Beach, Thomas G.

Abstract INTRODUCTION We examined the progression of extrapyramidal symptoms and signs in autopsy‐confirmed dementia with Lewy bodies (DLB), Parkinson's disease dementia (PDD), and Alzheimer's disease dementia (AD). METHODS Longitudinal data were obtained from Arizona Study of Aging and Neurodegenerative Disease, with PDD ( n = 98), AD ( n = 47) and DLB ( n = 48) further sub‐grouped as with or without parkinsonism (DLB+ and DLB−). Within‐group Unified Parkinson's Disease Rating Scale (UPDRS) ‐II and UPDRS‐III trajectories were analyzed using non‐linear mixed effects models. RESULTS In DLB, 65.6% had parkinsonism. Baseline UPDRS‐II and III scores (off‐stage) were highest ( P < 0.001) for PDD (mean ± SD 14.3 ± 7.8 and 27.4 ± 16.3), followed by DLB+ (6.0 ± 8.8 and 17.2 ± 17.1), DLB− (1.1 ± 1.3 and 3.3 ± 5.5) and AD (3.2 ± 6.1 and 8.2 ± 13.6). Compared to PDD, the DLB+ group had faster UPDRS‐III progression over 8‐years (Cohen's‐ d range 0.98 to 2.79, P < 0.001), driven by gait ( P < 0.001) and limb bradykinesia ( P = 0.02) subscales. DISCUSSION Motor deficits progress faster in DLB+ than PDD, providing insights about expected changes in motor function. Highlights Dementia with Lewy bodies has faster motor progression than Parkinson's disease dementia Linear and non‐linear mixed modeling analysis of longitudinal data was utilized Findings have implications for clinical prognostication and trial design

Abstract Cerebral white matter rarefaction (CWMR) was considered by Binswanger and Alzheimer to be due to cerebral arteriolosclerosis. Renewed attention came with CT and MR brain imaging, and neuropathological studies finding a high rate of CWMR in Alzheimer disease (AD). The relative contributions of cerebrovascular disease and AD to CWMR are still uncertain. In 1181 autopsies by the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND), large-format brain sections were used to grade CWMR and determine its vascular and neurodegenerative correlates. Almost all neurodegenerative diseases had more severe CWMR than the normal control group. Multivariable logistic regression models indicated that Braak neurofibrillary stage was the strongest predictor of CWMR, with additional independently significant predictors including age, cortical and diencephalic lacunar and microinfarcts, body mass index, and female sex. It appears that while AD and cerebrovascular pathology may be additive in causing CWMR, both may be solely capable of this. The typical periventricular pattern suggests that CWMR is primarily a distal axonopathy caused by dysfunction of the cell bodies of long-association corticocortical projection neurons. A consequence of these findings is that CWMR should not be viewed simply as “small vessel disease” or as a pathognomonic indicator of vascular cognitive impairment or vascular dementia.