Your search for: 'author:("Fischer, Corinne E.")' has returned 20 results. (0.033s) Save search

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: Fischer, Corinne E. | Kortebi, Ines | Karameh, Wael K. | Kumar, Sanjeev | Gallagher, Damien | Golas, Angela | Munoz, David | Barfett, Joseph | Butters, Meryl A. | Bowie, Christopher R. | Flint, Alastair | Rajji, Tarek | Herrmann, Nathan | Pollock, Bruce G. | Mulsant, Benoit | Schweizer, Tom A. | Mah, Linda | and the PACT-MD Study Group

Article Type: Research Article

Abstract: Background: Cardiovascular risk factors (CVRFs) have been linked to both depression and cognitive decline but their role in neuropsychiatric symptoms (NPS) has yet to be clarified. Objective: Understanding the role of CVRFs in the etiology of NPS for prospective treatments and preventive strategies to minimize these symptoms. Methods: We examined the distribution of NPS using the Neuropsychiatric Inventory (NPI) scores in three cohorts from the Prevention of Alzheimer’s Dementia with Cognitive Remediation Plus Transcranial Direct Current Stimulation in Mild Cognitive Impairment and Depression (PACt-MD) study: older patients with a lifetime history of major depressive disorder (MDD) in remission, patients with …mild cognitive impairment (MCI), and patients with combined MCI and MDD. We also examined the link between individual NPS and CVRFs, Framingham risk score, and Hachinski ischemic score in a combined sample. Results: Analyses were based on a sample of 140 subjects, 70 with MCI, 38 with MCI plus MDD, and 32 with MDD. There was no effect of age, gender, education, cognition, or CVRFs on the presence (NPI >1) or absence (NPI = 0) of NPS. Depression was the most prevalent affective NPS domain followed by night-time behaviors and appetite changes across all three diagnostic groups. Agitation and aggression correlated negatively while anxiety, disinhibition, night-time behaviors, and irritability correlated positively with CVRFs (all p -values <0.05). Other NPS domains showed no significant association with CVRFs. Conclusion: CVRFs are significantly associated with individual NPI sub-scores but not with total NPI scores, suggesting that different pathologies may contribute to different NPS domains. Show more

Keywords: Affective symptoms, sep alzheimer’s disease, sep cardiovascular diseases, sep cognitive dysfunction, sep dementia, sep major depressive disorder, sep mental status and dementia tests, sep neurobehavioral manifestations

DOI: 10.3233/JAD-181099

Citation: Journal of Alzheimer's Disease, vol. 67, no. 4, pp. 1305-1311, 2019

Authors: Yuen, Kimberley | Rashidi-Ranjbar, Neda | Verhoeff, Nicolaas Paul L.G. | Kumar, Sanjeev | Gallagher, Damien | Flint, Alastair J. | Herrmann, Nathan | Pollock, Bruce G. | Mulsant, Benoit H. | Rajji, Tarek K. | Voineskos, Aristotle N. | Fischer, Corinne E. | Mah, Linda | for the PACt-MD Study Group

Article Type: Research Article

Abstract: Background: Previous studies examining the link between neuropsychiatric symptoms (NPS) and biomarkers of Alzheimer’s disease (AD) may be confounded by remitted or past history of psychiatric illness, which in itself is associated with AD biomarkers such as reduced medial temporal lobe (MTL) volume. Objective: We examined associations between mood and anxiety-related NPS and MTL in older adults with mild cognitive impairment (MCI) free of lifetime history of depression. We hypothesized an inverse relationship between NPS severity and MTL. Methods: Forty-two MCI participants without current or past history of depression or other major psychiatric illness were assessed using the Neuropsychiatric Inventory-Questionnaire …(NPI-Q). Correlation and regression analyses were performed between selected NPI-Q items and regional MTL volumes from structural magnetic resonance imaging. Results: Sleep disturbances were inversely associated with several regional volumes within the MTL. Sleep disturbances remained significantly correlated with left hippocampal and amygdala volume following correction for multiple comparisons. In contrast, depression and anxiety were not correlated with MTL. Conclusions: The relationship between reduced MTL and sleep, but not with depressed or anxious states, in MCI free of lifetime history of depression, suggests a potential mechanism for sleep as a risk factor for AD. The current findings highlight the importance of accounting for remitted psychiatric conditions in studies of the link between NPS and AD biomarkers and support the need for further research on sleep as clinical biomarker of AD and target for AD prevention. Show more

Keywords: Alzheimer’s disease, depression, medial temporal lobe, mild cognitive impairment, neuroimaging biomarkers, neuropsychiatric symptoms, sleep

DOI: 10.3233/JAD-190160

Citation: Journal of Alzheimer's Disease, vol. 69, no. 2, pp. 413-421, 2019

Authors: Goodman, Michelle S. | Zomorrodi, Reza | Kumar, Sanjeev | Barr, Mera S. | Daskalakis, Zafiris J. | Blumberger, Daniel M. | Fischer, Corinne E. | Flint, Alastair | Mah, Linda | Herrmann, Nathan | Pollock, Bruce G. | Bowie, Christopher R. | Mulsant, Benoit H. | Rajji, Tarek K. | The PACt-MD Study Group

Collaborators: Mulsant, B.H. | Rajji, T.K. | Herrmann, N. | Pollock, B.G. | Lourenco, L. | Blumberger, D.M. | Bowie, C.R. | Butters, M. | Fischer, C.E. | Flint, A. | Gallagher, D. | Golas, A. | Graff, A. | Kennedy, J.L. | Kumar, S. | Mah, L. | Ovaysikia, S. | Rapoport, M. | Thorpe, K. | Verhoeff, N.P.L.G. | Voineskos, A.N.

Article Type: Research Article

Abstract: While several studies have found that neural oscillations play a key role in the functioning of working memory, the nature of aberrant oscillatory activity underlying working memory impairments in Alzheimer’s disease (AD) and mild cognitive impairment (MCI) remains largely unexplored. These individuals often display structural alterations in brain regions and pathways involved in working memory processes and therefore may also display altered oscillatory activity during memory activation. Electroencephalographic (EEG) activity was recorded during the N-back working memory task in three groups: AD (n  = 29), MCI (n  = 100), and healthy controls (HCs; n  = 40). Theta (4–7 Hz) and alpha (7.5–12 Hz) modulation was …measured in response to the stimulus presentation during correct and incorrect responses. This modulation represents the change in EEG activity associated with the stimulus onset and was measured as a ratio of post stimulus power to pre stimulus power. We also assessed the relationship between change in oscillatory power and working memory performance. Compared to HCs, the AD group demonstrated the lowest working memory accuracy and a smaller theta ratio for correct responses on the 2-back condition; the MCI group demonstrated a smaller theta ratio for correct responses on the 3-back condition. Finally, we observed that the theta ratio, but not the alpha ratio, was a significant predictor of working memory performance in the three groups for all conditions. Taken together, these behavioral and electrophysiological results suggest that in addition to impairments in working memory performance, modulation of theta, but not alpha power, may be impaired in MCI and AD. Show more

Keywords: Alpha power, Alzheimer’s disease, electroencephalography, mild cognitive impairment, theta power, working memory

DOI: 10.3233/JAD-181195

Citation: Journal of Alzheimer's Disease, vol. 68, no. 3, pp. 1085-1094, 2019

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: Fischer, Corinne E. | Ismail, Zahinoor | Youakim, James M. | Creese, Byron | Kumar, Sanjeev | Nuñez, Nicolas | Ryan Darby, R. | Di Vita, Antonella | D’Antonio, Fabrizia | de Lena, Carlo | McGeown, William J. | Ramit, Ravona | Rasmussen, Jill | Bell, Joanne | Wang, Huali | Bruneau, Marie-Andrée | Panegyres, Peter K. | Lanctôt, Krista L. | Agüera-Ortiz, Luis | Lyketsos, Constantine | Cummings, Jeffrey | Jeste, Dilip V. | Sano, Mary | Devanand, D.P. | Sweet, Robert A. | Ballard, Clive

Article Type: Research Article

Abstract: Background: Psychotic symptoms are common in Alzheimer’s disease (AD) and related neurodegenerative disorders and are associated with more rapid disease progression and increased mortality. It is unclear to what degree existing criteria are utilized in clinical research and practice. Objective: To establish research criteria for the diagnosis of psychosis in AD. Methods: The International Society to Advance Alzheimer’s Research and Treatment (ISTAART) Neuropsychiatric Symptoms (NPS) Professional Interest Area (PIA) psychosis subgroup reviewed existing criteria for psychosis in AD and related dementias. Through a series of in person and on-line meetings, a priority checklist was devised to capture features necessary for …current research and clinical needs. PubMed, Medline and other relevant databases were searched for relevant criteria. Results: Consensus identified three sets of criteria suitable for review including those of Jeste and Finkel, Lyketsos, and the Diagnostic and Statistical Manual for Mental Disorders , 5th edition. It was concluded that existing criteria could be augmented by including a more specific differentiation between delusions and hallucinations, address overlap with related conditions (agitation in particular), adding the possibility of symptoms emerging in the preclinical and prodromal phases, and building on developing research in disease biomarkers. Conclusion: We propose criteria, developed to improve phenotypic classification of psychosis in AD, and advance the research agenda in the field to improve epidemiological, biomarker, and genetics research in the field. These criteria serve as a complement to the International Psychogeriatric Association criteria for psychosis in neurocognitive disorders. Show more

Keywords: Alzheimer’s disease, criteria, delusions, hallucinations, mild cognitive impairment, psychosis

DOI: 10.3233/JAD-190828

Citation: Journal of Alzheimer's Disease, vol. 73, no. 3, pp. 1143-1156, 2020

Authors: Rajji, Tarek K. | Bowie, Christopher R. | Herrmann, Nathan | Pollock, Bruce G. | Bikson, Marom | Blumberger, Daniel M. | Butters, Meryl A. | Daskalakis, Zafiris J. | Fischer, Corinne E. | Flint, Alastair J. | Golas, Angela C. | Graff-Guerrero, Ariel | Kumar, Sanjeev | Lourenco, Lillian | Mah, Linda | Ovaysikia, Shima | Thorpe, Kevin E. | Voineskos, Aristotle N. | Mulsant, Benoit H. | for the PACt-MD Study Group

Article Type: Research Article

Abstract: Background: By the time Alzheimer’s disease and related disorders (ADRD) are diagnosed, efficacy of treatments is limited. Preventive interventions are urgently needed. Objective: To design a randomized controlled trial to assess a novel intervention that aims to prevent ADRD in high-risk groups. Methods: We report on the rationale and describe the design of a multisite randomized controlled trial that aims to prevent ADRD in older persons with: (1) mild cognitive impairment (MCI); (2) remitted major depressive disorder (MDD) without MCI; or (3) remitted MDD with MCI. Results: PACt-MD (Prevention of Alzheimer’s dementia with Cognitive remediation plus transcranial direct current stimulation …in Mild cognitive impairment and Depression) is a trial that randomized 375 older participants with MCI, MDD, or MCI + MDD to cognitive remediation (CR) plus transcranial direct current stimulation (tDCS) or sham-CR + sham-tDCS for 5 days/week for 8 weeks followed by boosters for 5 days/week once every 6 months until participants progress to MCI or ADRD, or the end of the study. Between boosters, participants are asked to train on CR daily. At baseline, end of 8 weeks, and yearly from baseline, participants undergo clinical, cognitive, and functional assessments. The primary aims are to compare the efficacy of CR + tDCS versus sham + sham in preventing: 1) long-term cognitive decline; and 2) incidence of ADRD or MCI. The secondary aim is to assess for cognitive improvement after the 8-week course. We will also explore the moderating and mediating effects of several biomarkers collected from the participants. Conclusion: PACt-MD is unique in combining brain stimulation and a psychosocial intervention to prevent ADRD. PACt-MD is also a platform for studying multi-domain biomarkers that will advance our understanding of the relationships among MCI, MDD, and ADRD. Show more

Keywords: Alzheimer’s disease and related disorders, cognitive remediation, major depressive disorder, mild cognitive disorder, PACt-MD, prevention, transcranial direct current stimulation, NCT02386670

DOI: 10.3233/JAD-200141

Citation: Journal of Alzheimer's Disease, vol. 76, no. 2, pp. 733-751, 2020

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

Authors: Kapoor, Arunima | Bartha, Robert | Black, Sandra E. | Borrie, Michael | Freedman, Morris | Gao, Fuqiang | Herrmann, Nathan | Mandzia, Jennifer | Ozzoude, Miracle | Ramirez, Joel | Scott, Christopher J.M. | Symons, Sean | Fischer, Corinne E. | Frank, Andrew | Seitz, Dallas | Wolf, Michael Uri | Verhoeff, Nicolaas Paul L.G. | Naglie, Gary | Reichman, William | Masellis, Mario | Mitchell, Sara B. | Tang-Wai, David F. | Tartaglia, Maria Carmela | Kumar, Sanjeev | Pollock, Bruce G. | Rajji, Tarek K. | Finger, Elizabeth | Pasternak, Stephen H. | ONDRI Investigators | Swartz, Richard H.

Article Type: Research Article

Abstract: Background/Objective: Structural brain magnetic resonance imaging (MRI) is not mandatory in Alzheimer’s disease (AD) research or clinical guidelines. We aimed to explore the use of structural brain MRI in AD/mild cognitive impairment (MCI) trials over the past 10 years and determine the frequency with which inclusion of standardized structural MRI acquisitions detects comorbid vascular and non-vascular pathologies. Methods: We systematically searched ClinicalTrials.gov for AD clinical trials to determine their neuroimaging criteria and then used data from an AD/MCI cohort who underwent standardized MRI protocols, to determine type and incidence of clinically relevant comorbid pathologies. Results: Of 210 AD clinical trials, …105 (50%) included structural brain imaging in their eligibility criteria. Only 58 (27.6%) required MRI. 16,479 of 53,755 (30.7%) AD participants were in trials requiring MRI. In the observational AD/MCI cohort, 141 patients met clinical criteria; 22 (15.6%) had relevant MRI findings, of which 15 (10.6%) were exclusionary for the study. Discussion: In AD clinical trials over the last 10 years, over two-thirds of participants could have been enrolled without brain MRI and half without even a brain CT. In a study sample, relevant comorbid pathology was found in 15% of participants, despite careful screening. Standardized structural MRI should be incorporated into NIA-AA diagnostic guidelines (when available) and research frameworks routinely to reduce diagnostic heterogeneity. Show more

DOI: 10.3233/JAD-191097

Citation: Journal of Alzheimer's Disease, vol. 74, no. 3, pp. 747-757, 2020

Authors: Ismail, Zahinoor | Agüera-Ortiz, Luis | Brodaty, Henry | Cieslak, Alicja | Cummings, Jeffrey | Fischer, Corinne E. | Gauthier, Serge | Geda, Yonas E. | Herrmann, Nathan | Kanji, Jamila | Lanctôt, Krista L. | Miller, David S. | Mortby, Moyra E. | Onyike, Chiadi U. | Rosenberg, Paul B. | Smith, Eric E. | Smith, Gwenn S. | Sultzer, David L. | Lyketsos, Constantine | for the NPS Professional Interest Area of the International Society of to Advance Alzheimer’s Research and Treatment (NPS-PIA of ISTAART)

Article Type: Research Article

Abstract: Background: Mild behavioral impairment (MBI) is a construct that describes the emergence at ≥50 years of age of sustained and impactful neuropsychiatric symptoms (NPS), as a precursor to cognitive decline and dementia. MBI describes NPS of any severity, which are not captured by traditional psychiatric nosology, persist for at least 6 months, and occur in advance of or in concert with mild cognitive impairment. While the detection and description of MBI has been operationalized in the International Society to Advance Alzheimer’s Research and Treatment – Alzheimer’s Association (ISTAART-AA) research diagnostic criteria, there is no instrument that accurately reflects MBI as …described. Objective: To develop an instrument based on ISTAART-AA MBI criteria. Methods: Eighteen subject matter experts participated in development using a modified Delphi process. An iterative process ensured items reflected the five MBI domains of 1) decreased motivation; 2) emotional dysregulation; 3) impulse dyscontrol; 4) social inappropriateness; and 5) abnormal perception or thought content. Instrument language was developed a priori to pertain to non-demented functionally independent older adults. Results: We present the Mild Behavioral Impairment Checklist (MBI-C), a 34-item instrument, which can easily be completed by a patient, close informant, or clinician. Conclusion: The MBI-C provides the first measure specifically developed to assess the MBI construct as explicitly described in the criteria. Its utility lies in MBI case detection, and monitoring the emergence of MBI symptoms and domains over time. Studies are required to determine the prognostic value of MBI for dementia development, and for predicting different dementia subtypes. Show more

DOI: 10.3233/JAD-160979

Citation: Journal of Alzheimer's Disease, vol. 56, no. 3, pp. 929-938, 2017