%0 Journal Article %J J Alzheimers Dis %D 2021 %T Longitudinal Trajectories in Cortical Thickness and Volume Atrophy: Superior Cognitive Performance Does Not Protect Against Brain Atrophy in Older Adults. %A Gardener, Samantha L %A Weinborn, Michael %A Sohrabi, Hamid R %A Doecke, James D %A Bourgeat, Pierrick %A Rainey-Smith, Stephanie R %A Shen, Kai-Kai %A Fripp, Jurgen %A Taddei, Kevin %A Maruff, Paul %A Salvado, Olivier %A Savage, Greg %A Ames, David %A Masters, Colin L %A Rowe, Christopher C %A Martins, Ralph N %X

BACKGROUND: Previous research has identified a small subgroup of older adults that maintain a high level of cognitive functioning well into advanced age. Investigation of those with superior cognitive performance (SCP) for their age is important, as age-related decline has previously been thought to be inevitable.

OBJECTIVE: Preservation of cortical thickness and volume was evaluated in 76 older adults with SCP and 100 typical older adults (TOAs) assessed up to five times over six years.

METHODS: Regions of interest (ROIs) found to have been associated with super-aging status (a construct similar to SCP status) in previous literature were investigated, followed by a discovery phase analyses of additional regions. SCPs were aged 70 + at baseline, scoring at/above normative memory (CVLT-II) levels for demographically similar individuals aged 30-44 years old, and in the unimpaired range for all other cognitive domains over the course of the study.

RESULTS: In linear mixed models, following adjustment for multiple comparisons, there were no significant differences between rates of thinning or volume atrophy between SCPs and TOAs in previously identified ROIs, or the discovery phase analyses. With only amyloid-β negative individuals in the analyses, again there were no significant differences between SCPs and TOAs.

CONCLUSION: The increased methodological rigor in classifying groups, together with the influence of cognitive reserve, are discussed as potential factors accounting for our findings as compared to the extant literature on those with superior cognitive performance for their age.

%B J Alzheimers Dis %V 81 %P 1039-1052 %8 2021 Jun 01 %G eng %N 3 %R 10.3233/JAD-201243 %0 Journal Article %J J Alzheimers Dis %D 2018 %T Utility of an Alzheimer's Disease Risk-Weighted Polygenic Risk Score for Predicting Rates of Cognitive Decline in Preclinical Alzheimer's Disease: A Prospective Longitudinal Study. %A Porter, Tenielle %A Burnham, Samantha C %A Milicic, Lidija %A Savage, Greg %A Maruff, Paul %A Lim, Yen Ying %A Li, Qiao-Xin %A Ames, David %A Masters, Colin L %A Rainey-Smith, Stephanie %A Rowe, Christopher C %A Salvado, Olivier %A Groth, David %A Verdile, Giuseppe %A Villemagne, Victor L %A Laws, Simon M %X

BACKGROUND: With the exception of APOE, genetic variants associated with increased Alzheimer's disease (AD) risk are characterized by small effect sizes. Polygenic risk scores (PRS) have shown utility in predicting AD risk; however, their utility for predicting decline in cognition at preclinical stages of AD is poorly understood.

OBJECTIVE: To validate associations of a 22-variant AD-risk-weighted PRS with AD risk and related biomarkers and to assess its utility to predict cognitive decline.

METHODS: The PRS was evaluated with respect to brain amyloid-β (Aβ) burden, cerebrospinal fluid (CSF) Aβ42, total-tau, and phospho-tau, and decline in cognition in 643 (570 cognitively normal (CN), 73 AD) PET-imaged participants from the longitudinal Australian Imaging, Biomarkers and Lifestyle (AIBL) Study of Ageing. Cognition was assessed using three composite measures; global cognition, verbal episodic memory, and a Pre-Alzheimer's Cognitive Composite (PACC).

RESULTS: PRS, both with and without APOE, were positively correlated with brain Aβ burden, CSF total-tau, and phospho-tau in CN older adults. Further, in CN biomarker positive (Aβhigh) participants, significant associations were observed with baseline and longitudinal cognition. However, this association was not observed after the removal of APOE. Partitioning the PRS into quartiles revealed that the PRS associations with cognitive decline in Aβhigh CN older adults is due to a saturating effect of APOE genotype.

CONCLUSIONS: An AD-risk-weighted PRS is associated with cognitive decline in CN older adults. However, this association is absent when APOE genotype is excluded from the PRS, suggesting that associations with cognitive decline in this model of polygenic risk are driven by APOE genotype alone. Further research is needed to define appropriate PRSs with greater utility for predicting preclinical AD cognitive decline.

%B J Alzheimers Dis %V 66 %P 1193-1211 %8 2018 %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/30412495?dopt=Abstract %R 10.3233/JAD-180713 %0 Journal Article %J J Alzheimers Dis %D 2016 %T Comparison of Prefrontal Atrophy and Episodic Memory Performance in Dysexecutive Alzheimer's Disease and Behavioral-Variant Frontotemporal Dementia. %A Wong, Stephanie %A Bertoux, Maxime %A Savage, Greg %A Hodges, John R %A Piguet, Olivier %A Hornberger, Michael %K Aged %K Alzheimer Disease %K Atrophy %K Databases, Factual %K Diagnosis, Differential %K Executive Function %K Female %K Frontotemporal Dementia %K Hippocampus %K Humans %K Image Processing, Computer-Assisted %K Magnetic Resonance Imaging %K Male %K Memory, Episodic %K Middle Aged %K Neuropsychological Tests %K Prefrontal Cortex %X

Alzheimer's disease (AD) sometimes presents with prominent executive dysfunction and associated prefrontal cortex atrophy. The impact of such executive deficits on episodic memory performance as well as their neural correlates in AD, however, remains unclear. The aim of the current study was to investigate episodic memory and brain atrophy in AD patients with relatively spared executive functioning (SEF-AD; n = 12) and AD patients with relatively impaired executive functioning (IEF-AD; n = 23). We also compared the AD subgroups with a group of behavioral-variant frontotemporal dementia patients (bvFTD; n = 22), who typically exhibit significant executive deficits, and age-matched healthy controls (n = 38). On cognitive testing, the three patient groups showed comparable memory profiles on standard episodic memory tests, with significant impairment relative to controls. Voxel-based morphometry analyses revealed extensive prefrontal and medial temporal lobe atrophy in IEF-AD and bvFTD, whereas this was limited to the middle frontal gyrus and hippocampus in SEF-AD. Moreover, the additional prefrontal atrophy in IEF-AD and bvFTD correlated with memory performance, whereas this was not the case for SEF-AD. These findings indicate that IEF-AD patients show prefrontal atrophy in regions similar to bvFTD, and suggest that this contributes to episodic memory performance. This has implications for the differential diagnosis of bvFTD and subtypes of AD.

%B J Alzheimers Dis %V 51 %P 889-903 %8 2016 %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/26923025?dopt=Abstract %R 10.3233/JAD-151016