Cerebrovascular Disease and Neurodegeneration in Alzheimer's Disease with and without a Strong Family History: A Pilot Magnetic Resonance Imaging Study in Dominican Republic

Abstract

The incidence and prevalence of Alzheimer's disease (AD) dementia are higher among Caribbean Hispanics than among non-Hispanic Whites. The causes of this health disparity remain elusive, partially because of the relative limited capacity for biomedical research in the developing countries that comprise Caribbean Latin America. To begin to address this issue, we were awarded a Development Research Award from the US NIH and Fogarty International Center in order to establish the local capacity to integrate magnetic resonance imaging (MRI) into studies of cognitive aging and dementia in Dominican Republic, establish collaborations with Dominican investigators, and conduct a pilot study on the role of cerebrovascular markers in the clinical expression of AD. Ninety older adult participants with and without AD dementia and with and without a strong family history of AD dementia received MRI scans and clinical evaluation. We quantified markers of cerebrovascular disease (white matter hyperintensities [WMH], presence of infarct, and presence of microbleed) and neurodegeneration (entorhinal cortex volume) and compared them across groups. Patients with AD dementia had smaller entorhinal cortex and greater WMH volumes compared with controls, regardless of family history status. This study provides evidence for the capacity to conduct MRI studies of cognitive aging and dementia in Dominican Republic. The results are consistent with the hypothesis that small vessel cerebrovascular disease represents a core feature of AD dementia, as affected participants had elevated WMH volumes irrespective of family history status.

Keywords: Alzheimer’s disease; cerebrovascular disease; developing countries; neurodegeneration.

Fig. 1.

Entorhinal cortex volume, adjusted for total cranial volume and age, across the four diagnostic group. Although the main effect of Diagnosis and post hoc comparisons were not statistically significant, a planned polynomial contrast (0 0 –1 –1) indicated that individuals with AD have smaller entorhinal cortex volumes than controls (contrast estimate = –5001.87, p = 0.004, 95% CI: –8396.99 to –1606.76). Error bars are standard errors. 95% CI for pairwise differences are as follows: NC– versus NC+ –393.18 to 381.36,p = 0.976; NC– versus AD– –117.15 to 523.61, p = 0.210; NC– versus AD+ –234.52 to 554.32, p = 0.422; NC+ versus AD– –226.40 to 644.69, p = 0.342; NC+ versus AD+ –339.32 to 670.95, p = 0.52; AD– versus AD+ –442.28 to 355.63, p = 0.829.

Fig. 2.

White matter hyperintensity volume, adjusted for total cranial volume and age, across the four diagnostic group. Both main effect of Diagnosis and planned polynomial contrasts (0011) indicated reliable differences between each of the two NC groups and each of the two AD groups (contrast estimate = –28.15, p = 0.031, 95% CI: –53.59 to –2.71). Error bars are standard errors. 95% CI for pairwise differences are as follows: NC– versus NC+ –2.64 to 3.16, p = 0.860; NC– versus AD– –6.90 to –2.10, p < 0.001; NC– versus AD+ –6.50 to –0.59, p = 0.09; NC+ versus AD– –8.02 to –1.49, p = 0.005;NC+versusAD+–7.59 to –0.017, p = 0.049;AD– versus AD+ –2.03 to 3.95, p = 0.525.

Fig. 3.

Regional WMH volume, adjusted for total cranial volume and age, across the four diagnostic group. Participants diagnosed with AD had greater WMH volumes than controls, particularly in frontal and parietal lobes. Error bars are standard errors.