Journal of Alzheimer's Disease - Volume Pre-press, issue Pre-press

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. Pre-press, no. Pre-press, pp. 1-11, 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. Pre-press, no. Pre-press, pp. 1-11, 2022

Authors: Godbee, Kali | Guccione, Lisa | Palmer, Victoria J. | Gunn, Jane | Lautenschlager, Nicola | Francis, Jill J.

Article Type: Research Article

Abstract: Background: Primary care practitioners are being called upon to work with their patients to reduce dementia risk. However, it is unclear who should do what with whom, when, and under what circumstances. Objective: This scoping review aimed to identify clinical guidelines for dementia risk reduction (DRR) in primary care settings, synthesize the guidelines into actionable behaviors, and appraise the guidelines for specificity. Methods: Terms related to “dementia”, “guidelines”, and “risk reduction” were entered into two academic databases and two web search engines. Guidelines were included if they referred specifically to clinical practices for healthcare professionals for …primary prevention of dementia. Included guidelines were analyzed using a directed content analysis method, underpinned by the Action-Actor-Context-Target-Time framework for specifying behavior. Results: Sixteen guidelines were included in the analysis. Together, the guidelines recommended six distinct clusters of actions for DRR. These were to 1) invite patients to discuss DRR, 2) identify patients with risk factors for dementia, 3) discuss DRR, 4) manage dementia risk factors, 5) signpost to additional support, and 6) follow up. Guidelines recommended various actors, contexts, targets, and times for performing these actions. Together, guidelines lacked specificity and were at times contradictory. Conclusion: Currently available guidelines allow various approaches to promoting DRR in primary care. Primary care teams are advised to draw on the results of the review to decide which actions to undertake and the locally appropriate actors, contexts, targets, and times for these actions. Documenting these decisions in more specific, local guidelines for promoting DRR should facilitate implementation. Show more

DOI: 10.3233/JAD-220382

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-14, 2022

Authors: Goodman, Zachary T. | Banerjee, Nikhil | Rooks, Joshua | McInerney, Katalina | Sun, Xiaoyan | Getz, Sarah | Kaur, Sonya | Sun-Suslow, Ni | Junco, Barbara | Levin, Bonnie E.

Article Type: Research Article

Abstract: Background: Frailty is directly linked to physical robustness and cognitive decline in older age. The Fried Frailty phenotype (FP) is a construct composed of five core symptoms that has been studied predominately in older age. There is little research contrasting the psychometric properties of the FP in mid-life versus older age. Objective: We compared the psychometric properties of the FP in mid-life and older age and investigated relationships between the FP and cognition. Methods: Frailty and neuropsychological assessments were completed on 361 adults, between 45 and 92 years of age, without primary neurological disorders. Confirmatory factor …analysis was used to examine FP, indicated by Grip Strength, Gait Speed, Physical Activity, Fatigue, and Weight Loss. Measurement invariance was tested in mid-life (45–64 years) versus older age (≥65 years). Associations were examined between FP and language, executive functions, memory, processing speed, and visuospatial domains as well as a Generalized Cognition factor. Age was tested as a moderator of these associations. Results: Weight Loss was a poor indicator of FP. Factor loadings were comparable across age groups; however, Fatigue was disproportionately higher among those in mid-life. FP was negatively associated with all cognitive domains and remained invariant across age groups. Conclusion: Results support the construct validity of the FP and document its stable associations with poorer cognition in middle and older life. Future research investigating central features of frailty earlier in life may offer avenues for developing targeted prevention measures and better characterization of individuals with elevated dementia risk. Show more

Keywords: Aging, cognition, confirmatory factor analysis, frailty, measurement invariance, neuropsychology, quantitative methods

DOI: 10.3233/JAD-215475

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-12, 2022

Authors: Vassilaki, Maria | Crowson, Cynthia S. | Davis III, John M. | Duong, Stephanie Q. | Jones, David T. | Nguyen, Aivi | Mielke, Michelle M. | Vemuri, Prashanthi | Myasoedova, Elena

Article Type: Research Article

Abstract: Background: Observational studies suggested that dementia risk in patients with rheumatoid arthritis (RA) is higher than in the general population. Objective: To examine the associations of RA with cognitive decline and dementia, and neuroimaging biomarkers of aging, Alzheimer’s disease, and vascular pathology in adult participants in the Mayo Clinic Study of Aging (MCSA). Methods: Participants with RA were matched 1:3 on age, sex, education, and baseline cognitive diagnosis to participants without RA. RA cases with MRI were also matched with non-cases with available MRI. All available imaging studies (i.e., amyloid and FDG PET, sMRI, and …FLAIR) were included. The study included 104 participants with RA and 312 without RA (mean age (standard deviation, SD) 75.0 (10.4) years, 33% male and average follow-up (SD) 4.2 (3.8) years). Results: Groups were similar in cognitive decline and risk of incident dementia. Among participants with neuroimaging, participants with RA (n  = 33) and without RA (n  = 98) had similar amyloid burden and neurodegeneration measures, including regions sensitive to aging and dementia, but greater mean white matter hyperintensity volume relative to the total intracranial volume (mean (SD)% : 1.12 (0.57)% versus 0.76 (0.69)% of TIV, p  = 0.01), and had higher mean (SD) number of cortical infarctions (0.24 (0.44) versus 0.05 (0.33), p  = 0.02). Conclusion: Although cognitive decline and dementia risk were similar in participants with and without RA, participants with RA had more abnormal cerebrovascular pathology on neuroimaging. Future studies should examine the mechanisms underlying these changes and potential implications for prognostication and prevention of cognitive decline in RA. Show more

Keywords: Cognitive decline, cognitive impairment, dementia, magnetic resonance imaging, rheumatoid arthritis

DOI: 10.3233/JAD-220368

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-12, 2022

Authors: Cavalli, Andrea | Lelli, Diana | Pedone, Claudio | Boccardi, Virginia | Mecocci, Patrizia | Antonelli Incalzi, Raffaele

Article Type: Research Article

Abstract: Background: Dementia is a risk factor for undernutrition. However, it is not clear if specific cognitive deficits have a higher risk of undernutrition and how much appetite/nutritional problems and caregiver stress mediate this association. Objective: To evaluate the relationship between nutritional status and severity of global and function-specific scores of cognitive dysfunctions, and to which extent this association is mediated by appetite/nutritional problems and caregiver stress. Methods: Cross-sectional analysis of the ReGAl study data, including 761 older adults attending a Memory Clinic. Nutritional status was evaluated with Mini Nutritional Assessment (MNA). The relationship between scores at …neuro-cognitive tests and risk of undernutrition was evaluated using logistic regression models adjusted for potential confounders. To allow comparison between different tests, all scores were standardized. Mediation analysis was used to evaluate how much appetite/nutritional problems and caregiver stress mediate this association. Results: Mean age was 77 years (SD: 9), 37.3% were women. Exploring different cognitive domains, a stronger association was documented for attentive matrices (OR:0.49, 95% CI: 0.34–0.72), the figure copy test (OR:0.63, 95% CI: 0.45–0.88), and the verbal judgement test (OR:0.61, 95% CI: 0.42–0.91). The proportion of the effect of cognition (MMSE) on nutritional status mediated by caregiver distress was 9.5% (95% CI: 0.002–0.27), the proportion mediated by appetite/nutritional problems was 11% (95% CI: –4.8–3.18). Conclusion: Risk of undernutrition is associated to cognitive decline; a stronger association was observed for attention, praxis, and reasoning. Caregiver distress is a mediator of this association. This information should be considered in the management plans of this population. Show more

Keywords: Appetite alteration, caregiver burden, dementia, malnutrition, Mini Nutritional Assessment

DOI: 10.3233/JAD-215732

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-8, 2022

Authors: Rosende-Roca, Maitée | Cañabate, Pilar | Moreno, Mariola | Preckler, Silvia | Seguer, Susana | Esteban, Ester | Tartari, Juan Pablo | Vargas, Liliana | Narvaiza, Leire | Pytel, Vanesa | Bojaryn, Urszula | Alarcon, Emilio | González-Pérez, Antonio | Gurruchaga, Miren Jone | Tárraga, Lluís | Ruiz, Agustín | Marquié, Marta | Boada, Mercè | Valero, Sergi

Article Type: Research Article

Abstract: Background: Neuropsychiatric symptoms (NPS) in Alzheimer’s disease (AD) can be disruptive for patients and their families. Objective: We aimed to classify patients based on NPS and to explore the relationship of these classes with sex and with caregiver burden. Methods: The study cohort comprised individuals with AD dementia diagnosed at Ace Alzheimer Center in Barcelona, Spain, between 2011–2020. NPS were ascertained by using the Neuropsychiatric Inventory-Questionnaire. Latent class analysis was used to identify clusters of individuals sharing a similar NPS profile. We evaluated the caregiver burden using the Zarit Burden Interview. Multivariable regression models were used …to obtain adjusted estimates of the association between sex, NPS classes, and caregiver burden. Results: A total of 1,065 patients with AD dementia and their primary caregivers were included. We classified patients into five different classes according to their NPS profile: “Affective”, “High-behavioral-disturbance”, “Negative-affect”, “Affective/deliriant”, and “Apathy”. We found that age, sex, and type of AD diagnosis differed greatly across classes. We found that patients from the “High-behavioral-disturbance” (OR = 2.56, 95% CI: 1.00–6.56), “Negative-affect” (OR = 2.72, 95% CI: 1.26–3.64), and “Affective/deliriant” (OR = 2.14, 95% CI: 1.26–3.64) classes were over two times more likely to have a female caregiver than those in “Apathy” class. These three classes were also the ones associated to the greatest caregiver burden in the adjusted analyses, which seems to explain the increased burden observed among female caregivers. Conclusion: Caregiver burden is highly dependent on the patient’s NPS profiles. Female caregivers provide care to patients that pose a greater burden, which makes them more susceptible to become overwhelmed. Show more

Keywords: Alzheimer’s disease, caregiver burden, gender, neurobehavioral manifestations, sex, women

DOI: 10.3233/JAD-215648

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-10, 2022

Authors: Torkpoor, Rozita | Frolich, Kristin | Nielsen, Rune T. | Londos, Elisabet

Article Type: Research Article

Abstract: Background: The number of people with a migration background and dementia is increasing in Europe. All patients with suspected dementia have the right to an appropriate cognitive assessment and correct diagnosis for optimal treatment and support. Rowland Universal Dementia Assessment Scale (RUDAS) cognitive screening instrument is less affected by language, culture, and educational background, and adapted for use in multicultural populations. Objective: To compare the diagnostic accuracy of RUDAS-S to the Swedish version of Mini-Mental State Examination (MMSE-SR) for detecting dementia in a multicultural group of outpatients in Swedish memory clinics. Methods: We tested 123 outpatients …(36 nonnative Swedish), in 4 memory clinics in Southern Sweden with RUDAS-S to supplement the usual cognitive assessment. Results: RUDAS-S had moderate to good diagnostic performance for detecting dementia in a multicultural population in Sweden, with an area under the receiver operating characteristic curve (AUC) of 0.81. At a cutoff score <25 its sensitivity was 0.92, specificity 0.60, and accuracy 76% . The AUC for the MMSE-SR was 0.79. At a cutoff score <23 its sensitivity was 0.65, specificity 0.81, and accuracy 73% . Conclusion: RUDAS-S is at least as accurate as MMSE-SR for detecting dementia in memory clinics in Sweden and can be used for all patients undergoing a cognitive assessment, irrespective of their cultural, language, and educational background. However, there is a need for other cross-cultural cognitive tests to complement RUDAS-S to extend cognitive examination. Show more

Keywords: Assessment, cognition, cross-cultural screening test, dementia, ethnic minority, immigrant, Mini-Mental State Examination, Rowland Universal Dementia Assessment Scale

DOI: 10.3233/JAD-220233

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-12, 2022

Authors: Freberg, Elissa | Taglialatela, Giulio

Article Type: Review Article

Abstract: Alzheimer’s disease (AD) and major depressive disorder (MDD) affect millions worldwide and both cause significant morbidity and mortality. While clinically distinctive, patients with MDD can present with memory dysfunction and patients with AD commonly report symptoms of depression. Additionally, brain pathology in MDD and AD both demonstrate decreased hippocampal volumes, and severe disease is associated with smaller hippocampal volumes in both disorders. Hippocampal neurogenesis occurs daily in healthy individuals, an impaired process in AD and MDD. MDD is thus suggested to be a risk factor for developing AD later in life; moreover, depression onset alongside AD indicates a worse prognosis. …Treatment options that target hippocampal neurogenesis are being evaluated for both diseases, and aerobic exercise has shown promising results. We searched PubMed for relevant review articles published since 2000 encompassing the topics of hippocampal neurogenesis and exercise in relation to depression and AD, including novel clinical trials if they contributed information not in the chosen reviews. While much data indicates that exercise increases hippocampal neurogenesis in both MDD and AD, mood improvement in MDD, mild quality of life and cognitive improvement in AD, and reduced risk of those with MDD developing AD in response to various exercise regimens, this result was not universal. Some data indicated no difference between exercise groups and controls. Further randomized control trials into exercise as an intervention in treating MDD and preventing AD is required. However, exercise is a low-risk, affordable treatment option and is a feasible additive therapy in patients with AD and MDD. Show more

Keywords: Alzheimer’s disease, cognitive dysfunction, depression, exercise, neurogenesis

DOI: 10.3233/JAD-210632

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-9, 2022

Authors: Serra, Laura | Giancaterino, Giulia | Giulietti, Giovanni | Petrosini, Laura | Di Domenico, Carlotta | Marra, Camillo | Caltagirone, Carlo | Bassi, Andrea | Cercignani, Mara | Bozzali, Marco

Article Type: Research Article

Abstract: Background: Cognitive reserve (CR) explains the individual resilience to neurodegeneration. Objective: The present study investigated the effect of CR in modulating brain cortical architecture. Methods: 278 individuals [110 Alzheimer’s disease (AD), 104 amnestic mild cognitive impairment (aMCI) due to AD, 64 healthy subjects (HS)] underwent a neuropsychological evaluation and 3T-MRI. Cortical thickness (CTh) and fractal dimension (FD) were assessed. Years of formal education were used as an index of CR by which participants were divided into high and low CR (HCR and LCR ). Within-group differences in cortical architecture were assessed as a function of …CR. Associations between cognitive scores and cortical measures were also evaluated. Results: aMCI-HCR compared to aMCI-LCR patients showed significant decrease of CTh in the right temporal and in the left prefrontal lobe. Moreover, they showed increased FD in the right temporal and in the left temporo-parietal lobes. Patients with AD-HCR showed reduced CTh in several brain areas and reduced FD in the left temporal cortices when compared with AD-LCR subjects. HS-HCR showed a significant increase of CTh in prefrontal areas bilaterally, and in the right parieto-occipital cortices. Finally, aMCI-HCR showed significant positive associations between brain measures and memory and executive performance. Conclusion: CR modulates the cortical architecture at pre-dementia stage only. Indeed, only patients with aMCI showed both atrophy (likely due to neurodegeneration) alongside richer brain folding (likely due to reserve mechanisms) in temporo-parietal areas. This opposite trend was not observed in AD and HS. Our data confirm the existence of a limited time-window for CR modulation at the aMCI stage. Show more

Keywords: Alzheimer’s disease, cognitive reserve, cortical thickness, fractal dimension, mild cognitive impairment

DOI: 10.3233/JAD-220377

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-14, 2022