Spectral signatures associated with cognitive aging, APOE4, amyloid‐β and measures of axonal integrity in cognitively unimpaired adults

Abstract

AbstractBackgroundOscillatory brain rhythms are a defining feature of neuronal activity that support cognition in humans. Previous studies that showed associations of spectral changes in individuals who harbor high risk for Alzheimer’s disease (AD) were limited to identify abnormalities within select brain regions defined apriori. Comprehensive whole‐brain spatiotemporal patterns of oscillatory changes associated with cognitive‐aging and with AD risk are only partly known. Our main goals were to understand how frequency specific spectral changes relate to cognitive abilities in normal aging and to identify oscillatory signatures that indicate pre‐symptomatic AD pathophysiological processes in cognitively unimpaired elderly.MethodsWe used magnetoencephalography (MEG) to study the spectral signatures within delta‐theta (2‐7Hz), alpha (8‐12Hz) and beta (13‐35Hz) oscillations, in cognitively unimpaired adults (n=70). Using a partial‐least‐square regression, we correlated spectral patterns to executive, memory, and processing‐speed abilities (n=40). Next, we compared the spectral signatures between amyloid‐β (Aβ)+ vs. Aβ‐ and between APOE‐Ɛ4+ vs. APOE‐Ɛ4‐, in sub‐cohorts evaluated with Aβ‐PET (n=46) and APOE4 (n=65), respectively. In a subset of participants (n=19), we also examined associations between spectral signatures and cerebrospinal fluid (CSF) markers indicating damage to: presynaptic (growth‐associated protein‐43, GAP43); postsynaptic (neurogranin, NG); axonal (neurofilament light chain, NFL), levels.ResultsAn age dependent, low‐grade, increase in alpha power and decrease in delta‐theta power were associated with better cognitive performance in memory, executive and processing speed (Figure‐1). APOE4+ individuals showed reduced alpha power within bilateral medial temporal and right precuneus, compared to APOE4‐. Aβ+ individuals showed a dual pattern of alpha change with increased frontal and reduced medial and lateral temporal cortex pattern and a frontally distributed increased delta‐theta power (Figure‐2). Higher CSF‐NFL was correlated with lower alpha power.ConclusionsOur findings demonstrate that higher alpha power indicates a positive spectral change towards better cognitive health in aging. Importantly, a reduced alpha power signature indicated early neurodegenerative changes, as demonstrated by: (1)Aβ+ individuals and APOE‐Ɛ4+ individuals showing reduced alpha power within the regions known for earliest tau accumulations; (2) lower alpha correlating with higher NFL, which reflects Aβ‐independent neurodegeneration. Collectively alpha signatures may indicate tau related neuropathology with aging and in early AD.