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

Authors: Fan, Xinxin | Li, Haining | Liu, Lin | Zhang, Kai | Zhang, Zhewei | Chen, Yi | Wang, Zhen | He, Xiaoli | Xu, Jinping | Hu, Qingmao

Article Type: Research Article

Abstract: Background: Structural magnetic resonance imaging (sMRI) is vital for early Alzheimer’s disease (AD) diagnosis, though confirming specific biomarkers remains challenging. Our proposed Multi-Scale Self-Attention Network (MUSAN) enhances classification of cognitively normal (CN) and AD individuals, distinguishing stable (sMCI) from progressive mild cognitive impairment (pMCI). Objective: This study leverages AD structural atrophy properties to achieve precise AD classification, combining different scales of brain region features. The ultimate goal is an interpretable algorithm for this method. Methods: The MUSAN takes whole-brain sMRI as input, enabling automatic extraction of brain region features and modeling of correlations …between different scales of brain regions, and achieves personalized disease interpretation of brain regions. Furthermore, we also employed an occlusion sensitivity algorithm to localize and visualize brain regions sensitive to disease. Results: Our method is applied to ADNI-1, ADNI-2, and ADNI-3, and achieves high performance on the classification of CN from AD with accuracy (0.93), specificity (0.82), sensitivity (0.96), and area under curve (AUC) (0.95), as well as notable performance on the distinguish of sMCI from pMCI with accuracy (0.85), specificity (0.84), sensitivity (0.74), and AUC (0.86). Our sensitivity masking algorithm identified key regions in distinguishing CN from AD: hippocampus, amygdala, and vermis. Moreover, cingulum, pallidum, and inferior frontal gyrus are crucial for sMCI and pMCI discrimination. These discoveries align with existing literature, confirming the dependability of our model in AD research. Conclusion: Our method provides an effective AD diagnostic and conversion prediction method. The occlusion sensitivity algorithm enhances deep learning interpretability, bolstering AD research reliability. Show more

Keywords: Alzheimer’s disease, deep learning, explainable deep learning, multilevel feature learning, structural MRI

DOI: 10.3233/JAD-230705

Citation: Journal of Alzheimer's Disease, vol. 97, no. 2, pp. 909-926, 2024

Authors: Gao, Ju | Leinonen, Henri | Wang, Evan J. | Ding, Mao | Perry, George | Palczewski, Krzysztof | Wang, Xinglong

Article Type: Research Article

Abstract: Background: Increasing evidence has highlighted retinal impairments in neurodegenerative diseases. Dominant mutations in TAR DNA-binding protein 43 (TDP-43) cause amyotrophic lateral sclerosis (ALS), and the accumulation of TDP-43 in the cytoplasm is a pathological hallmark of ALS, frontotemporal dementia (FTD), and many other neurodegenerative diseases. Objective: While homozygous transgenic mice expressing the disease-causing human TDP-43 M337V mutant (TDP-43M337V mice) experience premature death, hemizygous TDP-43M337V mice do not suffer sudden death, but they exhibit age-dependent motor-coordinative and cognitive deficits. This study aims to leverage the hemizygous TDP-43M337V mice as a valuable ALS/FTD disease model for the …assessment also of retinal changes during the disease progression. Methods: We evaluated the retinal function of young TDP-43M337V mice by full field electroretinogram (ERG) recordings. Results: At 3–4 months of age, well before the onset of brain dysfunction at 8 months, the ERG responses were notably impaired in the retinas of young female TDP-43M337V mice in contrast to their male counterparts and age-matched non-transgenic mice. Mitochondria have been implicated as critical targets of TDP-43. Further investigation revealed that significant changes in the key regulators of mitochondrial dynamics and bioenergetics were only observed in the retinas of young female TDP-43M337V mice, while these alterations were not present in the brains of either gender. Conclusions: Together our findings suggest a sex-specific vulnerability within the retina in the early disease stage, and highlight the importance of retinal changes and mitochondrial markers as potential early diagnostic indicators for ALS, FTD, and other TDP-43 related neurodegenerative conditions. Show more

Keywords: Alzheimer’s disease, amyotrophic lateral sclerosis, frontotemporal dementia, mitochondrial dynamics, OXPHOS, retina, sex differences, TDP-43

DOI: 10.3233/JAD-231102

Citation: Journal of Alzheimer's Disease, vol. 97, no. 2, pp. 927-937, 2024

Authors: Dingle, Sara E. | Milte, Catherine M. | Daly, Robin M. | Torres, Susan J.

Article Type: Research Article

Abstract: Background: Dementia, with the most common form being Alzheimer’s disease, is a global health issue and lifestyle-based strategies may reduce risk. Individuals with a family history of dementia are an important target group, but little is known about their attitudes and perceptions of dementia risk reduction. Objective: To elucidate the attitudes to and key considerations for multidomain lifestyle-based dementia prevention strategies in middle-aged Australians with a family history of dementia. Methods: Twenty participants (80% female; age range 47–65 years), undertook semi-structured phone-based interviews. Inductive thematic analysis of interview transcripts was conducted. Hierarchical coding …frames and illustrative quotes were compiled and critically challenged until a final set of themes was produced. Results: Some participants expressed a positive attitude toward lifestyle-based dementia prevention. Reasons related to wanting to future proof, believing that risk reduction is relevant at all life stages and/or that there is always room for improvement. Other participants had a negative attitude, expressing that they were already following a healthy lifestyle, did not feel it was relevant to them yet, and/or held a deterministic view that dementia is random. Important considerations congregated on the themes of being tailored/personalized, taking a holistic approach, and involving small, achievable steps. Conclusions: In individuals with a family history of dementia, a positive attitude to dementia prevention holds promise for intervention efforts, but in individuals expressing negative attitudes, further education and individual-level counselling may be warranted. Multidomain lifestyle-based preventive strategies also need to be tailored to the needs of key target groups to optimize appeal and effectiveness. Show more

Keywords: Alzheimer’s disease, dementia, lifestyle, prevention, qualitative study

DOI: 10.3233/JAD-230176

Citation: Journal of Alzheimer's Disease, vol. 97, no. 2, pp. 939-949, 2024

Authors: de la Perrelle, Lenore

Article Type: Article Commentary

Abstract: With an aging population, an increase in cases of Alzheimer’s disease and dementia worldwide poses a significant health burden. While we hope for a cure, preventing dementia by reducing risks is important for global population health. Prevention strategies are difficult to implement when facing inequality across the world for access to healthy lifestyles. An approach that centers on individual responsibility and health professional interventions for targeted groups may risk missing the policy and environmental drivers of change. Barriers and enablers need to be explored and interventions are needed at individual, structural and social levels to normalize mid-life risk reduction.

Keywords: Alzheimer’s disease, dementia risk reduction, family history, mid-life strategies, multidomain interventions

DOI: 10.3233/JAD-231348

Citation: Journal of Alzheimer's Disease, vol. 97, no. 2, pp. 951-952, 2024

Authors: Frentz, Ingeborg | van Arendonk, Joyce | Leeuwis, Anna E. | Vernooij, Meike W. | van der Flier, Wiesje M. | Bos, Daniel | De Deyn, Peter Paul | Wolters, Frank J. | Ikram, M. Arfan

Article Type: Research Article

Abstract: Background: Dementia is a multifactorial disease, with Alzheimer’s disease (AD) and vascular pathology often co-occurring in many individuals with dementia. Yet, the interplay between AD and vascular pathology in cognitive decline is largely undetermined. Objective: The aim of the present study was to examine the joint effect of arteriosclerosis and AD pathology on cognition in the general population without dementia. Methods: We determined the interaction between blood-based AD biomarkers and CT-defined arteriosclerosis on cognition in 2,229 dementia-free participants of the population-based Rotterdam Study (mean age: 68.9 years, 52% women) cross-sectionally. Results: Amyloid-β (Aβ)42 …and arterial calcification were associated with cognitive performance. After further adjustment for confounders in a model that combined all biomarkers, only arterial calcification remained independently associated with cognition. There was a significant interaction between arterial calcification and Aβ42 and between arterial calcification and the ratio of Aβ42/40 . Yet, estimates attenuated, and interactions were no longer statistically significant after adjustment for cardio metabolic risk factors. Conclusions: Arteriosclerosis and AD display additive interaction-effects on cognition in the general population, that are due in part to cardio metabolic risk factors. These findings suggest that joint assessment of arteriosclerosis and AD pathology is important for understanding of disease etiology in individuals with cognitive impairment. Show more

Keywords: Alzheimer’s disease, amyloid-β, arteriosclerosis, calcification, dementia, plasma biomarkers

DOI: 10.3233/JAD-230604

Citation: Journal of Alzheimer's Disease, vol. 97, no. 2, pp. 953-961, 2024

Authors: de Boer, Sterre C.M. | Riedl, Lina | Fenoglio, Chiara | Rue, Ishana | Landin-Romero, Ramon | Matis, Sophie | Chatterton, Zac | Galimberti, Daniela | Halliday, Glenda | Diehl-Schmid, Janine | Piguet, Olivier | Pijnenburg, Yolande A.L. | Ducharme, Simon

Article Type: Research Article

Abstract: Background: The behavioral variant of frontotemporal dementia (bvFTD) is very heterogeneous in pathology, genetics, and disease course. Unlike Alzheimer’s disease, reliable biomarkers are lacking and sporadic bvFTD is often misdiagnosed as a primary psychiatric disorder (PPD) due to overlapping clinical features. Current efforts to characterize and improve diagnostics are centered on the minority of genetic cases. Objective: The multi-center study DIPPA-FTD aims to develop diagnostic and prognostic algorithms to help distinguish sporadic bvFTD from late-onset PPD in its earliest stages. Methods: The prospective DIPPA-FTD study recruits participants with late-life behavioral changes, suspect for bvFTD or …late-onset PPD diagnosis with a negative family history for FTD and/or amyotrophic lateral sclerosis. Subjects are invited to participate after diagnostic screening at participating memory clinics or recruited by referrals from psychiatric departments. At baseline visit, participants undergo neurological and psychiatric examination, questionnaires, neuropsychological tests, and brain imaging. Blood is obtained to investigate biomarkers. Patients are informed about brain donation programs. Follow-up takes place 10-14 months after baseline visit where all examinations are repeated. Results from the DIPPA-FTD study will be integrated in a data-driven approach to develop diagnostic and prognostic models. Conclusions: DIPPA-FTD will make an important contribution to early sporadic bvFTD identification. By recruiting subjects with ambiguous or prodromal diagnoses, our research strategy will allow the characterization of early disease stages that are not covered in current sporadic FTD research. Results will hopefully increase the ability to diagnose sporadic bvFTD in the early stage and predict progression rate, which is pivotal for patient stratification and trial design. Show more

Keywords: Alzheimer’s disease, diagnostics, frontotemporal dementia, neurodegeneration, prognostics, psychiatric disorders

DOI: 10.3233/JAD-230829

Citation: Journal of Alzheimer's Disease, vol. 97, no. 2, pp. 963-973, 2024

Article Type: Correction

DOI: 10.3233/JAD-239014

Citation: Journal of Alzheimer's Disease, vol. 97, no. 2, pp. 975-976, 2024