Journal of Alzheimer's Disease - Volume 91, issue 2

Authors: Shirzadi, Zahra | Rabin, Jennifer | Launer, Lenore J. | Bryan, R. Nick | Al-Ozairi, Abdulla | Chhatwal, Jasmeer | Al-Ozairi, Ebaa | Detre, John A. | Black, Sandra E. | Swardfager, Walter | MacIntosh, Bradley J.

Article Type: Research Article

Abstract: Background: Metabolic and vascular risk factors (MVRF) are associated with neurodegeneration and poor cognition. There is a need to better understand the impact of these risk factors on brain health in the decades that precede cognitive impairment. Longitudinal assessments can provide new insight regarding changes in MVRFs that are related to brain imaging features. Objective: To investigate whether longitudinal changes in MVRF spanning up to 25 years would be associated with midlife brain volume and cognition. Methods: Participants were from the CARDIA study (N  = 467, age at year 25 = 50.6±3.4, female/male = 232/235, black/white = 161/306). Three models were developed, each …designed to capture change over time; however, we were primarily interested in the average real variability (ARV) as a means of quantifying MVRF variability across all available assessments. Results: Multivariate partial least squares that used ARV metrics identified two significant latent variables (partial correlations ranged between 0.1 and 0.26, p  < 0.01) that related MVRF ARV and regional brain volumes. Both latent variables reflected associations between brain volume and MVRF ARV in obesity, cholesterol, blood pressure, and glucose. Subsequent bivariate correlations revealed associations among MVRF factors, aggregate brain volume and cognition. Conclusion: This study demonstrates that MVRF variability over time is associated with midlife brain volume in regions that are relevant to later-life cognitive decline. Show more

Keywords: Brain volume, cognition, metabolic syndrome, partial least squares, vascular risk factors

DOI: 10.3233/JAD-220340

Citation: Journal of Alzheimer's Disease, vol. 91, no. 2, pp. 627-635, 2023

Authors: Wu, Jianfeng | Su, Yi | Zhu, Wenhui | Jalili Mallak, Negar | Lepore, Natasha | Reiman, Eric M. | Caselli, Richard J. | Thompson, Paul M. | Chen, Kewei | Wang, Yalin

Article Type: Research Article

Abstract: Background: Amyloid-β (Aβ) plaques and tau protein tangles in the brain are the defining ‘A’ and ‘T’ hallmarks of Alzheimer’s disease (AD), and together with structural atrophy detectable on brain magnetic resonance imaging (MRI) scans as one of the neurodegenerative (‘N’) biomarkers comprise the “ATN framework” of AD. Current methods to detect Aβ/tau pathology include cerebrospinal fluid (invasive), positron emission tomography (PET; costly and not widely available), and blood-based biomarkers (promising but mainly still in development). Objective: To develop a non-invasive and widely available structural MRI-based framework to quantitatively predict the amyloid and tau measurements. Methods: …With MRI-based hippocampal multivariate morphometry statistics (MMS) features, we apply our Patch Analysis-based Surface Correntropy-induced Sparse coding and max-pooling (PASCS-MP) method combined with the ridge regression model to individual amyloid/tau measure prediction. Results: We evaluate our framework on amyloid PET/MRI and tau PET/MRI datasets from the Alzheimer’s Disease Neuroimaging Initiative. Each subject has one pair consisting of a PET image and MRI scan, collected at about the same time. Experimental results suggest that amyloid/tau measurements predicted with our PASCP-MP representations are closer to the real values than the measures derived from other approaches, such as hippocampal surface area, volume, and shape morphometry features based on spherical harmonics. Conclusion: The MMS-based PASCP-MP is an efficient tool that can bridge hippocampal atrophy with amyloid and tau pathology and thus help assess disease burden, progression, and treatment effects. Show more

Keywords: Alzheimer’s disease, amyloid deposition, Braak12 tau-SUVR, Braak34 tau-SUVR, Centiloid, dictionary and correntropy-induced sparse coding, hippocampal multivariate morphometry statistics, tau deposition

DOI: 10.3233/JAD-220812

Citation: Journal of Alzheimer's Disease, vol. 91, no. 2, pp. 637-651, 2023

Authors: Hendriks, Stevie | Peetoom, Kirsten | Tange, Huibert | Papma, Janne | van der Flier, Wiesje M. | Koopmans, Raymond | Bakker, Christian | Köhler, Sebastian | de Vugt, Marjolein

Article Type: Research Article

Abstract: Background: Timely diagnosis and adequate care is important for persons with young-onset dementia (YOD) and their caregivers, due to the high impact of the disease. Initiating care can be difficult for the general practitioner (GP) and other healthcare professionals. Objective: Provide insight in the care use of persons with YOD and identify factors influencing care use. Methods: A primary care register was used for this study. Information on the care use of persons with YOD was extracted from the GPs written notes. Information entailed time until start of care use, reasons and factors influencing the GP’s …decision, and reasons and factors influencing actual care use were included. Analyses included quantitative explorative descriptive analyses, and qualitative manifest content analyses. Results: 75 persons with YOD were included in this study. The main reason for GPs to refer for diagnosis was concerns of caregivers. After diagnosis, 72% of the persons were assigned a case manager, 42.7% received day care, and 44% were admitted to a long-term care facility. A higher percentage of persons without a case manager was admitted to a long-term care facility (64%) compared to the persons with a case manager (36%). Reasons for not initiating care were reluctancy of the persons with YOD or their caregivers, the person deceased, or because the GP did not refer for care. Conclusion: Care use differed between persons due to different needs and reasons. Although most persons with YOD receive care in the years after diagnosis, there are still factors that could be improved. Show more

Keywords: Delivery of health care, dementia, middle aged

DOI: 10.3233/JAD-220713

Citation: Journal of Alzheimer's Disease, vol. 91, no. 2, pp. 653-662, 2023

Authors: Zijlmans, Jend L. | Riemens, Mariska S. | Vernooij, Meike W. | Ikram, M. Arfan | Luik, Annemarie I.

Article Type: Research Article

Abstract: Background: The cognitive reserve hypothesis aims to explain individual differences in susceptibility to the functional impact of dementia-related pathology. Previous research suggested that poor subjective sleep may be associated with a lower cognitive reserve. Objective: The objective was to investigate if actigraphy-estimated sleep and 24-hour activity rhythms are associated with cognitive reserve. Methods: This cross-sectional study included 1,002 participants from the Rotterdam Study (mean age: 65.0 years, standard deviation (SD): 7.1) who were assessed with actigraphy, five cognitive tests, and brain-MRI between 2009– 2014. Sleep and 24-hour activity rhythms were measured using actigraphy (mean days: 6.7, …SD: 0.5). Cognitive reserve was defined as a latent variable that captures variance across cognitive tests, while adjusting for age, sex, education, total brain volume, intracranial volume, and white matter hyperintensity volume. Associations of sleep and 24-hour activity rhythms with cognitive reserve were assessed using structural equation models. Results: Longer sleep onset latency (adjusted mean difference: – 0.16, 95% CI: – 0.24; – 0.08) and lower sleep efficiency (0.14, 95% CI: 0.05; 0.22) were associated with lower cognitive reserve. Total sleep time and wake after sleep onset were not significantly associated with cognitive reserve. After mutual adjustment, only the association of longer sleep onset latency remained significant (– 0.12, 95% CI: – 0.20; – 0.04). The 24-hour activity rhythm was not significantly associated with cognitive reserve. Conclusion: In conclusion, our study suggests that longer sleep onset latency is particularly associated with lower cognitive reserve. Future longitudinal work is needed to assess whether shortening the sleep onset latency could enhance cognitive reserve, in order to limit the susceptibility to the functional impact of dementia-related pathology. Show more

Keywords: Actigraphy, circadian rhythm, cognitive reserve, cohort study, sleep

DOI: 10.3233/JAD-220714

Citation: Journal of Alzheimer's Disease, vol. 91, no. 2, pp. 663-672, 2023

Authors: Matsuzono, Kosuke | Suzuki, Masayuki | Anan, Yuhei | Ozawa, Tadashi | Mashiko, Takafumi | Koide, Reiji | Tanaka, Ryota | Fujimoto, Shigeru

Article Type: Research Article

Abstract: Background: The relationship between transesophageal echocardiography findings and cognitive function. Objective: This study aimed to establish an association between transesophageal echocardiography findings and cognitive function in stroke survivors. Methods: A single-center study was conducted between April 1, 2017 and March 31, 2022. All subjects that were included had a past history of ischemic stroke and were admitted after >21 days from onset. The participants underwent cognitive function tests including a Mini-Mental State Examination, Revised Hasegawa Dementia Scale, Frontal Assessment Battery, and transesophageal echocardiography. Results: The results of 126 participants were analyzed. The cognitive function …of participants with a spontaneous echo contrast (+) in the left atrium including appendage or of those with an aorta-arch plaque with a maximum thickness ≥4 mm significantly worse while neither the patent foramen ovale nor the branch extending plaque influenced cognitive function (The median cognitive scores of the spontaneous echo contrast (–) versus (+) were 26 versus 22, p  < 0.01** , 26 versus 21, p  < 0.001*** , and 14 versus 11, p  < 0.01** . Those of the aortic-arch plaque max thickness (<4 mm) versus (≥4 mm) were 26 versus 25, p  < 0.05* , 27 versus 24, p  < 0.05* , and 15 versus 13, p  < 0.05* ). Conclusion: Our findings show that spontaneous echo contrast in the left atrium and aortic-arch atheroma detected by transesophageal echocardiography, were negatively associated with cognitive function. Show more

Keywords: Aortic-arch atheroma, cognitive function, examination, spontaneous echo contrast, transesophageal echocardiography

DOI: 10.3233/JAD-220763

Citation: Journal of Alzheimer's Disease, vol. 91, no. 2, pp. 673-681, 2023

Authors: Walker, Jamie M. | Dehkordi, Shiva Kazempour | Schaffert, Jeff | Goette, William | White III, Charles L. | Richardson, Timothy E. | Zare, Habil

Article Type: Research Article

Abstract: Background: The strongest risk factor for the development of Alzheimer’s disease (AD) is age. The progression of Braak stage and Thal phase with age has been demonstrated. However, prior studies did not include cognitive status. Objective: We set out to define normative values for Alzheimer-type pathologic changes in individuals without cognitive decline, and then define levels that would qualify them to be resistant to or resilient against these changes. Methods: Utilizing neuropathology data obtained from the National Alzheimer’s Coordinating Center (NACC), we demonstrate the age-related progression of Alzheimer-type pathologic changes in cognitively normal individuals (CDR = 0, n … = 542). With plots generated from these data, we establish standard lines that may be utilized to measure the extent to which an individual’s Alzheimer-type pathology varies from the estimated normal range of pathology. Results: Although Braak stage and Thal phase progressively increase with age in cognitively normal individuals, the Consortium to Establish a Registry for Alzheimer’s Disease neuritic plaque score and Alzheimer’s disease neuropathologic change remain at low levels. Conclusion: These findings suggest that an increasing burden of neuritic plaques is a strong predictor of cognitive decline, whereas, neurofibrillary degeneration and amyloid-β (diffuse) plaque deposition, both to some degree, are normal pathologic changes of aging that occur in almost all individuals regardless of cognitive status. Furthermore, we have defined the amount of neuropathologic change in cognitively normal individuals that would qualify them to be “resilient” against the pathology (significantly above the normative values for age, but still cognitively normal) or “resistant” to the development of pathology (significantly below the normative values for age). Show more

Keywords: Alzheimer’s disease, Braak stage, CERAD neuritic plaque score, cognitively normal, resilience, resistance, Thal phase

DOI: 10.3233/JAD-220898

Citation: Journal of Alzheimer's Disease, vol. 91, no. 2, pp. 683-695, 2023

Authors: Gorenflo, Maria P. | Davis, Pamela B. | Kendall, Ellen K. | Olaker, Veronica R. | Kaelber, David C. | Xu, Rong

Article Type: Research Article

Abstract: Background: Currently there are no effective therapies to prevent or halt the development of Alzheimer’s disease (AD). Multiple risk factors are involved in AD, including ischemic stroke (IS). Aspirin is often prescribed following IS to prevent blood clot formation. Observational studies have shown inconsistent findings with respect to the relationship between aspirin use and the risk of AD. Objective: To investigate the relationship between aspirin therapy after IS and the new diagnosis of AD in elderly patients. Methods: This retrospective cohort study leveraged a large database that contains over 90 million electronic health records to compare …the hazard rates of AD after IS in elderly patients prescribed aspirin versus those not prescribed aspirin after propensity-score matching for relevant confounders. Results: At 1, 3, and 5 years after first IS, elderly patients prescribed aspirin were less likely to develop AD than those not prescribed aspirin: Hazard Ratio = 0.78 [0.65,0.94], 0.81 [0.70,0.94], and 0.76 [0.70,0.92]. Conclusion: Our findings suggest that aspirin use may prevent AD in patients with IS, a subpopulation at high risk of developing the disease. Show more

Keywords: Alzheimer’s disease, aspirin, inflammation, ischemic stroke, mortality

DOI: 10.3233/JAD-220901

Citation: Journal of Alzheimer's Disease, vol. 91, no. 2, pp. 697-704, 2023

Authors: Delgado-Álvarez, Alfonso | Díez-Cirarda, María | Delgado-Alonso, Cristina | Hernández-Lorenzo, Laura | Cuevas, Constanza | Valles-Salgado, María | Montero-Escribano, Paloma | Gil-Moreno, María José | Matías-Guiu, Jorge | García-Ramos, Rocío | Matias-Guiu, Jordi A.

Article Type: Research Article

Abstract: Background: The Rowland Universal Dementia Assessment Scale (RUDAS) is a cognitive test with favorable diagnostic properties for detecting dementia and a low influence of education and cultural biases. Objective: We aimed to validate the RUDAS in people with Alzheimer’s disease (AD), Parkinson’s disease (PD), and multiple sclerosis (MS). Methods: We enrolled one hundred and fifty participants (60 with AD, 30 with PD, 60 with MS, and 120 healthy controls (HC)). All clinical groups completed a comprehensive neuropsychological battery, RUDAS, and standard cognitive tests of each disorder: MMSE, SCOPA-COG, and Symbol Digit Modalities Test. Intergroup comparisons between …clinical groups and HC and ROC curves were estimated. Random Forest algorithms were trained and validated to detect cognitive impairment using RUDAS and rank the most relevant scores. Results: The RUDAS scores were lower in patients with AD, and patients with PD and MS showed cognitive impairment compared to healthy controls. Effect sizes were generally large. The total score was the most discriminative, followed by the memory score. Correlations with standardized neuropsychological tests were moderate to high. Random Forest algorithms obtained accuracies over 80–90% using the RUDAS for diagnosing AD and cognitive impairment associated with PD and MS. Conclusion: Our results suggest the RUDAS is a valid test candidate for multi-disease cognitive screening tool in AD, PD, and MS. Show more

Keywords: Alzheimer’s disease, cognitive screening test, multiple sclerosis, Parkinson’s disease, RUDAS

DOI: 10.3233/JAD-220907

Citation: Journal of Alzheimer's Disease, vol. 91, no. 2, pp. 705-717, 2023

Authors: Kostev, Karel | Gessler, Nele | Wohlmuth, Peter | Arnold, Dirk | Bein, Berthold | Bohlken, Jens | Herrlinger, Klaus | Jacob, Louis | Koyanagi, Ai | Nowak, Lorenz | Smith, Lee | Wesseler, Claas | Sheikhzadeh, Sara | Wollmer, Marc Axel

Article Type: Research Article

Abstract: Background: Dementia has been identified as a major predictor of mortality associated with COVID-19. Objective: The objective of this study was to investigate the association between dementia and mortality in COVID-19 inpatients in Germany across a longer interval during the pandemic. Methods: This retrospective study was based on anonymized data from 50 hospitals in Germany and included patients with a confirmed COVID-19 diagnosis hospitalized between March 11, 2020 and July, 20, 2022. The main outcome of the study was the association of mortality during inpatient stays with dementia diagnosis, which was studied using multivariable logistic regression …adjusted for age, sex, and comorbidities as well as univariate logistic regression for matched pairs. Results: Of 28,311 patients diagnosed with COVID-19, 11.3% had a diagnosis of dementia. Prior to matching, 26.5% of dementia patients and 11.5% of non-dementia patients died; the difference decreased to 26.5% of dementia versus 21.7% of non-dementia patients within the matched pairs (n  = 3,317). This corresponded to an increase in the risk of death associated with dementia (OR = 1.33; 95% CI: 1.16–1.46) in the univariate regression conducted for matched pairs. Conclusion: Although dementia was associated with COVID-19 mortality, the association was weaker than in previously published studies. Further studies are needed to better understand whether and how pre-existing neuropsychiatric conditions such as dementia may impact the course and outcome of COVID-19. Show more

Keywords: COVID-19 diagnosis, dementia, elderly, Germany, hospital, mortality

DOI: 10.3233/JAD-220918

Citation: Journal of Alzheimer's Disease, vol. 91, no. 2, pp. 719-726, 2023

Authors: Mohr, Wiebke | Rädke, Anika | Afi, Adel | Weber, Niklas | Platen, Moritz | Mühlichen, Franka | Scharf, Annelie | Michalowsky, Bernhard | Hoffmann, Wolfgang

Article Type: Research Article

Abstract: Background: Person-centered care (PCC) requires knowledge about patient preferences. Among people living with cognitive impairments (PlwCI), evidence on quantitative, choice-based preferences, which allow to quantify, weigh, and rank care elements, is limited. Furthermore, data on the congruence of patient preferences with physicians’ judgements for PCC are missing. Such information is expected to support the implementation of PCC; state-of-the-art medical care aligned with patients’ preferences. Objective: To elicit patient preferences and physicians’ judgements for PCC and their congruence. Methods: Data from the mixed-methods PreDemCare study, including a cross-sectional, paper-and-pencil, interviewer-assisted analytic hierarchy process (AHP) survey conducted with …n  = 50 community-dwelling PlwCI and n  = 25 physicians. Individual AHP weights (preferences/judgements) were calculated with the principal eigenvector method and aggregated per group by aggregation of individual priorities mode. Individual consistency ratios (CRs) were calculated and aggregated per group. Group differences in preferences/judgements were investigated descriptively by means and standard deviations (SDs) of AHP weights, resulting ranks, and boxplots. Additionally, differences between groups were investigated with independent paired t -test/Mann Whitney U-test. Sensitivity of AHP results was tested by inclusion/exclusion of inconsistent respondents, with an accepted threshold at CR≤0.3 for patients, and CR≤0.2 for physicians, due to better cognitive fitness of the latter group. Results: Patient preferences and physicians’ judgements did not differ significantly, except for the criterion Memory Exercises (AHP weights (mean (SD)): 0.135 (0.066) versus 0.099 (0.068), p  = 0.01). We did not see rank-reversals of criteria after exclusion of inconsistent participants. Mean CR for patients at the criteria level was 0.261, and 0.181 for physicians. Conclusion: Physicians’ judgements in our setting aligned well with patients’ preferences. Our findings may be used to guide the implementation of preference-based PCC. Show more

Keywords: Dementia care, mild cognitive impairment, participatory research, patient-centered care, patient empowerment, patient engagement,, patient preference, physician-patient relations, shared decision-making

DOI: 10.3233/JAD-220753

Citation: Journal of Alzheimer's Disease, vol. 91, no. 2, pp. 727-741, 2023