Hsiung, Gink-Yuek

AbstractIntroductionLeisure activities impact brain aging and may be prevention targets. We characterized how physical and cognitive activities relate to brain health for the first time in autosomal dominant frontotemporal lobar degeneration (FTLD).MethodsA total of 105 mutation carriers (C9orf72/MAPT/GRN) and 69 non‐carriers reported current physical and cognitive activities at baseline, and completed longitudinal neurobehavioral assessments and brain magnetic resonance imaging (MRI) scans.ResultsGreater physical and cognitive activities were each associated with an estimated >55% slower clinical decline per year among dominant gene carriers. There was also an interaction between leisure activities and frontotemporal atrophy on cognition in mutation carriers. High‐activity carriers with frontotemporal atrophy (−1 standard deviation/year) demonstrated >two‐fold better cognitive performances per year compared to their less active peers with comparable atrophy rates.DiscussionActive lifestyles were associated with less functional decline and moderated brain‐to‐behavior relationships longitudinally. More active carriers “outperformed” brain volume, commensurate with a cognitive reserve hypothesis. Lifestyle may confer clinical resilience, even in autosomal dominant FTLD.

AbstractIntroductionConventional Z‐scores are generated by subtracting the mean and dividing by the standard deviation. More recent methods linearly correct for age, sex, and education, so that these “adjusted” Z‐scores better represent whether an individual's cognitive performance is abnormal. Extreme negative Z‐scores for individuals relative to this normative distribution are considered indicative of cognitive deficiency.MethodsIn this article, we consider nonlinear shape constrained additive models accounting for age, sex, and education (correcting for nonlinearity). Additional shape constrained additive models account for varying standard deviation of the cognitive scores with age (correcting for heterogeneity of variance).ResultsCorrected Z‐scores based on nonlinear shape constrained additive models provide improved adjustment for age, sex, and education, as indicated by higher adjusted‐R2.DiscussionNonlinearly corrected Z‐scores with respect to age, sex, and education with age‐varying residual standard deviation allow for improved detection of non‐normative extreme cognitive scores.

AbstractIntroductionThe Advancing Research and Treatment in Frontotemporal Lobar Degeneration and Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects longitudinal studies were designed to describe the natural history of familial‐frontotemporal lobar degeneration due to autosomal dominant mutations.MethodsWe examined cognitive performance, behavioral ratings, and brain volumes from the first time point in 320 MAPT, GRN, and C9orf72 family members, including 102 non–mutation carriers, 103 asymptomatic carriers, 43 mildly/questionably symptomatic carriers, and 72 carriers with dementia.ResultsAsymptomatic carriers showed similar scores on all clinical measures compared with noncarriers but reduced frontal and temporal volumes. Those with mild/questionable impairment showed decreased verbal recall, fluency, and Trail Making Test performance and impaired mood and self‐monitoring. Dementia was associated with impairment in all measures. All MAPT carriers with dementia showed temporal atrophy, but otherwise, there was no single cognitive test or brain region that was abnormal in all subjects.DiscussionImaging changes appear to precede clinical changes in familial‐frontotemporal lobar degeneration, but specific early clinical and imaging changes vary across individuals.

Abstract Introduction Quantitative in vivo measurement of brain amyloid burden is important for both research and clinical purposes. However, the existence of multiple imaging tracers presents challenges to the interpretation of such measurements. This study presents a direct comparison of Pittsburgh compound B–based and florbetapir‐based amyloid imaging in the same participants from two independent cohorts using a crossover design. Methods Pittsburgh compound B and florbetapir amyloid PET imaging data from three different cohorts were analyzed using previously established pipelines to obtain global amyloid burden measurements. These measurements were converted to the Centiloid scale to allow fair comparison between the two tracers. The mean and inter‐individual variability of the two tracers were compared using multivariate linear models both cross‐sectionally and longitudinally. Results Global amyloid burden measured using the two tracers were strongly correlated in both cohorts. However, higher variability was observed when florbetapir was used as the imaging tracer. The variability may be partially caused by white matter signal as partial volume correction reduces the variability and improves the correlations between the two tracers. Amyloid burden measured using both tracers was found to be in association with clinical and psychometric measurements. Longitudinal comparison of the two tracers was also performed in similar but separate cohorts whose baseline amyloid load was considered elevated (i.e., amyloid positive). No significant difference was detected in the average annualized rate of change measurements made with these two tracers. Discussion Although the amyloid burden measurements were quite similar using these two tracers as expected, difference was observable even after conversion into the Centiloid scale. Further investigation is warranted to identify optimal strategies to harmonize amyloid imaging data acquired using different tracers.