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Multiple sclerosis is characterized by areas of myelin destruction within the brain. These patchy areas, called plaques, generally surround blood vessels or are adjacent to the ventricles. Previously, seven cases have been described in which the appearance of multiple-sclerosis-like disease was associated with infection with the human immunodeficiency virus (HIV). The authors now present the cases of two HIV-positive men who developed a rapidly fatal, fulminating neurological disease which strongly resembled classic multiple sclerosis (MS). One man was a homosexual, and the other had no known risk factors for HIV infection. In one patient the onset of disease was heralded by the appearance of seventh cranial nerve palsy, right hemiparesis, and right hypesthesia. In the other, left hemiparesis, weight loss, impotence, myalgia, and diarrhea were the initial symptoms. In both cases, computed tomography revealed low-density nonenhancing lesions. Both men deteriorated rapidly; one died within one month of the onset of symptoms and the other died within two months. In both cases, an autopsy was performed, and the brain revealed lesions within the white matter with the histological features of multiple sclerosis plaques. The breakdown of myelin and the presence of inflammatory cells in 'cuffs' ringing the blood vessels were clearly visible under the microscope. The plaques showed no evidence of the presence of HIV when immunologically stained. The histopathological features of the disease were compatible with a diagnosis of multiple sclerosis. However, the rapid onset and equally rapid deterioration and death of the patients indicate that this cannot be the entire picture. The cases suggest that it may be possible for HIV infection, which frequently affects the brain, to result in an MS-like disease in some patients. (Consumer Summary produced by Reliance Medical Information, Inc.)

Objective: To determine whether years of education and the ε4 risk allele at APOE influence β-amyloid (Aβ) pathology similarly in asymptomatic individuals with a family history of sporadic Alzheimer disease (AD) and presymptomatic autosomal dominant AD mutation carriers., Methods: We analyzed cross-sectional data from 106 asymptomatic individuals with a parental history of sporadic AD (PREVENT-AD cohort; age 67.28 ± 4.72 years) and 117 presymptomatic autosomal dominant AD mutation carriers (DIAN cohort; age 35.04 ± 9.43 years). All participants underwent structural MRI and Aβ-PET imaging. In each cohort we investigated the influence of years of education, APOE ε4 status, and their interaction on Aβ-PET., Results: Asymptomatic individuals with a parental history of sporadic AD showed increased Aβ burden associated with APOE ε4 carriage and lower level of education, but no interaction between these. Presymptomatic mutation carriers of autosomal dominant AD showed no relation between APOE ε4 and Aβ burden, but increasing level of education was associated with reduced Aβ burden. The association between educational attainment and Aβ burden was similar in the 2 cohorts., Conclusions: While the APOE ε4 allele confers increased tendency toward Aβ accumulation in sporadic AD only, protective environmental factors, like increased education, may promote brain resistance against Aβ pathology in both sporadic and autosomal dominant AD., (© 2020 American Academy of Neurology.)

Objective: To investigate relationships between flortaucipir (FTP) uptake, age, and established Alzheimer disease (AD) markers in asymptomatic adults at increased risk of AD., Methods: One-hundred nineteen individuals with a family history of AD (Presymptomatic Evaluation of Experimental or Novel Treatments of Alzheimer's Disease [PREVENT-AD] cohort, mean age 67 ± 5 years) underwent tau-PET ([ 18 F]FTP), β-amyloid (Aβ)-PET ([ 18 F]NAV4694 [NAV]), and cognitive assessment. Seventy-four participants also had CSF phosphorylated tau and total tau data available. We investigated the association between age and FTP in this relatively young cohort of older adults. We also investigated regional FTP standardized uptake value ratio (SUVR) differences between Aβ-positive and Aβ-negative individuals and regional correlations between FTP and NAV retention. In cortical regions showing consistent associations across analyses, we assessed whether FTP was in addition related to CSF tau and cognitive performance. Lastly, we identified the lowest FTP value at which associations with Aβ-PET, CSF, and cognition were detectable., Results: Increased age was associated only with amygdala and transverse temporal lobe FTP retention. Aβ-positive individuals had higher FTP SUVR values in several brain regions, further showing correlation with NAV load through the cortex. Increased FTP SUVRs in medial temporal regions were associated with increased CSF tau values and worse cognition. The SUVRs at which associations between entorhinal FTP SUVR and other AD markers were first detected differed by modality, with a detection point of 1.12 for CSF values, 1.2 for Aβ-PET, and 1.4 for cognition., Conclusions: Relatively low FTP-PET SUVRs are associated with pathologic markers of AD in the preclinical phase of the disease. Adjustment in the tau threshold should be considered, depending on the purpose of the tau classification., (© 2020 American Academy of Neurology.)

Objective: To evaluate the safety and efficacy of low-dose naproxen for prevention of progression in presymptomatic Alzheimer disease (AD) among cognitively intact persons at risk., Methods: Investigation of Naproxen Treatment Effects in Pre-symptomatic Alzheimer's Disease (INTREPAD), a 2-year double-masked pharmaco-prevention trial, enrolled 195 AD family history-positive elderly (mean age 63 years) participants screened carefully to exclude cognitive disorder (NCT-02702817). These were randomized 1:1 to naproxen sodium 220 mg twice daily or placebo. Multimodal imaging, neurosensory, cognitive, and (in ∼50%) CSF biomarker evaluations were performed at baseline, 3, 12, and 24 months. A modified intent-to-treat analysis considered 160 participants who remained on-treatment through their first follow-up examination. The primary outcome was rate of change in a multimodal composite presymptomatic Alzheimer Progression Score (APS)., Results: Naproxen-treated individuals showed a clear excess of adverse events. Among treatment groups combined, the APS increased by 0.102 points/year (SE 0.014; p < 10 -12 ), but rate of change showed little difference by treatment assignment (0.019 points/year). The treatment-related rate ratio of 1.16 (95% confidence interval 0.64-1.96) suggested that naproxen does not reduce the rate of APS progression by more than 36%. Secondary analyses revealed no notable treatment effects on individual CSF, cognitive, or neurosensory biomarker indicators of progressive presymptomatic AD., Conclusions: In cognitively intact individuals at risk, sustained treatment with naproxen sodium 220 mg twice daily increases frequency of adverse health effects but does not reduce apparent progression of presymptomatic AD., Classification of Evidence: This study provides Class I evidence that, for people who are cognitively intact, low-dose naproxen does not significantly reduce progression of a composite indicator of presymptomatic AD., (Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Objective: To assess odor identification (OI) as an indicator of presymptomatic Alzheimer disease (AD) pathogenesis in cognitively normal aging individuals at increased risk of AD dementia., Methods: In 274 members of the PREVENT-AD cohort of healthy aging persons with a parental or multiple-sibling history of AD dementia, we assessed the cross-sectional association of OI with potential indicators of presymptomatic AD. Some 101 participants donated CSF, thus enabling assessment of AD pathology with the biomarkers total tau (t-tau), phospho-tau (P 181 -tau), and their ratios with β-amyloid (Aβ 1-42 ). Adjusted analyses considered age, cognition, APOE ε4 status, education, and sex as covariates. We measured OI using the University of Pennsylvania Smell Identification Test and cognitive performance using the Repeatable Battery for Assessment of Neuropsychological Status. Standard kits provided assays of the AD biomarkers. Analyses used robust-fit linear regression models., Results: Reduced OI was associated with lower cognitive score and older age, as well as increased ratios of CSF t-tau and P 181 -tau to Aβ 1-42 (all p < 0.02). However, the observed associations of OI with age and cognition were unapparent in adjusted models that restricted observations to CSF donors and included AD biomarkers. OI showed little association with CSF Aβ 1-42 alone except in APOE ε4 carriers having lowest-quartile Aβ 1-42 levels., Conclusions: These findings from healthy high-risk older individuals suggest that OI reflects degree of preclinical AD pathology, while its relationships with age and cognition result from the association of these latter variables with such pathology. Diminished OI may be a practical and affordable biomarker of AD pathology., (Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)