Journal of Alzheimer's Disease - Volume 71, issue 3

Authors: Noguchi-Shinohara, Moeko | Hirako, Kohei | Fujiu, Makoto | Sagae, Masahiko | Samuta, Hikaru | Nakamura, Hiroyuki | Yamada, Masahito

Article Type: Research Article

Abstract: Background: Both cigarette smoking and diabetes mellitus are well-established risk factors for development of dementia. However, the interaction between smoking and diabetes is yet unknown. Objective: In this study, we clarify association between smoking, diabetes, and dementia risk in older adults. Methods: Participants in this study included community residents aged 65 years and older who had participated in a health checkup in 2006, followed for 10 years (n  = 9,403) and had long-term care insurance information data. Furthermore, the risk estimates of smoking status and diabetes diagnosis on dementia adjusted for the competing risk of death prior …to dementia were analyzed. Results: During follow-up, 2,647 participants developed dementia. The smoking status–diabetes interaction on development of dementia was statistically significant (p ≤0.001). Among those patients exposed to both factors, 17% of risk of development of dementia was attributable to the interaction of these factors. Current smokers with diabetes had significantly greater risks of development of dementia than never smokers without diabetes (reference): multivariable-adjusted risk of dementia in current smokers without diabetes (subdistribution hazard ratio [sHR], 1.25; 95% confidence interval [CI], 1.05–1.48); never smokers with diabetes (1.31, 1.16–1.47); and current smokers with diabetes (1.86, 1.39–2.48). However, no such association was noted for former smokers with and without diabetes. Conclusions: Current smoking, but not former smoking, was associated with increased risk of development of dementia in older adults with and without diabetes. Moreover, the synergistic effect of current smoking and diabetes on dementia was noted. Show more

Keywords: Cigarette smoking, dementia, diabetes mellitus, insurance, long-term care

DOI: 10.3233/JAD-190340

Citation: Journal of Alzheimer's Disease, vol. 71, no. 3, pp. 833-840, 2019

Authors: Mayelle, Amandine | El Haj, Mohamad | Antoine, Pascal

Article Type: Research Article

Abstract: Background: People with Alzheimer’s disease (PwAD) remain able to speak coherently about their daily life for a long time, and their level of awareness could be determined through their discourse. In a grounded-theory approach, awareness of self and awareness of disease are intertwined and can be observed through three domains: mechanisms, objects and modes of expression. Objective: Based on preliminary results, in this article, we present the ASDA (Awareness of Self and Disease Assessment), a new subjective measurement tool for awareness in PwAD. To consider its use in research and practice, we initially performed validation analyses, including internal …consistency, test-retest reliability and interrater reliability analyses. Methods: The new assessment tool consists of a semi-structured interview and ratings of 22 items divided into three categories. As part of our observational study, we assessed a sample of 28 PwAD who participated in four interviews (one every two weeks). Results: The ASDA shows good homogeneity within the domains of awareness and a certain degree of stability between two measurement times and between investigators. Missing values in the results provided information regarding awareness levels within and across the subjects. Conclusion: The results suggest that awareness could be assessed through subjective experience without reference to a comparison. Show more

Keywords: Alzheimer’s disease, anosognosia, awareness, self, self-assessment

DOI: 10.3233/JAD-190371

Citation: Journal of Alzheimer's Disease, vol. 71, no. 3, pp. 841-850, 2019

Authors: Javanshiri, Keivan | Haglund, Mattias | Englund, Elisabet

Article Type: Research Article

Abstract: Background: Research concerning the potential roles of cardiovascular disease (CaVD) and diabetes mellitus (DM) as risk factors for Lewy body disease (LBD) is limited. These disorders are, however, established risk factors for vascular dementia (VaD) and have been proposed as risk factors for Alzheimer’s disease (AD). Objective: The aim of this study was to investigate the prevalence of CaVD and DM in LBD and compare the results with previous findings in cases with AD, VaD, and mixed AD-VaD (MD). Methods: Autopsy reports at the Clinical Department of Pathology in Lund from 2001–2018 were analyzed. All cases …with a complete neuropathological diagnosis of LBD were selected, not distinguishing between subjects with clinical Parkinson disease dementia and dementia with Lewy bodies, on the condition of a clinical diagnosis of dementia. Clinical data were retrieved through the patients’ medical records and the Swedish National Diabetes Register (NDR) and compared with those of the AD, VaD, and MD cases. Results: In LBD, there was less CaVD, significantly less DM (p  = 0.002) and likewise significantly less hypertension (p  < 0.001) than in VaD. The results of the LBD group were consistent with the results of the AD group. Conclusion: Our findings of a low prevalence of CaVD and CaVD risk factors in LBD and in AD argue against the association between these risk factors and their contribution to the development of neurodegenerative diseases. Show more

Keywords: Alzheimer’s disease, autopsy, cardiovascular disease, dementia, diabetes mellitus, hypertension, Lewy body disease, risk factors, vascular

DOI: 10.3233/JAD-190485

Citation: Journal of Alzheimer's Disease, vol. 71, no. 3, pp. 851-859, 2019

Authors: Schlegel, Petr | Novotny, Michal | Klimova, Blanka | Valis, Martin

Article Type: Research Article

Abstract: Alzheimer’s disease (AD) is one of the most common forms of dementia, which cannot be cured at the moment. Therefore, researchers also look for the alternative approaches to its treatment. It is suggested that changes in human gut microbiome mediated by exercise could influence the development and progression of AD and a new term “muscle-gut-brain axis” is introduced. There is much evidence to support this assumption. The gut microbiology is closely related to a wide range of diseases of the nervous system and therefore any negative qualitative and quantitative changes in the composition of the gut microbiota can potentially contribute …to the pathophysiology of AD. Research shows that the treatment of intestinal dysbiosis with probiotics/synbiotics/eubiotics can prevent or alleviate the symptoms of these chronic neurological diseases. Studies also point to the positive effects of movement on the health of seniors. A positive correlation can be found between cognitive functions and physical stress, both in the elderly and in AD patients. Even short-term interventions with a relatively low frequency seem to produce positive results, while physical activities can be performed by using relatively simple and cost-effective means. In addition, physical activity can significantly modulate gut microbiome. Thus, it can be concluded that physical activity in humans seems to correlate with gut microbiome, which can prevent the incidence and development of AD. Show more

Keywords: Alzheimer’s disease, cognitive disorders, dementia, exercise, microbiome, physical activity, probiotics

DOI: 10.3233/JAD-190460

Citation: Journal of Alzheimer's Disease, vol. 71, no. 3, pp. 861-878, 2019

Authors: Krishtal, Jekaterina | Metsla, Kristel | Bragina, Olga | Tõugu, Vello | Palumaa, Peep

Article Type: Research Article

Abstract: Alzheimer’s disease (AD) is a currently incurable neurodegenerative disorder being the major form of dementia worldwide. AD pathology is initiated by cerebral aggregation of amyloid-β (Aβ) peptides in the form of amyloid plaques; however, the mechanism how Aβ peptide aggregates participate in the disease progression and neurodegeneration is still under debate. Human neuroblastoma cell line SH-SY5Y is a convenient cellular model, which is widely used in biochemical and toxicological studies of neurodegenerative diseases. This model can be further improved by differentiation of the cells toward more neuron-like culture using different protocols. In the current study, dbcAMP, retinoic acid with TPA, …or BDNF were used for differentiation of SH-SY5Y cells, and the resulting cultures were tested for the toxicity toward the Aβ42 peptide. The toxicity of Aβ42 peptide depended on the type of differentiated cells: RA and TPA- differentiated cells were most resistant, whereas dbcAMP and RA/BDNF- differentiated cells were more sensitive to Aβ toxicity as compared with non-differentiated cells. The differentiated cultures provide more appropriate cellular models of human origin that can be used for studies of the mechanism of Aβ pathogenesis and for a screening of compounds antagonistic to the toxicity of Aβ peptides. Show more

Keywords: Alzheimer’s disease, amyloid-β, differentiation, SH-SY5Y, toxicity

DOI: 10.3233/JAD-190705

Citation: Journal of Alzheimer's Disease, vol. 71, no. 3, pp. 879-887, 2019

Authors: Bonfiglio, Viviana | Umegaki, Hiroyuki | Kuzuya, Masafumi

Article Type: Research Article

Abstract: Background: With multimorbidity increasing among older people, polypharmacy and the use of potentially inappropriate medications (PIMs) are assuming a prominent role in the life of the geriatric population. Objective: To investigate the association of polypharmacy and PIM use with a wide range of factors in older people with mild cognitive impairment (MCI) to mild dementia. Methods: The study population comprised 160 outpatients with a Clinical Dementia Rating of 0.5–1 and a Mini-Mental State Examination score of 20–30. Patients were classified as receiving polypharmacy when they took ≥5 different medications at the same time. PIMs were identified …using the STOPP-J criteria. Cognitive, neuropsychological, nutritional, and physical function tests were performed and body measurements taken. Quality of life (QOL) was assessed using both components of the EQ-5D scale, the index score and the visual analogue scale (QOL VAS). A comorbidity index was calculated for all participants. Results: PIM use was significantly associated with lower scores on the verbal fluency (initial letters) test and QOL index. Participants receiving polypharmacy showed an increased likelihood of worse frailty status and lower QOL VAS score. The number of medications was significantly associated with a worse frailty status. Conclusion: In a geriatric population with MCI to mild dementia, PIM use was associated with lower verbal fluency (initial letters) score and lower QOL, while the presence of polypharmacy was correlated with a worse frailty status and lower QOL. The number of medicines, instead, was correlated with a worse frailty status only. Show more

Keywords: Dementia, frailty, polypharmacy, potentially inappropriate medications, quality of life

DOI: 10.3233/JAD-190284

Citation: Journal of Alzheimer's Disease, vol. 71, no. 3, pp. 889-897, 2019

Authors: Pyun, Jung-Min | Kang, Min Ju | Youn, Young Chul | Park, Young Ho | Kim, SangYun

Article Type: Research Article

Abstract: Background: Although dementia with Lewy bodies (DLB) is a degenerative disease involving irreversible pathological changes and subsequent progressive cognitive decline, some patients have presented with improved cognitive function at follow-ups. Their clinical and neuropsychological characteristics and the factors influencing this improvement remain unclear. Objective: To investigate differences in clinical and neuropsychological characteristics between DLB patients with and without cognitive improvement at a one-year follow-up, and to identify predictive factors of cognitive improvement. Methods: This retrospective study included 60 DLB patients, 28 patients in the improved group, and 32 patients in the non-improved group. A multiple linear …regression model was used to compare changes in cognitive function test scores between groups over the course of one year. Binary logistic regression analysis was performed to determine the odds ratios (ORs) of depressive symptoms as a predictor for cognitive improvement. Results: The improved group showed significant increases in immediate and delayed verbal memory function in one year over the non-improved group. We also found that baseline depressive symptoms were associated with an increased probability of cognitive improvement (OR 1.234, CI 1.043– 1.460). Conclusion: Depressive symptoms at baseline were related to a higher probability of a cognitive improvement at one-year follow-up. In addition, immediate and delayed verbal memory function showed significant improvement during one year in improved patients compared to non-improved patients. Show more

Keywords: Cognitive improvement, dementia with Lewy bodies, depressive symptoms

DOI: 10.3233/JAD-190685

Citation: Journal of Alzheimer's Disease, vol. 71, no. 3, pp. 899-905, 2019

Authors: Guglielmotto, Michela | Repetto, Ivan Enrico | Monteleone, Debora | Vasciaveo, Valeria | Franchino, Claudio | Rinaldi, Sara | Tabaton, Massimo | Tamagno, Elena

Article Type: Research Article

Abstract:  Neuroinflammation is involved in the pathogenesis of Alzheimer’s disease, and the transcription factor NF-κ B is a player in this event. We found here that the ischemic damage alone or in association with Aβ1-42 activates the NF-κ B pathway, induces an increase of BACE1 and a parallel inhibition of Uch-L1 and TREM2, both in vitro and in vivo , in Tg 5XFAD and in human brains of sporadic AD. This mechanism creates a synergistic loop that fosters inflammation. We also demonstrated a significant protection exerted by the restoration of Uch-L1 activity. The rescue of the enzyme is able …to abolish the decrease of TREM2 and the parameters of neuroinflammation. Show more

Keywords: Alzheimer’s disease, neuroinflammation, NF-kB pathway, stroke, TREM2, Uch-L1

DOI: 10.3233/JAD-190494

Citation: Journal of Alzheimer's Disease, vol. 71, no. 3, pp. 907-920, 2019

Authors: Smith, Patrick J. | Mabe, Stephanie | Sherwood, Andrew | Babyak, Michael A. | Doraiswamy, P. Murali | Welsh-Bohmer, Kathleen A. | Kraus, William | Burke, James | Hinderliter, Alan | Blumenthal, James A.

Article Type: Research Article

Abstract: Background: Greater body weight has been associated impairments in neurocognition and greater dementia risk, although the mechanisms linking weight and neurocognition have yet to be adequately delineated. Objective: To examine metabolic mechanisms underlying the association between obesity and neurocognition. Methods: We conducted a secondary analysis of weight, neurocognition, and the potentially mediating role of metabolic and inflammatory biomarkers among 160 participants from the ENLIGHTEN trial of vascular cognitive impairment, no dementia (CIND). Neurocognition was assessed using a 45-minute assessment battery assessing Executive Function, Verbal and Visual Memory. We considered three metabolic biomarkers: insulin resistance (homeostatic model …assessment [HOMA-IR]), plasma leptin, and insulin-like growth factor (IGF-1). Inflammation was assessed using C-reactive protein. Multiple regression analyses were used. Results: Participants included 160 sedentary older adults with CIND. Participants tended to be overweight or obese (mean BMI = 32.5 [SD = 4.8]). Women exhibited higher BMI (p  = 0.043), CRP (p  < 0.001), and leptin (p  < 0.001) compared with men. Higher BMI levels were associated with worse performance on measures of Executive Function (β= –0.16, p  = 0.024) and Verbal Memory (β= –0.16, p  = 0.030), but not Visual Memory (β= 0.05, p  = 0.500). Worse metabolic biomarker profiles also were associated with lower Executive Function (β= –0.12, p  = 0.050). Mediation analyses suggested leptin was a plausible candidate as a mediator between BMI and Executive Function. Conclusions: In overweight and obese adults with vascular CIND, the association between greater weight and poorer executive function may be mediated by higher leptin resistance. Show more

Keywords: Cognitive function, executive function, inflammation, insulin sensitivity, leptin, metabolic function, obesity

DOI: 10.3233/JAD-190569

Citation: Journal of Alzheimer's Disease, vol. 71, no. 3, pp. 921-929, 2019

Authors: Bangen, Katherine J. | Armstrong, Nicole M. | Au, Rhoda | Gross, Alden L.

Article Type: Research Article

Abstract: Metabolic syndrome (MetS) has been linked to increased risk of developing cognitive impairment and dementia including Alzheimer’s disease. It remains unclear whether and at what stage in the adult lifespan MetS and its components begin to alter the trajectory of cognitive performance. In the present study, 2,892 Framingham Offspring participants completed health assessments every four years since 1971 and underwent repeat neuropsychological testing from 1999 to 2014. We estimated the associations of levels and changes in cognitive trajectories with hazard of MetS using a joint growth/survival model. All models were adjusted for baseline age, sex, education, and smoking status. Findings …showed that both mid-life and late-life MetS were associated with lower level of cognitive functioning but not cognitive trajectories. Associations were strongest among those who were nondemented and apolipoprotein (APOE ) ɛ 4 noncarriers. In addition, individuals with the most rapid cognitive decline were more likely to have MetS. The pattern of results showed that associations between MetS and cognition varied, depending upon whether the sample was stratified by genetic and cognitive status and whether we considered cognitive performance as a continuous variable or examined categorical groupings. Given that mid-life MetS was associated with poorer cognition at age 55, cognitive changes may occur early during the MetS process. Our findings suggest that those with MetS are at greater risk of dementia given their lower level of cognitive functioning and also suggest that MetS may be a risk factor for decline in the absence of known risk factors including the APOE ɛ 4 allele. Show more

Keywords: Aging, Alzheimer’s disease, apolipoprotein E, cognition, diabetes, metabolic syndrome, neuropsychology, vascular risk

DOI: 10.3233/JAD-190261

Citation: Journal of Alzheimer's Disease, vol. 71, no. 3, pp. 931-943, 2019