Syrjanen, Jeremy A.

Objective: Sphingolipids, including S1P (sphingosine-1-phosphate) and ceramides, have been associated with vascular tone, blood pressure regulation, cardiovascular outcomes, and mortality. However, the relationship between plasma sphingolipids and cerebrovascular disease has not been examined. We aimed to assess the cross-sectional association between plasma sphingolipids and white matter hyperintensity (WMH) volume, which is a marker of cerebrovascular disease. Approach and Results: We included 588 participants (302 men and 286 women), aged 60 to 93, enrolled in the population-based Mayo Clinic Study of Aging who had MRI and plasma sphingolipids at the same study visit. Fasting plasma was obtained, and ceramides and S1P were assayed using liquid chromatography-electrospray ionization tandem mass spectrometry. Fluid-attenuated inversion recovery was used to measure WMH volume, defined as percent total intracranial volume. We used linear regression to cross-sectionally examine the relationships between plasma sphingolipids and WMH; both were log-transformed. In multivariable analyses adjusting for age, sex, and hypertension, higher levels of ceramide C16:0 (b [95% CI]=0.24 [0.02–0.45]) and the ceramide ratios C16:0_24:0 (b [95% CI]=0.30 [0.12–0.48]) and C24:1_24:0 (b [95% CI]=0.24 [0.07–0.41]) were associated with a higher WMH volume. A higher ceramide score was also associated with higher WMH volume (b [95% CI]=0.03 (0.01–0.04]). We did not observe any association between S1P and WMH volume. Conclusions: Higher plasma ceramide C16:0 and 2 specific ceramide ratios (C16:0_24:0 and C24:1_24:0) are associated with greater WMH volumes, independent of hypertension, suggesting their utility for measurement of cerebrovascular disease.

AbstractIntroductionBehavior/Comportment/Personality (BEHAV) and Language (LANG) domains were added to the Clinical Dementia Rating (CDR®) for improving evaluation of patients with frontotemporal lobar degeneration (FTLD) (CDR® plus NACC FTLD).MethodsWe analyzed the CDR® plus NACC FTLD among participants from the baseline visit of the Advancing Research and Treatment for Frontotemporal Lobar Degeneration/Longitudinal Evaluation of Familial Frontotemporal Dementia Subjects Consortium.ResultsThe CDR® plus NACC FTLD was able to detect early symptoms in the mildly impaired participants who were rated as CDR® sum of boxes (CDR®‐SB) = 0. The CDR®‐SB was not sensitive, particularly in participants with mild nonfluent/agrammatic primary progressive aphasia. Participants with familial and sporadic behavioral variant FTD exhibited similar CDR® plus NACC FTLD profiles except that language impairment was more frequent in participants with mild sporadic behavioral variant FTD. Adding the BEHAV and/or LANG domains to the CDR®‐SB significantly enhanced discriminatory power in differentiating among the FTLD spectrum disorders.DiscussionThe BEHAV and LANG domains enable the CDR® plus NACC FTLD to capture early symptomatology of FTLD.

Abstract Introduction The aim of this study was to investigate the rates of lobar atrophy in the asymptomatic microtubule‐associated protein tau ( MAPT ) mutation carriers. Methods MAPT mutation carriers (n = 14; 10 asymptomatic, 4 converters from asymptomatic to symptomatic) and noncarriers (n = 13) underwent structural magnetic resonance imaging and were followed annually with a median of 9.2 years. Longitudinal changes in lobar atrophy were analyzed using the tensor‐based morphometry with symmetric normalization algorithm. Results The rate of temporal lobe atrophy in asymptomatic MAPT mutation carriers was faster than that in noncarriers. Although the greatest rate of atrophy was observed in the temporal lobe in converters, they also had increased atrophy rates in the frontal and parietal lobes compared to noncarriers. Discussion Accelerated decline in temporal lobe volume occurs in asymptomatic MAPT mutation carriers followed by the frontal and parietal lobe in those who have become symptomatic. The findings have implications for monitoring the progression of neurodegeneration during clinical trials in asymptomatic MAPT mutation carriers.