In vivo amyloid imaging in autopsy-confirmed Parkinson disease with dementia

Abstract

Methods:We performed detailed neuropathologic examination for 3 individuals with PDD who had PIB PET imaging within 15 months of death. Results:We observed elevated cortical uptake of [ 11 C]-PIB on in vivo PET imaging in 2 of the 3 cases. At autopsy, all 3 individuals had abundant cortical Lewy bodies (Braak PD stage 6), and were classified as low-probability Alzheimer disease (AD) based on NIA-Reagan criteria. The 2 PIB-positive individuals had abundant diffuse A␤ plaques but only sparse neuritic plaques and intermediate neurofibrillary tangle pathology. The PIB-negative individual had rare diffuse plaques, no neuritic plaques, and low neurofibrillary tangle burden. Individuals with Parkinson disease (PD) are nearly 6 times more likely to develop dementia than age-matched controls, and the majority of individuals with PD who survive more than 15 years after diagnosis will develop dementia. Conclusions:1,2 Clinicopathologic investigations have revealed heterogeneous histopathology, with Alzheimer disease (AD) pathology (amyloid plaques and neurofibrillary tangles) present in a subset of individuals with PD dementia (PDD).1 When present, AD pathology is typically found in conjunction with other neuropathologic changes, including limbic and cortical Lewy bodies and degeneration of subcortical monoaminergic and cholinergic pathways. The contribution of AD pathology to the pathogenesis of dementia in the setting of PD is thus uncertain. The presence of AD pathology has been postulated to influence clinical manifestations of dementia, for example masking features of dementia with Lewy bodies (DLB) such as hallucinations and fluctuations 3,4 or influencing the timing of dementia onset in patients with Lewy body disorders. 5Antemortem evaluation of A␤ plaque burden by PET imaging using amyloid-specific radiotracers can potentially clarify the role of these lesions in the pathogenesis of Lewy body-associated dementias (PDD and DLB). The tracer N-methyl-[11 C]2-(4Ј-methylaminophenyl)-6-hydroxybenzothiazole (or [ 11 C]-PIB for Pittsburgh Compound-B) has shown great promise for this purpose, demonstrating rapid diffusion across the blood-brain barrier, high affinity to a From the

CFS Biomarkers in Parkinson’s Disease

“…Another recent study reported an association between low levels of A 1-42 levels in 22 non-demented PD patients and worse performance at Digit Symbol test . Although the limitations of these studies, including the small sample size, the heterogeneity of clinical features of patients, the lack of a group of control, the results are interesting and support the role of amyloid plaques in the pathogenesis of dementia in PD patients, in line with a recent report of altered in vivo amyloid imaging in 2 autopsy-confirmed PDD patients (Burack et al, 2010). Table 2.…”

Cerebral Microbleeds in Patients with Dementia with Lewy Bodies and Parkinson Disease Dementia

“…4 Imaging studies that used 11 C-Pittsburgh compound-B positron-emission tomography, which can detect cerebral amyloid angiopathy and diffuse plaque and neuritic plaque, showed a low amyloid burden in patients with PDD, which was comparable to those in Parkinson's disease and in healthy controls. 20 Burack et al 21 performed a neuropathologic examination of 3 patients with PDD who underwent 11 C-Pittsburgh compound-B positron-emission tomography within 15 months of death, and cerebral amyloid angiopathy was absent in 2 and only mild in the third. Another factor that may explain the higher prevalence of CMBs in patients with DLB relative to those with PDD may be differences in characteristics of the amyloid plaque.…”

Performance of 11C-Pittsburgh Compound B PET Binding Potential Images in the Detection of Amyloid Deposits on Equivocal Static Images

“…Second, because subjects included various patients with or without AD as part of this retrospective study, the results of this research may not reflect pure AD-related amyloid pathology, because amyloid deposits occur in subjects with cerebral amyloid angiopathy (29) and Lewy body disease (30,31) and in cognitively intact subjects (32). Third, because of the small sample size, we were not able to refer to the relationship between visual 11 C-PiB-equivocal ratings and quantitative values, 11 C-PiB-equivocal and clinical findings including Mini-Mental State Examination, and that of small cortical amyloid deposits and noncognitive older subjects.…”