This study conducted a comprehensive cognitive, neuroimaging, and genetic analysis of 31 patients with primary progressive aphasia (PPA), a condition characterized by a decline in language functions lasting at least two years. The patients were classified into three distinct clinical variants: nonfluent progressive aphasia (NFPA), semantic dementia (SD), and logopenic progressive aphasia (LPA). Voxel-based morphometry (VBM) revealed that when all PPA patients were analyzed together, significant atrophy was observed in the left perisylvian region and anterior temporal lobes. However, when each clinical variant was considered separately, distinct patterns emerged: (1) NFPA, characterized by apraxia of speech and complex syntax deficits, showed atrophy in the left inferior frontal and insular regions; (2) SD, characterized by fluent speech and semantic memory deficits, was associated with anterior temporal damage; and (3) LPA, characterized by slow speech and impaired syntactic comprehension, exhibited atrophy in the left posterior temporal cortex and inferior parietal lobule. The frequency of the Apolipoprotein E ε4 haplotype varied among the variants, with 20% in NFPA, 0% in SD, and 67% in LPA. These findings suggest that different PPA clinical variants may correspond to distinct underlying pathological processes.This study conducted a comprehensive cognitive, neuroimaging, and genetic analysis of 31 patients with primary progressive aphasia (PPA), a condition characterized by a decline in language functions lasting at least two years. The patients were classified into three distinct clinical variants: nonfluent progressive aphasia (NFPA), semantic dementia (SD), and logopenic progressive aphasia (LPA). Voxel-based morphometry (VBM) revealed that when all PPA patients were analyzed together, significant atrophy was observed in the left perisylvian region and anterior temporal lobes. However, when each clinical variant was considered separately, distinct patterns emerged: (1) NFPA, characterized by apraxia of speech and complex syntax deficits, showed atrophy in the left inferior frontal and insular regions; (2) SD, characterized by fluent speech and semantic memory deficits, was associated with anterior temporal damage; and (3) LPA, characterized by slow speech and impaired syntactic comprehension, exhibited atrophy in the left posterior temporal cortex and inferior parietal lobule. The frequency of the Apolipoprotein E ε4 haplotype varied among the variants, with 20% in NFPA, 0% in SD, and 67% in LPA. These findings suggest that different PPA clinical variants may correspond to distinct underlying pathological processes.