Higher body mass index (BMI) in middle age could be a warning sign of dementia decades down the road, scientists reported this week, but weight loss leading up to a formal diagnosis could mask symptoms and confound patients.

Miki Kivimaki, PhD, and colleagues at University College London analyzed the data of more than one million American and European patients in a large-scale study of the relationship between dementia and obesity. Past data and meta-analyses have reflected contrasting results, Kivimaki et al. wrote in Alzheimer’s & Dementia—and now, clinicians might know why.

Kivimaki and his team pooled data from 1.3 million adults from 39 prospective cohort studies, according to their paper. BMI was assessed at baseline and patients were then tracked for an average of 16 years, after which the researchers used electronic health records to identify 6,894 patients who had developed dementia over the course of the trial.

Though Kivimaki and co-authors hypothesized BMI would have little to do with dementia one to two decades prior to its onset, they found that higher BMI was linked to increased risk of dementia when clinical follow-up was long. When follow-up was short, they wrote, a lower BMI was associated with higher dementia risk.

“The BMI-dementia association observed in longitudinal population studies such as ours is actually attributable to two processes,” Kivimaki said in a release from UCL. “One is an adverse effect of excess body fat on dementia risk. The other is weight loss due to preclinical dementia. For this reason, people who develop dementia may have a higher-than-average body mass index some 20 years before dementia onset, but close to overt dementia have a lower BMI than those who remain healthy.”

He said his study demonstrates both the adverse effects obesity can have on a patient’s body and the metabolic changes that can occur in a pre-dementia state. In the study, Kivimaki and colleagues found, each 5-unit increase in BMI was associated with between a 16 and 33 percent greater risk of dementia.

“Taken together, these findings provide new evidence for the hypothesis that the association between BMI and dementia is attributable to two distinct processes,” they wrote. “By dissecting these processes in stratified analyses, our study provides a plausible explanation for the inconsistencies in some of the prior studies on BMI and dementia.”