Abstract
IntroductionThe biological basis of cognitive impairment in parkinsonian diseases is believed to be multifactorial. We investigated the contribution of dopamine deficiency to cognition in Parkinson disease (PD) and dementia with Lewy bodies (DLB) with dopamine transporter (DAT) imaging.MethodsWe acquired 11C altropane PET, magnetic resonance imaging and cognitive testing in 19 nondemented subjects with PD, 10 DLB and 17 healthy control subjects (HCS). We analyzed DAT concentration in putamen, caudate, anterior cingulate (AC), orbitofrontal and prefrontal regions, using the Standardized Uptake Volume Ratio with partial volume correction, and we related DAT concentration and global cortical thickness to neuropsychological performance.ResultsDAT concentration in putamen and in caudate were similar in PD and DLB groups and significantly lower than in HCS. Reduced caudate DAT concentration was associated with worse Clinical Dementia Rating Scale–sum of boxes (CDR-SB) scores and visuospatial skills in DLB but not in PD or HCS groups. Adjusting for putamen DAT concentration, as a measure of severity of motor disease, caudate DAT concentration was lower in DLB than in PD. Higher AC DAT concentration was associated with lower putamen DAT concentration in DLB and with higher putamen DAT concentration in PD. Higher AC DAT concentration in DLB correlated with greater impairment in semantic memory and language.ConclusionsCaudate and AC dopamine dysfunction contribute in opposing directions to cognitive impairment in DLB.
Highlights
The biological basis of cognitive impairment in parkinsonian diseases is believed to be multifactorial
Reduced caudate dopamine transporter (DAT) concentration was associated with worse Clinical Dementia Rating Scale–sum of boxes (CDR-SB) scores and visuospatial skills in dementia with Lewy bodies (DLB) but not in Parkinson disease (PD) or healthy control subjects (HCS) groups
Mean Hoehn and Yahr (H&Y) values were comparable between DLB and PD subjects (P = 0.50), and Unified Parkinson’s Disease Rating Scale (UPDRS) scores were higher in DLB subjects than in PD subjects (P = 0.03)
Summary
The biological basis of cognitive impairment in parkinsonian diseases is believed to be multifactorial. We investigated the contribution of dopamine deficiency to cognition in Parkinson disease (PD) and dementia with Lewy bodies (DLB) with dopamine transporter (DAT) imaging. Neuropathological studies support multiple causative factors for cognitive impairment in Lewy body (LB) diseases. These factors include alpha-synuclein aggregation at synapses [1] and in cortical Lewy aggregates [2], amyloid deposition [3], and loss of the brain’s neuromodulators [4]. The dopamine transporter (DAT) is a reliable marker of dopamine neuron synapses in most brain regions. DAT levels are high in the striatum and moderate in multiple cortical regions, including the anterior cingulate and the orbitofrontal cortex [8,9]
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