Early brainstem [18F]THK5351 uptake is linked to cortical hyperexcitability in healthy aging.

BACKGROUNDNeuronal hyperexcitability characterizes the early stages of Alzheimer's disease (AD). In animals, early misfolded tau and amyloid-β (Aβ) protein accumulation - both central to AD neuropathology - promote cortical excitability and neuronal network dysfunction. In healthy humans, misfolded tau and Aβ aggregates are first detected, respectively, in the brainstem and frontomedial and temporobasal cortices, decades prior to the onset of AD cognitive symptoms.

Preserved wake-dependent cortical excitability dynamics predict cognitive fitness beyond age-related brain alterations.

Age-related cognitive decline arises from alterations in brain structure as well as in sleep-wake regulation. Here, we investigated whether preserved wake-dependent regulation of cortical function could represent a positive factor for cognitive fitness in aging. We quantified cortical excitability dynamics during prolonged wakefulness as a sensitive marker of age-related alteration in sleep-wake regulation in 60 healthy older individuals (50-69 y; 42 women).