Obesity is a risk factor for over 200 health conditions, and included on this list is Alzheimer’s disease . While the potential relationship of obesity with Parkinson’s disease is not as clear, abdominal obesity in particular has been suggested to be associated with a higher risk.
The mechanisms and pathways that result in neuroinflammation in Alzheimer’s and Parkinson’s diseases are fascinating, and can be explored in detail here and here. One of the postulated pathways, interestingly, is insulin resistance. When insulin resistance leads to elevated blood sugars and unfavorable cholesterol profiles, these conditions can damage the blood brain barrier. (Think of the blood brain barrier like a protective coating, keeping unwanted substances out of the brain.) Damage to the blood brain barrier creates an inflammatory state and makes the blood brain barrier leaky, creating more inflammation, and thus a vicious cycle propagates. Thus, insulin resistance is thought to feed the neuropathology of inflammatory conditions like Alzheimer’s disease. Leptin resistance and microbial dysbiosis (alterations in gut bacteria) are other postulated (and interrelated) contributing mechanisms.
It may seem counterintuitive that weight loss could be a good thing for people with Alzheimer’s or Parkinson’s, given that a decline in weight after midlife predicts a higher risk of cognitive impairment. A key point here is that a decline in weight very likely reflects unintentional weight loss, as can be seen in people with cognitive impairment. This must be distinguished from intentional weight loss. In studies of people with Alzheimer’s or Parkinson’s, it can be very difficult to separate intentional vs unintentional weight loss, to determine whether there is a benefit to intentional weight loss in people with obesity and either of these conditions.
A study of longitudinal survey data from Europe tried to disentagle this complicated relationship of body weight change and cognitive performance in the older population. They found that weight loss appears to be detrimental to cognition largely because it is a sign of physical deterioration, with the remaining effect possibly being due to other concomitant illness causing unintentional weight loss, and being driven by people who have low body mass index (BMI). They also found that weight gain becomes detrimental to congitive function as it accumulates in people with an already elevated BMI.
In a one year study of lifestyle-induced weight loss (caloric restriction) in 80 people aged 60 or older with obesity and mild cognitive impairment, weight loss was associated with improvements in verbal memory, verbal fluency, executive function, and global cognition.
This discussion is also relevant as regards treatment currently being explored for Alzheimer’s and/or Parkinson’s – specifically, the GLP1 receptor agonists. As blogged previously, early stage research has suggested potential benefit of GLP1RAs in people with Alzheimer’s dementia, and in people with Parkinson’s disease. These medications also cause weight loss, which may be a good thing for people with obesity, but may be undesired in people without obesity, or who are already unintentionally losing weight. More on this in an upcoming blog post – stay tuned!
BOTTOM LINE: Obesity is a risk factor for Alzheimer’s and potentially for Parkinson’s disease. Limited existing data suggests that intentional weight loss is beneficial for people with obesity and cognitive impairment, with much still to learn in this area.
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