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

Authors: Caruso, Giulia | Perri, Roberta | Fadda, Lucia | Caltagirone, Carlo | Carlesimo, Giovanni Augusto

Article Type: Research Article

Abstract: Background: It has long been debated whether performance on recall and recognition tests depends on the same or different memory systems and whether performance on these two tasks is dissociated in clinical populations. According to Dual process theories of recall , performance on recall and recognition tests dissociates in the relative reliance on frontal lobe related activities; in fact, the recall test requires more strategic retrieval of memoranda than the recognition task. By contrast, Dual process theories of recognition posit that performance on these tests differs in the relative contribution of recollection and familiarity memory processes in the two …tasks: both recollection and familiarity contribute to recognition judgments, but only recollection supports recall performance. Objective: The aim of this study was to clarify the cognitive processes involved in recall and recognition in patients with dementia. Methods: We administered a 15-word recall task followed by a yes/no recognition paradigm to 28 patients with Alzheimer’s disease (AD), 22 patients with the behavioral variant of frontotemporal dementia (bvFTD), and 45 normal controls (NCs). Results: Results showed that on the delayed recall task, bvFTD patients performed much better than AD patients but the two groups did not differ on any index of recognition performance. Conclusion: The present data support the hypothesis that the performance of the two groups is expression of the different reliance on recollection (more impaired in the AD than in the bvFTD group) and familiarity (similarly impaired in the two groups) in performance on recall and recognition tasks. Show more

Keywords: Alzheimer’s disease, familiarity, frontotemporal dementia, recall, recognition, recollection

DOI: 10.3233/JAD-200126

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-12, 2020

Authors: Keleman, Audrey | Wisch, Julie K. | Bollinger, Rebecca M. | Grant, Elizabeth A. | Benzinger, Tammie L. | Morris, John C. | Ances, Beau M. | Stark, Susan L.

Article Type: Research Article

Abstract: Background: Behavioral markers for Alzheimer’s disease (AD) are not included within the widely used amyloid-tau-neurodegeneration framework. Objective: To determine when falls occur among cognitively normal (CN) individuals with and without preclinical AD. Methods: This cross-sectional study recorded falls among CN participants (n  = 83) over a 1-year period. Tailored calendar journals recorded falls. Biomarkers including amyloid positron emission tomography (PET) and structural and functional magnetic resonance imaging were acquired within 2 years of fall evaluations. CN participants were dichotomized by amyloid PET (using standard cutoffs). Differences in amyloid accumulation, global resting state functional connectivity (rs-fc) intra-network signature, …and hippocampal volume were compared between individuals who did and did not fall using Wilcoxon rank sum tests. Among preclinical AD participants (amyloid-positive), the partial correlation between amyloid accumulation and global rs-fc intra-network signature was compared for those who did and did not fall. Results: Participants who fell had smaller hippocampal volumes (p  = 0.04). Among preclinical AD participants, those who fell had a negative correlation between amyloid uptake and global rs-fc intra-network signature (R = –0.75, p  = 0.012). A trend level positive correlation was observed between amyloid uptake and global rs-fc intra-network signature (R = 0.70, p  = 0.081) for preclinical AD participants who did not fall. Conclusion: Falls in CN older adults correlate with neurodegeneration biomarkers. Participants without falls had lower amyloid deposition and preserved global rs-fc intra-network signature. Falls most strongly correlated with presence of amyloid and loss of brain connectivity and occurred in later stages of preclinical AD. Show more

Keywords: Alzheimer’s disease, biomarkers, falls, resting state functional connectivity, volumetrics

DOI: 10.3233/JAD-200192

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-8, 2020

Authors: Monsees, Jessica | Schmachtenberg, Tim | Hoffmann, Wolfgang | Kind, Amy | Gilmore-Bykovskyi, Andrea | Kim, Alice J. | Thyrian, Jochen René

Article Type: Research Article

Abstract: Background: As the proportion of older people with migration background (PwM) increases, the proportion of older PwM with dementia might also increase. Dementia is underdiagnosed in this group and a large proportion of PwM with dementia and family caregivers are not properly supported. Healthcare utilization is lower among older migrant populations. Thus, a better understanding of how PwM and family caregivers perceive their situation and how they experience healthcare services is needed to improve utilization of the healthcare system. Objective: Analyze how family caregivers of PwM with dementia experience their situation, why healthcare services are utilized less often, …and what can be done to reverse this. Methods: Eight semi-structured interviews were conducted with people with Turkish migration background caring for PwM with dementia. Qualitative content analysis was used for data analysis. Results: Daily care was performed by one family member with the support of others. Healthcare services were used by most participants. Participants identified a need for better access to relevant information and incorporation of Turkish culture into healthcare services. Conclusion: PwM face similar challenges in taking care of persons with dementia as those without migration background. There is a willingness to use services, and services embracing Turkish culture would help to reduce hesitance and make affected people feel more comfortable, thereby increasing utilization and satisfaction. A limitation of this study is that participants were already connected to health services, which may not reflect the help-seeking behavior of those in the Turkish community who are not involved in healthcare. Show more

Keywords: Dementia, healthcare, healthcare services, migration, Turkish migration background, utilization

DOI: 10.3233/JAD-200184

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-11, 2020

Authors: Pedrini, Steve | Hone, Eugene | Gupta, Veer B. | James, Ian | Teimouri, Elham | Bush, Ashley I. | Rowe, Christopher C. | Villemagne, Victor L. | Ames, David | Masters, Colin L. | Rainey-Smith, Stephanie | Verdile, Giuseppe | Sohrabi, Hamid R. | Raida, Manfred R. | Wenk, Markus R. | Taddei, Kevin | Chatterjee, Pratishtha | Martins, Ian | Laws, Simon M. | Martins, Ralph N. | the AIBL Research Group

Article Type: Research Article

Abstract: Background: The link between cholesterol and Alzheimer’s disease (AD) has received much attention, as evidence suggests high levels of cholesterol might be an AD risk factor. The carriage of cholesterol and lipids through the body is mediated via lipoproteins, some of which, particularly apolipoprotein E (ApoE), are intimately linked with AD. In humans, high density lipoprotein (HDL) is regarded as a “good” lipid complex due to its ability to enable clearance of excess cholesterol via ‘cholesterol reverse transport’, although its activities in the pathogenesis of AD are poorly understood. There are several subclasses of HDL; these range from the newly …formed small HDL, to much larger HDL. Objective: We examined the major subclasses of HDL in healthy controls, mild cognitively impaired, and AD patients who were not taking statins to determine whether there were HDL profile differences between the groups, and whether HDL subclass levels correlated with plasma amyloid-β (Aβ ) levels or brain Aβ deposition. Methods: Samples from AIBL cohort were used in this study. HDL subclass levels were assessed by Lipoprint while Aβ 1–42 levels were assessed by ELISA. Brain Aβ deposition was assessed by PET scan. Statistical analysis was performed using parametric and non-parametric tests. Results: We found that small HDL subclass is reduced in AD patients and it correlates with cognitive performance while plasma Aβ concentrations do not correlate with lipid profile or HDL subfraction levels. Conclusion: Our data indicate that AD patients exhibit altered plasma HDL profile and that HDL subclasses correlate with cognitive performances. Show more

Keywords: Amyloid-β, apolipoprotein, blood, cholesterol, lipid transport

DOI: 10.3233/JAD-200291

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-12, 2020

Authors: Garrido, Sandra | Dunne, Laura | Stevens, Catherine J. | Chang, Esther | Clements-Cortes, Amy

Article Type: Research Article

Abstract: Background: Music programs have the potential to provide an effective non-pharmacological tool for caregivers to reduce depression and agitation and increase quality of life in people with dementia. However, where such programs are not facilitated by a trained music therapist, caregivers need greater access to information about how to use music most effectively in response to key challenges to care, and how to pre-empt and manage adverse responses. Objective: This study reports on the trial of a Guide for use of music with 45 people with dementia and their caregivers in residential care facilities and home-based care. …Methods: The study used a pre-post experimental design in which participants were randomly allocated to a treatment group or a waitlist control group. Results: Improvements to quality of life were found in the experimental group over the 6-week period. Significant increases in Interest, Responsiveness, Initiation, Involvement, and Enjoyment were reported for individual listening sessions. Conclusion: The Guide can provide an effective protocol for caregivers to follow in selecting music to manage particular challenges to care, confirming the need for caregivers to be prepared to monitor and manage potential negative responses. Show more

Keywords: Aged care, agitation, Alzheimer’s disease, arts-based therapies, geriatric depression, health guidelines

DOI: 10.3233/JAD-200457

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-8, 2020

Authors: Fung, Susan | Smith, Carole L. | Prater, Katherine E. | Case, Amanda | Green, Kevin | Osnis, Leah | Winston, Chloe | Kinoshita, Yoshito | Sopher, Bryce | Morrison, Richard S. | Garden, Gwenn A. | Jayadev, Suman

Article Type: Research Article

Abstract: Background: Early-onset familial Alzheimer disease (EOFAD) is caused by heterozygous variants in the presenilin 1 (PSEN1 ), presenilin 2 (PSEN 2), and APP genes. Decades after their discovery, the mechanisms by which these genes cause Alzheimer’s disease (AD) or promote AD progression are not fully understood. While it is established that presenilin (PS) enzymatic activity produces amyloid-β (Aβ ), PSs also regulate numerous other cellular functions, some of which intersect with known pathogenic drivers of neurodegeneration. Accumulating evidence suggests that microglia, resident innate immune cells in the central nervous system, play a key role in AD neurodegeneration. …Objective: Previous work has identified a regulatory role for PS2 in microglia. We hypothesized that PSEN2 variants lead to dysregulated microglia, which could further contribute to disease acceleration. To mimic the genotype of EOFAD patients, we created a transgenic mouse expressing PSEN2 N141I on a mouse background expressing one wildtype PS2 and two PS1 alleles. Results: Microglial expression of PSEN2 N141I resulted in impaired γ -secretase activity as well as exaggerated inflammatory cytokine release, NFκ B activity, and Aβ internalization. In vivo , PS2 N141I mice showed enhanced IL-6 and TREM2 expression in brain as well as reduced branch number and length, an indication of “activated” morphology, in the absence of inflammatory stimuli. LPS intraperitoneal injection resulted in higher inflammatory gene expression in PS2 N141I mice brain relative to controls. Conclusion: Our findings demonstrate that PSEN2 N141I heterozygosity is associated with disrupted innate immune homeostasis, suggesting EOFAD variants may promote disease progression through non-neuronal cells beyond canonical dysregulated Aβ production. Show more

Keywords: Alzheimer’s disease, cytokine, glia, inflammation, microglia, phagocytosis, presenilin

DOI: 10.3233/JAD-200492

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-14, 2020

Authors: Gallucci, Maurizio | Mazzarolo, Anna Paola | Focella, Lucia | Piovesan, Cinzia | Mazzetto, Manuela | Ramigni, Mauro | Marzetti, Emanuele

Article Type: Research Article

Abstract: Background: Frailty is a condition of increased vulnerability to exogenous and endogenous stressors, which is correlated with aging, functional decline, institutionalization, hospitalization, and mortality. Given the multifaceted nature of frailty, programs aimed at its prevention are recommended to act on multiple domains. Objective: The present intervention program aimed at assessing the effects of combined physical and cognitive training in older people with mild cognitive impairment (MCI) and at investigating how their frailty status changed over one year of follow-up. Methods: Two-hundred and seven participants were recruited among outpatients of the Cognitive Impairment Center who agreed to …receive a comprehensive assessment. Forty-six participants, who joined a structured program of physical activity and group readings for a period of one year, were defined as active. The remaining 161, who decided not to engage in those activities, were considered controls. In both groups, frailty status was assessed at baseline and over one year of follow-up. Results: Control participants showed twice the risk of becoming frail at 12 months compared with those in the active group. Participants in the active group had more than three times the probability of improving their frailty status compared with the control group from T0 to T12. Age and NPI scores were significantly associated with worsening frailty status. When analyses were restricted to participants who were robust at baseline, the frailty status varied significantly between groups over time. Conclusion: Findings of the present study confirm the beneficial effects of physical activity and reading to prevent frailty in older people with MCI. Show more

Keywords: Cognitive frailty, community, multi-domain intervention, neuroimaging, TREDEM registry

DOI: 10.3233/JAD-200542

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-11, 2020

Authors: Poptsi, Eleni | Moraitou, Despina | Tsardoulias, Emmanouil | Symeonidisd, Andreas L. | Tsolaki, Magda

Article Type: Research Article

Abstract: Background: The early diagnosis of neurocognitive disorders before the symptoms’ onset is the ultimate goal of the scientific community. REMEDES for Alzheimer (R4Alz) is a battery, designed for assessing cognitive control abilities in people with minor and major neurocognitive disorders. Objective: To investigate whether the R4Alz battery’s tasks differentiate subjective cognitive decline (SCD) from cognitively healthy adults (CHA) and mild cognitive impairment (MCI). Methods: The R4Alz battery was administered to 175 Greek adults, categorized in five groups a) healthy young adults (n  = 42), b) healthy middle-aged adults (n  = 33), c) healthy older adults (HOA; n  = 14), …d) community-dwelling older adults with SCD (n  = 34), and e) people with MCI (n  = 52). Results: Between the seven R4Alz subtasks, four showcased the best results for differentiating HOA from SCD: the working memory updating (WMCUT-S3), the inhibition and switching subtask (ICT/RST-S1&S2), the failure sets (FS) of the ICT/RST-S1&S2, and the cognitive flexibility subtask (ICT/RST-S3). The total score of the four R4Alz subtasks (R4AlzTot4) leads to an excellent discrimination among SCD and healthy adulthood, and to fare discrimination among SCD and MCI. Conclusion: The R4Alz battery is a novel approach regarding the neuropsychological assessment of people with SCD, since it can very well assist toward discriminating SCD from HOA. The R4Alz is able to measure decline of specific cognitive control abilities—namely of working memory updating, and complex executive functions—which seem to be the neuropsychological substrate of cognitive complaints in community dwelling adults of advancing age. Show more

Keywords: Cognitive control assessment battery, cognitively healthy adults, mild cognitive impairment, normative data, subjective cognitive decline

DOI: 10.3233/JAD-200562

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-18, 2020

Authors: Badji, Atef | de la Colina, Adrián Noriega | Boshkovski, Tommy | Sabra, Dalia | Karakuzu, Agah | Robitaille-Grou, Marie-Christine | Gros, Charley | Joubert, Sven | Bherer, Louis | Lamarre-cliche, Maxime | Stikov, Nikola | Gauthier, Claudine J. | Cohen-Adad, Julien | Girouard, Hélène

Article Type: Research Article

Abstract: Background: Vascular risk factors such as arterial stiffness play an important role in the etiology of Alzheimer’s disease (AD), presumably due to the emergence of white matter lesions. However, the impact of arterial stiffness to white matter structure involved in the etiology of AD, including the corpus callosum remains poorly understood. Objective: The aims of the study are to better understand the relationship between arterial stiffness, white matter microstructure, and perfusion of the corpus callosum in older adults. Methods: Arterial stiffness was estimated using the gold standard measure of carotid-femoral pulse wave velocity (cfPWV). Cognitive performance …was evaluated with the Trail Making Test part B-A. Neurite orientation dispersion and density imaging was used to obtain microstructural information such as neurite density and extracellular water diffusion. The cerebral blood flow was estimated using arterial spin labelling. Results: cfPWV better predicts the microstructural integrity of the corpus callosum when compared with other index of vascular aging (the augmentation index, the systolic blood pressure, and the pulse pressure). In particular, significant associations were found between the cfPWV, an alteration of the extracellular water diffusion, and a neuronal density increase in the body of the corpus callosum which was also correlated with the performance in cognitive flexibility. Conclusion: Our results suggest that arterial stiffness is associated with an alteration of brain integrity which impacts cognitive function in older adults. Show more

Keywords: Aging, Alzheimer’s disease, arterial spin labelling, arterial stiffness, corpus callosum, diffusion weighted imaging

DOI: 10.3233/JAD-200668

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-15, 2020

Authors: Fu, Pengfei | Yung, Ken Kin Lam

Article Type: Research Article

Abstract: Background: Ambient air pollution has been associated with Alzheimer’s disease (AD) in the elderly. However, its effects on AD have not been meta-analyzed comprehensively. Objective: We conducted a systematic review and meta-analysis to assess the associations between air pollution and AD incidence. Methods: We searched PubMed and Web of Science for indexed publications up to March 2020. Odds risk (OR) and confidence intervals (CI) were estimated for particulate matter (PM)10 (PM10 ), PM2.5 , ozone (O3 ), nitrogen dioxide (NO2 ), sulfur dioxide (SO2 ), and carbon monoxide (CO). The subgroup analysis was conducted based on …the pollution levels. Results: Nine studies were included in the meta-analysis and review. The OR per 10μ g/m3 increase of PM2.5 was 1.95 (95% CI: 0.88–4.30). The corresponding values per 10μ g/m3 increment of other pollutants were 1.03 (95% CI: 0.68–1.57) for O3 , 1.00 (95% CI: 0.89–1.13) for NO2 , and 0.95 (95% CI: 0.91–0.99) for PM10 (only one study), respectively. Overall OR of the five air pollutants above with AD was 1.32 (95% CI: 1.09–1.61), suggesting a positive association between ambient air pollution and AD incidence. The sub-analysis indicated that the OR (2.20) in heavily polluted regions was notably higher than that in lightly polluted regions (1.06). Although AD risk rate data related to SO2 or CO exposure are still limited, the epidemiologic and toxicological evidence indicated that higher concentration of SO2 or CO exposure increased risks of dementia, implying that SO2 or CO might have a potential impact on AD. Conclusion: Air pollution exposure may exacerbate AD development. Show more

Keywords: Air pollution, Alzheimer’s disease, meta-analysis, systematic review

DOI: 10.3233/JAD-200483

Citation: Journal of Alzheimer's Disease, vol. Pre-press, no. Pre-press, pp. 1-14, 2020