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 clinical trial involving 9361 older adults (50+) with hypertension but without diabetes or history of stroke has found that intensive control of blood pressure significantly reduced the risk of developing mild cognitive impairment.
While there was also a 15% reduction in dementia, this result did not reach statistical significance. This may have been due to the small number of new cases of dementia in the study groups.
Participants were randomly assigned to a systolic blood pressure goal of either less than 120 mm HG (intensive treatment) or less than 140 mm HG (standard treatment). They were then classified after five years as having no cognitive impairment, MCI or probable dementia.
The trial was stopped early due to its success in reducing cardiovascular disease. As a result, participants were on intensive blood pressure lowering treatment for a shorter period than originally planned. This impacted the number of cases of dementia occurring.
Hypertension affects more than half of Americans over age 50 and more than 75% of those older than 65.
The SPRINT MIND Investigators for the SPRINT Research Group. (2019). Effect of Intensive vs Standard Blood Pressure Control on Probable Dementia: A Randomized Clinical Trial. JAMA, 321(6), 553–561.
A large study using data from the famous Framingham Heart Study has compared changes in dementia onset over the last three decades. The study found that over time the age of onset has increased while the length of time spent with dementia has decreased.
The study involved 5,205 participants from the Framingham Original and Offspring cohorts. Four 5-year periods anchored to different baseline examinations (participants have been examined every four years) were compared. These baseline years are (on average, because participants’ schedules are different): 1978, 1989, 1996, 2006. Participants were those who were aged 60 or older and dementia-free at the start of a time period. There were at least 2000 participants in each time period. In total, there were 371 cases of dementia, and 43% of dementia cases survived more than 5 years after diagnosis.
It was found that the mean age of dementia onset increased by around two years per time period, while age at death increased by around one year. Length of survival after diagnosis decreased over time for everyone, taken as a whole, and also for each gender and education level, taken separately. Survival was almost 6 years in the first time period, and only three years in the last. But the mean age of onset was 80 in the first period, compared to over 86 in the last.
However, the changes haven’t been steady over the 30 years, but rather occurred mostly in those with dementia in 1986–1991 compared to 1977–1983.
Part of the reason for the changes is thought to be because of the reduced risk of stroke (largely because of better blood pressure management), and the better stroke treatments available. Stroke is a major risk factor for dementia. Other reasons might include lower burdens of multiple infections, better education, and better nutrition.
(2018). Are Trends in Dementia Incidence Associated With Compression in Morbidity? Evidence From The Framingham Heart Study.
The Journals of Gerontology: Series B. 73(suppl_1), S65 - S72.
A long-running study comparing African-Americans and Nigerians has found the incidence of dementia has fallen significantly over two decades among the African-Americans, but remained the same for the Nigerians (for whom it was lower anyway).
The study enrolled two cohorts, one in 1992 and one in 2001, who were evaluated every 2–3 years until 2009. The 1992 cohort included 1440 older African-Americans (70+) and 1774 Nigerian Yoruba; the 2001 cohort included 1835 African-Americans and 1895 Yoruba. None of the participants had dementia at study beginning.
The overall standardized annual incidence rate was 3.6% for the 1992 African-American cohort, and 1.4% for the 2001 cohort. For the Yoruba, it was 1.7% and 1.4%, respectively.
It's suggested that one reason for the improvement among African-Americans may be medications for cardiovascular conditions. Although both groups had similar rates of high blood pressure, this was recognized and treated in the American group but not in the Nigerian.
As you can see, African-Americans in the earlier cohort were more than twice as likely as Africans to develop dementia. Their decrease has brought them into line with the African rate.
Although the rate of new cases of dementia decreased, the African-Americans enrolling in 2001 had significantly higher rates of diabetes, hypertension and stroke, but also higher treatment rates, than the African-Americans who enrolled in 1992.
The finding offers hope that treatment can offset the expected increase in dementia resulting from the rise in lifestyle diseases.
(Submitted). Dementia incidence declined in African-Americans but not in Yoruba.
Alzheimer's & Dementia.
A large meta-analysis has concluded that having diabetes increases the chance that a person with mild cognitive impairment will progress to dementia by 65%.
There was no consistent evidence that hypertension or cholesterol levels increased the risk of someone with MCI progressing to dementia. Smoking was similarly not associated with increased risk, although the reason for this probably lies in mortality: smokers tend to die before developing dementia.
There was some evidence that having symptoms of psychiatric conditions, including depression, increased the risk of progressing to dementia.
There was some evidence that following a Mediterranean diet decreased the risk of an individual with amnestic MCI progressing to Alzheimer's, and that higher folate levels decrease the risk of progressing from MCI to dementia. The evidence regarding homocysteine levels was inconsistent.
The evidence indicates that level of education does not affect the risk of someone with MCI progressing to dementia.
Do note that all this is solely about progression from MCI to dementia, not about overall risk of developing dementia. Risk factors are complex. For example, cholesterol levels in mid-life are associated with the later development of dementia, but cholesterol levels later in life are not. This is consistent with cholesterol levels not predicting progression from MCI to dementia. Level of education is a known risk factor for dementia, but it acts by masking the damage in the brain, not preventing it. It is not surprising, therefore, that it doesn't affect progression from MCI to dementia, because higher education helps delay the start, it doesn't slow the rate of decline.
Do note also that a meta-analysis is only as good as the studies it's reviewing! Some factors couldn't be investigated because they haven't been sufficiently studied in this particular population (those with MCI).
The long-running Cache County study has previously found that 46% of those with MCI progressed to dementia within three years; this compared with 3% of those (age-matched) with no cognitive impairment at the beginning of the study.
More recently, data from the long-running, population-based Rotterdam study revealed that those diagnosed with MCI were four times more likely to develop dementia, over seven years. compared with those without MCI. Of those with MCI (10% of the 4,198 study participants), 40% had amnestic MCI — the form of MCI that is more closely associated with Alzheimer's disease.
The 2014 study also found that older age, positive APOE-ɛ4 status, low total cholesterol levels, and stroke, were all risk factors for MCI. Having the APOE-ɛ4 genotype and smoking were related only to amnestic MCI. Waist circumference, hypertension, and diabetes were not significantly associated with MCI. This may be related to medical treatment — research has suggested that hypertension and diabetes may be significant risk factors only when untreated or managed poorly.
(2015). Modifiable Predictors of Dementia in Mild Cognitive Impairment: A Systematic Review and Meta-Analysis.
American Journal of Psychiatry. 172(4), 323 - 334.
(2006). Conversion to dementia from mild cognitive disorder The Cache County Study.
Neurology. 67(2), 229 - 234.
de Bruijn, R.F.A.G. et al. Determinants, MRI Correlates, and Prognosis of Mild Cognitive Impairment: The Rotterdam Study. Journal of Alzheimer’s Disease, Volume 42/Supplement 3 (August 2014): 2013 International Congress on Vascular Dementia (Guest Editor: Amos D. Korczyn), DOI: 10.3233/JAD-132558.
The jugular venous reflux (JVR) occurs when the pressure gradient reverses the direction of blood flow in the veins, causing blood to leak backwards into the brain. A small pilot study has found an association between JVR and white matter changes in the brains of patients with Alzheimer’s disease and those with mild cognitive impairment. This suggests that cerebral venous outflow impairment might play a role in the development of white matter changes in those with Alzheimer’s.
JVR occurs when the internal jugular vein valves don’t open and close properly, which occurs more frequently in the elderly. The study involved 12 patients with Alzheimer’s disease, 24 with MCI, and 17 age-matched controls. Those with severe JVR were more likely to have hypertension, more and more severe white matter changes, and tended to have higher cerebrospinal fluid volumes.
Further research is needed to validate these preliminary findings.
Chung, C-P. et al. 2013. Jugular Venous Reflux and White Matter Abnormalities in Alzheimer’s Disease: A Pilot Study. Journal of Alzheimer’s Disease, 39 (3), 601-609.
A study following 837 people with MCI, of whom 414 (49.5%) had at least one vascular risk factor, has found that those with risk factors such as high blood pressure, diabetes, cerebrovascular disease and high cholesterol were twice as likely to develop Alzheimer's disease. Over five years, 52% of those with risk factors developed Alzheimer's, compared to 36% of those with no risk factors In total, 298 people (35.6%) developed Alzheimer's.
However, of those with vascular risk factors, those receiving full treatment for their vascular problems were 39% less likely to develop Alzheimer's disease than those receiving no treatment, and those receiving some treatments were 26% less likely to develop the disease.
Treatment of risk factors included using high blood pressure medicines, insulin, cholesterol-lowering drugs and diet control. Smoking and drinking were considered treated if the person stopped smoking or drinking at the start of the study.
(2011). Vascular risk factors promote conversion from mild cognitive impairment to Alzheimer disease.
Neurology. 76(17), 1485 - 1491.
Part of the Women's Health Initiative study looking at the effect of hormone therapy on thinking and memory in postmenopausal women, involving over 1400 women, has found those who had high blood pressure at the start of the study (eight years earlier) had significantly higher amounts of white matter lesions. Damage to white matter seems to be an independent risk factor for dementia. The finding adds to evidence suggesting that preventing hypertension helps protect against dementia. High blood pressure is common in the U.S. — of the nearly 99,000 women enrolled in the WHI study, 37.8% had hypertension. You can watch the researcher discussing the findings at http://www.eurekalert.org/multimedia/pub/19494.php?from=152110
Kuller, L. H., Margolis, K. L., Gaussoin, S. A., Bryan, N. R., Kerwin, D., Limacher, M., et al. (2009). Relationship of Hypertension, Blood Pressure, and Blood Pressure Control With White Matter Abnormalities in the Women's Health Initiative Memory Study (WHIMS) MRI Trial. The Journal of Clinical Hypertension, 9999(9999). doi: 10.1111/j.1751-7176.2009.00234.x.
Midlife hypertension has been confirmed as a risk factor for the development of dementia in late life, but there have been conflicting findings about the role of late-life hypertension. Now a five-year study involving 990 older adults (average age 83) with cognitive impairment but no dementia, has found that dementia developed at around the same rate among participants with and without hypertension, among those with memory dysfunction alone and those with both memory and executive dysfunction. However, among patients with executive dysfunction only, presence of hypertension was associated with double the risk of developing dementia (57.7 percent of those with high blood pressure progressed to dementia, vs. 28 percent of those without). The findings suggest that efforts to control to hypertension should be especially targeted to this group.
(2010). Hypertension, Executive Dysfunction, and Progression to Dementia: The Canadian Study of Health and Aging.
Arch Neurol. 67(2), 187 - 192.
Two mouse experiments have found that the drug carvedilol, prescribed for the treatment of hypertension, significantly improved synaptic transmission in Alzheimer's disease-type brains, and at a behavioral level significantly improved learning and memory.
(Submitted). Carvedilol as a potential novel agent for the treatment of Alzheimer's disease.
Neurobiology of Aging. In Press, Corrected Proof,
Arrieta-Cruz, I. et al. 2010. Carvedilol Reestablishes Long-Term Potentiation in a Mouse Model of Alzheimer’s Disease. Journal of Alzheimer's Disease, 21 (2), in press.
Older news items (pre-2010) brought over from the old website
Why sufferers from Alzheimer's disease might have lower blood pressure
A review of studies relating to dementia and blood pressure suggests that rather than low blood pressure being a causative factor for cognitive impairment, it is the failing memory that reduces blood pressure — by allowing the patient to forget the anxieties that cause stress. If confirmed, the finding also suggests that heart disease could be substantially reduced in old people simply by making them happier about themselves and their lives.
Sven, K. et al. 2008. Is sympathetic activation by stressful memories linked to the occurrence of hypertension and metabolic syndrome? Bioscience Hypotheses, 1 (4), 179-184.
Full text available at http://dx.doi.org/10.1016/j.bihy.2008.04.006
High blood pressure or irregular heartbeat linked to Alzheimer's disease progression
A study of 135 men and women newly diagnosed with Alzheimer’s found that those with high blood pressure at the time of diagnosis showed a rate of memory loss roughly 100% faster than those with normal blood pressure, and those with atrial fibrillation (an irregular heartbeat) showed a rate of memory decline that was 75% faster than those with normal heartbeats. The findings suggest that treating these conditions may also slow memory loss in Alzheimer’s sufferers.
Mielke, M.M. et al. 2007. Vascular factors predict rate of progression in Alzheimer disease. Neurology, 69, 1850-1858
Low blood pressure risk factor for Alzheimer's
A long-term study of 488 adults over 75 (the Bronx Aging Study) found that 122 participants developed dementia (65 Alzheimer’s, 28 vascular dementia, 29 other), and that the relative risk of dementia increased as a function of decreases in blood pressure (diastolic and mean arterial). Low diastolic BP significantly increased the risk of developing Alzheimer’s, but not vascular dementia. Those with mildly to moderately raised systolic BP had a reduced risk of developing Alzheimer’s. The risk of developing dementia was higher in those who had persistently low BP over 2 years.
Verghese, J., Lipton, R.B., Hall, C.B., Kuslansky, G. & Katz, M.J. 2003. Low blood pressure and the risk of dementia in very old individuals. Neurology, 61, 1667-1672.
High blood pressure and cholesterol are risk factors for Alzheimer's disease
A large-scale Finnish study following 1449 men and women over 21 years found that raised systolic blood pressure and high serum cholesterol concentration, particularly in combination, in midlife, increase the risk of Alzheimer's disease in later life. Raised diastolic blood pressure had no significant effect.
The study was reported in the British Medical Journal.