Repetitive Negative Thinking Linked With Alzheimer's Pathology

Repetitive negative thinking was tied to cognitive and neuropathological markers of Alzheimer's disease, a longitudinal study showed.

Patterns of repeated rumination or worry were associated with subsequent declines in global cognition, immediate memory, and delayed memory, reported Natalie Marchant, PhD, of University College London, and co-authors.

Repetitive negative thinking also was linked to global amyloid and entorhinal tau deposits, they wrote in Alzheimer's & Dementia.

"This study identifies a novel and potentially modifiable psychological process -- repetitive negative thinking -- that is associated with increased risk for dementia," Marchant said.

"As repetitive negative thinking is a commonly occurring symptom in depression and anxiety disorders, our finding could help explain the associations observed between those disorders and increased dementia risk," she told MedPage Today.

Anxiety and depression have been linked with subsequent dementia in earlier studies, and it's possible an overall thinking style central to these relationships may be a factor, she noted. "Certain thinking patterns implicated in depression and anxiety could be an underlying reason why people with those disorders are more likely to develop dementia," she said.

In their analysis, Marchant and her group studied 292 adults over age 55 with elevated risk of dementia (at least one first‐degree relative had Alzheimer's disease) in the PREVENT-AD cohort, and an additional 68 people from the IMAP+ neuroimaging cohort. In the PREVENT-AD cohort, 39% carried an APOE4 allele, a genetic risk factor for Alzheimer's disease. In the IMAP+ group, 24% were APOE4 carriers.

All participants performed in the normal range in neuropsychological tests, had no clinical evidence of a major neurological or psychiatric disorder, and had a Mini‐Mental State Examination (MMSE) score of 28 or higher (normal cognition).

Over 2 years, participants completed the 15-item Perseverative Thinking Questionnaire (PTQ), a self-reported measure to identify repetitive negative thinking, including patterns of rumination or worry. They also completed questionnaires to assess depression and anxiety symptoms.

Participants had longitudinal cognitive assessments; depending on the subgroup, cognition was assessed with either the MMSE or Montreal Cognitive Assessment (MoCA), or both. In the PREVENT-AD cohort, 113 people had amyloid‐PET and tau‐PET scans. All 68 people in the IMAP+ cohort had amyloid‐PET scans.

Baseline repetitive negative thinking was not associated with age, education, or APOE status. In the PREVENT-AD cohort, it was associated with female sex.

Over a 4-year period, people with higher repetitive negative thinking patterns experienced faster decline in global cognition (P=0.02), immediate memory (P=0.03), and delayed memory (P=0.04).

People with higher repetitive negative thought patterns also were more likely to have global amyloid (PREVENT‐AD: P=0.01; IMAP+: P=0.03) and entorhinal tau (P=0.02) deposits. Relationships remained after adjusting for potential confounders.

Depression and anxiety were associated with subsequent cognitive decline, but not with amyloid or tau deposition.

One explanation for the link between repetitive negative thinking and Alzheimer's biomarkers may be the stress pathway, the researchers suggested. "Repetitive negative thinking is associated with indicators of stress (e.g., elevated blood pressure, cortisol) and has been called a behavioral marker of chronic physiological stress," they wrote.

While the study aimed to investigate the "cognitive debt" hypothesis, which proposes that repetitive negative thinking raises Alzheimer's risk, the opposite may be true: amyloid and tau may aggregate first and disrupt neural circuitry, making it difficult for people to disengage from repetitive thoughts. The timeline in the study doesn't support negative causality, the authors observed. "Still, this was an observational study with relatively few participants meeting criteria for substantial amyloid deposition and no means to assess causality," they wrote.

The study looked at cognitively intact older adults with elevated dementia risk and findings can't be generalized to others in the community, they added.

Marchant and other European researchers currently are working on the Silver Sante Study, a large project to see whether supportive mental health interventions could help reduce dementia risk, targeting repetitive negative thinking in old age.

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