An 18-Year Follow-up of Overweight and Risk of Alzheimer Disease

Gustafson, Deborah; Rothenberg, Elisabet; Blennow, Kaj; Steen, Bertil; Skoog, Ingmar

doi:10.1001/archinte.163.13.1524

Cited by 717 publications

(574 citation statements)

References 27 publications

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“…Both clinical and experimental studies suggest that overweight is a contributing risk factor in Alzheimer's disease. This linkage is believed to be mediated by insulin resistance and/or dysfunction of the hypothalamic-pituitary-adrenal axis (31,37,38). Although corticosterone measurements were not performed in this study, the type 2 diabetic BBZDR/Wor rats examined here were obese and insulin resistant.…”

Section: Discussionmentioning

confidence: 83%

Alzheimer-Like Changes in Rat Models of Spontaneous Diabetes

2007

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OBJECTIVE-To examine whether changes characteristic of Alzheimer's disease occur in two rat models with spontaneous onset of type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS-The frontal cortices of 8-month-diabetic rats were examined with respect to neuronal densities, neurite degeneration, expression, and/or immunolocalization of amyloid precursor protein (APP), ␤-secretase, ␤-amyloid, COOH-terminal fragment (CTF), insulin receptor, IGF-1 receptor, glycogen synthase kinase 3-␤ (GSK-3␤), protein kinase B (Akt), phosphorylated (phospho-), synaptophysin, and phosphorylated neurofilaments (SMI-31).RESULTS-Neuronal loss occurred in both models, significantly more so in type 2 diabetic BBZDR/Wor rats compared with type 1 diabetic BB/Wor rats and was associated with a ninefold increase of dystrophic neurites. APP, ␤-secretase, ␤-amyloid, and CTF were significantly increased in type 2 diabetic rats, as was phospho-. The insulin receptor expression was decreased in type 1 diabetes, whereas IGF-1 receptor was decreased in both models, as were Akt and GSK-3␤ expression. CONCLUSIONS-The data show that ␤-amyloid and phosphoaccumulation occur in experimental diabetes and that this is associated with neurite degeneration and neuronal loss. The changes were more severe in the type 2 diabetic model and appear to be associated with insulin resistance and possibly hypercholesterolemia. The two models will provide useful tools to unravel further mechanistic associations between diabetes and Alzheimer's disease.

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Section: Discussionmentioning

confidence: 83%

Alzheimer-Like Changes in Rat Models of Spontaneous Diabetes

2007

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“…Adipose tissue is a potent source of peripheral IL-6 thought to account for approximately 30% of circulating levels (33). Further, greater BMI in middle and later life is associated with poorer cognitive function independently of age (52) and predicts temporal lobe and global brain atrophy, cognitive decline, and the incidence of dementia (35,(52)(53)(54)(55)(56). Animal studies also show that obesity is associated with impaired hippocampal LTP (57) and deficits in hippocampal-dependent learning and memory (58).…”

Section: Discussionmentioning

confidence: 99%

Interleukin-6 Covaries Inversely with Hippocampal Grey Matter Volume in Middle-Aged Adults

Marsland

Gianaros

Abramowitch

et al. 2008

Biological Psychiatry

309

224

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Background-Converging animal findings suggest that higher peripheral levels of inflammation are associated with activation of central inflammatory mechanisms that result in hippocampal neurodegeneration and related impairment of memory function. Consistent with animal findings, we have recently shown an inverse association between peripheral levels of interleukin-6 (IL-6), a relatively stable marker of systemic inflammation, and memory function in mid-life adults. In the current study, we extend this work to test whether systemic inflammation is associated with reduced grey matter volume of the hippocampus.

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“…Furthermore, individual components of MetS have been linked to the risk of developing CD and dementia. Midlife overweight or obesity [measured by body mass index (BMI)] and midlife central obesity (measured by waist circumference) have been related to an increased risk of CD [12][13][14][15], as well as late-life underweight and weight loss [16,17]. Epidemiological studies have disclosed an association between DM and increased risk of cognitive impairment and dementia [18,19].…”

Section: Introductionmentioning

confidence: 99%

Midlife Metabolic Profile and the Risk of Late-Life Cognitive Decline

Tortelli

Lozupone

Guerra

et al. 2017

JAD

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Abstract. Among metabolic syndrome components, the effects of higher plasma glucose levels on cognitive decline (CD) have been considered in few studies. We evaluated the associations among midlife glycemia, total cholesterol, high-density lipoprotein cholesterol, triglycerides, midlife insulin resistance [homeostasis model assessment for insulin resistance (HOMAindex)], and CD in the older subjects of the population-based MICOL Study (Castellana Grotte, Italy) at baseline (M1) and at follow-ups seven (M2) and twenty years later (M3). At M1, a dementia risk score and a composite cardiovascular risk score for dementia were calculated. For 797 subjects out of 833, we obtained a Mini-Mental State Examination (MMSE) score at M3, subdividing these subjects in three cognitive functioning subgroups: normal cognition, mild CD, and moderate-severe CD. Mean fasting glycemia at baseline was significantly higher in moderate-severe CD subgroup (114.6 ± 71.4 mg/dl) than in the normal cognition subgroup (101.2 ± 20.6). Adjusting for gender, age, and other metabolic components, higher fasting glycemia values both at M1 [odds ratio (OR) = 1.31; 95% confidence interval (CI): 1.08-1.59] and M2 (OR = 1.26; 95% CI: 1.01-1.57) were associated with an increased risk of moderate-severe CD. Mean HOMA index value was significantly higher in the moderate-severe CD subgroup (5.7 ± 9.4) compared to the normal cognition subgroup (2.9 ± 1.4) at M1. The dementia risk probability (MMSE < 24) increased moving through higher categories of the dementia risk score and decreased as long as the cardiovascular score increased. The present findings highlighted the indication to control blood glucose levels, regardless of a diagnosis of diabetes mellitus, as early as midlife for prevention of late-life dementia.

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An 18-Year Follow-up of Overweight and Risk of Alzheimer Disease

Abstract: Overweight is epidemic in Western societies. Our data suggest that overweight at high ages is a risk factor for dementia, particularly AD, in women. This may have profound implications for dementia prevention.

Cited by 717 publications

References 27 publications

Alzheimer-Like Changes in Rat Models of Spontaneous Diabetes

Alzheimer-Like Changes in Rat Models of Spontaneous Diabetes

Interleukin-6 Covaries Inversely with Hippocampal Grey Matter Volume in Middle-Aged Adults

Midlife Metabolic Profile and the Risk of Late-Life Cognitive Decline

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