Alzheimer's and Weight Fluctuation – Is There a Connection?

By Sharon Kanon
December 08, 2009

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.