Cognitive profiles of individual patients with Parkinson's disease and dementia: Comparison with dementia with Lewy bodies and Alzheimer's disease
ABSTRACT We describe the pattern of cognitive profiles within a community-based sample of patients with Parkinson's disease (PD) and dementia (PDD) using cluster analyses, and compare the results with data from patients with Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). Fifty patients with PDD and 39 with AD from Stavanger, Norway, and 62 patients with DLB from San Diego, CA, USA were diagnosed by either standardized clinical procedures or criteria (all PDD and all AD cases) or necropsy (all DLB cases). Four subgroups were identified: two subgroups with a subcortical cognitive profile (one with mild and one with moderate dementia severity), one subgroup with global impairment and severe dementia, and one subgroup with a cortical cognitive profile and moderate dementia. Of the patients with PDD and with DLB, 56% and 55%, respectively, had a subcortical cognitive profile, compared with only 33% of the AD patients. Conversely, 30% of the patients with PDD and 26% of those with DLB had a cortical cognitive profile, compared with 67% of the patients with AD. These findings suggest that in some patients with PDD, frontosubcortical changes are the main contributing factor to dementia, whereas in other patients, cortical and hippocampal changes are more important.
- SourceAvailable from: Alberto Serrano-Pozo
[Show abstract] [Hide abstract]
- "The new consortium criteria for the classification of Lewy body diseases (LBD) recognizes two clinical entities, the first denominated dementia with LBs (DLB) and the second PD dementia (PDD) (McKeith et al. 1996; Aarsland et al. 2004; Burn 2006; McKeith 2006; Lippa et al. 2007). While in patients with DLB, the clinical presentation is of dementia followed by parkinsonism, in patients with PDD the initial signs are of parkinsonism followed by dementia (Litvan et al. 1998; Janvin et al. 2006; McKeith 2006). Interestingly, the brains of patients with DLB and PDD display very similar pathology, with the exception that recent studies have shown extensive deposition of Ab and a-synuclein in the striatum and hippocampus in DLB compared to only a-synuclein in PDD cases (Duda et al. 2002; Jellinger and Attems 2006). "
ABSTRACT: The neuropathological hallmarks of Alzheimer disease (AD) include “positive” lesions such as amyloid plaques and cerebral amyloid angiopathy, neurofibrillary tangles, and glial responses, and “negative” lesions such as neuronal and synaptic loss. Despite their inherently cross-sectional nature, postmortem studies have enabled the staging of the progression of both amyloid and tangle pathologies, and, consequently, the development of diagnostic criteria that are now used worldwide. In addition, clinicopathological correlation studies have been crucial to generate hypotheses about the pathophysiology of the disease, by establishing that there is a continuum between “normal” aging and AD dementia, and that the amyloid plaque build-up occurs primarily before the onset of cognitive deficits, while neurofibrillary tangles, neuron loss, and particularly synaptic loss, parallel the progression of cognitive decline. Importantly, these cross-sectional neuropathological data have been largely validated by longitudinal in vivo studies using modern imaging biomarkers such as amyloid PET and volumetric MRI.Cold Spring Harbor perspectives in biology 09/2011; 3(9):a006189. DOI:10.1101/cshperspect.a006189 · 8.23 Impact Factor
[Show abstract] [Hide abstract]
- "The clinical profile of PD-MCI patients who are supposed to be at higher risk for PDD has been investigated in various studies, but these studies differ regarding the cut-off values used to define PD-MCI [12, 15–17]. Besides the fact that it is not known yet which PD-MCI subjects have the highest risk for conversion to PDD, it is not evaluated whether the choice of different cut-off values might have an impact on the interpretation of the PD-MCI phenotype. "
ABSTRACT: Comparable to Alzheimer's disease, mild cognitive impairment in Parkinson's disease (PD-MCI) is associated with an increased risk for dementia. However different definitions of PD-MCI may have varying predictive accuracy for dementia. In a cohort of 101 nondemented Parkinson patients who underwent neuropsychological testing, the frequency of PD-MCI subjects and PD-MCI subtypes (i.e., amnestic/nonamnestic) was determined by use of varying healthy population-based cut-off values. We also investigated the association between defined PD-MCI groups and ADL scales. Varying cut-off values for the definition of PD-MCI were found to affect frequency of PD-MCI subjects (9.9%-92.1%) and, maybe more important, lead to a "shift" of proportion of detected PD-MCI subtypes especially within the amnestic single-domain subtype. Models using a strict cut-off value were significantly associated with lower ADL scores. Thus, the use of defined cut-off values for the definition of PD-MCI is highly relevant for comparison purposes. Strict cut-off values may have a higher predictive value for dementia.05/2011; 2011:540843. DOI:10.4061/2011/540843
[Show abstract] [Hide abstract]
- "The pathology of AD and PD overlap in a heterogeneous group of conditions denominated jointly Lewy body disease (LBD) , , , , . While in patients with dementia with Lewy bodies (DLB) the clinical presentation is of dementia followed by parkinsonism, in patients with PD dementia (PDD) the initial signs are of parkinsonism followed by dementia , , , . In DLB, Aβ promotes α-syn aggregation and toxicity in vivo , and Aβ and α-syn might directly interact  to form hybrid channel like structures . "
ABSTRACT: Lewy body disease is a heterogeneous group of neurodegenerative disorders characterized by alpha-synuclein accumulation that includes dementia with Lewy bodies (DLB) and Parkinson's Disease (PD). Recent evidence suggests that impairment of lysosomal pathways (i.e. autophagy) involved in alpha-synuclein clearance might play an important role. For this reason, we sought to examine the expression levels of members of the autophagy pathway in brains of patients with DLB and Alzheimer's Disease (AD) and in alpha-synuclein transgenic mice. By immunoblot analysis, compared to controls and AD, in DLB cases levels of mTor were elevated and Atg7 were reduced. Levels of other components of the autophagy pathway such as Atg5, Atg10, Atg12 and Beclin-1 were not different in DLB compared to controls. In DLB brains, mTor was more abundant in neurons displaying alpha-synuclein accumulation. These neurons also showed abnormal expression of lysosomal markers such as LC3, and ultrastructural analysis revealed the presence of abundant and abnormal autophagosomes. Similar alterations were observed in the brains of alpha-synuclein transgenic mice. Intra-cerebral infusion of rapamycin, an inhibitor of mTor, or injection of a lentiviral vector expressing Atg7 resulted in reduced accumulation of alpha-synuclein in transgenic mice and amelioration of associated neurodegenerative alterations. This study supports the notion that defects in the autophagy pathway and more specifically in mTor and Atg7 are associated with neurodegeneration in DLB cases and alpha-synuclein transgenic models and supports the possibility that modulators of the autophagy pathway might have potential therapeutic effects.PLoS ONE 02/2010; 5(2):e9313. DOI:10.1371/journal.pone.0009313 · 3.23 Impact Factor