Metabolic disorders such as obesity and diabetes appear to share
risk factors with and may influence the development of Alzheimer's
disease and other forms of dementia, according to several reports
published in the March issue of Archives of Neurology.
The issue - a theme issue on neurological disorders related to
metabolic diseases - is being published in conjunction with a
JAMA theme issue on diabetes, obesity and their comorbidities. The
March issue of Archives of Ophthalmology, along with the April issues
of Archives of Pediatrics & Adolescent Medicine, Archives of
Dermatology and Archives of Surgery, will also feature research on this
Studies featured in this issue include the following:
Women With More Components of Metabolic Syndrome More Likely
to Develop Cognitive Impairment
Women with the cluster of cardiovascular risk factors known
collectively as the metabolic syndrome appear likely to develop
cognitive impairment over a four-year period. Kristine Yaffe, M.D., of
the University of California, San Francisco, and the San Francisco
Veterans' Affairs Medical Center, and colleagues assessed 4,895 older
women (average age 66.2) who did not have cognitive impairment at the
beginning of the study.
Of the 497 (10.2 percent) women who had the metabolic syndrome 7.2
percent (36) developed cognitive impairment during a four-year period,
compared with 4.1 percent (181 of 4,398) of those who did not have the
metabolic syndrome. Each additional component of the
syndrome - such as abdominal obesity, high blood pressure and low
HDL cholesterol levels - was associated with a 23 percent
increase in risk of cognitive impairment.
"As the obesity and sedentary lifestyle epidemic escalates
throughout the world, identification of the role of these modifiable
behaviors in increasing risk for development of deleterious outcomes,
such as cognitive impairment, is critical," the authors conclude.
"Future research should assess whether identification of cognitive
impairment among patients with the metabolic syndrome or more
aggressive clinical control of the factors that compose the metabolic
syndrome might lessen the risk of developing cognitive impairment in
( Arch Neurol . 2009;66:324-328.
Obesity Associated With Worsening Cognitive Function in
Older men with higher levels of fat appear more likely to experience
declines in cognitive function over seven years, but the same
association does not appear to occur in older women. Alka M. Kanaya,
M.D., of the University of Californiaâ€“San Francisco, and
colleagues studied 3,054 elderly individuals enrolled in the Health ABC
Participants' adiposity (fat level) was assessed by body mass index,
waist circumference, sagittal diameter (distance between the back and
the highest point of the abdomen), total fat mass and subcutaneous
(beneath the skin) and visceral fat (fat between the internal organs)
measured by computed tomography. Men whose measurements were higher
were more likely to experience declines in scores on a cognitive
functioning test administered at the beginning of the study and again
after three, five and eight years. However, no association was observed
"Women show trends toward inverse associations, with higher levels
of adiposity being associated with less cognitive change," the authors
write. "Traditional metabolic factors, adipocytokines [compounds
produced by fat tissue] and sex hormones do not explain this sex
difference. Future studies should confirm these longitudinal
associations with adiposity and cognitive change and investigate why
adiposity has inverse associations in men and women."
( Arch Neurol . 2009;66:329-335.
Obese Middle-Aged Adults and Underweight Older Adults Appear
to Have Increased Risk for Dementia
Midlife obesity may be associated with risk for dementia, but after
age 65, the relationship between body mass index and dementia appears
to reverse so that underweight individuals are at higher risk. Annette
L. Fitzpatrick, Ph.D., of the University of Washington, Seattle, and
colleagues analyzed data from 2,798 adults (average age 74.7) without
dementia. Participants reported their weight at age 50 (midlife) and
had their height and weight measured at age 65 or older (late life).
Over an average of 5.4 years of follow-up, 480 individuals developed
dementia, including 245 with Alzheimer's disease and 213 with vascular
dementia. In evaluations of midlife obesity, individuals with a body
mass index (BMI) of higher than 30 - classified as
obese - were more likely than those of a normal weight to develop
dementia. However, those who were underweight (BMI of lower than 20) in
late life had an increased risk of dementia, whereas being overweight
in late life was not associated with dementia and being obese appeared
to have a protective effect.
"The greatest dementia risk was found in underweight individuals at
older ages. These findings suggest the predictive ability of BMI
changes across time," the authors write. "These results help explain
the 'obesity paradox' as differences in dementia risk across time are
consistent with physical changes in the trajectory toward disability."
( Arch Neurol . 2009;66:336-342.
Heart Disease Risk Factors Associated With Faster Cognitive
Individuals with higher total and low-density lipoprotein (LDL, or
"bad") cholesterol levels and a history of diabetes appear to
experience a more rapid cognitive decline after developing Alzheimer's
disease. Elizabeth P. Helzner, Ph.D, and colleagues at the Columbia
University Medical Center, New York, studied 156 patients who were
diagnosed with Alzheimer's disease at an average age of 83.
During an average of 3.5 years of follow-up, those who had higher
LDL and total cholesterol levels before diagnosis experienced a more
rapid decline on cognitive test scores than those whose cholesterol
levels were in the normal range, as did those with a history of
diabetes when compared with those without diabetes.
The study "provides further evidence for the role of vascular risk
factors in the course of Alzheimer's disease," the authors conclude.
"Prevention or treatment of these conditions can potentially slow the
course of Alzheimer's disease."
( Arch Neurol . 2009;66:343-348.
Review: Insulin Resistance May Links Metabolic and Cognitive
Insulin resistance, when tissues in the body lose sensitivity to the
hormone that regulates glucose, may underlie both dementia and
metabolic disorders such as obesity and diabetes. In a review article,
Suzanne Craft, Ph.D., of Veterans Administration Puget Sound Health
Care System and University of Washington School of Medicine, Seattle,
writes that "considerable progress has been made in establishing
relationships among metabolic disorders and late-life dementing
illnesses," including through the common foundation of insulin
"A number of challenges must be addressed as we move forward to
determine the key mechanisms underlying these associations," Dr. Craft
concludes, including establishing clear definitions of both metabolic
and neurological conditions. "Future research aimed at identifying
mechanisms that underlie comorbid associations will not only provide
important insights into the causes and interdependencies of late-life
dementias, but will also inspire novel strategies for treating and
preventing these disorders."