Memory Research News in Alzheimer's & Dementia

Smell tests provide early evidence of dementia

  • It seems clear now that a substantial decline in sense of smell is a very early sign of developing MCI and Alzheimer's.
  • Several tests have been developed to assess this.
  • It should always be remembered that there is substantial difference between individuals in their 'natural' sense of smell, and this needs to be taken into account in any test.

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).

Smell test improves accuracy of MCI & Alzheimer's diagnosis

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.

A new smell test

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:

  • In the OPID (Odor Percept IDentification)-10 test, participants are presented with 10 odors (menthol, clove, leather, strawberry, lilac, pineapple, smoke, soap, grape, lemon) for two seconds each. They are then asked whether the scent is familiar and given a choice of four of the 10 words from which are asked to pick the best one that describes the odor.
  • The Odor Awareness Scale (OAS) assesses their overall attention to environmental odors and how they are affected emotionally and behaviorally by scents.
  • The OPID-20 test includes an additional 10 odors (banana, garlic, cherry, baby powder, grass, fruit punch, peach, chocolate, dirt, orange). Participants are first asked whether a presented odor was included in the OPID-10 test and then asked which word best describes the odor. Their ability to remember odors from the first test determines their POEM (Percepts of Odor Episodic Memory) score.
  • In the Odor Discrimination (OD) test, participants are presented with two consecutive odors and asked whether they were different or the same, a process that is repeated 12 times with different paired scents.

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.

Validation of UPSIT

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.


[4209] 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:

[4210] 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:

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.

Long-winded speech could be early sign of Alzheimer's

  • Rambling and long-winded explanations may be an early sign of mild cognitive impairment. The problem is not the increase in verbosity, however, but a growing inability to be precise.

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:

  • were much less concise in conveying information
  • produced much longer sentences
  • had a hard time staying on point
  • were much more roundabout in getting their point across.

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.

Diagnosing MCI at home

  • A Greek pilot study has shown that a self-administered cognitive training game can detect mild cognitive impairment (MCI).

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.


[4208] 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:

Higher coffee consumption linked to lower dementia risk in women

  • A large study adds to evidence that caffeine helps older women fight cognitive impairment and dementia.
  • This is supported by two animal studies showing precisely how caffeine is valuable for keeping the brain healthy.

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.


[4231] 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:

[4232] 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:

[4211] 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:

Age-related drop in body temperature worsens Alzheimer's disease

  • A mouse study suggests that some Alzheimer’s symptoms are made worse by falling body temperature — and are helped by improving body temperature.

Our bodies’ ability to regulate its temperature gets worse with age, along with a slowing metabolism. We also become more vulnerable to Alzheimer's as we age. A study compared mice genetically engineered to manifest Alzheimer's symptoms as they age with normal mice. They found that these transgenic mice were worse at maintaining their body temperature as they aged, with the difference reaching almost 1° Celsius by the age of 12 months.

Moreover, there was an increase in Alzheimer’s symptoms (such as a greater increase in abnormal tau proteins and loss of synaptic proteins) in transgenic mice when they were exposed to low temperatures.

But — and this is the exciting bit — when the mice were given one week in a 28°C environment, and their body temperature increased by 1°C, beta-amyloid production dropped substantially, and memory test results were comparable to those of normal mice.

While obviously these results need to be replicated in humans, the findings do suggest that improving body temperature might be helpful for those in early stages of Alzheimer’s. Body temperature can be increased through physical activity, diet, drugs, or simply by turning the heat up.


[4207] Vandal M, White PJ, Tournissac M, Tremblay C, St-Amour I, Drouin-Ouellet J, Bousquet M, Traversy M-T, Planel E, Marette A, et al. Impaired thermoregulation and beneficial effects of thermoneutrality in the 3×Tg-AD model of Alzheimer's disease. Neurobiology of Aging [Internet]. Submitted ;43:47 - 57. Available from:

Why people with Alzheimer's stop recognizing their loved ones

  • A finding that Alzheimer's sufferers' failure to recognize familiar faces is rooted in an impairment in holistic perception rather than memory loss, suggests new strategies to help patients recognize their loved ones for longer.

People with Alzheimer's disease develop problems in recognizing familiar faces. It has been thought that this is just part of their general impairment, but a new study indicates that a specific, face-related impairment develops early in the disease. This impairment has to do with the recognition of a face as a whole.

Face recognition has two aspects to it: holistic (seeing the face as a whole) and featural (processing individual features of the face). While both are useful in object recognition, expert recognition (and face recognition is usually something humans are expert in) is built on a shift from featural to holistic processing.

The study compared the ability of people with mild Alzheimer's and healthy age- and education-matched seniors to recognize faces and cars in photos that were either upright or upside down. It found that those with Alzheimer's performed comparably to the control group in processing the upside-down faces and cars. This type of processing requires an analysis of the various features. Those with Alzheimer’s also performed normally in recognizing upright cars (car experts are likely to use holistic processing, but those with less expertise will depend more on featural processing). However, they were much slower and less accurate in recognizing faces.

Realizing that impaired facial recognition is based on a holistic perception problem, rather than being simply another failure of memory, suggests that strategies such as focusing on particular facial features or on voice recognition may help patients recognize their loved ones for longer.


[4206] Lavallée MMaxime, Gandini D, Rouleau I, Vallet GT, Joannette M, Kergoat M-J, Busigny T, Rossion B, Joubert S. A Qualitative Impairment in Face Perception in Alzheimer’s Disease: Evidence from a Reduced Face Inversion Effect. Journal of Alzheimer's Disease [Internet]. 2016 ;51(4):1225 - 1236. Available from: