Specific Association of Worry and Amyloid‐β Deposition in Cognitive Unimpaired Older Adults

Abstract

AbstractBackgroundAnxiety symptoms are common in cognitively unimpaired (CU) older adults prior to the onset of cognitive impairment. Evidence suggests that anxiety symptoms may be sequelae of amyloid‐beta (Aβ) deposition in early Alzheimer’s disease (AD) and/or anxiety may potentiate the pathophysiologic process. Despite this pivotal role, the specific components of anxiety associated with high brain Aβ in CU older adults are relatively unknown. It was previously reported that Aβ deposition is associated with a global anxiety score measured by State‐Trait Anxiety Inventory‐6 (STAI‐6) but not depression measured by Geriatric Depression Scale (GDS) total scores. Here, we examined the specific associations of individual anxiety symptoms with Aβ.MethodOlder adult participants were screened for the Anti‐Amyloid Treatment in Asymptomatic Alzheimer’s study (“A4 study”) and underwent assessments of anxiety (STAI‐6), depression (GDS), cognitive performance (MMSE and Preclinical Alzheimer Cognitive Composite /PACC), subjective cognition (Cognitive Function Instrument/CFI) and cortical Aβ deposition using Florbetapir PET standardized uptake value ratio (SUVR). Linear regression models estimated associations of STAI‐6 items, “calm,” “tense,” “upset,” “relax,” “content,” and “worry,” with Aβ deposition, adjusting for multiple potential confounders.ResultThe sample (n = 4486) were older adults ages 65 ‐ 85 (mean [SD] age, 71.29 [4.67] years, included 2647 women (59%) and 1323 (29.5%) who were classified as Aβ+. STAI‐6 total score ranged from 6 ‐ 24 (Mean 9.9 [3.1]). A significant positive association was found between the anxiety item measuring “worry”, and Aβ, adjusting for age, sex, education, marital status, depression (GDS), objective cognition (MMSE or PACC), and subjective cognition (CFI) [Table 1]. There were other significant (negative) associations between items measuring “calm” and “relax” and Aβ in similar regression models. Only the association of “worry” with Aβ remained significant after further adjustment for global anxiety measured by the total STAI‐6 score.ConclusionIn a large, well‐characterized sample of CU older adults, worry was significantly and most strongly associated with Aβ, independent of psychosocial factors, subjective and objective cognition and global anxiety. These findings suggest that self‐reported worry may have unique explanatory value in the clinical assessment of CU older adults at high risk of AD and cognitive impairment.