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Effects of Diabetes and Adiposity on Cognition in Elders
Two studies suggest differential patterns of cognitive decline or dementia, one between men and women with increased adiposity, the other between patients with and without diabetes.
Most studies that have shown an association between obesity and increased risk for dementia have used surrogate measures of adiposity like body-mass index and waist circumference. Direct measurements of fat mass might be more accurate in older populations. Kanaya and colleagues examined whether radiographically ascertained measures of adiposity (dual energy x-ray absorptiometry and computed tomography) and standard surrogate measures of adiposity were both related to changes in cognitive function over a 7-year period in 3054 elders (baseline age range, 70–79). By almost all measures, both surrogate and direct, greater adiposity was significantly associated with greater cognitive decline in men, but not in women. Adjustments for demographics, activity level, blood pressure level, diabetes, and adipocytokine levels did not alter the findings.
Diabetes mellitus (DM) is another factor associated with increased risk for dementia. The few autopsy studies conducted to date have been inconsistent in showing histopathologic features of Alzheimer disease (AD) in demented patients with DM. To address these inconsistencies, Sonnen and colleagues tested the hypothesis that DM promotes specific processes that contribute to dementia. The investigators performed neuropathologic assessments on brain tissue from 196 participants in a community-based study of incident dementia and performed biochemical analyses on tissue samples from 82 of these participants. Two different patterns of cerebral damage were apparent: Those with dementia but without DM had higher amyloid-beta peptide levels and greater free-radical damage, whereas those with dementia and DM had more microvascular infarcts and activation of neuroinflammation. In patients with dementia, treatment of diabetes had only a modest effect on brain pathology, reducing neuritic plaque load but having no effect on cerebral amyloid angiopathy, atherosclerosis, microvascular infarcts, or gross infarcts.
Comment: Several longitudinal population-based investigations have demonstrated increased risk for dementia in association with diabetes, obesity, hypertension, and dyslipidemia (Eur J Pharmacol 2008; 585:97). These are well-established risk factors for atherosclerosis, raising the possibility that atherosclerosis is a final common pathway through which these factors are involved in the pathogenesis of dementia. The work of Sonnen and colleagues supports this possibility, demonstrating a novel pattern of brain injury in patients with dementia and DM, who had less accumulation of amyloid-beta peptide yet more microvascular infarcts and signs of neuroinflammation than dementia patients without DM. Similarly, previous work has established obesity as a risk factor for atherosclerosis (Clin Cardiol 2002; 25:205).
Given that a certain threshold of brain-tissue damage is required for expression of clinical dementia, perhaps the co-occurrence of two pathologic processes (as is often seen with DM) increases the risk for reaching this threshold. To the extent that these vascular risk factors are modifiable, they provide potential targets for therapeutic interventions.
— Joseph I. Friedman, MD
Dr. Friedman is Associate Professor of Psychiatry, Mount Sinai School of Medicine, New York City, and Science Director, Pilgrim Psychiatric Center, West Brentwood, New York.
Published in Journal Watch Neurology August 4, 2009
Citation(s):
Kanaya AM et al. Total and regional adiposity and cognitive change in older adults: The Health, Aging and Body Composition (ABC) Study. Arch Neurol 2009 Mar; 66:329.
- Original article (Subscription may be required)
- Medline abstract (Free)
Sonnen JA et al. Different patterns of cerebral injury in dementia with or without diabetes. Arch Neurol 2009 Mar; 66:315.
- Original article (Subscription may be required)
- Medline abstract (Free)
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