mild cognitive impairment
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.
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.
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.
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.
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.
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.
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.
 Vuoksimaa, E., McEvoy L. K., Holland D., Franz C. E., Kremen W. S., & Initiative for. the Alzhei
(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.
 Elman, J. A., Jak A. J., Panizzon M. S., Tu X. M., Chen T., Reynolds C. A., et al.
(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.
 Galetta, K. M., Chapman K. R., Essis M. D., Alosco M. L., Gillard D., Steinberg E., et al.
(2017). Screening Utility of the King-Devick Test in Mild Cognitive Impairment and Alzheimer Disease Dementia.
Alzheimer Disease & Associated Disorders. 31(2), 152.
 Therriault, J., Ng K. Pin, Pascoal T. A., Mathotaarachchi S., Kang M. Su, Struyfs H., et al.
(2018). Anosognosia predicts default mode network hypometabolism and clinical progression to dementia.
Neurology. 90(11), e932.
 Gerretsen, P., Chung J. Ku, Shah P., Plitman E., Iwata Y., Caravaggio F., et al.
(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 review of 34 longitudinal studies, involving 71,244 older adults, has concluded that depression is associated with greater cognitive decline.
The study included people who presented with symptoms of depression as well as those that were diagnosed as clinically depressed, but excluded any who were diagnosed with dementia at the start of study.
Previous research has found that depression is associated with an increased dementia risk.
The researchers recommend that preventative measures such as exercising, practicing mindfulness, and undertaking recommended therapeutic treatments, such as Cognitive Behaviour Therapy, might help protect cognitive health.
While the review included some studies into anxiety, the numbers were insufficient to draw a conclusion.
 John, A., Patel U., Rusted J., & Richards M.
(Submitted). Affective problems and decline in cognitive state in older adults: a systematic review and meta-analysis.
| Psychological Medicine. 49(3), 353 - 365.
A small study has found that a 12-week exercise program significantly improved cognition in both older adults with MCI and those who were cognitively healthy, but that effect on blood flow in the brain was different in these two groups.
While the exercise increased cerebral blood flow in the frontal cortex of those in the healthy group, those with MCI experienced decreases in cerebral blood flow. It has been speculated that the brain responds to early difficulties by increasing cerebral blood flow. This suggests that exercise may have the potential to reduce this compensatory blood flow and improve cognitive efficiency in those who are in the very early stages of Alzheimer's Disease.
The exercise training program consisted of four 30-minute sessions of moderate-intensity treadmill walking per week.
Both working memory and verbal fluency were tested (using the Rey Auditory Verbal Learning Test, and the Controlled Oral Word Association Test).
Changes in cerebral blood flow were measured in specific brain regions that are known to be involved in the pathogenesis of Alzheimer's disease, including the insula, the anterior cingulate cortex, and the inferior frontal gyrus.
Among those with MCI, decreased blood flow in the left insula and anterior cingulate cortex was strongly associated with improved verbal fluency.
Alfini, A. J. et al. 2019. Resting Cerebral Blood Flow After Exercise Training in Mild Cognitive Impairment. Journal of Alzheimer's Disease, 67 (2), 671-684.
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.
The APOE gene, the strongest genetic risk factor for Alzheimer’s disease, is known to be involved in cholesterol and lipid metabolism. Now the largest ever genetic study of Alzheimer’s disease, using DNA from more than 1.5 million people, has identified 90 points across the genome that were associated with an increased risk of both cardiovascular disease and Alzheimer’s disease.
The study focused on specific risk factors for heart disease (e.g., high BMI, type 2 diabetes, high cholesterol) to see if any were genetically related to Alzheimer’s risk. It was found that only those genes involved in lipid metabolism also related to Alzheimer's risk.
Six of the 90 regions had very strong effects on Alzheimer’s and heightened blood lipid levels, including several points within the CELF1/MTCH2/SPI1 region on chromosome 11 that was previously linked to the immune system.
The same genetic risk factors were also more common in people with a family history of Alzheimer’s, even though they had not themselves developed dementia or MCI.
The findings suggest that cardiovascular and Alzheimer's risk co-occur because of a shared genetic basis.
They also suggest a therapeutic target — namely, pathways involved in lipid metabolism.
Broce I, Karch C, Desikan R, et al. Dissecting the genetic relationship between cardiovascular risk factors and Alzheimer's disease. Acta Neuropathologica, published online Nov. 9, 2018.
Data from 1,215 older adults, of whom 173 (14%) were African-American, has found that, although brain scans showed no significant differences between black and white participants, cerebrospinal fluid (CSF) showed significantly lower levels of the brain protein tau in African-Americans.
While both groups showed the same (expected) pattern of higher tau levels being associated with greater chance of cognitive impairment, the absolute amounts of tau protein were consistently lower in African-Americans.
However, when APOE status was taken into account, it was found that those who held the low-risk variants of the “Alzheimer’s gene” had similar levels of tau, regardless of race. It was only African-Americans with the APOE4 gene variant that showed lower levels of tau.
This suggests that the APOE4 risk factor has different effects in African-Americans compared to non-Hispanic white Americans, and points to the need for more investigation into how Alzheimer’s develops in various populations.
Interestingly, another study, using data from 1798 patients (of whom 1690 were white), found that there was a strong gender difference in the association between APOE status and tau levels in the CSF.
Previous research has shown that the link between APOE4 and Alzheimer's is stronger in women than men. This study points to a connection with tau levels, as there was no gender difference in the association between APOE and amyloid-beta levels, amyloid plaques, or tau tangles.
Morris JC, Schindler SE, McCue LM, et al. Assessment of Racial Disparities in Biomarkers for Alzheimer Disease. JAMA Neurol. Published online January 07, 2019. doi:10.1001/jamaneurol.2018.4249
Hohman TJ, Dumitrescu L, Barnes LL, et al. Sex-Specific Association of Apolipoprotein E With Cerebrospinal Fluid Levels of Tau. JAMA Neurol. 2018;75(8):989–998. doi:10.1001/jamaneurol.2018.0821
One important reason for the greater cognitive problems commonly experienced as we age, is our increasing difficulty in ignoring distracting and irrelevant information. But it may be that in some circumstances that propensity can be used to help memory.
The study involved 25 younger (17-23) and 32 older adults (60-86), who were shown the faces and names of 24 different people and told to learn them. The names were written in bright blue text and placed on the forehead, and each photo was shown for 3 seconds. After the learning session, participants were immediately tested on their recall of the name for each face. The test was self-paced. Following a 10 minute interval, during which they were given psychological tests, they were shown more photos of faces, but this time were told to ignore the text — their task was to push a button when they saw the same face appear twice in a row. The text was varied: sometimes names, sometimes words, and sometimes nonwords. Ten of the same faces and names from the first task were repeated in the series of 108 trials; all items were repeated three times (thus, 30 repeated face-name pairs; 30 other face-name pairs; 24 face-word pairs; 24 face-nonword pairs). The photos were each displayed for 1.5 seconds. A delayed memory test was given after another 10 minutes of psychological testing. A cued-recall test was followed by a forced-choice recognition test.
Unsurprisingly, overall younger adults remembered more names than older adults, and both groups remembered more on the second series, with younger adults improving more. But younger adults showed no benefit for the repeated face-name pairs, while — on the delayed recall task only — older adults did.
Interestingly, there was no sign, in either group, of repeated names being falsely recalled or recognized. Nor did they significantly affect familiarity.
It seems that this sort of inadvertent repetition doesn’t improve memory for items (faces, names), but, specifically, the face-name associations. The study builds on previous research indicating that older adults hyperbind distracting names and attended faces, which produces better learning of these face-name pairs.
It’s suggested that repetition as distraction might act as a sort of covert retrieval practice that relies on a nonconscious process specifically related to the priming of relational associations. Perhaps older adults’ vulnerability to distraction is not simply a sign of degeneration, but reflects a change of strategy to one that increases receptiveness to environmental regularities that have predictive value. Younger adults have narrowed attention that, while it allows them greater focus on the task, also stops them noticing information that is immediately irrelevant but helpful further down the track.
The researchers are working on a training program to help older adults with MCI use this benefit to better remember faces and names.
Biss, Renée K., Rowe, Gillian, Weeks, Jennifer C., Hasher, Lynn, Murphy, Kelly J. 2018. Leveraging older adults’ susceptibility to distraction to improve memory for face-name associations. Psychology and Aging, 33(1), 158-164.
A small Japanese study has found evidence that those with amnestic mild cognitive impairment (aMCI) show a specific decline in their ability to recognize faces, and this is accompanied by changes in the way they scan faces.
The study involved 18 patients with aMCI and 18 age-matched healthy controls. Participants were tested on their ability to perceive and remember images of faces and houses.
Those with aMCI showed poorer memory for faces compared to their memory for houses, while control participants showed no difference between the two. Moreover, compared with controls, those with aMCI spent less time looking at the eyes in the image, while increasing the time they spent looking at the mouths of faces.
In general, people have an excellent memory for faces compared to other visual stimuli, and the eyes are particularly useful in helping us remember the face. The researchers suggest that damage to the brain region known as the fusiform face area (FFA) is responsible for the abnormal processing of faces. It is worth noting that a case study of a patient with acquired prosopagnosia revealed the same pattern of fixating on the mouth rather than the eyes.
The finding is consistent with several other studies showing impaired face processing in those with aMCI, but there is some controversy about that conclusion.
Full text available at https://www.nature.com/articles/s41598-017-14585-5
 Kawagoe, T., Matsushita M., Hashimoto M., Ikeda M., & Sekiyama K.
(2017). Face-specific memory deficits and changes in eye scanning patterns among patients with amnestic mild cognitive impairment.
Scientific Reports. 7(1), 14344.
Mild cognitive impairment (MCI) is a precursor of Alzheimer's disease, although having MCI does not mean you are definitely going to progress to Alzheimer's. A new study suggests that one sign of MCI development might be personality changes.
The study involved 277 cognitively healthy residents of a U.S. County, who had the apolipoprotein E (APOE) ɛ4 gene (otherwise known as the ‘Alzheimer’s gene’). Over the study period (around 7 years), 25 developed MCI. Their performance on the Neuroticism, Extraversion, and Openness Personality Inventory—Revised (delivered at the beginning of the study, as well as at other times during the study) was compared with that of the other 252 participants.
Neuroticism increased significantly more in those developing MCI, and openness decreased more. Those developing MCI also showed significantly greater depression, somatization, irritability, anxiety, and aggressive attitude. (Somatization refers to the tendency to generate physical manifestations in response to psychological distress.)
While such personality changes may be barely noticeable at this stage, it may be that diagnosing such early personality changes could help experts develop earlier, safer, and more effective treatments — or even prevention options — for the more severe types of behavior challenges that affect people with Alzheimer's disease.
 Caselli, R. J., Langlais B. T., Dueck A. C., Henslin B. R., Johnson T. A., Woodruff B. K., et al.
(2018). Personality Changes During the Transition from Cognitive Health to Mild Cognitive Impairment.
Journal of the American Geriatrics Society. 66(4), 671 - 678.
Data from over 11,500 participants in the Atherosclerosis Risk in Communities (ARIC) cohort has found evidence that orthostatic hypotension in middle age may increase the risk of cognitive impairment and dementia 20 years later.
Orthostatic hypotension is the name for the experience of dizziness or light-headedness on standing up. Previous research has suggested an association between orthostatic hypotension and cognitive decline in older adults.
In this study, participants aged 45-64 were tested for orthostatic hypotension in 1987. Those with it (703, around 6%) were 40% more likely to develop dementia in the next 20 years. They also had some 15% more cognitive decline.
Orthostatic hypotension was defined as a drop of 20 mmHg or more in systolic blood pressure or 10 mmHg or more in diastolic blood pressure, when the individual stood up after 20 minutes lying down.
More work is needed to understand the reason for the association.
Rawlings, Andreea. 2017. Orthostatic Hypotension is Associated with 20-year Cognitive Decline and Incident Dementia: The Atherosclerosis Risk in Communities (ARIC) Study. Presented March 10 at the American Heart Association's EPI|LIFESTYLE 2017 Scientific Sessions in Portland, Oregon.
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