Mixed Cerebrovascular And Alzheimer’s Type Pathology Mimicking Lewy Body Disease And Its Possible Contribution To the Increased Risk of Developing Cognitive Impairment In Elderly Patients with Bipolar Disorder/Schizophrenia
Authors: Coomar Lokesh , Frolov Andrey , Guzman Miguel , Martin John R. 
Published: May 2022

BackgroundIt has been recently reported that bipolar disorder (BD), as compared to other major adult psychiatric disorders, was associated with an increased risk of developing Parkinson’s disease (PD), cerebrovascular disease (CVD), and dementia in a later life (PMID: 33075191). The similar to BD increased risk of developing dementia was also observed for schizophrenia (SCZ) (PMID: 33075191). Surprisingly, the most common cause of dementia, Alzheimer’s disease (AD) (PMID: 31564456), was absent in elderly BD patients with cognitive impairment when AD was probed by its signature biomarkers in the cerebrospinal fluid (PMID: 26876913). Altogether, these data question AD contribution to the increased risk for dementia development in elderly patients with BD. Therefore, the main objective of this study was to address the above issue by probing postmortem AD related pathology in two brains of 83‐year‐old individuals. The first subject (D1) was diagnosed with BD, SCZ, and PD, whereas the second (D2) had Lewy Body Dementia (LBD). PD, PD dementia, and LBD constitute Lewy Body Disease (PMID: 30665447).ResultsParaffin embedded tissue sections from specific regions of each brain underwent H&E staining, as well as immunohistochemical staining for β‐amyloid and phospho‐tau. Upon examination, Lewy bodies were not observed in D1 and D2 brains and the substantia nigra was well preserved in both brains, thereby not confirming the respective PD and LBD diagnoses. However, D1 brain displayed Alzheimer’s type pathology in the frontal, temporal, and occipital cortices as well as in the hippocampus. The respective pathological features included senile plaques and neurofibrillary tangles (NFTs) in the cortices and hippocampus as well as granulovacuolar degeneration (GVD) in pyramidal neurons of the hippocampus. Interestingly, in the same brain, a strong diffused β‐amyloid staining of potential significance was observed within the cerebellar neurons. Overall, the severity of the respective Alzheimer’s type pathology in D1 brain could be characterized by its clinical stage as mild to moderate. Importantly, there were also vascular changes in D1 brain consistent with hypertensive CVD including hyaline atherosclerosis, microbleeds, and dilated Virchow Robin spaces. Some blood vessels showed β‐amyloid deposits within the vessel wall and lumen which is indicative of amyloid angiopathy. In D2 brain, the AD pathology was also present in the form of NFTs and GVD in the hippocampus and was accompanied by mild neuronal loss in the hippocampus and cortex. Striking vascular pathology including thick‐walled blood vessels with microbleeds was also observed.Conclusionsi) AD could be present in elderly BD/SCZ patients and advance to clinical stage associated with cognitive impairment. ii) CVD in conjunction with AD could mimic Lewy Body Disease and contribute to the increased risk of dementia development in older BD/SCZ patients. iii) A proper diagnosis of dementia associated with mixed CVD/AD pathology in elderly patients with BD/SCZ would be important for their adequate treatment and care.