early markers

Dementia sufferers become unaware of memory problems years before diagnosis

  • A large study found that people who developed dementia started to lose awareness of memory problems some 2½ years before dementia onset.
  • This loss of awareness was associated with three examples of neuropathology, including tau tangles and brain infarcts.

A ten-year study involving 2,092 older adults (average age 76) has found that people tended to lose awareness of memory problems two to three years before the onset of dementia.

Being unaware of your own memory problems is common in dementia, but previous research has focused on those already diagnosed with dementia. In this study, participants had no cognitive impairment at the beginning of the study.

Overall, subjective memory ratings taken annually were modestly correlated with performance (only modestly — people tend not to be that great at accurately assessing their own memory!), and this awareness was stable with age. However, in the subset of those who developed dementia (239 participants; 11%), this awareness started to deteriorate an average of 2.6 years before dementia was diagnosed (after which it dropped rapidly).

In a subset of those who died and had their brains examined (385 participants), a decline in memory awareness was associated with three pathologies:

  • tau tangles
  • gross cerebral infarcts
  • transactive response DNA-binding protein 43 pathology (TDP-43 is a protein involved in transcription, the first step in producing proteins from genes; mutations in the gene that produces TDP-43 have been linked to frontotemporal dementia and amyotrophic lateral sclerosis (ALS)).

There was no decline in memory awareness in those who didn't show any of these pathologies.

Those who were older at the beginning of the study were more likely to retain memory awareness longer, perhaps because they were more alert to memory problems.

http://www.theguardian.com/society/2015/aug/27/dementia-sufferers-start-losing-memory-up-to-three-years-before-condition-develops-us-study

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Early Markers

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

Measuring brain atrophy in patients with mild cognitive impairment

A study involving 269 patients with mild cognitive impairment provides evidence that a fully automated procedure called Volumetric MRI (that can be done in a clinical setting) can accurately and quickly measure parts of the medial temporal lobe and compare them to expected size. It also found that not only atrophy in the hippocampus but also the amygdala is associated with a greater risk of conversion to Alzheimer’s.

Kovacevic, S. et al. 2009. High-throughput, Fully Automated Volumetry for Prediction of MMSE and CDR Decline in Mild Cognitive Impairment. Alzheimer Disease & Associated Disorders, 23 (2), 139-145.

http://www.eurekalert.org/pub_releases/2009-06/uoc--mba061609.php

Cerebrospinal fluid shows Alzheimer's disease deterioration much earlier

A study involving 60 patients with subjective cognitive impairment, 37 patients with non-amnestic mild cognitive impairment, and 71 with amnestic mild cognitive impairment, has found that 52% of those with SCI, 68% of those with naMCI, and 79% of those with aMCI showed decreased concentrations of Aβ42 and increased concentrations of tau protein in the cerebrospinal fluid. The findings confirm the use of biomarkers in the CSF for very early diagnosis

Visser, P.J. et al. 2009. Prevalence and prognostic value of CSF markers of Alzheimer's disease pathology in patients with subjective cognitive impairment and mild cognitive impairment in the DESCRIPA study: a prospective, case-control study. The Lancet Neurology, 8 (7), 619–627.

http://www.eurekalert.org/pub_releases/2009-06/uog-cfs061809.php

Weight loss in old age may signal dementia

An 8-year study involving over 1,800 older Japanese Americans has found that those with lower body mass index (BMI) scores at the beginning of the study were 79% more likely to develop dementia than those with higher scores. In addition, those who lost weight over the study period at a faster rate were nearly three times more likely to develop dementia than those who lost weight more slowly, and this association was stronger in those who were overweight or obese to start.

Hughes, T.F. et al. 2009. Association between late-life body mass index and dementia: The Kame Project. Neurology, 72, 1741-1746.

http://www.eurekalert.org/pub_releases/2009-05/aaon-wli051209.php

New tool can help predict Alzheimer's risks

A new 15-point scale of risk factors for Alzheimer's has been developed and correctly classified 88% of the 3,375 older adults in the study. 56% of those with scores of 8 or higher developed dementia within six years, compared to 23% with moderate scores and just 4% with low scores. The risk factors include poor cognitive test performance (2–4 points), body mass index below 18.5 (2 points), older age (1–2 points), history of bypass surgery (1 point), slow physical performance (1 point), and lack of alcohol consumption (1 point), presence of the ApoE4 gene (1 point), MRI findings of white matter disease (1 point) or ventricular enlargement (1 point), internal carotid artery thickening on ultrasound (1 point).

Barnes, D.E. et al. 2009. Predicting risk of dementia in older adults. The late-life dementia risk index. Neurology, published May 13, 2009.

http://uk.reuters.com/article/scienceNews/idUKTRE54C77920090513

Eye tracking test detects mild cognitive impairment

A test first developed for use with nonhuman primates is now being used to detect mild cognitive impairment (MCI) in humans. The infrared eye-tracking test involves showing one image and then another after a 2-second delay, and then repeating the test 2 minutes later. Those without cognitive impairment spend most of their time looking at the new image, but it was found that those with MCI spent less time looking at the new picture, presumably because they have less memory of seeing the original image before. Those with Alzheimer's disease look at both images equally. It’s hoped that this test may allow dementia to be spotted much earlier.

Crutcher, M.D. et al. 2009. Eye Tracking During a Visual Paired Comparison Task as a Predictor of Early Dementia. American Journal of Alzheimer's Disease and Other Dementias, Published online February 26 2009.

http://www.eurekalert.org/pub_releases/2009-04/eu-yru041509.php

Shrinking in hippocampus precedes Alzheimer's

An imaging study of 64 Alzheimer's patients, 44 people with mild cognitive impairment, and 34 people with no memory or thinking problems, has found that those with smaller hippocampal volumes and higher rates of shrinkage were two to four times as likely to develop dementia over the study period (average 18 months) as those with larger volumes and a slower rate of atrophy. During that time, 23 of the people with MCI developed Alzheimer's, and three of the healthy participants.

Henneman, W.J.P. et al. 2009. Hippocampal atrophy rates in Alzheimer disease: Added value over whole brain volume measures. Neurology, 72, 999-1007.

http://www.eurekalert.org/pub_releases/2009-03/aaon-sih031009.php

Brain atrophy pattern in some MCI patients predicts Alzheimer's

A study of 84 patients with mild Alzheimer's, 175 patients with MCI and 139 healthy controls has revealed a pattern of regional brain atrophy in patients with MCI that indicates a greater likelihood of progression to Alzheimer's. Brain scans results showed widespread cortical atrophy in some patients with MCI, most importantly, atrophy in parts of the medial and lateral temporal lobes and in the frontal lobes — a pattern also present in the patients with mild Alzheimer's disease. Those exhibiting such atrophy declined significantly over a year and were more likely to progress to a probable diagnosis of Alzheimer's. MCI patients without that pattern of atrophy remained stable after a year. It should be noted that such atrophy affects not only memory, but also planning, organization, problem solving and language.

McEvoy, L.K. et al. 2009. Alzheimer Disease: Quantitative Structural Neuroimaging for Detection and Prediction of Clinical and Structural Changes in Mild Cognitive Impairment. Radiology, Published online February 6.

http://www.eurekalert.org/pub_releases/2009-02/rson-msb020309.php

Blood test could give early warning of Alzheimer’s risk

A simple blood test may enable us to predict whether someone will soon develop Alzheimer’s, allowing them to take action that might delay its development. In the study of 1,125 elderly persons without dementia, 104 (9.2%) of the participants developed Alzheimer’s over 4.6 years of follow-up. Higher blood levels of amyloid-beta 42 peptide at the onset of the study were associated with a threefold increased risk of Alzheimer’s, with the levels significantly declining at the onset of Alzheimer’s (perhaps because it has started accumulating in the brain).

Schupf, N. et al. 2008. Peripheral Aβ subspecies as risk biomarkers of Alzheimer's disease. PNAS, 105 (37), 14052-14057.

http://www.eurekalert.org/pub_releases/2008-09/cumc-rst090808.php

Women lose weight at least a decade before developing dementia

Another study has come out associating weight loss with later dementia. The study found that women who later developed dementia started losing weight up to 20 years before the disease was diagnosed. On average, those with dementia weighed 12 pounds less than those without the disease the year the disease was diagnosed. The association may be related to a loss in the sense of smell, and increasing apathy. The association was not found with men, probably because older men were less likely to be preparing their own food. The findings do of course conflict with others suggesting that obesity in middle-age may be a risk factor for dementia. More research is needed to clarify the situation.

Knopman, D.S. et al. 2007. Incident dementia in women is preceded by weight loss by at least a decade. Neurology, 69, 739-746.

http://www.eurekalert.org/pub_releases/2007-08/aaon-wlw081407.php

Simple test predicts 6-year risk of dementia

A 14-point index combining medical history, cognitive testing, and physical examination — a simple test that can be given by any physician — has been found to predict a person’s risk for developing dementia within six years with 87% accuracy. As measured by the index, the risk factors for developing dementia are an age of 70 or older, poor scores on two simple cognitive tests, slow physical functioning on everyday tasks such as buttoning a shirt or walking 15 feet, a history of coronary artery bypass surgery, a body mass index of less than 18, and current non-consumption of alcohol. The results do need to be validated in other populations — for example, they have not yet been tested on Hispanics or Asian-Americans.

The tests were described in a presentation at the 2007 International Conference on Prevention of Dementia, in Washington, DC.

http://www.eurekalert.org/pub_releases/2007-06/uoc--stp060707.php

Brain structure changes years before memory loss begins

Another study provides evidence that people who develop dementia or Alzheimer's disease experience brain structure changes years before any signs of memory loss begin. The study involved 136 people over the age of 65 who were considered cognitively normal at the beginning of the five-year study. By the end of the study, 23 people had developed MCI, and nine of the 23 went on to be diagnosed with Alzheimer's disease. Compared to the group that didn't develop memory problems, the 23 who developed MCI or Alzheimer's disease had less gray matter in key memory processing areas (specifically, anteromedial temporal lobes and left angular gyrus) even at the beginning of the study when they were cognitively normal. They also had lower cognitive test scores, though these scores were still within normal range.

Smith, C.D. et al. 2007. Brain structural alterations before mild cognitive impairment. Neurology, 68, 1268-1273.

http://www.eurekalert.org/pub_releases/2007-04/aaon-bsc041007.php

Memory complaints early warning for Alzheimer's

A post-mortem study of 90 older adults from the Rush Memory and Aging Project found that those who had yet to have any clinical symptoms of Alzheimer's disease still showed a strong link between their self-reported memory complaints and brain pathology associated with Alzheimer's disease.

Barnes, L.L., Schneider, J.A., Boyle, P.A., Bienias, J.L. & Bennett, D.A. 2006. Memory complaints are related to Alzheimer disease pathology in older persons. Neurology, 67, 1581-1585.

http://www.eurekalert.org/pub_releases/2006-11/rumc-cam113006.php

New early diagnostic test trialed

A mouse study has used a laser scan of the eyes to accurately diagnose Alzheimer's well before the disease was evident in the brain. The study follows on from earlier research revealing that beta-amyloid protein is evident in the eyes of Alzheimer’s patients. The test, which is a very quick and simple procedure, is now in the first stage of experimental trials in people.

The findings were announced at the annual meeting of the Optical Society of America.

http://www.sciencentral.com/articles/view.htm3?article_id=218392859

Link between increased weight-loss rate and dementia

Confirming earlier indications, a long-term study of the elderly has revealed that their average rate of weight loss doubles (from 0.6 pounds per year to 1.2 pounds per year) in the year before symptoms of Alzheimer's-type dementia first become detectable. The finding may be useful as one of several early biomarkers. The study analyzed data on 449 seniors, of whom 125 were eventually diagnosed with mild dementia. Interestingly, at the beginning of the study, this group weighed about 8lb less on average than the other participants, although the two groups lost weight at the same rate for four to five years, before weight loss increased in the group that would eventually be diagnosed with mild dementia. It is not yet known why there should be this connection between weight loss and dementia.

Johnson, D.K., Wilkins, C.H. & Morris, J.C. 2006. Accelerated weight loss in Alzheimer's disease precedes diagnosis. Archives of Neurology, 63, 1312-1317.

http://www.eurekalert.org/pub_releases/2006-09/wuso-bdf090806.php

Weight Loss Precedes Dementia Diagnosis In Women

A study has come out finding that, in women, declining weight precedes dementia by many years.
The retrospective study analyzed the medical records of 560 patients diagnosed with the onset of dementia between 1990 and 1994. The patients were matched with 560 controls. Among the women, average weight increased slightly over the preceding 30 years for the control group, but drifted downwards over the 30 years for those who developed dementia. The researchers suggest that changes in the brain interfered somehow with maintenance of body weight. The trend was not observed in men.

Findings were presented July 16 at the Alzheimer's Association International Conference on Alzheimer's Disease and Related Disorders in Madrid, Spain.

http://www.sciencedaily.com/releases/2006/07/060716090233.htm

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

Alzheimer's disease onset tied to lapses in attention

A new finding may lead to another tool to detect Alzheimer’s early, and also offers support for the idea that breakdowns in attention may be at the heart of many of the memory problems experienced by Alzheimer’s sufferers. The study, involving 94 older adults (average age mid-70s) who were either healthy controls or in the early stages of Alzheimer’s, found those in the early stages of Alzheimer's disease had greater difficulty shifting attention back and forth between competing sources of information in a dichotic listening task. The finding may also explain why early-stage patients start to struggle with everyday tasks that call for processing a lot of information, such as driving. Prior research has found that performance on dichotic listening predicts accident rates in commercial bus drivers.
[note: this study was briefly reported on in September, but only mentioning its use as an early test]

Duchek, J.M. & Balota, D.A. 2005. Failure to Control Prepotent Pathways in Early Stage Dementia of the Alzheimer's Type: Evidence from Dichotic Listening. Neuropsychology, 19 (5).

http://www.eurekalert.org/pub_releases/2005-11/wuis-ado110905.php

A new analysis of a standard brain test may help predict dementia

A new study gives promise of early diagnosis of Alzheimer’s. A computer analysis of an EEG (electroencephalograph) test was almost 95% accurate in predicting those people in their 60s and 70s who would develop dementia over the next 7 to 10 years. There were several distinctive features in the brain waves of those who would later show cognitive impairment. The study now needs to be replicated with a larger sample.

Prichep, L.S., John, E.R., Ferris, S.H., Rausch, L., Fang, Z., Cancro, R., Torossian, C. & Reisberg, B. 2005. Prediction of longitudinal cognitive decline in normal elderly with subjective complaints using electrophysiological imaging. Neurobiology of Aging, In Press, Corrected Proof, Available online 6 October 2005.

http://www.eurekalert.org/pub_releases/2005-10/dumc-ana100505.php

Biosensor reveals new information about ADDLs

A new method using nanoscale optical biosensors allows researchers to detect and estimate the size and structure of ADDLs in cerebrospinal fluid. It’s believed that only ADDLs of a certain size cause problems for neurons in the early stages of Alzheimer’s disease. It is hoped that eventually this technology will help us diagnose Alzheimer’s accurately in living people, and aid our understanding of how ADDLs are involved in Alzheimer’s.

Haes, A.J., van Duyne, R.P., Klein, W.L. & Chang, L. 2005. The paper, ANYL 396, was presented at 9:00 a.m., Wednesday, Aug. 31, during the "New Frontiers in Ultrasensitive Analysis: Nanobiotech, Single Molecule Detection, and Single Cell Analysis" symposium.

http://www.eurekalert.org/pub_releases/2005-08/acs-brn081905.php

Protein studies may lead to new Alzheimer's test

A new technique has identified more than 400 proteins in human spinal fluid — 40 times more than previously known. On average, one of every five proteins identified was substantially changed in patients with Alzheimer's disease compared to older people without neurological disease. The finding may lead to a new test for diagnosing Alzheimer’s.

Zhang, J., Goodlett, D.R., Quinn, J.F., Peskind, E., Kaye, J.A., Zhou, Y., Pan, C., Yi, E., Eng, J., Wang, Q., Aebersold, R.H. & Montine, T.J. 2005. Quantitative proteomics of cerebrospinal fluid from patients with Alzheimer disease Journal of Alzheimer's Disease, 7(2), 125-133.

http://www.eurekalert.org/pub_releases/2005-04/uow-psm041905.php

New test is first step in early detection of Alzheimer's disease

A new technique called bio-bar-code amplification (BCA) technology has been found to be able to detect miniscule amounts of ADDL in human cerebrospinal fluid, bringing promise of an early diagnostic test for Alzheimer’s. The researchers hope to develop the technology so that the test could be done using a blood or urine sample instead of cerebrospinal fluid, which is more difficult to obtain.

Georganopoulou, D.G., Chang, L., Nam, J.M., Thaxton, C.S., Mufson, E.J., Klein, W.L. & Mirkin, C.A. 2005. Nanoparticle-based detection in cerebral spinal fluid of a soluble pathogenic biomarker for Alzheimer's disease. Proceedings of the National Academy of Sciences, 102, 2273-2276.

http://www.eurekalert.org/pub_releases/2005-01/nu-nti012805.php
http://www.eurekalert.org/pub_releases/2005-01/nsf-nds012805.php

Smell test to help early diagnosis

One of the first types of memory affected by Alzheimer’s is olfactory memory – our database of smells. Researchers have now developed a simple scratch-and-sniff test that may enable Alzheimer’s to be detected in its very early stages. On the basis of a five-year study tracking 150 people with mild memory loss and Alzheimer's disease and 63 healthy adults, 10 specific odors proved to be the best predictors for Alzheimer's Disease: strawberry, smoke, soap, menthol, clove, pineapple, natural gas, lilac, lemon and leather. The test takes only 5 to 8 minutes, and seems to have comparable predictive ability as detailed memory and neuropsychological testing.

The findings were presented at the 2004 meeting of the American College of Neuropsychopharmacology.

http://www.eurekalert.org/pub_releases/2004-12/g-sfl121004.php

Antibody detection in Alzheimer's may improve diagnosis, treatment

A study has found that people with Alzheimer’s disease have three to four times more antibodies to RAGE (receptor for advanced glycation end products) and beta amyloid — both major players in Alzheimer’s — than their healthy counterparts. The ability to measure these specific antibody levels could lead to a method for very early diagnosis. The finding may also point to a new treatment approach. The study supports the theory that autoimmunity and resulting inflammation play a big role in Alzheimer’s.

Mruthinti, S., Buccafusco, J.J., Hill, W.D., Waller, J.L., Jackson, T.W., Zamrini, E.Y. & Schade, R.F. 2004. Autoimmunity in Alzheimer’s disease: increased levels of circulating IgGs binding Ab and RAGE peptides. Neurobiology of Aging, 25 (8), 1023-1032.

http://www.eurekalert.org/pub_releases/2004-06/mcog-adi060204.php

Loss of smell linked to key protein in Alzheimer's disease

Loss of smell is one of the first clinical signs of Alzheimer’s and Parkinson’s disease. Now researchers have linked smell loss in genetically altered mice with excessive levels of a key protein associated with these diseases. If smell function declines as the levels of this protein increase in brain regions associated with smelling, the research could validate the use of smell tests for diagnosing Alzheimer's disease.

Macknin, J.B., Higuchi, M., Lee, V.M-Y., Trojanowski, J.Q. & Doty, R.L. 2004. Olfactory dysfunction occurs in transgenic mice overexpressing human t protein. Brain Research, 1000, 174-178.

http://www.eurekalert.org/pub_releases/2004-03/uopm-los030304.php

Diagnosing Alzheimer's disease may soon be possible earlier

Diagnosing Alzheimer's disease is problematic because we have had no definitive tests for the disease (other than after death, by examining the brain). Recent research suggests that two markers in cerebrospinal fluid may indicate the presence of Alzheimers. This is exciting not only because it would make diagnosis easier, but because it might enable us to diagnose it much earlier. However, to be clinically useful, they will need to develop tests that use more readily available fluids (such as urine).

Praticò, D., Clark, C. M., Lee, V. M.-Y., Trojanowski, J. Q., Rokach, J., & FitzGerald, G. A. (2000). Increased 8,12-iso-iPF2α-VI in Alzheimer’s disease: Correlation of a noninvasive index of lipid peroxidation with disease severity. Annals of Neurology, 48(5), 809–812. doi:10.1002/1531-8249(200011)48:5<809::AID-ANA19>3.0.CO;2-9

Gene marker for late-onset Alzheimer's disease nearer discovery

Three independent studies have linked late-onset Alzheimer's disease to a locus on chromosome 10 that affects processing of the amyloid-beta protein, a peptide important in the formation of the characteristic amyloid plaques found in the brains of people with Alzheimer's disease. Researchers are optimistic the precise gene will be found in the next few years.
Before this, a particular form of the apolipoprotein E (APOE) gene on chromosome 19 has been the only widely recognized genetic risk factor in late onset Alzheimer’s disease. There is also some evidence of a risk factor gene on a region of chromosome 12.
So far, three genes have been found that are linked to the rare early-onset Alzheimer's (when symptoms appear before age 60).

Bertram, L., Blacker, D., Mullin, K., Keeney, D., Jones, J., Basu, S., … Tanzi, R. E. (2000). Evidence for Genetic Linkage of Alzheimer’s Disease to Chromosome 10q. Science, 290(5500), 2302–2303. doi:10.1126/science.290.5500.2302

Ertekin-Taner, N., Graff-Radford, N., Younkin, L. H., Eckman, C., Baker, M., Adamson, J., … Younkin, S. G. (2000). Linkage of Plasma Aβ42 to a Quantitative Locus on Chromosome 10 in Late-Onset Alzheimer’s Disease Pedigrees. Science, 290(5500), 2303–2304. doi:10.1126/science.290.5500.2303

Myers, A., Holmans, P., Marshall, H., Kwon, J., Meyer, D., Ramic, D., … Goate, A. M. (2000). Susceptibility Locus for Alzheimer’s Disease on Chromosome 10. Science, 290(5500), 2304–2305. doi:10.1126/science.290.5500.2304

http://www.eurekalert.org/pub_releases/2000-12/MCJ-Loc1-2112100.php

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Brains grow differently in babies with Alzheimer’s gene

A brain imaging study of 162 healthy babies (2-25 months) has found that those who carried the ApoE4 gene (60 of the 162) tended to have increased brain growth in areas in the

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One Alzheimer's risk gene may begin to affect brains from childhood

A gene linked to Alzheimer's has been linked to brain changes in childhood. This gene, SORL1, has two connections to Alzheimer’s: it carries the code for the sortilin-like receptor, which is involved in recycling some molecules before they develop into amyloid-beta; it is also involved in lipid metabolism, putting it at the heart of the vascular risk pathway.

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Gene variation associated with brain atrophy in MCI

Analysis of data from 237 patients with mild cognitive impairment (mean age 79.9) has found that, compared to those carrying the ‘normal’ ApoE3 gene (the most common variant of the ApoE gene), the ApoE4 carriers showed markedly greater rates of shrinkage in 13 of 15 brain regions thought to be key components of the brain networks disrupted in Alzheimer’s.

http://www.eurekalert.org/pub_releases/2014-01/rson-gva010714.php

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Memory complaints linked to higher risk of MCI & dementia

Data from 6257 older adults (aged 55-90) evaluated from 2005-2012 has revealed that concerns about memory should be taken seriously, with subjective complaints associated with a doubled risk of developing mild cognitive impairment or dementia, and subjective complaints supported by a loved one being associated with a fourfold risk. Complaints by a loved one alone were also associated with a doubled risk.

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New biomarker shows Alzheimer's disease long before symptoms

Analysis of mitochondrial DNA (mtDNA) in the cerebrospinal fluid has found that both symptomatic Alzheimer’s patients and asymptomatic patients at risk of Alzheimer’s showed a significant decrease in levels of circulating cell-free mtDNA in the CSF.

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Brainwaves indicate the presence and severity of Alzheimer's

Comparison of the EEGs of 27 healthy older adults, 27 individuals with mild Alzheimer's and 22 individuals with moderate cases of Alzheimer’s, has found statistically significant differences across the three groups, using an algorithm that dissects brain waves of varying frequencies.

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