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Original Investigation |

Risk Factors in Late Adolescence for Young-Onset Dementia in Men:  A Nationwide Cohort Study

Peter Nordström, PhD1; Anna Nordström, PhD2; Marie Eriksson, PhD3; Lars-Olof Wahlund, PhD4; Yngve Gustafson, PhD1
[+] Author Affiliations
1Department of Community Medicine and Rehabilitation, Section of Geriatric Medicine, Umeå University, Umeå, Sweden
2Department of Surgical and Perioperative Sciences, Section of Sports Medicine, Umeå University, Umeå, Sweden
3Department of Statistics, School of Business and Economics, Umeå University, Umeå, Sweden
4Department of Neurobiology, Care Sciences, and Society, Division of Clinical Geriatrics, Karolinska Institute, Stockholm, Sweden
JAMA Intern Med. 2013;173(17):1612-1618. doi:10.1001/jamainternmed.2013.9079.
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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.

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Figure 1.
The Cumulative Incidence of Different Types of Young-Onset Dementia With Increasing Age in the Study Cohort

AD indicates Alzheimer dementia; NUD, dementia of unspecified type; VD, vascular dementia.

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Figure 2.
Joint Effects of Overall Cognitive Function and Other Independent Risk Factors for Overall Risk of Young-Onset Dementia (YOD) in 487 Men

The bar graph depicts the number of risk factors present in each tertile of cognitive function, with hazard ratios (HRs) in the tabular material. Men in the highest tertile with no independent risk factor (alcohol or other drug intoxication, depression, neuroleptic use, stroke, lowest decile of height, highest decile of systolic blood pressure, and father’s dementia) were used as a reference. Hazard ratios were adjusted for age and year of conscription.

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