Your search for: 'author:("Fischer, Corinne E.")' has returned 20 results. (0.053s) Save search

Authors: Garcia-Segura, Monica Emili | Fischer, Corinne E. | Schweizer, Tom A. | Munoz, David G.

Article Type: Research Article

Abstract: Background: Aberrant motor behavior (AMB) is a neuropsychiatric symptom (NPS) prevalent in Alzheimer’s disease (AD), known to cause great distress to both patients and caregivers. Apolipoprotein E4 (APOE4 ) is the most important genetic predictor of AD, and it has been associated with high NPS prevalence. Objective: To investigate the neuropathological substrates and risk factors associated with AMB in AD patients. Methods: Cases with Braak stage I-II and CERAD 0-1 were classified as Low AD (LAD), while Braak stage III-IV and CERAD 2 were grouped as Intermediate AD (IAD). Cases with Braak stage V-VI and CERAD 3 were classified as …High AD (HAD) in accordance with NIA-Reagan criteria. All cases were stratified by APOE genotype, yielding No ɛ 4 & ɛ 4 and ɛ 4/ɛ 4 groups depending on ɛ 4 copy number within APOE . Presence of AMB was assessed using NPI-Q. Results and Conclusion: AMB increased in parallel with CERAD and Braak & Braak scores. Hypercholesterolemia, but no other cardiovascular risk factors, was associated with AMB in HAD. AMB prevalence in HAD was significantly increased in the presence of two APOE ɛ 4 alleles as compared to No ɛ 4 & ɛ 4. The relationship between homozygous APOE4 and AMB was strongly associated with the presence of both Lewy bodies and cerebral amyloid angiopathy pathologies in both sexes. Show more

Keywords: Aberrant motor behavior, Alzheimer’s disease, APOE gene, cerebral amyloid angiopathy, Lewy bodies, neuropathology, neuropsychiatric symptoms

DOI: 10.3233/JAD-190643

Citation: Journal of Alzheimer's Disease, vol. 72, no. 4, pp. 1077-1087, 2019

Authors: Kim, Julia | Schweizer, Tom A. | Fischer, Corinne E. | Munoz, David G.

Article Type: Research Article

Abstract: Background: The pathophysiology behind psychosis in patients with Alzheimer’s disease (AD) remains unknown. Recently, vascular risk factors have been recognized as important modifiers of the clinical presentation of AD. Objective: The purpose of our study is to investigate the mechanism through which vascular risk factors mediate psychosis and whether or not it involves cerebrovascular lesions. Methods: Data was provided by the National Alzheimer’s Coordinating Centre. The Uniform Data Set was used to collect information on subject-reported history of vascular risk factors, clinician-reported state of cognitive performance, and presence of psychosis based on the Neuropsychiatric Inventory Questionnaire (NPI-Q). The Neuropathology Data …Set was used to evaluate the presence of vascular lesions and the severity of AD pathology. Subjects with high probability of AD based on the NIA/AA Reagan criteria were included in the analysis. Results: We identified 1,459 patients with high probability of AD and corresponding NPI-Q scores. We confirmed the association between hypertension and diabetes on psychosis, specifically in delusions and the co-occurrence of delusions and hallucinations. Furthermore, the presence of white matter rarefaction based on pathological evaluation was associated with hallucinations. A history of vascular risk factors was positively associated with vascular lesions. However, vascular lesions in the presence of vascular risk factors did not increase the likelihood of psychosis. Furthermore, vascular lesions were not associated with greater cognitive or functional impairments in this group with severe AD pathology. Conclusion: Vascular risk factors and vascular lesions are independently associated with psychosis in patients with severe AD. However, vascular lesions are not the mechanism through which vascular risk factors mediate psychosis. Show more

Keywords: Cerebrovascular diseases, delusions, dementia, hallucinations, infarction, neuropathology, pathology, risk factors, vascular

DOI: 10.3233/JAD-160506

Citation: Journal of Alzheimer's Disease, vol. 55, no. 1, pp. 381-389, 2017

Authors: Sennik, Simrin | Schweizer, Tom A. | Fischer, Corinne E. | Munoz, David G.

Article Type: Research Article

Abstract: Background: Neuropsychiatric symptoms are common manifestations of Alzheimer’s disease (AD). A number of studies have targeted psychosis, i.e., hallucinations and delusions in AD, but few have assessed agitation/aggression in AD. Objective: To investigate the risk factors and pathological substrates associated with presence [A(+)] and absence [A(–)] of agitation/aggression (A) in autopsy-confirmed AD. Methods: Data was collected from the UDS data as of 2015 on the NACC database. Patients were stratified as intermediate (IAD) or high (HAD) pathological load of AD. Clinical diagnoses were not considered; additional pathological diagnoses were treated as variables. Analysis of data did not include a control …group or corrections for multiple comparisons. Results: 1,716 patients met the eligibility criteria; 31.2% of the IAD and 47.8% of the HAD patients were A(+), indicating an association with severity of pathology (p  = 0.001). Risk factors for A(+) included: age at initial visit, age at death, years of education, smoking (in females), recent cardiac events (in males), and clinical history of traumatic brain injury (TBI) (in males). A history of hypertension was not related to A(+). In terms of comorbidity, clinical diagnosis of Lewy body dementia syndrome was associated with A(+) but the association was not confirmed when pathological diagnosis based on demonstration of Lewy bodies was used as the criterion. The additional presence of phosphorylated TDP-43, but not tau pathologies, was associated with A(+)HAD. Vascular lesions, including lacunes, large arterial infarcts, and severity of atherosclerosis were negatively associated with A(+). Associated symptoms included delusions, hallucinations, and depression, but not irritability, aberrant motor behavior, sleep and night time behavioral changes, or changes in appetite and eating habits. Conclusions: Smoking, TBI, and phosphorylated TDP-43 are associated with A(+)AD in specific groups, respectively. A(+) is directly associated with AD pathology load and inversely with vascular lesions. Show more

Keywords: Alzheimer’s disease, agitation, aggression, neuropathology, (p)-TDP-43, traumatic brain injury, vascular lesions, vascular risk factors

DOI: 10.3233/JAD-160780

Citation: Journal of Alzheimer's Disease, vol. 55, no. 4, pp. 1519-1528, 2017

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

Article Type: Research Article

Abstract: Background: The relationship between sleep, neuropathology, and clinical manifestations of Alzheimer’s disease (AD) remains controversial. Objective: To determine whether nighttime behaviors (NTB) are associated with the development of AD histopathology or cognitive decline. Methods: We compared NTB prevalence in subjects with or without AD lesions, and with or without progressive cognitive decline. Subjects with either absent or severe plaques and tangles were identified from the National Alzheimer’s Disease Coordinating Center data sets and classified as cognitively declining if the standard deviation from their individual mean Mini-Mental Status Examination score was ≥2, and stable if <2 regardless of their initial score. …NTB was assessed using the Neuropsychiatric Inventory Questionnaire Quick Version (NPI-Q). Results: NTB was significantly greater in decliners than stable subjects in the group with severe histopathology as determined by frequent plaques (p  = 0.003) or high Braak stage (p  = 0.002). A similar significant trend was observed in subjects with absent plaques (p  = 0.019) or tangles (p  = 0.006). The prevalence of NTB was comparable between stable AD and non-AD subjects. NTB severity scores showed a similar pattern. Conclusion: The development of NTB as assessed by NPI-Q in subjects with or without AD lesions occurred concurrently with cognitive decline. Among cognitively stable subjects, the presence of AD histopathology did not alter NTB prevalence. Thus, NTB disruptions at the gross granularity level assessed by NPI-Q were much more closely related to cognitive decline than the formation of pathological lesions. Factors other than AD histopathology may mediate the association between NTB and cognitive decline. Show more

Keywords: Alzheimer’s disease, amyloid plaque, cognitive decline, neurofibrillary tangles, sleep

DOI: 10.3233/JAD-190907

Citation: Journal of Alzheimer's Disease, vol. 74, no. 3, pp. 839-850, 2020

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: Hird, Megan A. | Egeto, Peter | Fischer, Corinne E. | Naglie, Gary | Schweizer, Tom A.

Article Type: Research Article

Abstract: Background: Many individuals with Alzheimer’s disease (AD) and mild cognitive impairment (MCI) are at an increased risk of driving impairment. There is a need for tools with sufficient validity to help clinicians assess driving ability. Objective: Provide a systematic review and meta-analysis of the primary driving assessment methods (on-road, cognitive, driving simulation assessments) in patients with MCI and AD. Methods: We investigated (1) the predictive utility of cognitive tests and domains, and (2) the areas and degree of driving impairment in patients with MCI and AD. Effect sizes were derived and analyzed in a random effects model. Results: Thirty-two articles …(including 1,293 AD patients, 92 MCI patients, 2,040 healthy older controls) met inclusion criteria. Driving outcomes included: On-road test scores, pass/fail classifications, errors; caregiver reports; real world crash involvement; and driving simulator collisions/risky behavior. Executive function (ES [95% CI]; 0.61 [0.41, 0.81]), attention (0.55 [0.33, 0.77]), visuospatial function (0.50 [0.34, 0.65]), and global cognition (0.61 [0.39, 0.83]) emerged as significant predictors of driving performance. Trail Making Test Part B (TMT-B, 0.61 [0.28, 0.94]), TMT-A (0.65 [0.08, 1.21]), and Maze test (0.88 [0.60, 1.15]) emerged as the best single predictors of driving performance. Patients with very mild AD (CDR = 0.5) mild AD (CDR = 1) were more likely to fail an on-road test than healthy control drivers (CDR = 0), with failure rates of 13.6%, 33.3% and 1.6%, respectively. Conclusion: The driving ability of patients with MCI and AD appears to be related to degree of cognitive impairment. Across studies, there are inconsistent cognitive predictors and reported driving outcomes in MCI and AD patients. Future large-scale studies should investigate the driving performance and associated neural networks of subgroups of AD (very mild, mild, moderate) and MCI (amnestic, non-amnestic, single-domain, multiple-domain). Show more

Keywords: KeywordsAlzheimer’s disease, automobile driving, cognition, mild cognitive impairment

DOI: 10.3233/JAD-160276

Citation: Journal of Alzheimer's Disease, vol. 53, no. 2, pp. 713-729, 2016

Authors: Hird, Megan A. | Vesely, Kristin A. | Fischer, Corinne E. | Graham, Simon J. | Naglie, Gary | Schweizer, Tom A.

Article Type: Short Communication

Abstract: The areas of driving impairment characteristic of mild cognitive impairment (MCI) remain unclear. This study compared the simulated driving performance of 24 individuals with MCI, including amnestic single-domain (sd-MCI, n  = 11) and amnestic multiple-domain MCI (md-MCI, n  = 13), and 20 age-matched controls. Individuals with MCI committed over twice as many driving errors (20.0 versus 9.9), demonstrated difficulty with lane maintenance, and committed more errors during left turns with traffic compared to healthy controls. Specifically, individuals with md-MCI demonstrated greater driving difficulty compared to healthy controls, relative to those with sd-MCI. Differentiating between different subtypes of MCI may be important when …evaluating driving safety. Show more

Keywords: Automobile driving, cognition, computer simulation patient outcome assessment, mild cognitive impairment

DOI: 10.3233/JAD-160995

Citation: Journal of Alzheimer's Disease, vol. 56, no. 2, pp. 447-452, 2017

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: Showraki, Alireza | Murari, Geetanjali | Ismail, Zahinoor | Barfett, Joseph J. | Fornazzari, Luis | Munoz, David G. | Schweizer, Tom A. | Fischer, Corinne E.

Article Type: Research Article

Abstract: Background: Neuropsychiatric symptoms (NPS) are common, accelerate the conversion to dementia, and are associated with increased caregiver burden in Alzheimer’s disease (AD) and mild cognitive impairment (MCI). Objective: The aim of this study is to identify potential associations between the core cerebrospinal fluid (CSF) biomarkers (amyloid/tau) and NPS in AD/MCI. Methods: For this systematic review, four databases, PubMed (1946–2018), Cochrane (2005–2018), EMBASE (1947–2018), and PsycINFO (1806–2018) were searched for relevant observational studies using an extensive list of keywords. English studies were selected for critical appraisal based on our inclusion/exclusion criteria. Inclusion criteria were defined as 1) at least one AD …CSF biomarker has been measured; 2) at least one NPS has been assessed; and 3) analysis has been done to examine the association between core AD CSF biomarker and NPS (main outcome). Animal, postmortem, and review studies were excluded. Results: In total, 21 studies qualified for the systematic review. The overall picture regarding the association between NPS and AD CSF biomarkers is conflicting. However, agitation/aggression was significantly and consistently related to core AD CSF biomarkers. Moreover, depression was the only NPS to occasionally be associated with lower core AD CSF pathology. Conclusion: Our study has revealed agitation/aggression as the most consistent NPS related to core AD CSF biomarkers. Future studies are required to focus on other neglected NPS domains such as disinhibition. Moreover, why depression was the only NPS inversely associated with core AD CSF pathology remains to be elucidated. Our study also revealed a great degree of heterogeneity, hence calling for a more standardized “objective” approach for the evaluation of NPS. Show more

Keywords: Alzheimer’s disease, behavioral symptoms, biomarkers, cerebrospinal fluid, neuropsychiatry, systematic review

DOI: 10.3233/JAD-190365

Citation: Journal of Alzheimer's Disease, vol. 71, no. 2, pp. 477-501, 2019

Authors: Fischer, Corinne E. | Qian, Winnie | Schweizer, Tom A. | Millikin, Colleen P. | Ismail, Zahinoor | Smith, Eric E. | Lix, Lisa M. | Shelton, Paul | Munoz, David G.

Article Type: Research Article

Abstract: Background: The neuropathological correlates of psychosis in Alzheimer’s disease (AD) is unclear, with some studies reporting a correlation between psychosis and increased AD pathology while others have found no association. Objective: To determine the demographic, clinical, and neuropathological features associated with psychotic symptoms in clinically attributed and neuropathologically proven AD. Method: We separately reviewed two overlapping groups of clinically diagnosed (cAD) AD patients with neuropathology data and neuropathologically definite (npAD) cases (regardless of clinical diagnosis) from the NACC database, and explored the relationships between psychosis and clinical variables, neuropathologic correlates, and vascular risk factors. Delusions and hallucinations, defined according to …the NPI-Q, were analyzed separately. Results: 1,073 subjects in the database fulfilled our criteria (890 cAD and 728 npAD patients). 34% of cAD and 37% of npAD had psychotic symptoms during their illness. Hallucinations were associated with greater cognitive and functional impairments on the MMSE and CDR, while delusional patients showed less impairment on CDR, consistent across cAD and npAD groups. Burden of AD pathology appears to relate to presence of psychotic symptoms in the clinical AD group, but this result is not confirmed in the neuropathologically confirmed group suggesting the findings in the clinical group were due to misdiagnosis of AD. Lewy body pathology, subcortical arteriosclerotic leukoencephalopathy, and vascular risk factors, including a history of hypertension and diabetes, were associated with the development of psychosis. Method: Vascular and Lewy body pathologies and vascular risk factors are important modifiers of the risk of psychosis in AD. Show more

Keywords: Alzheimer’s disease, arteriosclerotic leukoencephalopathy, delusion, hallucination, neuropathology, psychosis, vascular pathology

DOI: 10.3233/JAD-150606

Citation: Journal of Alzheimer's Disease, vol. 50, no. 1, pp. 283-295, 2016