Exploratory analysis of neuropsychological and neuroanatomical correlates of progressive mild cognitive impairment in Parkinson's disease
ABSTRACT Parkinson's disease with mild cognitive impairment (PD-MCI) is a heterogeneous entity in terms of cognitive profiles and conversion to dementia. However, the risk factors for ongoing cognitive decline in patients with PD-MCI are not clearly defined.
51 patients with PD-MCI were prospectively followed-up for a minimum of 2 years. Subjects were classified as MCI converters (n=15) or MCI non-converters (n=36) based on whether they were subsequently diagnosed with PD dementia. We explored cognitive profiles and neuroanatomical characteristics of PD-MCI converters using voxel based morphometry (VBM) of grey matter (GM) density and region of interest based volumetric analysis of the substantia innominata (SI).
PD-MCI converters showed more severe cognitive deficits in frontal executive functions, immediate verbal memory and visual recognition memory compared with PD-MCI non-converters. VBM analysis revealed that PD-MCI converters had significantly lower GM density in the left prefrontal areas, left insular cortex and bilateral caudate nucleus compared with that in PD-MCI non-converters. The mean normalised SI volume was significantly smaller in both PD-MCI converters (1.19±0.35, p<0.001) and PD-MCI non-converters (1.52±0.27, p<0.001) compared with that in controls (1.87±0.19). PD-MCI converters had a significantly smaller normalised SI volume than PD-MCI non-converters (p<0.001).
Our data show that atrophy in the frontostriatal areas and cholinergic structures, as well as frontal lobe associated cognitive performance, may act as predictors of dementia in PD-MCI patients, suggesting distinctive patterns of cognitive profiles and a neuroanatomical basis for progressive PD-MCI.
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ABSTRACT: Objective: Prospective memory (PM) is the ability to keep in memory and realize future intentions. We aimed at investigating whether in Parkinson's disease (PD) PM deficits are related to mild cognitive impairment (MCI). Other aims were to investigate the cognitive abilities underlying PM performance, and the association between PM performance and measures of daily living functioning. Method: The study included 15 PD patients with single domain MCI, 15 with multiple domain MCI, 17 PD patients without cognitive disorders (PDNC) and 25 healthy controls (HCs). All subjects were administered a PM procedure that included focal (PM cue is processed in the ongoing task) and nonfocal (PM cue is not processed in the ongoing task) conditions. PD patients were administered an extensive neuropsychological battery and scales to assess daily living abilities. Results: PD patients with MCI (both single and multiple domains) showed lower accuracy on all PM conditions than both HC and PDNC patients. This was predicted by their scores on shifting indices. Conversely, PM accuracy of PDNC patients was comparable to HCs. Regression analyses revealed that PD patients' PM performance significantly predicted scores on daily living scales Conclusions: Results suggest that PM efficiency is not tout-court reduced in PD patients, but it specifically depends on the presence of MCI. Moreover, decreased executive functioning, but not episodic memory failure, accounts for a significant proportion of variance in PM performance. Finally, PM accuracy indices were found to be associated with measures of global daily living functioning and management of medication. (PsycINFO Database Record (c) 2015 APA, all rights reserved).Neuropsychology 02/2015; DOI:10.1037/neu0000184 · 3.43 Impact Factor
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ABSTRACT: Background and purposePatients with Parkinson's disease (PD) are at high risk for cognitive dysfunction. Non-pharmacological interventions have attracted increasing interest for enhancing PD patients' cognitive functions.Methods One-year follow-up data (T2) of a randomized controlled trial evaluating two 6-week cognitive trainings – a structured (NEUROvitalis, NV) and an unstructured (mentally fit, MF) program − compared with a waiting list control group (CG) in non-demented PD patients (Hoehn and Yahr I–III) are presented. Forty-seven PD patients were examined at T2. Effects on overall cognitive functions (Mini-Mental State Examination and DemTect) were compared between all groups with repeated measurement analyses of variance. A combined score of the percentage change value from baseline (T0) to T2 was calculated to identify patients who retained or improved their cognitive state (responders). The risk of developing mild cognitive impairment (MCI) was analyzed.ResultsSignificant time × treatment effects on overall cognitive functions were found for both training groups, each compared separately to the CG (DemTect, P < 0.05). Nine patients (56.3%) of the NV group, seven (41.2%) of the MF group and three (21.4%) of the CG were responders. Comparing NV to CG the odds ratio was 4.7 [95% confidence interval (0.8; 33.3)], and comparing MF to CG it was 2.6 [95% confidence interval (0.4; 17.4)]. MCI risk for patients without prior MCI was 40.0% in CG, 18.2% in MF and 18.2% in NV. The odds ratio was 3 comparing NV to CG, MF to CG.DiscussionThis study gives evidence that cognitive training may be effective to prevent cognitive decline and onset of MCI in PD patients.European Journal of Neurology 12/2014; DOI:10.1111/ene.12621 · 3.85 Impact Factor
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ABSTRACT: Cognitive impairment is common in PD, even in early stages. The construct of mild cognitive impairment has been used to identify clinically evident cognitive impairment without functional decline in PD patients (PD-MCI). The aim of the present study was to investigate brain connectivity associated with PD-MCI through RS-fMRI. RS-fMRI at 3T was collected in 42 PD patients and 20 matched healthy controls. Among PD patients, 21 were classified as having MCI (PD-MCI) and 21 as cognitively unimpaired (PD-nMCI) based on criteria for possible PD-MCI (level I category). Single-subject and group-level ICA was used to investigate the integrity of brain networks related to cognition in PD patients with and without MCI. Image data processing and statistical analysis were performed in BrainVoyager QX. In addition, we used VBM to test whether functional connectivity differences were related to structural abnormalities. PD-nMCI and PD-MCI patients compared with controls showed decreased DMN connectivity. PD-MCI patients, but not PD-nMCI, compared with controls, showed decreased functional connectivity of bilateral prefrontal cortex within the frontoparietal network. The decreased prefrontal cortex connectivity correlated with cognitive parameters but not with clinical variables. VBM analysis did not reveal any difference in local gray matter between patients and controls. Our findings suggest that an altered DMN connectivity characterizes PD patients, regardless of cognitive status, whereas a functional disconnection of the frontoparietal network could be associated with MCI in PD in the absence of detectable structural changes.Journal of Neurology 11/2014; 262(2). DOI:10.1007/s00415-014-7591-5 · 3.84 Impact Factor