Journal of Alzheimer's Disease - Volume 58, issue 1

Authors: Godin, Judith | Armstrong, Joshua J. | Rockwood, Kenneth | Andrew, Melissa K.

Article Type: Research Article

Abstract: Background: Frailty has been considered an antecedent and, to a lesser extent, an outcome of cognitive impairment. Both frailty and cognitive impairment are multiply determined and each is strongly related to age, making it likely that the two interact, especially as people age. In consequence, understanding their interaction and co-occurrence can offer insight into pathophysiology, prevention, and management. Objective: To examine the nature of the relationship between frailty and cognitive impairment using longitudinal data from the Survey of Health Aging and Retirement in Europe (SHARE), assessing for bidirectionality. Methods: We conducted secondary analyses using data …from the first two waves of SHARE. The sample (N = 11,941) was randomly split into two halves: one half for model development and one half for model confirmation. We used a 65 deficit Frailty Index and combined 5 cognitive deficits into a global cognitive impairment index. Cross-lagged path analysis within a structural equation modelling framework was used to examine the bi-directional relationship between the two measures. Results: After controlling for age, sex, social vulnerability, education, and initial cognitive impairment, each 0.10 increase in baseline frailty was associated with a 0.01 increase in cognitive impairment at follow-up (p  < 0.001). Likewise, each 0.1 increase in baseline cognitive impairment was associated with a 0.003 increase frailty at follow-up (p  < 0.01). Conclusion: Our findings underscore the importance of considering cognitive impairment in the context of overall health. Many people with dementia are likely to have other health problems, which need to be considered in concert to achieve optimal health outcomes. Show more

Keywords: Cognitive impairment, frail elderly, longitudinal study, social determinants of health

DOI: 10.3233/JAD-161280

Citation: Journal of Alzheimer's Disease, vol. 58, no. 1, pp. 231-242, 2017

Authors: Kunschmann, Ralf | Busse, Stefan | Frodl, Thomas | Busse, Mandy

Article Type: Research Article

Abstract: Patients suffering from cognitive decline such as mild cognitive impairment or neurodegenerative disorders including Alzheimer’s dementia, vascular dementia, frontotemporal dementia, and Lewy body dementia are often accompanied by symptoms like psychosis, depression, agitation, and apathy. Aging increases not only the prevalence of dementia but also the development of kidney disorders, which had emerged as possible risk factor of cognitive impairment and dementia. However, a contribution of renal dysfunction to psychosis associated with cognitive decline remains to be investigated. We addressed the question whether patients diagnosed with mild cognitive impairment or dementia and co-symptoms show alterations in serum parameters. Analyzing 309 …patients in total, we detected a positive correlation between the occurrence of psychotic symptoms and increased retention parameters in serum, including creatinine and urea levels and the estimated glomerular filtration rates. This was in particular detected in female patients. In male patients, psychotic symptoms were associated with an increased number of leukocytes in blood. We propose that clinicians should be aware of psychotic symptoms in patients with reduced cognitive functions that could be associated with changes in the retention parameters. Show more

Keywords: Dementia, estimated glomerular filtration rate, mild cognitive impairment, psychotic symptoms, poor renal function

DOI: 10.3233/JAD-161306

Citation: Journal of Alzheimer's Disease, vol. 58, no. 1, pp. 243-252, 2017

Authors: An, Hoyoung | Cho, Mi-Hyang | Kim, Dong-Hou | Chung, Seockhoon | Yoon, Seung-Yong

Article Type: Research Article

Abstract: Background: Intracranial accumulation of amyloid-β (Aβ) is a characteristic finding of Alzheimer’s disease (AD). It is thought to be the result of Aβ overproduction by neurons and impaired clearance by several systems, including degradation by microglia. Sleep disturbance is now considered a risk factor for AD, but studies focusing on how sleep modulates microglial handling of Aβ have been scarce. Objective: To determine whether phagocytosis and degradation of extracellular Aβ fibrils by BV2 microglial cells were impaired by treatment with orexin-A/B, a major modulator of the sleep-wake cycle, which may mimic sleep deprivation conditions. Methods: …BV2 cells were treated with orexin and Aβ for various durations and phagocytic and autophagic processes for degradation of extracellular Aβ were examined. Results: After treatment with orexin, the formation of actin filaments around Aβ fibrils, which is needed for phagocytosis, was impaired, and phagocytosis regulating molecules such as PI3K, Akt, and p38-MAPK were downregulated in BV2 cells. Orexin also suppressed autophagic flux, through disruption of the autophagosome-lysosome fusion process, resulting in impaired Aβ degradation in BV2 cells. Conclusions: Our results demonstrate that orexin can hinder clearance of Aβ through the suppression of phagocytosis and autophagic flux in microglia. This is a novel mechanism linking AD and sleep, and suggests that attenuated microglial function, due to sleep deprivation, may increase Aβ accumulation in the brain. Show more

Keywords: Actin, Alzheimer’s disease, dementia, orexin, sleep

DOI: 10.3233/JAD-170108

Citation: Journal of Alzheimer's Disease, vol. 58, no. 1, pp. 253-261, 2017

Authors: Xie, Bing | Liu, Zanchao | Liu, Wenxuan | Jiang, Lei | Zhang, Rui | Cui, Dongsheng | Zhang, Qingfu | Xu, Shunjiang

Article Type: Research Article

Abstract: Alzheimer’s disease (AD) is a complex multifactorial disease influenced by both genetic and epigenetic factors. This study was aimed to evaluate the interaction between brain-derived neurotrophic factor (BDNF ) promoter methylation status and tag single nucleotide polymorphisms (tag SNPs) on amnestic mild cognitive impairment (aMCI) and its conversion to AD. A total of 506 aMCI patients and 728 cognitive normal controls were included in the cross-sectional analysis. Patients (n  = 458) from aMCI cohort were selected in the 5-year longitudinal study and classified into two groups: aMCI-stable group (n  = 330) and AD-conversion group (n  = 128). BDNF promoter methylation was detected …by bisulfite-PCR amplification and pyrosequencing. Seven tag SNPs were genotyped by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Elevation of BDNF promoter methylation status was associated with aMCI and AD conversion. The higher methylation levels at CpG5 site showed significant main interactive effects between group and time (F  = 8.827, p  = 0.005). Genetic analysis revealed rs2030324 and rs6265 were associated with aMCI and rs6265 was associated with AD conversion. The interaction between DNA methylation of CpG5 and AA genotype of rs6265 had a risk role in the development of aMCI (p  = 0.019, OR = 1.233, 95% CI: 1.117–1.303) and its progression to AD (p  = 0.003, OR = 1.399, 95% CI: 1.198–1.477). The interactions between DNA methylation (CpG5) of the BDNF gene promoter and the tag SNP (rs6265) play important roles in the etiology of aMCI and its conversion to AD. Show more

Keywords: Alzheimer’s disease, amnestic mild cognitive impairment, BDNF, DNA methylation, follow-up study, Tag SNPs

DOI: 10.3233/JAD-170007

Citation: Journal of Alzheimer's Disease, vol. 58, no. 1, pp. 263-274, 2017

Authors: Mahinrad, Simin | Vriend, Annelotte E. | Jukema, J. Wouter | van Heemst, Diana | Sattar, Naveed | Blauw, Gerard Jan | Macfarlane, Peter W. | Clark, Elaine N. | de Craen, Anton J.M. | Sabayan, Behnam

Article Type: Research Article

Abstract: Background: Patients with advanced heart failure run a greater risk of dementia. Whether early cardiac structural changes also associate with cognitive decline is yet to be determined. Objective: We tested whether left ventricular hypertrophy (LVH) derived from electrocardiogram associates with cognitive decline in older subjects at risk of cardiovascular disease. Methods: We included 4,233 participants (mean age 75.2 years, 47.8% male) from PROSPER (PROspective Study of Pravastatin in the Elderly at Risk). LVH was assessed from baseline electrocardiograms by measuring the Sokolow-Lyon index. Higher levels of Sokolow-Lyon index indicate higher degrees of LVH. Cognitive domains …involving selective attention, processing speed, and immediate and delayed memory were measured at baseline and repeated during a mean follow-up of 3.2 years. Results: At baseline, LVH was not associated with worse cognitive function. During follow-up, participants with higher levels of LVH had a steeper decline in cognitive function including in selective attention (p  = 0.009), processing speed (p  = 0.010), immediate memory (p  < 0.001), and delayed memory (p  = 0.002). These associations were independent of cardiovascular risk factors, co-morbidities, and medications. Conclusion: LVH assessed by electrocardiogram associates with steeper decline in cognitive function of older subjects independent of cardiovascular risk factors and co-morbidities. This study provides further evidence on the link between subclinical cardiac structural changes and cognitive decline in older subjects. Show more

Keywords: Cardiovascular disease, cognitive function, elderly, left ventricular hypertrophy

DOI: 10.3233/JAD-161150

Citation: Journal of Alzheimer's Disease, vol. 58, no. 1, pp. 275-283, 2017

Authors: Edwards, Jodi D.

Article Type: Article Commentary

Abstract: Multiple cardiac pathologies have been shown to contribute to progressive cognitive decline and dementia in elderly populations, including left ventricular hypertrophy (LVH), a marker of prolonged exposure to hypertension. Although associations between chronic hypertension and cognitive function are thought to be mediated primarily by these end organ effects, there is increasing evidence that early changes in cardiac structure and function, such as LVH, may independently contribute to cognitive decline and impairment. In the current issue of the Journal of Alzheimer’s Disease , Mahinrad and colleagues report important new findings on the association between LVH and cognitive function that are incremental …to cardiovascular risk and co-morbidity, including hypertension. Emerging evidence that early changes in cardiac structure and function may independently contribute to cognitive decline in elderly populations has resulted in an increased interest in these preclinical substrates as potential treatment targets for the prevention of cognitive decline and in their putative contributions to the pathogenesis of dementia. Show more

Keywords: Cardiac dysfunction, cognition, hypertension, left ventricular hypertrophy

DOI: 10.3233/JAD-170234

Citation: Journal of Alzheimer's Disease, vol. 58, no. 1, pp. 285-288, 2017