Lifestyle-Dementia Links Persist Regardless of Risk Genes, French Study Shows

Lifestyle and other dementia risk factors were linked with cognitive changes independently of genetic risks for Alzheimer’s disease, a French prospective study found.

Across nearly 5,200 people in three French cities, worse scores on the Lifestyle for Brain (LIBRA) health risk scale at baseline were tied to both subsequent cognitive decline and dementia incidence, with no significant effect modification by APOE4 or other genes, reported Cécilia Samieri, DVM, PhD, of the University of Bordeaux, and co-authors.

The hazard ratio for dementia for a 1-point change in LIBRA scores was 1.09 in APOE4 non-carriers and 1.15 in APOE4 carriers (P=0.15), the researchers wrote in Alzheimer’s and Dementia. Similar findings emerged for an overall genetic risk score for cognitive decline.

The findings show that a “combination of lifestyle and other modifiable risk factors is associated with a lower risk of dementia, regardless of genetic susceptibility, including among those most at risk of Alzheimer’s disease — carriers of the APOE4 gene and other genetic variants as well,” said Samieri.

“This is clearly an encouraging message of prevention, as this work suggests that lifestyle modifications by targeted prevention are likely to be beneficial in all, including those most at risk of developing Alzheimer’s dementia,” she told MedPage Today.

Up to 40% of dementia cases may be delayed or slowed by 12 modifiable risk factors, according to the most recent Lancet Commission report. The LIBRA health risk score assesses and combines dementia risk factors and produces a weighted sum of components that includes lifestyle factors — healthy diet, engagement in regular exercise, cognitively stimulating activities, smoking, and alcohol consumption — plus cardiometabolic and renal factors, and depression. An increase of 1 point in the LIBRA score has been associated with a 19% higher risk for dementia and a 9% higher risk for cognitive impairment.

“A crucial question for public health and prevention is whether the risk of dementia attributable to genetic susceptibility may be lowered by acting on modifiable risk factors through global prevention programs,” Samieri and co-authors noted. “This is a key concept of precision prevention, in which the right intervention should target the right population (in the right window of opportunity).”

Besides APOE4, other Alzheimer’s and dementia risk loci have been identified in genome-wide association studies. These formed the basis for the genetic risk score used in the analysis.

The researchers followed 5,170 people in the Three-City Study, a population-based longitudinal study in France. Participants were recruited in 1999 and 2000 and were dementia-free at baseline. In-person follow-ups were conducted every 2 to 3 years for 12 years in Dijon, 15 years in Montpellier, and 17 years in Bordeaux.

At baseline, participants had an average age of 74 years, 66% were women, and 39% had an education level higher than secondary school. A total of 1,383 participants had low LIBRA scores; 2,503 had intermediate LIBRA scores; and 1,284 had high LIBRA scores. APOE4 carriers were evenly distributed across LIBRA levels (about 20% in each score level.)

Overall, 652 participants (13%) developed dementia over a mean follow-up time of 8.4 years. Dementia incidence climbed with increasing LIBRA scores (1.1 per 100 person-years in the lowest LIBRA quartile vs 2.3 per 100 person-years in the highest quartile).

Dementia incidence was higher in people with higher genetic risk, but rose with increasing LIBRA scores in all categories of genetic risk. In APOE4 carriers, for example, dementia incidence rates were 1.4 per 100 person-years in the low LIBRA category versus 3.3 per 100 person-years in the high LIBRA category. A similar pattern emerged for the genetic risk score.

Analyses of cognitive trajectories were consistent with dementia findings, the researchers noted. “Each 1-point increase in the LIBRA was associated with worse initial global cognition and with a steeper annual rate of cognitive decline, both in APOE4 carriers and non-carriers,” they wrote.

The study had limitations, Samieri and co-authors acknowledged. LIBRA scores were estimated at baseline only, and may have changed over time. Over the course of the study, loss to follow-up occurred. The study was observational, and reverse causality cannot be ruled out.

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