Alzheimers

Alzheimer's & other dementias

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, UPSIT was 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.

https://www.eurekalert.org/pub_releases/2016-12/uops-psc122016.php

https://www.eurekalert.org/pub_releases/2016-11/mgh-atr111416.php

http://www.eurekalert.org/pub_releases/2016-07/cumc-stm072516.php

Reference: 

[4209] Quarmley, M., Moberg P. J., Mechanic-Hamilton D., Kabadi S., Arnold S. E., Wolk D. A., et al.
(2017).  Odor Identification Screening Improves Diagnostic Classification in Incipient Alzheimer’s Disease.
Journal of Alzheimer's Disease. 55(4), 1497 - 1507.

[4210] Dhilla, A. Alefiya, Asafu-Adjei J., Delaney M. K., Kelly K. E., Gomez-Isla T., Blacker D., et al.
(2016).  Episodic memory of odors stratifies Alzheimer biomarkers in normal elderly.
Annals of Neurology. 80(6), 846 - 857.

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.

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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.

https://www.theguardian.com/society/2017/feb/21/long-winded-speech-could-be-early-sign-of-alzheimers-says-study

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Janet Sherman presented the findings at the annual meeting of the American Association for the Advancement of Science in Boston, in February 2017.

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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.

https://www.eurekalert.org/pub_releases/2017-02/ip-mci022317.php

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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.

https://www.eurekalert.org/pub_releases/2016-10/oupu-fwc100316.php

https://www.eurekalert.org/pub_releases/2016-08/ind-cai083016.php

https://www.eurekalert.org/pub_releases/2017-03/iu-cbe030717.php

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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.

http://www.eurekalert.org/pub_releases/2016-04/ul-dib040716.php

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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.

http://www.eurekalert.org/pub_releases/2016-04/uom-wdp040816.php

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Different kinds of physical activity improve brain volume & cut Alzheimer's risk

  • A large long-running study adds to growing evidence that higher levels of physical activity reduce brain atrophy and Alzheimer's risk, and shows that many types of aerobic activity are beneficial.

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.

http://www.eurekalert.org/pub_releases/2016-03/ip-dko030916.php

http://www.eurekalert.org/pub_releases/2016-03/uops-bmc031016.php

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Rates of new dementia cases may be falling

  • Data from the very long-running Framingham Heart Study adds to evidence that, for those with at least a high school education, the rate of dementia is declining. Improved cardiovascular health and treatment appears to be an important factor in this decline.

As we all know, people are living longer and obesity is at appalling levels. For both these (completely separate!) reasons, we expect to see growing rates of dementia. A new analysis using data from the long-running Framingham Heart Study offers some hope to individuals, however.

Looking at the rate of dementia during four distinct periods in the late 1970s, late 1980s, 1990s, and 2000s, using data from 5205 older adults (60+), the researchers found that there was a progressive decline in the incidence of dementia at a given age, with an average reduction of 20% per decade since the 1970s (22%, 38%, and 44% during the second, third, and fourth epochs, respectively).

There are two important things to note about this finding:

  • the decline occurred only in people with a high school education and above
  • the decline was more pronounced with dementia caused by vascular diseases, such as stroke.

The cumulative risk over five years, adjusted for age and gender, were:

  • 3.6 per 100 persons during the first period (late 1970s and early 1980s)
  • 2.8 per 100 persons during the second period (late 1980s and early 1990s)
  • 2.2 per 100 persons during the third period (late 1990s and early 2000s)
  • 2.0 per 100 persons during the fourth period (late 2000s and early 2010s).

Part of the reason for the decline is put down to the decrease in vascular risk factors other than obesity and diabetes, and better management of cardiovascular diseases and stroke. But this doesn't completely explain the decrease. I would speculate that other reasons might include:

  • increased mental stimulation
  • improvements in lifestyle factors such as diet and exercise
  • better health care for infectious and inflammatory conditions.

The finding is not completely unexpected. Recent epidemiological studies in the U.S., Canada, England, the Netherlands, Sweden and Denmark have all suggested that “a 75- to 85-year-old has a lower risk of having Alzheimer’s today than 15 or 20 years ago.” Which actually cuts to the heart of the issue: individual risk of dementia has gone down (for those taking care of their brain and body), but because more and more people are living longer, the numbers of people with dementia are increasing.

http://www.futurity.org/dementia-rates-decline-1119512-2/

http://www.scientificamerican.com/article/is-dementia-risk-falling/

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Fish reduces Alzheimer's risk for those with APOE gene

  • A new study finds that seafood consumption reduces Alzheimer's pathology, but only in those with the Alzheimer's gene APOEe4. While fish oil didn't appear to affect brain health, the omega-3 acid found in flaxseed did.

I've spoken before about how the presence or absence of the “Alzheimer's gene” may affect which lifestyle changes are beneficial for you. A new study has added to that idea with a finding that seafood consumption was associated with fewer signs of Alzheimer's-related pathology, but only among those with the APOEe4 gene.

Seafood consumption was also associated with increased mercury levels in the brain, with levels rising the more seafood was consumed. However, higher levels of mercury were not correlated with any neuropathologies.

Fish oil supplementation was not associated with any differences in neuropathology. However, higher levels of alpha-linolenic acid (an omega-3 fatty acid found in flaxseed, chia seeds, walnuts, etc) were associated with a reduced chance of cerebral infarctions.

The study involved 554 deceased participants (average age 89.9 years) from the long-running Memory and Aging Project (MAP) conducted by Rush University Medical Center. The participants had completed annual dietary questionnaires over a number of years. The brains of 286 participants were autopsied, to assess neuropathologies and mercury levels.

The average educational attainment of the participants was 14.6 years; 67% were women.

The finding tempers the evidence from many studies that eating fish reduces Alzheimer's risk. However, it is consistent with what I believe is becoming apparent: that there are different paths to Alzheimer's, and thus different factors involved in preventing it, depending on your own particular gene-environment attributes.

http://www.eurekalert.org/pub_releases/2016-02/nioe-scm020116.php

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How dementia risk varies among ethnic groups

  • A very large U.S. study looking at ethnic differences in dementia risk, has found that African-Americans show the highest rates of dementia, followed by blacks and American Indian/Alaska Natives, then Latinos and whites, with Asian-Americans having the lowest rates.

A study involving 14 years of health records from more than 274,000 Northern Californians has assessed the relative dementia risk of six different ethnicities.

The average annual rate of dementia was:

  • 26.6 cases per 1,000 for blacks
  • 22.2 cases per 1,000 for American Indians/Alaskan Natives
  • 19.6 cases per 1,000 for Latinos and Pacific Islanders
  • 19.3 cases per 1,000 for whites
  • 15.2 cases per 1,000 for Asian Americans.

But this is an annual rate, not particularly useful at a practical level. How do these numbers convert to lifetime risk? Statistical calculations estimate that among those who reach age 65 dementia-free, the following percentages of each ethnicity will develop dementia in the next 25 years:

  • 38% of blacks
  • 35% of American Indians/Alaskan Natives
  • 32% of Latinos
  • 30% of whites
  • 28% of Asian Americans
  • 25% of Pacific Islanders (this is probably the least reliable number, given the small number of Pacific Islanders in the sample).

The study population included 18,778 African-Americans, 4543 American Indians/Alaskan Natives, 21,000 Latinos, 206,490 white Americans, 23,032 Asian-Americans, and 440 Pacific Islanders.

http://www.eurekalert.org/pub_releases/2016-02/kp-lsf021016.php

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[4056] Mayeda, E. Rose, M. Glymour M., Quesenberry C. P., & Whitmer R. A.
(2016).  Inequalities in dementia incidence between six racial and ethnic groups over 14 years.
Alzheimer's & Dementia: The Journal of the Alzheimer's Association.

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