Early, Midlife Infections Up Alzheimer’s, Parkinson’s Risk

Early and midlife infections treated in outpatient or inpatient hospital settings upped the risk of a subsequent Alzheimer’s or Parkinson’s disease diagnosis, a case-control study in Sweden showed.

A hospital-treated infection 5 or more years before diagnosis was associated with a 16% higher risk of Alzheimer’s (95% CI 1.15-1.18, P<0.001) and a 4% higher risk of Parkinson’s (95% CI 1.02-1.06, P<0.001), according to Jiangwei Sun, PhD, of Karolinska Institute in Stockholm, and colleagues.

Multiple hospital-treated infections before age 40 doubled the risk of a subsequent Alzheimer’s diagnosis (OR 2.62, 95% CI 2.52-2.72, P<0.001) and raised the risk of a Parkinson’s diagnosis by about 40% (OR 1.41, 95% CI 1.29-1.53, P<0.001), the researchers reported in PLOS Medicine.

The associations were due primarily to Alzheimer’s and Parkinson’s diagnosed before age 60 (OR 1.93, 95% CI 1.89-1.98 for Alzheimer’s, P<0.001; OR 1.29, 95% CI 1.22-1.36 for Parkinson’s, P<0.001). No associations emerged for people diagnosed at age 60 or older.

Similar risks were seen for bacterial, viral, and other infections and for different sites of infection, including gastrointestinal and genitourinary infections. No associations were seen between infection and amyotrophic lateral sclerosis (ALS) diagnoses.

“These findings suggest that infectious events may be a trigger or amplifier of a pre-existing disease process, leading to the clinical onset of neurodegenerative disease at a relatively early age,” Sun told MedPage Today. “However, due to the observational nature of the study, these results do not formally prove a causal link.”

Potential viral and bacterial contributions to neurodegeneration have long been debated among researchers, observed Percy Griffin, PhD, director of scientific engagement for the Alzheimer’s Association, who wasn’t involved with the study.

“However, no study to date has demonstrated a strong causal relationship,” Griffin told MedPage Today.

“This paper suggests an association between infections treated at a hospital and neurodegenerative diseases like Alzheimer’s and Parkinson’s,” he said. “One potential explanation for this is the inflammatory response to having an infection — especially one serious enough that a hospital visit is necessary — could contribute to or accelerate the neurodegeneration process by impairing the integrating of the blood brain barrier.”

“But much more research is needed to better understand the underlying mechanisms driving this association,” Griffin pointed out.

The analysis included 291,941 Alzheimer’s disease cases (median age at diagnosis was 76.2 and 46.6% were men), 103,919 Parkinson’s disease cases (median age at diagnosis was 74.3 and 55.1% were men), and 10,161 ALS cases (median age at diagnosis was 69.3 and 56.8% were men).

Cases were people newly diagnosed with Alzheimer’s, Parkinson’s, or ALS from 1970 through 2016 in the Swedish National Patient Register. The register included all inpatient care since 1987 and over 80% of outpatient care since 2001. For each case, five controls matched on sex and year of birth were randomly selected from the general population.

Findings were adjusted for sex, year of birth, area of residence, education, family history of neurodegenerative disease, and Charlson comorbidity index. Infections within 5 years before diagnosis of Alzheimer’s, Parkinson’s, or ALS were excluded to reduce possible surveillance bias or reverse causation.

Excluding infections that occurred within 10 years before Alzheimer’s or Parkinson’s diagnosis confirmed the findings, the researchers noted.

“The underlying mechanisms for the link between infections and neurodegenerative disease may not be specific to certain pathogens or affected organs but possibly occur at the systemic level,” Sun and colleagues wrote. Infections may lead to the clinical onset of Alzheimer’s or Parkinson’s at relatively early ages among people with disease predispositions, the team added.

Limitations included potential misclassification of hospital-treated infections and neurodegenerative diseases due to incomplete coverage of National Patient Register data, the researchers acknowledged. Residual confounding also may have influenced outcomes.