Hemispheric asymmetry in neurodegenerative diseases

Hemispheric asymmetry in pathologic involvement is frequently observed in neurodegenerative disorders (NDD) and is responsible for differences in cognitive and motor clinical manifestations in individual patients. While asymmetry is modest in typical Alzheimer disease (AD), atypical AD presentations with prominent language impairment [logopenic/phonologic variant of primary progressive aphasia (L/Phv-PPA)] are associated with prevalent involvement of the language-dominant hemisphere. Similarly, in the frontotemporal dementia-amyotrophic lateral sclerosis (FTD-ALS) spectrum, the semantic (Sv) and nonfluent/agrammatic (Nf/Av) variants of PPA are due to asymmetric pathology involving the language-dominant hemisphere. A reversed (typically right-sided) pattern of asymmetry is often found in conditions associated with prominent disorders of behavior and social cognition (i.e., behavioral variant of frontotemporal degeneration-Bv FTD). Asymmetry is generally modest and less consistent in NDD with prevalent motor manifestations, such as Parkinson disease (PD). Overall, the pattern of hemispheric involvement reflects the network-specific selectivity of NDD and is compatible with the spreading of pathology along connection pathways.