Increased Alzheimer’s Disease Risk in Hospital-Treated Patients

Alzheimer's disease risk increases for hospitalized patients with shorter than a 5-year window.

Individuals hospitalized for a mental or behavioral disorder have an increased risk of subsequently developing Alzheimer’s disease (AD) during a 5-year window from the time of hospitalization, according to a Finnish study.

A team of researchers headed by Vesa Tapiainen, of the School of Pharmacy, University of Eastern Finland, conducted a nationwide nested case-control study of all Finnish clinically verified individuals with AD who were alive in 2005 and compared them with controls who were matched by age, sex, and region of residence (n=27,948 case-control pairs). The researchers analyzed the history of hospital-treated mental and behavioral disorders from 1972 onward, using diagnoses from the Hospital Discharge Register.

The diagnoses of “mental and behavioral disorders” included psychoactive substance use; schizophrenia, schizotypal and delusional disorder; depression and other mood disorders; neurotic, stress-related and somatoform disorders; and a category of “other disorders,” including organic disorders; manic episode or bipolar affective disorder; behavioral syndromes associated with physiological disturbances and physical factors; disorders of adult personality and behavior; mental retardation; disorders of psychological development; behavioral and emotional disorders with onset usually in childhood and adolescence; and unspecified mental disorders. An array of confounding comorbid chronic diseases were also taken into account.

The mean age of the study population was 79.7 (standard deviation [SD] 6.8), and the majority of the population (80.5%) was age ≥75. Of the population studied, 67.7% were women.

A total of 6.5% (n=3649) of the entire study population had a history of any mental and behavioral disorder requiring hospital treatment, and of disorders, depression and other mood disorders were the most frequent (37.5%). With the 5-year window between exposure and outcome, a history of mental and behavioral disorders was more frequent in patients with AD than in controls. Individuals with mental and behavioral disorders were younger (mean 78.7 [SD 7.3 vs 79.7 [SD 6.8]) and had more chronic diseases than patients without mental and behavioral disorders. There were no sex differences between the groups.

When a 5-year window was used, the mean difference between the first hospital admission due to any mental and behavioral disorder and date of AD diagnosis was 18.1 years (SD 8.9) in patients with AD vs 19.4 years in controls (SD 9.0).

The 5-year window was also important in the crude analysis, with any mental and behavioral disorder (odds ratio [OR] 1.09, 95% CI 1.02-1.17) and depression and other mood disorders (OR 1.18, 95% CI 1.06-1.32) associated with a higher risk for AD. However, these associations were no longer present when a 10-year window was applied. In fact, individuals with the longest window (>20 years) had lower odds of AD compared with individuals without a history of any mental or behavioral disorder. Indeed, the association became evident only in patients with a shorter than 5-year window.

“Our study showed that the [width] length of time window affects the association between mental and behavioral disorders and AD,” the investigators commented, noting that the association disappeared when the window was extended from 5 to 10 years. “These results may be due to misdiagnosis of prodromal symptoms of AD as mental and behavioral disorders,” they suggest.

The researchers also suggest a potential explanation for the inverse association between any mental and behavioral disorder and AD that was observed with windows longer than 20 years. Lithium, which is prescribed not only for bipolar disorder but also for depression and other mental disorders, may have had a preventive effect against AD, since lithium has been shown to decrease P-tau concentration in cerebrospinal fluid and improve cognitive skills in mild cognitively impaired patients, they note.

The researchers concluded that their study “underlines the importance of proper differential diagnostics of AD and mental and behavioral disorders” and highlights “the importance of appropriate time window in psychiatric and neuroepidemiology research.”

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Tapiainen V, Hartikainen S, Taipale H, et al. Hospital-treated mental and behavioral disorders and risk of Alzheimer’s disease: A nationwide nested case-control study [published online March 9, 2017]. Eur Psychiatry. doi:10.1016/j.eurpsy.2017.02.486.