The BDNF Val66Met polymorphism moderates the relationship between cognitive reserve and executive function

The concept of cognitive reserve (CR) has been proposed to account for observed discrepancies between pathology and its clinical manifestation due to underlying differences in brain structure and function. In 433 healthy older adults participating in the Tasmanian Healthy Brain Project, we investigated whether common polymorphic variations in apolipoprotein E (APOE) or brain-derived neurotrophic factor (BDNF) influenced the association between CR contributors and cognitive function in older adults. We show that BDNF Val66Met moderates the association between CR and executive function. CR accounted for 8.5% of the variance in executive function in BDNF Val homozygotes, but CR was a nonsignificant predictor in BDNF Met carriers. APOE polymorphisms were not linked to the influence of CR on cognitive function. This result implicates BDNF in having an important role in capacity for building or accessing CR

The PedsQL™ as a patient-reported outcome in children and adolescents with Attention-Deficit/Hyperactivity Disorder: a population-based study

BACKGROUND: Attention-Deficit/Hyperactivity Disorder (ADHD) is the most common chronic mental health condition in children and adolescents. The application of health-related quality of life (HRQOL) as a pediatric population health measure may facilitate risk assessment and resource allocation, the identification of health disparities, and the determination of health outcomes from interventions and policy decisions for children and adolescents with ADHD at the local community, state, and national health level. METHODS: An analysis from an existing statewide database to determine the feasibility, reliability, and validity of the 23-item PedsQL™ 4.0 (Pediatric Quality of Life Inventory™) Generic Core Scales as a patient-reported outcome (PRO) measure of pediatric population health for children and adolescents with ADHD. The PedsQL™ 4.0 Generic Core Scales (Physical, Emotional, Social, School Functioning) were completed by families through a statewide mail survey to evaluate the HRQOL of new enrollees in the State of California State's Children's Health Insurance Program (SCHIP). Seventy-two children ages 5–16 self-reported their HRQOL. RESULTS: The PedsQL™ 4.0 evidenced minimal missing responses, achieved excellent reliability for the Total Scale Score (α = 0.92 child self-report, 0.92 parent proxy-report), and distinguished between healthy children and children with ADHD. Children with ADHD self-reported severely impaired psychosocial functioning, comparable to children with newly-diagnosed cancer and children with cerebral palsy. CONCLUSION: The results suggest that population health monitoring may identify children with ADHD at risk for adverse HRQOL. The implications of measuring pediatric HRQOL for evaluating the population health outcomes of children with ADHD internationally are discussed

Amyloid-associated increases in longitudinal report of subjective cognitive complaints.

Introduction: To investigate whether baseline subjective cognitive complaints (SCCs) predict longitudinal decline on neuropsychological testing and whether SCC increases longitudinally, in the setting of high levels of amyloid burden. Methods: Two hundred seventy-nine clinically normal older participants (mean age = 73.7 ± 6.1 years) from the Harvard Aging Brain Study, a cohort of community-dwelling individuals, were followed longitudinally (4.27 ± 1.35 years) with annual subjective memory questionnaires and neuropsychological assessment. 11C Pittsburgh compound-B positron emission tomography was used to measure cortical amyloid and to classify status (Aβ+/Aβ-) at baseline. Results: Higher baseline SCC predicted more rapid cognitive decline on neuropsychological measures among those with elevated amyloid (t = -2.18, P < .0001). In addition, longitudinal report of SCC significantly increased over time, with SCC progression most pronounced among Aβ+ individuals (t = 2.24, P = .0005). Discussion: SCC may inform risk for future cognitive decline and track progression of self-perceived decline, particularly in those along the AD trajectory, providing potentially important indicators of clinical meaningfulness in AD prevention trials

The relationship between recall of recently versus remotely encoded famous faces and amyloidosis in clinically normal older adults.

Introduction: Alzheimer's disease (AD) patients exhibit temporally graded memory loss with remote memories remaining more intact than recent memories. It is unclear whether this temporal pattern is observable in clinically normal adults with amyloid pathology (i.e. preclinical AD). Methods: Participants were asked to recall the names of famous figures most prominent recently (famous after 1990) and remotely (famous from 1960-1980) and were provided with a phonemic cue to ensure that memory failure was not purely due to verbal retrieval weaknesses. In addition, participants identified line drawings of objects. Clinically normal older adults (n = 125) were identified as amyloid β positive or negative (Aβ+/-) using Pittsburgh compound B positron emission tomography. The relationship between Aβ+/- and recall of remote and recent famous face-names and objects was examined using repeated measures analyses and general linear models controlling for demographics and media usage. Results: When provided with a phonemic cue, Aβ+ participants recalled the names of fewer recent famous faces compared with Aβ- participants. However, recall of remote famous face-names and objects did not differ by Aβ group. Discussion: Relative sparing of remotely learned information compared with recently learned information is (1) detectable in the preclinical stages of AD and (2) related to amyloid pathology. Both this temporal gradient and assessment of person-centered rather than object-centered semantic information may be particularly meaningful for tracking early memory changes in the AD trajectory

Using subjective cognitive decline to identify high global amyloid in community-based samples: A cross-cohort study

Introduction: We aimed to examine the contribution of subjective cognitive decline (SCD) to reduce the number of β-amyloid (Aβ) positron emission tomography scans required for recruiting Aβ+ clinically normal individuals in clinical trials. Methods: Three independent cohorts (890 clinically normal: 72 yrs ± 6.7; Female: 43.4%; SCD+: 24%; apolipoprotein E [APOE] ε4+: 28.5%; Aβ+: 32%) were used. SCD was dichotomized from one question. Using logistic regression, we classified Aβ+ using the SCD dichotomy, APOEε4, sex, and age. Results: SCD increased odds of Aβ+ by 1.58 relative to non-SCD. Female APOEε4 carriers with SCD exhibited higher odds of Aβ+ (OR = 3.34), whereas male carriers with SCD showed a weaker, opposing effect (OR = 0.37). SCD endorsement reduces the number of Aβ positron emission tomography scans to recruit Aβ+ individuals by 13% and by 9% if APOEε4 status is known. Conclusion: SCD helps to classify those with high Aβ, even beyond the substantial effect of APOE genotype. Collecting SCD is a feasible method for targeting recruitment for those likely on the AD trajectory

Alzheimer's Disease Clinical Trial Research Adaptation Following COVID-19 Pandemic Onset: National Sample of Alzheimer's Clinical Trial Consortium Sites.

BackgroundThe COVID-19 pandemic created challenges in clinical research operations that required immediate and lasting changes.OjbectivesThe purpose of this study was to explore adaptations to clinical trial research due to COVID-19 and develop a theoretical framework of emergent strategies related to pandemic mitigation in a national network of Alzheimer's disease clinical trial sites.DesignThis qualitative study used a grounded theory approach including semi-structured interviews, constant comparative methods, and multi-level, iterative coding.ParticipantsTwenty-six member sites of the Alzheimer's Clinical Trial Consortium participated with a total of 49 participants.ResultsFindings demonstrate processes of adaptation following COVID-19 onset including establishing safety as priority, focus on scientific preservation, accommodations (creating policies, leadership mindset, maintaining operations, and determining research procedures), and evaluation of changes throughout the course of the pandemic. Communication and maintaining integrity were vital throughout these processes.ConclusionProcesses of accommodation among clinical research sites during the pandemic provide critical insights and direction for future clinical trials development and emergent methods in Alzheimer's disease and other therapeutic areas