A preliminary investigation of worry, cortical amyloid burden, and stressor-evoked brain and cardiovascular reactivity in older adults

J Affect Disord. 2024 Dec 15:367:623-631. doi: 10.1016/j.jad.2024.08.042. Epub 2024 Aug 14.

Abstract

Worry is a transdiagnostic symptom common to many neurocognitive disorders of aging, including early stages of Alzheimer's disease and related dementias (ADRD). Severe worry is associated with amyloid burden in cognitively intact older adults, yet the mechanisms underlying this association are not well understood. We hypothesize that this relationship involves altered brain and cardiovascular reactivity to acute stressors, a brain-body phenotype that also increases risk for cardiovascular disease. Twenty cognitively normal older adults (age 60 to 80) with varying levels of worry severity underwent positron emission tomography using Pittsburgh Compound-B and functional magnetic resonance imaging. We examined associations of worry severity and amyloid burden with cardiovascular reactivity, brain activation, and brain connectivity using a cognitive stressor task. Worry severity was not associated with global amyloid burden, but was associated with greater resting levels of cardiovascular physiology and lower systolic blood pressure reactivity. Worry severity also was associated with altered stressor-evoked activation and effective connectivity in brain circuits implicated in stress processing, emotion perception, and physiological regulation. These associations showed small to medium effect sizes. These preliminary findings introduce key components of a model that may link severe worry to ADRD risk via stressor-evoked brain-body interactions.

Keywords: Amyloid; Cardiovascular reactivity; Psychological stress; Worry; fMRI.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Amyloid / metabolism
  • Aniline Compounds
  • Anxiety* / metabolism
  • Anxiety* / physiopathology
  • Blood Pressure / physiology
  • Brain* / diagnostic imaging
  • Brain* / physiopathology
  • Female
  • Humans
  • Magnetic Resonance Imaging*
  • Male
  • Middle Aged
  • Positron-Emission Tomography*
  • Stress, Psychological* / metabolism
  • Stress, Psychological* / physiopathology
  • Thiazoles

Substances

  • 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
  • Aniline Compounds
  • Thiazoles
  • Amyloid