Journal of Alzheimer's Disease - Volume 99, issue 2

Authors: Bulycheva, Irina | Watanabe, Yumi | Kitamura, Kaori | Kabasawa, Keiko | Saito, Toshiko | Takahashi, Akemi | Kobayashi, Ryosaku | Oshiki, Rieko | Takachi, Ribeka | Tsugane, Shoichiro | Yamazaki, Osamu | Watanabe, Kei | Nakamura, Kazutoshi

Article Type: Research Article

Abstract: Background: Sleep is a potentially modifiable factor associated with dementia, including Alzheimer’s disease, but current evidence supporting this is insufficient. Objective: This study aimed to determine whether sleep duration and bedtime patterns are associated with the risk of dementia among middle-aged and older people. Methods: This cohort study had an eight-year follow-up period. Participants were 13,601 community-dwelling people aged 40–74 years living in Murakami (Niigata, Japan). Data were collected using a self-administered questionnaire. Predictors were self-reported sleep duration and bedtime, and the outcome was newly-diagnosed dementia determined using the long-term care insurance database. Covariates were demographic …characteristics, body mass index, smoking, alcohol consumption, total physical activity, insomnia symptoms, disease history, and either bedtime or sleep duration. Cox proportional hazard models were used to calculate hazard ratios (HRs). Results: The mean age of participants at baseline was 59.2 years. Over a mean follow-up period of 8.0 years, 319 cases of dementia were observed. A long self-reported sleep duration relative to the reference sleep duration (7 hours) was associated with increased dementia risk, with the “8 hours” group (adjusted HR = 1.30, 95% CI:0.99–1.73) and “≥9 hours” group (adjusted HR = 1.46, 95% CI:1.00–2.15) having an increased risk (marginally significant) relative to the reference group. Early bedtime was associated with increased dementia risk (adjusted p for trend = 0.0010), with the “21 : 00 or earlier” group (adjusted HR = 1.61, 95% CI:1.14–2.28) having an increased risk relative to the reference (“23 : 00”). Conclusions: A long self-reported sleep duration and early bedtime are both associated with increased dementia risk in middle-aged and older people Show more

Keywords: Alzheimer’s disease, bedtime, cohort study, dementia, sleep duration

DOI: 10.3233/JAD-231104

Citation: Journal of Alzheimer's Disease, vol. 99, no. 2, pp. 535-547, 2024

Authors: Asada, Takashi | Tanaka, Mieko | Araki, Wataru | Jon Lebowitz, Adam | Kakuma, Tatsuyuki

Article Type: Research Article

Abstract: Background: Interventions to prevent or attenuate cognitive decline and dementia in older adults are becoming increasingly important. Recently, cognitive training exercise can be via computer or mobile technology for independent or home use. Recent meta-analysis has reported that Computerized Cognitive Training (CCT) is effective at enhancing cognitive function in healthy older and Alzheimer’s disease adults, although little is known about individual characteristics of each computerized program. Objective: We developed a new CCT named Brain Training Based on Everyday Living (BTEL) to enhance cognitive capacity for Instrumental Activities of Daily Living (IADL). We aim to evaluate the efficacy of …the BTEL among cognitively healthy old individuals and to explore its concurrent validity and construct concept. Methods: We conducted a double-blind study where 106 individuals aged 65 years and older (intervened = 53, control = 53) worked on the active and placebo tasks three times a week over three months (clinical trial: UMIN000048730). The main results were examined using ANCOVA and calculating correlation coefficients. Results: We found no effect on total score of the three tests; however, there was significant effect for the BTEL on: recognition in MMSE, and immediate recall in HDSR. The tasks are associated with prefrontal cortex. In addition, correlations indicated that each BTEL domain had some validity as a cognitive assessment tool. Different from previous CCT, we determined the neuropsychological characteristics of specific cognitive tasks of the BTEL to a certain degree. Conclusions: We found modest efficacy of the BTEL in cognitively healthy old individuals and confirmed its concurrent validity and the conceptual construct. Show more

Keywords: Activities of daily living, Alzheimer’s disease, brain training, mild cognitive impairment, neuropsychology

DOI: 10.3233/JAD-231165

Citation: Journal of Alzheimer's Disease, vol. 99, no. 2, pp. 549-558, 2024

Authors: Scharf, Annelie | Kleinke, Fabian | Michalowsky, Bernhard | Rädke, Anika | Pfitzner, Stefanie | Mühlichen, Franka | Buchholz, Maresa | van den Berg, Neeltje | Hoffmann, Wolfgang

Article Type: Research Article

Abstract: Background: The healthcare needs of People living with Dementia (PlwD) (such as Alzheimer’s disease) are often unmet. Information about the needs of community-dwelling PlwD and their association with sociodemographic and clinical characteristics is needed to fill the knowledge gap regarding factors influencing unmet needs among PlwD and to conduct a comprehensive needs assessment to develop tailored interventions. Objective: To describe sociodemographic and clinical characteristics of the InDePendent study population with particular reference to determinants of unmet needs. Methods: We analyzed baseline data of the multi-centre cluster-randomized controlled trial (InDePendent) using descriptive statistics to describe patients’ sociodemographic …and clinical characteristics and Poisson regression models to predict unmet needs, separated by sex. Data were collected personally via face-to-face interviews. Results: Most of the n  = 417 participating PlwD were mild to moderately cognitively impaired, were not depressed, had an average of 10.8 diagnoses, took 6.7 medications, and had, on average, 2.4 unmet needs (62% of PlwD had at least one unmet need) measured by the Camberwell Assessment of Need for the Elderly (CANE). Low social support, a high body-mass-index, a lower education, functional impairment, and worse health status were associated with more unmet needs, regardless of sex. In women, higher unmet needs were associated with more depressive symptoms, a poor financial situation, living alone and not being recently treated by a general practitioner. In males, unmet needs increased with the number of medications taken. Conclusions: PlwD had a broad array of unmet healthcare needs, indicating primary healthcare provision improvement potentials. The results underscore the significance of early assessment of patient’s clinical characteristics and unmet needs as a basis for individualized gender-sensible intervention strategies.∥ClinicalTrials.gov Identifier: NCT04741932, Registered on February 5, 2021 Show more

Keywords: KeywordsAlzheimer’s disease, Camberwell Assessment of Need for the Elderly (CANE), dementia, elderly population, health services research, needs assessment, people with dementia, primary care, randomized controlled trial

DOI: 10.3233/JAD-231173

Citation: Journal of Alzheimer's Disease, vol. 99, no. 2, pp. 559-575, 2024

Authors: Li, Yaoru | Yang, Ziying | Zhang, Yanxin | Liu, Fang | Xu, Jing | Meng, Yaping | Xing, Gebeili | Ruan, Xuqin | Sun, Jun | Zhang, Nan

Article Type: Research Article

Abstract: Background: Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD) account for the vast majority of neurodegenerative dementias. AD and FTLD have different clinical phenotypes with a genetic overlap between them and other dementias. Objective: This study aimed to identify the genetic spectrum of sporadic AD and FTLD in the Chinese population. Methods: A total of 74 sporadic AD and 29 sporadic FTLD participants were recruited. All participants underwent whole-exome sequencing (WES) and testing for a hexanucleotide expansion in C9orf72 was additionally performed for participants with negative WES results. Results: Four known pathogenic or …likely pathogenic variants, including PSEN1 (p.G206D), MAPT (p.R5H), LRRK2 (p.W1434*), and CFAP43 (p.C934*), were identified in AD participants, and 1 novel pathogenic variant of ANXA11 (p.D40G) and two known likely pathogenic variants of MAPT (p.D177V) and TARDBP (p.I383V) were identified in FTLD participants. Twenty-four variants of uncertain significance as well as rare variants in risk genes for dementia, such as ABCA7, SORL1, TRPM7, NOS3, MPO , and DCTN1 , were also found. Interestingly, several variants in participants with semantic variant primary progressive aphasia were detected. However, no participants with C9orf72 gene variants were found in the FTLD cohort. Conclusions: There was a high frequency of genetic variants in Chinese participants with sporadic AD and FTLD and a complex genetic overlap between these two types of dementia and other neurodegenerative diseases. Show more

Keywords: Alzheimer’s disease, frontotemporal lobar degeneration, variant, whole-exome sequencing

DOI: 10.3233/JAD-231361

Citation: Journal of Alzheimer's Disease, vol. 99, no. 2, pp. 577-593, 2024

Authors: García-Carlos, Carlos Antonio | Basurto-Islas, Gustavo | Perry, George | Mondragón-Rodríguez, Siddhartha

Article Type: Research Article

Abstract: Background: Cognitive deficits observed in Alzheimer’s disease (AD) patients have been correlated with altered hippocampal activity. Although the mechanism remains under extensive study, neurofibrillary tangles and amyloid plaques have been proposed as responsible for brain activity alterations. Aiming to unveil the mechanism, researchers have developed several transgenic models of AD. Nevertheless, the variability in hippocampal oscillatory alterations found in different genetic backgrounds and ages remains unclear. Objective: To assess the oscillatory alterations in relation to animal developmental age and protein inclusion, amyloid-β (Aβ) load, and abnormally phosphorylated tau (pTau), we reviewed and analyzed the published data on peak …power, frequency, and quantification of theta-gamma cross-frequency coupling (modulation index values). Methods: To ensure that the search was as current as possible, a systematic review was conducted to locate and abstract all studies published from January 2000 to February 2023 that involved in vivo hippocampal local field potential recording in transgenic mouse models of AD. Results: The presence of Aβ was associated with electrophysiological alterations that are mainly reflected in power increases, frequency decreases, and lower modulation index values. Concomitantly, pTau accumulation was associated with electrophysiological alterations that are mainly reflected in power decreases, frequency decreases, and no significant alterations in modulation index values. Conclusions: In this study, we showed that electrophysiological parameters are altered from prodromal stages to the late stages of pathology. Thus, we found that Aβ deposition is associated with brain network hyperexcitability, whereas pTau deposition mainly leads to brain network hypoexcitability in transgenic models Show more

Keywords: Alzheimer’s disease, amyloid-β, cross-frequency coupling, hippocampus, network hyperexcitability, network hypoexcitability, oscillatory activity, phospho-tau

DOI: 10.3233/JAD-231365

Citation: Journal of Alzheimer's Disease, vol. 99, no. 2, pp. 595-607, 2024

Authors: Horvath, Alexandra | Quinlan, Patrick | Eckerström, Carl | Åberg, N. David | Wallin, Anders | Svensson, Johan

Article Type: Research Article

Abstract: Background: Insulin-like growth factor-I (IGF-I) regulates myelin, but little is known whether IGF-I associates with white matter functions in subjective and objective mild cognitive impairment (SCI/MCI) or Alzheimer’s disease (AD). Objective: To explore whether serum IGF-I is associated with magnetic resonance imaging – estimated brain white matter volumes or cognitive functions. Methods: In a prospective study of SCI/MCI (n  = 106) and AD (n  = 59), we evaluated the volumes of the total white matter, corpus callosum (CC), and white matter hyperintensities (WMHs) as well as Mini-Mental State Examination (MMSE), Trail Making Test A and B (TMT-A/B), and …Stroop tests I–III at baseline, and after 2 years. Results: IGF-I was comparable in SCI/MCI and AD (113 versus 118 ng/mL, p  = 0.44). In SCI/MCI patients, the correlations between higher baseline IGF-I and greater baseline and 2-year volumes of the total white matter and total CC lost statistical significance after adjustment for intracranial volume and other covariates. However, after adjustment for covariates, higher baseline IGF-I correlated with better baseline scores of MMSE and Stroop test II in SCI/MCI and with better baseline results of TMT-B and Stroop test I in AD. IGF-I did not correlate with WMH volumes or changes in any of the variables. Conclusions: Both in SCI/MCI and AD, higher IGF-I was associated with better attention/executive functions at baseline after adjustment for covariates. Furthermore, the baseline associations between IGF-I and neuropsychological test results in AD may argue against significant IGF-I resistance in the AD brain. Show more

Keywords: Alzheimer’s disease, attention, corpus callosum, executive function, insulin-like growth factor-I, magnetic resonance imaging, mild cognitive impairment, speed, subjective mild cognitive impairment, white matter hyperintensities

DOI: 10.3233/JAD-231026

Citation: Journal of Alzheimer's Disease, vol. 99, no. 2, pp. 609-622, 2024

Authors: Memon, Ashar | Moore, Jasmine A. | Kang, Chris | Ismail, Zahinoor | Forkert , Nils D.

Article Type: Research Article

Abstract: Background: While various biomarkers of Alzheimer’s disease (AD) have been associated with general cognitive function, their association to visual-perceptive function across the AD spectrum warrant more attention due to its significant impact on quality of life. Thus, this study explores how AD biomarkers are associated with decline in this cognitive domain. Objective: To explore associations between various fluid and imaging biomarkers and visual-based cognitive assessments in participants across the AD spectrum. Methods: Data from participants (N  = 1,460) in the Alzheimer’s Disease Neuroimaging Initiative were analyzed, including fluid and imaging biomarkers. Along with the Mini-Mental State Examination …(MMSE), three specific visual-based cognitive tests were investigated: Trail Making Test (TMT) A and TMT B, and the Boston Naming Test (BNT). Locally estimated scatterplot smoothing curves and Pearson correlation coefficients were used to examine associations. Results: MMSE showed the strongest correlations with most biomarkers, followed by TMT-B. The p-tau181/Aβ1–42 ratio, along with the volume of the hippocampus and entorhinal cortex, had the strongest associations among the biomarkers. Conclusions: Several biomarkers are associated with visual processing across the disease spectrum, emphasizing their potential in assessing disease severity and contributing to progression models of visual function and cognition. Show more

Keywords: Alzheimer’s disease, biomarkers, dementia, MRI, neuroimaging, visual processing

DOI: 10.3233/JAD-231084

Citation: Journal of Alzheimer's Disease, vol. 99, no. 2, pp. 623-637, 2024

Authors: Giraldo-Berrio, Daniela | Jimenez-Del-Rio, Marlene | Velez-Pardo, Carlos

Article Type: Research Article

Abstract: Background: Familial Alzheimer’s disease (FAD) presenilin 1 E280A (PSEN 1 E280A) is characterized by functional impairment and the death of cholinergic neurons as a consequence of amyloid-β (Aβ) accumulation and abnormal phosphorylation of the tau protein. Currently, there are no available therapies that can cure FAD. Therefore, new therapies are urgently needed for treating this disease. Objective: To assess the effect of sildenafil (SIL) on cholinergic-like neurons (ChLNs) harboring the PSEN 1 E280A mutation. Methods: Wild-type (WT) and PSEN 1 E280A ChLNs were cultured in the presence of SIL (25μ M) for 24 h. Afterward, proteinopathy, cell …signaling, and apoptosis markers were evaluated via flow cytometry and fluorescence microscopy. Results: We found that SIL was innocuous toward WT PSEN 1 ChLNs but reduced the accumulation of intracellular Aβ fragments by 87%, decreased the non-physiological phosphorylation of the protein tau at residue Ser202 /Thr205 by 35%, reduced the phosphorylation of the proapoptotic transcription factor c-JUN at residue Ser63 /Ser73 by 63%, decreased oxidized DJ-1 at Cys106 -SO3 by 32%, and downregulated transcription factor TP53 (tumor protein p53), BH-3-only protein PUMA (p53 upregulated modulator of apoptosis), and cleaved caspase 3 (CC3) expression by 20%, 32%, and 22%, respectively, compared with untreated mutant ChLNs. Interestingly, SIL also ameliorated the dysregulation of acetylcholine-induced calcium ion (Ca2+ ) influx in PSEN 1 E280A ChLNs. Conclusions: Although SIL showed no antioxidant capacity in the oxygen radical absorbance capacity and ferric ion reducing antioxidant power assays, it might function as an anti-amyloid and antiapoptotic agent and functional neuronal enhancer in PSEN 1 E280A ChLNs. Therefore, the SIL has therapeutic potential for treating FAD. Show more

Keywords: Alzheimer’s disease, amyloid-β , apoptosis, caspase 3, DJ-1, hydrogen peroxide, sildenafil

DOI: 10.3233/JAD-231169

Citation: Journal of Alzheimer's Disease, vol. 99, no. 2, pp. 639-656, 2024

Authors: Liu, Jiaqi | Sun, Sirui | Chen, Yongjie

Article Type: Research Article

Abstract: Background: Numerous studies have investigated the correlation between malondialdehyde (MDA) and cognitive decline. However, limited research has explored the interplay between superoxide dismutase (SOD), C-reactive protein (CRP), and MDA. Objective: This study aims to scrutinize the association between MDA and cognitive function in older adults, while also elucidating the roles of SOD and CRP within this relationship. Methods: Utilizing data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) spanning 2008–2009, 2011–2012, and 2014, this study included 2,696 eligible subjects. Cognitive function was evaluated using the Chinese version of the Mini-Mental State Examination (MMSE). Linear mixed-effects models …were employed to examine the links between MDA, SOD, CRP, and their interactions with cognitive function. Results: Elevated serum levels of MDA and CRP, as well as decreased serum SOD levels, were related to decreased cognitive function (β= –0.220 and –0.346, 95% CI: –0.399, –0.041 and –0.526, –0.167 for MDA and CRP; β= 0.384, 95% CI: 0.204, 0.564 for SOD). Notably, a significant interaction between MDA and SOD was detected (p  = 0.001). An increase per standard deviation in serum MDA levels was significantly associated with a 0.347-point lower MMSE score only in participants with normal cognitive function and high SOD levels (β= –0.347, 95% CI: –0.497, –0.197; p  < 0.001). Conclusions: Elevated serum MDA levels in the normal population with high SOD levels suggested diminished cognitive performance. Combining MDA with SOD could be pivotal in identifying older adults at risk of cognitive decline in clinical settings. Show more

Keywords: Alzheimer’s disease, cognitive decline, C-reactive protein malondialdehyde, mini-mental state examination score, superoxide dismutase

DOI: 10.3233/JAD-231278

Citation: Journal of Alzheimer's Disease, vol. 99, no. 2, pp. 657-665, 2024

Authors: Chu, Yili | Xie, Qihui | Meng, Rongrong | Leng, Bing | Cao, Zhenxiang

Article Type: Research Article

Abstract: Background: With the increasing popularity of the internet, a growing number of patients and their companions are actively seeking health-related information online. Objective: The aim of this study was to assess the quality and readability of online information about Alzheimer’s disease (AD) in China. Methods: A total of 263 qualified AD-related web pages from different businesses, governments, and hospitals were obtained. The quality of the web pages was assessed using the DISCERN tool, and the readability of the web pages was assessed using a readability measurement website suitable for the Chinese language. The differences in readability …and quality between different types of web pages were investigated, and the correlation between quality and readability was analyzed. Results: The mean overall DISCERN score was 40.93±7.5. The government group scored significantly higher than the commercial and hospital groups. The mean readability score was 12.74±1.27, and the commercial group had the lowest readability score. There was a positive correlation between DISCERN scores and readability scores. Conclusions: This study presents an evaluation of the quality and readability of health information pertaining to AD in China. The findings indicate that there is a need to enhance the quality and readability of web pages about AD in China. Recommendations for improvement are proposed in light of these findings. Show more

Keywords: Alzheimer’s disease, internet, quality evaluation, readability evaluation

DOI: 10.3233/JAD-231339

Citation: Journal of Alzheimer's Disease, vol. 99, no. 2, pp. 667-678, 2024