Increasing weight loss between midlife and late life is a marker for mild cognitive impairment (MCI), according to a report published online ahead of print February 1 in JAMA Neurology. “While weight loss may not be causally related to MCI, we hypothesize that weight loss may represent a prodromal stage or an early manifestation of MCI,” said Rabe E. Alhurani, MBBS, a neurologist at Mayo Clinic in Rochester, Minnesota, and his associates.
Recent studies have reported a link between weight loss and dementia, “but overall, the findings of different studies have been inconclusive,” they noted. To examine any association between weight loss over time and incident MCI, the investigators analyzed information in the population-based Mayo Clinic Study of Aging database, which included approximately 10,000 residents of Olmsted County, Minnesota, who were between ages 70 and 89 at the beginning of the study in 2004. They focused on 1,895 participants who were cognitively normal at entry into the study and whose medical records included data on weight and height from midlife (ie, ages 40 to 65) onward. All of these study subjects underwent a physical examination and an extensive neuropsychologic evaluation every 15 months for a mean of 4.4 years.
A total of 524 study participants developed MCI during follow-up. The mean weight loss since midlife was significantly greater for people who developed MCI (–2.0 kg) than for those who remained cognitively normal (–1.2 kg). After the data were adjusted to account for patient sex, education level, and APOE ε4 allele status, loss of weight after midlife was robustly associated with incident MCI, and a loss of 5 kg per decade corresponded to a 24% increase in risk of MCI, Dr. Alhurani and his associates reported.
These findings remained consistent across all categories of baseline weight, regardless of whether the participants were underweight, normal weight, overweight, or obese at enrollment. The effect sizes of the associations were greater in men than in women, but were significant in both sexes.
This study could not establish causality, but the researchers speculated that the association between weight loss and MCI could result from three possible mechanisms. First, the weight loss could stem from the “anorexia of aging,” meaning that dysfunctional production of certain hormones, such as cholecystokinin, leptin, cytokines, dynorphin, neuropeptide Y, and serotonin, or dysfunctional dietary intakes and energy metabolism could lead patients to eat less, which could in turn raise the risk of MCI.
Second, “neuropsychiatric symptoms such as depression and apathy, which are prodromal and predictors of MCI and dementia, may contribute to decreased appetite and weight loss prior to the diagnosis of these conditions,” they suggested.
Third, weight loss and MCI could share an etiology. Researchers have reported finding protein deposits, including deposits of Lewy bodies, tau, or amyloid, in the olfactory bulb and central olfactory pathways before the onset of dementia, and olfactory dysfunction is a marker for cognitive impairment and dementia. “Impairment in smell with related changes in taste may contribute to decreased appetite, reduced dietary intake, and the weight loss observed with MCI, Alzheimer dementia, and other neurodegenerative conditions,” said Dr. Alhurani.
—Mary Ann Moon