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

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