seniors

Mediterranean diet reduces brain shrinkage in old age

  • The Mediterranean diet is the diet most associated with cognitive and health benefits in older adults.
  • A new study has found larger brain volumes among those following this sort of diet, equivalent to that of brains five years younger.
  • Much of this was associated with two components of the diet in particular: eating fish regularly, and eating less meat.

Another study adds to the growing evidence that a Mediterranean diet is good for the aging brain.

The New York study used data from 674 non-demented older adults (average age 80). It found that those who closely followed such a diet showed significantly less brain shrinkage. Specifically, total brain volume was an average 13.11 milliliters greater, with grey matter volume 5 millilitres greater, and white matter 6.4 millilitres greater.

Eating at least five of the recommended Mediterranean diet components was associated with benefits equivalent to five years of age. By far the most important of these components was regular fish and reduced meat intake — at least 3 to 5 ounces of fish weekly; no more than 3.5 ounces of meat daily.

This is consistent with a considerable amount of research indicating the benefits of fish in fighting age-related cognitive decline.

http://www.theguardian.com/lifeandstyle/2015/oct/21/mediterranean-diet-may-slow-the-ageing-process-by-five-years

Reference: 

[4025] Gu, Y., Brickman A. M., Stern Y., Habeck C. G., Razlighi Q. R., Luchsinger J. A., et al.
(2015).  Mediterranean diet and brain structure in a multiethnic elderly cohort.
Neurology. 10.1212/WNL.0000000000002121.

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Alzheimer's disease consists of 3 distinct subtypes

  • A very small study points to three subtypes of Alzheimer's disease, each of which seems to be associated with:
    • different physiological abnormalities
    • different causes and risk factors
    • different symptoms / progression
    • different age-onsets.
  • This suggests that effective treatments need to be tailored to the subtype.

A two-year study which involved metabolic testing of 50 people, suggests that Alzheimer's disease consists of three distinct subtypes, each one of which may need to be treated differently. The finding may help explain why it has been so hard to find effective treatments for the disease.

The subtypes are:

  • Inflammatory, in which markers such as C-reactive protein and serum albumin to globulin ratios are increased.
  • Non-inflammatory, in which these markers are not increased but other metabolic abnormalities (such as insulin resistance, hypovitaminosis D, and hyper-homocysteinemia) are present. This tends to affect slightly older individuals than the first subtype: 80s rather than 70s.
  • Cortical, which affects relatively young individuals (typically 50s- early 70s) and appears more widely distributed across the brain than the other subtypes, showing widespread cortical atrophy rather than marked hippocampal atrophy. It typically presents with language and number difficulties first, rather than memory loss. Typically, there is an impaired ability to hold onto a train of thought. It is often misdiagnosed, typically affects people without a family history of Alzheimer's, who do not have an Alzheimer's-related gene, and is associated with a significant zinc deficiency (Zinc is implicated in multiple Alzheimer's-related metabolic processes, such as insulin resistance, chronic inflammation, ADAM10 proteolytic activity, and hormonal signaling. Zinc deficiency is relatively common, and associated with increasing age.).

The cortical subtype appears to be fundamentally a different condition than the other two.

I note a study I reported on last year, that found different molecular structures of amyloid-beta fibrils in the brains of Alzheimer's patients with different clinical histories and degrees of brain damage. That was a very small study, indicative only. However, I do wonder if there's any connection between these two findings. At the least, I think this approach a promising one.

The idea that there are different types of Alzheimer's disease is of course consistent with the research showing a variety of genetic risk factors, and an earlier study indicating at least two pathways to Alzheimer's.

It's also worth noting that the present study built on an earlier study, which showed that a program of lifestyle, exercise and diet changes designed to improve the body's metabolism reversed cognitive decline within 3-6 months in nine out of 10 patients with early Alzheimer's disease or its precursors. Note that this was a very small pilot program, and needs a proper clinical trial. Nevertheless, it is certainly very interesting.

http://www.eurekalert.org/pub_releases/2015-09/uoc--adc091615.php

Reference: 

Bredesen, D.E. 2015. Metabolic profiling distinguishes three subtypes of Alzheimer's disease. AGING, 7 (8), 595-600. Full text at http://www.impactaging.com/papers/v7/n8/full/100801.html

Bredesen, D.E. 2014. Reversal of cognitive decline: A novel therapeutic program. AGING, Vol 6, No 9 , pp 707-717. Full text at http://www.impactaging.com/papers/v6/n9/full/100690.html

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More evidence that stress increases risk of Alzheimer's

  • A stress hormone has been found to be associated with more amyloid-beta protein, in mice and human neurons.
  • The finding helps explain why stress is a risk factor for Alzheimer's.
  • A previous 38-year study supports this with the finding that women who scored highly in "neuroticism" in middle age, had a greater chance of later developing Alzheimer's.
  • This link was largely accounted for by chronic stress experienced by these women over the four decades.

A study involving both mice and human cells adds to evidence that stress is a risk factor for Alzheimer's.

The study found that mice who were subjected to acute stress had more amyloid-beta protein in their brains than a control group. Moreover, they had more of a specific form of the protein, one that has a particularly pernicious role in the development of Alzheimer's disease.

When human neurons were treated with the stress hormone corticotrophin releasing factor (CRF), there was also a significant increase in the amyloid proteins.

It appears that CRF causes the enzyme gamma secretase to increase its activity. This produces more amyloid-beta.

The finding supports the idea that reducing stress is one part of reducing your risk of developing Alzheimer's.

A neurotic personality increases the risk of Alzheimer's disease

An interesting study last year supports this.

The study, involving 800 women who were followed up some 40 years after taking a personality test, found that women who scored highly in "neuroticism" in middle age, have a greater chance of later developing Alzheimer's. People who have a tendency to neuroticism are more readily worried, distressed, and experience mood swings. They often have difficulty in managing stress.

The women, aged 38 to 54, were first tested in 1968, with subsequent examinations in 1974, 1980, 1992, 2000, and 2005. Neuroticism and extraversion were assessed in 1968 using the Eysenck Personality Inventory. The women were asked whether they had experienced long periods of high stress at each follow-up.

Over the 38 years, 153 developed dementia (19%), of whom 104 were diagnosed with Alzheimer's (13% of total; 68% of those with dementia).

A greater degree of neuroticism in midlife was associated with a higher risk of Alzheimer's and long-standing stress. This distress accounted for a lot of the link between neuroticism and Alzheimer's.

Extraversion, while associated with less chronic stress, didn't affect Alzheimer's risk. However, high neuroticism/low extraversion (shy women who are easily worried) was associated with the highest risk of Alzheimer's.

The finding supports the idea that long periods of stress increase the risk of Alzheimer's, and points to people with neurotic tendencies, who are more sensitive to stress, as being particularly vulnerable.

http://www.eurekalert.org/pub_releases/2015-09/uof-uhr091615.php

http://www.eurekalert.org/pub_releases/2014-10/uog-anp101414.php

Reference: 

[3996] Park, H-J., Ran Y., Jung J. In, Holmes O., Price A. R., Smithson L., et al.
(2015).  The stress response neuropeptide CRF increases amyloid-β production by regulating γ-secretase activity.
The EMBO Journal. 34(12), 1674 - 1686.

[3997] Johansson, L., Guo X., Duberstein P. R., Hällström T., Waern M., Östling S., et al.
(2014).  Midlife personality and risk of Alzheimer disease and distress A 38-year follow-up.
Neurology. 83(17), 1538 - 1544.

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Stroke speeds age-related cognitive decline

  • A large study shows stroke is associated not only with an immediate drop in cognitive ability, but also with faster declines in some cognitive functions.
  • The finding points to a need for better long-term care.

Data from 23,572 Americans from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study has revealed that those who survived a stroke went on to have significantly faster rates of cognitive decline as they aged.

Participants, who were aged 45 years or older, had no history of cognitive impairment at the beginning of the population-based study. Over the next five to seven years, 515 of them (2%) had a stroke.

Stroke was associated with an acute decline in global cognition, new learning, and verbal memory. Those who had a stroke showed faster declines in global cognition and executive function (but not new learning nor verbal memory) over the next years.

Global cognition was assessed using the Six-Item Screener [SIS]; new learning by the Consortium to Establish a Registry for Alzheimer Disease Word-List Learning; verbal memory by the Word-List Delayed Recall; executive function by the Animal Fluency Test.

The findings suggest a need for better long-term follow-up care for stroke survivors, including therapy to retain or even regain cognitive ability.

http://www.eurekalert.org/pub_releases/2015-07/uomh-mt070715.php

Reference: 

[3994] Levine, D.A., Galecki A.T., Langa K.M., & et al
(2015).  Trajectory of cognitive decline after incident stroke.
JAMA. 314(1), 41 - 51.

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Low vitamin D speeds age-related cognitive decline

  • On average, older adults with low levels of vitamin D showed much faster decline in episodic memory and executive function.
  • Older adults with dementia had significantly lower levels of vitamin D compared to those with MCI or normal cognition.
  • Low vitamin D was more common in African-Americans and Hispanics, compared to whites.

A study involving 382 older adults (average age 75) followed for around five years, has found that those who don’t get enough vitamin D may experience cognitive decline at a much faster rate than people who have adequate vitamin D.

Participants included 17.5% with dementia at the beginning of the study, 32.7% with MCI, and 49.5% cognitively healthy.

Those with dementia had lower levels of vitamin D than the other two groups.

While some people with low vitamin D didn’t show any cognitive decline and some with adequate vitamin D declined quickly, people with low vitamin D on average declined two to three times as fast as those with adequate vitamin D, in two crucial cognitive domains: episodic memory and executive function. Semantic memory and visuospatial ability were not significantly affected.

Factors such as age, gender, education, BMI, season of blood draw, vascular risk, and presence of the 'Alzheimer's gene', ApoE4, were controlled for.

Unlike previous studies of vitamin D and dementia, the participants were racially and ethnically diverse and included whites (41%), African Americans (30%), and Hispanics (25%). Nearly two-thirds (61%) had low vitamin D levels in their blood, including 54% of the whites and 70% of the African-Americans and Hispanics.

Vitamin D is primarily obtained through sun exposure. Accordingly, people with darker skin are more likely to have low levels of vitamin D because melanin blocks ultra-violet rays.

It remains to be seen whether Vitamin D supplements could slow cognitive decline.

http://www.futurity.org/vitamin-d-cognitive-decline-1003932/

 

Reference: 

[3992] Miller, J. W., Harvey D. J., Beckett L. A., & et al
(2015).  VItamin d status and rates of cognitive decline in a multiethnic cohort of older adults.
JAMA Neurology.

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Mental imagery training improves multiple sclerosis patients' cognition

  • Difficulties in remembering past events and imagining future ones are often experienced by those with multiple sclerosis.
  • A trial involving patients with MS has found that training in mentally visualizing imaginery scenarios can improve their ability to recall past events.
  • Deficits in event memory and imagination have also been found in older adults, so this finding might have wider application.

Training in a mental imagery technique has been found to help multiple sclerosis patients in two memory domains often affected by the disease: autobiographical memory and episodic future thinking.

The study involved 40 patients with relapsing-remitting MS, all of whom were receiving regular drug therapy and all of whom had significant brain atrophy. Participants were randomly assigned to one of three groups, one of which received the imagery training (17 participants), while the other two were controls — a control receiving a sham verbal training (10) and a control receiving no training (13). The six training sessions lasted two hours and occurred once or twice a week.

The training involved:

  • mental visualization exercises of increasing difficulty, using 10 items that the patient had to imagine and describe, looking at both static aspects (such as color and shape) and an action carried out with the item
  • guided construction exercises, using 5 scenarios involving several characters (so, for example, the patient might start with the general idea of a cook preparing a meal, and be guided through more complexities, such as the type of table, the ingredients being used, etc)
  • self-visualization exercises, in which the patient imagined themselves within a scenario.

Autobiographical memory and episodic future thinking were assessed, before and after, using an adapted version of the Autobiographical Interview, which involves subjects recalling events from earlier periods in their life, in response to specific cue words. The events are supposed to be unique, and the subjects are asked to recall as many details as possible.

Only those receiving the training showed a significant improvement in their scores.

Those who had the imagery training also reported an increase in general self-confidence, with higher levels of control and vitality.

Remembering past events and imagining future ones are crucial cognitive abilities, with more far-reaching impacts than may be immediately obvious. For example, episodic future thought is important for forming and carrying out intentions.

These are also areas which may be affected by age. A recent study, for example, found that older adults are less likely to spontaneously acquire items that would later allow a problem to be solved, and are also less likely to subsequently use these items to solve the problems. An earlier study found that older adults have more difficulty in imagining future experiences.

These results, then, that show us that people with deficits in specific memory domains can be helped by specific training, is not only of interest to those with MS, but also more generally.

http://www.eurekalert.org/pub_releases/2015-08/ip-mvi082515.php

Reference: 

[3984] Ernst, A., Blanc F., De Seze J., & Manning L.
(2015).  Using mental visual imagery to improve autobiographical memory and episodic future thinking in relapsing-remitting multiple sclerosis patients: A randomised-controlled trial study.
Restorative Neurology and Neuroscience. Preprint(Preprint), 1 - 18.

[3986] Lyons, A. D., Henry J. D., Rendell P. G., Corballis M. C., & Suddendorf T.
(2014).  Episodic foresight and aging..
Psychology and Aging. 29(4), 873 - 884.

[3987] Rendell, P. G., Bailey P. E., Henry J. D., Phillips L. H., Gaskin S., & Kliegel M.
(2012).  Older adults have greater difficulty imagining future rather than atemporal experiences..
Psychology and Aging. 27(4), 1089 - 1098.

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Movie study confirms older people are more distractible

Idiosyncratic brain activity among older people watching a thriller-type movie adds to evidence that:

  • age may affect the ability to perceive and remember the order of events (explaining why older adults may find it harder to follow complex plots)
  • age affects the ability to focus attention and not be distracted
  • age affects the brain's connectivity — how well connected regions work together.

A study involving 218 participants aged 18-88 has looked at the effects of age on the brain activity of participants viewing an edited version of a 1961 Hitchcock TV episode (given that participants viewed the movie while in a MRI machine, the 25 minute episode was condensed to 8 minutes).

While many studies have looked at how age changes brain function, the stimuli used have typically been quite simple. This thriller-type story provides more complex and naturalistic stimuli.

Younger adults' brains responded to the TV program in a very uniform way, while older adults showed much more idiosyncratic responses. The TV program (“Bang! You're dead”) has previously been shown to induce widespread synchronization of brain responses (such movies are, after all, designed to focus attention on specific people and objects; following along with the director is, in a manner of speaking, how we follow the plot). The synchronization seen here among younger adults may reflect the optimal response, attention focused on the most relevant stimulus. (There is much less synchronization when the stimuli are more everyday.)

The increasing asynchronization with age seen here has previously been linked to poorer comprehension and memory. In this study, there was a correlation between synchronization and measures of attentional control, such as fluid intelligence and reaction time variability. There was no correlation between synchronization and crystallized intelligence.

The greatest differences were seen in the brain regions controlling attention (the superior frontal lobe and the intraparietal sulcus) and language processing (the bilateral middle temporal gyrus and left inferior frontal gyrus).

The researchers accordingly suggested that the reason for the variability in brain patterns seen in older adults lies in their poorer attentional control — specifically, their top-down control (ability to focus) rather than bottom-up attentional capture. Attentional capture has previously been shown to be well preserved in old age.

Of course, it's not necessarily bad that a watcher doesn't rigidly follow the director's manipulation! The older adults may be showing more informed and cunning observation than the younger adults. However, previous studies have found that older adults watching a movie tend to vary more in where they draw an event boundary; those showing most variability in this regard were the least able to remember the sequence of events.

The current findings therefore support the idea that older adults may have increasing difficulty in understanding events — somthing which helps explain why some old people have increasing trouble following complex plots.

The findings also add to growing evidence that age affects functional connectivity (how well the brain works together).

It should be noted, however, that it is possible that there could also be cohort effects going on — that is, effects of education and life experience.

http://www.eurekalert.org/pub_releases/2015-08/uoc-ymt081415.php

Reference: 

[3978] Campbell, K. L., Shafto M. A., Wright P., Tsvetanov K. A., Geerligs L., Cusack R., et al.
(Submitted).  Idiosyncratic responding during movie-watching predicted by age differences in attentional control.
Neurobiology of Aging.

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Physical activity linked to greater mental flexibility in older adults

  • A correlation has been found between physical activity in healthy older adults and more variable resting-state brain activity.
  • More variable resting-state activity in older adults has previously been linked to better cognition.
  • No such correlation was found between cardiorespiratory fitness and resting-state brain activity.
  • The finding supports previous evidence linking higher levels of physical activity in old age with better cognition and brain health.

A study involving 100 healthy older adults (aged 60-80) has found that those with higher levels of physical activity showed more variable spontaneous brain activity in certain brain regions (including the precuneus, hippocampus, medial and lateral prefrontal, and temporal cortices). Moreover, this relationship was positively associated with better white-matter structure.

Higher rates of activity when the brain is “at rest” have previously been shown to be associated with better cognitive performance in older adults, especially in IQ and memory.

The brain regions showing this relationship all play an important role in major resting-state networks, including the default mode network, the motor network, and networks associated with executive control and salience detection. They are all highly connected.

Participants' physical activity over a week was measured using accelerometers. Cardiorespiratory fitness was also assessed. Participants were generally not very active and not very fit.

The findings add to evidence linking higher fitness and physical activity with greater brain integrity and higher cognitive performance. They are also consistent with previous studies showing an increase in such brain signal fluctuations among older adults participating in physical exercise programs.

Interestingly, level of brain activity fluctuations was only correlated with physical activity, not with cardiorespiratory fitness. This indicates that CRF and physical exercise cannot be considered as functional equivalents — there must be some aspects of physical activity not captured by a measure of cardiorespiratory fitness.

It's also worth noting that there wasn't a significant correlation between sedentary time and resting-state brain activity fluctuations, although this may be because the participants all showed not-very-dissimilar levels of sedentary time.

http://www.eurekalert.org/pub_releases/2015-08/uoia-slp082415.php

Reference: 

Burzynska AZ, Wong CN, Voss MW, Cooke GE, Gothe NP, Fanning J, et al. (2015) Physical Activity Is Linked to Greater Moment-To-Moment Variability in Spontaneous Brain Activity in Older Adults. PLoS ONE 10(8): e0134819. http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0134819

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Dementia sufferers become unaware of memory problems years before diagnosis

  • A large study found that people who developed dementia started to lose awareness of memory problems some 2½ years before dementia onset.
  • This loss of awareness was associated with three examples of neuropathology, including tau tangles and brain infarcts.

A ten-year study involving 2,092 older adults (average age 76) has found that people tended to lose awareness of memory problems two to three years before the onset of dementia.

Being unaware of your own memory problems is common in dementia, but previous research has focused on those already diagnosed with dementia. In this study, participants had no cognitive impairment at the beginning of the study.

Overall, subjective memory ratings taken annually were modestly correlated with performance (only modestly — people tend not to be that great at accurately assessing their own memory!), and this awareness was stable with age. However, in the subset of those who developed dementia (239 participants; 11%), this awareness started to deteriorate an average of 2.6 years before dementia was diagnosed (after which it dropped rapidly).

In a subset of those who died and had their brains examined (385 participants), a decline in memory awareness was associated with three pathologies:

  • tau tangles
  • gross cerebral infarcts
  • transactive response DNA-binding protein 43 pathology (TDP-43 is a protein involved in transcription, the first step in producing proteins from genes; mutations in the gene that produces TDP-43 have been linked to frontotemporal dementia and amyotrophic lateral sclerosis (ALS)).

There was no decline in memory awareness in those who didn't show any of these pathologies.

Those who were older at the beginning of the study were more likely to retain memory awareness longer, perhaps because they were more alert to memory problems.

http://www.theguardian.com/society/2015/aug/27/dementia-sufferers-start-losing-memory-up-to-three-years-before-condition-develops-us-study

Reference: 

[3979] Wilson, R. S., Boyle P. A., Yu L., Barnes L. L., Sytsma J., Buchman A. S., et al.
(2015).  Temporal course and pathologic basis of unawareness of memory loss in dementia.
Neurology. 10.1212/WNL.0000000000001935.

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No benefit in omega-3 supplements for cognitive decline

  • A large study of older adults with age-related macular degeneration found no cognitive benefit from taking omega-3 supplements, or supplements of lutein and zeaxanthin.

A large, five-year study challenges the idea that omega-3 fatty acids can slow age-related cognitive decline. The study, involving 4,000 older adults, was part of the Age-Related Eye Disease Study (AREDS), which established that daily high doses of certain antioxidants and minerals can help slow the progression of age-related macular degeneration. However, a follow-up study found the addition of omega-3 fatty acids to the AREDS formula made no difference.

Omega-3 fatty acids are believed to be responsible for the health benefits associated with regularly eating fish, which is associated with lower rates of AMD, cardiovascular disease, and possibly dementia.

In this study, participants from the AREDS study, all of whom had early or intermediate AMD, were randomly assigned to either omega-3, or lutein and zeaxanthin (nutrients found in large amounts in green leafy vegetables), or both, or a placebo. As they all had AMD, participants also took the AREDS formula, which includes vitamins C, E, beta carotene, and zinc. Cognitive testing took place at the beginning, at 2 years, and at 4 years.

There was no benefit to these supplements: all groups showed a similar rate of cognitive decline over the study period.

The researchers speculate that the failure to find a benefit may lie in the age of the participants — it may be that supplements, to be of benefit, need to be started earlier. The other possibility (and the one I myself give greater weight to, although both factors may well be influential) is that these nutrients need to be taken in food to be effective.

It should be noted that the omega-3 fatty acids taken were those found in fish, not those found in plant foods such as flaxseed, walnuts, soy products, and canola and soybean oils.

http://www.eurekalert.org/pub_releases/2015-08/nei-nss082115.php

http://www.eurekalert.org/pub_releases/2015-08/tjnj-eop082115.php

Reference: 

[3974] Chew, EY., Clemons TE., Agrón E., & et al
(2015).  Effect of omega-3 fatty acids, lutein/zeaxanthin, or other nutrient supplementation on cognitive function: The areds2 randomized clinical trial.
JAMA. 314(8), 791 - 801.

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