I have found the following publications to be comprehensive enough on the subject:
McKhann, Guy, Drachman, David, Folstein, Marshall, Katzman, Robert, et al. (1984) ‘Clinical diagnosis of Alzheimer’s disease: Report of the NINCDS-ADRDA Work Group* under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease’, Neurology, 34(7), p. 939.
Murayama, Shigeo and Saito, Yuko (2004) ‘Neuropathological diagnostic criteria for Alzheimer’s disease’, Neuropathology, 24(3), pp. 254–260.
Knopman, D. S., DeKosky, S. T., Cummings, J. L., Chui, H., et al. (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), pp. 1143–1153.
(More information can also be found at http://www.nice.org.uk/ -- but that would be more focused on the UK)
I would also add that there are new imaging agents such as the 18F-labeled florbetapir that was just recently FDA approved back in May 2012. This compound bind to amyloid-beta plaques and is used as a PET imaging agent. Currently, there isn't anything that exactly diagnoses someone with having AD, other than a post-mortem autopsy. There are many different imaging agents that use PET and SPECT isotopes. I would also encourage you to look for more recent publications such as 2010 and more recent. This area of research has changed very quickly over the years.
Cheers!
Also would like to add the neuropathological criteria, which are the gold standard:
Montine TJ, Phelps CH, Beach TG, Bigio EH, Cairns NJ, Dickson DW, et al. National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease: a practical approach. Acta neuropathologica. 2012 Jan;123(1):1-11.
As we know that clinical criteria, especially in the case of FTD can lead to misleading results (Toledo JB, Brettschneider J, Grossman M, Arnold SE, Hu WT, Xie SX, et al. CSF biomarkers cutoffs: the importance of coincident neuropathological diseases. Acta neuropathologica. 2012 Apr 22.)
I am sending to your attention updated information on the matter.
Telomere Length Shortening and Alzheimer Disease—A Mendelian Randomization StudyYiqiang Zhan, MD1; Ci Song, PhD1; Robert Karlsson, PhD1; Annika Tillander, PhD1; Chandra A. Reynolds, PhD2; Nancy L. Pedersen, PhD1; Sara Hägg, PhD1
[+-] Author Affiliations 1Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
2Department of Psychology, University of California, Riverside
JAMA Neurol. 2015;72(10):1202-1203. doi:10.1001/jamaneurol.2015.1513.
THe latest tests for early diagnosis
Two studies explore potential new blood tests for Alzheimer's disease
Published on November 10, 2015 at 1:25 AM · No Comments
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There is increasing evidence that the brain changes of Alzheimer's disease begin decades before memory and thinking problems occur, prompting the need for better methods of early detection for this progressive, fatal brain disease. Consequently, there is a growing school of thought that the most effective future Alzheimer's drug therapies will be administered to those who are at high risk of the disease before cognitive symptoms appear.
To bolster development of a simple, inexpensive, noninvasive test that can detect the risk of Alzheimer's disease, the Alzheimer's Association, the Crnic Institute for Down Syndrome, and the Global Down Syndrome Foundation ("Global") are funding two studies of potential new blood tests for Alzheimer's, including one that uses just one drop of blood:
One study will evaluate whether examining changes in ribonucleic acid (RNA) found in one drop of blood can accurately identify people who will develop Alzheimer's in individuals with Down syndrome who are at high risk for the disease. The study is being led by Marwan Sabbagh, M.D., Director of the Alzheimer's and Memory Disorders Division at the Barrow Neurological Institute in Phoenix, and Matt Huentelman, Ph.D., Associate Professor in the Neurogenomics Division Unit at the Translational Genomics Research Institute in Phoenix.
Another study will test whether a specific set of blood proteins can identify who is at risk for developing Alzheimer's in a unique, high -risk population, individuals with Down syndrome. The study is being led by Nicole Schupf, Ph.D., M.P.H., Dr.Ph.H., Professor of Epidemiology at Columbia University Medical Center in New York City, and Sid O'Bryant, Ph.D., Director of the Center for Alzheimer's and Neurodegenerative Disease Research at the University of North Texas Health Science Center in Fort Worth.
"Prevention of Alzheimer's dementia may be more effective and easily achieved than attempting to treat the disease once symptoms already exist and irreversible damage to the brain has already occurred," says Dean Hartley, Ph.D., Director of Science Initiatives for the Alzheimer's Association. "For this approach to be successful, we must be able to simply and accurately assess risk early in the disease process. The Alzheimer's Association and the Global Down Syndrome Foundation hope that these two exciting projects drive that effort forward."
"Autopsy is still the only way to definitively diagnose Alzheimer's disease," said Michelle Sie Whitten, President and CEO of the Global Down Syndrome Foundation. "If these researchers are successful we will be one step closer to catching Alzheimer's in its early stages and hopefully then be able to treat people with the disease earlier and actually prevent dementia from occurring, when new treatment options become available."
The grant awards are part of $1 million in new funding for Down syndrome-related Alzheimer's disease research. Four projects will receive $250,000 each through the joint funding effort.
Nearly all adults with Down syndrome begin developing the brain changes of Alzheimer's in their 30s. By age 55 or 60, it is estimated 55-70% will develop dementia. Because people with Down syndrome are at high risk for Alzheimer's, answers to important research questions about the disease may be developed more quickly in this population than by studying people with sporadic, late-onset Alzheimer's, where symptoms appear most often after age 65 - and in many cases not until the 70s or 80s.
"It used to be common for individuals with Down syndrome to die in their 30s, but because of medical advances they are now regularly living into their 50s and 60s. The irony is that they are now facing dementia due to Alzheimer's disease," says Huntington Potter, Ph.D., Director of Alzheimer's Research at the Crnic Institute for Down Syndrome and a Professor of Neurology at the University of Colorado, Denver. "At the same time, questions about Alzheimer's may be answered more quickly by studying this disease in people with Down syndrome because of their high risk for Alzheimer's and the earlier onset. Through this approach, people with Down syndrome have the opportunity to further our understanding of Alzheimer's disease and we have the opportunity to help this population."
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Scientists are not sure exactly why individuals with Down syndrome are at high risk for Alzheimer's disease but past research shows that a gene on chromosome 21 codes for the amyloid precursor protein (APP) that gets cut into fragments that accumulate into the hallmark amyloid brain plaques of Alzheimer's. People with Down syndrome are born with an extra copy of chromosome 21.
"The hope for our study is that the identification of RNA biomarkers for Alzheimer's could be used in a non-invasive blood test that requires just one drop of blood to assess an individual's risk of developing the disease, similar to the way a person with diabetes checks their blood sugar," says Sabbagh. "If we can learn early on that a person is at risk, the goal would be to start preventative therapies immediately. This could be a game changer."
"Our research could provide new information about potential biomarkers, including protein changes detected in blood, that could more accurately and easily predict the risk for Alzheimer's disease in people with Down syndrome," says Schupf. "If successful, we believe there is a chance that these biomarkers could also be used to assess Alzheimer's risk in all groups of people."
The Alzheimer's Association is the largest nonprofit funder of Alzheimer's research, having awarded more than $350 million to over 2,300 projects since 1982. The Association currently supports more than 350 ongoing research projects in 21 countries totaling more than $82 million.
The Global Down Syndrome Foundation raises funds for the Crnic Institute for Down Syndrome to underwrite critical research benefiting people with Down syndrome. To date, $5.7 million in research grants has been given to 33 investigators.
The two other research projects the Alzheimer's Association and Global are funding through the joint grant award effort are:
A test of a potential Alzheimer's drug treatment that reduces levels of toxic protein fragments in the brain of a mouse model of Down syndrome. The project is led by William Mobley, M.D., Ph.D., Chair of the Department of Neurosciences at the University of California, San Diego (UCSD) and Executive Director of UCSD's Down Syndrome Center for Research and Treatment.
A study to determine whether a protein called Dyrk1A influences the build-up of brain proteins that lead to the formation of plaques and tangles that are key features of Alzheimer's in a mouse model of Down syndrome. Dyrk1A is created by one of the genes on chromosome 21 and is overabundant in the brains of people with Down syndrome. The study is led by Fei Liu, Ph.D., Head of Molecular Neuroscience for the Research Foundation for Mental Hygiene, Inc. at the New York State Institute for Basic Research in Staten Island.
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Alzheimer's Association
Olfactory testing uses extended to Alzheimer’s disease
Published on November 20, 2015 at 5:15 PM · No Comments
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By Eleanor McDermid, Senior medwireNews Reporter
A simple olfactory test may help to identify people at increased risk of developing Alzheimer’s disease (AD) dementia, suggest findings from a population-based study.
Olfactory dysfunction, already considered a strong risk indicator for Parkinson’s disease, significantly predicted both amnestic mild cognitive impairment (MCI) and further progression to AD dementia among 1430 cognitively normal people aged an average of 79.5 years.
Rosebud Roberts (Mayo Clinic, Rochester, Minnesota, USA) and study co-authors suggest that “odor identification tests may have use for early detection of persons at risk of cognitive outcomes.”
A slow walking speed was associated with a higher level of brain amyloid deposits in a population of older adults at a high risk of developing dementia in a new study.
The study, published online in Neurology December 2, was conducted by a team led by Natalia del Campo, PhD, University Hospital Toulouse, France.
A simple, rapid test called the Head Turning Sign (HTS) may help to assess the presence of Alzheimer's disease (AD) dementia.Patients who turn their head toward their caregiver for assistance or cues to help them answer simple questions are more likely to have AD dementia than mild cognitive impairment (MCI) or frontotemporal dementia (FTD), a new study shows.
Genetic risk score may help detect Alzheimer's disease risk in healthy young adults
New research shows that a genetic risk score may detect those at higher risk for Alzheimer's disease long before symptoms appear—even possibly in healthy young adults, according to a study published in the July 6, 2016, online issue of Neurology, the medical journal of the American Academy of Neurology.
TORONTO ― The University of Pennsylvania Smell Identification Test (UPSIT) has potential as an inexpensive, noninvasive test to help diagnose Alzheimer's disease, a new study shows.
In a study of older adults, both a low score on the UPSIT and positive amyloid beta (Aβ) status predicted memory decline.
webmd.ads2.defineAd({id:'ads-pos-520',pos: 520}); "Reduced ability to identify odors has been seen in patients who are later diagnosed with Alzheimer's disease at autopsy. And decreased odor identification is also seen in those with mild memory symptoms and those who develop Alzheimer's disease dementia," said William Kreisl, MD, from the Taub Institute and Columbia University Medical Center in New York City.
He presented the study at a press briefing here at the Alzheimer's Association International Conference (AAIC) 2016.
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Tests that measure the sense of smell may soon become common in neurologists' offices. Scientists have been finding increasing evidence that the sense of smell declines sharply in the early stages of Alzheimer's, and now a new study from the Perelman School of Medicine at the University of Pennsylvania published today in the Journal of Alzheimer's Disease confirms that administering a simple "sniff test" can enhance the accuracy of diagnosing this dreaded disease.
The sniff test also appears to be useful for diagnosing a pre-dementia condition called mild cognitive impairment (MCI), which often progresses to Alzheimer's dementia within a few years.
Neurologists have been eager to find new ways to identify people who are at high risk of Alzheimer's dementia but do not yet show any symptoms. There is a widespread consensus that Alzheimer's medications now under development may not work after dementia has set in.
"There's the exciting possibility here that a decline in the sense of smell can be used to identify people at risk years before they develop dementia," said principal investigator David R. Roalf, PhD, an assistant professor in the department of Psychiatry at Penn.
Roalf and his colleagues used a simple, commercially available test known as the Sniffin' Sticks Odor Identification Test, in which subjects must try to identify 16 different odors. They administered the sniff test, and a standard cognitive test (the Montreal Cognitive Assessment), to 728 elderly people.
The subjects had already been evaluated by doctors at Penn with an array of neurological methods, and according to expert consensus had been placed in one of three categories: "healthy older adult," "mild cognitive impairment," or "Alzheimer's dementia." Roalf and his team used the results from the cognitive test alone, or combined with the sniff test, to see how well they identified subjects in each category.
The increasing use of biomarkers, such as β amyloid and tau, to diagnose Alzheimer's disease (AD) will likely lead to more accurate estimates of the true incidence and prevalence of the disease, concludes a new special report from the Alzheimer's Association (AA).
The report is included in the association's annual "2017 Alzheimer's Disease Facts and Figures" document.
AD biomarkers have the potential to facilitate earlier and more accurate diagnosis and treatment, according to the report, authored by Heather M. Snyder, PhD, senior director, medical & scientific operations, Alzheimer's Association, and colleagues.
High-definition eye scan could reveal crucial warning signs of Alzheimer's disease
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August 17, 2017
Cedars-Sinai neuroscience investigators have found that Alzheimer's disease affects the retina – the back of the eye – similarly to the way it affects the brain. The study also revealed that an investigational, noninvasive eye scan could detect the key signs of Alzheimer's disease years before patients experience symptoms.
Using a high-definition eye scan developed especially for the study, researchers detected the crucial warning signs of Alzheimer's disease: amyloid-beta deposits, a buildup of toxic proteins. The findings represent a major advancement toward identifying people at high risk for the debilitating condition years sooner.
The study, published today in JCI Insight, comes amid a sharp rise in the number of people affected by the disease. Today, more than 5 million Americans have Alzheimer's disease. That number is expected to triple by 2050, according to the Alzheimer's Association.
"The findings suggest that the retina may serve as a reliable source for Alzheimer's disease diagnosis," said the study's senior lead author, Maya Koronyo-Hamaoui, PhD, a principal investigator and associate professor in the departments of Neurosurgery and Biomedical Sciences at Cedars-Sinai.
"One of the major advantages of analyzing the retina is the repeatability, which allows us to monitor patients and potentially the progression of their disease."
Yosef Koronyo, MSc, a research associate in the Department of Neurosurgery and first author on the study, said another key finding from the new study was the discovery of amyloid plaques in previously overlooked peripheral regions of the retina. He noted that the plaque amount in the retina correlated with plaque amount in specific areas of the brain.
"Now we know exactly where to look to find the signs of Alzheimer's disease as early as possible," said Koronyo.
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Keith L. Black, MD, chair of Cedars-Sinai's Department of Neurosurgery and director of the Maxine Dunitz Neurosurgical Institute, who co-led the study, said the findings offer hope for early detection when intervention could be most effective.
"Our hope is that eventually the investigational eye scan will be used as a screening device to detect the disease early enough to intervene and change the course of the disorder with medications and lifestyle changes," said Black.
For decades, the only way to officially diagnose the debilitating condition was to survey and analyze a patient's brain after the patient died. In recent years, physicians have relied on positron emission tomography (PET) scans of the brains of living people to provide evidence of the disease but the technology is expensive and invasive, requiring the patient to be injected with radioactive tracers.
In an effort to find a more cost-effective and less invasive technique, the Cedars-Sinai research team collaborated with investigators at NeuroVision Imaging, Commonwealth Scientific and Industrial Research Organisation, University of Southern California, and UCLA to translate their noninvasive eye screening approach to humans.
The published results are based on a clinical trial conducted on 16 Alzheimer's disease patients who drank a solution that includes curcumin, a natural component of the spice turmeric. The curcumin causes amyloid plaque in the retina to "light up" and be detected by the scan. The patients were then compared to a group of younger, cognitively normal individuals.
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Simple odor identification tests may help track progression of Alzheimer's disease
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August 16, 2017
Odor identification tests may help scientists track the evolution of the disease in persons at risk
By the time you start losing your memory, it`s almost too late. That`s because the damage to your brain associated with Alzheimer's disease (AD) may already have been going on for as long as twenty years. Which is why there is so much scientific interest in finding ways to detect the presence of the disease early on. Scientists now believe that simple odor identification tests may help track the progression of the disease before symptoms actually appear, particularly among those at risk.
"Despite all the research in the area, no effective treatment has yet been found for AD," says Dr. John Breitner, the director of the Centre for Studies on Prevention of Alzheimer's Disease at the Douglas Mental Health Research Centre of McGill University. He is one of the authors of the study on the subject that was recently published in the journal Neurology. "But, if we can delay the onset of symptoms by just five years, we should be able to reduce the prevalence and severity of these symptoms by more than 50%."
Bubble gum or gasoline?
Close to 300 people with an average age of 63 who are at risk of developing AD because they had a parent who had suffered from the disease, were asked to take multiple choice scratch-and-sniff tests to identify scents as varied as bubble gum, gasoline or the smell of a lemon. One hundred of them also volunteered to have regular lumbar punctures to measure the quantities of various AD-related proteins whose presence in the cerebrospinal fluid (CSF).
The researchers found that those with the most difficulty in identifying odors were those in whom other, purely biological indicators of AD, were most evident.
"This is the first time that anyone has been able to show clearly that the loss of the ability to identify smells is correlated with biological markers indicating the advance of the disease," says Marie-Elyse Lafaille-Magnan, a doctoral student at McGill and the first author on the study. "For more than 30 years, scientists have been exploring the connection between memory loss and the difficulty that patients may have in identifying different odors. This makes sense because it's known that the olfactory bulb (involved with the sense of smell) and the entorhinal cortex (involved with memory and naming of odors) are among the first brain structures first to be affected by the disease."
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A cheaper way to track progression of Alzheimer's disease
"This means that a simple smell test may potentially be able to give us information about the progression of the disease that is similar to the much more invasive and expensive tests of the cerebrospinal fluid that are currently being used," the director of research program on Aging, Cognition and Alzheimer's disease of the Douglas Institute and one of the authors on the study. "However, problems identifying smells may be indicative of other medical conditions apart from AD and so should not be substituted for the current tests."
The researchers caution more that far more work needs to be done to see how changes in a person's ability to identify smells over time relates to the progression of the disease itself. For the time being, smell tests are simply one more avenue to explore as researchers look for ways to identify the disease before the symptoms actually begin to appear.
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https://www.mcgill.ca/newsroom/channels/news/could-olfactory-loss-point-alzheimers-disease-269504
Saliva testing of amyloid-β42 (Aβ42) levels may contribute to the prevention of Alzheimer's disease (AD) by determining AD risk and guidance on the use of prophylactic nonsteroidal anti-inflammatory drugs (NSAIDs), new research suggests.
Canadian investigators used a salivary ELISA test to measure Aβ42levels in saliva. They found that elevations in Aβ42 levels in persons at risk for developing AD were similar to levels in individuals who already had AD.
Given that AD is a neuroinflammatory process that begins as early as 10 years prior to the onset of cognitive deficits, the researchers suggest that NSAIDs, initiated a decade prior to the typical age of AD onset, may be effective in staving off these inflammatory effects in people whose Aβ42 concentrations are found to be high.
"We have known since the 1990s that people taking anti-inflammatory drugs are spared from getting AD, but what we didn't know then and know now is how soon before the disease you have to start taking these medications and roughly how much you need," lead author Patrick McGeer, MD, PhD, professor emeritus, Department of Psychiatry, University of British Columbia, Vancouver, Canada, told Medscape Medical News.
"The answers have been very slow in coming, but the knowledge that you can learn a lot from measuring saliva has provided the missing link," he said.
The report was published online March 13 in the Journal of Alzheimer's Disease.
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