Spontaneous oscillatory markers of cognitive status in two forms of dementia

Abnormal oscillatory brain activity in dementia may indicate incipient neuronal/synaptic dysfunction, rather than frank structural atrophy. Leveraging a potential link between the degree of abnormal oscillatory activity and cognitive symptom severity, one could localize brain regions in a diseased but pre-atrophic state, which may be more amenable to interventions. In the current study, we evaluated the relationships among cognitive deficits, regional volumetric changes, and resting-state magnetoencephalography abnormalities in patients with mild cognitive impairment (MCI; N = 10; age: 75.9 ± 7.3) or primary progressive aphasia (PPA; N = 12; 69.7 ± 8.0), and compared them to normal aging [young (N = 18; 24.6 ± 3.5), older controls (N = 24; 67.2 ± 9.7]. Whole-brain source-level resting-state estimates of relative oscillatory power in the delta (1-4 Hz), theta (4-7 Hz), alpha (8-12 Hz), and beta (15-30 Hz) bands were combined with gray matter volumes and cognitive scores to examine between-group differences and brain-behavior correlations. Language and executive function (EF) abilities were impaired in patients with PPA, while episodic memory was impaired in MCI. Widespread oscillatory speeding and volumetric shrinkage was associated with normal aging, whereas the trajectory in PPA indicated widespread oscillatory slowing with additional volumetric reductions. Increases in delta and decreases in alpha power uniquely predicted group membership to PPA. Beyond volumetric reductions, more delta predicted poorer memory. In patients with MCI, no consistent group difference among oscillatory measures was found. The contributions of delta/alpha power on memory abilities were larger than volumetric differences. Spontaneous oscillatory abnormalities in association with cognitive symptom severity can serve as a marker of neuronal dysfunction in dementia, providing targets for promising treatments.