Alzheimer's: Diagnosis & Assessment

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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

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.

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.

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.

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.

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.

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

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.

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.

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.

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."

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

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


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.

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.

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.

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.
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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.

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.

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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