mild cognitive impairment
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. Face-specific memory deficits and changes in eye scanning patterns among patients with amnestic mild cognitive impairment. Scientific Reports [Internet]. 2017 ;7(1):14344. Available from: https://www.nature.com/articles/s41598-017-14585-5
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 RJ, Langlais BT, Dueck AC, Henslin BR, Johnson TA, Woodruff BK, Hoffman‐Snyder C, Locke DEC. Personality Changes During the Transition from Cognitive Health to Mild Cognitive Impairment. Journal of the American Geriatrics Society [Internet]. 2018 ;66(4):671 - 678. Available from: https://onlinelibrary.wiley.com/doi/abs/10.1111/jgs.15182
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.
A study involving 35 adults with MCI found that those who exercised four times a week over a six-month period increased their volume of gray matter. But those who participated in aerobic exercise experienced significantly greater gains than those who just stretched, who also showed signs of white matter loss.
Aerobic activity included treadmill, stationary bike or elliptical training.
The study was presented at the annual meeting of the Radiological Society of North America (RSNA) in November, 2016.
In the past few months, several studies have come out showing the value of three different tests of people's sense of smell for improving the accuracy of MCI and Alzheimer's diagnosis, or pointing to increased risk. The studies also add to growing evidence that a decline in sense of smell is an early marker for mild cognitive impairment and Alzheimer’s. Indeed, it appears that this sensory loss is a very early symptom, preceding even the shrinking of the entorhinal cortex (the first brain region to show signs of atrophy).
A simple, commercially available test known as the Sniffin' Sticks Odor Identification Test, in which subjects must try to identify 16 different odors, was given to 728 older adults, as well as a standard cognitive test (the Montreal Cognitive Assessment).
The participants had already been evaluated by doctors and classified as being healthy (292 subjects), having MCI (174: 150 aMCI, 24 naMCI), or having Alzheimer's (262).
It was found that, while the cognitive test alone correctly classified 75% of people with MCI, the number rose to 87% when the sniff test results were added. Diagnosis of Alzheimer's, and of subtypes within MCI, was also improved.
The smell test normally takes 5 to 8 minutes to administer; the researchers are trying to get it down to 3 minutes, to encourage greater use.
Another recent study validates a new smell test which is rather more complicated. The test was developed because the standard University of Pennsylvania Smell Identification Test doesn’t take into account the great variation in olfactory ability among healthy individuals. The ability of normal individuals to recognize and discriminate between odors can vary by as much as 40 times!
The new test is actually four tests:
The study involved 183 older adults, of whom 70 were cognitively normal, 74 tested normal but were concerned about their cognitive abilities, 29 had MCI and 10 had been diagnosed with possible or probable Alzheimer's disease.
Results of the OPID-20 test significantly differentiated among the four groups of participants, and those results correlated with the thinning of the hippocampus and the entorhinal cortex. Participants' ability to remember a previously presented aroma, as reflected in the POEM score, was also significant, with participants with Alzheimer's disease performing at no better than chance.
POEM scores of the two cognitively normal groups were compared with what would have been predicted based on their ability to identify and differentiate between odors, as reflected in the OAS and OD tests. Poor POEM performers were more likely to have the ‘Alzheimer's gene’ (APOEe4), showed thinning of the entorhinal cortex, and poorer cognitive performance over time.
However, two 2016 studies support the use of the University of Pennsylvania Smell Identification Test (UPSIT), and suggest it may offer a practical, low-cost alternative to other tests.
In one study, UPSIT was administered to 397 older adults (average age 80) without dementia, who were also given an MRI scan to measure the thickness of the entorhinal cortex (the first brain region to be affected by Alzheimer's disease). After four years, 50 participants (12.6%) had developed dementia, and nearly 20% had signs of cognitive decline.
Low UPSIT scores, but not entorhinal cortical thickness, were significantly associated with dementia and Alzheimer's disease, and with cognitive impairment. Entorhinal cortical thickness was significantly associated with UPSIT score in those who transitioned from MCI to dementia.
In other words, it looks like impairment in odor identification precedes thinning in the entorhinal cortex.
In another study, UPSITwas administered to 84 older adults, of whom 58 had MCI, as well as either beta amyloid PET scanning or analysis of cerebrospinal fluid. After six months, 67% had signs of memory decline, and this was predicted by amyloid-beta levels (assessed by either method), but not UPSIT score. However, participants with a score of less than 35 were more than three times as likely to have memory decline as those with higher UPSIT scores.
The researchers suggest the association wasn’t as strong in this study because of the younger age of participants (median age 71), their higher education, and the short follow-up.
 Quarmley M, Moberg PJ, Mechanic-Hamilton D, Kabadi S, Arnold SE, Wolk DA, Roalf DR. Odor Identification Screening Improves Diagnostic Classification in Incipient Alzheimer’s Disease. Journal of Alzheimer's Disease [Internet]. 2017 ;55(4):1497 - 1507. Available from: http://content.iospress.com/articles/journal-of-alzheimers-disease/jad160842
 Dhilla AAlefiya, Asafu-Adjei J, Delaney MK, Kelly KE, Gomez-Isla T, Blacker D, Johnson KA, Sperling RA, Hyman BT, Betensky RA, et al. Episodic memory of odors stratifies Alzheimer biomarkers in normal elderly. Annals of Neurology [Internet]. 2016 ;80(6):846 - 857. Available from: http://onlinelibrary.wiley.com/doi/10.1002/ana.24792/abstract
Lee, Seonjoo et al. 2016. Predictive Utility of Entorhinal Cortex Thinning and Odor Identification Test for Transition to Dementia and Cognitive Decline in an Urban Community Population. Presented at the Alzheimer's Association's International Conference in Toronto.
Kreisl, William et al. 2016. Both Odor Identification and Amyloid Status Predict Memory Decline in Older Adults. Presented at the Alzheimer's Association's International Conference in Toronto.
A study comparing the language abilities of 22 healthy young individuals, 24 healthy older individuals and 22 people with MCI, has found that those with MCI:
So, for example, when given an exercise in which they had to join up three words (e.g., “pen”, “ink” and “paper”), the healthy volunteers typically joined the three in a simple sentence, while the MCI group gave circuitous accounts such as going to the shop and buying a pen.
Additionally, when asked to repeat phrases read out by the interviewer, those with MCI had trouble when given phrases involving ambiguous pronouns (e.g., “Fred visited Bob after his graduation”), although they had no trouble with more complex sentences.
A caveat: if you're just one of those people who has always talked like this, don't panic! It's a matter of change and deterioration, not a stable personality trait.
Janet Sherman presented the findings at the annual meeting of the American Association for the Advancement of Science in Boston, in February 2017.
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.
 Zygouris S, Ntovas K, Giakoumis D, Votis K, Doumpoulakis S, Segkouli S, Karagiannidis C, Tzovaras D, Tsolaki M. 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 [Internet]. 2017 ;56(2):619 - 627. Available from: http://content.iospress.com/articles/journal-of-alzheimers-disease/jad160518
Data from the Women's Health Initiative Memory Study, involving 6,467 postmenopausal women (65+) who reported some level of caffeine consumption, has found that those who consumed above average amounts of coffee had a lower risk of developing dementia.
Caffeine intake was estimated from a questionnaire. The median intake was 172 mg per day (an 8-ounce cup of brewed coffee contains 95mg of caffeine, 8-ounces of brewed black tea contains 47mg, so slightly less than 2 cups of coffee or less than 4 cups of tea). The women were cognitively assessed annually.
Over ten years, 388 were diagnosed with probable dementia (209) or MCI (179). Those who consumed above the median amount of caffeine had a 36% reduction in risk. The average intake in this group was 261 mg (3 cups of coffee), while the average intake for those below the median was 64 mg per day (less than one cup).
Risk factors such as hormone therapy, age, race, education, body mass index, sleep quality, depression, hypertension, prior cardiovascular disease, diabetes, smoking, and alcohol consumption, were taken into account.
The findings are consistent with other research finding a benefit for older women. It should not be assumed that the findings apply to men. It also appears that there may be a difference depending on education level. This sample had a high proportion of college-educated women.
It should also be noted that there was no clear dose-response effect — we could put more weight on the results if there was a clear relationship between amount of caffeine and benefit. Part of the problem here, however, is that it’s difficult to accurately assess the amount of caffeine, given that it’s based on self-report intake of coffee and tea, and the amount of caffeine in different beverages varies significantly.
Moreover, we do have a couple of mechanisms for caffeine to help fight age-related cognitive decline.
A recent study using rats modified to have impaired receptors for the adenosine A2A produced rats showing typical characteristics of an aging brain. In humans, too, age-related cognitive decline has been associated with over-activation of these receptors and dysfunction in glucocorticoid receptors.
The rat study shows that over-activation of the adenosine A2A receptors reduces the levels of glucocorticoid receptors in the hippocampus, which in turn impairs synaptic plasticity and cognition. In other words, it is the over-activation of the adenosine receptors that triggers a process that ends with cognitive impairment.
The point of all this is that caffeine inhibits the adenosine A2A receptors, and when the rats were given a caffeine analogue, their memory deficits returned to normal.
Another more recent study has found that caffeine increases the production of an enzyme that helps prevent tau tangles.
Building on previous research finding that an enzyme called NMNAT2 not only protects neurons from stress, but also helps prevent misfolded tau proteins (linked to Alzheimer’s, and other neurodegenerative disorders), the study identified 24 compounds (out of 1,280 tested) as having potential to increase the production of NMNAT2. One of the most effective of these was caffeine.
When caffeine was given to mice modified to produce lower levels of NMNAT2, the mice began to produce the same levels of the enzyme as normal mice.
 Driscoll I, Shumaker SA, Snively BM, Margolis KL, Manson JAE, Vitolins MZ, Rossom RC, Espeland MA. Relationships Between Caffeine Intake and Risk for Probable Dementia or Global Cognitive Impairment: The Women’s Health Initiative Memory Study. The Journals of Gerontology: Series A [Internet]. 2016 ;71(12):1596 - 1602. Available from: https://academic.oup.com/biomedgerontology/article/71/12/1596/2513764/Relationships-Between-Caffeine-Intake-and-Risk-for
 Batalha VL, Ferreira DG, Coelho JE, Valadas JS, Gomes R, Temido-Ferreira M, Shmidt T, Baqi Y, Buée L, Müller CE, et al. The caffeine-binding adenosine A2A receptor induces age-like HPA-axis dysfunction by targeting glucocorticoid receptor function. Scientific Reports [Internet]. 2016 ;6:31493. Available from: http://www.nature.com/srep/2016/160811/srep31493/full/srep31493.html
 Ali YO, Bradley G, Lu H-C. Screening with an NMNAT2-MSD platform identifies small molecules that modulate NMNAT2 levels in cortical neurons. Scientific Reports [Internet]. 2017 ;7:43846. Available from: http://www.nature.com/srep/2017/170307/srep43846/full/srep43846.html
Data from 876 patients (average age 78) in the 30-year Cardiovascular Health Study show that virtually any type of aerobic physical activity can improve brain volume and reduce Alzheimer's risk.
A higher level of physical activity was associated with larger brain volumes in the frontal, temporal, and parietal lobes including the hippocampus, thalamus and basal ganglia. Among those with MCI or Alzheimer's (25% of the participants), higher levels of physical activity were also associated with less brain atrophy. An increase in physical activity was also associated with larger grey matter volumes in the left inferior orbitofrontal cortex and the left precuneus.
Further analysis of 326 of the participants found that those with the highest energy expenditure were half as likely to have developed Alzheimer's disease five years later.
Physical activity was assessed using the Minnesota Leisure-Time Activities questionnaire, which calculates kilocalories/week using frequency and duration of time spent in 15 different leisure-time activities: swimming, hiking, aerobics, jogging, tennis, racquetball, walking, gardening, mowing, raking, golfing, bicycling, dancing, calisthenics, and riding an exercise cycle.
The study does not look at whether some types of physical activity are better than others, unfortunately, but its message that overall physical activity, regardless of type, helps in the fight against cognitive impairment is encouraging.
 Raji CA, Merrill DA, Eyre H, Mallam S, Torosyan N, Erickson KI, Lopez OL, Becker JT, Carmichael OT, H. Gach M, et al. Longitudinal Relationships between Caloric Expenditure and Gray Matter in the Cardiovascular Health Study. Journal of Alzheimer's disease: JAD. 2016 .
Dr McPherson's practical, research-based books are instantly available as digital downloads from the Mempowered store (all formats), Kindle Store, Kobo Store, and iTunes. They are also available in paperback.