Risk factors in late adolescence for young-onset dementia in men: a nationwide cohort study

Abstract

Importance: Young-onset dementia (YOD), that is, dementia diagnosed before 65 years of age, has been related to genetic mutations in affected families. The identification of other risk factors could improve the understanding of this heterogeneous group of syndromes.

Objective: To evaluate risk factors in late adolescence for the development of YOD later in life.

Design: We identified the study cohort from the Swedish Military Service Conscription Register from January 1, 1969, through December 31, 1979. Potential risk factors, such as cognitive function and different physical characteristics, were assessed at conscription. We collected other risk factors, including dementia in parents, through national register linkage.

Participants: All Swedish men conscripted for mandatory military service (n=488,484) with a mean age of 18 years.

Setting: Predominantly Swedish men born from January 1, 1950, through December 31, 1960.

Exposure: Potential risk factors for dementia based on those found in previous studies, data available, and quality of register data.

Main outcomes and measure: All forms of YOD.

Results: During a median follow-up of 37 years, 487 men were diagnosed as having YOD at a median age of 54 years. In multivariate Cox regression analysis, significant risk factors (all P< .05) for YOD included alcohol intoxication (hazard ratio, 4.82 [95% CI, 3.83-6.05]); population-attributable risk, 0.28), stroke (2.96 [2.02-4.35]; 0.04), use of antipsychotics (2.75 [2.09-3.60]; 0.12), depression (1.89 [1.53-2.34]; 0.28), father's dementia (1.65 [1.22-2.24]; 0.04), drug intoxication other than alcohol (1.54 [1.06-2.24]; 0.03), low cognitive function at conscription (1.26 per 1-SD decrease [1.14-1.40]; 0.29), low height at conscription (1.16 per 1-SD decrease [1.04-1.29]; 0.16), and high systolic blood pressure at conscription (0.90 per 1-SD decrease [0.82-0.99]; 0.06). The population-attributable risk associated with all 9 risk factors was 68%. Men with at least 2 of these risk factors and in the lowest third of overall cognitive function were found to have a 20-fold increased risk of YOD during follow-up (hazard ratio, 20.38 [95% CI, 13.64-30.44]).

Conclusions and relevance: In this nationwide cohort, 9 independent risk factors were identified that accounted for most cases of YOD in men. These risk factors were multiplicative, most were potentially modifiable, and most could be traced to adolescence, suggesting excellent opportunities for early prevention.