Journal of Alzheimer's Disease - Volume 85, issue 3

Authors: Li, Weihua | Zhao, Zhilian | Liu, Min | Yan, Shaozhen | An, Yanhong | Qiao, Liyan | Wang, Guihong | Qi, Zhigang | Lu, Jie

Article Type: Research Article

Abstract: Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by cognitive decline and memory impairment. Amnestic mild cognitive impairment (aMCI) is the intermediate stage between normal cognitive aging and early dementia caused by AD. It can be challenging to differentiate aMCI patients from healthy controls (HC) and mild AD patients. Objective: To validate whether the combination of 18 F-fluorodeoxyglucose positron emission tomography (18 F-FDG PET) and diffusion tensor imaging (DTI) will improve classification performance compared with that based on a single modality. Methods: A total of thirty patients with AD, sixty patients …with aMCI, and fifty healthy controls were included. AD was diagnosed according to the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer’s Disease and Related Disorders Association (NINCDS-ADRDA) criteria for probable. aMCI diagnosis was based on Petersen’s criteria. The 18 F-FDG PET and DTI measures were each used separately or in combination to evaluate sensitivity, specificity, and accuracy for differentiating HC, aMCI, and AD using receiver operating characteristic analysis together with binary logistic regression. The rate of accuracy was based on the area under the curve (AUC). Results: For classifying AD from HC, we achieve an AUC of 0.96 when combining two modalities of biomarkers and 0.93 when using 18 F-FDG PET individually. For classifying aMCI from HC, we achieve an AUC of 0.79 and 0.76 using the best individual modality of biomarkers. Conclusion: Our results show that the combination of two modalities improves classification performance, compared with that using any individual modality. Show more

Keywords: Alzheimer’s disease, diffusion tensor imaging, 18F-FDG PET, mild cognitive impairment

DOI: 10.3233/JAD-215338

Citation: Journal of Alzheimer's Disease, vol. 85, no. 3, pp. 1063-1075, 2022

Authors: Britz, Jesse | Ojo, Emmanuel | Dhukhwa, Asmita | Saito, Takashi | Saido, Takaomi C. | Hascup, Erin R. | Hascup, Kevin N. | Tischkau, Shelley A.

Article Type: Research Article

Abstract: Background: Circadian disruption has long been recognized as a symptom of Alzheimer’s disease (AD); however, emerging data suggests that circadian dysfunction occurs early on in disease development, potentially preceding any noticeable cognitive deficits. Objective: This study compares the onset of AD in male and female wild type (C57BL6/J), transgenic (AβPP/PS1), and knock-in (APPNL-F/NL-F ) AD mouse models from the period of plaque initiation (6 months) through 12 months. Methods: Rhythmic daily activity patterns, glucose sensitivity, cognitive function (Morris water maze, MWM), and AD pathology (plaques formation) were assessed. A comparison was made across …sexes. Results: Sex-dependent hyperactivity in AβPP/PS1 mice was observed. In comparison to C57BL/6J animals, 6-month-old male AβPP/PS1 demonstrated nighttime hyperactivity, as did 12-month-old females. Female AβPP/PS1 animals performed significantly worse on a MWM task than AβPP/PS1 males at 12 months and trended toward increased plaque pathology. APPNL-F/NL-F 12-month-old males performed significantly worse on the MWM task compared to 12-month-old females. Significantly greater plaque pathology occurred in AβPP/PS1 animals as compared to APPNL-F/NL-F animals. Female AβPP/PS1 animals performed significantly worse than APPNL-F/NL-F animals in spatial learning and memory tasks, though this was reversed in males. Conclusion: Taken together, this study provides novel insights into baseline sex differences, as well as characterizes baseline diurnal activity variations, in the AβPP/PS1 and APPNL-F/NL-F AD mouse models. Show more

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

DOI: 10.3233/JAD-210629

Citation: Journal of Alzheimer's Disease, vol. 85, no. 3, pp. 1077-1093, 2022

Authors: Smith, Lee | Shin, Jae Il | Oh, Hans | Carmichael, Christina | Jacob, Louis | Stefanac, Sinisa | Lindsay, Rosie K. | Soysal, Pinar | Veronese, Nicola | Tully, Mark A. | Butler, Laurie | Barnett, Yvonne | Koyanagi, Ai

Article Type: Research Article

Abstract: Background: The effect of weight modification on future dementia risk is currently a subject of debate and may be modified by age. Objective: The aim of the present study was to investigate the association between body mass index (BMI) status with mild cognitive impairment (MCI) (a preclinical stage of dementia) in middle-aged and older adults residing in six low- and middle-income countries using nationally representative data. Methods: Cross-sectional data from the Study on Global Ageing and Adult Health (SAGE) were analyzed. MCI was defined using the National Institute on Aging-Alzheimer’s Association criteria. BMI …(kg/m2 ) was based on measured weight and height and categorized as: underweight (<18.5), normal (18.5–24.9), overweight (25.0–29.9), and obese (≥30.0). Multivariable logistic regression analysis and meta-analysis were conducted to assess associations. Results: Data on 32,715 individuals aged ≥50 years with preservation in functional abilities were analyzed [mean (SD) age 62.1 (15.6) years; 51.7% females]. Among those aged 50–64 years, compared to normal weight, underweight (OR = 1.44; 95% CI = 1.14–1.81), overweight (OR = 1.17; 95% CI = 1.002–1.37), and obesity (OR = 1.46; 95% CI = 1.09–1.94) were all significantly associated with higher odds for MCI. In those aged ≥65 years, underweight (OR = 0.71; 95% CI = 0.54–0.95) and overweight (OR = 0.72; 95% CI = 0.55–0.94) were associated with significantly lower odds for MCI, while obesity was not significantly associated with MCI. Conclusion: The results of the study suggest that the association between BMI and MCI is likely moderated by age. Future longitudinal studies are required to confirm or refute the present findings before recommendations for policy and practice can be made. Show more

Keywords: Aged, body mass index, cognitive dysfunction, obesity

DOI: 10.3233/JAD-215345

Citation: Journal of Alzheimer's Disease, vol. 85, no. 3, pp. 1095-1105, 2022

Authors: Mayà, Gerard | Sarto, Jordi | Compta, Yaroslau | Balasa, Mircea | Ximelis, Teresa | Aldecoa, Iban | Gelpi, Ellen | Sánchez-Valle, Raquel | Molina-Porcel, Laura

Article Type: Research Article

Abstract: Background: For neuroscience research, the study of brain tissue of neurologically unimpaired subjects is crucial to interpret findings in neurodegenerative diseases. Sub-optimal neurological follow-up and the presence of neuropathological lesions in supposedly asymptomatic subjects casts doubt as to whether these subjects present an undetected underlying neurodegenerative disease or are resilient to neurodegeneration. Objective: We aimed to assess whether the control donors registered in the Neurological Tissue Bank-Hospital Clínic-IDIBAPS (NTB-HCI) are still free of cognitive symptoms at follow-up and to evaluate the feasibility and utility of a telephone-based screening. Methods: All control subjects older …than 65 years registered at the NTB-HCI database were selected for the study. After a structured telephone interview, those subjects already diagnosed with a neurological disease were excluded. Then, a cognitive screening was performed, including the telephone version of the Mini-Mental State Examination (t-MMSE) and the eight-item interview (AD-8) to the subject and to one informant (AD-8i). Results: In total, 73.8% of the registered donors collaborated in the study. Only 21.4% had at least one of the three cognitive screening tools impaired, and 2.7% had a profile highly suggestive of cognitive impairment. AD-8i correlated moderately with t-MMSE. Conclusion: Telephone-based neurologic screening in control donors is feasible and was within the normal range in most of the subjects in our cohort. Albeit, the involvement of neurologists and periodic neurological screenings are desirable in a control subjects brain donor program, AD8-i could be used to screen the control’s neurological status in the absence of accurate clinical data at the time of the death. Show more

Keywords: AD-8, brain bank, cognitive symptoms, neurological healthy controls, neurological screening, telephone-based screening, telephone MMSE

DOI: 10.3233/JAD-215444

Citation: Journal of Alzheimer's Disease, vol. 85, no. 3, pp. 1107-1113, 2022

Authors: Sakr, Fatemah | Dyrba, Martin | Bräuer, Anja | Teipel, Stefan | for the Alzheimer’s Disease Neuroimaging Initiative

Article Type: Research Article

Abstract: Background: Lipidomics may provide insight into biochemical processes driving Alzheimer’s disease (AD) pathogenesis and ensuing clinical trajectories. Objective: To identify a peripheral lipidomics signature associated with AD pathology and investigate its potential to predict clinical progression. Methods: We used Bayesian elastic net regression to select plasma lipid classes associated with the CSF pTau/Aβ42 ratio as a biomarker of AD pathology in preclinical and prodromal AD cases from the ADNI cohort. Consensus clustering of the selected lipid classes was used to identify lipidomic endophenotypes and study their association with clinical progression. …Results: In the APOE4 -adjusted model, ether-glycerophospholipids, lyso-glycerophospholipids, free-fatty acids, cholesterol esters, and complex sphingolipids were found to be associated with the CSF pTau/Aβ42 ratio. We found an optimal number of five lipidomic endophenotypes in the prodromal and preclinical cases, respectively. In the prodromal cases, these clusters differed with respect to the risk of clinical progression as measured by clinical dementia rating score conversion. Conclusion: Lipid alterations can be captured at the earliest phases of AD. A lipidomic signature in blood may provide a dynamic overview of an individual’s metabolic status and may support identifying different risks of clinical progression. Show more

Keywords: Alzheimer’s disease, heterogeneity, lipidomics, risk assessment

DOI: 10.3233/JAD-201504

Citation: Journal of Alzheimer's Disease, vol. 85, no. 3, pp. 1115-1127, 2022

Authors: Chang, Yu-Ling | Luo, Di-Hua | Huang, Tsung-Ren | Goh, Joshua O.S. | Yeh, Su-Ling | Fu, Li-Chen

Article Type: Research Article

Abstract: Background: Mild cognitive impairment (MCI), which is common in older adults, is a risk factor for dementia. Rapidly growing health care demand associated with global population aging has spurred the development of new digital tools for the assessment of cognitive performance in older adults. Objective: To overcome methodological drawbacks of previous studies (e.g., use of potentially imprecise screening tools that fail to include patients with MCI), this study investigated the feasibility of assessing multiple cognitive functions in older adults with and without MCI by using a social robot. Methods: This study included 33 …older adults with or without MCI and 33 healthy young adults. We examined the utility of five robotic cognitive tests focused on language, episodic memory, prospective memory, and aspects of executive function to classify age-associated cognitive changes versus MCI. Standardized neuropsychological tests were collected to validate robotic test performance. Results: The assessment was well received by all participants. Robotic tests assessing delayed episodic memory, prospective memory, and aspects of executive function were optimal for differentiating between older adults with and without MCI, whereas the global cognitive test (i.e., Mini-Mental State Examination) failed to capture such subtle cognitive differences among older adults. Furthermore, robot-administered tests demonstrated sound ability to predict the results of standardized cognitive tests, even after adjustment for demographic variables and global cognitive status. Conclusion: Overall, our results suggest the human–robot interaction approach is feasible for MCI identification. Incorporating additional cognitive test measures might improve the stability and reliability of such robot-assisted MCI diagnoses. Show more

Keywords: Cognitive assessment, dementia, health care, human–robot interaction, mild cognitive impairment, older adults

DOI: 10.3233/JAD-215015

Citation: Journal of Alzheimer's Disease, vol. 85, no. 3, pp. 1129-1142, 2022

Authors: Wen, Chen | Bi, Yan-Lin | Hu, Hao | Huang, Shu-Yi | Ma, Ya-Hui | Hu, He-Ying | Tan, Lan | Yu, Jin-Tai

Article Type: Research Article

Abstract: Background: Subjective cognitive decline (SCD) might occur at the early stages of dementia. Individuals with SCD have an increased risk of subsequent objective cognitive decline and greater rates of progression to dementia. Objective: We aimed to explore the associations between SCD and cerebrospinal fluid (CSF) biomarkers of Alzheimer’s disease (AD) pathology in cognitively normal individuals. Methods: A total of 1,099 cognitively normal elders with available data on CSF biomarkers of AD pathology (Aβ42 , P-tau, and T-tau) were included in our analysis. Linear regression was used to examine the associations of SCD status …and SCD severity with CSF biomarkers. Additionally, a review was conducted to discuss the associations between SCD and CSF biomarkers of AD pathology. Results: After adjustments for covariates, SCD and SCD severity showed significant associations with CSF Aβ42 (SCD: β= –0.0003, p  = 0.0263; SCD severity: β= –0.0004, p  = 0.0046), CSF T-tau/Aβ42 ratio (SCD: β= 0.1080, p  = 0.0064; SCD severity: β= 0.1129, p  = 0.0009) and CSF P-tau/Aβ42 ratio (SCD: β= 0.0167, p  = 0.0103; SCD severity: β= 0.0193, p  = 0.0006) rather than T-tau and P-tau compared with cognitively normal individuals. In the review, a total of 28 studies were finally included after reviewing 174 articles. CSF Aβ42 was lower in SCD than cognitively normal (CN) individuals, but higher than those with objective cognitive decline. However, CSF tau pathology showed no difference between SCD and CN. Conclusion: The results indicated that pathophysiological changes in CSF Aβ pathology occurred in individuals with SCD, which provide new insights into early intervention of AD. Show more

Keywords: Alzheimer’s disease, cerebrospinal fluid biomarker, subjective cognitive decline

DOI: 10.3233/JAD-215178

Citation: Journal of Alzheimer's Disease, vol. 85, no. 3, pp. 1143-1151, 2022

Authors: Lutski, Miri | Rasooli, Iris | Sternberg, Shelley | Lemberger, John | Mery, Nisim | Shohat, Tamy | Zucker, Inbar

Article Type: Research Article

Abstract: Background: Data on the rate of dementia is essential for planning and developing appropriate services at the national level. Objective: We report the prevalence and incidence of dementia, based on electronic health records available for the whole population. Methods: This national dementia dataset was established as a part of the National Program to Address Alzheimer’s and Other Types of Dementia. Data from medical health records for all persons aged 45+ in Israel, for 2016, were extracted from the databases of the four health maintenance organizations. Dementia cases were identified based on either recorded dementia diagnosis, through …International Classification of Diseases (ICD-9 and ICD-10) or dispensation of anti-dementia drugs. The date of first diagnosis was determined by the earliest recording. Results: A total of 65,951 persons with dementia, aged 45+, were identified from electronic health data. Based on both ICD codes and anti-dementia drugs, the prevalence rates of dementia among individuals aged 45+ and 65+ in 2016 were 2.5%and 6.4%, respectively, and the incidence rates were 0.49%and 1.3%, respectively. Based on ICD codes alone, the prevalence rates of dementia among individuals aged 45+ and 65+ in 2016 were 2.1%and 5.4%respectively, and the incidence rates were 0.36%and 0.96%respectively. The rates were higher among females compared to males and paradoxically lower in lower socioeconomic status compared to higher statuses. Conclusion: This data collection reflects the present access of dementia patients to medical care resources and provides the basis for service planning and future dementia policies. Show more

Keywords: Dementia, early-onset dementia, electronic health data, incidence, national dataset, prevalence

DOI: 10.3233/JAD-215048

Citation: Journal of Alzheimer's Disease, vol. 85, no. 3, pp. 1153-1161, 2022

Authors: Yang, Li | Xuan, Cheng | Yu, Caiyan | Zheng, Pinpin | Yan, Jing

Article Type: Research Article

Abstract: Background: With the accelerating aging process, the number of participants with Alzheimer’s disease (AD) is rising sharply, causing a huge economic burden. Objective: This study aimed to identify blood protein and metabolic biomarkers and explore the diagnostic model for AD among elderly in southeast China. Methods: We established a cohort among population with high risk AD in Zhejiang Province in 2018. Case and control groups each consisting of 45 subjects, matched for gender and age, were randomly selected from the cohort. Based on bioinformatics research, PRM/MRM technology was used to detect candidate biomarkers. Ensemble-based feature selection …and machine learning methods was used to screen important variables as risk indicators for AD. Based on the risk biomarkers, the risk diagnostic model of AD in the elderly was constructed and evaluated. Results: Cystine and CPB2 were evaluated as biomarkers. The diagnostic model is constructed using logistic regression algorithm with the best cutoff value, sensitivity, specificity, and accuracy of 0.554, 0.895, 0.976, and 0.938, respectively, which determined by Youden’s index. The results showed that the model with protein and metabolite had a high efficiency. Conclusion: It showed that the diagnostic model constructed by Cystine and CPB2 had a good performance on sample classification. This study was of great significance for the early screening and diagnosis of AD, timely intervention, control and delay the development of dementia in southeast China. Show more

Keywords: Alzheimer’s disease, biomarker, diagnostic model, elderly

DOI: 10.3233/JAD-215119

Citation: Journal of Alzheimer's Disease, vol. 85, no. 3, pp. 1163-1174, 2022

Authors: Kimmel, Hannah J. | Levine, Deborah A. | Whitney, Rachael T. | Forman, Jane | Plassman, Brenda L. | Fagerlin, Angela | Welsh-Bohmer, Kathleen Anne | Reale, Bailey K. | Galecki, Andrzej T. | Blair, Emilie | Langa, Kenneth M. | Giordani, Bruno | Kollman, Colleen | Wang, Jing | Zahuranec, Darin B.

Article Type: Research Article

Abstract: Background: Older patients (≥65 years) with mild cognitive impairment (MCI) are undertreated for cardiovascular disease (CVD). One reason for this disparity could be that patients with MCI might underestimate the chances of CVD and overestimate dementia. Objective: To compare conceptions of health risk between older patients with MCI and normal cognition (NC) and their care partners. Methods: We conducted a multi-center mixed-methods study of patient-care partner dyads completing written quantitative surveys (73% response rate; 127 dyads: 66 MCI and 61 NC) or semi-structured interviews (20 dyads: 11 MCI, and 9 NC). Surveys assessed two-year patient risks …of dementia, heart attack, stroke, and fall. Interviews assessed similar health risks and reasons for risk perceptions. Results: On surveys, a similarly low proportion of MCI and NC patients felt they were at risk of stroke (5% versus 2%; p  = 0.62) and heart attack (2% versus 0%; p  = 0.99). More MCI than NC patients perceived dementia risk (26% versus 2%; p  < 0.001). Care partners’ survey findings were similar. Interviews generally confirmed these patterns and also identified reasons for future health concerns. For both MCI and NC dyads, personal experience with cognitive decline or CVD (personal or family history) increased concerns about each disease. Additionally, perceptions of irreversibility and lack of treatment for cognitive decline increased concern about dementia. Conclusion: Less use of CVD treatments in MCI seems unlikely to be driven by differential perceptions of CVD risk. Future work to improve awareness of CVD risks in older patients and dementia risk in patients with MCI are warranted. Show more

Keywords: Dementia, family caregivers, heart disease risk factors, mild cognitive impairment, risk assessment

DOI: 10.3233/JAD-215155

Citation: Journal of Alzheimer's Disease, vol. 85, no. 3, pp. 1175-1187, 2022