Dementia and Alzheimer’s Disease: Exercise is Good – Studies, Not Always

There is significant evidence that exercise is helpful in lowering one’s risk of dementia by regular moderate to vigorous exercise. And every month a plethora of articles appears reporting on positive impact or no impact at all on a variety of factors from diet and supplements to exercise.

A number of studies have indicated that starting and maintaining an exercise program has been helpful. But, we also need to define what may not be helpful. Exercise below a certain aerobic level, may just not count as preventative exercise for dementia and cognitive decline.

And I realize my bias in favor of exercise, so I must admit that some reviews have found the evidence is weak that exercise is helpful in avoiding cognitive decline.

Reported studies need to be subject to evaluation. One can not blindly accept the authors’ interpretation of the results. The results and protocol need to be rationally evaluated in an absence of hype.

I’m not sure that a recent study by Sink et. al. which did not find a positive correlation between activity and cognition was scrutinized thoroughly in the media. Looking closely at this study we find that they used a good number of patients and controls. But we see that the inclusion criteria of being able to cover 400 meters in 15 minutes is not what many would consider to be an aerobic exercise activity. The study was restricted to those over 70. And the data was not gathered using a Fitbit, Pedometer, GPS motion detector or observation. The data was self-reported.

So what do we know as a result of this study:

  • Being able to move at a speed of 1 mile/hour for 30 minutes  (400 meters in 15 minutes) several times a week is not enough exercise to measurably diminish cognitive decline (it may have other benefits though).
  • Data acquisition by self-reporting may not be optimal. An objective measurement should be used in conjunction with a device to do and record these measurements.
  • The life style changes here may have been too little and too late to have an impact.
  • Commencing exercise prior to age 70 may be better than beginning later. If beginning later, results may only be seen if the individual is capable of exercising a moderate level.
  • Media coverage is often limited in interpretation and assessment of the meaning  of a study’s results.

In a predefined subgroup of those aged 80 and over and with worse starting fitness they did find an improvement in “executive function”.

“Despite the lack of overall benefit, our prespecified subgroup analyses of participants aged 80 years or older and those with lower baseline physical performance demonstrated that the physical activity group had better performance on executive function tasks than those in the health education group at 24 months. This finding is important because executive function is the most sensitive cognitive domain to exercise interventions,40 and preserving it is required for independence in instrumental activities of daily living. Future physical activity interventions, particularly in vulnerable older adult groups (eg, ≥80 years of age and those with especially diminished physical functioning levels), may be warranted.”

The authors did consider as the first possible explanation that the exercise level was insufficient to produce changes in the cognitive measures, but this escaped the media blitz. In reading the article, conclusions and discussion, the study was well designed, properly randomized and controlled, used an adequate sample size. The possibilities leading to the observed results were thoroughly discussed. But again, the subtleties were not discussed in the media and the headlines you saw were that exercise was not useful in preventing cognitive decline. As with most studies the media would lead you to believe that the current study overturns all previous thinking and is the only thing to follow.

Bayesian reasoning allows for new information to be added into the mix of the prior thought and research on any topic. That should be done and the meaning of that should be clear to anyone writing about science literature. One study doesn’t usually replace all thinking, it is added to it in that successive approximation of the truth that we reach for through science.

So the same recommendation to exercise, in my mind, holds. It still has the most evidence pointing in its favor. And for those older individuals who are not able to exercise as vigorously, exercise is still likely to have positive impact on mood and other neurological and physical functions not measured in this study.And I’d suggest more education on EBM and study evaluation for those charged with distributing results of medical studies. And please read the study.

References:

Effect of a 24-Month Physical Activity Intervention vs Health Education on Cognitive Outcomes in Sedentary Older Adults Sink, KM et. al. JAMA. 2015;314(8):781-790. doi:10.1001/jama.2015.9617.

Exercise counteracts declining hippocampal function in aging and Alzheimer’s disease. Intlekofer, K, Cotman, C.  NEUROBIOLOGY OF DISEASE · JUNE 2012

Physical activity and cognitive function in individuals over 60 years of age: a systematic review. Clin Interv Aging. 2014 Apr 12;9:661-82. doi: 10.2147/CIA.S55520. eCollection 2014.  Carvalho ARea IMParimon TCusack BJ

Erickson, KI, Barr, LL, Weinstein, AM, Banducci, SE, Akl, SL, Santo, NM, Leckie, RL, Oakley, M, Saxton, J, Aizenstein, HJ, Becker, JT, Lopez, OL. (in press). Measuring physical activity with accelerometry in a community sample with dementia. Journal of the American Geriatic Society.

Weinstein, AM, Voss, MW, Prakash, RS, Chaddock L, Szabo, A, White, SM, Wojcicki, TR, Mailey, E, McAuley, E, Kramer, AF, Erickson, KI. (2012). The association between aerobic fitness and executive function is mediated by prefrontal cortex volume. Brain, Behavior, and Immunity, 26:811-9.

 

Erickson KI, Miller DL, Roecklein KA. (2012). The aging hippocampus: interactions between exercise, depression, and BDNF. Neuroscientist, 18: 82-97.

Okonkwo, O, Schultz,S et. al. Physical activity attenuates age-related biomarker alterations in preclinical AD. Neurology November 4, 2014 vol. 83 no. 19 1753-1760

 Brown, B, Bourgeat, P et. al. Influence of BDNF Val66Met on the relationship between physical activity and brain volumeNeurology. October 7, 2014 vol. 83 no. 15 1345-1352

Addendum:

Abstract of a British J of Sports Medicine editorial (Exercise is medicine, for the body and the brain, 2014):

“Cognitive decline is one of the most pressing healthcare issues of the 21st century. Worldwide, one new case of major cognitive decline (ie, dementia) is detected every 4 s. Given that no effective pharmacological treatment to alter the progress of cognitive decline exists, there is much interest in lifestyle approaches for preventing or treating dementia. Ideally, such strategies should be cost-efficient and widely accessible at a societal level to have the largest benefit for older adults with varying income and functional status levels.

One attractive solution that aligns with the above criteria is exercise. However, despite a large and consistent pool of evidence generated over the past five decades linking exercise to improved cognitive functions in older adults,2 there is a reluctance among academics, healthcare practitioners and the public alike to embrace exercise as a prevention and treatment strategy for cognitive decline. For example, the National Institutes of Health (NIH) consensus statement from 20103 concedes that there appears to be preliminary data to support the efficacy of exercise in improving cognitive function. However, they caution that there is currently no strong evidence to suggest that modifiable lifestyle factors can alter the trajectory of cognitive decline. Adding fuel to the fire are publications such as a 2013 systematic review of randomised controlled trials (RCTs) (prior to 31 October 2011) reporting ‘weak’ evidence for the effects of exercise on cognition.4 We must highlight that the search strategy used in that systematic review failed to capture many pertinent papers providing evidence from RCTs that exercise promotes cognitive and brain plasticity not only in healthy older adults but also in those with cognitive impairment. Furthermore, there are a number of animal studies that provide insight into the molecular and cellular mechanisms by which exercise promotes neuroplasticity.”

Let’s Get Physical – Olivia Newton John

Exercise is good for the mind and the soul

Another study has demonstrated that those who exercise regularly have a decreased incidence of depression.

The new study titled “Depressive Symptoms and Physical Activity During 3 Decades in Adult Life” appeared in JAMA Psychiatry in the issue published Oct 15, 2014.

At each age group, those who exercised had a lower incidence of depression than those who did not. Those who took up exercise were doing better 5 years later than those who continued to not exercise.

This is one more reason to exercise regularly. Exercise is good for ails you or for what might ail you in a few years!

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Moving is Exercise (Competing Tunes below)

Resveratrol: 700 Bottles of Wine On The Wall

Red wine has long been hailed as good for your health. Years ago it was found to contain resveratrol, adding to the good reputation of red wine. Nearly 10 years ago resveratrol was first believed to have beneficial actions by virtue of its activating sirtuin 1 (SIRT1) which

Resveratrol (image courtesy Wikipedia)

is an NAD+ dependent deacetylase thought to protect against several metabolic disorders including  type 2 diabetes, Alzheimer’s disease, hearing loss (actually SIRT3), and cardiovascular disease. The actions of sirloins are believed to mimic the effect of caloric restriction on lifespan and disease in mammals. The actual caloric restriction needed to have beneficial effects though is too great for humans to attempt although gluttony is clearly both the opposite and detrimental to good health.

Recent research shows that things are more complicated than that, as research seems to do in many fields. Apparently it there is an intermediary reaction in which phospodiesterases which hydrolyze cAMP are inhibited. Skeletal muscle and white fat tissue responds to resveratrol by increasing the levels of cAMP. We need more research before we are able to use resveratrol as medicine.

Nature Reviews Molecular Cell Biology (Feb 29, 2012) quotes Andrew Murray, interviewed by the Telegraph of Cambridge University, UK about how much red wine it would take to ingest enough resveratrol to have physiological action. He is quoted as saying “you would need to drink about 700 bottles [of red wine] to get a meaningful dose.”

In short, it may be that researchers who like red wine, hail the miracles of red wine, those who like coffee, hail coffee. And the same may go for chocolate. Perhaps the effects of each augment the other which would be better than canceling each other out.

 

Sunscreens: Hype and Reality (repost 2007)

Sunscreens are helpful in reducing exposure to the harmful effects of UVA and UVB. These types of solar radiation contribute to the development of premature skin aging, wrinkling and both malignant and non-malignant skin cancer. Basal Cell Cancer and Melanoma, among other types of skin cancer has an increased incidence in sun exposed individuals. Some have estimated that only about 20% of melanomas are related to skin cancer. Other disfiguring cancers, including basal cell though seem to have a very high correlation with sun exposure.

Melanoma has multiple risk factors which include fair complexion, blonde or red hair color, blue, blue/green eye color (skin phototypes I/II), total sun exposure and a history of blistering sun burns. Genetics, or inherited risks may include genetically linked disorders such as the dysplastic nevus syndrome. The overall risk has increased dramatically over the last 50 years or so. In 1935 the lifetime risk for developing melanoma was 1:1500 in 1935 and grew to 1:74 in 2000. It is estimated that it will grow to 1:50 in 2010. It is estimated that over 53,000 new cases of melanoma are diagnosed now each year. A good number of these are diagnosed at an early stage.

Today’s New York Times implicitly criticizes Neutrogenia for a campaign in which they imply that not using sunscreen and their products is akin to suicide. It includes a clip in which a woman holds up a photo and says “My sister killed herself. She died of skin cancer.” Since melanoma can occur in people with little sun exposure and the majority of it may, this is in bad taste. There isn’t even a campaign that strong for lung cancer sponsored by Nicorette. Continue reading Sunscreens: Hype and Reality (repost 2007)

Exercise Is Good For Your Brain (Repost)

repost (from November 2011)

Running Mice Live Longer With Degenerative Brain Disorder
Running Mice Live Longer With Degenerative Brain Disorder

Cognitive decline with aging is an increasingly important research topic. This past November (2011) Science Magazine produced a special issue on the brain including   a summary article and a main article which discusses the impact on a specific neurodegenerative disease (spinocerebellar ataxia type 1) in mice.

A “mild” exercise regimen helped the mice live significantly longer. The effects lasted for a considerable time, even after stopping the exercise program. The disease studied has features in common with Alzheimer’s in that an insoluble protein that accumulates in nerves is involved. Exercise has been shown to have positive effects on Alzheimer’s disease and the research here on how exercise impacts the proteins and future exercise on a variety of growth factors produced during exercise may help in producing strategies for Alzheimer’s disease and numerous other degenerative diseases.

The accompanying summary article states:

“In addition to the benefits of exercise on brain health and cognitive function, it may promote slowing neurodegenerative disease progression. For example, exercise slowed the decline in cognitive abilities of Alzheimer’s disease patients and improved postural stability and balance in Parkinson’s disease patients.”

References:

Another Reason to ExerciseAaron D. Gitler. Science 4 November 2011: Vol. 334 no. 6056 pp. 606-607. DOI: 10.1126/science.1214714

Exercise and Genetic Rescue of SCA1 via the Transcriptional Repressor Capicua. John D. Fryer, Peng Yu et. al. Science 4 November 2011: Vol. 334 no. 6056 pp. 690-693 DOI: 10.1126/science.121267