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Alzheimer’s and weight fluctuation – is there a connection?

By Sharon Kanon

Unexpected findings of a new Israeli study reveal possible links between weight gain and dementia in middle age.

A new study from Israel shows a reduced risk of dementia among men who maintain minimal mid-life weight fluctuations.

Is being overweight a risk factor for Alzheimer’s disease and other dementias? Do fluctuations in weight in middle age mean you’re in danger of dementia? With obesity and dementia both major health problems in the 21st century, any research that discovers a relationship between the two is news.

For years researchers have been exploring the enigmatic connection between dementia and weight. A long-term study begun at the Tel Aviv University (TAU) School of Medicine in 1963, with a follow-up in 1999-2000, examined possible links between weight and dementia.

The original study included 10,059 men aged 40-65, all of whom were employed by the city or state in Haifa, Tel Aviv and Jerusalem. Of the 1,890 men (mean age 82) reached in a follow-up phone survey 36-37 years later, and further examined medically, 307 (16 percent) had dementia, whereas 1,407 had no cognitive impairment; the others had only mild cognitive impairment.

Characterized by plaques and tangles in the brain, gunky substances called beta amyloids, Alzheimer’s afflicts more than 35 million people worldwide, and five million in the US alone. A new report, released in November by Alzheimer’s Disease International, made the ominous forecast that the prevalence of the disease will nearly double every 20 years. It now afflicts one out of every eight people aged 65 years and older, and one in two people over the age of 85.

Israeli study reveals surprises

The TAU research is one of the few major longitudinal studies of a large population that was planned and executed according to high standards – each participant was interviewed and assessed in the follow-up – providing important data on the relationship between Body Mass Index (BMI), tricep skinfolds, and weight fluctuation and dementia. Some of the TAU study’s findings reveal unexpected links.

“This study showed for the first time a reduced risk of dementia among men surviving long-term who had maintained minimal mid-life weight fluctuations,” says Uri Goldbourt, professor of Epidemiology and Preventive Medicine at the Sackler School of Medicine at TAU, speaking at a conference on obesity in Tel Aviv last month.

Interviewed by ISRAEL21c, Goldbourt was eager to clarify. “The study did not study dieting specifically,” he says emphatically. “Weight changes in mid-age could occur because of illness, trauma, or other reasons. We are talking about working Israeli men in 1963, among whom dieting was rare.” Draw your own conclusions about the implications for mid-life dieters who do not keep their weight stable.

The follow-up study found dementia in almost 17 percent of the men who had been in the “normal weight” category. Using the BMI (a weight to height ratio), a 30% higher prevalence of dementia was found in men who had been obese (BMI over 30) during the initial study. No less at risk, according to the findings, were men who had been underweight, with BMI under 20.

The difference in dementia between overweight men with body mass indexes between 25 and 30 and the “norm” was negligible. Among those slightly overweight men, the prevalence of dementia was very slightly less than in men with normal BMIs.

Jumping to weighty conclusions

Jumping to a conclusion that could appeal to overeaters during the holiday season, one Israeli newspaper captioned its story: “Study finds overweight Israelis are better protected against Alzheimer’s.”

“I did not say and do not think that being overweight carries benefits,” Goldbourt is quick to point out. “All I said is that the threshold of 25 kg/meters squared mislabels many individuals as overweight. The expectation that we in the western world maintain the same weight from our wedding day to our golden anniversary 50 years later is silly,” adds the professor.

Challenging the widespread definition of BMI between 25 and 27 kg per meter squared (55-60 pounds per square foot) as being overweight, Goldbourt asserts: “It is not borne out of long-term observation of disease and mortality among middle-aged or elderly men and women.”

Goldbourt is the last person to condone couch potatoes. He, himself, is a runner, has taken part in several marathons and is past chairman of the Israel Track and Field Federation, which has close ties to European and to World Track and Field Federations.

And the professor is very careful to avoid the pitfall of seeing a cause-effect relationship between “overweight” individuals and Alzheimer’s. The study provides only a statistical association between mid-life weight and late-life dementia, he says. He was also involved in another study that found that people who ruminated over problems (not to the point of neurosis) and survived beyond age 75 years had less dementia in late-life.

The little-known tricep index

The researchers revealed another little known index – the folds in the tricep muscles of the upper arms. Of the men with skinfolds that measured 18 to 43 millimeters (.71-1.69 inches) in the initial study, only 15% exhibited dementia in the follow-up; of those whose skinfolds had initially measured four to seven millimeters (.16-.28 inches), 21% later exhibited dementia.

“The findings indicate only an inverse association, not a ‘protection’ against cognitive decline,” explains Goldbourt. “This measurement was often used in the 1950s and ‘60s. We don’t know whether skinfold size correlated in any way with numbers of men who died in the interim. The association of skinfold size with dementia, if it is valid, may have an unknown mechanism. Perhaps early childhood events, or traumas, or choosing manual labor led to reduced upper-arm fat later in life.

“An important difference between the cohort we studied and others is that manual labor was done primarily by the least-educated participants. It is on-the-job occupation I am referring to. Off-job physical activity, today’s style, was quite rare in middle-aged male immigrants to Israel in 1963. It was a tough time. Believe me, it was rare to see someone jogging.”

Last year, the online issue of Neurology (March 26, 2008) reported on a study conducted at Kaiser Permanente, a Division of Research in Northern California, that showed that those with a larger belly in mid-life (ages 40 to 45) who were also overweight were 2.3 times more likely to be afflicted with dementia in their 70s. Obese individuals, those with BMIs over 30 who have a belly, are 3.6 times at risk. Belly fat produces hormones that get to the brain, apparently accelerating brain dysfunction.

Kaiser findings differ from those of TAU in the study of BMI. Overweight individuals (BMI 25-30) had a 35% increased risk of dementia; while obese (BMI over 30) people had a whopping 74% risk. In a study of skinfold, a direct correlation was found between skinfold size and dementia, instead of inverse.

More intense, refined research is needed

In the world of research, where different studies using different variables and methodologies do not find the same ratio of risk or draw the same conclusions, there is certainly a need to intensify and refine the research, such as searching for red flag factors in middle age that may lead to dementia in later life.

Unraveling the mystery of the connection between weight and dementia requires careful investigation of many variables, including types of fat, when accumulated, inflammation, genetic factors and perhaps even a better index than BMI.

Socio-economic factors also seem to be associated with risk of dementia. Goldbourt and his associate at Mount Sinai Medical Center in New York, Prof. Michal Schnaider-Beeri, in collaboration with others at TAU, plan to conduct more studies that will relate dementia among long-term survivors to personal, familial, economic and other parameters in middle age.

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