31 results on '"Coventry, Christina"'
Search Results
2. Focal amyloid and asymmetric tau in an imaging-to-autopsy case of clinical primary progressive aphasia with Alzheimer disease neuropathology
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Martersteck, Adam, Ayala, Ivan, Ohm, Daniel T., Spencer, Callen, Coventry, Christina, Weintraub, Sandra, Bigio, Eileen H., Mesulam, M. -Marsel, Geula, Changiz, and Rogalski, Emily
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- 2022
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3. Modularity and granularity across the language network-A primary progressive aphasia perspective
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Mesulam, M.-Marsel, Coventry, Christina A., Rader, Benjamin M., Kuang, Alan, Sridhar, Jaiashre, Martersteck, Adam, Zhang, Hui, Thompson, Cynthia K., Weintraub, Sandra, and Rogalski, Emily J.
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- 2021
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4. Phenotypically concordant distribution of pick bodies in aphasic versus behavioral dementias.
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Kawles, Allegra, Keszycki, Rachel, Minogue, Grace, Zouridakis, Antonia, Ayala, Ivan, Gill, Nathan, Macomber, Alyssa, Lubbat, Vivienne, Coventry, Christina, Rogalski, Emily, Weintraub, Sandra, Mao, Qinwen, Flanagan, Margaret E., Zhang, Hui, Castellani, Rudolph, Bigio, Eileen H., Mesulam, M.-Marsel, Geula, Changiz, and Gefen, Tamar
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TEMPORAL lobe ,PARIETAL lobe ,ALZHEIMER'S disease ,FRONTOTEMPORAL lobar degeneration ,PREFRONTAL cortex - Abstract
Pick's disease (PiD) is a subtype of the tauopathy form of frontotemporal lobar degeneration (FTLD-tau) characterized by intraneuronal 3R-tau inclusions. PiD can underly various dementia syndromes, including primary progressive aphasia (PPA), characterized by an isolated and progressive impairment of language and left-predominant atrophy, and behavioral variant frontotemporal dementia (bvFTD), characterized by progressive dysfunction in personality and bilateral frontotemporal atrophy. In this study, we investigated the neocortical and hippocampal distributions of Pick bodies in bvFTD and PPA to establish clinicopathologic concordance between PiD and the salience of the aphasic versus behavioral phenotype. Eighteen right-handed cases with PiD as the primary pathologic diagnosis were identified from the Northwestern University Alzheimer's Disease Research Center brain bank (bvFTD, N = 9; PPA, N = 9). Paraffin-embedded sections were stained immunohistochemically with AT8 to visualize Pick bodies, and unbiased stereological analysis was performed in up to six regions bilaterally [middle frontal gyrus (MFG), superior temporal gyrus (STG), inferior parietal lobule (IPL), anterior temporal lobe (ATL), dentate gyrus (DG) and CA1 of the hippocampus], and unilateral occipital cortex (OCC). In bvFTD, peak neocortical densities of Pick bodies were in the MFG, while the ATL was the most affected in PPA. Both the IPL and STG had greater leftward pathology in PPA, with the latter reaching significance (p < 0.01). In bvFTD, Pick body densities were significantly right-asymmetric in the STG (p < 0.05). Hippocampal burden was not clinicopathologically concordant, as both bvFTD and PPA cases demonstrated significant hippocampal pathology compared to neocortical densities (p < 0.0001). Inclusion-to-neuron analyses in a subset of PPA cases confirmed that neurons in the DG are disproportionately burdened with inclusions compared to neocortical areas. Overall, stereological quantitation suggests that the distribution of neocortical Pick body pathology is concordant with salient clinical features unique to PPA vs. bvFTD while raising intriguing questions about the selective vulnerability of the hippocampus to 3R-tauopathies. [ABSTRACT FROM AUTHOR]
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- 2024
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5. Familial language network vulnerability in primary progressive aphasia
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Weintraub, Sandra, Rader, Benjamin, Coventry, Christina, Sridhar, Jaiashre, Wood, Jessica, Guillaume, Kyla A., Coppola, Giovanni, Ramos, Eliana Marisa, Bonakdarpour, Borna, Rogalski, Emily J., and Mesulam, M. Marsel
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- 2020
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6. Differential neurocognitive network perturbation in amnestic and aphasic Alzheimer disease
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Martersteck, Adam, Sridhar, Jaiashre, Rader, Benjamin, Coventry, Christina, Parrish, Todd, Mesulam, M.-Marsel, and Rogalski, Emily
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- 2020
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7. APOE is a correlate of phenotypic heterogeneity in Alzheimer disease in a national cohort
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Weintraub, Sandra, Teylan, Merilee, Rader, Benjamin, Chan, Kwun C.G., Bollenbeck, Mark, Kukull, Walter A., Coventry, Christina, Rogalski, Emily, Bigio, Eileen, and Mesulam, M.-Marsel
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- 2020
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8. Distinct and shared neuropsychiatric phenotypes in FTLD-tauopathies.
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Keszycki, Rachel, Kawles, Allegra, Minogue, Grace, Zouridakis, Antonia, Macomber, Alyssa, Gill, Nathan, My Vu, Hui Zhang, Coventry, Christina, Rogalski, Emily, Weintraub, Sandra, Mesulam, M.-Marsel, Geula, Changiz, and Gefen, Tamar
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STATISTICS ,ANALYSIS of variance ,CONFIDENCE intervals ,AUTOPSY ,FRONTOTEMPORAL lobar degeneration ,TAUOPATHIES ,FISHER exact test ,REGRESSION analysis ,NEUROPSYCHOLOGICAL tests ,DEMENTIA ,QUESTIONNAIRES ,DESCRIPTIVE statistics ,RESEARCH funding ,DATA analysis software ,DATA analysis ,LOGISTIC regression analysis ,ODDS ratio ,PHENOTYPES ,LONGITUDINAL method ,SYMPTOMS - Abstract
Frontotemporal lobar degeneration (FTLD) with tau pathology (FTLD-tau) commonly causes dementia syndromes that include primary progressive aphasia (PPA) and behavioral variant frontotemporal dementia (bvFTD). Cognitive decline in PPA and bvFTD is often accompanied by debilitating neuropsychiatric symptoms. In 44 participants with PPA or bvFTD due to autopsy-confirmed FTLD-tau, we characterized neuropsychiatric symptoms at early and late disease stages and determined whether the presence of certain symptoms predicted a specific underlying FTLD-tauopathy. Participants completed annual research visits at the Northwestern University Alzheimer's Disease Research Center. All participants had an initial Global Clinical Dementia Rating (CDR) Scale score ≤ 2, and neuropsychiatric symptoms were evaluated via the Neuropsychiatric Inventory-Questionnaire (NPI-Q). We assessed the frequency of neuropsychiatric symptoms across all participants at their initial and final visits and performed logistic regression to determine whether symptoms predicted a specific FTLDtau pathologic diagnosis. Across the FTLD-tau cohort, irritability and apathy were most frequently endorsed at initial and final visits, respectively, whereas psychosis was highly uncommon at both timepoints. Irritability at initial visit predicted greater odds of a 4-repeat compared to a 3-repeat tauopathy (OR = 3.95, 95% CI = 1.10-15.83, p < 0.05). Initial sleep disturbance predicted greater odds of progressive supranuclear palsy (PSP) compared to other FTLD-tau subtypes (OR = 10.68, 95% CI = 2.05-72.40, p < 0.01). Appetite disturbance at final evaluation predicted lower odds of PSP (OR = 0.15, 95% CI = 0.02-0.74, p < 0.05). Our findings suggest that characterization of neuropsychiatric symptoms can aid in the prediction of underlying FTLD-tauopathies. Given considerable pathologic heterogeneity underlying dementias, neuropsychiatric symptoms may be useful for differential diagnosis and treatment planning. [ABSTRACT FROM AUTHOR]
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- 2023
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9. Eye movements as a measure of word comprehension deficits in primary progressive aphasia
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Karpouzian-Rogers, Tatiana, Hurley, Rob, Seckin, Mustafa, Moeller, Stacey, Gill, Nathan, Zhang, Hui, Coventry, Christina, Nelson, Matthew, Weintraub, Sandra, Rogalski, Emily, and Marsel Mesulam, M.
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- 2022
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10. Neuropathological fingerprints of survival, atrophy and language in primary progressive aphasia.
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Mesulam, M Marsel, Coventry, Christina A, Bigio, Eileen H, Sridhar, Jaiashre, Gill, Nathan, Fought, Angela J, Zhang, Hui, Thompson, Cynthia K, Geula, Changiz, Gefen, Tamar, Flanagan, Margaret, Mao, Qinwen, Weintraub, Sandra, and Rogalski, Emily J
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BRAIN , *ALZHEIMER'S disease , *PICK'S disease of the brain , *PROGRESSIVE supranuclear palsy , *APHASIA , *ATROPHY , *DNA-binding proteins , *RESEARCH funding , *NEURODEGENERATION - Abstract
Primary progressive aphasia is a neurodegenerative disease that selectively impairs language without equivalent impairment of speech, memory or comportment. In 118 consecutive autopsies on patients with primary progressive aphasia, primary diagnosis was Alzheimer's disease neuropathological changes (ADNC) in 42%, corticobasal degeneration or progressive supranuclear palsy neuropathology in 24%, Pick's disease neuropathology in 10%, transactive response DNA binding proteinopathy type A [TDP(A)] in 10%, TDP(C) in 11% and infrequent entities in 3%. Survival was longest in TDP(C) (13.2 ± 2.6 years) and shortest in TDP(A) (7.1 ± 2.4 years). A subset of 68 right-handed participants entered longitudinal investigations. They were classified as logopenic, agrammatic/non-fluent or semantic by quantitative algorithms. Each variant had a preferred but not invariant neuropathological correlate. Seventy-seven per cent of logopenics had ADNC, 56% of agrammatics had corticobasal degeneration/progressive supranuclear palsy or Pick's disease and 89% of semantics had TDP(C). Word comprehension impairments had strong predictive power for determining underlying neuropathology positively for TDP(C) and negatively for ADNC. Cortical atrophy was smallest in corticobasal degeneration/progressive supranuclear palsy and largest in TDP(A). Atrophy encompassed posterior frontal but not temporoparietal cortex in corticobasal degeneration/progressive supranuclear palsy, anterior temporal but not frontoparietal cortex in TDP(C), temporofrontal but not parietal cortex in Pick's disease and all three lobes with ADNC or TDP(A). There were individual deviations from these group patterns, accounting for less frequent clinicopathologic associations. The one common denominator was progressive asymmetric atrophy overwhelmingly favouring the left hemisphere language network. Comparisons of ADNC in typical amnestic versus atypical aphasic dementia and of TDP in type A versus type C revealed fundamental biological and clinical differences, suggesting that members of each pair may constitute distinct clinicopathologic entities despite identical downstream proteinopathies. Individual TDP(C) participants with unilateral left temporal atrophy displayed word comprehension impairments without additional object recognition deficits, helping to dissociate semantic primary progressive aphasia from semantic dementia. When common and uncommon associations were considered in the set of 68 participants, one neuropathology was found to cause multiple clinical subtypes, and one subtype of primary progressive aphasia to be caused by multiple neuropathologies, but with different probabilities. Occasionally, expected clinical manifestations of atrophy sites were absent, probably reflecting individual peculiarities of language organization. The hemispheric asymmetry of neurodegeneration and resultant language impairment in primary progressive aphasia reflect complex interactions among the cellular affinities of the degenerative disease, the constitutive biology of language cortex, familial or developmental vulnerabilities of this network and potential idiosyncrasies of functional anatomy in the affected individual. [ABSTRACT FROM AUTHOR]
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- 2022
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11. Communication Partner Engagement: A Relevant Factor for Functional Outcomes in Speech–Language Therapy for Aphasic Dementia.
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Rogalski, Emily, Roberts, Angela, Salley, Elizabeth, Saxon, Marie, Fought, Angela, Esparza, Marissa, Blaze, Erin, Coventry, Christina, Mesulam, Marek-Marsel, Weintraub, Sandra, Mooney, Aimee, Khayum, Becky, and Rademaker, Alfred
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TREATMENT of dementia ,STATISTICS ,SPEECH therapy ,CONFIDENCE ,FUNCTIONAL status ,VIDEOCONFERENCING ,APHASIA ,TREATMENT effectiveness ,RANDOMIZED controlled trials ,COMMUNICATION ,DESCRIPTIVE statistics ,STATISTICAL sampling ,DATA analysis ,RECEIVER operating characteristic curves ,TELEMEDICINE - Abstract
Objectives Previous reports established the feasibility of a telehealth model for delivering speech–language therapy via Internet videoconferencing, which connects individuals with primary progressive aphasia (PPA) to an expert speech and language pathologist for treatment. This study reports feasibility of the same telehealth intervention in a larger set of progressive aphasia participants and explores factors potentially influencing functional intervention outcomes. Methods Participants with PPA or progressive aphasia in the context of a neurodegenerative dementia syndrome and their communication partners were enrolled into an 8-session intervention, with 3 evaluations (baseline, 2 months, and 6 months postenrollment). Half of the participants were randomized into a "check-in" group and received 3-monthly half-hour sessions postintervention. Mixed linear models with post hoc testing and percent change in area under the curve were used to examine communication confidence over time, as well as the influence of check-in sessions and the role of communication partner engagement on communication confidence. Results Communication confidence improved at the 2-month evaluation and showed no significant decline at the 6-month evaluation. Item-level analysis revealed gains in communication confidence across multiple communication contexts. Gains and maintenance of communication confidence were only present for the engaged communication partner group and were not bolstered by randomization to the check-in group. Discussion Internet-based, person-centered interventions demonstrate promise as a model for delivering speech–language therapy to individuals living with PPA. Maintenance is possible for at least 6 months postenrollment and is better for those with engaged communication partners, which supports the use of dyadic interventions. [ABSTRACT FROM AUTHOR]
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- 2022
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12. The Reliability of Telepractice Administration of the Western Aphasia Battery–Revised in Persons With Primary Progressive Aphasia.
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Rao, Leela A., Roberts, Angela C., Schafer, Rhiana, Rademaker, Alfred, Blaze, Erin, Esparza, Marissa, Salley, Elizabeth, Coventry, Christina, Weintraub, Sandra, Mesulam, M.-Marsel, and Rogalski, Emily
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DIAGNOSIS of aphasia ,RELIABILITY (Personality trait) ,CONFIDENCE intervals ,RESEARCH methodology evaluation ,DIFFERENTIAL diagnosis ,VIDEOCONFERENCING ,SPEECH evaluation ,SEVERITY of illness index ,INFORMED consent (Medical law) ,PEARSON correlation (Statistics) ,DESCRIPTIVE statistics ,TELEMEDICINE - Abstract
Purpose: The use of telepractice in the field of communication disorders offers an opportunity to provide care for those with primary progressive aphasia (PPA). The Western Aphasia Battery–Revised (WAB-R) is used for differential diagnosis, to assess severity of aphasia, and to identify a language profile of strengths and challenges. Telehealth administration of the WAB-R is supported for those with chronic aphasia due to stroke but has not yet been systematically explored in neurodegenerative dementia syndromes. To fill this gap, in-person and telehealth performance on the WAB-R from participants with mild to moderate PPA was compared. Method: Nineteen participants with mild to moderate PPA were administered the WAB-R in person and over videoconferencing. Videoconferencing administration included modifications to the testing protocol to ensure smooth completion of the assessment. Subtest and Aphasia Quotient (WAB-AQ) summary scores were compared using concordance coefficients to measure the relationship between the administration modes. Results: In-person and telehealth scores showed strong concordance for the WAB-AQ, Auditory Verbal Comprehension subtest, and Naming & Word Finding subtest. The Spontaneous Speech test summary score had slightly lower concordance, indicating the need for caution when comparing these scores across administration modes. Conclusion: These findings support extending the use of telehealth administration of the WAB-R via videoconferencing to those with mild to moderate PPA given appropriate modifications to testing protocol. [ABSTRACT FROM AUTHOR]
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- 2022
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13. Cortical and subcortical pathological burden and neuronal loss in an autopsy series of FTLD-TDP-type C.
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Kawles, Allegra, Nishihira, Yasushi, Feldman, Alex, Gill, Nathan, Minogue, Grace, Keszycki, Rachel, Coventry, Christina, Spencer, Callen, Lilek, Jaclyn, Ajroud, Kaouther, Coppola, Giovanni, Rademakers, Rosa, Rogalski, Emily, Weintraub, Sandra, Zhang, Hui, Flanagan, Margaret E, Bigio, Eileen H, Mesulam, M -Marsel, Geula, Changiz, and Mao, Qinwen
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NERVOUS system abnormalities ,PATHOGENESIS ,AUTOPSY ,FRONTOTEMPORAL lobar degeneration ,APHASIA ,ATROPHY ,DNA-binding proteins ,RESEARCH funding ,FRONTOTEMPORAL dementia - Abstract
The TDP-43 type C pathological form of frontotemporal lobar degeneration is characterized by the presence of immunoreactive TDP-43 short and long dystrophic neurites, neuronal cytoplasmic inclusions, neuronal loss and gliosis and the absence of neuronal intranuclear inclusions. Frontotemporal lobar degeneration-TDP-type C cases are commonly associated with the semantic variant of primary progressive aphasia or behavioural variant frontotemporal dementia. Here, we provide detailed characterization of regional distributions of pathological TDP-43 and neuronal loss and gliosis in cortical and subcortical regions in 10 TDP-type C cases and investigate the relationship between inclusions and neuronal loss and gliosis. Specimens were obtained from the first 10 TDP-type C cases accessioned from the Northwestern Alzheimer's Disease Research Center (semantic variant of primary progressive aphasia, n = 7; behavioural variant frontotemporal dementia, n = 3). A total of 42 cortical (majority bilateral) and subcortical regions were immunostained with a phosphorylated TDP-43 antibody and/or stained with haematoxylin-eosin. Regions were evaluated for atrophy, and for long dystrophic neurites, short dystrophic neurites, neuronal cytoplasmic inclusions, and neuronal loss and gliosis using a semiquantitative 5-point scale. We calculated a 'neuron-to-inclusion' score (TDP-type C mean score - neuronal loss and gliosis mean score) for each region per case to assess the relationship between TDP-type C inclusions and neuronal loss and gliosis. Primary progressive aphasia cases demonstrated leftward asymmetry of cortical atrophy consistent with the aphasic phenotype. We also observed abundant inclusions and neurodegeneration in both cortical and subcortical regions, with certain subcortical regions emerging as particularly vulnerable to dystrophic neurites (e.g. amygdala, caudate and putamen). Interestingly, linear mixed models showed that regions with lowest TDP-type C pathology had high neuronal dropout, and conversely, regions with abundant pathology displayed relatively preserved neuronal densities (P < 0.05). This inverse relationship between the extent of TDP-positive inclusions and neuronal loss may reflect a process whereby inclusions disappear as their associated neurons are lost. Together, these findings offer insight into the putative substrates of neurodegeneration in unique dementia syndromes. [ABSTRACT FROM AUTHOR]
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- 2022
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14. Relationships among tau burden, atrophy, age, and naming in the aphasic variant of Alzheimer's disease.
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Martersteck, Adam, Sridhar, Jaiashre, Coventry, Christina, Weintraub, Sandra, Mesulam, M.‐Marsel, and Rogalski, Emily
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Introduction: Examination of pathologic, anatomic, and cognitive relationships has been limited in primary progressive aphasia (PPA) with underlying Alzheimer's disease (AD) neuropathology. Methods: Spatial relationships between tau positron emission tomography (PET), cortical thickness, age, and naming on the Boston Naming Test (BNT) in PPA with biomarker evidence of AD (PPA‐AD) were examined. Results: Higher tau PET burden was associated with atrophy and younger age. There was a significant left‐lateralized relationship between lower BNT and more atrophy, and between lower BNT and increased tau burden. Variance in naming was primarily shared between tau and atrophy (51%), but naming was uniquely explained more by atrophy (32%) than tau (16%). Higher left anterior temporal tau burden was associated with greater 1‐year rate of decline in naming. Discussion: PPA‐AD has a similar relationship between abnormal biomarkers as first described in amnestic AD, with differing spatial extent, reflecting the left‐lateralized nature of the language network. [ABSTRACT FROM AUTHOR]
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- 2021
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15. Amygdalar pathology in early neuropsychiatric phenotypes due to 3R‐Pick disease.
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Keszycki, Rachel M, Kawles, Allegra, Minogue, Grace, Zouridakis, Antonia, Macomber, Alyssa, Lubbat, Vivienne, Coventry, Christina, Rogalski, Emily J, Weintraub, Sandra, Flanagan, Margaret E, Castellani, Rudolph J, Mesulam, Marsel, Geula, Changiz, and Gefen, Tamar
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Background: Persons with dementia syndromes such as primary progressive aphasia (PPA) and behavioral variant frontotemporal dementia (bvFTD) often develop neuropsychiatric symptoms (NPS). Various neurodegenerative diseases may cause PPA or bvFTD, including frontotemporal lobar degeneration (FTLD) with 3‐repeat tau pathology (Pick disease, "PiD"). Limbic regions implicated in mood and behavior, such as the amygdala, are highly impacted in FTLD with PiD. This study quantified Pick bodies and activated microglia in the amygdala of individuals with antemortem diagnosis of PPA or bvFTD and postmortem PiD neuropathology and examined associations with initial NPS. Method: We identified 16 right‐handed cases from the Northwestern University Alzheimer's Disease Research Center brain bank with bvFTD (N = 8) or PPA (N = 8) due to PiD with unilateral amygdala tissue (basolateral region) available. Fifteen cases had data on 12 NPS assessed via the Neuropsychiatric Inventory‐Questionnaire (NPI‐Q) from their earliest visit. We performed AT‐8 or HLA‐DR immunohistochemistry on amygdala sections to visualize Pick bodies or HLA‐DR+ activated microglia, respectively. We quantified the density of Pick bodies per mm3 via modified unbiased stereology and used HALO software (Indica Labs) to quantify percent area of HLA‐DR immunopositivity. We assessed differences between clinical groups via Welch's t‐test (Pick bodies) or repeated‐measures two‐way ANOVA (HLA‐DR). Pearson clinicopathologic correlations were examined between Pick bodies or HLA‐DR immunopositivity and initial endorsement of total (out of 12) or behavioral/comportmental (apathy, disinhibition, motor stereotypies, or appetite disturbance) NPI‐Q symptoms. Result: Amygdalar Pick body densities were similar between PPA (M = 28,822/mm3) and bvFTD (M = 29,114/mm3) cases. Compared to bvFTD, PPA cases trended towards a lower percent area of HLA‐DR immunopositivity (5.54% vs. 2.39%, p<0.10). There was no significant relationship between Pick Body density and initial NPIQ symptoms endorsed across all cases. However, area of HLA‐DR immunopositivity was positively correlated with initial endorsement of total (r = 0.47, p<0.10) and behavioral/comportmental (r = 0.54, p<0.05) NPI‐Q symptoms. Conclusion: Our findings suggest that microglial pathology in the amygdala contributes to early neuropsychiatric presentations in PiD, particularly symptoms reflective of behavioral/comportmental disturbance. Future study will investigate the impact of neuronal size and density in the amygdala on NPS in these dementia syndromes due to PiD. [ABSTRACT FROM AUTHOR]
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- 2023
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16. 45 Longitudinal Performance on Three Words Three Shapes Test in Primary Progressive Aphasia.
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Rodriguez, Janelli, Mather, Molly A, Simon, Sarah N, Coventry, Christina A, Rogalski, Emily, Mesulam, M.-Marsel, and Weintraub, Sandra
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WORD recognition ,ALZHEIMER'S disease ,AGRAMMATISM ,VERBAL memory ,COGNITION ,APHASIA ,MEMORY disorders - Abstract
Objective: Primary progressive aphasia (PPA) is a dementia syndrome characterized by initial development of progressive language deficits in the absence of impairment in other cognitive domains. It has historically been difficult to assess the presence or nature of true memory deficits in this population due to interference from language disturbance on task performance. The Three Words Three Shapes test (3W3S) is a relatively easy memory task that evaluates both verbal and nonverbal memory within the same modality and assesses different aspects of memory, including incidental encoding, effortful encoding, delayed recall, and recognition. Persons with PPA show a material-specific dissociation in performance on 3W3S; specifically, deficits in incidental encoding and recall are limited to verbal, not nonverbal material, in PPA, with preserved recognition of both types of information. However, it is unknown whether this pattern persists over time as the disease progresses. Participants and Methods: Participants were 73 participants enrolled in an observational PPA research study at the Mesulam Center for Cognitive Neurology and Alzheimer's Disease (Mage = 66.75 years, SD = 6.77; Meducation = 16.11 years, SD = 2.38; 51% female). Participants were subtyped as semantic (n = 15), logopenic (n = 27), or agrammatic PPA (n = 31) based on Gorno-Tempini et al., 2011, using 3W3S and other neuropsychological measures as described previously. Participants were followed at 2-year intervals and tests were administered longitudinally. All participants in the current study had 3W3S scores from at least two research visits collected between September 2012 and September 2022. Results: There were no significant baseline group differences on 3W3S performance, except for better incidental encoding in the logopenic than the semantic group for shapes (p =.040) and words (p =.043). We then conducted a mixed measures ANOVAs to determine baseline within-person comparisons between words vs shapes. Within individuals, performance on incidental encoding, effortful encoding, and recognition was worse for words than shapes (p s <.01). There was an interaction between material and group for delayed recall (p <.001) such that there was a significantly larger discrepancy between word and shape recall in the semantic (Mdiff = -9.14) compared to logopenic (M diff = -3.07) and agrammatic groups (Mdiff = -2.13). Repeated measures ANOVAs determined changes in scores over time collapsed across PPA subtypes. Incidental encoding (ps = <.01), effortful encoding (ps <.05), and delayed recall (p s <.01) declined for both words and shapes over time. Copy and recognition of words (ps <.05), but not shapes declined over time. Conclusions: The current results are consistent with prior findings of relative preservation of memory for nonverbal compared to verbal material in PPA as measured by 3W3S, especially in the semantic subtype. Learning and recall of words and shapes declined over time in all groups, whereas there was selective decline in copy and recognition of words compared to shapes. These results provide evidence of differential patterns of decline in certain aspects of memory over time in PPA and highlight the relative preservation of memory in this language-focused dementia even over time. [ABSTRACT FROM AUTHOR]
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- 2023
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17. Functional decline in the aphasic variant of Alzheimer's disease.
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Moeller, Stacey, Sridhar, Jaiashre, Martersteck, Adam, Coventry, Christina, Kuang, Alan, Zhang, Hui, Weintraub, Sandra, Mesulam, M.‐Marsel, and Rogalski, Emily
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Introduction: Primary progressive aphasia (PPA) is a clinical dementia syndrome associated with frontotemporal lobar degeneration (FTLD) or Alzheimer's disease (AD). Impairment in activities of daily living is essential for dementia diagnosis, yet less is known about the neuropathologic impact on functional decline in PPA, especially over time. Methods: Activities of Daily Living Questionnaire (ADLQ) ratings were compared by suspected underlying pathology between 17 PPAAβ+ and 11 PPAAβ– participants at 6‐month intervals for 2 years using a linear mixed‐effects model. A general linear model examined associations between functional decline and cortical thickness at baseline. Results: Groups did not differ in demographics or aphasia severity at baseline, yet overall and subdomain scores of the ADLQ were significantly worse for PPAAβ+ compared to PPAAβ‐ (P =.015) at each interval across 18 months. Discussion: Functional decline appears more pronounced and disrupts more aspects of life activities for individuals with non‐semantic PPA with suspected AD versus non‐AD neuropathology. [ABSTRACT FROM AUTHOR]
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- 2021
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18. Memory Resilience in Alzheimer Disease With Primary Progressive Aphasia.
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Mesulam, M.-Marsel, Coventry, Christina, Kuang, Alan, Bigio, Eileen H., Qinwen Mao, Flanagan, Margaret E., Gefen, Tamar, Sridhar, Jaiashre, Geula, Changiz, Hui Zhang, Weintraub, Sandra, Rogalski, Emily J., Mao, Qinwen, and Zhang, Hui
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- 2021
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19. Accumulation of neurofibrillary tangles and activated microglia is associated with lower neuron densities in the aphasic variant of Alzheimer's disease.
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Ohm, Daniel T., Fought, Angela J., Martersteck, Adam, Coventry, Christina, Sridhar, Jaiashre, Gefen, Tamar, Weintraub, Sandra, Bigio, Eileen, Mesulam, M.‐Marsel, Rogalski, Emily, and Geula, Changiz
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MICROGLIA ,ALZHEIMER'S disease ,NEURONS ,CEREBRAL atrophy ,NEUROFIBRILLARY tangles ,APHASIC persons ,LANGUAGE disorders ,NEUROMYELITIS optica - Abstract
The neurofibrillary tangles (NFT) and amyloid‐ß plaques (AP) that comprise Alzheimer's disease (AD) neuropathology are associated with neurodegeneration and microglial activation. Activated microglia exist on a dynamic spectrum of morphologic subtypes that include resting, surveillant microglia capable of converting to activated, hypertrophic microglia closely linked to neuroinflammatory processes and AD neuropathology in amnestic AD. However, quantitative analyses of microglial subtypes and neurons are lacking in non‐amnestic clinical AD variants, including primary progressive aphasia (PPA‐AD). PPA‐AD is a language disorder characterized by cortical atrophy and NFT densities concentrated to the language‐dominant hemisphere. Here, a stereologic investigation of five PPA‐AD participants determined the densities and distributions of neurons and microglial subtypes to examine how cellular changes relate to AD neuropathology and may contribute to cortical atrophy. Adjacent series of sections were immunostained for neurons (NeuN) and microglia (HLA‐DR) from bilateral language and non‐language regions where in vivo cortical atrophy and Thioflavin‐S‐positive APs and NFTs were previously quantified. NeuN‐positive neurons and morphologic subtypes of HLA‐DR‐positive microglia (i.e., resting [ramified] microglia and activated [hypertrophic] microglia) were quantified using unbiased stereology. Relationships between neurons, microglia, AD neuropathology, and cortical atrophy were determined using linear mixed models. NFT densities were positively associated with hypertrophic microglia densities (P < 0.01) and inversely related to neuron densities (P = 0.01). Hypertrophic microglia densities were inversely related to densities of neurons (P < 0.01) and ramified microglia (P < 0.01). Ramified microglia densities were positively associated with neuron densities (P = 0.02) and inversely related to cortical atrophy (P = 0.03). Our findings provide converging evidence of divergent roles for microglial subtypes in patterns of neurodegeneration, which includes hypertrophic microglia likely driving a neuroinflammatory response more sensitive to NFTs than APs in PPA‐AD. Moreover, the accumulation of both NFTs and activated hypertrophic microglia in association with low neuron densities suggest they may collectively contribute to focal neurodegeneration characteristic of PPA‐AD. [ABSTRACT FROM AUTHOR]
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- 2021
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20. Montreal Cognitive Assessment (MoCA) Performance and Domain-Specific Index Scores in Amnestic Versus Aphasic Dementia.
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Wood, Jessica L., Weintraub, Sandra, Coventry, Christina, Xu, Jiahui, Zhang, Hui, Rogalski, Emily, Mesulam, Marek-Marsel, and Gefen, Tamar
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MONTREAL Cognitive Assessment ,COGNITION disorders ,LOGISTIC regression analysis ,ALZHEIMER'S disease ,DEMENTIA ,ANALYSIS of covariance - Abstract
Objective: The Montreal Cognitive Assessment (MoCA) is a popular and simple-to-administer screening instrument to detect cognitive impairment. The MoCA generates a total score and six domain-specific index scores: (1) Memory, (2) Executive Functioning, (3) Attention, (4) Language, (5) Visuospatial, and (6) Orientation. It is unclear whether these MoCA scores can differentiate between distinct clinical dementia syndromes. This study compared MoCA Index scores between amnestic dementia of the Alzheimer's type (DAT) and primary progressive aphasia (PPA), a language-based dementia. Method: Baseline MoCA data were analyzed from 33 DAT, 37 PPA, and 83 cognitively normal individuals enrolled in the Clinical Core of the Northwestern Alzheimer's Disease Center. A one-way analysis of covariance adjusted for age was used to compare MoCA scores among groups. A logistic regression model was implemented to observe individual likelihood of group affiliation based on MoCA Index scores. Results: The mean MoCA total score was significantly higher in controls compared to both patient groups (p <.001) but did not differ between DAT and PPA groups. However, in accordance with salient clinical features commonly observed in DAT versus PPA, Memory and Orientation Index scores were lowest in the DAT group (p <.001), whereas Language and Attention Index scores were lowest in the PPA group (p <.001). Multivariate logistic regression analysis showed that the individual effects of Memory (p =.001), Language (p =.002), and Orientation (p =.025) Indices were significant. Conclusions: MoCA Index scores can help differentiate among distinct cognitive syndromes, suggesting it may be a useful brief screening tool to detect domain-specific cognitive impairment. [ABSTRACT FROM AUTHOR]
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- 2020
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21. Neuropathologic basis of in vivo cortical atrophy in the aphasic variant of Alzheimer's disease.
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Ohm, Daniel T., Fought, Angela J., Rademaker, Alfred, Kim, Garam, Sridhar, Jaiashre, Coventry, Christina, Gefen, Tamar, Weintraub, Sandra, Bigio, Eileen, Mesulam, Marek Marsel, Rogalski, Emily, and Geula, Changiz
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CEREBRAL atrophy ,ALZHEIMER'S disease ,ENTORHINAL cortex ,NEUROFIBRILLARY tangles ,NEUROLINGUISTICS ,APHASIC persons - Abstract
The neuropathologic basis of in vivo cortical atrophy in clinical dementia syndromes remains poorly understood. This includes primary progressive aphasia (PPA), a language‐based dementia syndrome characterized by asymmetric cortical atrophy. The neurofibrillary tangles (NFTs) and amyloid‐ß plaques (APs) of Alzheimer's disease (AD) can cause PPA, but a quantitative investigation of the relationships between NFTs, APs and in vivo cortical atrophy in PPA‐AD is lacking. The present study measured cortical atrophy from corresponding bilateral regions in five PPA‐AD participants with in vivo magnetic resonance imaging scans 7–30 months before death and acquired stereologic estimates of NFTs and dense‐core APs visualized with the Thioflavin‐S stain. Linear mixed models accounting for repeated measures and stratified by hemisphere and region (language vs. non‐language) were used to determine the relationships between cortical atrophy and AD neuropathology and their regional selectivity. Consistent with the aphasic profile of PPA, left language regions displayed more cortical atrophy (P = 0.01) and NFT densities (P = 0.02) compared to right language homologues. Left language regions also showed more cortical atrophy (P < 0.01) and NFT densities (P = 0.02) than left non‐language regions. A subset of data was analyzed to determine the predilection of AD neuropathology for neocortical regions compared to entorhinal cortex in the left hemisphere, which showed that the three most atrophied language regions had greater NFT (P = 0.04) and AP densities (P < 0.01) than the entorhinal cortex. These results provide quantitative evidence that NFT accumulation in PPA selectively targets the language network and may not follow the Braak staging of neurofibrillary degeneration characteristic of amnestic AD. Only NFT densities, not AP densities, were positively associated with cortical atrophy within left language regions (P < 0.01) and right language homologues (P < 0.01). Given previous findings from amnestic AD, the current study of PPA‐AD provides converging evidence that NFTs are the principal determinants of atrophy and clinical phenotypes associated with AD. [ABSTRACT FROM AUTHOR]
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- 2020
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22. is a correlate of phenotypic heterogeneity in Alzheimer disease in a national cohort.
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Weintraub, Sandra, Teylan, Merilee, Rader, Benjamin, Chan, Kwun C. G., Bollenbeck, Mark, Kukull, Walter A., Coventry, Christina, Rogalski, Emily, Bigio, Eileen, and Mesulam, M.-Marsel
- Published
- 2020
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23. 56 Stereological Densities of Neuronal Tau Inclusions in Corticobasal Degeneration are Anatomically Distinct in PPA vs bvFTD.
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Minogue, Grace, Kawles, Allegra, Zouridakis, Antonia, Keszycki, Rachel, Coventry, Christina, Gill, Nathan, Zhang, Hui, Rogalski, Emily, Weintraub, Sandra, Mao, Qinwen, Flanagan, Margaret, Castellani, Rudolph, Mesulam, M-Marsel, Geula, Changiz, and Gefen, Tamar
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FRONTOTEMPORAL lobar degeneration ,TEMPORAL lobe ,PREFRONTAL cortex ,TAU proteins ,PARIETAL lobe ,FRONTOTEMPORAL dementia - Abstract
Objective: Primary progressive aphasia (PPA) is a dementia syndrome characterized early in its course by gradual dissolution of language and is associated with asymmetric atrophy in the language-dominant hemisphere (usually left). In contrast, behavioral variant frontotemporal dementia (bvFTD) is a dementia syndrome characterized by a progressive early decline in personality and comportment and is associated with relatively symmetric or rightward predominant bifrontal atrophy. This study analyzed the regional and hemispheric distributions of neuronal tau inclusions of the corticobasal degeneration variant of FTLD-tau pathology (FTLD-CBD) in individuals with PPA or bvFTD. The goal was to establish clinicopathologic concordance between FTLD-CBD and behavioral/comportmental vs aphasic dementia syndromes. Participants and Methods: Seven participants were clinically diagnosed with PPA and 6 were diagnosed with bvFTD. All had FTLD-CBD as the principal neuropathologic diagnosis at postmortem study. Sections from the following cortical regions were stained immunohistochemically with AT-8 to visualize neuronal tau inclusions: bilateral middle frontal gyrus (MFG), inferior parietal lobule (IPL), superior temporal gyrus (STG); and unilateral occipital cortex (OCC). Bilateral anterior temporal lobes (ATL) were analyzed in PPA cases only. Unbiased stereological analysis was performed to compare regional and hemispheric distributions between and within PPA vs. bvFTD groups. Results: Overall neocortical (MFG+STG+IPL) tau densities were significantly greater in the PPA group compared to the bvFTD group (p<0.05). Within the bvFTD group, the highest densities of tau inclusions were observed in the right MFG (mean=6,871.17; SD=3,220). In the PPA group, highest densities were observed in the left ATL (mean=9,901.81; SD=6,871). There was leftward hemispheric asymmetry of tau inclusions in IPL, STG and ATL which trended towards significance in the latter (p=0.083). Cortical distributions were symmetric or rightward predominant within the bvFTD group. Occipital cortex was devoid of inclusions. Conclusions: Preliminary stereological findings of FTLD-CBD tau inclusions suggest that the distributions of pathologic tau are different across two distinct clinical dementia phenotypes. The presence of left-sided neuronal tau inclusions in PPA is concordant with the aphasic phenotype whereas symmetric and frontal-predominant densities in bvFTD are consistent with comportmental dysfunction. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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24. Distinct regional and hemispheric tau distributions in Primary Progressive Aphasia with neuropathologic Progressive Supranuclear Palsy: A stereological study.
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Zouridakis, Antonia, Kawles, Allegra, Minogue, Grace, Keszycki, Rachel M, Coventry, Christina, Weintraub, Sandra, Rogalski, Emily J, Flanagan, Margaret E, Mao, Qinwen, Bigio, Eileen H, Mesulam, M.‐Marsel, Geula, Changiz, and Gefen, Tamar
- Abstract
Background: Primary Progressive Aphasia (PPA) is a dementia syndrome characterized by isolated and progressive impairment of language and focal atrophy of left‐hemispheric cortical regions. PPA presents with various underlying FTLD‐tauopathies such as Pick's disease (PiD), corticobasal degeneration (CBD), and progressive supranuclear palsy (PSP). This study investigated clinicopathologic concordance between the aphasic phenotype of PPA and regional distributions of PSP markers quantified in language‐related cortical areas and the dentate gyrus (DG) of the hippocampus—an area of interest due to intact memory exhibited in PPA. Another goal was to compare regional distributions of tau‐positive markers in PSP compared to CBD and PiD to identify differential susceptibility patterns across FTLD‐tauopathies. Method: Paraffin‐embedded sections were stained immunohistochemically with AT‐8 to visualize neuronal tau inclusions and astrocytes containing phosphorylated tau in 8 right‐handed cases with PPA and autopsy‐confirmed PSP. Modified unbiased stereology was performed in bilateral middle frontal gyrus (MFG) and inferior parietal lobule (IPL), and left DG. A secondary analysis compared distributions of tau markers in cases with PiD (N = 6; tau‐positive inclusions) and CBD (N = 4; tau‐positive inclusions + astrocytic plaques). One‐way ANOVAs and students' t‐tests were used to analyze distributions. Result: Within the PSP group, there was significant left‐sided asymmetric predominance of tau‐positive neuronal inclusions and astrocytic tau in cortical areas; left MFG showed over double the total marker density vs right (3,490 vs 1,549 counts/mm3, respectively; p<0.05). In PSP, there was significantly less tau‐positive inclusions and astrocytes in the DG relative to cortical regions, where the ratio of left‐sided dentate‐to‐cortical inclusions was ∼1:2. This was remarkably lower than dentate‐to‐cortical ratios of ∼2:1 in CBD and ∼3:1 in PiD (p<0.01). Finally, PSP cases showed significantly greater astrocytic tau in cortical regions compared to CBD, by ∼100 fold in the left hemisphere (p<0.01). Conclusion: Findings from this stereological study of PPA with FTLD‐PSP show leftward cortical predominance of pathology concordant with the salience of the aphasic phenotype. Dentate predominance of pathology in PPA due to FTLD‐tau remains a mystery. The relative distribution of dentate‐to‐cortical tau pathology is different across FTLD‐tau species, offering insights into the selective vulnerability of distinct neuronal populations in neurodegenerative dementias. [ABSTRACT FROM AUTHOR]
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- 2023
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25. THALAMIC MORPHOLOGY IN THE APHASIC VARIANT OF AD
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Paxton, Holly, Cobia, Derin, Sridhar, Jaiashre, Coventry, Christina, Weintraub, Sandra, Mesulam, Marsel, and Rogalski, Emily J.
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- 2019
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26. Primary Progressive Aphasia has a Unique Signature Distinct from Dementia of the Alzheimer's Type and Behavioral Variant Frontotemporal Dementia Regardless of Pathology.
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Gefen, Tamar, Mao, Qinwen, Kohler, Missia, Moeller, Stacey, Kawles, Allegra, Coventry, Christina, Spencer, Callen, Lilek, Jaclyn, Ajroud, Kaouther, Feldman, Alex, Flanagan, Margaret, Rogalski, Emily, Weintraub, Sandra, Rademaker, Alfred, Geula, Changiz, Mesulam, M -Marsel, and Bigio, Eileen
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- 2020
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27. P4‐598: THALAMIC MORPHOLOGY IN THE APHASIC VARIANT OF AD.
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Paxton, Holly, Cobia, Derin, Sridhar, Jaiashre, Coventry, Christina, Weintraub, Sandra, Mesulam, Marsel, and Rogalski, Emily J.
- Published
- 2019
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28. Cortical and subcortical pathological burden and neuronal loss in an autopsy series of FTLD-TDP-type C.
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Kawles A, Nishihira Y, Feldman A, Gill N, Minogue G, Keszycki R, Coventry C, Spencer C, Lilek J, Ajroud K, Coppola G, Rademakers R, Rogalski E, Weintraub S, Zhang H, Flanagan ME, Bigio EH, Mesulam MM, Geula C, Mao Q, and Gefen T
- Subjects
- Atrophy, Autopsy, DNA-Binding Proteins genetics, Gliosis, Humans, Aphasia, Primary Progressive pathology, Frontotemporal Dementia pathology, Frontotemporal Lobar Degeneration pathology, Nervous System Malformations
- Abstract
The TDP-43 type C pathological form of frontotemporal lobar degeneration is characterized by the presence of immunoreactive TDP-43 short and long dystrophic neurites, neuronal cytoplasmic inclusions, neuronal loss and gliosis and the absence of neuronal intranuclear inclusions. Frontotemporal lobar degeneration-TDP-type C cases are commonly associated with the semantic variant of primary progressive aphasia or behavioural variant frontotemporal dementia. Here, we provide detailed characterization of regional distributions of pathological TDP-43 and neuronal loss and gliosis in cortical and subcortical regions in 10 TDP-type C cases and investigate the relationship between inclusions and neuronal loss and gliosis. Specimens were obtained from the first 10 TDP-type C cases accessioned from the Northwestern Alzheimer's Disease Research Center (semantic variant of primary progressive aphasia, n = 7; behavioural variant frontotemporal dementia, n = 3). A total of 42 cortical (majority bilateral) and subcortical regions were immunostained with a phosphorylated TDP-43 antibody and/or stained with haematoxylin-eosin. Regions were evaluated for atrophy, and for long dystrophic neurites, short dystrophic neurites, neuronal cytoplasmic inclusions, and neuronal loss and gliosis using a semiquantitative 5-point scale. We calculated a 'neuron-to-inclusion' score (TDP-type C mean score - neuronal loss and gliosis mean score) for each region per case to assess the relationship between TDP-type C inclusions and neuronal loss and gliosis. Primary progressive aphasia cases demonstrated leftward asymmetry of cortical atrophy consistent with the aphasic phenotype. We also observed abundant inclusions and neurodegeneration in both cortical and subcortical regions, with certain subcortical regions emerging as particularly vulnerable to dystrophic neurites (e.g. amygdala, caudate and putamen). Interestingly, linear mixed models showed that regions with lowest TDP-type C pathology had high neuronal dropout, and conversely, regions with abundant pathology displayed relatively preserved neuronal densities (P < 0.05). This inverse relationship between the extent of TDP-positive inclusions and neuronal loss may reflect a process whereby inclusions disappear as their associated neurons are lost. Together, these findings offer insight into the putative substrates of neurodegeneration in unique dementia syndromes., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2022
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29. Relationships among tau burden, atrophy, age, and naming in the aphasic variant of Alzheimer's disease.
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Martersteck A, Sridhar J, Coventry C, Weintraub S, Mesulam MM, and Rogalski E
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- Age Factors, Aged, Alzheimer Disease pathology, Brain Cortical Thickness, Female, Humans, Male, Positron-Emission Tomography, Temporal Lobe pathology, Aphasia, Primary Progressive diagnostic imaging, Aphasia, Primary Progressive pathology, Atrophy pathology, Brain pathology, Language Tests statistics & numerical data, tau Proteins metabolism
- Abstract
Introduction: Examination of pathologic, anatomic, and cognitive relationships has been limited in primary progressive aphasia (PPA) with underlying Alzheimer's disease (AD) neuropathology., Methods: Spatial relationships between tau positron emission tomography (PET), cortical thickness, age, and naming on the Boston Naming Test (BNT) in PPA with biomarker evidence of AD (PPA-AD) were examined., Results: Higher tau PET burden was associated with atrophy and younger age. There was a significant left-lateralized relationship between lower BNT and more atrophy, and between lower BNT and increased tau burden. Variance in naming was primarily shared between tau and atrophy (51%), but naming was uniquely explained more by atrophy (32%) than tau (16%). Higher left anterior temporal tau burden was associated with greater 1-year rate of decline in naming., Discussion: PPA-AD has a similar relationship between abnormal biomarkers as first described in amnestic AD, with differing spatial extent, reflecting the left-lateralized nature of the language network., (© 2021 the Alzheimer's Association.)
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- 2021
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30. Functional decline in the aphasic variant of Alzheimer's disease.
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Moeller S, Sridhar J, Martersteck A, Coventry C, Kuang A, Zhang H, Weintraub S, Mesulam MM, and Rogalski E
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- Aged, Humans, Neuropsychological Tests statistics & numerical data, Activities of Daily Living, Alzheimer Disease pathology, Aphasia, Primary Progressive pathology
- Abstract
Introduction: Primary progressive aphasia (PPA) is a clinical dementia syndrome associated with frontotemporal lobar degeneration (FTLD) or Alzheimer's disease (AD). Impairment in activities of daily living is essential for dementia diagnosis, yet less is known about the neuropathologic impact on functional decline in PPA, especially over time., Methods: Activities of Daily Living Questionnaire (ADLQ) ratings were compared by suspected underlying pathology between 17 PPA
Aβ+ and 11 PPAAβ- participants at 6-month intervals for 2 years using a linear mixed-effects model. A general linear model examined associations between functional decline and cortical thickness at baseline., Results: Groups did not differ in demographics or aphasia severity at baseline, yet overall and subdomain scores of the ADLQ were significantly worse for PPAAβ+ compared to PPAAβ- (P = .015) at each interval across 18 months., Discussion: Functional decline appears more pronounced and disrupts more aspects of life activities for individuals with non-semantic PPA with suspected AD versus non-AD neuropathology., (© 2021 the Alzheimer's Association.)- Published
- 2021
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31. Nosology of Primary Progressive Aphasia and the Neuropathology of Language.
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Mesulam M-, Coventry C, Bigio EH, Geula C, Thompson C, Bonakdarpour B, Gefen T, Rogalski EJ, and Weintraub S
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- Humans, Language, Alzheimer Disease, Aphasia, Primary Progressive, Frontotemporal Dementia, Frontotemporal Lobar Degeneration
- Abstract
Primary progressive aphasia (PPA) is a dementia syndrome associated with several neuropathologic entities, including Alzheimer's disease (AD) and all major forms of frontotemporal lobar degeneration (FTLD). It is classified into subtypes defined by the nature of the language domain that is most impaired. The asymmetric neurodegeneration of the hemisphere dominant for language (usually left) is one consistent feature of all PPA variants. This feature offers unique opportunities for exploring mechanisms of selective vulnerability in neurodegenerative diseases and the neuroanatomy of language. This chapter reviews some of the current trends in PPA research as well as the challenges that remain to be addressed on the nosology, clinicopathologic correlations, and therapy of this syndrome.
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- 2021
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