10. BRAIN PARENCHYMA AND VASCULATURE AMYLOID: CLINICAL IMPLICATIONS OF A QUADRUPLE HIT?

Introduction

Cerebral amyloid angiopathy (CAA) is a disease of small and medium-sized vessels that affects the arteries in the cerebral cortex and the overlying leptomeninges. Over the disease course, amyloid progressively deposits in the vessel walls, producing fragile vessels that are susceptible to hemorrhage, ischemia, and inflammation. Patients typically present with intra-cerebral hemorrhages and transient focal neurological episodes. We discuss a patient with cerebrovascular imaging markers of CAA plus confirmed Alzheimer's disease (AD), neuropsychiatric symptoms (NPS) of dementia, and combat post-traumatic stress disorder (PTSD) who has remained cognitively and functionally stable for three years despite worsening disease burden on imaging.

Methods

A 73-year-old male war veteran with combat PTSD, CAA, AD, hypertension, hyperlipidemia, paroxysmal atrial fibrillation, and superior mesenteric artery dissection presented to our academic center geropsychiatry clinic in 2021 with six months of paranoia and verbal outbursts. His symptoms of cognitive decline date back to 2015, and neuropsychiatric testing in 2017 linked these initial frontal system weaknesses to active PTSD. In 2020, he was diagnosed with mild AD dementia confirmed by cerebrospinal fluid AD biomarkers with elevated total tau (t-tau) at 249 pg/ml; elevated phosphorylated tau (p-tau)/Abeta42 ratio at 0.054; decreased amyloid beta1-42 (Abeta42) at 505 pg/ml; and elevated p-tau = 27.1 pg/ml. A brain MRI showed multiple microhemorrhages and superficial siderosis on the right temporal lobe, indicating probable CAA. The patient's wife reported increased agitation over trivial matters, jealousy, and inferences of infidelity. The patient started memantine 10 mg daily and received NPS of dementia psychoeducation. After three years, his cognitive and functional statuses were stable. A repeat MRI in 2023 showed increasing punctate foci and mildly increased generalized volume loss of the bilateral temporal and occipital lobes. Despite NPS improvement and stabilization, the patient's disease progressed.

Results

CAA is a common co-pathology of AD, occurring in 20–100% of AD cases. Traditionally, cognitive decline in CAA has been thought to result from intra-cerebral hemorrhage and/or AD pathology. More recent research suggests CAA-specific pathways of neurodegeneration. As the current case alludes, there may also be co-occurring neuroprotective pathways at work. Through a biopsychosocial lens, we investigate potential genetic factors, medication positive effects, and lifestyle choices that may have contributed to the patient's relative cognitive stability.

Conclusions

This case provides insights into the clinical course of CAA, the pathophysiology of neurodegeneration in CAA, and potential mediators of disease burden.