Social activity mediates locus coeruleus tangle-related cognition in older adults.

The locus coeruleus-noradrenaline system regulates brain-wide neural activity involved in cognition and behavior. Integrity of this subcortical neuromodulatory system is proposed to be a substrate of cognitive reserve that may be strengthened by lifetime cognitive and social activity. Conversely, accumulation of tau tangles in the brainstem locus coeruleus nuclei is recently studied as a very early marker of Alzheimer's disease (AD) pathogenesis and cognitive vulnerability, even among older adults without cognitive impairment or significant cerebral AD pathologies. This clinical-pathologic study examined whether locus coeruleus tangle density was cross-sectionally associated with lower antemortem cognitive performance and social activity among 142 cognitively unimpaired and impaired older adults and whether social activity, a putative reserve factor, mediated the association of tangle density and cognition. We found that greater locus coeruleus tangle density was associated with lower social activity for the whole sample and in the cognitively unimpaired group alone and these associations were independent of age, sex, education, depressive symptoms, and burden of cerebral amyloid and tau. The association of locus coeruleus tangle density with lower cognitive performance was partially mediated by level of social activity. These findings implicate the locus coeruleus-noradrenaline system in late-life social function and support that locus coeruleus tangle pathology is associated with lower levels of social activity, independent of cerebral AD pathologies, and specifically among older adults who are cognitively unimpaired. Early brainstem pathology may impact social function, and level of social function, in turn, influences cognition, prior to canonical stages of AD.

Specific Association of Worry With Amyloid-ß But Not Tau in Cognitively Unimpaired Older Adults.

OBJECTIVE: Anxiety disorders and subsyndromal anxiety symptoms are highly prevalent in late life. Recent studies support that anxiety may be a neuropsychiatric symptom during preclinical Alzheimer's disease (AD) and that higher anxiety is associated with more rapid cognitive decline and progression to cognitive impairment. However, the associations of specific anxiety symptoms with AD pathologies and with co-occurring subjective and objective cognitive changes have not yet been established. METHODS: Baseline data from the A4 and Longitudinal Evaluation of Amyloid Risk and Neurodegeneration studies were analyzed. Older adult participants (n = 4,486) underwent assessments of anxiety (State-Trait Anxiety Inventory-6 item version [STAI]), and cerebral amyloid-beta (Aß; 18F-florbetapir) PET and a subset underwent tau (18F-flortaucipir) PET. Linear regressions estimated associations of Aß in a cortical composite and tau in the amygdala, entorhinal, and inferior temporal regions with STAI-Total and individual STAI item scores. Models adjusted for age, sex, education, marital status, depression, Apolipoprotein ε4 genotype, and subjective and objective cognition (Cognitive Function Index-participant; Preclinical Alzheimer Cognitive Composite). RESULTS: Greater Aß deposition was significantly associated with higher STAI-Worry, adjusting for all covariates, but not with other STAI items or STAI-Total scores. In mediation analyses, the association of Aß with STAI-Worry was partially mediated by subjective cognition with a stronger direct effect. No associations were found for regional tau deposition with STAI-Total or STAI-Worry score. CONCLUSION: Greater worry was associated with Aß but not tau deposition, independent of subjective and objective cognition in cognitively unimpaired (CU) older adults. These findings implicate worry as an early, specific behavioral marker and a possible therapeutic target in preclinical AD.

A Remotely Delivered, Personalized Music Therapy Pilot Intervention for Lonely Older Adults During the Covid-19 Pandemic.

Introduction: This study investigated a remotely delivered, therapist-facilitated, personalized music listening intervention for community-dwelling older adults experiencing loneliness during the Covid-19 pandemic. We assessed its feasibility and individuals' experiences of social connection and emotional well-being during the intervention. Methods: Ten cognitively unimpaired older adults who endorsed loneliness completed eight weekly sessions with a board-certified music therapist via Zoom. Participants were guided in developing two online personalized music playlists and were asked to listen to playlists for at least one hour daily. Feasibility metrics were attendance, accessibility, and compliance rates. Post-study interview responses were analyzed using a rapid qualitative methodology. Exploratory pre- and post-study measures of loneliness and other aspects of psychological well-being were obtained using validated questionnaires. Results: Ten participants (mean age 75.38 [65 to 85] years, 80% women) were enrolled from March to August 2021. Attendance and compliance rates were 100% and the accessibility rate was 90%. Most participants associated music with positive memories before the program and many reported that the intervention prompted them to reconnect with music or listen to music with greater intention. They cited increased connection from interacting with the music therapist and the music itself, as well as specific positive emotional impacts from integrating music into their daily lives. Median pre- to post-questionnaire measures of psychological function all changed in an improved direction. Discussion: Remotely delivered music therapy may be a promising intervention to promote regular music listening and socioemotional well-being in lonely older adults.

Evaluating Feasibility, Value and Characteristics of an Intergenerational Friendly Telephone Visit Program During the Covid-19 Pandemic.

OBJECTIVE: Volunteer organizations offer telephone outreach to older adults to relieve feelings of loneliness and to promote emotional well-being, though the feasibility, perceived value, and characteristics of the participant experience of these community interventions have not been well-studied. We examined these elements of an intergenerational college-based telephone call program during the Covid-19 pandemic. METHODS: Community-dwelling older adults and undergraduate volunteers engaged in eight, weekly, 30-minute, unscripted telephone conversations. Feasibility criteria included enrollment, retention, and attendance rates. A rapid qualitative analysis of program evaluation responses was used to extract themes related to participants' experiences of the intervention. RESULTS: Ten older adults (mean age [range] 74.53 [70-84] years, 88% women) and nine undergraduates were enrolled from February to August 2021, achieving recruitment targets and enrollment rates of 76.9% and 90%. Seven out of the 10 enrolled dyads completed the full series of eight telephone conversations and qualitative assessments over an average of 10.5 weeks. Most older adults who completed the call schedule valued the conversations as a source of social connection, noting the mutuality, respect, and broadened perspective that characterized their intergenerational relationships. Undergraduates described value in giving to others and in conversations that stimulated personal reflection and feelings of closeness. Undergraduates frequently described their experience as novel and broadening of their perspectives. CONCLUSION: Though study completion rate and participant experience varied across dyads, we found qualitative evidence of perceived value, active relationship-building and broadened perspectives among many older adults and undergraduates who completed an intergenerational telephone program.

A Scoping Review of Interventions for Spousal Bereavement in Older Adults.

The loss of a spouse is a common and natural life event for older adults. Nearly one of four older bereaved spouses experience prolonged grief, impaired function or chronic depression. Mechanisms underlying these and other long-term health risks are not well understood. We conducted a scoping literature review to examine the interventions and outcomes that have been studied for late-life spousal bereavement to date. We identified 22 studies of group and individual-level interventions with most studies concerning grief processes within the first year. Nearly all studies evaluated emotional and psychological symptoms of loss and a small number evaluated the restoration of adaptive functioning. Four interventions addressed the treatment of complicated grief or grief with major depressive disorder. Qualitative studies explored themes of spirituality and mindfulness. There were 17 controlled studies, including 13 randomized controlled trials. Findings were eclectic, with evidence supporting mindfulness techniques in a group format for emotional and life satisfaction outcomes; an individual, function-based therapy addressing sleep to improve emotion and function; an individual, writing-based emotional expression therapy for short-term improvement in emotion and function; nortriptyline for the treatment of bereavement-related major depressive disorder; a group-based, complicated grief therapy for this condition; an internet-based CBT intervention for prolonged grief; and pharmacotherapy for cardiovascular changes during bereavement. These findings highlight the small literature of methodologically strong intervention studies addressing spousal bereavement in older adults and the need for greater exploration of relevant biological, social, cognitive and behavioral factors to improve short and long term health outcomes.

Social Engagement and Amyloid-ß-Related Cognitive Decline in Cognitively Normal Older Adults.

OBJECTIVE: Public health recommendations promote social engagement to reduce risk of cognitive decline and dementia. The objective of this study was to evaluate the longitudinal associations of social engagement and cognition in cognitively normal older adults with varying levels of neocortical amyloid-ß, the Alzheimer's disease (AD) pathologic marker. METHODS: Two hundred seventeen men and women, age 63-89 underwent assessments for social engagement and cognitive performance at baseline and 3 years later using the Community Healthy Activities Model Program for Seniors questionnaire and the Preclinical Alzheimer Cognitive Composite (PACC). Amyloid-ß was measured using Pittsburgh compound B-PET. Multivariable regression models estimated main and interactive effects of baseline social engagement and amyloid-ß on cognitive change. Reciprocal models estimated main and interactive effects of baseline cognitive performance and amyloid-ß on change in social engagement. RESULTS: Baseline social engagement was associated with PACC change as a modifier but not as a main effect. Lower baseline social engagement was associated with greater amyloid-ß-related PACC decline, while higher baseline social engagement was associated with relative preservation of PACC scores (ß = 0.05, p = 0.03). Reciprocally, lower baseline PACC score was associated with decline in social engagement score (ß = 1.1, p = 0.02). This association was not modified by amyloid-ß, and there was no direct association of amyloid-ß with change in social engagement. CONCLUSIONS: Low social engagement may be a marker of neurocognitive vulnerability in older adults who are cognitively normal but have evidence of AD pathophysiologic change. Understanding changes in social engagement in older adults may lead to earlier diagnosis of AD and advances in evidence-based prevention and treatment.

Associations of Widowhood and ß-Amyloid With Cognitive Decline in Cognitively Unimpaired Older Adults.

Importance: To reduce the rising incidence of clinical impairment due to Alzheimer disease, it is essential to define older adults at highest risk. Widowhood may be an unrecognized factor contributing to accelerated clinical progression along the Alzheimer disease pathway among cognitively unimpaired older adults. Objective: To determine whether widowhood status and level of brain ß-amyloid (ie, the Alzheimer disease pathologic protein) are additively or interactively associated with cognitive decline among cognitively unimpaired older adults. Design, Setting, and Participants: In this cohort study, 257 married, widowed, and unmarried (ie, never married, divorced, or separated) participants from the Harvard Aging Brain Study longitudinal cohort underwent baseline evaluation of neocortical ß-amyloid levels using Pittsburgh compound B positron emission tomography and 4 annual cognitive assessments. Data were collected from September 2010 to February 2017 and analyzed from July 2018 to July 2019. Main Outcomes and Measures: Cognitive performance was measured using the Preclinical Alzheimer Cognitive Composite. Results: Of the 257 participants, 153 (59.5%) were women, and the mean (SD) age was 73.5 (6.1) years; 145 participants (56.4%) were married (66 [45.5%] women), 77 (30.0%) were unmarried (56 [72.7%] women), and 35 (13.6%) were widowed (31 [88.6%] women). Compared with married participants, widowed participants demonstrated worsening cognitive performance after adjusting for age, sex, socioeconomic status, depression, and ß-amyloid levels (ß = -0.11; 95% CI, -0.19 to -0.04; P = .002) with no difference observed between married and unmarried participants. Furthermore, widowed participants with higher baseline ß-amyloid levels exhibited steeper cognitive decline (ß = -0.22; 95% CI, -0.42 to -0.03; P = .02), indicating both independent and interactive associations of ß-amyloid levels and widowhood with cognition. In a secondary model using dichotomous ß-amyloid-marital status groupings, the rate of cognitive decline among widowed participants with high ß-amyloid was nearly 3 times faster than among married participants with high ß-amyloid (widowed, high ß-amyloid: ß, -0.33; 95% CI, -0.46 to -0.19; P < .001; married, high ß-amyloid: ß, -0.12; 95% CI, -0.18 to -0.01; P < .001). Conclusions and Relevance: In a sample of cognitively unimpaired older adults, being widowed was associated with accelerated ß-amyloid-related cognitive decline during 3 years. Cognitively unimpaired, widowed older adults were particularly susceptible to Alzheimer disease clinical progression, emphasizing the need for increased research attention and evidenced-based interventions for this high-risk group.