Dementia onset occurred 22 years after stroke in an elderly patient whose postmortem analysis revealed extensive Alzheimer’s and vascular pathology alongside rare genetic variants also linked to cancer, according to a recent study.
Researchers detailed a rare case of remarkably delayed dementia onset following stroke, with findings published in the Open Journal of Pathology. The study investigated an 85-year-old male who experienced a massive ischemic stroke at age 59, presenting with right-sided paralysis and aphasia. Dementia was not clinically observed until 22 years later, and the patient ultimately died of bladder cancer.
To investigate the neuropathological and genetic contributors to this unusually protracted latency period for late-onset post-stroke dementia (LOPSD), researchers conducted a detailed postmortem analysis using histological, immunohistochemical, and genetic methodologies. Brain tissue was processed and stained with hematoxylin and eosin and Bielschowsky silver stain and further assessed for phospho-tau and β-amyloid peptide 1-42 accumulation. Gross anatomical examination revealed a large necrotic lesion involving the frontal, parietal, and temporal lobes of the left cerebral hemisphere, with an enlarged left frontal horn of the lateral ventricle—a feature frequently observed in patients with Alzheimer’s disease (AD).
Histopathological analysis confirmed extensive neuronal loss and white matter rarefaction in the cerebral cortices. Numerous amyloid plaques were identified throughout the cortex and hippocampus, along with neurofibrillary tangles localized to the hippocampus. Vascular pathology was prominent, with arteriosclerosis, cerebral amyloid angiopathy, cerebral microbleeds, and enlarged perivascular spaces detected in the frontal cortex, hippocampus, and basal ganglia.
Genomic screening via whole exome sequencing was conducted using next-generation sequencing, yielding 92 percent exome coverage at 50× depth. After stringent filtering, the researchers identified rare (minor allele frequency ≤ 0.01) deleterious variants in over 100 genes, categorized into cardiovascular disease, stroke, cognitive impairment, AD, vascular dementia, and Parkinson’s disease. Notably, mucin gene family members MUC2, MUC4, and MUC6 demonstrated pleiotropic roles across dementia and cancer categories, including bladder cancer—the patient’s cause of death.
The findings indicate a potential involvement of the gut-brain and bladder-gut-brain axes, as well as cancer–neurodegeneration interactions, in the pathogenesis of LOPSD. As a single-patient case study, the results may inform future research on molecular links between cancer and neurodegenerative disease.
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