ABSTRACT
Infections, which can prompt neuroinflammation, may be a risk factor for dementia1-5. More information is needed concerning associations across different infections and different dementias, and from longitudinal studies with long follow-ups. This New Zealand-based population register study tested whether infections antedate dementia across three decades. We identified individuals born between 1929 and 1968 and followed them from 1989 to 2019 (n = 1,742,406, baseline age = 21-60 years). Infection diagnoses were ascertained from public hospital records. Dementia diagnoses were ascertained from public hospital, mortality and pharmaceutical records. Relative to individuals without an infection, those with an infection were at increased risk of dementia (hazard ratio 2.93, 95% confidence interval 2.68-3.20). Associations were evident for dementia diagnoses made up to 25-30 years after infection diagnoses. Associations held after accounting for preexisting physical diseases, mental disorders and socioeconomic deprivation. Associations were evident for viral, bacterial, parasitic and other infections, and for Alzheimer's disease and other dementias, including vascular dementia. Preventing infections might reduce the burden of neurodegenerative conditions.
ABSTRACT
BACKGROUND: Rising midlife mortality in the United States is largely attributable to 'deaths of despair' (deaths from suicide, drug poisonings, and alcohol-related diseases) and deaths from cardiometabolic conditions. Although despair- and cardiometabolic-related mortality are increasing concurrently, it is unclear whether they share common developmental origins. We tested adolescent psychopathology as a potential common origin of midlife diseases of despair and cardiometabolic risk. METHODS: Participants (N = 4578) were from the National Longitudinal Study of Adolescent to Adult Health, a nationally representative cohort followed from adolescence to early midlife. Adolescent psychopathology included depression, anxiety, eating disorders, PTSD, conduct disorder, and ADHD at ages 11-18. Diseases of despair (suicidality, substance misuse, pain, and sleep problems) and cardiometabolic risk (hypertension, hyperlipidemia, high-risk waist circumference, diabetes, and cardiovascular conditions) were multi-modally measured at ages 33-43. RESULTS: At midlife, adolescents who experienced psychopathology exhibited more indicators of despair-related diseases and cardiometabolic risk (IRRs = 1.67 [1.46-1.87] and 1.13 [1.04-1.21], respectively), even after accounting for demographics, adolescent SES, and adolescent cognitive ability. Associations were evident for internalizing and externalizing conditions, and in a dose-response fashion. In mediation analyses, low education explained little of these associations, but early-adult substance use explained 21.5% of psychopathology's association with despair-related diseases. Midlife despair-related diseases and cardiometabolic risk co-occurred within individuals (IRR = 1.12 [1.08-1.16]). Adolescent psychopathology accounted for 8.3% of this co-occurrence, and 16.7% together with adolescent SES and cognitive ability. CONCLUSIONS: Adolescent psychopathology precedes both diseases of despair and cardiometabolic risk. Prevention and treatment of psychopathology may mitigate multiple causes of poor midlife health, reducing premature mortality.
