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Protective effects of APOE e2 against disease progression in subcortical vascular mild cognitive impairment patients: A three-year longitudinal study.

ABSTRACT: Although the association between apolipoprotein E (APOE) genotype and disease progression is well characterized in patients with Alzheimer's disease, such a relationship is unknown in patients with subcortical vascular cognitive impairment. We evaluated whether APOE genotype is associated with disease progression in subcortical vascular mild cognitive impairment (svMCI) patients. We prospectively recruited 72 svMCI patients (19 APOE4 carriers, 42 APOE3 homozygotes, and 11 APOE2 carriers). Patients were annually followed-up with brain MRI and neuropsychological tests for three years and underwent a second Pittsburgh compound B (PiB)-PET at a mean interval of 32.3 months. Amyloid-ß burden was quantified by PiB standardized uptake value ratio (SUVR), and the amount of small vessel disease was quantified by number of lacune and small vessel disease score on MRI. We also measured cortical thickness. During the three years of follow-up, compared to the APOE3 homozygotes, there was less increase in PiB SUVR among APOE2 carriers (p?=?0.023), while the APOE genotype did not show significant effects on small vessel disease progression. APOE2 carriers also showed less cortical thinning (p?=?0.023) and a slower rate of cognitive decline (p?=?0.009) compared to those with APOE3 homozygotes. Our findings suggest that, in svMCI patients, APOE2 has protective effects against amyloid-ß accumulation, cortical thinning, and cognitive decline.

SUBMITTER: Kim YJ

PROVIDER: S-EPMC5432504 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Protective effects of APOE e2 against disease progression in subcortical vascular mild cognitive impairment patients: A three-year longitudinal study.

Kim Yeo Jin YJ Seo Sang Won SW Park Seong Beom SB Yang Jin Ju JJ Lee Jin San JS Lee Juyoun J Jang Young Kyoung YK Kim Sung Tae ST Lee Kyung-Han KH Lee Jong Min JM Lee Jae-Hong JH Kim Jae Seung JS Na Duk L DL Kim Hee Jin HJ

Scientific reports 20170515 1

Although the association between apolipoprotein E (APOE) genotype and disease progression is well characterized in patients with Alzheimer's disease, such a relationship is unknown in patients with subcortical vascular cognitive impairment. We evaluated whether APOE genotype is associated with disease progression in subcortical vascular mild cognitive impairment (svMCI) patients. We prospectively recruited 72 svMCI patients (19 APOE4 carriers, 42 APOE3 homozygotes, and 11 APOE2 carriers). Patien ...[more]

PMID: 28507298

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Project description:Subcortical vascular mild cognitive impairment (svMCI) is the predementia stage of subcortical vascular dementia (SVaD). The aim of this research is to explore and compare cerebral gray matter (GM) volume reduction in svMCI patients and SVaD patients, and to investigate the relationship between cerebral GM volume reduction and cognitive deficits.Thirty one svMCI patients, 29 SVaD patients, and 31 healthy controls were recruited in our research. They conducted neuropsychological tests and brain structural magnetic resonance imaging (MRI) examination. To detect cerebral GM volume reduction in svMCI patients and SVaD patients, we used statistical parametric mapping 8-voxel-based morphometry 8 (SPM8-VBM8) method to analyze MRI data. To detect the relationship between cerebral GM volume reduction and cognitive deficits, multiple linear regression analysis was used.Compared with healthy controls, svMCI patients showed cerebral GM volume reduction in hippocampus and parahippocampal gyrus, insula and superior temporal gyrus. Compared with healthy controls, SVaD patients exhibited more atrophy which encompasses all of these areas plus anterior and middle cingulate, inferior temporal gyrus, orbitofrontal cortex, and superior frontal gyrus. In svMCI patients, cerebral GM volume reduction correlated with memory loss, attention dysfunction, and language dysfunction; in SVaD patients, besides those cognitive deficits, cerebral GM volume reduction correlated with more cognitive impairments, including executive dysfunction, neuropsychiatric symptom, and depression.Our findings prove that both svMCI patients and SVaD patients exhibit cerebral GM volume reduction and there may exist a hierarchy between svMCI and SVaD, and cerebral GM volume reduction in both svMCI patients and SVaD patients correlates with cognitive deficits, which can help us understand the mechanism of cognitive impairments in svMCI patients and SVaD patients, and diagnose SVaD at its early stage.

Project description:ImportanceCerebrovascular disease (CVD) and Alzheimer disease are significant causes of cognitive impairment in the elderly. However, few studies have evaluated the relationship between CVD and β-amyloid burden in living humans or their synergistic effects on cognition. Thus, there is a need for better understanding of mild cognitive impairment (MCI) before clinical deterioration begins.ObjectiveTo determine the synergistic effects of β-amyloid burden and CVD on cognition in patients with subcortical vascular MCI (svMCI).Design, setting, and participantsA cross-sectional study was conducted using a hospital-based sample at a tertiary referral center. We prospectively recruited 95 patients with svMCI; 67 of these individuals participated in the study. Forty-five patients with amnestic MCI (aMCI) were group matched with those with svMCI by the Clinical Dementia Rating Scale Sum of Boxes.Main outcomes and measuresWe measured β-amyloid burden using positron emission tomography with carbon 11-labeled Pittsburgh Compound B (PiB). Cerebrovascular disease was quantified as white matter hyperintensity volume detected by magnetic resonance imaging fluid-attenuated inversion recovery. Detailed neuropsychological tests were performed to determine the level of patients' cognitive impairment.ResultsOn evaluation, 22 of the svMCI group (33%) and 28 of the aMCI group (62%) were found to be PiB positive. The mean PiB retention ratio was lower in patients with svMCI than in those with aMCI. In svMCI, the PiB retention ratio was associated with cognitive impairments in multiple domains, including language, visuospatial, memory, and frontal executive functions, but was associated only with memory dysfunction in aMCI. A significant interaction between PiB retention ratio and white matter hyperintensity volume was found to affect visuospatial function in patients with svMCI.Conclusions and relevanceMost patients with svMCI do not exhibit substantial amyloid burden, and CVD does not increase β-amyloid burden as measured by amyloid imaging. However, in patients with svMCI, amyloid burden and white matter hyperintensity act synergistically to impair visuospatial function. Therefore, our findings highlight the need for accurate biomarkers, including neuroimaging tools, for early diagnosis and the need to relate these biomarkers to cognitive measurements for effective use in the clinical setting.

Dataset Information

Protective effects of APOE e2 against disease progression in subcortical vascular mild cognitive impairment patients: A three-year longitudinal study.

Publications

Protective effects of APOE e2 against disease progression in subcortical vascular mild cognitive impairment patients: A three-year longitudinal study.

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