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Authors: Atayde, Adrienne L. | Fischer, Corinne E. | Schweizer, Tom A. | Munoz, David G.

Article Type: Research Article

Abstract: Background: The temporal relationship between sleep, Alzheimer’s disease (AD), and cognitive impairment remains to be further elucidated. Objective: First, we aim to determine whether the Neuropsychiatric Inventory–Questionnaire (NPI-Q) assessed nighttime behaviors prior to cognitive decline influence the rate of cognitive deterioration in pathologically confirmed AD, and second, to assess the possible interactions with APOE allele and cerebral amyloid angiopathy (CAA). Methods: The rate of cognitive decline between cognitively asymptomatic participants from the National Alzheimer Coordinating Center who eventually received a neuropathologic diagnosis of AD with (+NTB) or without (−NTB) nighttime behaviors were compared using independent samples t -test. Participants were …stratified by APOE carrier and CAA status. Demographic and patient characteristics were assessed using descriptive statistics, and the independent samples t -test was used for continuous variables and chi-square test for categorical variables. The significance level was set at p ≤0.05. Results: The rate of cognitive decline was greater in +NTB (n  = 74; 3.30 points/year) than −NTB (n  = 330; 2.45 points/year) (p  = 0.016), even if there was no difference in cognitive status at onset. This difference was restricted to APOE ɛ4 carriers (p  = 0.049) and positive CAA participants (p  = 0.020). Significance was not reached in non-carriers (p  = 0.186) and negative CAA (p  = 0.364). APOE and CAA were not differentially distributed between the NTB groups. Conclusion: NPI-Q assessed nighttime behaviors, a surrogate for sleep disturbances, are associated with more rapidly deteriorating cognition in patients with AD neuropathology who are also carriers of APOE ɛ4 or show CAA. Show more

Keywords: Alzheimer’s disease, Apolipoprotein E, cerebral amyloid angiopathy, cognitive decline, neuropsychiatric symptoms, sleep

DOI: 10.3233/JAD-215276

Citation: Journal of Alzheimer's Disease, vol. 86, no. 3, pp. 1137-1147, 2022

Authors: Fischer, Corinne E. | Churchill, Nathan | Leggieri, Melissa | Vuong, Veronica | Tau, Michael | Fornazzari, Luis R. | Thaut, Michael H. | Schweizer, Tom A.

Article Type: Research Article

Abstract: Background: Repeated exposure to long-known music has been shown to have a beneficial effect on cognitive performance in patients with AD. However, the brain mechanisms underlying improvement in cognitive performance are not yet clear. Objective: In this pilot study we propose to examine the effect of repeated long-known music exposure on imaging indices and corresponding changes in cognitive function in patients with early-stage cognitive decline. Methods: Participants with early-stage cognitive decline were assigned to three weeks of daily long-known music listening, lasting one hour in duration. A cognitive battery was administered, and brain activity was measured before and after intervention. …Paired-measures tests evaluated the longitudinal changes in brain structure, function, and cognition associated with the intervention. Results: Fourteen participants completed the music-based intervention, including 6 musicians and 8 non-musicians. Post-baseline there was a reduction in brain activity in key nodes of a music-related network, including the bilateral basal ganglia and right inferior frontal gyrus, and declines in fronto-temporal functional connectivity and radial diffusivity of dorsal white matter. Musician status also significantly modified longitudinal changes in functional and structural brain measures. There was also a significant improvement in the memory subdomain of the Montreal Cognitive Assessment. Conclusion: These preliminary results suggest that neuroplastic mechanisms may mediate improvements in cognitive functioning associated with exposure to long-known music listening and that these mechanisms may be different in musicians compared to non-musicians. Show more

Keywords: Alzheimer’s disease, cognitive reserve, functional MRI, imaging, MRI, music

DOI: 10.3233/JAD-210610

Citation: Journal of Alzheimer's Disease, vol. 84, no. 2, pp. 819-833, 2021

Authors: Golas, Angela C. | Salwierz, Patrick | Rajji, Tarek K. | Bowie, Christopher R. | Butters, Meryl A. | Fischer, Corinne E. | Flint, Alastair J. | Herrmann, Nathan | Mah, Linda | Mulsant, Benoit H. | Pollock, Bruce G. | Taghdiri, Foad | Wang, Wei | Tartaglia, M. Carmela

Article Type: Short Communication

Abstract: Major depressive disorder (MDD) is a risk factor for Alzheimer’s disease (AD). Cerebrovascular disease (CVD) is implicated in MDD and AD. Our study compared participants with AD positive and negative cerebrospinal fluid (CSF) biomarkers on neuropsychological performance, remitted MDD status, and CVD burden. Next, we compared AD-CSF biomarkers and white matter hyperintensities (WMH) burden among three groups: mild cognitive impairment (MCI) (n  = 12), MCI with remitted MDD (MDD+MCI) (n  = 12), and remitted MDD alone (MDD) (n  = 7). Few participants (18%) with MCI+MDD exhibited AD(+) biomarkers. Nearly all participants had moderate-severe WMH. WMH may contribute to cognitive impairment or depression in …MCI patients with AD(-) biomarkers. Show more

Keywords: Alzheimer’s disease, cerebrovascular disease, major depressive disorder, mild neurocognitive disorder

DOI: 10.3233/JAD-221097

Citation: Journal of Alzheimer's Disease, vol. 92, no. 4, pp. 1219-1227, 2023

Authors: Dissanayake, Andrew S. | Tan, Yu Bin | Bowie, Christopher R. | Butters, Meryl A. | Flint, Alastair J. | Gallagher, Damien | Golas, Angela C. | Herrmann, Nathan | Ismail, Zahinoor | Kennedy, James L. | Kumar, Sanjeev | Lanctot, Krista L. | Mah, Linda | Mulsant, Benoit H. | Pollock, Bruce G. | Rajji, Tarek K. | Tau, Michael | Maraj, Anika | Churchill, Nathan W. | Tsuang, Debby | Schweizer, Tom A. | Munoz, David G. | Fischer, Corinne E.

Article Type: Research Article

Abstract: Background: Recent work suggests that APOE ɛ 4/4 females with Alzheimer’s disease (AD) are more susceptible to developing neuropsychiatric symptoms (NPS). Objective: To examine the interaction of sex and APOE ɛ 4 status on NPS burden using two independent cohorts: 1) patients at risk for AD with mild cognitive impairment and/or major depressive disorder (n  = 252) and 2) patients with probable AD (n  = 7,261). Methods: Regression models examined the interactive effects of sex and APOE ɛ 4 on the number of NPS experienced and NPS Severity. APOE ɛ 3/4 and APOE ɛ 4/4 were pooled in the at-risk cohort due …to the sample size. Results: In the at-risk cohort, there was a significant sex*APOE ɛ 4 interaction (p  = 0.007) such that the association of APOE ɛ 4 with NPS was greater in females than in males (incident rate ratio (IRR) = 2.0). APOE ɛ 4/4 females had the most NPS (mean = 1.9) and the highest severity scores (mean = 3.5) of any subgroup. In the clinical cohort, APOE ɛ 4/4 females had significantly more NPS (IRR = 1.1, p  = 0.001, mean = 3.1) and higher severity scores (b  = 0.31, p  = 0.015, mean = 3.7) than APOE ɛ 3/3 females (meanNPS  = 2.9, meanSeverity  = 3.3). No association was found in males. Conclusion: Our study suggests that sex modifies the association of APOE ɛ 4 on NPS burden. APOE ɛ 4/4 females may be particularly susceptible to increased NPS burden among individuals with AD and among individuals at risk for AD. Further investigation into the mechanisms behind these associations are needed. Show more

Keywords: Alzheimer’s disease, APOE4, behavioral and psychological symptoms of dementia, biomarkers, gender differences, major depressive disorder, mild cognitive impairment, neuropsychiatry, Neuropsychiatric Inventory Questionnaire, psychosis

DOI: 10.3233/JAD-220586

Citation: Journal of Alzheimer's Disease, vol. 90, no. 4, pp. 1571-1588, 2022

Authors: Agüera-Ortiz, Luis | Babulal, Ganesh M. | Bruneau, Marie-Andrée | Creese, Byron | D’Antonio, Fabrizia | Fischer, Corinne E. | Gatchel, Jennifer R. | Ismail, Zahinoor | Kumar, Sanjeev | McGeown, William J. | Mortby, Moyra E. | Nuñez, Nicolas A. | de Oliveira, Fabricio F. | Pereiro, Arturo X. | Ravona-Springer, Ramit | Rouse, Hillary J. | Wang, Huali | Lanctôt, Krista L.

Article Type: Review Article

Abstract: Psychotic phenomena are among the most severe and disruptive symptoms of dementias and appear in 30% to 50% of patients. They are associated with a worse evolution and great suffering to patients and caregivers. Their current treatments obtain limited results and are not free of adverse effects, which are sometimes serious. It is therefore crucial to develop new treatments that can improve this situation. We review available data that could enlighten the future design of clinical trials with psychosis in dementia as main target. Along with an explanation of its prevalence in the common diseases that cause dementia, we present …proposals aimed at improving the definition of symptoms and what should be included and excluded in clinical trials. A review of the available information regarding the neurobiological basis of symptoms, in terms of pathology, neuroimaging, and genomics, is provided as a guide towards new therapeutic targets. The correct evaluation of symptoms is transcendental in any therapeutic trial and these aspects are extensively addressed. Finally, a critical overview of existing pharmacological and non-pharmacological treatments is made, revealing the unmet needs, in terms of efficacy and safety. Our work emphasizes the need for better definition and measurement of psychotic symptoms in dementias in order to highlight their differences with symptoms that appear in non-dementing diseases such as schizophrenia. Advances in neurobiology should illuminate the development of new, more effective and safer molecules for which this review can serve as a roadmap in the design of future clinical trials. Show more

Keywords: Clinical trials, dementia, delusions, hallucinations, investigational therapies, psychotic disorders

DOI: 10.3233/JAD-215483

Citation: Journal of Alzheimer's Disease, vol. 88, no. 4, pp. 1203-1228, 2022