Longitudinal Associations of Mental Disorders With Dementia

Abstract

IMPORTANCE Mental disorders are an underappreciated category of modifiable risk factors for dementia. Developing an evidence base about the link between mental disorders and dementia risk requires studies that use large, representative samples, consider the full range of psychiatric conditions, ascertain mental disorders from early life, use long follow-ups, and distinguish between Alzheimer disease and related dementias. OBJECTIVE To test whether mental disorders antedate dementia across 3 decades of observation. DESIGN, SETTING, AND PARTICIPANTS This population-based administrative register study of mental disorders and Alzheimer disease and related dementias included all individuals born in New Zealand between 1928 and 1967 who resided in the country for any time during the 30-year observation period between July 1988 and June 2018. Data were from the New Zealand Integrated Data Infrastructure, a collection of whole-of-population administrative data sources linked at the individual level. Data were analyzed from October 2020 to November 2021.EXPOSURES Diagnoses of mental disorders were ascertained from public-hospital records.MAIN OUTCOMES AND MEASURES Diagnoses of dementia were ascertained from public-hospital records, mortality records, and pharmaceutical records. RESULTSOf 1 711 386 included individuals, 866 301 (50.6%) were male, and individuals were aged 21 to 60 years at baseline. Relative to individuals without a mental disorder, those with a mental disorder were at increased risk of developing subsequent dementia (relative risk [RR], 4.24; 95% CI, 4. hazard ratio, 6.49; 95% CI,). Among individuals with dementia, those with a mental disorder developed dementia a mean of 5.60 years (95% CI, 5.31-5.90) earlier than those without a mental disorder. Associations held across sex and age and after accounting for preexisting chronic physical diseases and socioeconomic deprivation. Associations were present across different types of mental disorders and self-harm behavior (RRs ranged from 2.93 [95% CI, 2.66-3.21] for neurotic disorders to 6.20 [95% CI, 5.67-6.78] for psychotic disorders), and were evident for Alzheimer disease (RR, 2.76; 95% CI,) and all other dementias (RR, 5.85; 95% CI, 5.58-6.13).CONCLUSIONS AND RELEVANCE In this study, mental disorders were associated with the onset of dementia in the population. Ameliorating mental disorders in early life might also ameliorate neurodegenerative conditions and extend quality of life in old age.

Association of Oxidative Stress–Induced Nucleic Acid Damage With Psychiatric Disorders in Adults

“…Given that there was an association with NA-OXS across many different diagnoses and matrices, and given that NA-OXS was not specifically increased in the brain, we consider it more likely to be an epiphenomenon of the psychiatric conditions rather than a pathophysiologic factor underlying specific psychopathology. This finding is consistent with growing evidence showing general, transdiagnostic signs of accelerated aging and age-related illness in psychiatric disorders . Interestingly, a 2016 meta-analysis on DNA damage from oxidative stress in patients with cardiovascular disorders reported SMDs between patients and controls in the same order of magnitude as reported in our study …”

“…In many comparisons, SMDs in “nonorganic” psychiatric disorders (eg, psychotic and mood disorders) were of a magnitude similar to that of paradigmatic organic disorders of the dementias. Given the known roles of DNA and RNA damage from oxidation in molecular aging, ubiquitously increased NA-OXS could be an important biological mechanism driving the severely increased morbidity and mortality from age-related medical conditions in psychiatric disorders …”

Association Between Psychological Distress and Incident Dementia in a Population-Based Cohort in Finland

“…Overall, the increase in the dementia risk (hazard) associated with the psychological distress symptoms in our study was around 20% in the Poisson model, and it was not fully caused by reverse causation. As assumed, the effect sizes were smaller than those reported for psychiatric disorders, which are likely to represent more severe situations. Our results agree with previous longitudinal studies reporting multiple symptoms of psychological distress or an aggregate of the different symptoms associated with modestly increased risk of dementia in etiological models .…”

Alzheimer's disease genetic burden is associated with mid‐life depression among persons with normal cognition

“…Community‐based prospective cohort studies have found that depression, either mid‐life or late‐life depression, was associated with a two‐fold higher risk for subsequent development of Alzheimer's disease (AD) or vascular dementia 1–6 . The prospective studies in late‐life depression were conducted in about 50,000 community‐based participants who had depression in the absence of dementia at baseline and were followed over time for a median of 5 years 4 .…”