Journal of Alzheimer's Disease - Volume 97, issue 2

Authors: Ahmed, Tahera | Zhang, Ping | Kumar, Kuldeep

Article Type: Research Article

Abstract: Background: Alzheimer’s disease (AD) is a particular type of dementia that currently lacks a definitive treatment and cure. It is possible to reduce the risk of developing AD and mitigate its severity through modifications to one’s lifestyle, regular diet, and alcohol-drinking habits. Objective: The objective of this study is to examine the daily dietary patterns of individuals with AD compared to healthy controls, with a focus on nutritional balance and its impact on AD. Methods: This study incorporated multiple-factor analysis (MFA) to evaluate dietary patterns and employed Random Forest (RF) classifier and Sparse …Logistic Regression (SLR) for Variable Importance analysis to identify food items significantly associated with AD. Results: MFA revealed trends in the data and a strong correlation (Lg = 0.92, RV = 0.65) between the daily consumption of processed food and meat items in AD patients. In contrast, no significant relationship was found for any daily consumed food categories within the healthy control (HC) group. Food items such as meat pie, hamburger, ham, sausages, beef, capsicum, and cabbage were identified as important variables associated with AD in RF and SLR analyses. Conclusions: The findings from MFA indicated that the diversity or equilibrium of daily diet might play a potential role in AD development. RF and SLR classifications exhibit among the processed foods, especially deli meats and food made with meat items, are associated with AD. Show more

Keywords: AIBL database, Alzheimer’s disease, dietary habits, multiple factor analysis, random forest, sparse logistic regression

DOI: 10.3233/JAD-230634

Citation: Journal of Alzheimer's Disease, vol. 97, no. 2, pp. 777-790, 2024

Authors: Schröder, Valerie E. | Skrozic, Amna | Erz, Dorothee | Kaysen, Anne | Fritz, Joëlle V. | Loureiro, Joao M. | McIntyre, Deborah | Pauly, Laure | Kemp, Jennifer | Schmitz, Sabine K. | Wagner, Sophie | Reyes, Margarita | Soare, Ruxandra | Satagopam, Venkata | Vega, Carlos | Gawron, Piotr | Roomp, Kirsten | Conde, Patricia Martins | Klucken, Jochen | Köhler, Sebastian | Hartmann, Tobias | Dodel, Richard | Leist, Anja K. | Kalbe, Elke | Krüger, Rejko

Article Type: Research Article

Abstract: Background: With continuously aging societies, an increase in the number of people with cognitive decline is to be expected. Aside from the development of causative treatments, the successful implementation of prevention strategies is of utmost importance to reduce the high societal burden caused by neurodegenerative diseases leading to dementia among which the most common cause is Alzheimer’s disease. Objective: The aim of the Luxembourgish “programme dementia prevention (pdp )” is to prevent or at least delay dementia in an at-risk population through personalized multi-domain lifestyle interventions. The current work aims to provide a detailed overview of the methodology …and presents initial results regarding the cohort characteristics and the implementation process. Methods: In the frame of the pdp , an extensive neuropsychological evaluation and risk factor assessment are conducted for each participant. Based on the results, individualized multi-domain lifestyle interventions are suggested. Results: A total number of 450 participants (Mean age = 69.5 years; SD = 10.8) have been screened at different recruitment sites throughout the country, among whom 425 participants (94.4%) met the selection criteria. Conclusions: We provide evidence supporting the feasibility of implementing a nationwide dementia prevention program and achieving successful recruitment of the target population by establishing a network of different healthcare providers. Show more

Keywords: Alzheimer’s disease, cognition, dementia prevention, healthy aging, mild cognitive impairment, multi-domain lifestyle interventions, neuropsychological assessment, personalized prevention, risk factor assessment, subjective cognitive decline

DOI: 10.3233/JAD-230794

Citation: Journal of Alzheimer's Disease, vol. 97, no. 2, pp. 791-804, 2024

Authors: Li, Kuan-Ying | Lin, Bin-Tse | Hsu, Shu-Ting | Chien, Ching-Fang | Chang, Yang-Pei | Yang, Yuan-Han

Article Type: Research Article

Abstract: Background: Neuropsychiatric symptoms (NPS) are distressing for patients with dementia, often accelerating functional decline and nursing home placement. Medications such as quetiapine are used to alleviate NPS, but their side effects require cautious use. Liquid formulations such as quetiapine oral suspension suit specific populations; however, real-world data on their use in patients with dementia are limited. Objective: The purpose of this retrospective, naturalistic study was to provide preliminary data on the effects of treatment with quetiapine oral suspension on behavioral and psychiatric disturbances in Alzheimer’s disease (AD) outpatients in Taiwan. Methods: Between January 2022 and June …2023, data were collected from outpatients with a diagnosis of probable AD who received treatment with Qting® (quetiapine oral solution 25 mg/ml). Primary outcome measures were changes in Neuropsychiatric Inventory (NPI) total score and its sub-items from baseline to the endpoint. Results: We recruited 66 AD patients with a mean age of 72.1±7.6 years, most of whom were female (69.7%). Twenty-three patients had data on neuropsychological test and NPI scores before and after quetiapine treatment. There was no significant change in global cognitive function from baseline to the endpoint. A significant reduction in NPI total score after quetiapine treatment was noted, while the effect on NPI sub-items was limited. The average maintenance dose was 1.5±0.6 ml. Conclusions: We demonstrated our clinical experience of the use of quetiapine oral solution in AD patients with NPS. Our results showed that quetiapine oral solution treatment significantly improved these symptoms at a relatively low dose. Show more

Keywords: Alzheimer’s disease, antipsychotic, liquid, neuropsychiatric symptoms, quetiapine

DOI: 10.3233/JAD-231007

Citation: Journal of Alzheimer's Disease, vol. 97, no. 2, pp. 805-811, 2024

Authors: Zhang, Erdong | Dai, Fengqiu

Article Type: Research Article

Abstract: Background: The pathophysiology of Alzheimer’s disease (AD) involves the interplay of three different processes: pyroptosis, apoptosis, and necroptosis. Objective: To explore role of PANoptosis, a novel pro-inflammatory programmed cell death pathway, in AD patients. Methods: We performed a consensus clustering analysis to identify distinct transcriptional profiles in the samples using the R package “ConsensusClusterPlus”. The PANoptosis key genes were obtained by crossing the WGCNA brown module and differentially expressed PANoptosis genes. We accomplished regression analyses using the LASSO-Cox method, combined with pathological status and gene expression data. At the same time, we also constructed PANscore system. …The expression of PANoptosis hub genes were validated by qRT-PCR in AD transgenic mice. Results: Our study utilized tissue expression profile data from AD patients to construct three distinct PANoptosis patterns, each with unique molecular and clinical characteristics. We have created a risk scoring system called PANscore, which can analyze patterns specific for each AD patient. Additionally, we observed significantly lower levels of follicular helper T (Tfh) cells in the high PANscore and AD patients. Further analysis revealed a significant negative correlation of Tfh with GSDMD and MLKL . Conclusions: These findings provide a roadmap for personalized patient stratification, enabling clinicians to develop personalized treatment plans for AD patients and advance the field of precision medicine. Show more

Keywords: Alzheimer’s disease, diagnostic, infiltrating immune cells, PANoptosis, PANscore

DOI: 10.3233/JAD-231103

Citation: Journal of Alzheimer's Disease, vol. 97, no. 2, pp. 813-828, 2024

Authors: Raji, Cyrus A. | Meysami, Somayeh | Hashemi, Sam | Garg, Saurabh | Akbari, Nasrin | Ahmed, Gouda | Chodakiewitz, Yosef Gavriel | Nguyen, Thanh Duc | Niotis, Kellyann | Merrill, David A. | Attariwala, Rajpaul

Article Type: Research Article

Abstract: Background: The potential neuroprotective effects of regular physical activity on brain structure are unclear, despite links between activity and reduced dementia risk. Objective: To investigate the relationships between regular moderate to vigorous physical activity and quantified brain volumes on magnetic resonance neuroimaging. Methods: A total of 10,125 healthy participants underwent whole-body MRI scans, with brain sequences including isotropic MP-RAGE. Three deep learning models analyzed axial, sagittal, and coronal views from the scans. Moderate to vigorous physical activity, defined by activities increasing respiration and pulse rate for at least 10 continuous minutes, was modeled with brain volumes …via partial correlations. Analyses adjusted for age, sex, and total intracranial volume, and a 5% Benjamini-Hochberg False Discovery Rate addressed multiple comparisons. Results: Participant average age was 52.98±13.04 years (range 18–97) and 52.3% were biologically male. Of these, 7,606 (75.1%) reported engaging in moderate or vigorous physical activity approximately 4.05±3.43 days per week. Those with vigorous activity were slightly younger (p  < 0.00001), and fewer women compared to men engaged in such activities (p  = 3.76e-15). Adjusting for age, sex, body mass index, and multiple comparisons, increased days of moderate to vigorous activity correlated with larger normalized brain volumes in multiple regions including: total gray matter (Partial R  = 0.05, p  = 1.22e-7), white matter (Partial R  = 0.06, p  = 9.34e-11), hippocampus (Partial R  = 0.05, p  = 5.96e-7), and frontal, parietal, and occipital lobes (Partial R  = 0.04, p ≤1.06e-5). Conclusions: Exercise-related physical activity is associated with increased brain volumes, indicating potential neuroprotective effects. Show more

Keywords: Alzheimer’s disease, brain volumes, deep learning, magnetic resonance imaging, physical activity

DOI: 10.3233/JAD-230740

Citation: Journal of Alzheimer's Disease, vol. 97, no. 2, pp. 829-839, 2024

Authors: El Haffaf, Lyna Mariam | Ronat, Lucas | Cannizzaro, Adriana | Hanganu, Alexandru

Article Type: Research Article

Abstract: Background: Hyperactive neuropsychiatric symptoms (NPS) (i.e., agitation, disinhibition, and irritability) are among the most challenging symptoms to manage in Alzheimer’s disease (AD). However, their underlying brain correlates have been poorly studied. Objective: We aimed to investigate the associations between the total score of hyperactive NPS and brain structures in participants with AD, mild cognitive impairment (MCI), and cognitively normal older adults (CN). Methods: Neuropsychiatric and 3T MRI data from 216 AD, 564 MCI, and 660 CN participants were extracted from the Alzheimer’s Disease Neuroimaging Initiative database. To define NPS and brain structures’ associations, …we fitted a general linear model (GLM) in two ways: 1) an overall GLM including all three groups (AD, MCI, CN) and 2) three pair-wise GLMs (AD versus MCI, MCI versus CN, AD versus CN). The cortical changes as a function of NPS total score were investigated using multiple regression analyses. Results: Results from the overall GLM include associations between 1) agitation and the right parietal supramarginal surface area in the MCI-CN contrast, 2) disinhibition and the cortical thickness of the right frontal pars opercularis and temporal inferior in the AD-MCI contrast, and 3) irritability and the right frontal pars opercularis , frontal superior, and temporal superior volumes in the MCI-CN contrast. Conclusions: Our study shows that each hyperactive NPS is associated with distinct brain regions in AD, MCI, and CN (groups with different levels of cognitive performance). This suggests that each NPS is associated with a unique signature of brain morphology, including variations in volume, thickness, or area. Show more

Keywords: Agitation, Alzheimer’s disease, cognitively normal older adults, cortical structures, disinhibition, irritability, magnetic resonance imaging, mild cognitive impairment, neuropsychiatric symptoms

DOI: 10.3233/JAD-220857

Citation: Journal of Alzheimer's Disease, vol. 97, no. 2, pp. 841-853, 2024

Authors: Britz, Jesse | Ojo, Emmanuel | Haque, Nazmul | Dhukhwa, Asmita | Hascup, Erin R. | Hascup, Kevin N. | Tischkau, Shelley A.

Article Type: Research Article

Abstract: Background: Chronic disruption of the circadian timing system, often reflected as a loss of restful sleep, also includes myriad other pathophysiological effects. Objective: The current study examined how chronic circadian disruption (CD) could contribute to pathology and rate of progression in the AβPP/PS1 mouse model of Alzheimer’s disease (AD). Methods: A chronic CD was imposed until animals reached 6 or 12 months of age in AβPP/PS1 and C57BL/6J control mice. Home cage activity was monitored for a period of 3–4 weeks prior to the endpoint along with a single timepoint measure of glucose sensitivity. To assess …long term effects of CD on the AD phenotype, animals were re-entrained to a no disruption (ND) schedule just prior to the endpoint, after which a Morris water maze (MWM) was used to assess spatial learning and memory. Results: Dampening of nighttime activity levels occurred in disrupted animals, and female animals demonstrated a greater adaptability to CD. Diminished arginine vasopressin (AVP) and vasoactive intestinal peptide (VIP) levels in the suprachiasmatic nucleus (SCN) of 12-month male AβPP/PS1 exposed to the CD paradigm were observed, potentially accounting for the diminished re-entrainment response. Similarly, CD worsened performance in the MWM in 12-month male AβPP/PS1 animals, whereas no effect was seen in females. Conclusions: Collectively, these findings show that exposure to chronic CD impairs circadian behavioral patterns and cognitive phenotypes of AβPP/PS1 mouse model in a sex-dependent manner. Show more

Keywords: Alzheimer’s disease, amyloid-β, arginine vasopressin, circadian disruption, circadian rhythm, cognition, glial fibrillary acidic protein, metabolism, vasoactive intestinal peptide

DOI: 10.3233/JAD-230089

Citation: Journal of Alzheimer's Disease, vol. 97, no. 2, pp. 855-870, 2024

Authors: Miyano, Takashi | Ayukawa, Yasunori | Anada, Takahisa | Takahashi, Ichiro | Furuhashi, Hiroko | Tokunaga, Shoji | Hirata, Akie | Nakashima, Naoki | Kato, Koichiro | Fukuda, Haruhisa

Article Type: Research Article

Abstract: Background: An association between poor oral health and cognitive decline has been reported. Most of these studies have considered the number of teeth as a criterion, only a few studies have analyzed the relationship between occlusal status and Alzheimer’s disease (AD). Objective: To elucidate whether posterior occlusal contact is associated with AD, focusing on the Eichner classification, among an older population aged 65 years or older in Japan. Methods: This study used monthly claims data of National Health Insurance in Japan from April 2017 to March 2020. The outcome was newly diagnosed AD …defined according to ICD-10 code G30. The number of teeth was estimated by dental code data, and occlusal contact was divided into three categories, namely A, B, and C, according to the Eichner classification. Multivariate Cox proportional hazards models were used to analyze the association between a new diagnosis of AD and the Eichner classification. Results: A total of 22,687 participants were included, 560 of whom had newly diagnosed AD during a mean follow-up period of 12.2 months. The AD participants had a lower proportion of Eichner A and a higher proportion of Eichner C. After adjusting for covariates, hazard ratios (95% confidence intervals) with Eichner B and C were 1.34 (1.01–1.77) and 1.54 (1.03–2.30), respectively. Conclusion: In older people aged≥65 years old, reduced posterior occlusal contact as well as tooth loss have an impact on AD. This study emphasizes the importance of paying attention to occlusal contacts to reduce the risk of AD. Show more

Keywords: Alzheimer’s disease, eichner classification, healthcare administrative claims, occlusal contacts

DOI: 10.3233/JAD-230449

Citation: Journal of Alzheimer's Disease, vol. 97, no. 2, pp. 871-881, 2024

Authors: Fan, Xiang | Cai, Yuan | Zhao, Lei | Liu, Wanting | Luo, Yishan | Au, Lisa Wing Chi | Shi, Lin | Mok, Vincent Chung Tong

Article Type: Research Article

Abstract: Background: Pilot study showed that Alzheimer’s disease resemblance atrophy index (AD-RAI), a machine learning-derived MRI-based neurodegeneration biomarker of AD, achieved excellent diagnostic performance in diagnosing AD with moderate to severe dementia. Objective: The primary objective was to validate and compare the performance of AD-RAI with conventional volumetric hippocampal measures in diagnosing AD with mild dementia. The secondary objectives were 1) to investigate the association between imaging biomarkers with age and gender among cognitively unimpaired (CU) participants; 2) to analyze whether the performance of differentiating AD with mild dementia from CU will improve after adjustment for age/gender. …Methods: AD with mild dementia (n  = 218) and CU (n  = 1,060) participants from 4 databases were included. We investigated the area under curve (AUC), sensitivity, specificity, and balanced accuracy of AD-RAI, hippocampal volume (HV), and hippocampal fraction (HF) in differentiating between AD and CU participants. Among amyloid-negative CU participants, we further analyzed correlation between the biomarkers with age/gender. We also investigated whether adjustment for age/gender will affect performance. Results: The AUC of AD-RAI (0.93) was significantly higher than that of HV (0.89) and HF (0.89). Subgroup analysis among A + AD and A- CU showed that AUC of AD-RAI (0.97) was also higher than HV (0.94) and HF (0.93). Diagnostic performance of AD-RAI and HF was not affected by age/gender while that of HV improved after age adjustment. Conclusions: AD-RAI achieves excellent clinical validity and outperforms conventional volumetric hippocampal measures in aiding the diagnosis of AD mild dementia without the need for age adjustment. Show more

Keywords: Alzheimer’s disease, machine learning, mild dementia, MRI, sensitivity and specificity

DOI: 10.3233/JAD-230574

Citation: Journal of Alzheimer's Disease, vol. 97, no. 2, pp. 883-893, 2024

Authors: Robinson, Carling G. | Coleman, Tia | Buciuc, Marina | Singh, Neha Atulkumar | Pham, Nha Trang Thu | Machulda, Mary M. | Graff-Radford, Jonathan | Whitwell, Jennifer L. | Josephs, Keith A.

Article Type: Research Article

Abstract: Background: Posterior cortical atrophy (PCA) and logopenic progressive aphasia (LPA) are two common atypical Alzheimer’s disease (AD) variants. Little is known about behavioral and neuropsychiatric symptoms or activities of daily living (ADLs) in PCA and LPA, and whether they differ across syndromes. Objective: To characterize the behavioral and neuropsychiatric profiles and ADLs of PCA and LPA and compare presence/absence and severity of symptoms between syndromes. Methods: Seventy-eight atypical AD patients, 46 with PCA and 32 with LPA, completed the Neuropsychiatric Inventory Questionnaire (NPI-Q) and Cambridge Behavioral Inventory-Revised (CBI-R) at baseline and longitudinally over-time. Mann-Whitney U and …Fisher’s Exact Tests assessed for differences in symptoms between the two syndromes with significance set at p ≤0.01. To eliminate demographic differences as confounders the groups were matched, and differences reanalyzed. Results: PCA were younger at onset (p  = 0.006), at time of baseline assessment (p  = 0.02) and had longer disease duration (p  = 0.01). Neuropsychiatric symptoms were common in PCA and LPA, although more common and severe in PCA. At baseline, PCA had a higher NPI-Q total score (p  = 0.01) and depression subscore (p  = 0.01) than LPA. Baseline total CBI-R scores were also higher in PCA than LPA (p  = 0.001) with PCA having worse scores in all 10 CBI-R categories. Longitudinally, there was no difference between groups on the NPI-Q. However, on the CBI-R, PCA had faster rates of worsening on self-grooming (p  = 0.01) and self-dressing (p  = 0.01) compared to LPA. Conclusions: Behavioral and neuropsychiatric symptoms are common in PCA and LPA although these symptoms are more common and severe in PCA. Show more

Keywords: Alzheimer’s disease, atypical Alzheimer’s disease, behavioral, logopenic progressive aphasia, neuropsychiatric, posterior cortical atrophy

DOI: 10.3233/JAD-230652

Citation: Journal of Alzheimer's Disease, vol. 97, no. 2, pp. 895-908, 2024