Is Cerebrovascular Disease a Core Pathological Feature of Alzheimer’s Disease? Examination of a Sample of Spanish-speaking Latinx Older Adults with Late-onset Alzheimer’s Disease

Alzheimer\u27s disease (AD) is the most common cause of dementia. With no available treatments to cure or slow its progress, AD’s impact on the U.S. public health system is projected to increase four-fold by 2050. Emerging research implicates cerebrovascular disease (CVD) in the pathology and clinical presentation of AD, although its precise relationship with AD remains unclear. The present study examined the pathological and neurocognitive impact of three CVD biomarkers in a community sample of older adults (N=90). Participants were either diagnosed with AD (N=39) or control participants (N=39), and from families with either a strong history of AD (two or more siblings with AD) or without (no siblings with AD). CVD markers included white matter hyperintensities (WMHs), microbleeds, and infarcts. Neurocognitive markers included two measures each of memory, language, and executive functioning. Entorhinal cortex (EC) volume was utilized as a biomarker for AD-related neurodegeneration. By examining participants varying in both diagnostic status and genetic risk for AD, we were able to investigate whether CVD represents a core feature of AD (indicated by increased CVD in all AD participants regardless of family history) or whether CVD represents a comorbidity in AD (indicated by increased CVD only among AD participants with a family history of AD). Results showed that AD participant had greater total and regional WMHs, particularly in frontal, parietal, and occipital lobes, and lower EC volumes than control participants, regardless of family history of AD (p\u3e0.05). AD participants were also at greater risk for exhibiting microbleeds (2.57X) and infarcts (1.43X) than control participants; however, these differences were not significant (p\u3e0.05). There was no evidence of any interaction between CVD and AD biomarkers. As expected, AD participants performed worse than control participants on all measures. There was no evidence of any direct relationship between CVD and neurocognitive performance. Overall, our results provided partial support for the role of CVD (i.e., WMHs) in AD pathology, and no evidence for its impact on neurocognitive functioning in AD. Nonetheless, investigations of CVD in AD remain an important area of investigation and could provide insights leading to future therapeutic interventions