Dopamine and choline transporter imaging in DLB & AD

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DESCRIPTION (provided by applicant): Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) are the two most common causes of dementia. AD is characterized by initial deficits in memory and language function while DLB is characterized by initial deficits in: i) attention, frontal-subcortical/executive function, and yisuospatial/praxis skills; ii) parkinsonian motor signs; and iii) persistent visual hallucinations. Differences in striatal dopaminergic and cortical cholinergic neuron integrity have been implicated in the contrasting clinical presentations of AD and DLB in cross-sectional studies. The candidate proposes to employ a longitudinal design to identify temporal correlations between in vivo biomarkers of cortical cholinergic and striatal dopaminergic neuron integrity (assessed via SECT imaging of 123I-IBVM choline vesicular transporter [CVT] and 99mTc-TRODAT-1 dopamine plasma membrane transporter [DMT] binding) and measures of cognitive, parkinsonian, and psychotic symptoms in AD, DLB, and normal older control subjects(NOCS). Specific Aim 1: Identify temporal relationships between striatal dopaminergic neuron integrity and differential patterns of cognitive impairment and parkinsonian signs in DLB, AD, and NOCS over a four-year follow-up period. Hypothesis 1a: Striatal 99mTC-TRODAT-1 DMT binding will be positively correlated with attention (Digit Vigilance test) and frontal-subcortical, executive function (Self-Oriented Pointing Test) in DLB, AD, and normal older subjects at 0, 2, & 4 years. Attention and frontal-subcortical/executive function will be more impaired and 99mTc-TRODAT-1 binding lower in DLB > AD > NOCS at all time points. Hypothesis 1b: Striatal 99mTc-TRODAT-1 DMT binding will be inversely related to parkinsonian signs in DLB and AD at 0,2, & 4 years. Parkinsonian signs and loss of 99mTc-TRODAT-1 binding will be more severe in DLB > AD > NOCS at all time points. Specific Aim 2: Identify temporal relationships between cortical cholinergic neuron integrity and differential patterns of cognitive impairment in DLB, AD, and NOCS over a four-year follow-up period. Hypothesis 2a: 123I-IBVM CVT binding in temporal cortex will be negatively correlated with memory (Wechsler logical memory scale) and language (Boston Naming Test) function in AD, DLB, and normal older subjects at 0, 2, & 4 years. Memory and language impairment and loss of 123I-IBVM binding will be more severe in AD > DLB > NOCS at all time points. Hypothesis 2b: 123I-IBVM CVT binding in parietal and occipital cortex will be inversely related to visuospatial/praxis abilities (Wechsler block design) at 0, 2, & 4 years. Impairment in visuospatial/praxis abilities and loss of 123I-IBVM binding will be greater in DLB > AD > NOCS at all time points. Specific Aim 3: Characterize relationships between cholinergic and dopaminergic neuron integrity and psychotic symptoms in DLB and AD and demonstrate persistence over time. Hypothesis 3: Temporal lobe CVT binding will be inversely related to visual hallucinations in DLB and auditory hallucinations in AD at 0, 2, & 4 years.