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Distribution and clinical impact of apolipoprotein E4 in subjective memory impairment and early mild cognitive impairment.

ABSTRACT: The apolipoprotein E (APOE) e4 allele is the most common genetic variant associated with Alzheimer's disease (AD). We sought to investigate the distribution of APOE genotypes across the full clinical AD spectrum including AD, late-stage amnestic mild cognitive impairment (L-aMCI), early-stage aMCI (E-aMCI), subjective memory impairment (SMI), and controls. We prospectively recruited 713 AD patients, 735 aMCI patients, 575 SMI patients, and 8,260 individuals as controls. The frequency of the APOE e4 allele revealed an ordered fashion in the AD (30.8%), L-aMCI (24.0%), E-aMCI (15.1%), SMI (11.7%), and control (9.1%) groups. APOE e3/e4 and e4/e4 genotype frequencies also appeared in an ordered fashion in the AD group (39.1% of e3/e4 and 10.9% of e4/e4), as well as the L-aMCI (28.3% and 9.4%), E-aMCI (22.3% and 3.7%), SMI (18.3% and 1.9%), and control (15.1% and 0.8%) groups. In the comparisons of APOE e3/e3 vs. e3/e4 genotypes, all patient groups had a higher frequency of APOE e3/e4 relative to the control group. Relative to the SMI and E-aMCI groups, the AD and L-aMCI groups had higher frequency of the APOE e3/e4 genotype, and the AD group had a higher frequency relative to the L-aMCI group. However, there was no significant difference between the E-aMCI and SMI groups. In our longitudinal data, APOE e4 carrier showed a steeper incline slope in a clinical dementia rating sum of boxes (CDR-SB) score than APOE e4 non-carrier in SMI (B?=?0.0066, p?=?0.0104), E-aMCI (B?=?0.0313, p?

SUBMITTER: Cho H

PROVIDER: S-EPMC7414226 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Distribution and clinical impact of apolipoprotein E4 in subjective memory impairment and early mild cognitive impairment.

Cho Hanna H Kim Young-Eun YE Chae Wonjeong W Kim Ko Woon KW Kim Jong-Won JW Kim Hee Jin HJ Na Duk L DL Ki Chang-Seok CS Seo Sang Won SW

Scientific reports 20200807 1

The apolipoprotein E (APOE) e4 allele is the most common genetic variant associated with Alzheimer's disease (AD). We sought to investigate the distribution of APOE genotypes across the full clinical AD spectrum including AD, late-stage amnestic mild cognitive impairment (L-aMCI), early-stage aMCI (E-aMCI), subjective memory impairment (SMI), and controls. We prospectively recruited 713 AD patients, 735 aMCI patients, 575 SMI patients, and 8,260 individuals as controls. The frequency of the APOE ...[more]

PMID: 32770103

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Project description:Background: The spectrum of early Alzheimer's disease (AD) is thought to include subjective cognitive impairment, early mild cognitive impairment (eMCI), and late mild cognitive impairment (lMCI). Choline dysfunction affects the early progression of AD, in which the basal nucleus of Meynert (BNM) is primarily responsible for cortical cholinergic innervation. The aims of this study were to determine the abnormal patterns of BNM-functional connectivity (BNM-FC) in the preclinical AD spectrum (SCD, eMCI, and lMCI) and further explore the relationships between these alterations and neuropsychological measures. Methods: Resting-state functional magnetic resonance imaging (rs-fMRI) was used to investigate FC based on a seed mask (BNM mask) in 28 healthy controls (HC), 30 SCD, 24 eMCI, and 25 lMCI patients. Furthermore, the relationship between altered FC and neurocognitive performance was examined by a correlation analysis. The receiver operating characteristic (ROC) curve of abnormal BNM-FC was used to specifically determine the classification ability to differentiate the early AD disease spectrum relative to HC (SCD and HC, eMCI and HC, lMCI and HC) and pairs of groups in the AD disease spectrum (eMCI and SCD, lMCI and SCD, eMCI and lMCI). Results: Compared with HC, SCD patients showed increased FC in the bilateral SMA and decreased FC in the bilateral cerebellum and middle frontal gyrus (MFG), eMCI patients showed significantly decreased FC in the bilateral precuneus, and lMCI individuals showed decreased FC in the right lingual gyrus. Compared with the SCD group, the eMCI group showed decreased FC in the right superior frontal gyrus (SFG), while the lMCI group showed decreased FC in the left middle temporal gyrus (MTG). Compared with the eMCI group, the lMCI group showed decreased FC in the right hippocampus. Interestingly, abnormal FC was associated with certain cognitive domains and functions including episodic memory, executive function, information processing speed, and visuospatial function in the disease groups. BNM-FC of SFG in distinguishing eMCI from SCD; BNM-FC of MTG in distinguishing lMCI from SCD; BNM-FC of the MTG, hippocampus, and cerebellum in distinguishing SCD from HC; and BNM-FC of the hippocampus and MFG in distinguishing eMCI from lMCI have high sensitivity and specificity. Conclusions: The abnormal BNM-FC patterns can characterize the early disease spectrum of AD (SCD, eMCI, and lMCI) and are closely related to the cognitive domains. These new and reliable findings will provide a new perspective in identifying the early disease spectrum of AD and further strengthen the role of cholinergic theory in AD.

Project description:BACKGROUND:Subjective cognitive decline (SCD) and anxiety symptoms both predict neurocognitive disorders, but the two correlate strongly with each other. It is unclear whether they reflect two independent disease processes in the development of neurocognitive disorders and hence deserve separate attention. This cohort study examined whether SCD and anxiety symptoms demonstrate independent risks of mild cognitive disorder and dementia (MCI/dementia). METHODS:The study included 14,066 participants aged ??50?years and diagnosed with normal cognition at baseline, recruited from Alzheimer's Disease Centers across the USA. The participants were evaluated for SCD and anxiety symptoms at baseline and followed up almost annually for incident MCI/dementia (median follow-up 4.5?years; interquartile range 2.2-7.7?years). SCD and anxiety symptoms were included in Cox regression to investigate their independent risks of MCI/dementia. RESULTS:SCD and anxiety symptoms demonstrated independent risks of MCI/dementia, with HR 1.9 (95% CI 1.7-2.1) and 1.3 (95% CI 1.2-1.5), respectively. Co-occurring SCD and anxiety symptoms demonstrated the highest risk (HR 2.4, 95% CI 1.9-2.9)-participants in this group had a 25% probability of developing MCI/dementia by 3.1?years (95% 2.4-3.7), compared to 8.2?years among those without SCD or anxiety (95% CI 7.9-8.6). The results remained robust even in the sensitivity analyses that took into account symptom severity and consistency of symptoms in the first 2 annual visits. CONCLUSIONS:The findings suggest that clinicians should not dismiss one over the other when patients present with both SCD and anxiety and that both constructs may potentially be useful to identify high-risk populations for preventive interventions and trials. The findings also point to the need for further research to clarify on the neurobiological distinctions between SCD and anxiety symptoms, which may potentially enrich our understanding on the pathogenesis of neurocognitive disorders.

Dataset Information

Distribution and clinical impact of apolipoprotein E4 in subjective memory impairment and early mild cognitive impairment.

Publications

Distribution and clinical impact of apolipoprotein E4 in subjective memory impairment and early mild cognitive impairment.

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