Distinct brain networks underlie cognitive dysfunction in Parkinson and Alzheimer diseases

Abstract

Objective: To determine whether cognitive impairment in Parkinson disease (PD) and Alzheimer disease (AD) derives from the same network pathology.Methods: We analyzed 18 F-fluorodeoxyglucose PET scans from 40 patients with AD and 40 agematched healthy controls from the Alzheimer's Disease Neuroimaging Initiative and scanned an additional 10 patients with AD and 10 healthy controls at The Feinstein Institute for Medical Research to derive an AD-related metabolic pattern (ADRP) analogous to our previously established PD cognition-related pattern (PDCP) and PD motor-related pattern (PDRP). We computed individual subject expression values for ADRP and PDCP in 89 patients with PD and correlated summary scores for cognitive functioning with network expression. We also evaluated changes in ADRP and PDCP expression in a separate group of 15 patients with PD scanned serially over a 4-year period.Results: Analysis revealed a significant AD-related metabolic topography characterized by covarying metabolic reductions in the hippocampus, parahippocampal gyrus, and parietal and temporal association regions. Expression of ADRP, but not PDCP, was elevated in both AD groups and correlated with worse cognitive summary scores. Patients with PD showed slight ADRP expression, due to topographic overlap with the network underlying PD motor-related pattern degeneration, but only their PDCP expression values increased as cognitive function and executive performance declined. Longitudinal data in PD disclosed an analogous dissociation of network expression. Conclusions:Cognitive dysfunction in PD is associated with a specific brain network that is largely spatially and functionally distinct from that seen in relation to AD. Cognitive impairment is commonly observed in patients with Parkinson disease (PD), even early in the clinical course, 1,2 but its cause remains unclear. The postmortem observation of amyloid-b plaques and tau neurofibrilliary tangles, pathologic hallmarks of Alzheimer disease (AD), in individuals with PD and dementia has led to the hypothesis that the cognitive changes in PD are caused by comorbid AD.3-5 Many patients with PD have substantial cognitive loss without forming plaques and tangles, however, and the severity of neuropsychological deficits in patients with PD with coexisting cortical Lewy body and AD-like pathology correlates only with From the Center for Neurosciences (P.J.M., M.N., W

Metabolic patterns across core features in dementia with lewy bodies

“…The evidence of relatively spared MTL metabolism is in keeping with several magnetic resonance imaging (MRI) studies evaluating pattern of atrophy in DLB and suggests that this finding may increase the specificity of the differential diagnosis between AD and DLB across most disease stages. [36][37][38][39][40] By contrast, VH negatively covaried with bilateral frontal cortex and precuneus metabolism and more mildly with parietal metabolism. By contrast, to date striatal metabolism has not been systematically investigated in patients with probable DLB.…”

Quantifying brain metabolism from FDG‐PET images into a probability of Alzheimer's dementia score

“…There have been inconsistent findings of DAT‐related metabolism in the cerebellum. An earlier study has found reduced metabolism in the cerebellum, while a more recent study has found increased metabolism in the cerebellum (Ishii et al, ; Mattis et al, ). Interestingly, cerebellar metabolism is reported to correlate with deficits in memory performance and social skills (Newberg et al, ).…”

A multivariate metabolic imaging marker for behavioral variant frontotemporal dementia

“…Before the identification of bFDRP, a retrospective chart review was performed to determine the patient enrollment based on published clinical criteria for the corresponding disorders (i.e., bvFTD [4], AD [5], semantic dementia [SD], and progressive nonfluent aphasia [PNFA] [16]). Enrolled subjects for this study included a total of 35 patients scanned at Center‐A (25 bvFTD and 10 AD), 73 patients scanned at Center‐B (44 bvFTD, 17 SD, and 12 PNFA), and 40 AD subjects randomly retrieved from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (http://adni.loni.usc.edu; see http://www.adni-info.org; previously studied at Center‐A [17]). Table 1 summarizes the demographic information of participants.…”