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.
- Journal of neurology, neurosurgery, and psychiatry 07/2013; 85(1). DOI:10.1136/jnnp-2013-305392 · 5.58 Impact Factor
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ABSTRACT: To evaluate whether white matter hyperintensities (WMHs) may act as an independent predictor for progression of cognitive status, the authors analyzed the longitudinal effects of WMHs on cognitive dysfunction in non-demented patients with Parkinson's disease (PD). A total of 111 patients with PD were enrolled, including subjects with mild cognitive impairment (MCI, n = 65) and cognitively normal subjects (CN, n = 46). These individuals were classified as MCI converters (n = 22) or MCI non-converters (n = 43) and CN converters (n = 18) or CN non-converters (n = 28) based on whether they were subsequently diagnosed with PD dementia or PD-MCI during a minimum 24-month follow-up. The WMH burden and the Cholinergic Pathway Hyperintensities Scale (CHIPS) and their relationships to longitudinal changes in cognitive performance were examined. PD-MCI converters had larger WMH volume (14421.0 vs. 5180.4, P < 0.001) and higher CHIPS score (22.6 vs. 11.2, P = 0.001) compared with PD-MCI non-converters. Logistic regression analysis revealed in patients with PD-MCI that WMH volume (odds ratio 1.616, P = 0.009) and CHIPS score (odds ratio 1.084, P = 0.007) were independently associated with PD dementia conversion. However, WMH volume and CHIPS score did not differ between PD-CN converters and PD-CN non-converters. In patients with PD-MCI, both WMH volume and CHIPS score were closely associated with longitudinal decline in general cognition, semantic fluency and Stroop test scores. The present study demonstrates that WMH burden is a significant predictor of conversion from PD-MCI to PD dementia and is related to ongoing decline in frontal-lobe-based cognitive performance.European Journal of Neurology 03/2014; 21(6). DOI:10.1111/ene.12412 · 3.85 Impact Factor
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ABSTRACT: The next several decades will see an exponential rise in the number of patients with disorders of memory and cognition, and of Alzheimer's disease in particular. Impending demographic shifts, an absence of effective treatments, and the significant burden these conditions place on patients, caregivers, and society, mean there is an urgent need to develop novel therapies. Deep brain stimulation (DBS) is a neurosurgical procedure that is a standard-of-care for many patients with treatment-refractory Parkinson's disease, dystonia, and essential tremor. DBS has proven to be an effective means of modulating activity in disrupted motor circuitry, and has shown promise as a modulator of other dysfunctional circuits, including for mood and anxiety disorders. The deficits in Alzheimer's disease and other disorders of memory and cognition are also beginning to be thought of as arising from dysfunction in neural circuits. Such dysfunction may be amenable to modulation using focal brain stimulation. A global experience is now emerging for the use of DBS for these conditions, targeting key nodes in the memory circuit, including the fornix and nucleus basalis of Meynert. Such work holds promise as a novel therapeutic approach for one of medicine's most urgent priorities.Journal of the American Society for Experimental NeuroTherapeutics 04/2014; 11(3). DOI:10.1007/s13311-014-0275-0 · 3.88 Impact Factor