Negative Thinking Tied to Cognitive Decline, Alzheimer's Pathology

Megan Brooks

June 11, 2020

Repetitive negative thinking (RNT) is a modifiable psychological risk factor for Alzheimer's disease (AD), new research suggests.

Investigators at University College London (UCL), United Kingdom, found that RNT was associated with a decline in cognitive function and amyloid and tau deposition in cognitively healthy older adults.

A number of psychological disorders, including depression and anxiety, have previously been linked to an increased risk for dementia. These risks have generally been considered independently, lead investigator Natalie Marchant, PhD, told Medscape Medical News.

Natalie Marchant, PhD

"The cognitive debt hypothesis proposes that these psychological risk factors may not be independent, and in fact frequently share a style of thinking — repetitive negative thinking — which may help explain the risk observed with these psychological disorders.

"Here, for the first time, we provide initial empirical support for the cognitive debt hypothesis by showing that repetitive negative thinking is associated with markers of increased dementia risk," she added.

The study was published online June 7 in Alzheimer's & Dementia.

Heightened Stress Response

The investigators analyzed data on 292 cognitively normal adults aged 55 or older from the Pre-symptomatic Evaluation of Experimental or Novel Treatments for Alzheimer's Disease (PREVENT-AD), including 113 with amyloid-positron emission tomography (PET) and tau-PET scans. They also analyzed data on 68 adults with amyloid-PET scans from the Multi-Modal Neuroimaging in Alzheimer's Disease (IMAP+) cohort. These 68 were either cognitively healthy or had subjective cognitive decline.

All participants completed the 15-item self-report Perseverative Thinking Questionnaire (PTQ), which measures levels of RNT and has been validated for use in both clinical and nonclinical populations. They also completed standard measures of depression and anxiety.

Over a 4-year period, higher levels of RNT were associated with more rapid decline in global cognition (P = .02), as well as immediate (P = .03) and delayed memory (P = .04).

RNT was also associated with higher levels of tau deposition (P = .02) in the entorhinal cortex (a region of early aggregation), and with global brain amyloid in both cohorts (PREVENT-AD: P = .01; IMAP+: P = .03) even after accounting for known predictors of amyloid deposition including age, APOE e4 status and cognitive function. 

Depression and anxiety were also associated with subsequent cognitive decline but not with amyloid or tau deposition. This suggests symptoms of depression and anxiety may be more indicative of age- or nonspecific dementia-related decline whereas RNT may be a more precise marker for AD, the researchers suggest. 

The researchers note that the PREVENT-AD cohort includes individuals at elevated risk of dementia (ie, those with at least one first-degree relative with AD) and, therefore, the findings from the current study may not be generalizable to a broader population of older adults.

Marchant said there are several potential pathways to explain why RNT might be associated with increased dementia risk.

Sustained RNT has been shown to affect the vascular system, including increased blood pressure and heart rate, and there is ample research on vascular risk factors for dementia, she said.

"RNT is also associated with a heightened stress response, and there is increasing research showing that chronic stress is both bad for your body and your brain," Marchant added.

"Importantly," she noted, excessive rumination and worry can be modified through cognitive behavioral therapy and mindfulness-based interventions.

"Whether a reduction in RNT subsequently reduces risk for dementia is not yet known, but this is something I am investigating in my current research," said Marchant.

Neurotoxic Effects

Commenting on the findings for Medscape Medical News, Rudolph Tanzi, PhD, professor of neurology at Harvard University and vice chair of neurology at Massachusetts General Hospital, Boston, said, the impact of RNT is "something we don't think about enough."

"Positive thinking affects the health of the entire body and the brain. Negative thoughts create negative consequences. There is a lot of science behind it. We need to take this seriously," said Tanzi, who was not associated with the study.

With repetitive worry or rumination, he added, "you are inducing stress in the brain and you are also adversely affecting neuroplasticity. Rumination can lead to neurochemical changes in the brain, including an increase in production of the stress hormone cortisol that is neurotoxic and can lead to inflammation. Inflammation can also cause tangles and plaques in the brain, so you can get the full gamut of Alzheimer's pathology."

The study had no specific funding. The authors have disclosed no relevant financial relationships. Tanzi is coauthor of the book, "The Healing Self: A Revolutionary New Plan to Supercharge Your Immunity and Stay Well for Life."

Alz Dement. Published online June 7, 2020. Full text

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