genotypes modify the obesity paradox in dementia.

BACKGROUND

While obesity in midlife is a risk factor for dementia, several studies suggested that obesity also protected against dementia, hence so-called obesity paradox. The current study aims to address the relationship between apolipoprotein E () genotype and obesity in dementia.

METHODS

Clinical and neuropathological records of the National Alzheimer's Coordinating Center (NACC) in the USA, which longitudinally followed approximately 20 000 subjects with different cognitive statues, genotype and obesity states, were reviewed.

RESULTS

Obesity was associated with cognitive decline in early elderly cognitively normal individuals without , especially those with . Neuropathological analyses adjusted for dementia status showed that carriers tended to have more microinfarcts and haemorrhages due to obesity. On the other hand, obesity was associated with a lower frequency of dementia and less cognitive impairment in individuals with mild cognitive impairment or dementia. Such trends were particularly strong in carriers. Obesity was associated with fewer Alzheimer's pathologies in individuals with dementia.

CONCLUSIONS

Obesity may accelerate cognitive decline in middle to early elderly cognitive normal individuals without likely by provoking vascular impairments. On the other hand, obesity may ease cognitive impairment in both individuals with dementia and individuals at the predementia stage, especially those with , through protecting against Alzheimer's pathologies. These results support that genotype modifies the obesity paradox in dementia.