Dataset Information

Amyloid is linked to cognitive decline in patients with Parkinson disease without dementia.

ABSTRACT:

Objective

To determine whether amyloid burden, as indexed by Pittsburgh compound B (PiB) retention, identifies patients with Parkinson disease with mild cognitive impairment (PD-MCI) compared to those with normal cognition (PD-nl). A related aim is to determine whether amyloid burden predicts cognitive decline in a cohort of subjects with PD without dementia.

Methods

In this prospective cohort study, we examined 46 subjects with PD without dementia, of whom 35 had normal cognition and 11 met criteria for PD-MCI at study baseline. All subjects underwent standardized neurologic and neuropsychological examinations and PiB PET at baseline, and clinical examinations were conducted annually for up to 5 years.

Results

At baseline, precuneus PiB retention did not distinguish PD-MCI from PD-nl. Subjects with PD-MCI declined more rapidly than PD-nl subjects on cognitive tests of memory, executive function, and activation retrieval. Of the 35 PD-nl subjects, 8 progressed to PD-MCI and 1 to dementia; of the 11 PD-MCI subjects, 5 converted to dementia. Both higher PiB retention and a diagnosis of PD-MCI predicted a greater hazard of conversion to a more severe diagnosis. Baseline PiB retention predicted worsening in executive function over time. The APOE ?4 allele also related to worsening in executive function, as well as visuospatial function, activation retrieval, and performance on the Mini-Mental State Examination. In contrast to its relation to cognitive decline, PiB retention did not affect progression of motor impairment.

Conclusions

At baseline measurements, amyloid burden does not distinguish between cognitively impaired and unimpaired subjects with PD without dementia, but our data suggest that amyloid contributes to cognitive, but not motor, decline over time.

SUBMITTER: Gomperts SN

PROVIDER: S-EPMC3589197 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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Publications

Amyloid is linked to cognitive decline in patients with Parkinson disease without dementia.

Gomperts Stephen N SN Locascio Joseph J JJ Rentz Dorene D Santarlasci Andrea A Marquie Marta M Johnson Keith A KA Growdon John H JH

Neurology 20121212 1

<h4>Objective</h4>To determine whether amyloid burden, as indexed by Pittsburgh compound B (PiB) retention, identifies patients with Parkinson disease with mild cognitive impairment (PD-MCI) compared to those with normal cognition (PD-nl). A related aim is to determine whether amyloid burden predicts cognitive decline in a cohort of subjects with PD without dementia.<h4>Methods</h4>In this prospective cohort study, we examined 46 subjects with PD without dementia, of whom 35 had normal cognition ...[more]

PMID: 23243071

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Project description:BackgroundIn Alzheimer's disease, amyloid- β (A β) peptides aggregate in the lowering CSF amyloid levels - a key pathological hallmark of the disease. However, lowered CSF amyloid levels may also be present in cognitively unimpaired elderly individuals. Therefore, it is of great value to explain the variance in disease progression among patients with A β pathology.MethodsA cohort of n=2293 participants, of whom n=749 were A β positive, was selected from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database to study heterogeneity in disease progression for individuals with A β pathology. The analysis used baseline clinical variables including demographics, genetic markers, and neuropsychological data to predict how the cognitive ability and AD diagnosis of subjects progressed using statistical models and machine learning. Due to the relatively low prevalence of A β pathology, models fit only to A β-positive subjects were compared to models fit to an extended cohort including subjects without established A β pathology, adjusting for covariate differences between the cohorts.ResultsA β pathology status was determined based on the A β42/A β40 ratio. The best predictive model of change in cognitive test scores for A β-positive subjects at the 2-year follow-up achieved an R2 score of 0.388 while the best model predicting adverse changes in diagnosis achieved a weighted F1 score of 0.791. A β-positive subjects declined faster on average than those without A β pathology, but the specific level of CSF A β was not predictive of progression rate. When predicting cognitive score change 4 years after baseline, the best model achieved an R2 score of 0.325 and it was found that fitting models to the extended cohort improved performance. Moreover, using all clinical variables outperformed the best model based only on a suite of cognitive test scores which achieved an R2 score of 0.228.ConclusionOur analysis shows that CSF levels of A β are not strong predictors of the rate of cognitive decline in A β-positive subjects when adjusting for other variables. Baseline assessments of cognitive function accounts for the majority of variance explained in the prediction of 2-year decline but is insufficient for achieving optimal results in longer-term predictions. Predicting changes both in cognitive test scores and in diagnosis provides multiple perspectives of the progression of potential AD subjects.

Dataset Information

Amyloid is linked to cognitive decline in patients with Parkinson disease without dementia.

Objective

Methods

Results

Conclusions

Publications

Amyloid is linked to cognitive decline in patients with Parkinson disease without dementia.

Similar Datasets

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