Sleep slow wave changes during the middle years of life

Slow waves (SW; < 4 Hz and > 75 mu V) during non-rapid eye movement (NREM) sleep in humans are characterized by hyperpolarization [surface electroencephalogram (EEG) SW negative phase], during which cortical neurons are silent, and depolarization (surface EEG positive phase), during which the cortical neurons fire intensively. We assessed the effects of age, sex and topography on the dynamics of SW characteristics in a large population (n = 87) of healthy young (23.3 +/- 2.4 years) and middle-aged (51.9 +/- 4.6 years) volunteers. Older subjects showed lower SW density and amplitude than young subjects. Age-related lower SW density in men was especially marked in prefrontal/frontal brain areas, where they originate more frequently. Older subjects also showed longer SW positive and negative phase durations. These last results indicate that, in young subjects, cortical neurons would synchronously enter the SW hyperpolarization and depolarization phases, whereas this process would take longer in older subjects, leading to lower slope and longer SW positive and negative phases. Importantly, after controlling for SW amplitude, middle-aged subjects still showed lower slope than young subjects in prefrontal, frontal, parietal and occipital derivations. Age-related effects on SW density, frequency and positive phase duration were more prominent at the beginning of the night, when homeostatic sleep pressure is at its highest. Age-related SW changes may be associated with changes in synaptic density and white matter integrity and may underlie greater sleep fragmentation and difficulty in recuperating and maintaining sleep under challenges in older subjects.