Diffuse Lewy body disease presenting as Parkinson's disease with progressive aphasia

Primary progressive aphasia (PPA) is a progressive language disorder often due to an underlying neurodegenerative disease. The most common pathologies associated with PPA include frontotemporal lobar degeneration (FTLD)-tau, FTLD-associated with transactivation response DNA-binding protein of 43 kDa (TDP-43) (FTLD-TDP), and Alzheimer's disease (AD). Accumulating evidence has suggested that Lewy body disease (LBD) can also be associated with PPA. We herein report a 78-year-old Caucasian woman who initially presented with levodopa-responsive parkinsonism at age 67 and later developed cognitive impairment, visual hallucinations, rapid eye movement sleep behavior disorder, and progressive aphasia, characterized by reduced spontaneous speech, word-finding difficulty, and difficulties in writing and reading. ¹⁸ Fluorodeoxyglucoase (FDG)-positron emission tomography (PET) performed at the age of 73 years identified hypometabolism in the frontal (right > left), temporal (left > right), and parietal (left > right) lobes. Neuropathological assessment revealed diffuse LBD (DLBD), AD, and TDP-43 stage 6 with prehippocampal sclerosis. Senile plaques were numerous, but only a few neurofibrillary tangles were present in the neocortex. The Braak neurofibrillary tangle stage was IV, and the Thal amyloid phase was 3. Lewy-related pathology was severe in the neocortex, as well as limbic cortices, basal forebrain, amygdala, and brainstem. Compared to 166 DLBD cases with a clinical diagnosis of dementia with Lewy bodies (DLB), the Lewy body count of the patient in this report was highest in the inferior parietal cortex, followed by midfrontal and superior temporal cortices. The findings suggest that severe cortical LBD pathology has contributed to her progressive aphasia. Autopsy cases of LBD presenting as PPA have been reported, but patients with PD and autopsy-proven DLBD who later developed progressive aphasia have not been reported. Our findings indicate that PD can be associated with progressive aphasia later in the disease course. Although uncommon, LBD should be considered as a differential diagnosis of progressive aphasia.