Amyloid and tau burden relate to longitudinal changes in the performance of complex everyday activities among cognitively unimpaired older adults: results from the performance-based Harvard Automated Phone Task.

Background: Changes in everyday functioning constitute a clinically meaningful outcome, even in the early stages of Alzheimer's disease. Performance-based assessments of everyday functioning might help uncover these early changes. We aimed to investigate how changes over time in everyday functioning relate to tau and amyloid in cognitively unimpaired older adults. Methods: Seventy-six cognitively unimpaired participants (72 ± 6 years old, 61% female) completed multiple Harvard Automated Phone Task (APT) assessments over 2.0 ± 0.9 years. The Harvard APT consists of three tasks, performed through an automated phone system, in which participants refill a prescription (APT-Script), select a new primary care physician (APT-PCP), and transfer money to pay a bill (APT-Bank). Participants underwent Pittsburgh compound-B and flortaucipir positron emission tomography scans at baseline. We computed distribution volume ratios for a cortical amyloid aggregate and standardized uptake volume ratios for medial temporal and neocortical tau regions. In separate linear mixed models, baseline amyloid by time and tau by time interactions were used to predict longitudinal changes in performance on the Harvard APT tasks. Three-way amyloid by tau by time interactions were also investigated. Lastly, we examined associations between tau and change in Harvard APT scores in exploratory voxel-wise whole-brain analyses. All models were adjusted for age, sex, and education. Results: Amyloid [unstandardized partial regression coefficient estimate (ß) = -0.007, 95% confidence interval (95% CI) = (-0.013, -0.001)], and medial temporal tau [ß = -0.013, 95% CI = (-0.022, -0.004)] were associated with change over time in years on APT-PCP only, i.e., higher baseline amyloid and higher baseline tau were associated with steeper rate of decline of APT-PCP. Voxel-wise analyses showed widespread associations between tau and change in APT-PCP scores over time. Conclusion: Even among cognitively unimpaired older adults, changes over time in the performance of cognitively complex everyday activities relate to cortical amyloid and widespread cerebral tau burden at baseline. These findings support the link between Alzheimer's disease pathology and function and highlight the importance of measuring everyday functioning in preclinical disease stages.

Longitudinal associations of apathy and regional tau in mild cognitive impairment and dementia: Findings from the Alzheimer's Disease Neuroimaging Initiative.

Introduction: It is important to study apathy in Alzheimer's disease (AD) to better understand its underlying neurobiology and develop effective interventions. In the current study, we sought to examine the relationships between longitudinal apathy and regional tau burden in cognitively impaired older adults from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Methods: Three hundred and nineteen ADNI participants with mild cognitive impairment (MCI) or AD dementia underwent flortaucipir (FTP) tau positron emission tomography (PET) imaging and clinical assessment with the Neuropsychiatric Inventory (NPI) annually. Longitudinal NPI Apathy (NPI-A) scores were examined in relation to baseline tau PET signal in three a priori selected regions implicated in AD and AD-related apathy (supramarginal gyrus, entorhinal cortex [EC] and rostral anterior cingulate cortex [rACC]). Secondary models were adjusted for global cognition (Mini-Mental State Examination score) and cortical amyloid (florbetapir PET). Results: Higher baseline supramarginal gyrus and EC tau burden were each significantly associated with greater NPI-A over time, while rACC tau was associated with higher NPI-A but did not predict its trajectory over time. These results were retained for supramarginal and EC tau after adjusting models for global cognition and cortical amyloid. Discussion: Our findings suggest that baseline in vivo tau burden in parietal and temporal brain regions affected in AD, and less so in a medial frontal region involved in motivational control, is associated with increasing apathy over time in older adults with MCI and AD dementia. Future work studying emergent apathy in relation to not only core AD pathology but also circuit level dysfunction may provide additional insight into the neurobiology of apathy in AD and opportunities for intervention. Highlights: Tau (Flortaucipir PET) in regions implicated in AD was associated with increasing apathy over timeCortical amyloid was also found to be a robust predictor of the trajectory of apathyEvidence of synergy between regional tau and amyloid in overall higher levels of apathy.

Associations of the Harvard Automated Phone Task and Alzheimer's Disease Pathology in Cognitively Normal Older Adults: Preliminary Findings.

BACKGROUND: Detecting clinically meaningful changes in instrumental activities of daily living (IADL) at the earliest stages of Alzheimer's disease (AD) is critical. OBJECTIVE: The objective of this exploratory study was to examine the cross-sectional relationship between a performance-based IADL test, the Harvard Automated Phone Task (APT), and cerebral tau and amyloid burden in cognitively normal (CN) older adults. METHODS: Seventy-seven CN participants underwent flortaucipir tau and Pittsburgh Compound B amyloid PET. IADL were assessed using the three Harvard APT tasks: prescription refill (APT-Script), health insurance company call (APT-PCP), and bank transaction (APT-Bank). Linear regression models were used to determine associations between each APT task and entorhinal cortex, inferior temporal, or precuneus tau with or without an interaction with amyloid. RESULTS: Significant associations were found between APT-Bank task rate and interaction between amyloid and entorhinal cortex tau, and APT-PCP task and interactions between amyloid and inferior temporal and precuneus tau. No significant associations were found between the APT tasks and tau or amyloid alone. CONCLUSION: Our preliminary findings suggest an association between a simulated real-life IADL test and interactions of amyloid and several regions of early tau accumulation in CN older adults. However, some analyses were underpowered due to the small number of participants with elevated amyloid, and findings should be interpreted with caution. Future studies will further explore these associations cross-sectionally and longitudinally in order to determine whether the Harvard APT can serve as a reliable IADL outcome measure for preclinical AD prevention trials and ultimately in the clinic setting.

Exploring the relationship between retrieval practice, self-efficacy, and memory.

Retrieval practice effect refers to improved memory on a final test for information retrieved one or more times. Although past theoretical work identifies cognitive mechanisms to explain retrieval practice benefits, it is possible that improving self-efficacy during learning may also contribute to better memory, in line with limited past work showing a relationship between self-efficacy and memory. Across two experiments, we examine the potential relationship between retrieval practice, self-efficacy, and memory. In Experiment 1, we examined the extent change in self-efficacy accounted for improved memory on a final test after retrieval practice compared with restudy. In Experiment 2, we gave participants (false) feedback that was either negative (i.e., you performed worse than others), neutral (i.e., you performed the same as others), or positive (i.e., you performed better than others) to more directly assess the effects of self-efficacy on memory under retrieval practice conditions. Results of Experiment 1 showed a significant retrieval practice effect, with memory on the final test being better after retrieval practice compared with restudy. Self-efficacy did not significantly mediate the retrieval practice effect. Results of Experiment 2, however, showed that decreases in self-efficacy due to (false) negative feedback resulted in worse memory performance compared with neutral feedback. Such findings may suggest that change in self-efficacy after retrieval practice attempts, particularly negative feedback, affects memory at final test. Overall, these findings suggest a relationship between retrieval practice, self-efficacy, and memory, and imply that interventions that influence self-efficacy may be a plausible mechanism to modulate memory under some conditions.

Predicting and remembering the behaviors of social targets: how prediction accuracy affects episodic memory.

BACKGROUND: Decades of research has investigated the relationship between memory and future thinking. Although some of this work has shown that memory forms the basis of making predictions about the future, less work has investigated how the outcome of those predictions (whether consistent or inconsistent with what one predicts) is later remembered. Limited past works suggests that memory for outcomes that are consistent with what one predicts are better remembered that predictions that are inconsistent. To advance understanding of the relationship between episodic memory and future thinking, the current investigation examines how the outcome of predictions affects memory after the predicted events takes place. METHODS: In this experiment, participants first learned trait information about social targets. Then, participants imagined scenarios involving targets and the self (i.e., the participant) and made predictions about which behaviors targets would perform based on the trait information associated with targets participants learned earlier. Participants were then told the behaviors the targets actually performed (i.e., prediction outcome), which was either consistent or inconsistent with predictions, before then taking a memory test for prediction outcomes (what the social target actually did). RESULTS: Results showed memory for prediction-consistent outcomes was better than for prediction-inconsistent outcomes, suggesting people exhibit enhanced memory for events that are in line with predictions based on existing contents of memory (e.g., what one knows; schemas), which is in line with the limited past work in this domain. CONCLUSION: Overall, finding better memory for prediction-consistent outcomes may reflect an adaptive function in memory, where people show enhanced memory for episodes when they play out as predicted, and aligned with the current contents of memory.

Racial and socioeconomic status differences in stress, posttraumatic growth, and mental health in an older adult cohort during the COVID-19 pandemic.

Background: The COVID-19 pandemic has disproportionately impacted the most vulnerable and widened the health disparity gap in both physical and mental well-being. Consequentially, it is vital to understand how to best support elderly individuals, particularly Black Americans and people of low socioeconomic status, in navigating stressful situations during the COVID-19 pandemic and beyond. The aim of this study was to investigate perceived levels of stress, posttraumatic growth, coping strategies, socioeconomic status, and mental health between Black and non-Hispanic, White older adults, the majority over the age of 70. Additionally, we investigated which variables, if any, were associated with posttraumatic growth in these populations. Methods: One hundred seventy-six community dwelling older adults (mean age = 76.30 ±8.94), part of two observational studies (The Harvard Aging Brain Study and Instrumental Activities of Daily Living Study) in Massachusetts, US, were included in this cross-sectional study. The survey, conducted from March 23, 2021 to May 13, 2021, measured perceived stress, behavioral coping strategies, posttraumatic growth, and mental health during the COVID-19 pandemic. We investigated associations with post-traumatic growth in a multiple linear regression model and examined their differences by race with t-tests, Wilcoxon rank-sum tests, and Fisher's exact tests. A second multiple linear regression model was used to examine which coping strategies were associated with posttraumatic growth. Findings: Our results indicated no significant difference between the groups in terms of mental health or stress. However, Black participants showed significantly greater posttraumatic growth compared to non-Hispanic, White participants. Additionally, the coping strategies of religion and positive reframing were found to be significantly associated with posttraumatic growth. Furthermore, even with the effects of stress and coping strategies controlled for, race remained significantly associated with posttraumatic growth. Interpretation: The COVID-19 pandemic has differentially impacted Black and non-Hispanic White older adults. These results may help encourage further analysis on geriatric psychiatry as well as understanding how cultural values and adaptations impact posttraumatic growth and mental health in diverse populations. Funding: The Harvard Aging Brain Study (HABS) has been funded by NIH-NIA P01 AG036694 (PI: Reisa Sperling). The IADL study is funded by the National Institute on Aging (R01 AG053184, PI: Gad A. Marshall).