63, 97-101.

http://www.eurekalert.org/pub_releases/2006-01/uopm-tpf010606.php

Key genetic risk for Alzheimer's linked to myelin breakdown

Myelin, the fatty insulation coating the brain's internal wiring, builds up in childhood, and breaks down as we age. Myelin is critical for speedy communication between neurons. A new study supports a growing body of evidence that myelin breakdown is a key contributor to the onset of Alzheimer disease later in life. Moreover, it has also revealed that the severity and rate of myelin breakdown in healthy older individuals is associated with ApoE status. Thus both age, the most important risk factor for Alzheimer disease, and ApoE status, the second-most important risk factor, seem to act through the process of myelin breakdown.

Bartzokis, G., Lu, P.H., Geschwind, D.H., Edwards, N., Mintz, J. & Cummings, J.L. 2006. Apolipoprotein E Genotype and Age-Related Myelin Breakdown in Healthy Individuals: Implications for Cognitive Decline and Dementia. Archives of General Psychiatry, 63, 63-72.

http://www.eurekalert.org/pub_releases/2006-01/uoc--isl122805.php

Study links Alzheimer's and Down’s syndrome

New research suggests the cognitive problems observed in Alzheimer’s are related to defects in the machinery controlling neuronal connections — PAK enzyme signaling pathways. PAK (p21-activated kinase) enzymes form a family that includes two members (PAK1 and PAK3) that play critical roles in learning and memory. Humans with genetic loss of PAK3 have severe mental retardation. The study reveals that both PAK1 and PAK3 are abnormally distributed and reduced in Alzheimer patients, and that beta-amyloid was directly involved in PAK signaling deficits. The finding suggests therapies designed to address the PAK defect could treat cognitive problems in both patient populations.

Zhao, L. et al. 2006. Role of p21-activated kinase pathway defects in the cognitive deficits of Alzheimer disease. Nature Neuroscience, 9, 234–242.

http://www.eurekalert.org/pub_releases/2006-01/uoc--sid012506.php

New technique finds higher levels of creatine in Alzheimer’s brains

Creatine is involved in the maintaining the energy balance in the brain, but creatine, being small and very soluble, is difficult to detect. A new study has now succeeded in detecting creatine in situ, in brain tissue, and has found relatively large deposits in the hippocampus of Alzheimer’s brains. The finding suggests an overlooked aspect of energy disturbance in Alzheimer's disease, but further research is needed to understand it.
Gallant, M. et al. 2006. Focally Elevated Creatine Detected in Amyloid Precursor Protein (APP) Transgenic Mice and Alzheimer Disease Brain Tissue. Journal of Biological Chemistry, 281, 5-8.
http://www.eurekalert.org/pub_releases/2005-12/uow-iar122105.php

More light on apoE4 and Alzheimer’s

A mutant form of a protein that transports cholesterol, apolipoprotein E (apoE) has long been recognized as a causative factor for Alzheimer's disease, but exactly how has been unclear. 299 amino acids are associated with apoE4, but new research has now found which of these amino acids are toxic. These toxic fragments all reside in the mitochondria (the “energy powerhouse” of the cell). The finding suggests a new therapeutic approach, involving blocking interaction of apoE4 fragments with the mitochondria.

Ye, S. et al. 2005. Apolipoprotein (apo) E4 enhances amyloid peptide production in cultured neuronal cells: ApoE structure as a potential therapeutic target. Proceedings of the National Academy of Science, 102 (51), 18700-18705.

http://www.eurekalert.org/pub_releases/2005-12/gi-gsl121405.php

p25 only good in small doses

Elevated levels of a key brain regulatory enzyme called Cdk5 and an associated regulatory protein called p25 have been found in the brains of Alzheimer’s patients. A new mouse study has found that switching on p25 in the hippocampus for only two weeks actually enhanced learning and memory compared to normal mice; however mice in which p25 had been switched on for six weeks showed impaired learning and memory. These mice also showed significant brain atrophy and loss of hippocampal neurons. The two-week pulse of p25 did not cause neurodegeneration and had long-lasting effects on enhancing memory. The researchers suggest that p25 might be produced to compensate for the loss of Cdk5 activity during aging, however chronically high levels lead to neuronal cell death. The findings are consistent with several recent studies suggesting that in the development of Alzheimer’s, compensatory mechanisms that initially enhance neuroplasticity eventually become maladaptive when chronically activated.

Fischer, A., Sananbenesi, F., Pang, P.T., Lu, B. & Tsai, L-H. 2005. Opposing roles of transient and prolonged expression of p25 in synaptic plasticity and hippocampus-dependent memory. Neuron, 48, 825–838.

http://www.eurekalert.org/pub_releases/2005-12/cp-aje120505.php

“Default” brain activity implicated in Alzheimer's disease

Here’s an unexpected finding: imaging of the brains of 764 adults of various ages has revealed that the regions that are active when people are in “default mode” — not concentrating on anything in particular, just musing to yourself — are the same regions that develop plaques in Alzheimer’s. They also found that, when asked to concentrate on a specific task, individuals with Alzheimer’s showed increased activity in these posterior cortical regions, rather than the decreased activity seen in young, healthy adults. The researchers speculate that dementia may in fact be a consequence of normal cognitive function — a possibility that hasn’t heretofore been considered. The findings raise the hope of developing methods to detect precursors of the disease long before it develops.

Buckner, R.L. et al. 2005. Molecular, Structural, and Functional Characterization of Alzheimer's Disease: Evidence for a Relationship between Default Activity, Amyloid, and Memory. Journal of Neuroscience, 25, 7709-7717.

http://www.eurekalert.org/pub_releases/2005-08/hhmi-bai082405.php

How Alzheimer's impacts important brain cell function

Researchers have found that synaptic proteins, proteins involved in brain cell communications, decrease in the brains of Alzheimer's patients compared to healthy brains from people in the same age range. The decrease in the frontal cortex was more severe than in other portions of the brain. They also found synaptic protein levels were even lower in the brains of patients in the early stages of Alzheimer's disease, suggesting that the loss of these proteins happens very early in the disease process. The reduction of synaptic proteins may be caused by mitochondrial dysfunction, a well-documented occurrence in Alzheimer's.

Reddy, P.H., Mani, G., Park, B.S., Jacques, J., Murdoch, G., Whetsell, W.Jr., Kaye, J. & Manczak, M. 2005. Differential loss of synaptic proteins in Alzheimer’s disease: Implications for synaptic dysfunction Journal of Alzheimer's Disease, 7(2),103-117.

http://www.eurekalert.org/pub_releases/2005-04/ohs-ord040605.php

Research clarifies how Alzheimer's medicines work

New research clarifies how cholinesterase inhibitors alleviate mild-to-moderate Alzheimer's. When scientists chemically blocked receptors for an important neurotransmitter called acetylcholine, even healthy young people found it significantly harder to learn and remember – especially in the face of interference. Cholinesterase inhibitors slow the breakdown of acetylcholine. The finding also helps explain why Parkinson's disease, dementia due to multiple strokes, multiple sclerosis and schizophrenia, are all also associated with memory problems — all these conditions, like Alzheimer’s, are associated with lower levels of acetylcholine in the brain.

Atri, A., Norman, K.A., Nicolas, M.M., Cramer, S.C., Hasselmo, M.E., Sherman, S., Kirchhoff, B.A., Greicius, M.D., Breiter, H.C. & Stern, C.E. 2004. Central Cholinergic Receptors Impairs New Learning and Increases Proactive Interference in a Word Paired-Associate Memory Task. Behavioral Neuroscience, 118 (1).

http://www.eurekalert.org/pub_releases/2004-02/apa-rch020904.php

Why diet, hormones, exercise might delay Alzheimer’s

A theory that changes in fat metabolism in the membranes of nerve cells play a role in Alzheimer's has been supported in a recent study. The study found significantly higher levels of ceramide and cholesterol in the middle frontal gyrus of Alzheimer's patients. The researchers suggest that alterations in fats (especially cholesterol and ceramide) may contribute to a "neurodegenerative cascade" that destroys neurons in Alzheimer's, and that the accumulation of ceramide and cholesterol is triggered by the oxidative stress brought on by the presence of the toxic beta amyloid peptide. The study also suggests a reason for why antioxidants such as vitamin E might delay the onset of Alzheimer's: treatment with Vitamin E reduced the levels of ceramide and cholesterol, resulting in a significant decrease in the number of neurons killed by the beta amyloid and oxidative stress.

Cutler, R.G., Kelly, J., Storie, K., Pedersen, W.A., Tammara, A., Hatanpaa, K., Troncoso, J.C. & Mattson, M.P. 2004. Involvement of oxidative stress-induced abnormalities in ceramide and cholesterol metabolism in brain aging and Alzheimer's disease. PNAS, 101, 2070-5.

http://www.eurekalert.org/pub_releases/2004-02/aaft-nsm021004.php

Late-life Alzheimer's begins in midlife

A new model of human brain aging identifies midlife breakdown of myelin, a fatty insulation with very high cholesterol content that wraps tightly around axons (part of the neurons) and enables messages to pass along the “wiring” of the brain speedily, as a possible key to the onset of Alzheimer's disease later in life. Imaging studies and examination of brain tissue shows that the brain's wiring develops until middle age and then begins to decline as the breakdown of myelin triggers a destructive domino affect. It is suggested that genetic factors coupled with the brain's own developmental process of increasing cholesterol and iron levels in middle age help degrade the myelin. The complex connections that take the longest to develop and allow humans to think at their highest level are among the first to deteriorate as the brain's myelin breaks down in reverse order of development. The model suggests that the best time to address the inevitability of myelin breakdown is when it begins, in middle age. Possible preventive therapies include cholesterol- and iron-lowering medications, anti-inflammatory medications, diet and exercise programs and possibly hormone replacement therapy designed to prevent menopause rather than simply ease the symptoms. Education and cognitively stimulating activities may also stimulate the production of myelin.

Bartzokis, G. 2003. Age-related myelin breakdown: a developmental model of cognitive decline and Alzheimer's disease. Neurobiology of Aging, 25(1), 5-18.

http://www.eurekalert.org/pub_releases/2003-12/uoc--mbc122303.php

A nicotine by-product implicated in Alzheimer’s

A previously unrecognized chemical process has been discovered, by which a chemical called nornicotine, naturally present in tobacco and produced as a metabolite of nicotine, permanently and irreversibly modifies proteins in the body. These modified proteins interact with other chemicals in the body to form a variety of compounds known as advanced glycation endproducts. Advanced glycation endproducts have previously been implicated in numerous diseases including diabetes, cancer, atherosclerosis, and Alzheimer’s disease.

Dickerson, T.J. & Janda, K.D. 2002. A previously undescribed chemical link between smoking and metabolic disease. Proc. Natl. Acad. Sci. USA, 99 (23), 15084-15088.

http://www.eurekalert.org/pub_releases/2002-10/sri-aka102402.php

tags development: 

tags problems: 

Genetic test shows risk of cognitive impairment rather than Alzheimer’s

Analysis of data from 418 older adults (70+) has found that carriers of the ‘Alzheimer’s gene’, APOEe4, were 58% more likely to develop mild cognitive impairment compared to non-carriers. However, ε4 carriers with

04/2013

Mynd: 

tags development: 

tags memworks: 

tags problems: 

Diet affects your chance of cognitive impairment in old age

November, 2012

A large study reveals that a diet with high levels of carbohydrate and sugar greatly increases the chance of developing MCI or dementia, while high levels of fat and protein reduce the risk.

In a large Mayo Clinic study, self-reported diet was found to be significantly associated with the risk of seniors developing mild cognitive impairment or dementia over a four-year period.

The study involved 1,230 older adults (70-89) who completed a 128-item food-frequency questionnaire about their diet during the previous year. Of these, around three-quarters (937) showed no signs of cognitive impairment at the beginning of the study period, and were asked to return for follow-up cognitive assessments. These assessments took place every 15 months. After about four years, 200 (21%) had developed mild cognitive impairment (MCI) or dementia.

The likelihood of cognitive deterioration was significantly affected by the type of diet. Those with the highest carbohydrate intake were nearly twice as likely to develop cognitive impairment compared to those with the lowest carbohydrate consumption, and when total fat and protein intake were taken into account, they were 3.6 times likelier to develop impairment.

Those with the highest sugar intake were 1.5 times more likely to develop cognitive impairment.

But — a finding that will no doubt surprise many — those with the highest fat consumption were 42% less likely to develop cognitive impairment, compared to those with the lowest level of fats.

Less surprisingly, those with highest intake of protein had a reduced risk of 21%.

In other words, the worst diet you can have, if you want to keep your brain healthy, is one that receives most of its calories from carbohydrates and sugar, and relatively little from fats and protein.

The findings about carbs, sugar, and protein are consistent with other research. The finding regarding fats is somewhat more surprising. The inconsistency may lie in the type of fat. Research implicating high-fat diets as a risk factor in Alzheimer’s have used saturated fats. Diets high in olive oil, on the other hand, have been found to be beneficial.

It seems likely that the danger of carbs and too much sugar lies in the effects on glucose and insulin metabolism. Saturated fats also interfere with glucose metabolism. Alzheimer’s has sometimes been called Type 3 diabetes, because of its association with insulin problems.

Reference: 

Roberts RO, Roberts LA, Geda YE, Cha RH, Pankratz VS, O'Connor HM, Knopman DS, Petersen RC. 2012. Relative intake of macronutrients impacts risk of mild cognitive impairment or dementia. Journal of Alzheimers Disease, 32(2), 329-39.

Source: 

Topics: 

tags development: 

tags lifestyle: 

tags problems: 

Reviving a failing sense of smell through training

January, 2012

A rat study reveals how training can improve or impair smell perception.

The olfactory bulb is in the oldest part of our brain. It connects directly to the amygdala (our ‘emotion center’) and our prefrontal cortex, giving smells a more direct pathway to memory than our other senses. But the olfactory bulb is only part of the system processing smells. It projects to several other regions, all of which are together called the primary olfactory cortex, and of which the most prominent member is the piriform cortex. More recently, however, it has been suggested that it would be more useful to regard the olfactory bulb as the primary olfactory cortex (primary in the sense that it is first), while the piriform cortex should be regarded as association cortex — meaning that it integrates sensory information with ‘higher-order’ (cognitive, contextual, and behavioral) information.

Testing this hypothesis, a new rat study has found that, when rats were given training to distinguish various odors, each smell produced a different pattern of electrical activity in the olfactory bulb. However, only those smells that the rat could distinguish from others were reflected in distinct patterns of brain activity in the anterior piriform cortex, while smells that the rat couldn’t differentiate produced identical brain activity patterns there. Interestingly, the smells that the rats could easily distinguish were ones in which one of the ten components in the target odor had been replaced with a new component. The smells they found difficult to distinguish were those in which a component had simply been deleted.

When a new group of rats was given additional training (8 days vs the 2 days given the original group), they eventually learned to discriminate between the odors the first animals couldn’t distinguish, and this was reflected in distinct patterns of brain activity in the anterior piriform cortex. When a third group were taught to ignore the difference between odors the first rats could readily distinguish, they became unable to tell the odors apart, and similar patterns of brain activity were produced in the piriform cortex.

The effects of training were also quite stable — they were still evident after two weeks.

These findings support the idea of the piriform cortex as association cortex. It is here that experience modified neuronal activity. In the olfactory bulb, where all the various odors were reflected in different patterns of activity right from the beginning (meaning that this part of the brain could discriminate between odors that the rat itself couldn’t distinguish), training made no difference to the patterns of activity.

Having said that, it should be noted that this is not entirely consistent with previous research. Several studies have found that odor training produces changes in the representations in the olfactory bulb. The difference may lie in the method of neural recording.

How far does this generalize to the human brain? Human studies have suggested that odors are represented in the posterior piriform cortex rather than the anterior piriform cortex. They have also suggested that the anterior piriform cortex is involved in expectations relating to the smells, rather than representing the smells themselves. Whether these differences reflect species differences, task differences, or methodological differences, remains to be seen.

But whether or not the same exact regions are involved, there are practical implications we can consider. The findings do suggest that one road to olfactory impairment is through neglect — if you learn to ignore differences between smells, you will become increasingly less able to do so. An impaired sense of smell has been found in Alzheimer’s disease, Parkinson's disease, schizophrenia, and even normal aging. While some of that may well reflect impairment earlier in the perception process, some of it may reflect the consequences of neglect. The burning question is, then, would it be possible to restore smell function through odor training?

I’d really like to see this study replicated with old rats.

Reference: 

Source: 

Topics: 

tags development: 

tags memworks: 

tags problems: 

tags strategies: 

Helping Alzheimer's sufferers

Behavioral and cognitive strategies that can help those suffering from Alzheimer's.

Older news items (pre-2010) brought over from the old website

Memory grows less efficient very early in Alzheimer's

A study of 109 healthy older adults (average age 75), 41 older adults with very early Alzheimer's, 13 with early Alzheimer's, and 35 younger adults (25 or younger) has found that those with Alzheimer’s — even those in the very early stages — were significantly less efficient than their healthy age peers at remembering items according to their value. It may be that Alzheimer's makes it harder for people to encode what they learn in a strategic way. This research suggests the potential for improved memory training.

Castel, A.D., Balota, D.A. & McCabe, D.P. 2009. Memory Efficiency and the Strategic Control of Attention at Encoding: Impairments of Value-Directed Remembering in Alzheimer's Disease. Neuropsychology, 23 (3), 297-306.

http://www.eurekalert.org/pub_releases/2009-05/apa-mgl042909.php

Pictures better than words for memory-damaged patients

We’ve long known that pictures are remembered better than words. Now a study has found that this picture superiority still exists in those with mild cognitive impairment and very mild Alzheimer’s disease. Moreover, frontally-based brainwave patterns were similar to those of controls when pictures were being retrieved, but not for words. The findings support the idea that those with mild Alzheimer’s can successfully use implicit memory (memory without conscious awareness) to support recognition, and this may point to new strategies for dealing with their memory problems.

Castel, A.D., Balota, D.A. & McCabe, D.P. 2009. Memory Efficiency and the Strategic Control of Attention at Encoding: Impairments of Value-Directed Remembering in Alzheimer's Disease. Neuropsychology, 23 (3), 297-306.

http://www.physorg.com/news160307482.html

Treating sleep apnea in Alzheimer's patients helps cognition

A study of 52 men and women with mild to moderate Alzheimer's disease and obstructive sleep apnea (OSA) has found significant improvement in patients' neurological test scores after continuous positive airway pressure (CPAP) treatment. CPAP also reduced daytime sleepiness, a common complaint of Alzheimer's patients and their caregivers. The prevalence of OSA in patients with dementia has been estimated to be as high as 70 to 80%.

Ancoli-Israel, S. et al. 2008. Cognitive Effects of Treating Obstructive Sleep Apnea in Alzheimer's Disease: A Randomized Controlled Study. Journal of the American Geriatrics Society, 56 (11),2076-2081.

http://www.eurekalert.org/pub_releases/2008-12/uoc--tsa120308.php

Hypnosis shown to reduce symptoms of dementia

This one’s really quite weird. A study found that people living with dementia who received hypnosis therapy over a nine month period showed an improvement in concentration, memory and socialization compared to groups receiving the normal treatment (who declined in these measures) and those attending a regular discussion group (who stayed the same). Relaxation, motivation and daily living activities also improved with the use of hypnosis. The findings point to the role of depression and anxiety in worsening the symptoms of dementia. The latest follow-up study has found that many of the benefits in the hypnosis group were maintained 12 months later.

Duff, S.C. & Nightingale, D.J. 2008. Long-term outcomes of hypnosis in changing the quality of life in patients with dementia. European Journal of Clinical Hypnosis, 7 (1)

http://www.eurekalert.org/pub_releases/2008-07/uol-hst072808.php
http://www.sciencedaily.com/releases/2008/07/080728111402.htm

More sleep improves cognition in Alzheimer patients with OSA

A study involving 52 participants with an average age of 77.8 years who had Alzheimer disease and obstructive sleep apnea (OSA) has found that it was increases in total sleep time in those given continuous positive airway pressure treatment that was associated with improvements in cognition, rather than improvement in oxygen levels. This suggests that the cognitive dysfunction associated with OSA in patients with dementia may be in part an effect of short sleep time.

The findings were presented at SLEEP 2008, the 22nd Annual Meeting of the Associated Professional Sleep Societies (APSS).

http://www.eurekalert.org/pub_releases/2008-06/aaos-iit050708.php

Mediterranean diet may help Alzheimer's patients live longer

A study of 192 people with Alzheimer's disease has found that those who most closely followed a Mediterranean diet were 76% less likely to die during the 4 ½ year study period compared to those who followed the diet the least. A previous study by the same researchers found that healthy people who eat a Mediterranean diet lowered their risk of developing Alzheimer's disease. The Mediterranean diet includes a high intake of vegetables, legumes, fruits, cereals, fish, monounsaturated fatty acids; a low intake of saturated fatty acids, dairy products, meat and poultry; and a mild to moderate amount of alcohol.

Scarmeas, N., Luchsinger, J.A., Mayeux, R. & Stern, Y. 2007. Mediterranean diet and Alzheimer disease mortality. Neurology, 69, 1084-1093.

http://www.sciencedaily.com/releases/2007/09/ 070910162411.htm
http://www.eurekalert.org/pub_releases/2007-09/aaon-mdm090407.php

Alzheimer's weight gain initiative improved patients' intellectual abilities

In a small, three-month study, Swedish researchers have found a way to increase the weight of people with Alzheimer's, with consequent improved intellectual abilities, by improving communication and patient involvement, altering meal routines and providing a more homely eating environment.

Mamhidir et al. 2007. Weight increase in patients with dementia and alteration in meal routines and meal environment after integrity promoting care. Journal of Clinical Nursing, 16, 987-996.

http://www.eurekalert.org/pub_releases/2007-05/bpl-awg051507.php

Enhanced environment restores memory in mice with neurodegeneration

Research involving genetically engineered mice has found that mice whose brains had lost a large number of neurons due to neurodegeneration regained long-term memories and the ability to learn after their surroundings were enriched with toys and other sensory stimuli. The same effect was also achieved through the use of a drug that encourages neuronal growth. The findings suggest not only new approaches to treatment for those with Alzheimer's or other neurodegenerative diseases, but also supports recent suggestions that "memory loss" may be an inaccurate description of the kinds of mental deficits associated with neurodegenerative diseases. The memories are still there; they are simply inaccessible.

Fischer, A., Sananbenesi, F., Wang, X., Dobbin, M. & Tsai, L-H. 2007. Recovery of learning and memory is associated with chromatin remodelling. Nature, 447, 178-182.

http://www.eurekalert.org/pub_releases/2007-04/hhmi-eer042507.php

Computer-based 'games' enhance mental function in Alzheimer's patients

An interactive multimedia internet-based game has been shown to benefit cognition in patients with Alzheimer's disease more than classic exercises of mental stimulation commonly used with dementia patients. The study compared patients receiving no cognitive intervention, those enrolled in a daily program that included 2.5 to 3.5 hours of cognitive stimulation tasks, musical therapy, arts and crafts, physical activity and programs that reinforced instrumental activities of daily living, and those who also used an interactive multimedia internet-based system which allowed them to carry out a variety of different cognitive stimulation tasks at varying levels of difficulty throughout the day. After 12 weeks, both intervention groups performed better on tests than the control group; at 24 weeks, the dual-intervention group did better than the program-only group. The study points to the value of cognitive stimulation to slow the rate of cognitive loss.

Tárraga, L. et al. 2006. A randomised pilot study to assess the efficacy of an interactive, multimedia tool of cognitive stimulation in Alzheimer’s disease. Journal of Neurology, Neurosurgery and Psychiatry, 77, 1116-1121.

http://www.eurekalert.org/pub_releases/2006-10/uopm-ce102306.php

Elders with dementia can tap into memory stores to give advice

Surprisingly, it appears that the best way to converse with an Alzheimer’s patient may be to ask them for advice. In two studies, researchers found that adults with moderate to severe symptoms of dementia can still be quite coherent and informative when asked for advice. In the first study, 14 people with early to advanced stages of dementia were asked about marriage, children and church in a purely social way, such as "Tell me about your children," and then later were asked for advice on the same topics, as in, "I'm thinking about having children. What kind of advice can you give me on that?" Patients were more coherent, informative and focused on the topic when asked for advice as opposed to when they were simply asked about their children, church or marriage. In the second study, six adults with dementia and six older adults without dementia, were given a booklet of pictures to guide them in teaching someone a simple recipe. Both groups successfully taught students to prepare the recipes, although those with dementia did need more prompting to finish the task.

Dijkstra, K., Bourgeois, M., Youmans, G. & Hancock, A. 2006. Implications of an Advice-Giving and Teacher Role on Language Production in Adults With Dementia. Gerontologist, 46, 357-366.

http://www.eurekalert.org/pub_releases/2006-07/fsu-sew071706.php

Missing eyeglasses impair activities for a third of nursing home patients with Alzheimer's disease

A study of nearly 100 Alzheimer’s patients in nursing homes has determined that one third of them were not using or did not have glasses that were strong enough to correct their eyesight. Apart from causing disorientation, limiting mobility and increasing the chance of falls, the loss of vision is likely to impact on mental stimulation, by making it difficult or impossible to engage in mentally stimulating activities such as reading or watching television.

Koch, J.M., Datta, G., Makhdoom, S. & Grossberg, G.T. 2005. Unmet Visual Needs of Alzheimer’s Disease Patients in Long-term Care Facilities. Journal of the American Medical Directors Association, 6(4), 233-237.

http://www.eurekalert.org/pub_releases/2005-07/slu-mem071905.php

New memory aid helps dementia sufferers remember

An innovative memory aid based on an interactive multimedia computer system aims to stimulate more enjoyable, rewarding conversation between sufferers and those who care for them. CIRCA (Computer Interactive Reminiscence and Conversation Aid) involves a simple touch-screen with easy-to-follow instructions; it displays a choice of three random categories (entertainment, local life etc) and three media (music, photo, video). The images, video or sound clips then act as a memory trigger and conversation prompt. During development, CIRCA was tested on 40 dementia sufferers with very encouraging results. CIRCA could become available on the market in 2-3 years.

http://www.eurekalert.org/pub_releases/2005-06/eaps-nma061505.php

Weight loss may be an early sign of dementia in the elderly

An analysis of data from 1,890 men who were participants in The Honolulu-Asia Aging Study has found that the weight loss common in people with dementia begins 2-4 years before the onset of clinical dementia symptoms. It’s possible that treatment interventions directed toward maintaining optimal nutrition and preventing excess weight loss could slow the disease.

Stewart, R., Masaki, K., Xue, Q-L., Peila, R., Petrovitch, H., White, L.R. & Launer, L.J. 2005. A 32-Year Prospective Study of Change in Body Weight and Incident Dementia: The Honolulu-Asia Aging Study. Archives of Neurology, 62, 55-60.

http://www.eurekalert.org/pub_releases/2005-01/jaaj-wlm010505.php

Studies suggest people with early AD can still learn

A new study suggests that people who have early stage Alzheimer's disease could be more capable of learning than previously thought. The study found that mildly impaired Alzheimer’s patients who participated in 3-to-4 months of cognitive rehabilitation had a 170% improvement, on average, in their ability to recall faces and names and a 71% improvement in their ability to provide proper change for a purchase. The participants also could respond to and process information more rapidly and were better oriented to time and place. These improvements were still evident 3 months after the cognitive training ended.

Loewenstein, D.A., Acevedo, A., Czaja, S.J. & Duara, R. 2004. Cognitive Rehabilitation of Mildly Impaired Alzheimer Disease Patients on Cholinesterase Inhibitors. American Journal of Geriatric Psychiatry, 12(4), 395-402.

http://www.eurekalert.org/pub_releases/2004-07/nioa-ssp062904.php

Alzheimer's may leave some forms of memory intact

A new study has demonstrated that people with Alzheimer's disease retain the capability for a specific form of memory used for rote learning of skills, despite their other memory loss. The finding suggests new strategies to improve training and rehabilitative programs for Alzheimer's sufferers. It also confirms other studies suggesting that a number of brain systems are more intact in Alzheimer's than previously thought.

[1219] Lustig, C., & Buckner R. L.
(2004).  Preserved Neural Correlates of Priming in Old Age and Dementia.
Neuron. 42(5), 865 - 875.

http://www.eurekalert.org/pub_releases/2004-06/hhmi-als060404.php
http://www.eurekalert.org/pub_releases/2004-06/cp-ssh060304.php

Program helps physical and behavioral well-being of Alzheimer's patients

A controlled trial of 153 community-dwelling patients diagnosed with Alzheimer’s examined the effectiveness of a home-based exercise program combined with caregiver training in behavioral management techniques in reducing functional dependence and delay institutionalization. The program resulted in improved physical health and less depression. Specifically, after three months, those receiving the training were more likely to exercise at least 60 minutes a week, to have fewer days of restricted activity, to have improved scores for physical role functioning, and improved Cornell Depression Scale for Depression in Dementia scores, and have less institutionalization due to behavioral disturbance.

Teri, L. et al. 2003. Exercise Plus Behavioral Management in Patients With Alzheimer Disease: A Randomized Controlled Trial. JAMA, 290, 2015-2022.

Alzheimer patients who scored well on memory tests show unique compensatory brain activity

A study of 12 healthy older adults and 11 older patients with probable early-stage Alzheimer's compared their performance in a series of semantic and episodic memory tasks on a computer screen, using PET scans. Overall, Alzheimer's patients performed less accurately on the semantic and episodic tasks compared to the normal controls. However, the range of scores was quite large in the Alzheimer group, with some performing poorly and others performing within the normal range. For those patients who did better on the memory tasks, researchers found that their prefrontal network activity was more expansive compared to the error-prone patients. This additional activity was happening in the right frontal and temporoparietal areas. It was a unique neural pattern not found in the controls either. This provides the most direct evidence to date that Alzheimer's patients can use additional neural resources in the prefrontal cortex to compensate for losses attributable to the degenerative process of the disease.

Grady, C.L., McIntosh, A.R., Beig, S., Keightley, M.L., Burian, H. & Black, S.E. 2003. Evidence from Functional Neuroimaging of a Compensatory Prefrontal Network in Alzheimer's Disease. Journal of Neuroscience, 23, 986-993.

http://www.eurekalert.org/pub_releases/2003-02/bcfg-apw013103.php

Memory training may help some Alzheimer's patients

Following anecdotal "success stories" of memory training provided by rehabilitation experts, researchers in London conducted a controlled study to see whether such training could be standardized for a larger group of people, and whether the benefits of training endured. The study involved 12 participants with probable Alzheimer's Disease (AD) at the minimal or mild stage, when they still had some capacity for learning. The researchers then trained participants to remember the names of people whom they had difficulty naming from a set of 12 photos that included people in their social network and famous people. They used such memory aids as mnemonic devices, which use the image to jog memory through some kind of meaningful association; "vanishing cues," a method in which participants fill in more and more letters in the person's name, until they can recall that name without any help; and "expanding rehearsal," in which people test themselves on what they've learned, in spaced intervals over time. All training minimized the chance of errors, which helped to reduce distress and raise confidence. By training participants' memory for just half of their photo sets, researchers were able to compare memory training with no training, for each participant. Participants learned the face-name association at the rate of one per week, adding each new pair to their practice until they worked at all six pairs. They continued practicing until a one-month follow-up test of the face-name pairs. Testing was repeated at three, six and 12 months. The memory training produced a statistically significant improvement in group performance on free recall of trained items. Participants kept their memory gains six months after training, and scores remained above baseline levels after 12 months -- even without further practice. Not all participants benefited from the training. Further research is needed to discover what distinguishes those who benefitted from those who didn’t. One factor that was found, was that those who were more aware of their memory problems were more likely to respond well to memory training.

Clare, L.,Wilson, B.A., Carter, G., Roth, I., Hodges & J.R. 2002. Relearning Face-Name Associations in Early Alzheimer's Disease. Neuropsychology, 16 (4), 538-47.

http://www.eurekalert.org/pub_releases/2002-10/apa-mtm101502.php

Helping Alzheimer's sufferers remember

Alzheimer sufferers recalled significantly more details of long-ago events when music was played during recall. Recent memory was not affected. It is suggested that music could be played at particular times when better recall is desirable, such as when relatives visit.

The study involved 23 older adults with mild-to-moderate dementia. Participants were tested in each of four auditory background conditions presented randomly, one week apart: quiet; cafeteria noise; familiar music (first movement of Vivaldi's “The Four Seasons”); novel music (Fitkin's “Hook”). Questions were drawn from three life eras: up to age 20; around ages 20—50; and recent past and present. Sound conditions (music or noise) were significantly better than quiet (mean recall 67% vs 61%). There was no difference between familiar and novel music, but there was a small difference between noise and music (66% vs 68%). This difference was greater for remote memory; there was no difference between noise and music for memory of recent past. Overall, the Alzheimer's patients had much better recall for older memories.

The improvement in recall for the sound conditions over quiet, and the similarity between all sound conditions, points to arousal as the crucial factor. The greater effectiveness of music compared to noise may signal an associational effect. Further research exploring the effects of different pieces of music would help clarify this.

Valentine, E. & Foster, N. 2000. Reported at the British Psychological Society's London Conference, December 20.

http://www.guardian.co.uk/uk/2000/dec/24/paulharris.theobserver1

tags development: 

tags problems: 

Coffee and a healthy diet reduce the risk of Alzheimer’s

August, 2011

Recent studies show why a low-fat, low-carb diet, and caffeinated coffee, help protect against developing Alzheimer’s disease.

Dietary changes affect levels of biomarkers associated with Alzheimer's

In a study involving 20 healthy older adults (mean age 69.3) and 29 older adults who had amnestic mild cognitive impairment (mean age 67.6), half the participants were randomly assigned to a high–saturated fat/high–simple carbohydrate diet (HIGH) and half to a low–saturated fat/low–simple carbohydrate diet (LOW) for four weeks, in order to investigate the effects on biomarkers associated with Alzheimer’s.

For the healthy participants, the LOW diet decreased the level of amyloid-beta 42 in the cerebrospinal fluid, while the HIGH diet increased its level. The HIGH diet also lowered the CSF insulin concentration. For those with aMCI, the LOW diet increased the levels of amyloid-beta 42 and increased the CSF insulin concentration. For both groups, the level of apolipoprotein E in the CSF increased in the LOW diet and decreased in the HIGH diet.

For both groups, the LOW diet improved performance on delayed visual recall tests, but didn’t affect scores on other cognitive measures (bear in mind that the diet was only followed for a month).

The researchers suggest that the different results of the unhealthy diet in participants with aMCI may be due to the diet’s short duration. The fact that diet was bringing about measurable changes in CSF biomarkers so quickly, and that the HIGH diet moved healthy brains in the direction of Alzheimer’s, speaks to the potential of dietary intervention.

Why coffee helps protect against Alzheimer's disease

Support for the value of coffee in decreasing the risk of Alzheimer’s comes from a mouse study, which found that an as yet unidentified ingredient in coffee interacts with caffeine in such a way that blood levels of a growth factor called GCSF (granulocyte colony stimulating factor) increases. GCSF is a substance greatly decreased in patients with Alzheimer's disease and demonstrated to improve memory in Alzheimer's mice.

The finding points to the value of caffeinated coffee, as opposed to decaffeinated coffee or to other sources of caffeine. Moreover, only "drip" coffee was used; the researchers caution that they don’t know whether instant caffeinated coffee would provide the same GCSF response.

There are three ways that GCSF seems to improve memory performance in the Alzheimer's mice: by recruiting stem cells from bone marrow to enter the brain and remove beta-amyloid protein; by increasing the growth of new synapses; by increasing neurogenesis.

The amount of coffee needed to provide this protection, however, is estimated to be about 4 to 5 cups a day. The researchers also believe that this daily coffee intake is best begun at least by middle age (30s – 50s), although starting even in older age does seem to have some protective effect.

Weirdly (I thought), the researchers remarked that "The average American gets most of their daily antioxidants intake through coffee". Perhaps this points more to the defects in their diet than to the wonders of coffee! But the finding is consistent with other research showing an association between moderate consumption of coffee and decreased risk of Parkinson's disease, Type II diabetes and stroke.

A just-completed clinical trial has investigated GCSF treatment to prevent Alzheimer's in patients with mild cognitive impairment, and the results should be known soon.

Reference: 

[2442] Bayer-Carter, J. L., Green P. S., Montine T. J., VanFossen B., Baker L. D., Watson S. G., et al.
(2011).  Diet Intervention and Cerebrospinal Fluid Biomarkers in Amnestic Mild Cognitive Impairment.
Arch Neurol. 68(6), 743 - 752.

Cao, C., Wang, L., Lin, X., Mamcarz, M., Zhang, C., Bai, G., Nong, J., Sussman, S. & Arendash, G.  2011.Caffeine Synergizes with Another Coffee Component to Increase Plasma GCSF: Linkage to Cognitive Benefits in Alzheimer's Mice. Journal of Alzheimer's Disease, 25(2), 323-335.

Source: 

Topics: 

tags development: 

tags lifestyle: 

tags problems: 

Predicting memory loss in healthy older adults

February, 2011

Having the ‘Alzheimer’s gene’ and showing reduced brain activity during a mental task combined to correctly predict future cognitive decline in 80% of healthy elders.

In a study in which 78 healthy elders were given 5 different tests and then tested for cognitive performance 18 months later, two tests combined to correctly predict nearly 80% of those who developed significant cognitive decline. These tests were a blood test to identify presence of the ‘Alzheimer’s gene’ (APOE4), and a 5-minute fMRI imaging scan showing brain activity during mental tasks.

The gene test in itself correctly classified 61.5% of participants (aged 65-88; mean age 73), showing what a strong risk factor this is, but when taken with activity on the fMRI test, the two together correctly classified 78.9% of participants. Age, years of education, gender and family history of dementia were not accurate predictors of future cognitive decline. A smaller hippocampus was also associated with a greater risk of cognitive decline.

These two tests are readily available and not time-consuming, and may be useful in identifying those at risk of MCI and dementia.

Reference: 

Woodard, J.L.  et al. 2010. Prediction of Cognitive Decline in Healthy Older Adults using fMRI. Journal of Alzheimer’s Disease, 21 (3), 871-885.

Source: 

Topics: 

tags development: 

tags problems: 

Pages

Subscribe to RSS - Alzheimer's Disease