Journal of Alzheimer's Disease - Volume 89, issue 2

Authors: Janssen, Niels | Handels, Ron L. | Wimo, Anders | Antikainen, Riitta | Laatikainen, Tiina | Soininen, Hilkka | Strandberg, Timo | Tuomilehto, Jaakko | Kivipelto, Miia | Evers, Silvia M.A.A. | Verhey, Frans R.J. | Ngandu, Tiia

Article Type: Research Article

Abstract: Background: The association between health-related quality of life (HRQoL) and care costs in people at risk for cognitive decline is not well understood. Studying this association could reveal the potential benefits of increasing HRQoL and reducing care costs by improving cognition. Objective: In this exploratory data analysis we investigated the association between cognition, HRQoL utilities and costs in a well-functioning population at risk for cognitive decline. Methods: An exploratory data analysis was conducted using longitudinal 2-year data from the FINGER study (n = 1,120). A change score analysis was applied using HRQoL utilities and total …medical care costs as outcome. HRQoL utilities were derived from the Short Form Health Survey-36 (SF-36). Total care costs comprised visits to a general practitioner, medical specialist, nurse, and days at hospital. Analyses were adjusted for activities of daily living (ADL) and depressive symptoms. Results: Although univariable analysis showed an association between cognition and HRQoL utilities, multivariable analysis showed no association between cognition, HRQoL utilities and total care costs. A one-unit increase in ADL limitations was associated with a -0.006 (p < 0.001) decrease in HRQoL utilities and a one-unit increase in depressive symptoms was associated with a -0.004 (p < 0.001) decrease in HRQoL utilities. Conclusion: The level of cognition in people at-risk for cognitive decline does not seem to be associated with HRQoL utilities. Future research should examine the level at which cognitive decline starts to affect HRQoL and care costs. Ideally, this would be done by means of cross-validation in populations with various stages of cognitive functioning and decline. Show more

Keywords: At-risk, care costs, cognition,, cognitive decline, dementia,, HRQoL utilities, sf-6d

DOI: 10.3233/JAD-215304

Citation: Journal of Alzheimer's Disease, vol. 89, no. 2, pp. 623-632, 2022

Authors: Weigand, Alexandra J. | Macomber, Alyssa J. | Walker, Kayla S. | Edwards, Lauren | Thomas, Kelsey R. | Bangen, Katherine J. | Nation, Daniel A. | Bondi, Mark W.

Article Type: Research Article

Abstract: Background: Studies have demonstrated that both tau and cardiovascular risk are associated with cognitive decline, but the possible synergistic effects of these pathologic markers remain unclear. Objective: To explore the interaction of AD biomarkers with a specific vascular risk marker (pulse pressure) on longitudinal cognition. Methods: Participants included 139 older adults from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Biomarkers of tau, amyloid-β (Aβ), and vascular risk (pulse pressure) were assessed. Neuropsychological assessment provided memory, language, and executive function domain composite scores at baseline and 1-year follow-up. Multiple linear regression examined interactive effects of pulse pressure with …tau PET independent of Aβ PET and Aβ PET independent of tau PET on baseline and 1-year cognitive outcomes. Results: The interaction between pulse pressure and tau PET significantly predicted 1-year memory performance such that the combined effect of high pulse pressure and high tau PET levels was associated with lower memory at follow-up but not at baseline. In contrast, Aβ PET did not significantly interact with pulse pressure to predict baseline or 1-year outcomes in any cognitive domain. Main effects revealed a significant effect of tau PET on memory, and no significant effects of Aβ PET or pulse pressure on any cognitive domain. Conclusion: Results indicate that tau and an indirect marker of arterial stiffening (pulse pressure) may synergistically contribute to memory decline, whereas Aβ may have a lesser role in predicting cognitive progression. Tau and vascular pathology (particularly in combination) may represent valuable targets for interventions intended to slow cognitive decline. Show more

Keywords: Amyloid PET, cardiovascular risk, cognition, executive function, memory, pulse pressure, tau PET

DOI: 10.3233/JAD-220026

Citation: Journal of Alzheimer's Disease, vol. 89, no. 2, pp. 633-640, 2022

Authors: Dominguez Perez, Sophia | Phillips, Jeffrey S. | Norise, Catherine | Kinney, Nikolas G. | Vaddi, Prerana | Halpin, Amy | Rascovsky, Katya | Irwin, David J. | McMillan, Corey T. | Xie, Long | Wisse, Laura E.M. | Yushkevich, Paul A. | Kallogjeri, Dorina | Grossman, Murray | Cousins, Katheryn A.Q.

Article Type: Research Article

Abstract: Background: An understudied variant of Alzheimer’s disease (AD), the behavioral/dysexecutive variant of AD (bvAD), is associated with progressive personality, behavior, and/or executive dysfunction and frontal atrophy. Objective: This study characterizes the neuropsychological and neuroanatomical features associated with bvAD by comparing it to behavioral variant frontotemporal dementia (bvFTD), amnestic AD (aAD), and subjects with normal cognition. Methods: Subjects included 16 bvAD, 67 bvFTD, 18 aAD patients, and 26 healthy controls. Neuropsychological assessment and MRI data were compared between these groups. Results: Compared to bvFTD, bvAD showed more significant visuospatial impairments (Rey Figure copy and recall), …more irritability (Neuropsychological Inventory), and equivalent verbal memory (Philadelphia Verbal Learning Test). Compared to aAD, bvAD indicated more executive dysfunction (F-letter fluency) and better visuospatial performance. Neuroimaging analysis found that bvAD showed cortical thinning relative to bvFTD posteriorly in left temporal-occipital regions; bvFTD had cortical thinning relative to bvAD in left inferior frontal cortex. bvAD had cortical thinning relative to aAD in prefrontal and anterior temporal regions. All patient groups had lower volumes than controls in both anterior and posterior hippocampus. However, bvAD patients had higher average volume than aAD patients in posterior hippocampus and higher volume than bvFTD patients in anterior hippocampus after adjustment for age and intracranial volume. Conclusion: Findings demonstrated that underlying pathology mediates disease presentation in bvAD and bvFTD. Show more

Keywords: Alzheimer’s disease, behavioral, behavioral variant frontotemporal dementia, cognitive domains, cortical thinning, frontal variant, hippocampal volumes, neuropsychiatric symptoms

DOI: 10.3233/JAD-215728

Citation: Journal of Alzheimer's Disease, vol. 89, no. 2, pp. 641-658, 2022

Authors: Richards, Marcus | James, Sarah N. | Lu, Kirsty | Livingston, Gill | Schott, Jonathan M. | Lane, Christopher A. | Barnes, Josephine | Parker, Thomas D. | Sudre, Carole H. | Cash, David M. | Coath, William | Fox, Nicholas | Davis, Daniel H.J.

Article Type: Research Article

Abstract: Background: Using the British 1946 birth cohort we previously estimated life course paths to the Addenbrooke’s Cognitive Examination (ACE-III). Objective: We now compared those whose ACE-III scores were expected, worse and better than predicted from the path model on a range of independent variables including clinical ratings of cognitive impairment and neuroimaging measures. Methods: Predicted ACE-III scores were categorized into three groups: those with Expected (between –1.5 and 1.5 standard deviation; SD); Worse (< –1.5 SD); and Better (>1.5 SD) scores. Differences in the independent variables were then tested between these three groups. Results: …Compared with the Expected group, those in the Worse group showed independent evidence of progressive cognitive impairment: faster memory decline, more self-reported memory difficulties, more functional difficulties, greater likelihood of being independently rated by experienced specialist clinicians as having a progressive cognitive impairment, and a cortical thinning pattern suggestive of preclinical Alzheimer’s disease. Those in the Better group showed slower verbal memory decline and absence of independently rated progressive cognitive impairment compared to the Expected group, but no differences in any of the other independent variables including the neuroimaging variables. Conclusion: The residual approach shows that life course features can map directly to clinical diagnoses. One future challenge is to translate this into a readily usable algorithm to identify high-risk individuals in preclinical state, when preventive strategies and therapeutic interventions may be most effective. Show more

Keywords: Addenbrooke’s Cognitive Examination-III, birth cohort, cognitive state, life course, residuals

DOI: 10.3233/JAD-220296

Citation: Journal of Alzheimer's Disease, vol. 89, no. 2, pp. 659-667, 2022

Authors: Xu, Qing | Zou, Kai | Deng, Zhao’an | Zhou, Jianbang | Dang, Xinghong | Zhu, Shenglong | Liu, Liang | Fang, Chunxia

Article Type: Research Article

Abstract: Background: For community-dwelling elderly individuals without enough clinical data, it is important to develop a method to predict their dementia risk and identify risk factors for the formulation of reasonable public health policies to prevent dementia. Objective: A community elderly survey data was used to establish machine learning prediction models for dementia and analyze the risk factors. Methods: In a cluster-sample community survey of 9,387 elderly people in 5 subdistricts of Wuxi City, data on sociodemographics and neuropsychological self-rating scales for depression, anxiety, and cognition evaluation were collected. Machine learning models were developed to predict their …dementia risk and identify risk factors. Results: The random forest model (AUC = 0.686) had slightly better dementia prediction performance than logistic regression model (AUC = 0.677) and neural network model (AUC = 0.664). The sociodemographic data and psychological evaluation revealed that depression (OR = 3.933, 95% CI = 2.995–5.166); anxiety (OR = 2.352, 95% CI = 1.577–3.509); multiple physical diseases (OR = 2.486, 95% CI = 1.882–3.284 for three or above); “disability, poverty or no family member” (OR = 1.859, 95% CI = 1.337–2.585) and “empty nester” (OR = 1.339, 95% CI = 1.125–1.595) in special family status; “no spouse now” (OR = 1.567, 95% CI = 1.118–2.197); age older than 80 years (OR = 1.645, 95% CI = 1.335–2.026); and female (OR = 1.214, 95% CI = 1.048–1.405) were risk factors for suspected dementia, while a higher education level (OR = 0.365, 95% CI = 0.245–0.546 for college or above) was a protective factor. Conclusion: The machine learning models using sociodemographic and psychological evaluation data from community surveys can be used as references for the prevention and control of dementia in large-scale community populations and the formulation of public health policies. Show more

Keywords: Community survey, dementia, machine learning, prediction model, risk factors

DOI: 10.3233/JAD-220316

Citation: Journal of Alzheimer's Disease, vol. 89, no. 2, pp. 669-679, 2022

Authors: Cascini, Silvia | Agabiti, Nera | Marino, Claudia | Acampora, Anna | Balducci, Maria | Calandrini, Enrico | Davoli, Marina | Bargagli, Anna Maria

Article Type: Research Article

Abstract: Background: The identification of risk factors for SARS-CoV-2 infection and mortality in patients with dementia is a key aspect to support clinical decisions and public health interventions. Objective: To assess the incidence of SARS-CoV-2 infection and COVID-19 related death in a cohort of patients with dementia residing in the Lazio region and to investigate predicting factors for both infection and mortality. Methods: This population-based study used information from administrative databases and the SARS-CoV-2 infection surveillance system. Patients with dementia (age ≥65) were enrolled as of December 31, 2019 and followed-up until February 28, 2021. Cumulative risk …of infection and death within 60 days of infection onset, and age-standardized incidence (SIR) and mortality (SMR) ratios were calculated. Logistic regression models were applied to identify factors associated with infection and mortality. Results: Among 37,729 dementia patients, 2,548 had a diagnosis of SARS-CoV-2 infection. The crude risk of infection was 6.7%. An increase in risk of infection was observed both in women (SIR 1.72; 95% CI 1.64–1.80) and men (SIR 1.43; 95% CI 1.33–1.54). Pneumonia, cerebrovascular and blood diseases, femur fracture, anxiety, antipsychotic and antithrombotic use were associated with an increased risk of infection. The crude risk of death was 31.0%, the SMRs 2.32 (95% CI 2.05–2.65) for men, and 2.82 (95% CI 2.55–3.11) for women. Factors associated with mortality included: male gender, age ≥85, symptoms at the diagnosis, antipsychotic and systemic antibiotics treatment. Conclusion: These findings emphasize the need of close and tailored monitoring of dementia patients to reduce the impact of COVID-19 on this fragile population. Show more

Keywords: Administrative databases, Alzheimer’s disease, cohort study, COVID-19, dementia, prognostic factors, SARS-CoV-2 infection

DOI: 10.3233/JAD-220369

Citation: Journal of Alzheimer's Disease, vol. 89, no. 2, pp. 681-693, 2022

Authors: Tahami Monfared, Amir Abbas | Stern, Yaakov | Doogan, Stephen | Irizarry, Michael | Zhang, Quanwu

Article Type: Research Article

Abstract: Background: Social media data may be especially effective for studying diseases associated with high stigma, such as Alzheimer’s disease (AD). Objective: We primarily aimed to identify issues/challenges experienced by patients with AD using natural language processing (NLP) of social media posts. Methods: We searched 130 public social media sources between January 1998 and December 2021 for AD stakeholder social media posts using NLP to identify issues/challenges experienced by patients with AD. Issues/challenges identified by ≥10% of any AD stakeholder type were described. Illustrative posts were selected for qualitative review. Secondarily, issues/challenges were organized into a conceptual …AD identification framework (ADIF) and representation of ADIF categories within clinical instruments was assessed. Results: We analyzed 1,859,077 social media posts from 30,341 AD stakeholders (21,011 caregivers; 7,440 clinicians; 1,890 patients). The most common issues/challenges were Worry/anxiety (34.2%), Pain (33%), Malaise (28.7%), Confusional state (27.1%), and Falls (23.9%). Patients reported a markedly higher volume of issues/challenges than other stakeholders. Patient posts reflected the broader scope of patient burden, caregiver posts captured both patient and caregiver burden, and clinician posts tended to be targeted. Less than 5% of the high frequency issues/challenges were in the “function and independence” and “social and relational well-being” categories of the ADIF, suggesting these issues/challenges may be difficult to capture. No single clinical instrument covered all ADIF categories; “social and relational well-being” was least represented. Conclusion: NLP of AD stakeholder social media data revealed a broad spectrum of real-world insights regarding patient burden. Show more

Keywords: Alzheimer’s disease, dementia, mild cognitive impairment, natural language processing, online social networking, patient reported outcome measures, social media

DOI: 10.3233/JAD-220422

Citation: Journal of Alzheimer's Disease, vol. 89, no. 2, pp. 695-708, 2022

Authors: Liampas, Ioannis | Hatzimanolis, Alex | Siokas, Vasileios | Yannakoulia, Mary | Kosmidis, Mary H. | Sakka, Paraskevi | Hadjigeorgiou, Georgios M. | Scarmeas, Nikolaos | Dardiotis, Efthimios

Article Type: Research Article

Abstract: Background: It is unclear whether the main antihypertensive medication classes (diuretics, calcium channel blockers, beta-blockers, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers (ARBs)) are associated with different risks of cognitive decline. Published evidence is conflicting and stems mainly from observational studies. Objective: To investigate the differential effects of antihypertensives on the risks of developing dementia and cognitive decline, with a specific focus on the vascular component of the mechanisms underlying these interactions. Methods: Older adults with a history of hypertension and without dementia were drawn from the population-based HELIAD cohort. Age-, gender-, education-, and antihypertensive …medication- (five dichotomous exposures) adjusted Cox proportional-hazards models and generalized estimating equations were performed to appraise the associations of baseline antihypertensive therapy with dementia incidence and cognitive decline (quantified using a comprehensive neuropsychological battery). Analyses were subsequently adjusted for clinical vascular risk (dyslipidemia, diabetes mellitus, smoking, cardiovascular, and cerebrovascular history) and genetic susceptibility to stroke (using polygenic risk scores generated according to the MEGASTROKE consortium GWAS findings). Results: A total of 776 predominantly female participants (73.61±4.94 years) with hypertension and a mean follow-up of 3.02±0.82 years were analyzed. Baseline treatment was not associated with the risk of incident dementia. ARB users experienced a slower yearly global cognitive [2.5% of a SD, 95% CI = (0.1, 4.9)] and language [4.4% of a SD, 95% CI = (1.4, 7.4)] decline compared to non-users. The fully adjusted model reproduced similar associations for both global cognitive [β= 0.027, 95% CI =  (–0.003, 0.057)], and language decline [β= 0.063, 95% CI = (0.023, 0.104)]. Conclusion: ARBs may be superior to other antihypertensive agents in the preservation of cognition, an association probably mediated by vascular-independent mechanisms. Show more

Keywords: Angiotensin converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, calcium channel blockers, diuretics, genetic predisposition to disease, longitudinal

DOI: 10.3233/JAD-220439

Citation: Journal of Alzheimer's Disease, vol. 89, no. 2, pp. 709-719, 2022

Authors: Bu, Kun | Patel, Devashru | Morris, Robert | Han, Weiru | Umeukeje, Gibret | Zhu, Tianrui | Cheng, Feng

Article Type: Research Article

Abstract: Background: Dysphagia has been reported as an adverse event for patients receiving rivastigmine for Alzheimer’s disease (AD) treatment. Objective: The purpose of this study was to determine the association between dysphagia and the usage of rivastigmine by using the pharmacovigilance data from the FDA Adverse Event Reporting System (FAERS). Methods: The risk of dysphagia in patients who took rivastigmine was compared with those of patients who took other medications. In addition, this study sought to determine if the dysphagia risk was influenced by sex, age, dosage, and medication routes of administration. Results: When compared …to patients prescribed donepezil, galantamine, or memantine, individuals prescribed rivastigmine were almost twice as likely to report dysphagia as an adverse event. The dysphagia risk in individuals prescribed rivastigmine is comparable to individuals prescribed penicillamine but significantly higher than clozapine, drugs of which have been previously shown to be associated with elevated dysphagia likelihood. Individuals older than 80 were 122% more likely to report having dysphagia after being prescribed rivastigmine than patients that were 50–70 years of age. Oral administration of rivastigmine was associated with approximately 2 times greater likelihood of reporting dysphagia relative to users of the transdermal patch. In addition, dysphagia showed higher association with pneumonia than other commonly reported adverse events. Conclusion: Patients prescribed rivastigmine were at greater risk of reporting dysphagia as an adverse event than patients prescribed many other medicines. This increase in dysphagia occurrence may be attributed to the dual inhibition of both acetylcholinesterase and butyrylcholinesterase. Show more

Keywords: Exelon, FAERS, FDA, patch, pharmacovigilance, pneumonia, swallow, transdermal

DOI: 10.3233/JAD-220583

Citation: Journal of Alzheimer's Disease, vol. 89, no. 2, pp. 721-731, 2022

Authors: Bawa, Kritleen K. | Ba, Joycelyn | Kiss, Alex | Wang, RuoDing | Feng, Vivian | Swardfager, Walter | Andreazza, Ana | Gallagher, Damien | Marotta, Giovanni | Herrmann, Nathan | Lanctôt, Krista L.

Article Type: Research Article

Abstract: Background: The co-occurrence of apathy and executive dysfunction, a correlate of vascular cognitive impairment (VCI), is highly prevalent, yet facilitating factors are largely unknown. Objective: This study investigates the relationship between lipid peroxidation, apathy, and executive dysfunction in patients at risk for VCI. Methods: In participants with coronary artery disease, who are at a high risk of VCI, apathy (Apathy Evaluation Scale), and executive function (composite z-score based on age and education population norms from trails making test B, animal naming, and phonemic fluency tests) were assessed. Serum concentrations of an early (lipid hydroperoxide (LPH)) and …late (8-isoprostane (8-ISO)) lipid peroxidation marker, were measured and the 8-ISO/LPH ratio was calculated. Results: Participants (n  = 206, age±SD = 63.0±7.5, 80% men, total years of education = 15.9±3.4, AES score = 28.3±8.8, executive function = 0±1) demonstrated significantly different 8-ISO/LPH ratios between groups (F(3, 202) = 10.915, p  < 0.001) with increasing levels in the following order: no apathy or executive dysfunction, only executive dysfunction (executive function composite score≤–1), only apathy (AES≥28), and both apathy and executive dysfunction. A model adjusting for demographics showed that lipid peroxidation was associated with both apathy (B(SE) = 4.63 (0.954), t  = 4.852, p  < 0.001) and executive function (B(SE) = –0.19 (0.079), t  = –2.377, p  = 0.018). However, when controlling for both demographics and vascular risk factors, lipid peroxidation was associated with only apathy (B(SE) = 3.11 (0.987), t  = 3.149, p  = 0.002). Conclusion: The results highlight a potentially important involvement of lipid peroxidation in the co-occurrence of apathy and executive dysfunction in those at risk for VCI. Show more

Keywords: Apathy, cardiac rehabilitation, cognition, cognitive dysfunction, coronary artery disease, executive function, lipid peroxidation, oxidative stress

DOI: 10.3233/JAD-220274

Citation: Journal of Alzheimer's Disease, vol. 89, no. 2, pp. 733-743, 2022