Language impairment in Parkinson's disease: fMRI study of sentence reading comprehension.

Parkinson's disease (PD) affects the language processes, with a significant impact on the patients' daily communication. We aimed to describe specific alterations in the comprehension of syntactically complex sentences in patients with PD (PwPD) as compared to healthy controls (HC) and to identify the neural underpinnings of these deficits using a functional connectivity analysis of the striatum. A total of 20 patients PwPD and 15 HC participated in the fMRI study. We analyzed their performance of a Test of sentence comprehension (ToSC) adjusted for fMRI. A task-dependent functional connectivity analysis of the striatum was conducted using the psychophysiological interaction method (PPI). On the behavioral level, the PwPD scored significantly lower (mean ± sd: 77.3 ± 12.6) in the total ToSC score than the HC did (mean ± sd: 86.6 ± 8.0), p = 0.02, and the difference was also significant specifically for sentences with a non-canonical word order (PD-mean ± sd: 69.9 ± 14.1, HC-mean ± sd: 80.2 ± 11.5, p = 0.04). Using PPI, we found a statistically significant difference between the PwPD and the HC in connectivity from the right striatum to the supplementary motor area [SMA, (4 8 53)] for non-canonical sentences. This PPI connectivity was negatively correlated with the ToSC accuracy of non-canonical sentences in the PwPD. Our results showed disturbed sentence reading comprehension in the PwPD with altered task-dependent functional connectivity from the right striatum to the SMA, which supports the synchronization of the temporal and sequential aspects of language processing. The study revealed that subcortical-cortical networks (striatal-frontal loop) in PwPD are compromised, leading to impaired comprehension of syntactically complex sentences.

Comorbid Neurodegeneration in Primary Progressive Aphasia: Clinicopathological Correlations in a Single-Center Study.

Introduction: Primary progressive aphasia (PPA) is a clinically variable syndrome manifesting as slow progressive loss of speech and language with multiple underlying neurodegenerative pathologies. Materials and Methods: We included data from nine PPA patients with available autopsies. We then retrospectively reviewed all available medical records, neuropsychology, and MRI results to confirm the corresponding subtypes of PPA and compared them with postmortem neuropathological results. Results: Clinical presentations corresponded to the nonfluent/agrammatic variant in six cases, the semantic variant in one case, the logopenic variant in one case, and the mixed variant (concomitant nonfluent/agrammatic plus semantic variant) in one case. Patients with a broader clinical presentation, i.e., combining manifestations of one PPA subtype and symptoms of another PPA variant, had autopsy comorbidities showing multiple neurodegenerative disorders. Of the nine subjects enrolled in the study, Alzheimer's disease (AD) was found in eight cases; however, in only one case, AD was detected as an isolated neuropathological substrate of PPA. In eight brain samples, different comorbid neuropathologies were detected: three cases with comorbid AD and dementia with Lewy bodies, two cases with comorbid AD and TDP-43 pathology, one case with comorbid AD and complex tauopathies, and one case with comorbid AD with both tau and TDP-43 deposits. Finally, one case had comorbid tau and TDP-43 pathology but without comorbid AD pathology. Conclusions: Our observation suggests that PPA cases could be more heterogeneous in their etiology than previously thought and underlying neurodegenerative comorbidities should be considered in routine practice, especially if the clinical presentation of PPA is atypical.

Corpus callosum hypersignals and focal atrophy: Neuroimaging findings in globular glial tauopathy type I.

BACKGROUND AND PURPOSE: Globular glial tauopathies (GGTs) have heterogeneous presentations; little evidence regarding typical clinical and magnetic resonance imaging (MRI) presentations are available. METHODS: We retrospectively assessed MRIs from three postmortem-confirmed GGT cases, in two patients with atypical progressive aphasia and one with corticobasal syndrome. RESULTS: We suggest that four principal concomitant MRI findings characterize GGT type I: a sagittal callosal hyperintense band, marked focal callosal atrophy suggesting white matter degeneration originating in cortical areas responsible for symptoms (anterior atrophy in predominantly language manifestations and posterior atrophy in predominantly apraxia), periventricular white matter lesions, and mild-to-moderate brain stem atrophy. CONCLUSIONS: We observed four concomitant MRI abnormalities in patients with atypical dementia, parkinsonism, and late incomplete supranuclear gaze palsy. Two patients had atypical progressive aphasia and one had corticobasal syndrome.

Neurocognitive Predictors of Understanding of Intentions in Parkinson Disease.

OBJECTIVES: Theory of Mind (ToM), the ability to understand other people's mental states, is essential in everyday social interactions. The relationship between cognitive domains and ToM impairment in Parkinson disease (PD) has been receiving growing attention with ambiguous findings. The objective of the current study was to ascertain which cognitive domain predicts understanding of intentions and the impact of PD-specific clinical measures on ToM performance. A secondary aim was to evaluate whether cognitive impairment mediates the relationship between severity of illness and ToM impairment. METHODS: Fifty-one nondemented patients with idiopathic PD, ranging from early to advanced stages, were enrolled. A comprehensive neurocognitive battery and 2 ToM tasks (Hinting Task and Comic Strip Task) were administered during the patients' best "on" medication state. RESULTS: Only the task of measuring working memory capacity was significantly associated with both ToM tasks (Hinting Task Spearman rank correlation [ rs] = 0.309, P ≤ .05; Comic Strip Task rs = 0.595, P ≤ .01). Patients with more progressed disease and higher doses of dopaminergic medication performed significantly worse in the Comic Strip Task. Based on the mediation analysis, relationship between the severity of the illness and understanding of intentions was mediated by cognitive flexibility. CONCLUSION: In PD, understanding of intentions is related to neurocognition, with working memory and cognitive flexibility playing a crucial role. The severity of PD predicts ToM performance.

Globular Glial Tauopathy Type I Presenting as Atypical Progressive Aphasia, With Comorbid Limbic-Predominant Age-Related TDP-43 Encephalopathy.

Globular glial tauopathies (GGTs) have heterogeneous presentations with little available information regarding typical clinical manifestations. We report on a case of atypical primary progressive aphasia (PPA) due to comorbid GGT and limbic transactive response DNA binding protein of 43 kDa (TDP-43) proteinopathy. The initial clinical phenotype was compatible with the nonfluent-agrammatical variant of PPA and early hippocampal amnesia. Progressively, parkinsonism and supranuclear oculomotor impairment occurred, and finally, late mutism with frontal-type dementia, impaired comprehension, and behavioral manifestations developed. The neuropathology was characteristic of GGT type I with vascular changes and comorbid limbic-predominant age-related TDP-43 encephalopathy (LATE). Our findings expand the clinical spectrum of GGTs to include a complex progressive aphasia syndrome. The extraordinary feature, in this case, was the combination of two progressive aphasia subtypes, that is, the early nonfluent-agrammatical variant and the late semantic variant. Our findings also expand the spectrum of neuropathological comorbidities in GGT.

Genetic Alzheimer Disease and Sporadic Dementia With Lewy Bodies: A Comorbidity Presenting as Primary Progressive Aphasia.

We report a 44-year-old woman, with a family history of early-onset dementia, presenting with primary progressive aphasia. This clinically variable syndrome has multiple underlying pathologies, and correlations between clinical manifestations and postmortem neuropathologic findings are controversial. Our patient suffered worsening language impairment with major word-finding difficulties but preserved comprehension. She also developed episodic memory impairment. Her condition progressed to dementia with behavioral changes. Magnetic resonance imaging showed early left perisylvian and bitemporal atrophy. The patient died shortly afterward from colon cancer. Neuropathologic examination revealed advanced early-onset Alzheimer and Lewy body disease, plus a clinically nonrelevant metastasis of her colon cancer in her left parietal lobe. Genetic examination revealed a p.Glu184Asp mutation in the presenilin1 gene. Our findings confirm the importance of a thorough appreciation for the clinical and neuropathologic correlations in patients with atypical neurodegenerative dementias.

Sentence comprehension in Slovak-speaking patients with Alzheimer's disease.

BACKGROUND: According to some studies, sentence comprehension is diminished in Alzheimer's disease (AD) patients, but they differ on what underlies the sentence comprehension impairment. Sentence comprehension in AD patients has been studied mainly in the English language. It is less clear how patients with AD speaking a morphologically rich language with grammatical morphemes indicating case and through it even thematic roles process reversible sentences. AIMS: To compare the comprehension of various syntactic constructions in Slovak-speaking AD patients and cognitively intact elderly people. We were concerned with the influence of the following aspects on sentence comprehension: its length, the order of thematic roles and the presence of a morphological cue placed on the first noun (or at the beginning of a sentence). METHODS & PROCEDURES: We used our own Slovak test of sentence comprehension based on matching pictures to spoken sentences. These sentences contain transitive verbs and two nouns (person/animal), one functioning as a subject and the other as an object, which both can perform the action expressed by the verb. We assessed 62 healthy elderly people and two groups of AD patients. The first group consisted of 34 participants with a mild degree of AD and the other group of 43 participants with a moderate degree of AD. OUTCOME & RESULTS: Statistical comparisons showed that the elderly controls were significantly better in the comprehension of simple active OVS (object-verb-subject word order) sentences and complex EO sentences (a centre-embedded relative clause with a relative pronoun substituting for an object) than patients with a mild degree of AD. In patients with a moderate degree of AD, comprehension of all tested sentence types was worse than in healthy elderly people. The results also indicated that even mild AD patients have more serious problems with processing sentences with non-canonical order of thematic roles regardless of a morphological cue at the beginning of a sentence. CONCLUSION & IMPLICATIONS: The results point to diminished sentence comprehension in patients with AD. In the group of mild AD patients, the order of thematic roles played a significant role in their sentence comprehension. Even though the grammatical morphemes clearly code the functions of words in the Slovak language, mild AD patients do not process them in sentences with a non-canonical order of thematic roles at the same level as the healthy controls. Patients with moderate AD have significant problems even with the comprehension of sentences with a canonical order of thematic roles. These difficulties seem to be a consequence of insufficient resources for language processing.