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Regional neuropathology distribution and verbal fluency impairments in Parkinson's disease.

ABSTRACT: BACKGROUND:Verbal fluency deficits are common in patients with Parkinson's disease. The association of these impairments with regional neuropathological changes is unexplored. OBJECTIVES:Determine if patients with verbal fluency impairments have greater neuropathological burden in frontal, temporal, and limbic regions and if Lewy bodies or neurofibrillary tangles were associated with verbal fluency impairments. METHODS:Data was derived from the Arizona Study of Aging and Neurodegenerative Disorders. 47 individuals who completed phonemic and semantic verbal fluency tasks and met clinicopathological criteria for Parkinson's disease (with and without comorbid Alzheimer's disease) were included. Impairment on fluency tasks was defined by normative data, and the density of neuropathology in temporal, limbic, and frontal regions was compared between groups. RESULTS:Individuals with semantic fluency impairments had greater total pathology (Lewy bodies + neurofibrillary tangles) in limbic structures (W = 320.0, p?=?.033, rpb?=?.33), while those who had phonemic fluency impairments had increased total neuropathology in frontal (W?=?364.5, p?=?.011, rpb?=?.37), temporal (W?=?356.5, p?=?.022, rpb?=?.34), and limbic regions (W?=?357.0, p?=?.024, rpb?=?.34). Greater Lewy body density was found in those with verbal fluency impairments, though trends for greater neurofibrillary tangle density were noted as well. CONCLUSIONS:Impaired phonemic fluency was associated with higher Lewy body and tangle burden in frontal, temporal, and limbic regions, while impaired semantic fluency was associated with greater limbic pathology. Though neurofibrillary tangles trended higher in several regions in those with impaired verbal fluency, higher Lewy body density in general was associated with verbal fluency deficits. Implications for research and clinical practice are discussed.

SUBMITTER: El-Nazer R

PROVIDER: S-EPMC6774852 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Regional neuropathology distribution and verbal fluency impairments in Parkinson's disease.

El-Nazer Rasheda R Adler Charles H CH Beach Thomas G TG Belden Christine M CM Artz Jonathan J Shill Holly A HA Driver-Dunckley Erika E Mehta Shyamal H SH Sabbagh Marwan N MN Serrano Geidy E GE Sue Lucia I LI Zamrini Edward E Benge Jared F JF

Parkinsonism & related disorders 20190510

<h4>Background</h4>Verbal fluency deficits are common in patients with Parkinson's disease. The association of these impairments with regional neuropathological changes is unexplored.<h4>Objectives</h4>Determine if patients with verbal fluency impairments have greater neuropathological burden in frontal, temporal, and limbic regions and if Lewy bodies or neurofibrillary tangles were associated with verbal fluency impairments.<h4>Methods</h4>Data was derived from the Arizona Study of Aging and Ne ...[more]

PMID: 31109728

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Project description:ObjectiveThe current study was designed to achieve 2 primary objectives: (a) determine the moderating effect of mild cognitive impairments (MCI) on intraindividual variability in semantic and letter fluency performance taking into account longitudinal annual assessments; and (b) establish predictive utility for intraindividual variability in semantic and letter fluency performance as a risk factor of incident MCI.MethodsParticipants were community-residing older adults (n = 514; M age = 75.89 ± 6.45; 55.1% female). Sixty participants were diagnosed with MCI at baseline and 50 developed incident MCI during the follow-up. We operationalized intraindividual variability as word generation slopes derived from 3 consecutive time intervals during the standard 1-min administration of both letter and semantic fluency tasks (i.e., 0-20 s, 21-40 s, and 41-60 s).ResultsLinear mixed effects models revealed significant within task slope effects for semantic (estimate = -8.350; p < .0001; 95% confidence interval [CI] = -8.604, -8.095) and letter (estimate = -5.068; p < .0001; 95% CI [-5.268, -4.869]) fluency indicating that word generation declined over the course of both tasks. The two-way interactions of MCI × Slope were significant for semantic (estimate = 1.34; p = .001; 95% CI [0.551, 2.126]) and letter (estimate = 0.733; p = .020; 95% CI [0.116, 1.350]) fluency indicating attenuated slopes among MCI participants compared to controls taking into account repeated annual assessments. Cox proportional-hazards models revealed that attenuated word generation slope, at baseline, in semantic (hazard ratio [HR] = 2.063; p = .015; 95% = 1.149 to 3.702) but not letter (HR = 0.704; p = .243; 95% CI [0.391, 1.269]) fluency was associated with increased risk of incident MCI.ConclusionIntraindividual variability in verbal fluency performance has clinical and predictive utility; it can be easily incorporated into testing batteries in clinical and research settings. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Project description:BackgroundRecent clinical studies point to rapid and sustained clinical, cognitive, and behavioral improvement in both Alzheimer's disease and primary progressive aphasia following weekly perispinal administration of etanercept, a TNF-alpha inhibitor that acts by blocking the binding of this cytokine to its receptors. This outcome is concordant with recent basic science studies suggesting that TNF-alpha functions in vivo as a gliotransmitter that regulates synaptic function in the brain. We hypothesized that perispinal etanercept had the potential to improve verbal function in Alzheimer's disease, so we included several standarized measures of verbal ability to evaluate language skills in a clinical trial of perispinal etanercept for Alzheimer's disease.MethodsThis was a prospective, single-center, open-label, pilot study, in which 12 patients with mild-to-severe Alzheimer's disease were administered etanercept, 25-50 mg, weekly by perispinal administration for six months. Two additional case studies are presented.ResultsTwo-tailed, paired t-tests were conducted comparing baseline performance to 6-month performance on all neuropsychological measures. Test batteries included the California Verbal Learning Test-Second Edition, Adult Version; Logical Memory I and II(WMS-LM-II) from the Wechsler Memory Scale-Abbreviated; the Comprehensive Trail Making Test (TMT); Boston Naming Test; and letter(FAS) and category verbal fluency. All measures revealed a significant effect except for the Boston Naming Test and the TMT-4, with WMS-LM-II being marginally significant at p = .05. The FAS test for letter fluency was most highly significant with a p < 0.0007. In addition, rapid improvement in verbal fluency and aphasia in two patients with dementia, beginning minutes after perispinal etanercept administration, is documented.ConclusionIn combination with the previously reported results of perispinal etanercept in Alzheimer's disease and primary progressive aphasia, these results further argue that larger scale studies of this therapeutic intervention, including Phase 3 trials, are warranted in dementias. In addition, these results may provide insight into the basic pathophysiologic mechanisms underlying Alzheimer's disease and related forms of dementia, and suggest the existence of novel, rapidly reversible, TNF-mediated pathophysiologic mechanisms in Alzheimer's disease which are worthy of further investigation.

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Regional neuropathology distribution and verbal fluency impairments in Parkinson's disease.

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Regional neuropathology distribution and verbal fluency impairments in Parkinson's disease.

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