Latest Research News
Memory tests predict brain atrophy and Alzheimer's disease
Data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), involving 230 cognitively normal individuals and 394 individuals with diagnosed with MCI on the basis of one episodic test, has found that performance on two tests markedly improved the identification of those whose MCI was more serious.
MCI can be a step on the road to Alzheimer's, but it can also be a reversible condition, and it’s obviously helpful to be able to distinguish the two.
The study compared those with MCI whose memory performance was impaired only in one (story recall) or two (story recall and word list recall) tests. Those who performed poorly in both showed Alzheimer's biomarkers in the cerebrospinal fluid that more closely resembled Alzheimer's patients than those who only did poorly in one test. Moreover, they showed faster brain atrophy in the medial temporal lobes.
Alzheimer's disease was diagnosed within the three-year study period in around half of the participants who performed poorly in both tests, but in only 16% of those with a poor performance on one test.
Clock drawing test should be done routinely in patients with high blood pressure
An Argentinian study involving 1,414 adults with high blood pressure has concluded that the clock drawing test for detecting cognitive dysfunction should be conducted routinely in patients with high blood pressure
A higher prevalence of cognitive impairment was found with the clock drawing test (36%) compared to the MMSE (21%). Three out ten patients who had a normal MMSE score had an abnormal clock drawing result. The disparity in results between the two tests was greatest in middle aged patients.
The clock drawing test is particularly useful for evaluating executive functions, which are the cognitive function most likely to be damaged by untreated high blood pressure.
The clock drawing test involves being given a piece of paper with a 10 cm diameter circle on it, and having to write the numbers of the clock in the correct position inside the circle and then draw hands on the clock indicating the time "twenty to four".
The average blood pressure was 144/84 mmHg, average age was 60 years, and 62% were women.
The findings were presented at ESC Congress 2018.
Repeated cognitive testing can mask early signs of dementia
Those suspected of cognitive impairment often undergo repeated cognitive testing over time — indeed it is the change over time that is most diagnostic. However, most cognitive functions get better with practice. A new study involving 995 middle- to late-middle-aged men has found that, indeed, there were significant practice effects in most cognitive domains, and diagnoses of MCI doubled from 4.5 to 9% after correcting for practice effects.
Verb fluency helpful in detecting early cognitive impairment and predicting dementia
A large study involving 1820 adults (44+), of whom 568 were cognitively healthy, 885 had MCI, and 367 mild Alzheimer's, found that verb fluency worsened at each stage of cognitive decline, and worse scores in verb fluency task were significantly related to development of MCI, and progression from MCI to dementia. Worsening verb fluency was also associated with a faster decline to MCI, but not to faster progression from MCI to dementia.
Most previous research with word fluency has used category and letter fluency tasks (which demand generating names) rather than verb fluency, but verb fluency is more cognitively demanding than generating names, and may thus be a more sensitive tool.
Effectiveness of brief, simple test to screen for MCI
A brief, simple number naming test has been found to differentiate between cognitively healthy older adults and those with MCI or Alzheimer's.
The King-Devick (K-D) test is a one- to two-minute rapid number naming test that has previously been found useful in the detection of concussion, as well as in detecting level of impairment in other neurological conditions such as Parkinson's disease and multiple sclerosis. The K-D test can be quickly administered by non-professional office staff on either a tablet (iPad) or in a paper version.
The test accurately distinguished the controls from the cognitively impaired individuals more than 90% of the time.
The study involved 206 older adults, including 135 cognitively healthy individuals, 39 people with MCI, and 32 Alzheimer's patients.
The test will need to be validated in larger samples.
Not being aware of memory problems predicts onset of Alzheimer's
A number of studies have shown that people’s own subjective impressions of memory problems should not be discounted, but they shouldn’t be given too much weight either, since many people are over-anxious nowadays about their prospects of dementia. But there is a further complication to this issue, which is that being unaware of one’s own memory problems is typical of Alzheimer's.
Anosognosia is the name for this condition of not being able to recognize one’s memory problems.
A study involving 450 patients who experienced mild memory deficits, but were still capable of taking care of themselves, assessed this awareness by asking both the patients and their close relatives about the patient’s cognitive abilities. Anosognosia was diagnosed when a patient reported having no cognitive problems but the family member reported significant difficulties.
The study found that those suffering from anosognosia had impaired brain metabolic function and higher rates of amyloid deposition. Two years later, they were more likely to have developed dementia.
A study involving 1,062 older adults (55-90), including 191 people with Alzheimer's disease, 499 with MCI and 372 healthy controls, found that those with anosognosia had reduced glucose uptake in specific brain regions. Glucose uptake is impaired in Alzheimer's disease.
Cognitive test differentiates between Alzheimer's and normal aging
The hippocampus, one of the earliest brain regions affected in Alzheimer's, has a number of important memory functions. One of these is relational memory — the hippocampus can bind together pieces of information stored in different parts of the brain, so that, for example, you can remember the name when you see the associated face.
A new cognitive test that assesses relational memory has been found to be effective in distinguishing cognitive impairment that reflects very early mild Alzheimer's from normal aging.
The test involves a circle divided into three parts, each having a unique design. After studying a circle, participants needed to pick its exact match from a series of 10 circles, presented one at a time.
People with very mild Alzheimer's disease did worse overall on the task than those in the healthy aging group, who, in turn, did worse than a group of young adults. Moreover, those with Alzheimer's were particularly susceptible to interference from intervening lure stimuli. Including this in the analysis improved the test’s ability to differentiate between those who did and those who did not have Alzheimer's. It also provides evidence that Alzheimer's is qualitatively different from normal age-related cognitive decline, not simply an extension of it.
The study involved 90 participants, including 30 young adults, 30 cognitively healthy older adults, and 30 with very early Alzheimer's.
(2018). Modifying the minimum criteria for diagnosing amnestic MCI to improve prediction of brain atrophy and progression to Alzheimer’s disease.
Brain Imaging and Behavior.
(2018). Underdiagnosis of mild cognitive impairment: A consequence of ignoring practice effects.
Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring. 10, 372 - 381.
Alegret M, Peretó M, Pérez A, Valero S, Espinosa A, Ortega G, Hernández I, Mauleón A, Rosende-Roca M, Vargas L, Rodríguez-Gómez O, Abdelnour C, Berthier ML, Bak TH, Ruiz A, Tárraga L, Boada M. The Role of Verb Fluency in the Detection of Early Cognitive Impairment in Alzheimer's Disease Journal of Alzheimer's Disease 2018.
(2017). Screening Utility of the King-Devick Test in Mild Cognitive Impairment and Alzheimer Disease Dementia.
Alzheimer Disease & Associated Disorders. 31(2), 152.
(2018). Anosognosia predicts default mode network hypometabolism and clinical progression to dementia.
Neurology. 90(11), e932.
(2017). Anosognosia Is an Independent Predictor of Conversion From Mild Cognitive Impairment to Alzheimer’s Disease and Is Associated With Reduced Brain Metabolism.
The Journal of Clinical Psychiatry. 78(9), 1187 - 1196.
Monti, J. M., Balota, D. A., Warren, D. E., & Cohen, N. J. (2014). Very mild Alzheimer׳s disease is characterized by increased sensitivity to mnemonic interference. Neuropsychologia, 59, 47–56. https://doi.org/10.1016/j.neuropsychologia.2014.04.007
A Canadian study involving 40 older adults (59-81), none of whom were aware of any major memory problems, has found that those scoring below 26 on the Montreal Cognitive Assessment (MoCA) dementia screening test also showed shrinking of the anterolateral entorhinal cortex. This brain region is the first affected in the development of Alzheimer's disease. The study found specifically that this area of the brain is involved in configural processing — that is, processing the spatial arrangement of an object's elements. Accordingly, this task provides a very early indicator of developing Alzheimer's.
You can do a preliminary assessment of your memory using Baycrest's scientifically-validated, online brain health assessment tool, Cogniciti at http://www.cogniciti.com.
(Submitted). Human anterolateral entorhinal cortex volumes are associated with cognitive decline in aging prior to clinical diagnosis.
Neurobiology of Aging.
Following on from a previous study showing that such a virtual supermarket game administered by a trained professional can detect MCI, a small study used a modified Virtual SuperMarket Remote Assessment Routine (VSM-RAR) that was self-administered by the patient at home on their own, for a period of one month.
Using the average score over 20 assessments, the game correctly diagnosed MCI 91.8% of the time, a level of diagnostic accuracy similar to the most accurate standardized neuropsychological tests.
The study involved six patients with MCI and six healthy older adults.The level of diagnostic accuracy was better using the average score than in the previous study in which only a single score was used.
A tablet PC was provided to the participants, on which to play the game.
(2017). A Preliminary Study on the Feasibility of Using a Virtual Reality Cognitive Training Application for Remote Detection of Mild Cognitive Impairment.
Journal of Alzheimer's Disease. 56(2), 619 - 627.
After Alzheimer's disease, the next most common type of dementia is Lewy Body disease. Far less widely known, this form of dementia is often diagnosed quite late. A new study has validated a simple rating scale that non-specialist clinicians can use to quickly and effectively diagnose LBD in about three minutes.
The Lewy Body Composite Risk Score (LBCRS) is a simple, one-page survey with structured yes/no questions for six non-motor features that are present in patients with LBD, but are much less commonly found in other forms of dementia.
The study involved 256 patients referred from the community. The LBCRS was able to discriminate between Alzheimer's disease and LBD with 96.8% accuracy, and provided sensitivity of 90% and specificity of 87%.
Earlier diagnosis will not only reduce the strain on sufferers and their families, but also reduce the risk of inappropriate medications that can have potentially serious adverse consequences, and increase the opportunity to receive appropriate symptomatic therapies at the earliest stages when they are likely to be most effective.
(2015). Improving the clinical detection of Lewy body dementia with the Lewy body composite risk score.
Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring. 1(3), 316 - 324.
A new questionnaire has been developed that very quickly determines whether or not a person has dementia and whether it's very mild, mild, moderate or severe. The 10-item questionnaire takes only 3-5 minutes and can be completed by a caregiver, friend or family member.
Testing on 239 individuals with various forms of dementia and 28 healthy controls has shown the results are comparable to the gold standard used presently, which takes several hours for an experienced professional to administer, interpret and score.
The "Quick Dementia Rating System" (QDRS) was developed by a leading neuroscientist, James E. Galvin, who has developed a number of dementia screening tools. The questionnaire covers:
- memory and recall
- decision-making and problem-solving abilities
- activities outside the home
- function at home and hobbies
- toileting and personal hygiene
- behavior and personality changes
- language and communication abilities
- attention and concentration.
The total score is derived by summing up the 10 fields and each area has five possible answers increasing in severity of symptoms. The 10 areas capture the prominent symptoms of mild cognitive impairment, Alzheimer's disease, and non-Alzheimer's neurocognitive disorders including Lewy Body Dementia, frontotemporal degeneration, vascular dementia, chronic traumatic encephalopathy and depression.
The speed and ease of this questionnaire makes it a very useful initial screening tool. However, there are several caveats to its use now. At the moment, it has only been validated in the context of a memory disorders clinic, where prevalence of MCI and dementia is high. The next step would be to evaluate it in the context of settings where dementia prevalence is lower, such as 'ordinary' health clinics. Additionally, most of the study participants were Caucasian. Most importantly, inter-rater reliability has not yet been assessed (that is, the degree to which different scorers agree).
The Quick Dementia Rating System is copyrighted and permission to use this tool is required. QDRS is available at no cost to clinicians, researchers and not-for-profit organizations.
(2015). The Quick Dementia Rating System (QDRS): A rapid dementia staging tool.
Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring. 1(2), 249 - 259.
Data from 6257 older adults (aged 55-90) evaluated from 2005-2012 has revealed that concerns about memory should be taken seriously, with subjective complaints associated with a doubled risk of developing mild cognitive impairment or dementia, and subjective complaints supported by a loved one being associated with a fourfold risk. Complaints by a loved one alone were also associated with a doubled risk. Among those with MCI, subjective complaints supported by a loved one were associated with a threefold risk of converting to dementia.
Of the 4414 initially cognitively normal, 14% developed MCI or dementia over the course of the study (around 5 years); of the 1843 with MCI, 41% progressed to dementia.
(2014). The source of cognitive complaints predicts diagnostic conversion differentially among nondemented older adults.
Alzheimer's & Dementia. 10(3), 319 - 327.
Cognitive testing for dementia has a problem in that low scores on some tests may simply reflect a person's weakness in some cognitive areas, or the presence of a relatively benign form of mild cognitive impairment (one that is not going to progress to dementia). A 2008 study found that one of every six healthy adults scored poorly on two or more of 10 tests in a brief cognitive battery. Following this up, the same researchers now show that a more holistic view might separate those who are on the path to dementia from those who are not.
Data from 395 clinical patients (aged 60+) and 135 healthy older adults has revealed that, while the cognitively normal produce a pattern of scores on 13 cognitive tests that fits a bell-shaped curve, those experiencing some level of dementia produce a more skewed pattern. Increasingly lower scores and degree of positive skew was also associated with worsening dementia.
(2014). Within-person distributions of neuropsychological test scores as a function of dementia severity.
Neuropsychology. 28(2), 254 - 260.
Late-life depression is associated with an increased risk for all-cause dementia, Alzheimer’s disease, and, most predominantly, vascular dementia, a new study shows.
A new meta-analysis extends previous research showing a link between depression and Alzheimer’s disease to late-life depression and dementia. The analysis of 23 studies concluded that those with late-life depression were significantly more likely to develop dementia (1.85 times more likely), and that the risk of developing vascular dementia was significantly greater than that of developing Alzheimer’s (2.52 vs 1.65).
Late-life depression is estimated to affect 15% of older adults (65+) in the U.S. It has been associated to social isolation, as well as poorer health.
Interestingly, another recent study has explored the difficulties of disentangling major depression and early Alzheimer’s in older adults, given the overlap in symptoms. The study, involving 120 older depressed patients, found that tests of episodic memory were most predictive of Alzheimer’s (as compared to other cognitive tests, for example, in executive function).
http://www.futurity.org/health-medicine/late-life-depression-may-boost-dementia-risk/ (Press release, 1st study)
http://newoldage.blogs.nytimes.com/2013/05/01/does-depression-contribute-to-dementia/ (Commentary, 1st study)
(2013). Late-life depression and risk of vascular dementia and Alzheimer’s disease: systematic review and meta-analysis of community-based cohort studies.
The British Journal of Psychiatry. 202(5), 329 - 335.
(0). Neuropsychological indicators of preclinical Alzheimer's disease among depressed older adults.
Aging, Neuropsychology, and Cognition. 1 - 30.
New research suggests that reliance on the standard test Alzheimer's Disease Assessment Scale—Cognitive Behavior Section (ADAS-Cog) to measure cognitive changes in Alzheimer’s patients is a bad idea. The test is the most widely used measure of cognitive performance in clinical trials.
Using a sophisticated method of analysis ("Rasch analysis"), analysis of ADAS-Cog data from the AD Neuroimaging Initiative (675 measurements from people with mild Alzheimer's disease, across four time points over two years) revealed that although final patient score seemed reasonable, at the component level, a ceiling effect was revealed for eight out of the 11 parts of the ADAS-Cog for many patients (32-83%).
Additionally, for six components (commands, constructional praxis, naming objects and fingers, ideational praxis, remembering test instructions, spoken language), the thresholds (points of transition between response categories) were not ordered sequentially. The upshot of this is that, for these components, a higher score did not in fact confirm more cognitive impairment.
The ADAS-Cog has 11 component parts including memory tests, language skills, naming objects and responding to commands. Patients get a score for each section resulting in a single overall figure; different sections have different score ranges. A low total score signals better cognitive performance; total score range is 0-70, with 70 being the worst.
It seems clear from this that the test seriously underestimates cognitive differences between people and changes over time. Given that this is the most common cognitive test used in clinical trials, we have to consider whether these flaws account for the failure of so many drug trials to find significant benefits.
Among the recommended ways to improve the ADAS-Cognitive (including the need to clearly define what is meant by cognitive performance!), the researchers suggest that a number of the components should be made more difficult, and that the scoring function of those six components needs to be investigated.
(2012). Putting the Alzheimer's cognitive test to the test II: Rasch Measurement Theory.
Alzheimer's & Dementia.
A small study shows how those on the road to Alzheimer’s show early semantic problems long before memory problems arise, and that such problems can affect daily life.
The study compared 25 patients with amnestic MCI, 27 patients with mild-to-moderate Alzheimer's and 70 cognitively fit older adults (aged 55-90), on a non-verbal task involving size differences (for example, “What is bigger: a key or a house?”; “What is bigger: a key or an ant?”). The comparisons were presented in three different ways: as words; as images reflecting real-world differences; as incongruent images (e.g., a big ant and a small house).
Both those with MCI and those with AD were significantly less accurate, and significantly slower, in all three conditions compared to healthy controls, and they had disproportionately more difficulty on those comparisons where the size distance was smaller. But MCI and AD patients experienced their biggest problems when the images were incongruent – the ant bigger than the house. Those with MCI performed at a level between that of healthy controls and those with AD.
This suggests that perceptual information is having undue influence in a judgment task that requires conceptual knowledge.
Because semantic memory is organized according to relatedness, and because this sort of basic information has been acquired a long time ago, this simple test is quite a good way to test semantic knowledge. As previous research has indicated, the problem doesn’t seem to be a memory (retrieval) one, but one reflecting an actual loss or corruption of semantic knowledge. But perhaps, rather than a loss of data, it reflects a failure of selective attention/inhibition — an inability to inhibit immediate perceptual information in favor of more relevant conceptual information.
How much does this matter? Poor performance on the semantic distance task correlated with impaired ability to perform everyday tasks, accounting (together with delayed recall) for some 35% of the variance in scores on this task — while other cognitive abilities such as processing speed, executive function, verbal fluency, naming, did not have a significant effect. Everyday functional capacity was assessed using a short form of the UCSD Skills Performance Assessment scale (a tool generally used to identify everyday problems in patients with schizophrenia), which presents scenarios such as planning a trip to the beach, determining a route, dialing a telephone number, and writing a check.
The finding indicates that semantic memory problems are starting to occur early in the deterioration, and may be affecting general cognitive decline. However, if the problems reflect an access difficulty rather than data loss, it may be possible to strengthen these semantic processing connections through training — and thus improve general cognitive processing (and ability to perform everyday tasks).
(2012). Semantic Distance Abnormalities in Mild Cognitive Impairment: Their Nature and Relationship to Function.
American Journal of Psychiatry. 169(12), 1275 - 1283.
Dementia is a progressive illness, and its behavioral and psychological symptoms are, for caregivers, the most difficult symptoms to manage. While recent research has demonstrated how collaborative care can reduce these symptoms and reduce stress for caregivers, the model requires continuous monitoring of the symptoms. What’s needed is a less arduous way of monitoring changes in symptoms.
A new questionnaire for assessing dementia progression has now been validated. The Healthy Aging Brain Care Monitor is simple, user-friendly and sensitive to change in symptoms. Its 31 items cover cognitive, functional, and behavioral and psychological symptoms of the patient, as well as caregiver quality of life, and takes about six minutes for a caregiver to complete.
Some of the specific items that may be of interest include:
- Repeating the same things over and over
- Forgetting the correct month or year
- Handling finances
- Planning, preparing or serving meals
- Learning to use a tool, appliance, or gadget
You can see the full questionnaire at http://www.indydiscoverynetwork.org/HealthyAgingBrainCareMonitor.html. The HABC Monitor and scoring rules are available without charge.
The four factors (cognitive; functional; behavioral and psychological; caregiver quality of life) were all significantly correlated, with one exception: cognitive and caregiver quality of life.
The validating study involved 171 caregivers, of whom 52% were the children of the patients, 34% were spouses, 6% were siblings, and 4% were grandchildren. The participant group included 61% identifying as white, 38% African-American, and 1% other. Only 1% was Hispanic.
The study found good internal consistency (0.73–0.92); good correlations with the longer and more detailed Neuropsychiatric Inventory (NPI) total score and NPI caregiver distress score; and greater sensitivity to three-month change compared with NPI “reliable change” groups.
The value of this new clinical tool lies in its brevity. Described as a ‘blood pressure cuff’ for dementia symptoms, the one-page questionnaire is designed to fit into a health visit easily.
The researchers note some caveats, including the fact that it was validated in a memory care practice setting and not yet in a primary care setting, and (more importantly) only over a three-month period. Future projects will assess its sensitivity to change over longer periods, and in primary care.
(2012). Practical clinical tool to monitor dementia symptoms: the HABC-Monitor.
Clinical Interventions in Aging. 143 - 143.
Full text available at http://www.dovepress.com/articles.php?article_id=10106
New data from the ongoing validation study of the Alzheimer's Questionnaire (AQ), from 51 cognitively normal individuals (average age 78) and 47 aMCI individuals (average age 74), has found that the AQ is effective in identifying not only those with Alzheimer’s but also those older adults with mild cognitive impairment.
Of particular interest is that four questions were strong indicators of aMCI. These related to:
- repeating questions and statements,
- trouble knowing the date or time,
- difficulties managing finances, and
- decreased sense of direction.
The AQ consists of 21 yes/no questions designed to be answered by a relative or carer. The questions fall into five categories: memory, orientation, functional ability, visuospatial ability, and language. Six of these questions are known to be predictive of AD and are given extra weighting, resulting in a score out of 27. A score above 15 was indicative of AD, and between 5 and 14 of aMCI. Scores of 4 or lower indicate that the person does not have significant memory problems.
The questionnaire is not of course definitive, but is intended as an indicator for further testing. Note, too, that all participants in this study were Caucasian.
The value and limitations of brief cognitive screenings
The value of brief cognitive screenings combined with offering further evaluation is demonstrated in a recent large VA study, which found that, of 8,342 Veterans aged 70+ who were offered screening (the three-minute Mini-Cog), 8,063 (97%) accepted, 2,081 (26%) failed the screen, and 580 (28%) agreed to further evaluation. Among those accepting further evaluation, 93% were found to have cognitive impairment, including 75% with dementia.
Among those who declined further evaluation, 17% (259/1,501) were diagnosed with incident cognitive impairment through standard clinical care. In total, the use of brief cognitive screenings increased the numbers with cognitive impairment to 11% (902/8,063) versus 4% (1,242/28,349) in similar clinics without this program.
Importantly, the limits of such questionnaires were also demonstrated: 118 patients who passed the initial screen nevertheless requested further evaluation, and 87% were found to have cognitive impairment, including 70% with dementia.
This should not be taken as a reason not to employ such cognitive tests! There are two points that should, I think, be taken from this:
- Routine screening of older adults is undoubtedly an effective strategy for identifying those with cognitive impairment.
- Individuals who pass such tests but nevertheless believe they have cognitive problems should be taken seriously.
(2012). Informant-reported cognitive symptoms that predict amnestic mild cognitive impairment.
BMC Geriatrics. 12(1), 3 - 3.
Full text available at http://www.biomedcentral.com/1471-2318/12/3
(2012). Finding Dementia in Primary Care: The Results of a Clinical Demonstration Project.
Journal of the American Geriatrics Society. 60(2), 210 - 217.
A telephone survey of around 17,000 older women (average age 74), which included questions about memory lapses plus standard cognitive tests, found that getting lost in familiar neighborhoods was highly associated with cognitive impairment that might indicate Alzheimer’s. Having trouble keeping up with a group conversation and difficulty following instructions were also significantly associated with cognitive impairment. But, as most of us will be relieved to know, forgetting things from one moment to the next was not associated with impairment!
Unsurprisingly, the more memory complaints a woman had, the more likely she was to score poorly on the cognitive test.
The 7 memory lapse questions covered:
- whether they had recently experienced a change in their ability to remember things,
- whether they had trouble remembering a short list of items (such as a shopping list),
- whether they had trouble remembering recent events,
- whether they had trouble remembering things from one second to the next,
- whether they had difficulty following spoken or written instructions,
- whether they had more trouble than usual following a group conversation or TV program due to memory problems,
- whether they had trouble finding their way around familiar streets.
Because this survey was limited to telephone tests, we can’t draw any firm conclusions. But the findings may be helpful for doctors and others, to know which sort of memory complaints should be taken as a flag for further investigation.
(2011). Specific Subjective Memory Complaints in Older Persons May Indicate Poor Cognitive Function.
Journal of the American Geriatrics Society. 59(9), 1612 - 1617.
A simple new cognitive assessment tool with only 16 items appears potentially useful for identifying problems in thinking, learning and memory among older adults. The Sweet 16 scale is scored from zero to 16 (with 16 representing the best score) and includes questions that address orientation (identification of person, place, time and situation), registration, digit spans (tests of verbal memory) and recall. The test requires no props (not even pencil and paper) and is easy to administer with a minimum of training. It only takes an average of 2 minutes to complete.
A score of 14 or less correctly identified 80% of those with cognitive impairment (as identified by the Informant Questionnaire on Cognitive Decline in the Elderly) and correctly identified 70% of those who did not have cognitive impairment. In comparison, the standard MMSE correctly identified 64% of those with cognitive impairment and 86% of those who were not impaired. In other words, the Sweet 16 missed diagnosing 20% of those who were (according to this other questionnaire) impaired and incorrectly diagnosed as impaired 30% of those who were not impaired, while the MMSE missed 36% of those who were impaired but only incorrectly diagnosed as impaired 14% of those not impaired.
Thus, the Sweet 16 seems to be a great ‘first cut’, since its bias is towards over-diagnosing impairment. It should also be remembered that the IQCDE is not the gold standard for cognitive impairment; its role here is to provide a basis for comparison between the new test and the more complex MMSE. In comparison with a clinician’s diagnosis, Sweet 16 scores of 14 or less occurred in 99% of patients diagnosed by a clinician to have cognitive impairment and 28% of those without such a diagnosis.
The great benefit of the new test is of course its speed and simplicity, and it seems to offer great promise as an initial screening tool. Another benefit is that it supposedly is unaffected by the patient’s education, unlike the MMSE. The tool is open access.
The Sweet 16 was developed using information from 774 patients who completed the MMSE, and then validated using a different group of 709 older adults.
(2010). Development and Validation of a Brief Cognitive Assessment Tool: The Sweet 16.
Arch Intern Med. archinternmed.2010.423 - archinternmed.2010.423.
Confirming earlier research, a study involving 257 older adults (average age 75) has found that a two-minute questionnaire filled out by a close friend or family member is more accurate that standard cognitive tests in detecting early signs of Alzheimer’s.
The AD8 asks questions about changes in everyday activities:
- Problems with judgment, such as bad financial decisions;
- Reduced interest in hobbies and other activities;
- Repeating of questions, stories or statements;
- Trouble learning how to use a tool or appliance, such as a television remote control or a microwave;
- Forgetting the month or year;
- Difficulty handling complicated financial affairs, such as balancing a checkbook;
- Difficulty remembering appointments; and
- Consistent problems with thinking and memory.
Problems with two or more of these are grounds for further evaluation. The study found those with AD8 scores of 2 or more were very significantly more likely to have early biomarkers of Alzheimer’s (abnormal Pittsburgh compound B binding and cerebrospinal fluid biomarkers), and was better at detecting early stages of dementia than the MMSE. The AD8 has now been validated in several languages and is used in clinics around the world.
(2010). Relationship of dementia screening tests with biomarkers of Alzheimer’s disease.
Brain. 133(11), 3290 - 3300.
A computerized self test (CST) has been developed that is 96% accurate in diagnosing Alzheimer’s and MCI-A (compared to 71% for the MMSE and 69% for the Mini-Cognitive — tests currently in use). Moreover, the test accurately classified 91% of the six experimental groups (control, MCI, early Alzheimer's, mild to moderate, moderate to severe, and severe) as compared to 54% for the MMSE and 48% for the Mini-Cog. The brief, interactive online test is designed to be used in the primary care setting, where physicians may not have detailed training in recognizing cognitive impairments.
Dougherty, J.H. Jr. et al. 2010. The Computerized Self Test (CST): An Interactive, Internet Accessible Cognitive Screening Test For Dementia. Journal of Alzheimer's Disease, 20 (1), 185-195.
The journal article is available at http://iospress.metapress.com/content/a1242x878323454x/fulltext.pdf
Older news items (pre-2010) brought over from the old website
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. http://gupea.ub.gu.se/dspace/handle/2077/19395
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 http://medschool.slu.edu/agingsuccessfully/pdfsurveys/slumsexam_05.pdf
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.