Foster CM, Kennedy KM, Rodrigue KM. Differential Aging Trajectories of Modulation of Activation to Cognitive Challenge in APOE ε4 Groups: Reduced Modulation Predicts Poorer Cognitive Performance. J Neurosci. 2017 Jul 19;37(29):6894-6901. Epub 2017 Jun 26 PubMed.
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Arizona Alzheimer's Consortium
This interesting study found an association between the difficulty of a visuospatial judgment task and deactivation of the precuneus and other regions in the default mode network, a preferential relationship between age and less task-dependent DMN deactivation in APOE4 carriers, and an association between age-related task-dependent DMN deactivation and performance in the APOE4 carrier group.
The findings support and extend prior findings from other task-dependent functional MRI studies, and they raise a number of equally interesting questions. For instance, to what extent are the associations with task difficulty generalizable to those tasks unrelated to visuospatial perception, memory, or judgment? To what extent are the findings temporally associated with preclinical evidence of Aβ pathology, which typically begins in the same regions? And how does the reduced precuneus deactivation compare to task performance, PET or CSF measures of amyloid burden, or other AD biomarkers in predicting a person’s subsequent cognitive course?
View all comments by Eric M. ReimanI found this study fascinating, logical, and consistent with what we know about early cortical regions involved in preclinical Alzheimer’s disease, i.e., the precuneus region. This physiological “decline” (quotes reflect the cross-sectional nature of the study so decline is inferred from the age interaction) may well represent early cortical physiological disruption due to early AD-related pathology, and while this is fascinating, it also reflects the major weakness of this study, namely, the lack of biomarker data. Is this an APOE ε4-age effect or is this actually an APOE ε4 induced preclinical AD effect? Is this a cause of the early pathology or an effect of it? The authors address this nicely in their discussion. Also, while this study again shows how sensitive image-related measures of cortical physiology can be to early AD changes, we lack longitudinal neuropsychological data, so whether this precedes longitudinally assessed cognitive decline or not is unknown. Bottom line, this is a nice study showing very early precuneus physiological alteration in APOE4 carriers that precedes clinically evident cognitive impairment.
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