Modified RCTU Score: A Semi-Quantitative, Visual Tool for Predicting Alzheimer's Conversion from aMCI.

This research evaluated the modified RCTU score, derived from amyloid PET scans, for predicting the progression from amnestic Mild Cognitive Impairment (aMCI) to Alzheimer's Disease (AD). aMCI patients underwent baseline evaluations, including amyloid PET. AD conversion was identified through neuropsychological tests after observation. The RCTU was modified by segmenting frontal, parietal, and temporal lobes into left and right, resulting in seven areas. Scores from both modified and conventional RCTU were analyzed and compared. Among 45 patients, 12 progressed to AD (over 17.8 ± 6.8 months). AD converters showed higher scores in modified RCTU scores. Modified RCTU score had strong correlations with amyloid SUVR (r > 0.7). Modified RCTU sum score was the significant covariate of AD conversion. Modified RCTU could determine the asymmetry of amyloid deposits. We demonstrated that symmetric deposits of amyloid showed a higher risk for AD conversion when analyzed using modified RCTU. The modified RCTU score is a promising method for predicting AD conversion, correlating strongly with amyloid SUVR.

Evaluating the Effectiveness of Community-Based Dementia Caregiver Intervention on Caregiving Burden, Depression, and Attitude Toward Dementia: A Quasi-experimental Study.

Objective: Accumulating evidence of the effects of dementia caregiving on individuals, society, and health has generated intervention studies to reduce the stress among family caregivers of people with dementia. This study aims to evaluate the effectiveness of a family support program, community-based dementia caregiver intervention (CDCI), among family caregivers of people with dementia compared with a control group (no intervention). Patients and Methods: This study is a quasi-experimental, non-randomized controlled trial conducted in six dementia relief centers of a community healthcare center in Korea. Family caregivers of 83 patients with dementia were recruited; of these 78 were included in the final study, with 40 in the intervention group and 38 in the control group. Analysis of covariance (ANCOVA) was used to compare the mean difference in the scores of the total short-form Zarit Burden Interview (SZBI), personal strain, role strain, depression, and attitude between the groups. Results: Compared with controls, in the intervention group, the adjusted mean score of personal strain (F = 4.353, t = 0.041) and attitude toward dementia (F = 10.284, t = 0.002) differed significantly after the intervention, with a small to moderate effect. There was no significant difference in the total SZBI, role strain, or depression mean score. Conclusion: The findings suggest that CDCI may be an effective intervention strategy to reduce personal strain and enhance the attitudes of family caregivers of people with dementia.

Distinct Neural Correlates of Executive Function by Amyloid Positivity and Associations with Clinical Progression in Mild Cognitive Impairment.

PURPOSE: This study aimed to identify the neural basis of executive function (EF) in amnestic mild cognitive impairment (aMCI) according to beta-amyloid (Aß) positivity. Furthermore, we explored if the identified brain areas could serve as predictors for clinical progression. MATERIALS AND METHODS: We included individuals with aMCI using data from [18F]-florbetapir-positron emission tomography (PET), fluorodeoxyglucose-PET, and EF scores, as well as follow-up clinical severity scores at 1 and 5 years from baseline from the Alzheimer's Disease Neuroimaging Initiative database. The correlations between EF score and regional cerebral glucose metabolism (rCMglc) were analyzed separately for aMCI with low Aß burden (aMCI Aß-, n=230) and aMCI with high Aß burden (aMCI Aß+, n=268). Multiple linear regression analysis was conducted to investigate the associations between rCMglc and clinical progression. RESULTS: Longitudinal courses differed between aMCI Aß- and aMCI Aß+ groups. On average, aMCI Aß- subjects maintained their level of clinical severity, whereas aMCI Aß+ subjects showed progression. EF impairment in aMCI Aß- was related to the anterior cingulate cortex (ACC), whereas that in aMCI Aß+ was related to Alzheimer's Disease-vulnerable brain regions. ACC and the posterior cingulate cortex were associated with clinical progression in aMCI Aß- and aMCI Aß+, respectively. CONCLUSION: Our findings suggest that although MCI subjects showed similar behavioral phenotypes at the time of diagnosis, EF and further progression were associated with different brain regions according to Aß burden. Clarification of the etiologies and nature of EF impairment in aMCI are critical for disease prognosis and management.

APOE Promoter Polymorphism-219T/G is an Effect Modifier of the Influence of APOE ε4 on Alzheimer's Disease Risk in a Multiracial Sample.

Variants in the APOE gene region may explain ethnic differences in the association of Alzheimer's disease (AD) with ε4. Ethnic differences in allele frequencies for three APOE region SNPs (single nucleotide polymorphisms) were identified and tested for association in 19,398 East Asians (EastA), including Koreans and Japanese, 15,836 European ancestry (EuroA) individuals, and 4985 African Americans, and with brain imaging measures of cortical atrophy in sub-samples of Koreans and EuroAs. Among ε4/ε4 individuals, AD risk increased substantially in a dose-dependent manner with the number of APOE promoter SNP rs405509 T alleles in EastAs (TT: OR (odds ratio) = 27.02, p = 8.80 × 10-94; GT: OR = 15.87, p = 2.62 × 10-9) and EuroAs (TT: OR = 18.13, p = 2.69 × 10-108; GT: OR = 12.63, p = 3.44 × 10-64), and rs405509-T homozygotes had a younger onset and more severe cortical atrophy than those with G-allele. Functional experiments using APOE promoter fragments demonstrated that TT lowered APOE expression in human brain and serum. The modifying effect of rs405509 genotype explained much of the ethnic variability in the AD/ε4 association, and increasing APOE expression might lower AD risk among ε4 homozygotes.

Prognostic value of Alzheimer's biomarkers in mild cognitive impairment: the effect of age at onset.

OBJECTIVE: The aim of this study is to assess the impact of age at onset on the prognostic value of Alzheimer's biomarkers in a large sample of patients with mild cognitive impairment (MCI). METHODS: We measured Aß42, t-tau, hippocampal volume on magnetic resonance imaging (MRI) and cortical metabolism on fluorodeoxyglucose-positron emission tomography (FDG-PET) in 188 MCI patients followed for at least 1 year. We categorised patients into earlier and later onset (EO/LO). Receiver operating characteristic curves and corresponding areas under the curve (AUCs) were performed to assess and compar the biomarker prognostic performances in EO and LO groups. Linear Model was adopted for estimating the time-to-progression in relation with earlier/later onset MCI groups and biomarkers. RESULTS: In earlier onset patients, all the assessed biomarkers were able to predict cognitive decline (p < 0.05), with FDG-PET showing the best performance. In later onset patients, all biomarkers but t-tau predicted cognitive decline (p < 0.05). Moreover, FDG-PET alone in earlier onset patients showed a higher prognostic value than the one resulting from the combination of all the biomarkers in later onset patients (earlier onset AUC 0.935 vs later onset AUC 0.753, p < 0.001). Finally, FDG-PET showed a different prognostic value between earlier and later onset patients (p = 0.040) in time-to-progression allowing an estimate of the time free from disease. DISCUSSION: FDG-PET may represent the most universal tool for the establishment of a prognosis in MCI patients and may be used for obtaining an onset-related estimate of the time free from disease.

Amyloid-independent functional neural correlates of episodic memory in amnestic mild cognitive impairment.

PURPOSE: Although amnestic mild cognitive impairment (aMCI) could have various biological characteristics, little attention has been given to the nature of episodic memory decline in aMCI with pathophysiologies other than Alzheimer's disease (AD), i.e., aMCI with low beta-amyloid (Aß) burden. This study aimed to identify the functional neural basis of episodic memory impairment in aMCI with Aß burden negative (aMCI-Aß-) and to compare these results with aMCI with Aß burden positive (aMCI-Aß+). METHODS: Individuals with aMCI (n = 498) were selected from the Alzheimer's Disease Neuroimaging Initiative database. Based on the mean florbetapir standard uptake value ratio, participants were classified as aMCI-Aß- or aMCI-Aß+. Correlations between memory scores and regional cerebral glucose metabolism (rCMglc) were analyzed separately for the two subgroups using a multiple regression model. RESULTS: For aMCI-Aß-, significant positive correlations between memory and rCMglc were found in the bilateral claustrum, right thalamus, left anterior cingulate cortex, left insula, and right posterior cingulate. For aMCI-Aß+, significant positive correlations between memory and rCMglc were found in the temporoparietal areas. These correlation patterns remained unchanged when clinical severity was added as a covariate CONCLUSION: Our findings indicate that memory impairment in aMCI-Aß- is related to multimodal integrative processing and the attentional control system, whereas memory impairment in aMCI-Aß+ is related to the typical brain memory systems and AD signature. These results suggest that although the two subgroups are clinically in the same category as aMCI, the memory impairment process depends on completely different functional brain regions according to their Aß burden level.

Astrocytosis measured by ¹¹C-deprenyl PET correlates with decrease in gray matter density in the parahippocampus of prodromal Alzheimer's patients.

PURPOSE: The Alzheimer's disease (AD) pathology is characterized by fibrillar amyloid deposits and neurofibrillary tangles, as well as the activation of astrocytosis, microglia activation, atrophy, dysfunctional synapse, and cognitive impairments. The aim of this study was to test the hypothesis that astrocytosis is correlated with reduced gray matter density in prodromal AD. METHODS: Twenty patients with AD or mild cognitive impairment (MCI) underwent multi-tracer positron emission tomography (PET) studies with (11)C-Pittsburgh compound B ((11)C-PIB), (18) F-Fluorodeoxyglucose ((18) F-FDG), and (11)C-deuterium-L-deprenyl ((11)C-DED) PET imaging, as well as magnetic resonance imaging (MRI) scanning, cerebrospinal fluid (CSF) biomarker analysis, and neuropsychological assessments. The parahippocampus was selected as a region of interest, and each value was calculated for four different imaging modalities. Correlation analysis was applied between DED slope values and gray matter (GM) densities by MRI. To further explore possible relationships, correlation analyses were performed between the different variables, including the CSF biomarker. RESULTS: A significant negative correlation was obtained between DED slope values and GM density in the parahippocampus in PIB-positive (PIB + ve) MCI patients (p = 0.025) (prodromal AD). Furthermore, in exploratory analyses, a positive correlation was observed between PIB-PET retention and DED binding in AD patients (p = 0.014), and a negative correlation was observed between PIB retention and CSF Aß42 levels in MCI patients (p = 0.021), while the GM density and CSF total tau levels were negatively correlated in both PIB + ve MCI (p = 0.002) and MCI patients (p = 0.001). No significant correlation was observed with FDG-PET and with any of the other PET, MRI, or CSF biomarkers. CONCLUSIONS: High astrocytosis levels in the parahippocampus of PIB + ve MCI (prodromal AD) patients suggest an early preclinical influence on cellular tissue loss. The lack of correlation between astrocytosis and CSF tau levels, and a positive correlation between astrocytosis and fibrillar amyloid deposition in clinical demented AD together indicate that parahippocampal astrocytosis might have some causality within the amyloid pathology.

Health-promoting behaviour among women with abdominal obesity: a conceptual link to social support and perceived stress.

AIM: To identify a conceptual link among health-promoting behaviour, interpersonal support and perceived stress and to examine whether the link between interpersonal support and health-promoting behaviour would be mediated by perceived stress among women with abdominal obesity. BACKGROUND: Abdominal obesity is a strong risk factor for cardiovascular disease in women and its reduction can be achieved by weight loss. Adopting health-promoting behaviour may be critical for successful weight loss. DESIGN: A cross-sectional, correlational study design. METHOD: Study participants were 126 women with abdominal obesity, who comprised a baseline sample in the Community-based, Heart and Weight Management Trial. The Data were collected between September 2010-November 2011. A multiple regression analysis and Sobel's test were performed. FINDINGS: Higher levels of interpersonal support and lower levels of perceived stress were significantly associated with higher levels of health-promoting behaviour, after controlling for age, obesity-related comorbidity, postmenopausal status and current smoking in the regression models. The association between interpersonal support and health-promoting behaviour was significantly mediated by perceived stress in the Sobel's test; the magnitude of the association between interpersonal support and health-promoting behaviour decreased when adding perceived stress to the predictor variables in the regression model. CONCLUSION: Our findings indicate the practical significance of identifying the levels of interpersonal support and perceived stress among women seeking weight management interventions. Nurses need to develop effective strategies for enhancing social support and stress management skills in weight management interventions for facilitating health-promoting behaviour.