Tabet, N. (2005) BMJ 331 454-455
EDITOR-Whitmer et al report further evidence supporting the association between obesity and dementia.1 Although the mechanism is still far from being understood, the authors alluded to the involvement of adiposity with inflammation and its markers.
One possible mechanism linking obesity with dementia is oxidative stress resulting from an increased intake of processed sugars and fats, which is the hall-mark of the modern diet. Rats maintained on a diet high in refined sugar and fat generated higher concentrations of free radicals.2 3 In contrast, caloric restriction in animals leads to reduced production of free radicals by mitochondria and increased longevity.4
Whitmer et al acknowledge that the lack of nutritional assessment was a limitation of their study. If such data had been available they would have shed light specifically on a possible relation between fat and sugar intake and risk of dementia, especially as a diet rich in these substances is linked to obesity. We recently showed that patients with dementia eating a diet high in fat and carbohydrates have an increased blood activity of glutathione peroxidase, an endogenous antioxidant, which may be a compensatory response to an increased oxidative stress in dementia.5
Whitmer et al say that all cause dementia diagnoses included dementia, Alzheimer's disease, and vascular dementia.1 However, their data did not include differentiation between these subsets, especially between Alzheimer's disease and vascular dementia. Whether obesity was preferentially associated with either vascular dementia or Alzheimer's disease, or both, would be interesting, especially as the neuropathological aetiology of these two disorders is different.
1. Whitmer RA, Gunderson EP, Barrett-Connor E, Quesenberry CP, Yaffe K. Obesity in middle age and future risk of dementia: a 27 year longitudinal population based study. BMJ 2005;330: 1360-2.
2. Hennig B, Slim R, Toborek M, Malecki A, Robertson LW. Effects of lipids and antioxidants on PCB-mediated dysfunction of vascular endothelial cells (EC). Central Eur J Public Health 2000;8: S18-9.
3. Kashiwagi A, Shinozaki K, Nishio Y, Okamura T, Toda N, Kikkawa R. Free radical production in endothelial cells as a pathogenetic factor vascular dysfunction in the insulin resistance state. Diabetes Res Clin Pract 1999;45: 199-203.
4. Gredilla R, Barja G. The role of oxidative stress in relation to caloric restriction and longevity. Endocrinology 2005;26: Epub1-20.
5. Tabet N, Mantle D, Walker Z, Orrell M. Higher fat and carbohydrate intake in dementia patients is associated with increased blood glutathione peroxidase activity. Int Psychogeriatr 2005;17: 91-8.