Alzheimer's: Diagnosis & Assessment

About these topic collections

I’ve been reporting on memory research for over ten years and these topic pages are simply collections of all the news items I have made on a particular topic. They do not pretend to be in any way exhaustive! I cover far too many areas within memory to come anywhere approaching that. What I aim to do is provide breadth, rather than depth. Outside my own area of cognitive psychology, it is difficult to know how much weight to give to any study (I urge you to read my blog post on what constitutes scientific evidence). That (among other reasons) is why my approach in my news reporting is based predominantly on replication and consistency. It's about the aggregate. So here is the aggregate of those reports I have at one point considered of sufficient interest to discuss. If you know of any research you would like to add to the collection, feel free to write about it in a comment (please provide a reference).

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

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

Early Markers

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. 

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. 

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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).

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.

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.

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.

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.

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.

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.

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.

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

Cognitive tests

Effective new cognitive screening test for detection of Alzheimer's

A new cognitive test for detecting Alzheimer's has been developed, and designed to be suitable for non-specialist use. The TYM ("test your memory") involves 10 tasks including ability to copy a sentence, semantic knowledge, calculation, verbal fluency and recall ability. It has been tested on 540 healthy individuals and 139 patients with diagnosed Alzheimer's or mild cognitive impairment. Healthy controls completed the test in an average time of five minutes and gained an average score of 47 out of 50, compared to 45 for those with mild cognitive impairment, 39 for those with non-Alzheimer dementias and 33 for those with Alzheimer’s. Among controls, the average score was not affected by age until after 70, when it showed a small decline. There were no gender or geographical background differences in performance. The TYM detected 93% of patients with Alzheimer's, compared to only 52% by the widely used mini-mental state examination.

Brown, J. et al. 2009. Self administered cognitive screening test (TYM) for detection of Alzheimer’s disease: cross sectional study. BMJ, 338:b2030, doi: 10.1136/bmj.b2030
Full text available here.

Early identification of dementia increasingly difficult

A study comparing nondemented 70-year-olds examined in the early 1970s with nondemented 70-year-olds examined in the year 2000 has revealed that those who were examined in 2000 scored much higher on non-memory cognitive tests than those examined 30 years earlier — indicating that such tests can no longer be used to predict future dementia. Moreover, although memory loss was a predictor for later development of dementia, it wasn’t conclusive —not everybody with poor memory developed dementia. This was particularly true of the very old (85 year olds).

Sacuiu, S.F. 2009. Prodromal Cognitive Signs of Dementia. Doctoral thesis from Sahlgrenska Academy, University of Gothenburg.

Degree of test variability improves dementia diagnosis

A study of nearly 900 older adults has found that the degree of variability in performance across neuropsychological tests, measured within a person, improved the prediction of dementia above and beyond one's level of performance on each test alone.

Holtzer, R. et al. 2008. Within-Person Across-Neuropsychological Test Variability and Incident Dementia. JAMA, 300(7), 823-830.

New criterion may improve identification of dementia risk in highly educated older adults

A shift in the cutoff point on the widely used cognitive screening tool, the mini-mental state examination (MMSE), is suggested for highly educated older adults, in order to more effectively assess the risk of dementia.

Bryant, S.E. et al. 2008. Detecting Dementia With the Mini-Mental State Examination in Highly Educated Individuals. Archives of Neurology, 65 (7), 963-967.

New 'everyday cognition' scale tracks how older adults function in daily life

A new, carefully validated questionnaire called Everyday Cognition (ECog) has been developed by seven psychologists. The 39-question screening tool is designed to enable mild functional problems in older adults to be quickly and easily identified. The questionnaire needs to be filled out by someone who knows an older adult well, such as a spouse, adult child, or close friend. It looks at everyday function in seven key cognitive domains: memory, language, semantic (factual) knowledge, visuospatial abilities, planning, organization and divided attention. The test has been shown to be sensitive to early changes present in Mild Cognitive Impairment, and unlike other cognitive tests, does not appear to be strongly influenced by education level. The test even differentiated between people diagnosed with mild impairment in memory only and those mildly impaired in several areas.

Farias, S.T. et al. 2008. The Measurement of Everyday Cognition (ECog): Scale Development and Psychometric Properties. Neuropsychology, 22 ( 4), 531-544.

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.

Personality changes may help detect Lewy bodies dementia

Dementia with Lewy bodies is the second most common neurodegenerative cause of dementia. It shares characteristics with both Alzheimer's and Parkinson's disease, but some medications used to treat Alzheimer's patients are potentially dangerous for people with dementia with Lewy bodies. Early diagnosis is therefore important. A new study has found that people with dementia with Lewy bodies often display passive personality changes some time before cognitive deficits are evident, offering hope that a simple personality test might help diagnosis.

Galvin, J.E., Malcom, H., Johnson, D. & Morris, J.C. 2007. Personality traits distinguishing dementia with Lewy bodies from Alzheimer disease. Neurology, 68, 1895-1901.

New dementia screening tool detects early cognitive problems

A new screening tool for dementia — the Saint Louis University Mental Status Examination (SLUMS) — appears to work better in identifying mild cognitive problems in the elderly than the commonly used Mini Mental Status Examination — particularly for the more educated patients. It takes a clinician about seven minutes to administer the SLUMS, which supplements the Mini Mental Status Examination by asking patients to perform tasks such as doing simple math computations, naming animals, recalling facts and drawing the hands on a clock. The SLUMS is available at this link

Tariq, S.H. et al. 2006. Comparison of the Saint Louis University Mental Status Examination and the Mini-Mental State Examination for Detecting Dementia and Mild Neurocognitive Disorder—A Pilot Study. American Journal of Geriatric Psychiatry, 14, 900-910.

More sensitive tests for predicting Alzheimer's

The first study used data from 119 participants in the Longitudinal Aging Study Amsterdam. The memory test scores of those who two years later developed Alzheimer's were compared with the scores of those who stayed healthy. Three tests were very good at predicting who would later develop Alzheimer's: a Paired-Associate Learning Test, which cued participants to recall five semantically related and five semantically unrelated pairs of words; a Perceptual Identification Task, which measured how fast participants read aloud words briefly presented on a computer screen; a Visual Association Test, which cued participants to recall six line drawings of common objects that had been presented earlier in an illogical interaction with another object or cue. On the word-pair memory test, people destined to develop Alzheimer's disease didn't do any better when words were related than when they weren't, suggesting they’d already lost deep semantic knowledge. On the word-reading test, word repetition didn't help high-risk participants to perform better, a sign that implicit learning was impaired. The popular Mini Mental Status Exam (MMSE), a test mainly sensitive to episodic memory, was not as good a predictor.
In the second study, a dichotic listening task, which measures how well people process information when they hear one thing in the left ear and another in the right ear, was found to also be predictive of Alzheimer’s, confirming that people have problems with selective attention very early in the disease.

Spaan, P.E.J., Raaijmakers, J.G.W. & Jonker, C. 2005. Early Assessment of Dementia: The Contribution of Different Memory Components. Neuropsychology, 19 (5).

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).

Early warning signs of Alzheimer's show up years before official diagnosis

A meta-analysis of 47 studies of Alzheimer's disease has revealed that people can show early warning signs across several cognitive domains years before they are officially diagnosed, confirming that Alzheimer's causes general deterioration and tends to follow a stable preclinical stage with a sharp drop in function. People at the preclinical stage showed marked preclinical deficits in global cognitive ability, episodic memory, perceptual speed, and executive functioning; along with somewhat smaller deficits in verbal ability, visuospatial skill, and attention. There was no preclinical impairment in primary memory. There is no clear qualitative difference between the normal 75-year old and a preclinical Alzheimer’s sufferer; instead it seems that the normal elderly person, the preclinical Alzheimer’s person, and the early clinical Alzheimer’s patient represent three instances on a continuum of cognitive capabilities.

Bäckman, L., Jones, S., Berger, A-K. & Laukka, E.J. 2005. Cognitive impairment in preclinical Alzheimer's disease: A meta-analysis. Neuropsychology, 19 (4).

More sensitive test norms better predict who might develop Alzheimer's disease

Early diagnosis of Alzheimer's is becoming more important with new medical and psychological interventions that can slow (but not stop) the course of the disease. Given this, it is suggested that more sensitive testing may be necessary for highly intelligent people, who, on average, show clinical signs of Alzheimer's later than the general population. Once they show such signs, they decline much faster. A study of 42 older people with IQ's of 120 or more, used two different test norms to forecast problems: the standard norm, derived from a large cross-section of the population, or an adjusted high-IQ norm that measured changes against the individual's higher ability level. The raised cutoffs predicted that 11 of the 42 individuals were at risk for future decline – compared with standard cutoffs, which indicated they were normal. True to the former prediction, three and a half years later, nine of those 11 people had declined. Six of those went on to develop mild cognitive impairment (MCI), a transitional illness from normal aging to a dementia (of which one type is Alzheimer's). Five of these individuals have since received a diagnosis of Alzheimer's disease, two years after this study was submitted. It is also suggested that, at the other end of the scale, those with below-average intelligence have the potential for being misdiagnosed as 'demented' when they are not, and the norms should be adjusted downwards accordingly.

Rentz, D.M., Huh, T.J., Faust, R.R., Budson, A.E., Scinto, L.F.M., Sperling, R.A. & Daffner, K.R. 2004. Use of IQ-Adjusted Norms to Predict Progressive Cognitive Decline in Highly Intelligent Older Individuals. Neuropsychology, 18 (1).

New method of distinguishing Alzheimer's from Lewy body dementia

Looking at specific changes in alertness and cognition may provide a reliable method for distinguishing Alzheimer's from dementia with Lewy bodies (DLB) and normal aging. Four characteristics significantly distinguished patients with DLB from persons with Alzheimer’s and normal elderly controls: daytime drowsiness and lethargy despite getting enough sleep the night before; falling asleep two or more hours during the day; staring into space for long periods and episodes of disorganized speech. "For the normal elderly control group, one or two of these behaviors was found in only 11 percent of the group. For the patients with AD, one or two of these behaviors were not uncommon, but over 63% of the patients with DLB had three or four of these behaviors.” DLB accounts for as much as 20 to 35% of the dementia seen in the United States.

Ferman, T.J., Smith, G.E., Boeve, B.F., Ivnik, R.J., Petersen, R.C., Knopman, D., Graff-Radford, N., Parisi, J. & Dickson, D.W. 2004. DLB fluctuations: Specific features that reliably differentiate DLB from AD and normal aging. Neurology, 62,181-187.

Brief telephone questionnaire screens for early signs of dementia

Researchers have developed a brief telephonic questionnaire that helps distinguish between persons with early signs of dementia and persons with normal cognitive function. The questionnaire provides a way to reach out to persons with dementia whose impairment otherwise may go undetected until substantial cognitive deterioration has occurred. The questionnaire consists of a test of delayed recall and 2 questions that ask whether the person needs help with remembering to take medications or with planning a trip for errands. It is estimated that of 100 people who score positive on this test, 42 will actually have cognitive impairment. In other words, this does not provide a diagnosis of Alzheimer’s, but provides evidence that further evaluation is required. The rate of false positives compares favorably to other types of screening tests. A further study is underway to confirm the validity and reliability of the test.

Fillit, H. et al. 2003. A Brief Telephonic Instrument to Screen for Cognitive Impairment in a Managed Care Population. Journal of Clinical Outcomes Management, , 419-429.

Verbal memory tests predict dementia

The Longitudinal Aging Study Amsterdam tested the memories of a large group of elderly people on two occasions, two years apart. Performance on the memory tests was then compared between those who developed dementia during those two years and those who did not. It was found that those who later were found to have dementia were scarcely better at remembering word pairs clearly linked in meaning (for example, pipe - cigar) than word pairs without such a link (for example nail - butter), on the first test. (those who not have dementia two years later did, as is usual, benefit from such a link in meaning). In addition, those in the early stage of dementia did not benefit from the repeated presentation of words. The results suggest a means by which elderly people in the early stages of dementia can be identified, which is important because the drugs used to inhibit dementia only work in the earliest stages of the disease.

This was revealed in doctoral research by the neuropsychologist Pauline Spaan from the University of Amsterdam.

Verbal memory test best indicator of who will have Alzheimer's disease

A meta-analysis of 31 studies involving a total of 1,144 Alzheimer's patients and 6,046 healthy controls, supports the use of the California Verbal Learning Test in predicting future Alzheimer’s type dementia. Long delay recall and percent recall were the best predictors, with executive function type measures also being predictive but less so than both the long and short delay memory tests. Changes in the hippocampus were the best volumetric or neuroimaging measure but in general volumetric measures were less sensitive to preclinical stages of the dementia than were the neuropsychological tests. It should be noted that a decline in various types of memory, especially verbal episodic memory, is also observable in normal elderly; the crucial factor in determining a pre-dementia state lies in the size of the memory deficit.

Zakzanis, K.K. & Boulos, M.I. 2002. A Meta-Analysis of ApoE Genotype and Neuropsychologic and Neuroanatomic Changes in Preclinical Alzheimer's Disease. Presentation at the 110th Annual Convention of the American Psychological Association (APA) on August 25.

Early diagnosis of Alzheimer's

An analysis of data from 40 participants enrolled in a long-term study at the UCSD Alzheimer’s Disease Research Center (ADRC) found that "paper-and-pencil" cognitive skills tests administered to normal subjects averaging 75 years of age contained early signs of cognitive decline in those subjects who later developed Alzheimer’s disease. All participants were symptom-free when they took the test. The differences were quite subtle - only some performance measures were affected.

Jacobson MW, Delis DC, Bondi MW, Salmon DP. Do neuropsychological tests detect preclinical Alzheimer's disease: Individual-test versus cognitive-discrepancy score analyses. Neuropsychology. 2002;16(2):132–139.