Central obesity and increased risk of dementia more than three decades later

To the Editor:

We read with interest the article by Whitmer et al.,¹ who provide evidence of a longitudinal link between middle-life visceral obesity and dementia risk. It is now apparent that intra-abdominal fat may play a role in other health complications in addition to cardiovascular disease (CVD). Unfortunately, the underlying mechanisms are still unclear.

To explain the observations that overall adiposity is linked both to cognitive decline and CVD and that concurrent CVD is often seen in older patients with dementia, we recently reviewed current physiopathologic theories.^2,3 We concluded that visceral adipose tissue (VAT) is consistently implicated in cognitive decline rather than body mass index.

In addition, women who experience changes in body composition and fat distribution after menopause transition are at an increased risk of Alzheimer disease (AD). This is due to a stronger link to vascular factors (proinflammatory molecules) and metabolic complications (insulin resistance, dyslipidemia, hypertension).³

Luchsinger et al. have hypothesized that in people over 65, a short-term (5-year follow-up) prospective association seems modified by age and is different depending on the anthropometric measure.⁴ However, a life course contribution to chronic diseases is recognized.² The study by Whitmer et al.¹ supports the previously suggested theory^2,3 particularly when multiple adjustments for concurrent VAT-related complications (diabetes, hypertension, hyperlipidemia, and CVDs) are considered. In this respect, the role of VAT as endocrine organ, which is able to release a number of mediators, appears fundamental.

The confounding effect of insulin resistance should be recognized but it should also be noted that a chronic low-grade inflammation is a precondition associated with obesity duration. Reduction in VAT, particularly through physical activity, is efficacious in improving metabolic profile and inflammation. However, long-term …