Citations

Objective To investigate the associations between age, vascular health, and Alzheimer disease (AD) imaging biomarkers in an elderly sample. Methods We identified 430 individuals along the cognitive continuum aged >60 years with amyloid positron emission tomography (PET), tau PET, and magnetic resonance imaging (MRI) scans from the population‐based Mayo Clinic Study of Aging. A subset of 329 individuals had fluorodeoxyglucose (FDG) PET. We ascertained presently existing cardiovascular and metabolic conditions (CMC) from health care records and used the summation of presence/absence of hypertension, hyperlipidemia, cardiac arrhythmias, coronary artery disease, congestive heart failure, diabetes mellitus, and stroke as a surrogate for vascular health. We used global amyloid from Pittsburgh compound B PET, entorhinal cortex tau uptake (ERC‐tau) from tau‐PET, and neurodegeneration in AD signature regions from MRI and FDG‐PET as surrogates for AD pathophysiology. We dichotomized participants into CMC = 0 (CMC − ) versus CMC > 0 (CMC + ) and tested for age‐adjusted group differences in AD biomarkers. Using structural equation models (SEMs), we assessed the impact of vascular health on AD biomarker cascade (amyloid leads to tau leads to neurodegeneration) after considering the direct and indirect age, sex, and apolipoprotein E effects. Results CMC + participants had significantly greater neurodegeneration than CMC − participants but did not differ by amyloid or ERC‐tau. The SEMs showed that (1) vascular health had a significant direct and indirect impact on neurodegeneration but not on amyloid; and (2) vascular health, specifically the presence of hyperlipidemia, had a significant direct impact on ERC‐tau. Interpretation Vascular health had quantifiably greater impact on neurodegeneration in AD regions than on amyloid deposition. Longitudinal studies are warranted to clarify the relationship between tau deposition and vascular health. Ann Neurol 2017;82:706–718

AbstractBackgroundDepression is highly prevalent in individuals with coronary artery disease (CAD) and increases the risk of future cardiac events and mortality. Sphingolipids have been implicated in the pathophysiology of both CAD and depression. This study assessed the association between plasma sphingolipid concentrations and depressive symptoms in CAD subjects.MethodsDepressive symptoms were measured using the depression subscale of the self‐reported Hospital Anxiety and Depression Scale (HADS). Sphingolipid concentrations were measured from fasting plasma samples using high‐performance liquid chromatography‐coupled electrospray ionization tandem mass spectrometry (LC/MS/MS). Linear regression models were used to assess associations between log‐transformed concentrations of plasma sphingolipids and depressive symptoms.ResultsA total of 111 CAD patients (mean (SD) age = 63.6 ± 6.4, 84.7% male) were included. In linear regression analyses, higher plasma concentrations of ceramides C16:0 (β = 0.204, p = .026) and C18:0 (β = 0.209, p = .023) and sphingomyelin SM18:1 (β = 0.210, p = .024) were significantly associated with higher HADS depression subscale score after adjusting for covariates.ConclusionSphingolipids, in particular the ceramide species C16:0 and C18:0 and the sphingomyelin species SM18:1, may be implicated in the pathophysiology of depression in CAD. The association between plasma sphingolipid concentrations and depression should be further examined in CAD patients and in other populations.

ABSTRACTObjective: The purpose of this study was to examine the discrepancies between the clinical diagnosis of parkinsonism and neuropathological findings in a population‐based cohort with parkinsonian disorders.Background: The specific clinical diagnosis of parkinsonism is challenging, and definite confirmation requires neuropathological evaluation. Currently, autopsies are seldom performed, and most brain autopsies represent atypical or diagnostically unresolved cases.Methods: We used a defined population‐based incidence cohort with clinical parkinsonism (n = 669) from the Rochester Epidemiology Project in Olmsted County, Minnesota, 1991‐2010. We reviewed reports of all patients who underwent neuropathologic examination at autopsy (n = 60; 9%) and applied consensus pathologic guidelines for neurodegenerative disease diagnosis.Results: Among the 60 patients examined pathologically, the median time from the last recorded clinical diagnosis to death was 7 years (range from 2 to 17 years). Clinical–pathological concordance was found in 52 cases (86.7%), whereas 8 (13.3%) had a clinical‐pathological discrepancy. Four patients with a clinical diagnosis of idiopathic Parkinson's disease had no pathological evidence of Lewy bodies or α‐synucleinopathy; of these, pathological diagnoses were Alzheimer's disease (2 cases), progressive supranuclear palsy (1 case), and vascular parkinsonism (1 case). Two patients with clinical diagnoses of "dementia with Lewy bodies" and one patient with an "unspecified parkinsonism" had a pathological diagnosis of Alzheimer's disease without concomitant α‐synuclein lesions. One patient with clinically diagnosed "progressive supranuclear palsy" had indeterminate pathological findings without α‐synuclein or Aβ‐ or tau‐immunoreactive lesions at autopsy.Conclusions: Overall, the clinical diagnoses of parkinsonian subtypes had good concordance with pathological confirmation (86.7%). However, clinical–pathological discrepancies were documented in 13.3%. © 2017 International Parkinson and Movement Disorder Society