Journal of Alzheimer's Disease - Volume 99, issue 3

Authors: Khandia, Rekha | Gurjar, Pankaj | Romashchenko, Victoria | Al-Hussain, Sami A. | Alexiou, Athanasios | Zouganelis, George | Zaki, Magdi E.A.

Article Type: Research Article

Abstract: Background: Autophagy and apoptosis are cellular processes that maintain cellular homeostasis and remove damaged or aged organelles or aggregated and misfolded proteins. Stress factors initiate the signaling pathways common to autophagy and apoptosis. An imbalance in the autophagy and apoptosis, led by cascade of molecular mechanism prior to both processes culminate into neurodegeneration. Objective: In present study, we urge to investigate the codon usage pattern of genes which are common before initiating autophagy and apoptosis. Methods: In the present study, we took up eleven genes (DAPK1, BECN1, PIK3C3 (VPS34 ), BCL2, MAPK8, …BNIP3  L (NIX ), PMAIP1 , BAD, BID, BBC3, MCL1 ) that are part of molecular signaling mechanism prior to autophagy and apoptosis. We analyzed dinucleotide odds ratio, codon bias, usage, context, and rare codon analysis. Results: CpC and GpG dinucleotides were abundant, with the dominance of G/C ending codons as preferred codons. Clustering analysis revealed that MAPK8 had a distinct codon usage pattern compared to other envisaged genes. Both positive and negative contexts were observed, and GAG-GAG followed by CTG-GCC was the most abundant codon pair. Of the six synonymous arginine codons, two codons CGT and CGA were the rarest. Conclusions: The information presented in the study may be used to manipulate the process of autophagy and apoptosis and to check the pathophysiology associated with their dysregulation. Show more

Keywords: Alzheimer’s disease, apoptosis, autophagy, codon context, codon pairs, rare codons, relative synonymous codon usage

DOI: 10.3233/JAD-240158

Citation: Journal of Alzheimer's Disease, vol. 99, no. 3, pp. 927-939, 2024

Authors: Bruinsma, Jeroen | Loukas, Vasileios S. | Kassiotis, Thomas | Heger, Irene | Rosenberg, Anna | Visser, Leonie N. C. | Mangialasche, Francesca | Fotiadis, Dimitrios I. | Hanke, Sten | Crutzen, Rik

Article Type: Research Article

Abstract: Background: Unhealthy behavior increases the risk of dementia. Various socio-cognitive determinants influence whether individuals persist in or alter these unhealthy behaviors. Objective: This study identifies relevant determinants of behavior associated to dementia risk. Methods: 4,104 Dutch individuals (40–79 years) completed a screening questionnaire exploring lifestyle behaviors associated with dementia risk. Subsequently, 3,065 respondents who engaged in one or more unhealthy behaviors completed a follow-up questionnaire investigating socio-cognitive determinants of these behaviors. Cross-tables were used to assess the accuracy of participants’ perceptions regarding their behavior compared to recommendations. Confidence Interval-Based Estimation of Relevance (CIBER) …was used to identify the most relevant determinants of behavior based on visual inspection and interpretation. Results: Among the respondents, 91.3% reported at least one, while 65% reported two or more unhealthy lifestyle behaviors associated to dementia risk. Many of them were not aware they did not adhere to lifestyle recommendations. The most relevant determinants identified include attitudes (i.e., lacking a passion for cooking and finding pleasure in drinking alcohol or smoking), misperceptions on social comparisons (i.e., overestimating healthy diet intake and underestimating alcohol intake), and low perceived behavioral control (i.e., regarding changing physical inactivity, altering diet patterns, and smoking cessation). Conclusions: Individual-level interventions that encourage lifestyle change should focus on enhancing accurate perceptions of behaviors compared to recommendations, while strengthening perceived control towards behavior change. Given the high prevalence of dementia risk factors, combining interventions at both individual and environmental levels are likely to be the most effective strategy to reduce dementia on a population scale. Show more

Keywords: Alzheimer’s disease, behavioral medicine, dementia, health promotion, health risk behaviors, prevention, public health

DOI: 10.3233/JAD-231369

Citation: Journal of Alzheimer's Disease, vol. 99, no. 3, pp. 941-952, 2024

Authors: Sato, Kenichiro | Niimi, Yoshiki | Ihara, Ryoko | Suzuki, Kazushi | Iwata, Atsushi | Iwatsubo, Takeshi

Article Type: Research Article

Abstract: Background: Primary outcome measure in the clinical trials of disease modifying therapy (DMT) drugs for Alzheimer’s disease (AD) has often been evaluated by Clinical Dementia Rating sum of boxes (CDRSB). However, CDR testing requires specialized training and 30–50 minutes to complete, not being suitable for daily clinical practice. Objective: Herein, we proposed a machine-learning method to estimate CDRSB changes using simpler cognitive/functional batteries (Mini-Mental State Examination [MMSE] and Functional Activities Questionnaire [FAQ]), to replace CDR testing. Methods: Baseline data from 944 ADNI and 171 J-ADNI amyloid-positive participants were used to build machine-learning models …predicting annualized CDRSB changes between visits, based on MMSE and FAQ scores. Prediction performance was evaluated with mean absolute error (MAE) and R2 comparing predicted to actual rmDeltaCDRSB/rmDeltayear. We further assessed whether decline in cognitive function surpassing particular thresholds could be identified using the predicted rmDeltaCDRSB/rmDeltayear. RESULTS: The models achieved the minimum required prediction errors (MAE < 1.0) and satisfactory prediction accuracy (R2 >0.5) for mild cognitive impairment (MCI) patients for changes in CDRSB over periods of 18 months or longer. Predictions of annualized CDRSB progression>0.5, >1.0, or >1.5 demonstrated a consistent performance (i.e., Matthews correlation coefficient>0.5). These results were largely replicated in the J-ADNI case predictions. CONCLUSIONS: Our method effectively predicted MCI patient deterioration in the CDRSB based solely on MMSE and FAQ scores. It may aid routine practice for disease-modifying therapy drug efficacy evaluation, without necessitating CDR testing at every visit. Show more

Keywords: Alzheimer’s disease, clinical dementia rating, disease-modifying therapy, efficacy assessment, machine-learning, prediction

DOI: 10.3233/JAD-231426

Citation: Journal of Alzheimer's Disease, vol. 99, no. 3, pp. 953-963, 2024

Authors: Chong, Joanna Su Xian | Tan, Yi Jayne | Koh, Amelia Jialing | Ting, Simon Kang Seng | Kandiah, Nagaendran | Ng, Adeline Su Lyn | Zhou, Juan Helen

Article Type: Research Article

Abstract: Background: Alzheimer’s disease (AD) and behavioral variant frontotemporal dementia (bvFTD) show differential vulnerability to large-scale brain functional networks. Plasma neurofilament light (NfL), a promising biomarker of neurodegeneration, has been linked in AD patients to glucose metabolism changes in AD-related regions. However, it is unknown whether plasma NfL would be similarly associated with disease-specific functional connectivity changes in AD and bvFTD. Objective: Our study examined the associations between plasma NfL and functional connectivity of the default mode and salience networks in patients with AD and bvFTD. Methods: Plasma NfL and neuroimaging data from patients …with bvFTD (n  = 16) and AD or mild cognitive impairment (n  = 38; AD + MCI) were analyzed. Seed-based functional connectivity maps of key regions within the default mode and salience networks were obtained and associated with plasma NfL in these patients. RESULTS: We demonstrated divergent associations between NfL and functional connectivity in AD + MCI and bvFTD patients. Specifically, AD + MCI patients showed lower default mode network functional connectivity with higher plasma NfL, while bvFTD patients showed lower salience network functional connectivity with higher plasma NfL. Further, lower NfL-related default mode network connectivity in AD + MCI patients was associated with lower Montreal Cognitive Assessment scores and higher Clinical Dementia Rating sum-of-boxes scores, although NfL-related salience network connectivity in bvFTD patients was not associated with Neuropsychiatric Inventory Questionnaire scores. CONCLUSIONS: Our findings indicate that plasma NfL is differentially associated with brain functional connectivity changes in AD and bvFTD. Show more

Keywords: Alzheimer’s disease, behavioral variant frontotemporal dementia, plasma neurofilament light, resting state functional connectivity

DOI: 10.3233/JAD-231251

Citation: Journal of Alzheimer's Disease, vol. 99, no. 3, pp. 965-980, 2024

Authors: Jaen, Jocelyn | Grodstein, Francine | Lajous, Martín | Bello-Chavolla, Omar Yaxmehen | Gómez-Flores-Ramos, Liliana | Yang, Jingyun | Bennett, David A. | Marquez, David X. | Lamar, Melissa

Article Type: Research Article

Abstract: Background: US-based Latinos have lower education and income combined with higher health risks than non-Latino whites, but often ‘paradoxically’ evidence better health-related outcomes. Less work has investigated this paradox for cognitive-related outcomes despite nativity diversity. Objective: We evaluated cognitive aging within older Latinos of diverse nativity currently living in the US and participating in Rush Alzheimer’s Disease Center studies. Methods: Participants without baseline dementia, who completed annual neuropsychological assessments (in English or Spanish) were grouped by US-born (n  = 117), Mexico-born (n  = 173), and born in other Latin American regions (LAr-born = 128). Separate regression models examined associations between …nativity and levels of (N  = 418) or change in (n  = 371; maximum follow-up ∼16 years) global and domain-specific cognition. Results: Demographically-adjusted linear regression models indicated that foreign-born nativity was associated with lower levels of global cognition and select cognitive domains compared to US-born Latinos. No associations of nativity with cognitive decline emerged from demographically-adjusted mixed-effects models; however, Mexico-born nativity appeared associated with slower declines in working memory compared to other nativity groups (p -values ≥ 0.051). Mexico-born Latinos had relatively higher vascular burden and lower education levels than other nativity groups; however, this did not alter results. Conclusions: Nativity differences in baseline cognition may be due, in part, to accumulated stressors related to immigration and acculturation experienced by foreign-born Latinos which may hasten meeting criteria for dementia later in life. In contrast, Mexico-born participants’ slower working memory declines, taken in the context of other participant characteristics including vascular burden, suggests the Hispanic Paradox may relate to factors with the potential to affect cognition Show more

Keywords: Alzheimer’s disease, Hispanic Paradox, Latinos, nativity, working memory

DOI: 10.3233/JAD-231358

Citation: Journal of Alzheimer's Disease, vol. 99, no. 3, pp. 981-991, 2024

Authors: Wang, Linlin | Zhang, Xuezhen | Wang, Lei | Guo, Miaomiao | Yang, Qihang | Chen, Xiaogang | Sha, Hong

Article Type: Research Article

Abstract: Background: Early recognition of dementia like Alzheimer’s disease is crucial for disease diagnosis and treatment, and existing objective tools for early screening of cognitive impairment are limited. Objective: To investigate age-related behavioral indicators of dual-task cognitive performance and gait parameters and to explore potential objective markers of early cognitive decline. Methods: The community-based cognitive screening data was analyzed. Hierarchical cluster analysis and Pearson correlation analysis were performed on the 9-item subjective cognitive decline (SCD-9) scores, walking-cognitive dual-task performance, walking speed, and gait parameters of 152 participants. The significant differences of indicators that may related to cognitive …decline were statistically analyzed across six age groups. A mathematical model with age as the independent variable and motor cognition composite score as the dependent variable was established to observe the trend of motor cognition dual-task performance with age. Results: Strong correlation was found between motor cognitive scores and SCD and age. Gait parameters like the mean value of ankle angle, the left-right difference rate of ankle angle and knee angle and the coefficient of variation of gait cycle showed an excellent correlation with age. Motor cognition scores showed a decreasing trend with age. The slope of motor cognition scores with age after 50 years (k  = –1.06) was six times higher than that before 50 years (k  = –0.18). Conclusions: Cognitive performance and gait parameters in the walking-cognitive dual-task state are promising objective markers that could characterize age-related cognitive decline. Show more

Keywords: Age, Alzheimer’s disease, cognitive decline, motor cognitive assessment, objective markers, walking-cognitive dual task

DOI: 10.3233/JAD-240066

Citation: Journal of Alzheimer's Disease, vol. 99, no. 3, pp. 993-1004, 2024

Authors: Wu, Can | Ruan, Tingting | Yuan, Yalan | Xu, Chunshuang | Du, Lijuan | Wang, Fang | Xu, Shujun

Article Type: Research Article

Abstract: Background: Alzheimer’s disease (AD) is a progressive neurodegeneration disease. Physical activity is one of the most promising modifiable lifestyles that can be effective in slowing down the progression of AD at an early stage. Objective: Explore the molecular processes impaired in AD that were conversely preserved and enhanced by physical activity. Methods: Integrated transcriptomic analyses were performed in datasets that contain AD patients and elders with different degrees of physical activity. The changes of the hub genes were validated through analyzing another two datasets. The expression of the hub genes was further detected …in the hippocampus and cortexes of APP/PS1 transgenic mice with or without physical activity by Quantitative polymerase chain reaction (qPCR). Results: Cross-comparison highlighted 195 DEGs displaying opposed regulation patterns between AD and high physical activity (HPA). The common DEGs were predominantly involved in synaptic vesicle recycling and synaptic transmission, largely downregulated in AD patients but upregulated in the elders with HPA. Two key modules and four hub genes that were related to synaptic vesicle turnover were obtained from the PPI network. The expression of these hub genes (SYT1, SYT4, SH3GL2, and AP2M1 ) was significantly decreased in AD transgenic mice and was reversed by HPA training. Conclusions: HPA may reverse AD pathology by upregulating a range of synaptic vesicle transport related proteins which might improve the efficiency of synaptic vesicle turnover and facilitate inter-neuronal information transfer. The study provides novel insights into the mechanisms underlining the protective effects of HPA on AD. Show more

Keywords: Alzheimer’s disease, physical activity, synaptic connectivity, synaptic transmission, synaptic vesicle cycling, transcriptomic analysis

DOI: 10.3233/JAD-240123

Citation: Journal of Alzheimer's Disease, vol. 99, no. 3, pp. 1005-1022, 2024

Authors: Youssef, Hossam | Gatto, Rodolfo G. | Pham, Nha Trang Thu | Petersen, Ronald C. | Machulda, Mary M. | Reichard, R. Ross | Dickson, Dennis W. | Jack, Clifford R. | Whitwell, Jennifer L. | Josephs, Keith A.

Article Type: Research Article

Abstract: Background: TAR DNA binding protein 43 (TDP-43) has been shown to be associated with whole hippocampal atrophy in primary age-related tauopathy (PART). It is currently unknown which subregions of the hippocampus are contributing to TDP-43 associated whole hippocampal atrophy in PART. Objective: To identify which specific hippocampal subfield regions are contributing to TDP-43-associated whole hippocampal atrophy in PART. Methods: A total of 115 autopsied cases from the Mayo Clinic Alzheimer Disease Research Center, Neurodegenerative Research Group, and the Mayo Clinic Study of Aging were analyzed. All cases underwent antemortem brain volumetric MRI, neuropathological assessment …of the distribution of Aβ (Thal phase), and neurofibrillary tangle (Braak stage) to diagnose PART, as well as assessment of TDP-43 presence/absence in the amygdala, hippocampus and beyond. Hippocampal subfield segmentation was performed using FreeSurfer version 7.4.1. Statistical analyses using logistic regression were performed to assess for associations between TDP-43 and hippocampal subfield volumes, accounting for potential confounders. Results: TDP-43 positive patients (n  = 37, 32%), of which 15/15 were type-α, had significantly smaller whole hippocampal volumes, and smaller volumes of the body and tail of the hippocampus compared to TDP-43 negative patients. Subfield analyses revealed an association between TDP-43 and the molecular layer of hippocampal body and the body of cornu ammonis 1 (CA1), subiculum, and presubiculum regions. There was no association between TDP-43 stage and subfield volumes. Conclusions: Whole hippocampal volume loss linked to TDP-43 in PART is mainly due to volume loss occurring in the molecular layer, CA1, subiculum and presubiculum of the hippocampal body. Show more

Keywords: Alzheimer’s disease, Cornu Ammonis 1, LATE-NC, primary age-related tauopathy, TAR DNA binding Protein 43, type-alpha

DOI: 10.3233/JAD-240136

Citation: Journal of Alzheimer's Disease, vol. 99, no. 3, pp. 1023-1032, 2024

Authors: Rolandsson, Olov | Tornevi, Andreas | Steneberg, Pär | Edlund, Helena | Olsson, Tommy | Andreasson, Ulf | Zetterberg, Henrik | Blennow, Kaj

Article Type: Research Article

Abstract: Background: Individuals with type 2 diabetes (T2D) have an increased risk of cognitive symptoms and Alzheimer’s disease (AD). Mis-metabolism with aggregation of amyloid-β peptides (Aβ) play a key role in AD pathophysiology. Therefore, human studies on Aβ metabolism and T2D are warranted. Objective: The objective of this study was to examine whether acute hyperglycemia affects plasma Aβ1–40 and Aβ1–42 concentrations in individuals with T2D and matched controls. Methods: Ten participants with T2D and 11 controls (median age, 69 years; range, 66–72 years) underwent hyperglycemic clamp and placebo clamp (saline infusion) in …a randomized order, each lasting 4 hours. Aβ1–40 , Aβ1–42 , and insulin-degrading enzyme (IDE) plasma concentrations were measured in blood samples taken at 0 and 4 hours of each clamp. Linear mixed-effect regression models were used to evaluate the 4-hour changes in Aβ1–40 and Aβ1–42 concentrations, adjusting for body mass index, estimated glomerular filtration rate, and 4-hour change in insulin concentration. Results: At baseline, Aβ1–40 and Aβ1–42 concentrations did not differ between the two groups. During the hyperglycemic clamp, Aβ decreased in the control group, compared to the placebo clamp (Aβ1–40 : p  = 0.034, Aβ1–42 : p  = 0.020), IDE increased (p  = 0.016) during the hyperglycemic clamp, whereas no significant changes in either Aβ or IDE was noted in the T2D group. Conclusions: Clamp-induced hyperglycemia was associated with increased IDE levels and enhanced Aβ40 and Aβ42 clearance in controls, but not in individuals with T2D. We hypothesize that insulin-degrading enzyme was inhibited during hyperglycemic conditions in people with T2D. Show more

Keywords: Alzheimer’s disease, amyloid-β, cognition, endocrinology and metabolism specialty, hyperglycemia, type 2 diabetes

DOI: 10.3233/JAD-230628

Citation: Journal of Alzheimer's Disease, vol. 99, no. 3, pp. 1033-1046, 2024

Authors: Estrella, Mayra L. | Tarraf, Wassim | Kuwayama, Sayaka | Gallo, Linda C. | Salazar, Christian R. | Stickel, Ariana M. | Mattei, Josiemer | Vásquez, Priscilla M. | Eldeirawi, Kamal M. | Perreira, Krista M. | Penedo, Frank J. | Isasi, Carmen R. | Cai, Jianwen | Zeng, Donglin | González, Hector M. | Daviglus, Martha L. | Lamar, Melissa

Article Type: Research Article

Abstract: Background: Higher allostatic load (AL), a multi-system measure of physiological dysregulation considered a proxy for chronic stress exposure, is associated with poorer global cognition (GC) in older non-Hispanic white adults. However, evidence of these associations in middle-aged and older US-based Hispanic/Latino adults is limited. Objective: To examine associations of AL with level of cognition, performance in cognition 7 years later, and change in cognition over 7 years among middle-aged and older US-based Hispanic/Latino adults. Methods: We used data (n  = 5,799, 45–74 years at baseline) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) and SOL-Investigation of …Neurocognitive Aging (SOL-INCA). The AL score comprised 16 biomarkers representing cardiometabolic, glucose, cardiopulmonary, parasympathetic, and inflammatory systems (higher scores = greater dysregulation). Cognitive outcomes included GC and individual tests of verbal learning and memory, world fluency (WF), Digit Symbol Substitution (DSS), and Trail Making (Parts A & B). Survey-linear regressions assessed associations of AL with performance in cognition at baseline, 7 years later, and via 7-year cognitive change scores adjusting for sociodemographic characteristics, lifestyle factors, and depressive symptoms. Results: Higher AL was associated with lower baseline performance in GC and WF; and lower 7-year follow-up performance in these same measures plus DSS and Trail Making Parts A & B. Higher AL was associated with more pronounced 7-year change (reduction) in GC and on WF and DSS tests. Conclusions: Findings extend previous evidence in predominantly older non-Hispanic white cohorts to show that AL is related to level of and change in GC (as well as WF and DSS) among middle-aged and older US-based Hispanic/Latino adults. Show more

Keywords: Allostatic load, Alzheimer’s disease, cognitive function, Hispanic/Latino

DOI: 10.3233/JAD-230796

Citation: Journal of Alzheimer's Disease, vol. 99, no. 3, pp. 1047-1064, 2024

Authors: Aguilar, Byron J. | Jasuja, Guneet K. | Li, Xuyang | Shishova, Ekaterina | Palacios, Natalia | Berlowitz, Dan | Morin, Peter | O’Connor, Maureen K. | Nguyen, Andrew | Reisman, Joel | Leng, Yue | Zhang, Raymond | Monfared, Amir Abbas Tahami | Zhang, Quanwu | Xia, Weiming

Article Type: Research Article

Abstract: Background: Diagnostic codes can be instrumental for case identification in Alzheimer’s disease (AD) research; however, this method has known limitations and cannot distinguish between disease stages. Clinical notes may offer more detailed information including AD severity and can complement diagnostic codes for case identification. Objective: To estimate prevalence of mild cognitive impairment (MCI) and AD using diagnostics codes and clinical notes available in the electronic healthcare record (EHR). Methods: This was a retrospective study in the Veterans Affairs Healthcare System (VAHS). Health records from Veterans aged 65 years or older were reviewed during Fiscal Years (FY) …2010–2019. Overall, 274,736 and 469,569 Veterans were identified based on a rule-based algorithm as having at least one clinical note for MCI and AD, respectively; 201,211 and 149,779 Veterans had a diagnostic code for MCI and AD, respectively. During FY 2011–2018, likely MCI or AD diagnosis was defined by≥2 qualifiers (i.e., notes and/or codes)≥30 days apart. Veterans with only 1 qualifier were considered as suspected MCI/AD. Results: Over the 8-year study, 147,106 and 207,225 Veterans had likely MCI and AD, respectively. From 2011 to 2018, yearly MCI prevalence increased from 0.9% to 2.2%; yearly AD prevalence slightly decreased from 2.4% to 2.1%; mild AD changed from 22.9% to 26.8%, moderate AD changed from 26.5% to 29.1%, and severe AD changed from 24.6% to 30.7% Conclusions: The relative distribution of AD severities was stable over time. Accurate prevalence estimation is critical for healthcare resource allocation and facilitating patients receiving innovative medicines. Show more

Keywords: Alzheimer’s disease,, electronic health record, mild cognitive impairment, prevalence, veterans affairs

DOI: 10.3233/JAD-240027

Citation: Journal of Alzheimer's Disease, vol. 99, no. 3, pp. 1065-1075, 2024

Authors: Kurihara, Masanori | Kondo, Soichiro | Ohse, Kensuke | Nojima, Hisashi | Kikkawa-Saito, Emiko | Iwata, Atsushi

Article Type: Research Article

Abstract: Background: Although Lumipulse assays and conventional ELISA are strongly correlated, the precise relationship between their measured values remains undetermined. Objective: To determine the relationship between Lumipulse and ELISA measurement values. Methods: Patients who underwent cerebrospinal fluid (CSF) Alzheimer’s disease (AD) biomarker measurements and consented to biobanking between December 2021 and June 2023 were included. The relationship between values measured via Lumipulse assays and conventional ELISA were evaluated by Passing-Bablok analyses for amyloid-β 1-42 (Aβ42 ), total tau (t-tau), and phospho-tau 181 (p-tau 181). Studies using both assays were systematically searched for in PubMed and summarized after …quality assessment. Results: Regression line slopes and intercepts were 1.41 (1.23 to 1.60) and –77.8 (–198.4 to 44.5) for Aβ42 , 0.94 (0.88 to 1.01) and 98.2 (76.9 to 114.4) for t-tau, and 1.60 (1.43 to 1.75) and –21.1 (–26.9 to –15.6) for p-tau181. Spearman’s correlation coefficients were 0.90, 0.95, and 0.95 for Aβ42 , t-tau, and p-tau181, respectively. We identified 13 other studies that included 2,117 patients in total. Aβ42 slope varied among studies, suggesting inter-lab difference of ELISA. The slope and intercept of t-tau were approximately 1 and 0, respectively, suggesting small proportional and systematic differences. Conversely, the p-tau181 slope was significantly higher than 1, distributed between 1.5–2 in most studies, with intercepts significantly lower than 0, suggesting proportional and systematic differences. Conclusions: We characterized different relationship between measurement values for each biomarker, which may be useful for understanding the differences in CSF biomarker measurement values on different platforms and for future global harmonization. Show more

Keywords: Alzheimer’s disease, amyloid-β, biomarkers, cerebrospinal fluid, fully-automated, chemiluminescent enzyme immunoassay (CLEIA), enzyme-linked immunosorbent assay (ELISA), standardization, systematic review, tau proteins

DOI: 10.3233/JAD-240185

Citation: Journal of Alzheimer's Disease, vol. 99, no. 3, pp. 1077-1092, 2024

Authors: Zakrzewski, Jessica J. | Davis, Jennifer D. | Gemelli, Zachary T. | Korthauer, Laura E.

Article Type: Research Article

Abstract: Background: There are significant public health benefits to delaying the onset of Alzheimer’s disease (AD) in individuals at risk. However, adherence to brain healthy behaviors is low. The Health Belief Model proposes that specific beliefs are mediators of behavior change. Objective: To characterize health belief measures from the Science of Behavior Change Research Network (SBCRN) in an older adult population and associations between health beliefs, AD risk, and current health behaviors. Methods: A total of 172 individuals from the Rhode Island AD Prevention Registry participated. SBCRN health belief measures included assessments of future …time perspective, self-efficacy, deferment of gratification, and consideration of future consequences. Outcome measures included individual AD risk index score, dementia risk awareness, and lifestyle behaviors including physical, cognitive, and social activity. Results: Participants who were older had higher scores for AD risk, lower future time perspective, and lower generalized self-efficacy (all at p  < 0.001). Higher generalized self-efficacy was related to increased physical activity (p  < 0.010). Higher future time perspective (p  < 0.001) and generalized self-efficacy (p  = 0.48) were associated with lower AD risk score. Subjective cognitive decline (SCD) was associated with lower self-efficacy, ability to delay gratification, and a less expansive future time perspective. Conclusions: Greater self-efficacy and perceived future time remaining were associated with lower AD risk and greater engagement in physical activity. SCD was associated with health beliefs that may negatively affect engagement in positive brain health behaviors. Assessment of and psychoeducation about these intrapersonal health belief constructs may be important targets for behavioral interventions to reduce AD risk. Show more

Keywords: Alzheimer’s disease, clinical trial, genetic risk testing, prevention, subjective cognitive decline

DOI: 10.3233/JAD-230977

Citation: Journal of Alzheimer's Disease, vol. 99, no. 3, pp. 1093-1104, 2024

Authors: Downer, Brian | Milani, Sadaf | Grasso, Stephanie | Lucas, Fernando Llanos | Mehta, Neil

Article Type: Research Article

Abstract: Background: Better English proficiency and higher frequency of using English among non-native speakers are associated with lower dementia risk. Objective: We investigated if Mexican American older adults who use English and Spanish to a more similar degree demonstrate better cognitive function than those who use one language more than the other. Methods: We used data from waves one (1992/93) to eight (2012/13) of the Hispanic Established Population for the Epidemiological Study of the Elderly. At baseline, participants were asked what language they usually use across communicative contexts. We based dual language on participants’ use of Spanish …and English within and across contexts. We categorized participants as low (n  = 1,145), medium (n  = 717), and high (n  = 702) dual-language users. Linear mixed models were used to estimate the association between dual-language use, baseline Mini-Mental State Examination (MMSE) scores, and change in MMSE. Results: Participants in the medium and high dual-language use categories scored 1.91 points and 3.03 points higher at wave one compared to the low dual-language use category. Adjusting for education reduced the association between dual-language use and baseline MMSE (medium B  = 0.99 SE = 0.19 p  < 0.01; high B  = 1.41 SE = 0.21 p  < 0.01). The association between dual-language use and decline in the MMSE was not statistically significant. Conclusions: Greater dual-language use was associated with higher MMSE scores but not change in MMSE scores among Mexican Americans aged 65 and older. Future work should characterize bilingualism with greater nuance and use more rigorous cognitive measures to identify the components of the bilingual experience that may benefit the cognitive functioning of older adult bilinguals. Show more

Keywords: Alzheimer’s disease, cognitive aging, cohort studies, Hispanic, multilingualism

DOI: 10.3233/JAD-231187

Citation: Journal of Alzheimer's Disease, vol. 99, no. 3, pp. 1105-1115, 2024

Authors: Moon, Hasom | Ham, Hongki | Yun, Jihwan | Shin, Daeun | Lee, Eun Hye | Kim, Hee Jin | Seo, Sang Won | Na, Duk L. | Jang, Hyemin

Article Type: Research Article

Abstract: Background: Amyloid-β (Aβ) commonly coexists and impacts prognosis in subcortical vascular cognitive impairment (SVCI). Objective: This study aimed to examine the differences in clinical and neuroimaging variables between Aβ-positive and Aβ-negative SVCI and to propose a prediction model for Aβ positivity in clinically diagnosed SVCI patients. Methods: A total of 130 patients with SVCI were included in model development, and a separate cohort of 70 SVCI patients was used in external validation. The variables for the prediction model were selected by comparing the characteristics of the Aβ-negative and Aβ-positive SVCI groups. The final model was determined …using a stepwise method. The model performance was evaluated using the receiver operating characteristic (ROC) curve and a calibration curve. A nomogram was used for visualization. Results: Among 130 SVCI patients, 70 (53.8%) were Aβ-positive. The Aβ-positive SVCI group was characterized by older age, tendency to be in the dementia stage, a higher prevalence of APOE ɛ 4, a lower prevalence of lacune, and more severe medial temporal atrophy (MTA). The final prediction model, which excluded MTA grade following the stepwise method for variable selection, demonstrated good accuracy in distinguishing between Aβ-positive and Aβ-negative SVCI, with an area under the curve (AUC) of 0.80. The external validation demonstrated an AUC of 0.71. Conclusions: The findings suggest that older age, dementia stage, APOE ɛ 4 carrier, and absence of lacunes may be predictive of Aβ positivity in clinically diagnosed SVCI patients. Show more

Keywords: Alzheimer’s disease, amyloid-β , dementia, mild cognitive impairment, subcortical vascular cognitive impairment

DOI: 10.3233/JAD-240196

Citation: Journal of Alzheimer's Disease, vol. 99, no. 3, pp. 1117-1127, 2024

Authors: Gamm, Simone | Ummel, Deborah | Vasil, Nancy | Grenier, Sébastien

Article Type: Research Article

Abstract: Background: A diagnosis of Alzheimer’s disease (AD) is a crucial moment in an individual’s existence and represents a major life change that often results in psychological distress, diminish of perceived quality of life, and loss of independence. It is important to better understand the emotional experience of people with dementia to intervene according to their specific needs. Objective: The aim of the research was to get insight to the emotional experience of people with AD shortly after its discovery and the consequences thereof. Methods: A qualitative exploratory design was engaged, and in-depth interviews were conducted with …ten French-speaking participants over 70 years recently diagnosed. Interviews were guided by Heideggerian phenomenology about movements in the worldview of individuals. The transcribed data was subjected to interpretative phenomenological analysis. Results: Following the diagnosis, participants experienced either shock or denial. Emotions felt were unpleasant and disturbing for most of them. Especially when participants were confronted with news concerning the illness, they experienced incomprehension. They engaged in an oscillatory motion of connection and disconnection to establish new meanings of their worldview. Thinking about the past seemed to diminish their worries, to reinforce the possibility to fulfil a significant place in their existence and to maintain their autonomy. Conclusions: When participants could express their emotional experience and their concerns, they regained a sense of control in their life that seemed du reduce their distress. With this insight, intervention could be adapted to the specific needs of people with AD to enhance their self-determination and quality of life. Show more

Keywords: Alzheimer’s disease, dementia, diagnosis, distress, emotions, interpretative phenomenological analysis, qualitative research, quality of life, self determination

DOI: 10.3233/JAD-231403

Citation: Journal of Alzheimer's Disease, vol. 99, no. 3, pp. 1129-1145, 2024

Authors: Costantini, Erica | Carrarini, Claudia | Calisi, Dario | De Rosa, Matteo | Simone, Marianna | Di Crosta, Adolfo | Palumbo, Rocco | Cipollone, Alessia | Aielli, Lisa | De Laurentis, Maria | Colarusso, Lucilla | Pilotto, Andrea | Padovani, Alessandro | Konstantinidou, Fani | Gatta, Valentina | Stuppia, Liborio | Cipollone, Francesco | Di Nicola, Marta | Reale, Marcella | Bonanni, Laura

Article Type: Research Article

Abstract: Background: Neuroinflammation, with altered peripheral proinflammatory cytokine production, plays a major role in the pathogenesis of neurodegenerative diseases, such as Alzheimer’s disease (AD), while the role of inflammation in dementia with Lewy bodies (DLB) is less known and the results of different studies are often in disagreement. Objective: The present study aimed to investigate the levels of TNFα and IL-6 in serum and supernatants, and the related DNA methylation in patients affected by DLB and AD compared to healthy controls (HCs), to clarify the role of epigenetic mechanisms of DNA promoter methylation on of pro-inflammatory cytokines overproduction. …Methods: Twenty-one patients with DLB and fourteen with AD were frequency-matched for age and sex with eleven HCs. Clinical evaluation, TNFα and IL-6 gene methylation status, cytokine gene expression levels and production in serum and peripheral blood mononuclear cell (PBMC) supernatants were performed. Results: In AD and DLB patients, higher serum levels of IL-6 and TNFα were detected than in HCs. Differences in LPS-stimulated versus spontaneous PBMCs were observed between DLB, AD, and HC in the levels of TNFα (p  = 0.027) and IL-6 (p  < 0.001). Higher levels were also revealed for sIL-6R in DLB (p  < 0.001) and AD (p  < 0.001) in comparison with HC.DNA hypomethylation in IL-6 and TNFα CpG promoter sites was detected for DLB and AD patients compared to the corresponding site in HCs. Conclusions: Our preliminary study documented increased levels of IL-6 and TNFα in DLB and AD patients to HCs. This overproduction can be due to epigenetic mechanisms regarding the hypomethylation of DNA promoters. Show more

Keywords: Alzheimer’s disease, epigenetic, IL-6, inflammation, Lewy body disease, peripheral biomarkers, TNFα

DOI: 10.3233/JAD-231471

Citation: Journal of Alzheimer's Disease, vol. 99, no. 3, pp. 1147-1158, 2024