Mixed Cerebrovascular and Alzheimer’s Type Pathology Mimicking Lewy Body Disease and Its Possible Contribution to Cognitive Impairment in Elderly Patients with Bipolar Disorder/Schizophrenia

Abstract

The fast aging human population requires new approaches to reliable diagnosis and proper treatment of dementia in elderly patients with psychiatric disorders such as bipolar disorder (BD) and schizophrenia (SCZ). As compared to other psychiatric disorders, BD and SCZ are characterized by increased and similar risk for dementia as well as cerebrovascular (CVD) and Parkinson’s (PD) diseases independent of the patient’s age. There are reports in the literature suggesting BD and SCZ in older patients could cause dementia without contribution from the neurodegenerative diseases, including Alzheimer’s disease (AD), due to the absence of the known neuropathology associated with cognitive decline in such individuals. This view contradicts a plethora of data highlighting AD as a major cause of dementia in the elderly. This issue was addressed by examining postmortem cerebral pathology in an 83-year-old female diagnosed with BD, SCZ, and PD (D1) and comparing it to that of a second donor (D2), an age-matched male diagnosed with Lewy Body Dementia (LBD). Upon thorough histochemical and immunohistochemical examinations of both brains, the PD and LBD diagnoses in D1 and D2 were not confirmed. Instead, AD-related pathology was observed in both subjects with AD advancing to its clinical stage (mild to moderate) only in D1. Diffuse β-amyloid peptide 1-42 (Aβ1-42) staining, most likely reflecting a presence of the Aβ1-42 soluble form, was also detected in cerebellar neurons and cerebellar extracellular space in D1 and D2. Cerebrovascular pathology was pronounced and distinct in both brains and included amyloid angiopathy, hyaline atherosclerosis, microbleeds, and dilated Virchow Robin spaces in D1 as well as thick-walled blood vessels with microbleeds in D2. It was concluded that a mixed AD and cerebrovascular pathology could mimic Lewy Body Disease and potentially contribute to dementia development in elderly BD and SCZ patients.