Journal of Alzheimer's Disease - Volume 57, issue 2

Authors: Rawtaer, Iris | Gao, Qi | Nyunt, Ma Shwe Zin | Feng, Lei | Chong, Mei Sian | Lim, Wee Shiong | Lee, Tih-Shih | Yap, Philip | Yap, Keng Bee | Ng, Tze Pin

Article Type: Research Article

Abstract: Background: Indicators of social isolation or support such as living alone, loneliness, being married, and life satisfaction are possible psychosocial risk and protective factors for dementia. Objective: We investigate the associations of these overlapping psychosocial factors with incident MCI-dementia (neurocognitive disorder) in a population cohort. Methods: Using data from 1601 participants of the Singapore Longitudinal Ageing Study (SLAS) who were free of MCI or dementia at baseline and followed up to 8 years, we estimated hazards ratio (HR) of association of living alone, loneliness, being married, and high life satisfaction with incident MCI-dementia. Results: …In univariate analyses, individual HRs of association with incident MCI-dementia for living alone was 1.86 [1.18 – 2.95], (p  = 0.008), loneliness was 1.26 [0.86 – 1.84], (p  = 0.23), being married was 0.54 [0.39 – 0.75] (p  < 0.0001), and being very satisfied with life was 0.59 [0.38–0.91]), (p  = 0.017). Adjusted mutually for other psychosocial variables, and for age, sex, education, ethnicity, smoking, alcohol, dyslipidemia, hypertension, diabetes, central obesity, history of stroke or heart disease, APOE-ɛ 4, depression, physical, social, and productive activities, only being married (0.68 [0.47–0.99], p  = 0.044), and being very satisfied with life (0.61 [0.39 – 0.96], p  = 0.034) remained significant variables associated with lower risks of developing MCI-dementia. Conclusion: Individuals who were married and those who were very satisfied with life are protected against the risk of developing MCI and dementia. Controlling for the adverse effects of being without spousal support and low life satisfaction, living alone or a feeling of loneliness were not associated with increased risk of MCI-dementia. Show more

Keywords: Dementia, epidemiology, living alone, protective factors, risk factors

DOI: 10.3233/JAD-160862

Citation: Journal of Alzheimer's Disease, vol. 57, no. 2, pp. 603-611, 2017

Authors: Dong, Jing | Qin, Wei | Wei, Cuibai | Tang, Yi | Wang, Qi | Jia, Jianping

Article Type: Research Article

Abstract: Background: Presenilin-1 (PSEN1 ) is the most frequently mutated gene in familial Alzheimer’s disease (AD), whereas only several novel mutations have been reported in China and functional studies were seldom conducted. Objective: We describe a novel PSEN1 K311R mutation in two Chinese families with late-onset AD and its functional impact on amyloid-β protein precursor (AβPP) processing and tau phosphorylation. Methods: The mutation was detected by direct sequencing of PSEN1 exon 9. HEK293 cells stably expressing wild-type APP 695 (HEK293-APP 695wt ) were transfected with plasmids containing human wild-type PSEN1 , PSEN1 K311R mutation, …and PSEN1 E280A mutation to compare the K311R mutation’s effects on AβPP processing with other groups. In addition, each group of cells were co-transfected with plasmids harboring PSEN1 and human wild-type MAPT complementary DNA to study the mutation’s impacts on tau phosphorylation. Results: The K311R mutation was detected in probands of two late-onset AD families. Expression of the K311R or E280A mutation increased amyloid-β (Aβ)42 levels but decreased Aβ40 levels, resulting in an overall increase in the Aβ42 /Aβ40 ratio compared to those in wild-type PSEN1 transfected cells (p  < 0.05). The K311R or E280A mutation also increased the levels of phosphorylated tau compared to wild-type PSEN1 (p  < 0.05). Conclusion: The K311R mutation might contribute to AD pathogenesis by overproducing toxic Aβ species and enhancing tau phosphorylation. Further in-depth studies are needed to decipher the pathogenic mechanisms of the K311R mutation in terms of AβPP cleavage, tau phosphorylation, and other presenilin-1 mediated functional pathways. Show more

Keywords: Amyloid-β, familial Alzheimer’s disease, mutation, presenilin, tau

DOI: 10.3233/JAD-161188

Citation: Journal of Alzheimer's Disease, vol. 57, no. 2, pp. 613-623, 2017

Authors: Abdelnour, Carla | Rodríguez-Gómez, Octavio | Alegret, Montserrat | Valero, Sergi | Moreno-Grau, Sonia | Sanabria, Ángela | Hernández, Isabel | Rosende-Roca, Maitee | Vargas, Liliana | Mauleón, Ana | Sánchez, Domingo | Espinosa, Ana | Ortega, Gemma | Pérez-Cordón, Alba | Diego, Susana | Gailhajanet, Anna | Guitart, Marina | Sotolongo-Grau, Óscar | Ruiz, Agustín | Tárraga, Lluís | Boada, Mercè

Article Type: Research Article

Abstract: Background: Recruitment methods can determine sample characteristics in mild cognitive impairment and Alzheimer’s disease dementia, but little is known about its influence in subjective cognitive decline (SCD). Objective: To determine the influence of two types of recruitment methods in the characteristics of individuals with SCD. Methods: We select and compare clinical and neuropsychological features, and frequency of APOE ɛ 4 allele of 326 subjects with SCD from two cohorts: Open House Initiative (OHI) versus Memory Unit (MU). A logistic regression analysis (LRA), using gender and years of education as covariates, was used to examine the …neuropsychological variables. Results: The OHI sample were mostly women (75.9% versus 64.5%, p  < 0.05), with higher educational level (12.15 [3.71] versus 10.70 [3.80] years, p  = 0.001), and more family history of dementia (138 [62.7%] versus 44 [41.5%], p  < 0.001) than the MU sample. Also, the OHI sample showed better overall neuropsychological performance than the MU sample, and after a LRA, this trend continued in automatic response inhibition capacity, abstract reasoning, and recognition memory. We did not find differences in age, depression history, and/or APOE ɛ 4 allele frequency. Conclusion: SCD subjects showed different demographic and neuropsychological characteristics depending on the recruitment method, which should be taken into account in the design of research studies with this target population. Show more

Keywords: Alzheimer’s disease, patient recruitment, research subject recruitment, sampling studies, subjective cognitive decline

DOI: 10.3233/JAD-160915

Citation: Journal of Alzheimer's Disease, vol. 57, no. 2, pp. 625-632, 2017

Authors: Lutski, Miri | Weinstein, Galit | Goldbourt, Uri | Tanne, David

Article Type: Research Article

Abstract: Background: The role of insulin resistance (IR) in the pathogenesis of cognitive performance is not yet clear. Objective: To examine the associations between IR and cognitive performance and change in cognitive functions two decades later in individuals with cardiovascular disease with and without diabetes. Methods: A subset of 489 surviving patients (mean age at baseline 57.7±6.5 y) with coronary heart disease who previously participated in the secondary prevention Bezafibrate Infarction Prevention (BIP trial; 1990–1997), were included in the current neurocognitive study. Biochemical parameters including IR (using the homeostasis model of assessment; HOMA-IR) were measured at …baseline. During 2004–2008, computerized cognitive assessment and atherosclerosis parameters were measured (T1; n  = 558; mean age 72.6±6.4 years). A second cognitive assessment was performed during 2011–2013 (T2; n  = 351; mean age 77.2±6.4 years). Cognitive function, overall and in specific domains, was assessed. We used linear regression models and linear mixed models to evaluate the differences in cognitive performance and decline, respectively. Results: Controlling for potential confounders, IR (top HOMA-IR quartile versus others) was associated with subsequent poorer cognitive performance overall (β= –4.45±Standard Error (SE) 1.54; p  = 0.004) and on tests of memory and executive function among non-diabetic patients (β= –7.16±2.38; p  = 0.003 and β= –3.33±1.84; p  = 0.073, respectively). Moreover, among non-diabetic patients, IR was related to a greater decline overall (β= –0.17±0.06; p  = 0.008), and in memory (β= –0.22±0.10; p  = 0.024) and executive function (β= –0.19±0.08; p  = 0.012). The observed associations did not differ after excluding subjects with prevalent stroke or dementia. Conclusion: IR is related to subsequent poorer cognitive performance and greater cognitive decline among patients with cardiovascular disease with and without diabetes. Show more

Keywords: Cardiovascular disease, cognitive decline, cognitive impairments, insulin resistance

DOI: 10.3233/JAD-161016

Citation: Journal of Alzheimer's Disease, vol. 57, no. 2, pp. 633-643, 2017