Friday, April 10, 2015

Putting Research Connecting BMI & Dementia in Its Proper Context

Image result for laurel and hardy

Being Too Fat or Too Thin in Midlife Raises the Risk for Alzheimer's
Evelyn Smith
M. S. in Library Science, University of North Texas (2012)

An article published today in the English tabloid, the Daily Mail, has set me on a quest to verify if its claims are true--that individuals with a low Body Mass Index are more likely to develop Alzheimer's and other types of dementia than those who are overweight. Since no article on Alzheimer's, or any other medical issue, should exist, in isolation, I have surveyed both popular articles found Online as well as abstracts of peer-reviewed research. From what I have been able to determine, both those who are obese and the exceptionally slim in middle age stand a better chance of being diagnosed with Mild Cognitive Impairment and eventually developing Alzheimer's Disease primarily because obesity is also responsible for chronic diseases like Type 2 diabetes and cardiovascular disease that make it all the more likely that a middle-aged man or woman will be diagnosed with late-stage Alzheimer's later in life.

Thus, no one is exempt from trying to maintain a Mediterranean-style diet and getting off the couch for at least thirty minutes of aerobic exercise five days a week. As for maintaining a normal BMI index between 21 and 25, that means that American women need to start dieting when they can no longer fit into a Misses size 14.  For a 5 foot 6 inch woman, that means losing seven pounds. Then again, the truly thin put a similar strain on their bodies. Accordingly, after reading this response to the Daily Mail article, most readers will want to throw away any junk food in the house and instead of watching TV or surfing the Web decide to take the dog for a long walk.

Hope, Jenny. (2015 April 10). Could being skinny in middle age raise your risk of dementia? Underweight people third more like to develop diseases. Daily Mail. Retrieved from http://www.dailymail.co.uk/news/article-3032915/Could-skinny-middle-age-raise-risk-dementia-Underweight-people-likely-develop-diseases.html

A study recently published in The Lancet Diabetes and Endocrinology Journal contradicts earlier research linking a high Body Mass Index, 25 BMI and over, with Alzheimer's, for it finds that being underweight in middle age raises the risk of dementia by 30 percent (Hope, 2015, April 10, para. 1-5 & 16). Accordingly, general practitioners may need to rethink how to best identify those patients that are most at risk, paying particular attention to the causes and consequences of this link, according to research Stuart Pocock (Hope, 2015, April10, para. 5-6).

To establish a correlation between BMI and Alzheimer's, London researchers examined two decades worth of data on 958,191 patients with the average BMI of 26.5 and the average age of 55. After a nine-year followup, physicians diagnosed patients with dementia (Hope, 2015, April 10, para. 9-12).

Patients with a BMI of less than 20 percent were 34 percent more likely to develop dementia than those of normal weight with a BMI between 21 and 24.99 (Hope, 2015, April 10, para. 12-13). Moreover the truly obese with a BMI of 40 or greater were the least likely to develop Alzheimer's (Hope, 2015, April 10, para. 14).

Then again, physicians treating “grossly obese” patients may have paid more attention to their obvious health risks—like diabetes and cardiovascular disease—than those whose patients were severely underweight. Thus, the Lancet study may reveal more about the diagnostic practices of British GP's than it does about the possibility of developing Alzheimer's (Hope, 2015, April 10, para. 16-18). Previous research has linked obesity with an increased risk of dementia, so the best game plan for preventing Alzheimer's—along with chronic diseases influenced by lifestyle—remains exercising regularly and maintaining a healthy, [low-fat, Mediterranean-style] diet (Hope, 2015, April 10, para. 19 & 22).

See also:

Normal weight ranges: Body mass index (BMI). (2015). American Cancer Society. Retrieved from http://www.cancer.org/cancer/cancercauses/dietandphysicalactivity/bodyweightandcancerrisk/body-weight-and-cancer-risk-adult-bmi

US standard clothing size. (2015). Wikipedia. Retrieved from http://en.wikipedia.org/wiki/US_standard_clothing_size


Image result for bmi
Where does your BMI fall?
Popular articles that relate both being underweight and overweight with an increased risk of dementia nicely balanced out The Daily Mail article.

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Annotated Popular Articles Connecting BMI with Dementia Risk
Conis, Elena. (2008, June 9). If you're too heavy or too thin, dementia risks may rise. Weight Loss: A How-to Guide/ Explain This. Los Angeles Times. Retrieved from http://articles.latimes.com/2008/jun/09/health/he-explain

Being obese as well as being too thin can increase the risk of dementia, according to a study conducted by Yauta Wang and fellow researchers at Johns Hopkins University and the University of Iowa and published in Obesity Reviews: Thus, if body weight is plotted on a U-shaped graph, having a BMI of 30 or higher increases the risk of dementia by 40 percent as does having a BMI of less than 18.5. Additionally, middle-aged obesity alone eventually increases the risk of dementia in the very elderly by 80 percent (Conis, 2008, June 9, para. 1-4).

To determine these findings, Wang and colleagues took another look at longitudinal studies published before 1995 that investigated the link between dementia and body weight in adults aged 40 and over and came up with 10 relevant studies—all of which “produced a mixed bag of results”, However, their analysis concluded that controlling for obesity could reduce Alzheimer's by 20 percent (Conis, 2008, June 9, para. 5-7). Nevertheless, Wang doesn't want anyone “to over interpret the findings”, although a review of decade long studies evaluating adults before they turn 60 does show a strong connection between obesity and dementia (Conis, 2008, June 9, para. 8-9). Wang, however, admitted that researchers as yet don't know how obesity affects cognitive decline, although it might simply indicate other risk factors for dementia like a lack of physical activity and depression (Conis, 2008, June 9, para. 10).

Dybuncio, Monica. (2011, November 22). Is being thin a warning sign of Alzheimer's? CBS News. Retrieved from http://www.cbsnews.com/news/is-being-thin-a-warning-sign-of-alzheimers/

Researchers from the University of Kansas School of Medicine published in the November 22, 2011 issue of Neurology document that biological markers for Alzheimer's are more common in thin patients than their heavier counterparts (Dybuncio, 2011, November 22, para. 2).

After examining 506 healthy patients using brain imaging and cerebrospinal fluid tests, researchers found that 85 percent of those who had a BMI below 25 showed signs of brain plaque, compared with 48 percent of those who were overweight (Dybuncio, 2011, November 22, para. 3).

Dr. Jeffrey Burns, the associate director of the University of Kansas Alzheimer's Disease Center, speculates that “this might be due to damage in the area of the brain called the hypothalamus that plays a role in regulating energy metabolism and intake”, although Dr. Burns also suggested that more studies are needed to confirm the hypothesis that thinness might indicate an eventual diagnosis of Alzheimer's (Dybuncio, 2011, November 22 para. 4).

The Kansas study also emphasizes that while biomarkers for Alzheimer's can be found by brain scans, the early signs of Alzheimer's may manifest themselves in other parts of the body as well since the brain regulates hunger, fullness, and blood flow (Dybuncio, 2011, November 22, para. 5).

Kounang, Nadia. (2012, January 2). Study:: Fat hormone increases risk of dementia in women. The Chart. CNN. Retrieved from http://thechart.blogs.cnn.com/2012/01/02/study-fat-hormone-increases-risk-of-dementia-in-women/

The increased production of the adiponectin hormone, particularly in women, which produces excess weight around the waist may pose a risk factor for Alzheimer's and other types of dementia (Kounang, 2012, January 2, para. 1-2).   While fat cells that help regulate the body's response to insulin produce adiponectin to lower the risk of Type 2 diabetes, older women diagnosed with dementia also have higher levels of this hormone. In other words, while researchers expected adiponectin to protect older women from dementia, it had the opposite effect (Kounang, 2012, January 2, para. 4-5).

In this longitudinal study, researchers followed 841 volunteers who had originally enrolled in the Framingham Heart study that begin track over 5,000 participants so that researchers could learn the factors that led to heart disease starting in 1948. Beginning in the 1980s, they observed 541 women over the next 13 years, 159 of whom developed some form of dementia. A statistical analysis of their findings showed that increased levels of adiponectin increased the risk of dementia by 60 percent and for Alzheimer's by 90 percent (Kounang, 2012, January 2, para. 6-7).

The study also suggested that a link between nutrition and dementia since adiponectin levels inversely correlate with BMI: Conversely, older women (over age 75) with higher BMIs had lower levels of adiponectin and lower rates of dementia. Unfortunately, not enough male survivors were available to participate in this follow-up to the orginal Framingham Heart Study to determine if the same correlation held true for older men (Kounang, 2012, January 2, para. 8-9).  Even so, for women over 60—and most probably for all adults over and under 60 as well—being too thin along with being too fat “may not be a good thing” for either the mind or body (Kounang, 2012, January 2, para. 10).

Nordqvist, Christian. (2011, November 22). Alzheimer'--Is being thin an early sign? MNT [Medical News Today]. Retrieved from http://www.medicalnewstoday.com/articles/238042.php

During the earliest stages of Alzheimer's (years before the individual even develops Mild Cognitive Impairment), individuals are more likely to be thin rather than obese while overweight, middle-aged adults stand a higher chance of developing Alzheimer's later in life, according to a University of Kansas Alzheimer's Center Study that has established a link between Body Mass Index (BMI) and Alzheimer's (Nordqvist, 2011, November 22, para. 1).

Using biomarkers that detect Alzheimer's symptoms years before the disease otherwise starts to show itself, Jeffery M. Burns and his colleagues performed brain imaging techniques on and obtained cerebrospinal fluid from 506 participants enrolled in the Alzheimer's Disease Neuroimaging Initiative—a population that included those with no memory problems as well as individuals diagnosed with Mild Cognitive Impairment and Alzheimer's (Nordqvist, 2011, November 22 para. 2-4). Participants diagnosed with Alzheimer's had a lower BMI than those without the biomarkers. Additionally, 85 percent of the study participants diagnosed with MCI had a BMI below 25 compared with the 48 percent of those MCI diagnosed individuals who were overweight (Nordquvist, 2011, November 22, para. 5-6).

Body weight and dementia risk—the evidence. (2014). Your Brain Matters. Retrieved from http://yourbrainmatters.org.au/body-weight-and-dementia-risk-%E2%80%93-evidence

Clinical evidence associates central obesity (or an apple-shaped body) with an increased risk of developing dementia. Furthermore, researchers have yet to determine whether midlife weight loss lessens the risk (Body weight, 2014, para. 1). In early old age, from 65 to 75, however, a U-shaped relationship exists between BMI and dementia risk, for both those over and underweight are more at risk. However, research has linked a lower BMI and weight loss with dementia in older adults over age 75. Moreover, weight loss may predate the onset of dementia by more than 10 years (Body weight, 2014, para. 2-3).

A review of the findings on the relationship between BMI and dementia throughout the lifespan is as follows:
  • Central adiposity in middle age predicts dementia in old age;
  • The relation between high adiposity and dementia decreases with older age;
  • Waist circumference--a measure of central adiposity--may better predict dementia than a high BMI does;

  • Lower BMIs in midlife predict dementia in the elderly (over age 75);

  • Weight loss may precede dementia diagnosis by decades.
(Luchsinger, J. A., 2009, p. p. 25-21)

Considering these findings, maintaining a healthy weight--neither too fat or too thin--is the best strategy for all adults to follow for “optimizing” brain health since not being overweight lowers blood pressure as well as improving blood lipids levels and insulin resistance (Body weight, 2014, para. 5). The reason: Insulin resistance and hyperinsulemia associated with obesity may reduce the clearance of beta amyloid plaque from the brain while medical research has long linked obesity with an increased risk for cardiovascular disease, which, in turn, raises the risk of developing dementia (Body weight, 2014, para. 6).

Reference:

Luchsinger, J. A. and Gustafson, R. D. (2009, January). Adiposity and Alzheimer's Disease. Current Opinion in Clinical Nutrition and Metablic Care, 1, 15-21. doi: 10.1097.MMC06013e32831c8c71. [Abstract only]. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/19057182

Online articles intended for a general audience, in turn, point the way to peer-reviewed articles published in medical journal that furnish a scientific foundation for attention-getting articles.
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Peer-Reviewed Studies Correlating BMI with Dementia Risk
Image result for apple shaped body
Apple-shaped bodies indicate a high BMI.
Anstey, K. J., Cherbuin, M., and Budge, M., et al. (2011, May). Body mass Index in midlife and late-life as a risk-factor for dementia: A meta-analysis of prospective studies. Obesity Review, 12(5). doi: 10.1111/j.1467-789X.2010.00825.x. [Abstract only]. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/21348917

A meta-analysis of 16 articles reporting on 15 prospective studies whose follow-ups ranged from 3.2 to 36 years, sampling 25,624 participants found that those who were obese in midlife were more likely to be diagnosed with dementia; however, a continuous BMI in late life didn't necessarily equate with dementia. Researchers concluded that either being underweight or overweight in midlife increased the risk of developing dementia.

Berti, V., Murray, J., and Spector, N., et al. (2015). Nutrient patterns and brain biomarkers of Alzheimer's disease in cognitively healthy individuals. The Journal of Nutrition Health and Aging, 19 (4), 413-23. doi: 10.1007/s1260-014-0534-0. [Abstract only]. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/25809805

In a cross-sectional study, researchers followed 52 cognitively normal individuals, assessing their dietary intake of 35 nutrients associated with cognitive function and Alzheimer's. The study linked specific dietary nutrient patients with biomarkers of Alzheimer's in currently cognitively healthy individuals, thus indicating that dietary interventions may reduce Alzheimer's risk.

Chen, Y. C., Chen, T. F., and Yip, P. K. (2010, February). Body Mass Index (BMI) at an early age and the risk of dementia. Archives of Gerontology and Geriatrics, Suppl 1:S48-52. doi: 10.1016/S0167-4943(10)70013-3. [Abstract only]. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/20171457

In a case-controlled study of 286 dementia patients and 268 cognitively-healthy controls between 2007 and 2009 that collected BMI information from questionnaires and previous medical records, men and women who had too low a BMI in their 20s and 40s had a significantly increased risk for Alzheimer's and vascular dementia compared with those with a normal BMI while women with a high BMI during their 20s and 40s increased their risk for vascular dementia. However, since the risk of dementia followed a U-shaped curve, those individuals with the lowest BMI's from their 20s through their 40s were more likely to develop Alzheimer's and vascular dementia.

Chu, Leungwing. (2012, July). Low BMI predicts incident Alzheimer's Disease in older adults with amnestic Mild Cognitive Impairment: A three-year perspective cohort study. Alzheimer's & Dementia, 8(4), Supplement, pp. 323. [Full text]. doi: http://dx.doi.org/10.1016/j.jalz.2012.05.892. Retrieved from http://www.alzheimersanddementia.com/article/S1552-5260(12)01024-2/fulltext#

University of Hong Kong researchers followed Chinese adults aged 55 to 93 diagnosed with Mild Cognitive Impairment, during which time, 25.4 percent progressed to Alzheimer's Disease, and after adjusting for age, sex, and apolipoprotein E genotype, researchers found that a low BMI and ischemic heart disease were independent predictors that indicated that MCI would eventually progress to Alzheimer's Disease.

Crook, Benjamin B., Johnson, David K., and Burns, Jeffrey M. (2010, April-June). Body Mass Index and cognitive decline in Mild Cognitive Impairment. Alzheimer's Disease Associative Disorders, 24(2), 126-130. doi: 10.1097/WAD.0b013e3181abbf3f. [Full text]. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3068614/

University of Kansas researchers conducted neuropsychological and clinical evaluations at baseline, six months, and one year on 286 individuals diagnosed with Mild Cognitive Impairment who were also enrolled in the Alzheimer's Disease Neuroimaging Initiative while also using height and weight to calculate BMI. The study associated lower baseline BMI with significant declines in cognitive performance using the Mini—Mental-State-Examination, the Alzheimer's Disease Assessment Scale Cognitive subscale and a global cognitive composite. They thus concluded that a lower BMI correlates with a more rapid cognitive decline in those patients diagnosed with MCI (Abstract, para. 1-4).

Note: While the abstract adequately summarizes this article, it is also important to read its first full paragraph that notes that while research has associated a high BMI  (25 and higher) in midlife with an increased risk of Alzheimer's, after age 65, a lower BMI (18.5 and lower) correlates with an increased risk of developing dementia (Crook, 2010, April-June, para. 1).

Dahl, A. K., Hassing, L. B., and Fransson, E. T., et al. (2013, February) Body Mass Index across midlife and cognitive change in late life. International Journal of Obesity (London), 37(2), 296-302. doi: 10.1038/ijo.2012.37. [Free article]. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/22450854

Investigating the association between a high BMI in midlife (from 40 to 60 years) and cognitive decline, Swedish researchers documented that individuals who were overweight in early midlife displayed a significantly lower cognitive performance in late life as well as a steeper decline in mental abilities. However, those who were either underweight or overweight in late midlife had lower cognitive abilities late in life. Additionally, a declining weight across midlife rather than maintaining a low weight late into midlife correlated with lessened thinking skills.

Elwood, P., Galate, J., and Palmer, S., et al. (2013, December 9). Healthy lifestyles reduce the risk of chronic diseases and dementia. Evidence from the Caerphilly cohort study. PloS One, 8(12), doi: 10.1371/journal.pone.0081877. e-collection 2013

Following 2,235 men aged 45-59 in Caerphilly, Wales, for 30 years beginning in 1979 showed that a healthy lifestyle (non-smoking, an acceptable BMI, a high fruit and vegetable intake, regular physical activity, and low to moderate alcohol consumption) delayed vascular disease for 12 years and reduced all-cause mortality for men following at least four of the five healthy living protocols while it also reduce the incidence of cognitive impairment.

Garcia-Ptacek, S., Faxen-Irving, G., and Cermakova, P. (2014, November). Body Mass Index in dementia. European Journal of Clinical Nutrition. 68 (11) 1204-09. doi: 10.1038/ejcn.2014.199. [Abstract only]. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/25271014

Higher BMIs correlate with impaired cognition while middle age obesity corresponds with an increased risk of dementia in old age. However, in the oldest elderly (over age 75), higher BMIs indicate better cognition and decreased mortality. Thus, lifelong trends might better offer a more accurate cognitive forecast than single BMI measurements.

Gelber, R. P., Petrovitch, H., and Masaki, K. H., et al. (2012, January). Lifestyle and the risk of dementia in Japanese-American men. Journal of the American Geriatric Society, (60(1), 118-23. doi: 10.111/j.1532-5415.2dl.03768.x. [Abstract only]. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/22211390

When the Honolulu-Asia Aging Study followed 3,468 Japanese-American males whose mean age was 52 between 1965 and 1968 for 25 years, researchers determined that those men with the lowest risk for Alzheimer's displayed the following midlife habits: 1) not smoking, 2) a BMI of less than 25.0 kg and more than 18.5 kg, 3) physically active, 4) follows a healthy diet, based on the ratio of monounsaturated to saturated fats. For the 6.4 percent diagnosed with dementia, a high BMI was “most strongly associated” with a risk for dementia. Men who adhered to all four low-risk characteristics had the lowest incidence for dementia.


Mattson, M. P. (2015, March). Lifelong brain health is a lifelong challenge: From evolutionary principles to empirical evidence. Aging Research Reviews, 20C:37-45. doi: 10.1016/j.arr.2014.12.011. [Abstract only]. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/25576651

Because the brain evolved to ensure success in acquiring food, the brain functions best when humans are hungry and physically active. Thus, studies using both animal models and humans demonstrate the benefits of regular exercise and intermittent fasting on cognitive function. However, a “sedentary and overindulgent lifestyle” leads to obesity, diabetes, and cardiovascular disease—all of which increase the risk of developing Alzheimer's.

Naderal, E. K., Radcliffe, S. H., and Dale, M. C.(2009, November 18). Review: Obesity and Alzheimer's Disease: A link between body weight and cognitive function in old age. American Journal of Alzheimer's Disease & Other Dementias, 24(6), 445-449. doi: 10.1177/1533317509348208. Sage Journals. Abstract only. Retrieved from http://aja.sagepub.com/content/24/6/445.short

Research has yet to determine the link between obesity and cognitive impairment, but its “negative impact on cognitive function” may result from the vascular defects, impaired insulin metabolism, and defects in the glucose transport mechanism in the brain that a high BMI causes.

Profenno, L.A., Porsteinsson, A. P., and Faraone, S. V. (2010, March 15). Meta-analysis of Alzheimer's disease risk with obesity, diabetes, and related disorders. Biological Psychiatry, 67(6), 5-5-512. [Abstract only]. Science Direct. Retrieved from http://www.sciencedirect.com/science/article/pii/S0006322309002261

After reviewing longitudinal and epidemiological studies on BMI, diabetes, metabolic syndrome, and glucose insulin levels, a meta-analysis concludes that both obesity and diabetes “significantly and independently” increase the risk of late-onset Alzheimer's, although the level of risk is less than those with the APOE4 allele: “Physiological changes common to obesity and diabetes plausibly promote Alzheimer's.”

Rantanen, K. K. Strandberg, A. Y., and Pitkala, K., et al. (2014, December). Cholesterol in midlife increases the risk of Alzheimer's Disease during an up to 43-year follow-up. European Geriatric Medicine, 5(6) 390-394. doi: 10.1016/j.eurger.2014.05.002. Science Direct. [Abstract only]. Retrieved from http://www.sciencedirect.com/science/article/pii/S1878764914000795

Surveying the cholesterol levels of 3,293 men of whom 205 had verified Alzheimer's, this follow-up of the Helsinki Businessman Study, which has kept track of male Finnish business executives since 1964, revealed that those men ultimately diagnosed with Alzheimer had a higher total cholesterol level than their controls, chosen in 2007. Moreover, higher cholesterol levels corresponded with a 22 percent increased risk for developing Alzheimer's.

Titova, O. E., Ax, E., and Brooks, S. J. (2013, December). Mediterranean diet habits in older individuals: Associations with cognitive functioning and brain volumes. Experimental Gerontology, 48 (12),1443-8. doi: 10.1016/j.exger.2013.10.002. [Abstract only]. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/24126083

Keeping weekly food diaries, Uppsala, Sweden, seniors recorded their dietary intake whereupon five years later they underwent a cognitive test battery used to screen for dementia while volumetric magnetic resonance imaging determined their brain volume. Low consumption of meat and meat products correlated with better performances on the 7MStest and a greater brain volume.

Tolpanen, A. M., Ngandu, T., and Kareholt, I., et al. (2014). Midlife and late-life body mass index and late-life dementia: Results from a perspective population based cohort. Journal of Alzheimer's Disease: JAD, 38(1), 201-09. doi: 10.3233/JAD-136698. [Abstract only]. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/23948937
The association of midlife BMI (mean age 50.2) and late-life BMI (mean age 71.2) and the incidence of dementia later (mean-age75.7) in a longitudinal study based on cardiovascular risk conducted in Eastern Finland with a follow-up of 2 years found a link between a higher BMI midlife and a higher risk of dementia and Alzheimer's Disease while a lower BMI in late-life correlated with a higher risk for dementia.
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