Journal of Alzheimer's Disease - Volume 73, issue 3

Authors: Ezzati, Ali | Harvey, Danielle J. | Habeck, Christian | Golzar, Ashkan | Qureshi, Irfan A. | Zammit, Andrea R. | Hyun, Jinshil | Truelove-Hill, Monica | Hall, Charles B. | Davatzikos, Christos | Lipton, Richard B. | for the Alzheimer’s Disease Neuroimaging Initiative

Article Type: Research Article

Abstract: Background: Amyloid-β positivity (Aβ+) based on PET imaging is part of the enrollment criteria for many of the clinical trials of Alzheimer’s disease (AD), particularly in trials for amyloid-targeted therapy. Predicting Aβ positivity prior to PET imaging can decrease unnecessary patient burden and costs of running these trials. Objective: The aim of this study was to evaluate the performance of a machine learning model in estimating the individual risk of Aβ+ based on gold-standard of PET imaging. Methods: We used data from an amnestic mild cognitive impairment (aMCI) subset of the Alzheimer’s Disease Neuroimaging Initiative (ADNI) …cohort to develop and validate the models. The predictors of Aβ status included demographic and ApoE4 status in all models plus a combination of neuropsychological tests (NP), MRI volumetrics, and cerebrospinal fluid (CSF) biomarkers. Results: The models that included NP and MRI measures separately showed an area under the receiver operating characteristics (AUC) of 0.74 and 0.72, respectively. However, using NP and MRI measures jointly in the model did not improve prediction. The models including CSF biomarkers significantly outperformed other models with AUCs between 0.89 to 0.92. Conclusions: Predictive models can be effectively used to identify persons with aMCI likely to be amyloid positive on a subsequent PET scan. Show more

Keywords: Alzheimer’s disease, amyloid imaging, machine learning, mild cognitive impairment, predictive analytics

DOI: 10.3233/JAD-191038

Citation: Journal of Alzheimer's Disease, vol. 73, no. 3, pp. 1211-1219, 2020

Authors: Rundek, Tatjana | Gardener, Hannah | Dias Saporta, Anita Seixas | Loewenstein, David A. | Duara, Ranjan | Wright, Clinton B. | Dong, Chuanhui | Levin, Bonnie | Elkind, Mitchell S.V. | Sacco, Ralph L.

Article Type: Research Article

Abstract: Background: Modifiable vascular risk factors (VRF) have been implicated in cognitive impairment. Objective: We compared the prediction of cognitive performance between the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) dementia risk score, a validated tool to estimate dementia risk using VRF, and the Northern Manhattan Study (NOMAS) global vascular risk score (GVRS), created to predict vascular events. Methods: The CAIDE and GVRS scores were calculated based on baseline VRF among 1,290 stroke-free participants in the prospective population-based NOMAS MRI cohort (mean age 64±8 years, 60% women; 66% Hispanic, 17% Black, 15% White; 46% completed …high school). Domain-specific Z-scores were derived for episodic and semantic memory, executive function, and processing speed, and averaged to calculate global cognition. Results: The CAIDE score was associated with worse global cognition at initial assessment (Beta per SD = –0.347, p  < 0.0001), and with greater decline over time (Beta per SD = –0.033, p  = 0.02). These associations were largely due to age and education, and the association with cognitive decline was not significant after adjusting for age, sex, and education. The GVRS was inversely associated with global cognition at initial testing (Beta per SD = –0.247, p  < 0.0001) and greater decline over time (Beta per SD = –0.127, p  < 0.0001), which persisted after adjusting for sociodemographics. The associations for both scores with initial cognitive performance were driven by executive function and processing speed, and the GVRS was associated with decline in episodic memory and processing speed. Conclusions: The GVRS was a stronger predictor of cognitive decline than the CAIDE in a multi-ethnic urban cohort. The inclusion of glucose and smoking in the GVRS, which are absent in CAIDE, likely explains the better performance of the GVRS. Show more

Keywords: Cognition, dementia, epidemiology, risk score, vascular risk factors

DOI: 10.3233/JAD-190925

Citation: Journal of Alzheimer's Disease, vol. 73, no. 3, pp. 1221-1231, 2020

Authors: McMichael, Alan J. | Zafeiridi, Evi | Passmore, Peter | Cunningham, Emma L. | McGuinness, Bernadette

Article Type: Research Article

Abstract: Background: Understanding factors associated with mortality after a dementia diagnosis can provide essential information to the person with dementia, their family, and caregivers. To date very little is known about the factors associated with mortality after a dementia diagnosis in Northern Ireland. Objective: To determine how demographic and other factors such as deprivation and comorbidity medications influence mortality rates after a dementia diagnosis in Northern Ireland and whether these factors are influenced through nursing home transitions. Methods: 25,418 people prescribed anti-dementia medication were identified through the enhanced prescribing database between 2010 and 2016. The impact of …covariates including age, gender, marital status, deprivation measure, urban/rural classification, and comorbidity medications were examined using cox proportional hazard models with hazard ratios (HR) and 95% confidence intervals. Results: Between 2010 and 2016, 12,129 deaths occurred, with 114 deaths/1,000 person years. Males had significantly higher mortality rates in comparison to females (HR = 1.28; 95% CI = 1.23–1.33); this was true regardless of whether the person with dementia transitioned to a nursing home. People prescribed anti-dementia drugs living with lower levels of deprivation had significantly lower mortality rates in comparison to people living with the highest levels of deprivation (HR = 0.93; 95% CI = 0.89–0.97). Diabetic (HR = 1.18; 95% CI = 1.07–1.29) and anti-arrhythmic (HR = 2.44; 95% CI = 1.01–5.91) medication in particular significantly influenced mortality. Conclusion: Male gender, higher comorbidity medications, and living in areas of higher deprivation significantly increased mortality rates for people prescribed anti-dementia drugs in our study population. When comorbidity medications were classified, only anti-arrhythmia and diabetic medications significantly increased mortality. Future research should continue to investigate factors which influence mortality after a dementia diagnosis. Show more

Keywords: Cohort studies, dementia, epidemiology, mortality

DOI: 10.3233/JAD-190751

Citation: Journal of Alzheimer's Disease, vol. 73, no. 3, pp. 1233-1242, 2020

Authors: Lampela, Pasi | Tolppanen, Anna-Maija | Koponen, Marjaana | Tanskanen, Antti | Tiihonen, Jari | Hartikainen, Sirpa | Taipale, Heidi

Article Type: Research Article

Abstract: Background: Asthma and chronic obstructive pulmonary disease (COPD) are common comorbidities in persons with Alzheimer’s disease (AD). However, pharmacotherapy of these diseases may have opposite mechanisms of action; anticholinergics in asthma/COPD and acetylcholinesterase inhibitors (AChEI) in AD. Objective: To investigate whether existing asthma/COPD affects the choice of AD medication, and the survival of the patients with AD. Methods: In this retrospective cohort study, data from the MEDALZ-study, which includes all community-dwelling persons with AD during 2005–2011 in Finland (n  = 70718) was utilized. Persons with asthma/COPD (N = 7211) were defined as having a special reimbursement for asthma/COPD, or …long-term use (≥250 days) of inhaled anticholinergics, inhaled corticosteroids, or leukotriene antagonists during the year before AD diagnosis. We compared persons with and without asthma/COPD regarding the choice of the initial antidementia medication (AChEI versus memantine) with logistic regression and mortality with Cox regression model during the follow-up (up to end of 2015). Results: Memantine was favored over AChEIs as first-line treatment to AD in persons with asthma/COPD compared to those without asthma/COPD (odds ratio 1.23, 95% confidence interval (CI) 1.15–1.31). Memantine was also more commonly used among those who used multiple asthma/COPD medications (7.9% of memantine initiators used ≥3 asthma/COPD medications compared with 5.5% of those who initiated with AChEI). Mortality was higher in persons with asthma/COPD compared to those without asthma/COPD (adjusted hazard ratio 1.10, 95% CI 1.07–1.13). Conclusion: More frequent use of memantine instead of AChEI may result from an attempt to prevent possible worsening of asthma/COPD by AChEIs. Vulnerable persons with both AD and asthma/COPD need individually assessed pharmacotherapy for their medical conditions. Show more

Keywords: Alzheimer’s disease, anticholinergics, asthma, cholinesterase inhibitors, chronic obstructive pulmonary disease, dementia, older person

DOI: 10.3233/JAD-190850

Citation: Journal of Alzheimer's Disease, vol. 73, no. 3, pp. 1243-1251, 2020

Authors: Alzubaidi, Hamzah | Saidawi, Ward | Hussein, Amal | Hasan, Sanah

Article Type: Research Article

Abstract: Background: The global prevalence of Alzheimer’s disease (AD) and its treatment costs are projected to increase significantly, placing increasing pressure on health systems to create new models of care. Community pharmacists are well-positioned to provide medication management for people with AD. In Arabic-speaking countries, little is known about pharmacists’ knowledge and practices in caring for people with AD. Objective: To evaluate community pharmacists’ knowledge of AD and its management, counseling skills, and dispensing patterns when caring for people with AD and their caregivers in the United Arab Emirates (UAE). Methods: A large-scale cross-sectional survey of community …pharmacists was conducted in three cities in the UAE using stratified random sampling. The questionnaire comprised of validated tools to measure knowledge and open-ended questions. A logistic regression model was conducted to predict counseling comprehensiveness. Results: A total of 325 community pharmacists completed the questionnaire. The mean knowledge scores about AD and its pharmacotherapy were 57.0% and 67.6%, respectively. Major shortcomings in pharmacists’ practices were identified; history-taking, adherence assessment, and counseling were provided by 2.2%, 9.3%, and 17.3%, respectively. A minority provided comprehensive counselling; the multivariate analysis yielded new insights into pharmacist characteristics associated with such counseling. Conclusion: Pharmacists did not provide structured patient-centered care for people with AD. Community pharmacists did not provide adequate counseling, did not assess adherence-related issues appropriately, and had deficient knowledge. To develop patient-centered pharmacy-based services for Arabic-speaking communities, a multifaceted approach is required that goes beyond improving pharmacy workforce knowledge and communication skills to address broader sociocultural, legislative, and financial factors. Show more

Keywords: Alzheimer’s disease, Arabs, community pharmacy services, counseling, knowledge, medication therapy management

DOI: 10.3233/JAD-190804

Citation: Journal of Alzheimer's Disease, vol. 73, no. 3, pp. 1253-1264, 2020