July 22, 2015
2 min read

High perceived stress increases risk for cognitive impairment among APOE-ε4 non-carriers

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High levels of perceived stress significantly increased risk for incident amnestic mild cognitive impairment among APOE-ε4 non-carriers, according to data from the Einstein Aging Study presented at the Alzheimer’s Association International Conference.

“High levels of perceived stress represent a potentially remediable risk factor for onset of Alzheimer’s disease. APOE-ε4 is known to increase risk of [amnestic mild cognitive impairment]/dementia,” study researcher Mindy J. Katz, MPH, of the Albert Einstein College of Medicine in New York City, and colleagues wrote. “Herein, we test the hypothesis that APOE-ε4 status may modify the effects of perceived stress on the onset of [amnestic mild cognitive impairment], in a potential gene-environment interaction.”

Researchers evaluated 473 individuals (mean age, 79.9 years) who did not have dementia at baseline, had at least two annual evaluations and known APOE-ε4 status. Study participants completed the Perceived Stress Scale (PSS) at baseline. Researchers defined amnestic mild cognitive impairment as having objective memory impairment, subjective complaints and absence of functional decline or dementia.

During an average follow-up of 4.06 years, there were 79 cases of amnestic mild cognitive impairment.

High stress was associated with an increased risk for amnestic mild cognitive impairment onset among APOE-ε4 non-carriers (HR = 2.54; P = .0009). Stress had a lesser affect among APOE-ε4 carriers (HR = 0.32; P = .09).

Cox models indicated PSS scores were a predictor of amnestic mild cognitive impairment among individuals without APOE-ε4 (HR = 2.51; P = .001) but not among those with APOE-ε4.

“We found that baseline perceived stress is significantly associated with risk of incident [amnestic mild cognitive impairment] only among APOE-ε4 non-carriers. Stress and [hypothalamic pituitary adrenal] axis dysregulation in APOE-ε4 carriers may be a ‘consequence’ of synaptic loss in [amnestic mild cognitive impairment/Alzheimer’s disease]. In APOE-ε4 non-carriers, stress may play a more important role in the etiology of [amnestic mild cognitive impairment/Alzheimer’s disease],” Katz and colleagues wrote. “Further understanding of individuals most susceptible to effects of stress during the preclinical phase of [amnestic mild cognitive impairment] may lead to better targeting of prevention and treatment efforts.” – by Amanda Oldt


Katz MJ, et al. Perceived stress, APOE status and risk of amnestic mild cognitive impairment: results from the Einstein aging study. Presented at: Alzheimer’s Association International Conference; July 18-23, 2015; Washington, D.C.

Disclosure: Healio.com/Psychiatry was unable to confirm relevant financial disclosures.