Journal of Alzheimer's Disease - Volume 52, issue 3

Authors: Vercambre, Marie-Noël | Okereke, Olivia I. | Kawachi, Ichiro | Grodstein, Francine | Kang, Jae H.

Article Type: Research Article

Abstract: To investigate whether a positive transition into retirement may be associated with later cognitive aging, we included a subset of 4,926 Nurses’ Health Study participants who retired from work at ages 60–69, then provided a subjective assessment of the change in overall quality of life (QOL) with retirement. Subsequently (range: 1 month to 4.7 years later), when all were aged 70+ years, they completed a baseline telephone cognitive battery evaluating global cognition, episodic memory, and executive function. They had up to three follow-up cognitive assessments. Controlling for various occupational factors before retirement and socioeconomic, lifestyle, and health-related factors as of …the baseline cognitive assessment, we used generalized linear models for repeated measures to estimate mean differences in rates of cognitive decline across categories of QOL transition at retirement: “worse”, “same”, or “better”. Over a median 6 years of follow-up, the global cognitive score change was –0.123 on average. Compared with women who reported no change in QOL at retirement (31%), women who reported improvement (61%) showed a significantly slower rate of cognitive decline (difference = +0.011 95% CI = 0.004, 0.019). This mean difference was equivalent to that observed between women who were 2 years apart in age. No significant differences in cognitive decline rates were observed for the women who reported worsened QOL (8%). Secondary analyses to address possible reverse causation showed robust associations. A positive transition into retirement was associated with better maintenance of cognitive function over time in aging women. These findings need to be replicated in other populations. Show more

Keywords: Aging, cognition, cohort studies, epidemiology, quality of life, retirement

DOI: 10.3233/JAD-150867

Citation: Journal of Alzheimer's Disease, vol. 52, no. 3, pp. 887-898, 2016

Authors: Huang, Han-Chang | Zheng, Bo-Wen | Guo, Yu | Zhao, Jian | Zhao, Jiang-Yan | Ma, Xiao-Wei | Jiang, Zhao-Feng

Article Type: Research Article

Abstract: Epidemiological data imply links between the increasing incidences of Alzheimer’s disease (AD) and type 2 diabetes mellitus. In this study, an AD rat model was established by combining treatments with intracerebroventricular streptozotocin (icv-STZ) and subcutaneous D-galactose, and the effects of curcumin on depressing AD-like symptoms were investigated. In the AD model group, rats were treated with icv-STZ in each hippocampus with 3.0 mg/kg of bodyweight once and then were subcutaneously injected with D-galactose daily (125 mg/kg of bodyweight) for 7 weeks. In the curcumin-protective group, after icv-STZ treatment, rats were treated with D-galactose (the same as in the AD model group) and …intraperitoneally injected with curcumin daily (10 mg/kg of bodyweight) for 7 weeks. Vehicle-treated rats were treated as control. Compared with the vehicle control, the amount of protein carbonylation and glutathione in liver, as well as malondialdehyde in serum, were upregulated but glutathione peroxidase activity in blood was downregulated in the AD model group. The shuttle index and locomotor activity of rats in the AD model group were decreased compared with the vehicle control group. Furthermore, AD model rats showed neuronal damage and neuron loss with formation of amyloid-like substances and neurofibrillary tangles, and the levels of both β-cleavage of AβPP and phosphorylation of tau (Ser396) were significantly increased compared with the vehicle control group. Notably, compared with the AD model group, oxidative stress was decreased and the abilities of active avoidance and locomotor activity were improved, as well as attenuated neurodegeneration, in the curcumin-protective group. These results imply the applications of this animal model for AD research and of curcumin in the treatment of AD. Show more

Keywords: Alzheimer’s disease, animal model, curcumin, D-galactose, neurodegeneration, streptozotocin

DOI: 10.3233/JAD-150872

Citation: Journal of Alzheimer's Disease, vol. 52, no. 3, pp. 899-911, 2016

Authors: Zhan, Yafeng | Ma, Jianhua | Alexander-Bloch, Aaron F. | Xu, Kaibin | Cui, Yue | Feng, Qianjin | Jiang, Tianzi | Liu, Yong | for the Alzheimer’s Disease Neuroimaging Initiative

Article Type: Research Article

Abstract: Alzheimer’s disease (AD) is associated with abnormal resting-state network (RSN) architecture of the default mode network (DMN), the dorsal attention network (DAN), the executive control network (CON), the salience network (SAL), and the sensory-motor network (SMN). However, little is known about the disrupted intra- and inter-network architecture in mild cognitive impairment (MCI). Here, we employed a priori defined regions of interest to investigate the intra- and inter-network functional connectivity profiles of these RSNs in longitudinal participants, including normal controls (n  = 23), participants with early MCI (n  = 26), and participants with late MCI (n  = 19). We found longitudinal alterations of …functional connectivity within the DMN, where they were correlated with variation in cognitive ability. The SAL as well as the interaction between the DMN and the SAL were disrupted in MCI. Furthermore, our results demonstrate that longitudinal alterations of functional connectivity are more profound in earlier stages as opposed to later stages of the disease. The increased severity of cognitive impairment is associated with increasingly altered RSN connectivity patterns, suggesting that disruptions in functional connectivity may contribute to cognitive dysfunction and may represent a potential biomarker of impaired cognitive ability in MCI. Earlier prevention and treatment may help to delay disease progression to AD. Show more

Keywords: Default mode network, early mild cognitive impairment, late mild cognitive impairment, resting-state network, salience network

DOI: 10.3233/JAD-160008

Citation: Journal of Alzheimer's Disease, vol. 52, no. 3, pp. 913-927, 2016

Authors: Vandepitte, Sophie | Van Den Noortgate, Nele | Putman, Koen | Verhaeghe, Sofie | Faes, Kristof | Annemans, Lieven

Article Type: Research Article

Abstract: Background: Dementia is known as a major public health problem affecting both patients and caregivers, and placing a high financial strain upon society. In community-dwelling patients, it is important to support informal caregivers in order to help them sustain their demanding role. Previous reviews about effectiveness of such supporting strategies often included a small number of studies, focused only on particular supportive types, particular outcomes, or solely on caregivers. Objective: A general systematic review was conducted investigating effectiveness of different supportive strategies on at least the well-being of the caregiver or the care-recipient. Methods: A …systematic literature search was conducted in Web of Science and PubMed. An adapted version of the Downs and Black (1998) checklist was used to assess methodological quality. A new classification was developed to group different types of caregiver support. Results: Fifty-three papers met the inclusion criteria. Although 87% of the interventions were to some extent effective, methods and findings were rather inconsistent. Psychoeducational interventions generally lead to positive outcomes for caregivers, and delay permanent institutionalization of care-recipients. Cognitive behavioral therapy decreases dysfunctional thoughts among caregivers. Occupational therapy decreases behavioral problems among patients and improves self-efficacy of caregivers. In general, those interventions tailored on individual level generate better outcomes. Comparative research on respite care was very rare. Conclusions: Despite methodological inconsistency, supporting caregivers appears to be an effective strategy often improving well-being of caregiver or care-recipient and resulting in additional benefits for society. However, there is a need for more research on the (cost)-effectiveness of respite care. Show more

Keywords: Alzheimer’s disease, caregiver, dementia, effectiveness, support

DOI: 10.3233/JAD-151011

Citation: Journal of Alzheimer's Disease, vol. 52, no. 3, pp. 929-965, 2016

Authors: Connors, Michael H. | Ames, David | Boundy, Karyn | Clarnette, Roger | Kurrle, Sue | Mander, Alastair | Ward, John | Woodward, Michael | Brodaty, Henry

Article Type: Research Article

Abstract: Background: Dementia is a terminal illness. While various baseline characteristics of patients, such as age, sex, and dementia severity, are known to predict mortality, little research has examined how changes in patients’ symptoms over time predict survival. There are also limited data on patients seen in memory clinics, as opposed to other health care settings, and whether antipsychotic medications are associated with mortality in dementia once patients’ demographic and clinical features are controlled for. Objective: To identify predictors of mortality in patients with dementia. Method: Of 970 patients recruited from nine memory clinics around Australia, …779 patients had dementia at baseline. Patients completed measures of dementia severity, cognition, functional ability, neuropsychiatric symptoms, caregiver burden, and medication use at baseline and at regular intervals over a three-year period. Mortality data were obtained from state registries eight years after baseline. Results: Overall, 447 (57.4%) of the patients with dementia died within the eight years. Older age, male sex, more severe dementia and functional impairment at baseline, greater decline in dementia severity and functional impairment over six months, taking a larger number of medications, and use of atypical antipsychotic medication predicted earlier mortality. Conclusions: The findings confirm that demographic and diagnostic features predict the survival of patients with dementia. Importantly, the findings indicate that changes in dementia severity and functional impairment over time predict mortality independently of baseline levels, and provide further evidence for the higher mortality risk of patients taking antipsychotic medications. Show more

Keywords: Death, dementia, longitudinal study, mortality, predictors

DOI: 10.3233/JAD-150946

Citation: Journal of Alzheimer's Disease, vol. 52, no. 3, pp. 967-974, 2016

Authors: Colin, Julie | Allouche, Ahmad | Chauveau, Fabien | Corbier, Catherine | Pauron-Gregory, Lynn | Lanhers, Marie-Claire | Claudepierre, Thomas | Yen, Frances T. | Oster, Thierry | Malaplate-Armand, Catherine

Article Type: Research Article

Abstract: Oligomeric amyloid-β (Aβ) peptide contributes to impaired synaptic connections and neurodegenerative processes, and as such, represents a primary therapeutic target for Alzheimer’s disease (AD)-modifying approaches. However, the lack of efficacy of drugs that inhibit production of Aβ demonstrates the need for a better characterization of its toxic effects, both on synaptic and neuronal function. Here, we used conditioned medium obtained from recombinant HEK-AβPP cells expressing the human amyloid-β protein precursor (Aβ-CM), to investigate Aβ-induced neurotoxic and synaptotoxic effects. Characterization of Aβ-CM revealed that it contained picomolar amounts of cell-secreted Aβ in its soluble form. Incubation of primary cortical neurons with …Aβ-CM led to significant decreases in synaptic protein levels as compared to controls. This effect was no longer observed in neurons incubated with conditioned medium obtained from HEK-AβPP cells grown in presence of the γ-secretase inhibitor, Semagacestat or LY450139 (LY-CM). However, neurotoxic and pro-apoptotic effects of Aβ-CM were only partially prevented using LY-CM, which could be explained by other deleterious compounds related to chronic oxidative stress that were released by HEK-AβPP cells. Indeed, full neuroprotection was observed in cells exposed to LY-CM by additional treatment with the antioxidant resveratrol, or with the pluripotent n -3 polyunsaturated fatty acid docosahexaenoic acid. Inhibition of Aβ production appeared necessary but insufficient to prevent neurodegenerative effects associated with AD due to other neurotoxic compounds that could exert additional deleterious effects on neuronal function and survival. Therefore, association of various types of protective agents needs to be considered when developing strategies for AD treatment. Show more

Keywords: Alzheimer’s disease, cell-generated Aβ peptide, neuronal apoptosis, neuroprotection, oxidative stress, synaptic proteins

DOI: 10.3233/JAD-151110

Citation: Journal of Alzheimer's Disease, vol. 52, no. 3, pp. 975-987, 2016

Authors: Iaccarino, Leonardo | Marelli, Sara | Iannaccone, Sandro | Magnani, Giuseppe | Ferini-Strambi, Luigi | Perani, Daniela

Article Type: Research Article

Abstract: Background/Objective: To evaluate the prevalence of REM sleep behavior disorder (RBD) in a sample of Dementia with Lewy Bodies (DLB) and Alzheimer’s Disease (AD) patients and compare the patterns of brain glucose metabolism in DLB patients with or without the sleep disturbances. Methods: In this retrospective study, the presence of probable RBD was ascertained for 27 clinically diagnosed DLB patients and 11 AD patients by a self-administered RBD Single-Question Screen (RBD1Q), followed by a sleep structured interview by experts in sleep disorders blinded to clinical information. For 18 F-FDG-PET metabolic comparisons, we considered an additional 13 DLB …patients with negative history for sleep disturbance. We performed DLB within-group comparisons covarying for age and disease duration. Results: The RBD1Q questionnaire identified 20 out of 27 DLB RBD+ and 7 out of 27 DLB RBD–. None of the AD patients was positive to RBD1Q test. 18 F-FDG-PET hypometabolism at the single- and group-level tested by means of an optimized SPM approach revealed the typical DLB metabolic pattern. Each DLB patient showed a predominant occipital hypometabolism. The SPM voxel-based comparisons revealed significant brain metabolic differences, namely a more severe metabolic decrease in DLB RBD+ in the dorsolateral and medial frontal regions, left precuneus, bilateral superior parietal lobule and rolandic operculum, and amygdala. Discussion: We found a high prevalence of RBD in DLB and none in AD, as identified by the RBD1Q questionnaire, indicating its utility in clinical practice. DLB patients with or without RBD show different hypometabolism patterns that might reflect differences in underlying pathology. Show more

Keywords: Brain metabolism, dementia, dementia with Lewy bodies, 18F-FDG-PET, REM sleep behavior disorder, sleep

DOI: 10.3233/JAD-151000

Citation: Journal of Alzheimer's Disease, vol. 52, no. 3, pp. 989-997, 2016

Authors: Conde-Sala, Josep L. | Turró-Garriga, Oriol | Portellano-Ortiz, Cristina | Viñas-Diez, Vanesa | Gascón-Bayarri, Jordi | Reñé-Ramírez, Ramón

Article Type: Research Article

Abstract: The objective was to analyze the factors that influence self-perceived quality of life (QoL) in patients with Alzheimer’s disease (AD), contrasting two different longitudinal models. A total of 127 patients were followed up over 24 months. The instruments applied were: Quality of Life in Alzheimer’s Disease scale (QoL-AD), Geriatric Depression Scale-15, Anosognosia Questionnaire-Dementia, Disability Assessment in Dementia, Neuropsychiatric Inventory, and the Mini-Mental State Examination. Two models for grouping patients were tested: 1) Baseline score on the QoL-AD (QoL-Baseline), and 2) Difference in QoL-AD score between baseline and follow-up (QoL-Change). Generalized estimating equations were used to analyze longitudinal data, and multinomial …regression analyses were performed. Over the follow-up period the QoL-Baseline model showed greater variability between groups (Wald χ 2  = 172.3, p  < 0.001) than did the QoL-Change model (Wald χ 2  = 1.7, p  = 0.427). In the QoL-Baseline model the predictive factors were greater depression (odds ratio [OR] = 1.20; 95% CI: 1.00– 1.45) and lower functional ability (OR = 0.92; 95% CI: 0.85– 0.99) for the Low QoL group (< 33 QoL-AD), and less depression (OR = 0.68; 95% CI: 0.52– 0.88), more anosognosia (OR = 1.07; 95% CI: 1.01– 1.13), and fewer neuropsychiatric symptoms (OR = 0.95; 95% CI: 0.91– 0.99) for the High-QoL group (>37 QoL-AD). The model based on baseline scores (QoL-Baseline) was better than the QoL-Change model in terms of identifying trajectories and predictors of QoL in AD. Show more

Keywords: Alzheimer’s disease, analytic models, anosognosia, depression, longitudinal study, quality of life

DOI: 10.3233/JAD-160040

Citation: Journal of Alzheimer's Disease, vol. 52, no. 3, pp. 999-1012, 2016

Authors: Zahodne, Laura B. | Schupf, Nicole | Brickman, Adam M. | Mayeux, Richard | Wall, Melanie M. | Stern, Yaakov | Manly, Jennifer J.

Article Type: Research Article

Abstract: Background: Previous research has identified multiple risk and protective factors for late onset Alzheimer’s disease (LOAD). However, it is not known whether these risk and protective factors differ for individuals who are cognitively stable versus those already experiencing declines. Objective: This study examined how dementia risk factors differ across subgroups of older adults defined by memory trajectory. This line of research may lead to more individualized risk profiles. Methods: Risk factors for incident LOAD were compared across previously-validated groups of older adults exhibiting different memory trajectories (“Stable-High,” “Stable-Low,” “Decliner,” “Rapid Decliner”) using stratified Cox regressions. Participants …included 2,593 racially/ethnically diverse older adults (mean age of 76 at study entry) in the Washington Heights-Inwood Columbia Aging Project. Results: Predictors of incident dementia differed across trajectory groups: older age only incurred independent risk in stable groups, education did not incur independent protection in the rapidly declining group, depression only incurred independent risk in the stable-low group, stroke incurred independent risk in the two extreme groups, and APOE -ɛ 4 only incurred independent risk in the rapidly declining group. Conclusion: The finding that different risk factors for LOAD were associated with specific memory trajectories may reflect the existence of resilience or vulnerability factors that modify the individual influences of risk/protective factors. This study highlights the utility of considering interactions between dementia risk factors and a patient’s unique cognitive history. Show more

Keywords: Aging, Alzheimer’s disease, dementia, memory, neuropsychology

DOI: 10.3233/JAD-151114

Citation: Journal of Alzheimer's Disease, vol. 52, no. 3, pp. 1013-1020, 2016

Authors: Xu, Xin | Hilal, Saima | Collinson, Simon L. | Chan, Qun Lin | Yi Chong, Eddie Jun | Ikram, Mohammad Kamran | Venketasubramanian, Narayanaswamy | Cheng, Ching-Yu | Wong, Tien Yin | Chen, Christopher Li-Hsian

Article Type: Research Article

Abstract: Background: A total cerebrovascular disease (CeVD) burden scale was previously constructed and an inverse association of CeVD burden and cognition was found. However, the generalizability of the CeVD scale has not been examined. Objective: The objective was to validate the previously constructed total CeVD burden scale by establishing its association with cognitive function and dementia diagnosis in a community sample. Methods: Eligible participants were assessed on an extensive neuropsychological battery and underwent MRI scans. The total CeVD scale, comprising markers of both small- and large-vessel diseases, was derived according to previously described criteria. Association of …total CeVD burden with global and domain-based cognitive performance and dementia diagnostic utility of the scale was established. Results: A total of 863 participants were included in the analysis. A stepwise association of CeVD burden score with global and domain-specific cognitive function was found. Per score increase on the total CeVD burden scale was associated with 3.6 (95% CI = 2.1–6.4) times higher odds of dementia compared to dementia-free. Discussion: The total CeVD burden scale is associated with cognition and dementia in a community sample. Longitudinal studies are required to establish the predictive ability of this scale. Show more

Keywords: Cerebrovascular disease, cognition, dementia, diagnosis, vascular burden

DOI: 10.3233/JAD-160139

Citation: Journal of Alzheimer's Disease, vol. 52, no. 3, pp. 1021-1028, 2016