Book Reviews

THE SILVERLAKE EXPERIMENT. By Lamar T. Empey and Steven G. Lubeck. Chicago: Aldine Publishing Company, 1971. Pp. x, 354. $12.50. THE FEAR OF CONSPIRACY: IMAGES OF UN-AMERICAN SUBVERSION FROM THE REVOLUTION TO THE PRESENT. Edited with commentary by David Brion Davis.Ithaca: Cornell University Press, 1971. Pp. xxiv, 362.$10.00. THE INTERNATIONAL LAW OF CIVIL WAR. Edited by Richard A. Falk. Baltimore: The Johns Hopkins Press, 1971. Pp. xix, 452. $15.00. THE DEATH OF THE GREAT SPIRIT: AN ELEGY FOR THE AMERICAN INDIAN. By Earl Shorris. New York: Simon and Schuster, 1971. Pp. 253.$6.95

White matter integrity and vulnerability to Alzheimer's disease: Preliminary findings and future directions

AbstractNeuroimaging biomarkers that precede cognitive decline have the potential to aid early diagnosis of Alzheimer's disease (AD). A body of diffusion tensor imaging (DTI) work has demonstrated declines in white matter (WM) microstructure in AD and its typical prodromal state, amnestic mild cognitive impairment. The present review summarizes recent evidence suggesting that WM integrity declines are present in individuals at high AD-risk, prior to cognitive decline. The available data suggest that AD-risk is associated with WM integrity declines in a subset of tracts showing decline in symptomatic AD. Specifically, AD-risk has been associated with WM integrity declines in tracts that connect gray matter structures associated with memory function. These tracts include parahippocampal WM, the cingulum, the inferior fronto-occipital fasciculus, and the splenium of the corpus callosum. Preliminary evidence suggests that some AD-risk declines are characterized by increases of radial diffusivity, raising the possibility that a myelin-related pathology may contribute to AD onset. These findings justify future research aimed at a more complete understanding of the neurobiological bases of DTI-based declines in AD. With continued refinement of imaging methods, DTI holds promise as a method to aid identification of presymptomatic AD. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease

Tapinarof in the treatment of psoriasis: A review of the unique mechanism of action of a novel therapeutic AhR modulating agent (TAMA)

Tapinarof, a novel, first-in-class small-molecule topical therapeutic aryl hydrocarbon receptor (AhR) modulating agent (TAMA), is in clinical development for the treatment of psoriasis and atopic dermatitis. The efficacy of tapinarof in psoriasis is attributed to its specific binding and activation of AhR, a ligand-dependent transcription factor, leading to the downregulation of pro-inflammatory cytokines, including interleukin-17, and regulation of skin barrier protein expression to promote skin barrier normalization. AhR signaling regulates gene expression in immune cells and skin cells, and has critical roles in the regulation of skin homeostasis. Tapinarof-mediated AhR signaling underlies the mechanistic basis for the significant efficacy and acceptable tolerability observed in early phase clinical trials of tapinarof cream in the treatment of psoriasis

Cardiorespiratory Fitness Diminishes the Effects of Age on White Matter Hyperintensity Volume

White matter hyperintensities (WMHs) are among the most commonly observed marker of cerebrovascular disease. Age is a key risk factor for WMH development. Cardiorespiratory fitness (CRF) is associated with increased vessel compliance, but it remains unknown if high CRF affects WMH volume. This study explored the effects of CRF on WMH volume in community-dwelling older adults. We further tested the possibility of an interaction between CRF and age on WMH volume. Participants were 76 adults between the ages of 59 and 77 (mean age = 65.36 years, SD = 3.92) who underwent a maximal graded exercise test and structural brain imaging. Results indicated that age was a predictor of WMH volume (beta = .32, p = .015). However, an age-by-CRF interaction was observed such that higher CRF was associated with lower WMH volume in older participants (beta = -.25, p = .040). Our findings suggest that higher levels of aerobic fitness may protect cerebrovascular health in older adults

Endothelial Function Is Associated with White Matter Microstructure and Executive Function in Older Adults

Age-related declines in endothelial function can lead to cognitive decline. However, little is known about the relationships between endothelial function and specific neurocognitive functions. This study explored the relationship between measures of endothelial function (reactive hyperemia index; RHI), white matter (WM) health (fractional anisotropy, FA, and WM hyperintensity volume, WMH), and executive function (Trail Making Test (TMT); Trail B - Trail A). Participants were 36 older adults between the ages of 59 and 69 (mean age = 63.89 years, SD = 2.94). WMH volume showed no relationship with RHI or executive function. However, there was a positive relationship between RHI and FA in the genu and body of the corpus callosum. In addition, higher RHI and FA were each associated with better executive task performance. Tractography was used to localize the WM tracts associated with RHI to specific portions of cortex. Results indicated that the RHI-FA relationship observed in the corpus callosum primarily involved tracts interconnecting frontal regions, including the superior frontal gyrus (SFG) and frontopolar cortex, linked with executive function. These findings suggest that superior endothelial function may help to attenuate age-related declines in WM microstructure in portions of the corpus callosum that interconnect prefrontal brain regions involved in executive function

33354 Efficacy of apremilast in patients with mild to moderate psoriasis assessed by the physician global assessment and body surface area composite tool: Post hoc analysis from ADVANCE

Background: In ADVANCE (NCT03721172), apremilast 30 mg BID (APR) demonstrated significantly greater sPGA response vs. PBO at Week 16 (22% vs. 4%; P \u3c.0001) in patients with mild-to-moderate psoriasis. The Physician Global Assessment and Body Surface Area Composite Tool (PGA × BSA) is a simple, sensitive measure of psoriasis severity for patients with BSA\u3c10%. We performed a post hoc analysis of the efficacy results from ADVANCE using the PGA×BSA. Methods: This current post hoc analysis included all randomized patients. Missing data were imputed by multiple imputation. PGAxBSA-50/75/90 was 50%, 75% and 90% improvement in PGAxBSA from baseline. Results: Of 595 randomized patients (APR: 297; PBO: 298), baseline characteristics were similar for mean BSA (APR: 6.4; PBO: 6.3), sPGA score 2 (APR 31%; PBO: 31%), sPGA score 3 (APR: 69%; PBO: 70%), and mean PGA×BSA (APR: 17.6; PBO: 17.5). At Week 16, significantly more patients achieved PGAxBSA-50/75/90 response with APR vs. PBO: PGA×BSA-50, 67% vs. 26% (P \u3c.0001), difference 41%, 95%CI (32.7,48.5) PGA×BSA-75, 46% vs. 13% (P \u3c.0001), difference 33%, 95%CI (25.8,40.2) PGA×BSA-90, 27% vs. 3% (P \u3c.0001), difference 24%, 95%CI (18.3,29.6) A significant improvement from baseline at Week 16 in PGA×BSA was observed with APR vs PBO: Mean % change (SE) in PGA×BSA, -51.8 (4.2) vs. 1.97 (4.3); difference (95%CI): -53.8 (-65.4, -42.2), P \u3c.0001. Conclusions: The PGA×BSA Composite Tool appeared to be a sensitive and a relevant measure for mild-to-moderate psoriasis that showed significantly greater treatment differences at 50%, 75%, and 90% response thresholds at Week 16 with APR compared with PBO in ADVANCE

Non-Fasting High-Density Lipoprotein Is Associated With White Matter Microstructure in Healthy Older Adults

A growing body of evidence indicates that biomarkers of cardiovascular risk may be related to cerebral health. However, little is known about the role that non-fasting lipoproteins play in assessing age-related declines in a cerebral biomarker sensitive to vascular compromise, white matter (WM) microstructure. High-density lipoprotein cholesterol (HDL-C) is atheroprotective and low-density lipoprotein cholesterol (LDL-C) is a major atherogenic lipoprotein. This study explored the relationships between non-fasting levels of cholesterol and WM microstructure in healthy older adults. A voxelwise and region of interest approach was used to determine the relationship between cholesterol and fractional anisotropy (FA). Participants included 87 older adults between the ages of 59 and 77 (mean age = 65.5 years, SD = 3.9). Results indicated that higher HDL-C was associated with higher FA in diffuse regions of the brain when controlling for age, sex, and body mass index (BMI). HDL-C was also positively associated with FA in the corpus callosum and fornix. No relationship was observed between LDL-C and FA. Findings suggest that a modifiable lifestyle variable associated with cardiovascular health may help to preserve cerebral WM

Non-fasting High-Density Lipoprotein Is Associated With White Matter Microstructure in Healthy Older Adults

A growing body of evidence indicates that biomarkers of cardiovascular risk may be related to cerebral health. However, little is known about the role that non-fasting lipoproteins play in assessing age-related declines in a cerebral biomarker sensitive to vascular compromise, white matter (WM) microstructure. High-density lipoprotein cholesterol (HDL-C) is atheroprotective and low-density lipoprotein cholesterol (LDL-C) is a major atherogenic lipoprotein. This study explored the relationships between non-fasting levels of cholesterol and WM microstructure in healthy older adults. A voxelwise and region of interest approach was used to determine the relationship between cholesterol and fractional anisotropy (FA). Participants included 87 older adults between the ages of 59 and 77 (mean age = 65.5 years, SD = 3.9). Results indicated that higher HDL-C was associated with higher FA in diffuse regions of the brain when controlling for age, sex, and body mass index (BMI). HDL-C was also positively associated with FA in the corpus callosum and fornix. No relationship was observed between LDL-C and FA. Findings suggest that a modifiable lifestyle variable associated with cardiovascular health may help to preserve cerebral WM

26085 Key efficacy and safety of apremilast in patients with mild to moderate plaque psoriasis in the phase 3 ADVANCE trial

Background: In ADVANCE, apremilast 30 mg BID (APR) demonstrated efficacy in mild-to-moderate psoriasis vs placebo (PBO). We report subgroup analyses by baseline psoriasis-involved BSA (≤5%, \u3e5%). Methods: Biologic-naive adults with mild-to-moderate psoriasis (sPGA 2-3, BSA 2%-15%, PASI 2-15) inadequately controlled with or intolerant to ≥1 topical were randomized to APR or PBO for 16 weeks. At Week 16, endpoints were compared between treatment groups and by baseline BSA. Results: At baseline, 284 patients had BSA ≤5% (APR: 143; PBO: 141); 311 had BSA \u3e5% (APR: 154; PBO: 157). Overall, a greater proportion of APR patients achieved the primary endpoint, sPGA response (score 0/1 [clear/almost clear] with ≥2-point reduction at Week 16) vs PBO (21.6% vs 4.1%, P 5%: 54.6% vs 14.9%, P 5%: 45.4% vs 17.6%, P 5%: 50.6% vs 19.2%, P 5%: 11.0 vs 10.0 DLQI 5-point improvement (baseline DLQI \u3e5): - BSA≤5%: 56.6% vs 31.2%, P =.0002 - BSA\u3e5%: 64.4% vs 36.4%, P ˂.0001. Conclusions: Greater proportions of patients achieved efficacy outcomes and greater improvements in QOL with APR vs PBO. Comparable improvements were observed between mild and moderate subgroups