Comments about SuperAging and SuperAgers

Since the study byKatzman et al. [1], the finding that cognitively intact individuals may have significant amounts of Alzheimer’s disease (AD) pathology has been a fertile source of studies. One way to understand this anomalous finding has been to consider cognitive reserve [2] Basically, both earlyand later-life experiences, including education and other enrichment oriented activities, provide a buffer, not against neuropathology but against its impact on cognition. The twist in this study by Dang et al. [3] was that once pathology was evident in the form of Ab deposition, cognition was not preserved over time. This study and an equally important and complementary study published by this group in 2018 tell a consistent story [4]. To recapitulate, that paper, utilizing a group of SuperAgers defined psychometrically and a group of otherwise cognitively intact individuals from Australian Imaging, Biomarkers and Lifestyle study (identical to the 2019 groups), studied memory performance over a 9-year period. Briefly, the SuperAgers had higher baseline performance. When the groups were divided into Ab1 and Ab2, slope of performance over time in the SuperAger and control groups were similar. The Ab1 group in both the control and SuperAger groups declined, whereas the Ab2 groups demonstrated increases in performance almost certainly due to practice effects. The memory construct was reasonable on the face of it (but see below). In the second study (2019), reviewed here, a similar pattern held, but this time with respect to magnetic resonance imaging volumetric measures, including total gray matter and hippocampus, with one small difference. The Ab2 groups showed small volume decreases over time consistent with aging effects. In short, being a SuperAger was not neuroprotective. Given similarities in slopes of decline, it was reasonably proposed their baseline elevation simply delayed the point at which a clinical of mild cognitive impairment or AD was reached. This was born out in differences in incident mild cognitive impairment and AD between the SuperAger and control groups, the former being lower (with an OR 5 .19 for mild cognitive impairment). Now for some comments. These can be grouped as to relating to what is happening to the right of baseline and to the left. Superficially, Ab aggregation appears to be the culprit here. It was likely driven by apolipoprotein E (APOE) ε4 ge-