%0 Journal Article %J J Alzheimers Dis %D 2019 %T APOE ɛ4 Carriers Show Delayed Recovery of Verbal Memory and Smaller Entorhinal Volume in the First Year After Ischemic Stroke. %A Werden, Emilio %A Khlif, Mohamed Salah %A Bird, Laura J %A Cumming, Toby %A Bradshaw, Jennifer %A Khan, Wasim %A Pase, Matthew %A Restrepo, Carolina %A Veldsman, Michele %A Egorova, Natalia %A Patel, Sheila K %A Gottlieb, Elie %A Brodtmann, Amy %X

BACKGROUND: The apolipoprotein E (APOE) gene ɛ4 allele is a risk factor for Alzheimer's disease and cardiovascular disease. However, its relationship with cognition and brain volume after stroke is not clear.

OBJECTIVE: We compared cognition and medial temporal lobe volumes in APOEɛ4 carriers and non-carriers in the first year after ischemic stroke.

METHODS: We sampled 20 APOEɛ4 carriers and 20 non-carriers from a larger cohort of 135 ischemic stroke participants in the longitudinal CANVAS study. Participants were matched on a range of demographic and stroke characteristics. We used linear mixed-effect models to compare cognitive domain z-scores (attention, processing speed, executive function, verbal and visual memory, language, visuospatial function) and regional medial temporal lobe volumes (hippocampal, entorhinal cortex) between groups at each time-point (three, 12-months post-stroke), and within groups across time-points. APOE gene single nucleotide polymorphisms (SNPs; rs7412, rs429358) were genotyped on venous blood.

RESULTS: APOEɛ4 carriers and non-carriers did not differ on any demographic, clinical, or stroke variable. Carriers performed worse than non-carriers in verbal memory at three months post-stroke (p = 0.046), but were better in executive function at 12 months (p = 0.035). Carriers demonstrated a significant improvement in verbal memory (p = 0.012) and executive function (p = 0.015) between time-points. Non-carriers demonstrated a significant improvement in visual memory (p = 0.0005). Carriers had smaller bilateral entorhinal cortex volumes (p <  0.05), and larger-right-sided and contralesional hippocampal volumes, at both time-points (p <  0.05).

CONCLUSION: APOE ɛ4 is associated with delayed recovery of verbal memory function and reduced entorhinal cortex volumes in the first year after ischemic stroke.

%B J Alzheimers Dis %V 71 %P 245-259 %8 2019 Sep 3 %G eng %N 1 %R 10.3233/JAD-190566 %0 Journal Article %J J Alzheimers Dis %D 2016 %T Diagnostic Distortions: A Case Report of Progressive Apraxia of Speech. %A Brodtmann, Amy %A Pemberton, Hugh %A Darby, David %A Vogel, Adam P %X

Apraxia of speech (AOS) can be the presenting symptom of neurodegenerative disease. The position of primary progressive AOS in the nosology of the dementias is still controversial. Despite seeing many specialists, patients are often misdiagnosed, in part due to a lack of quantitative measures of speech dysfunction. We present a single case report of a patient presenting with AOS, including acoustic analysis, language assessment, and brain imaging. A 52-year-old woman presenting with AOS had remained undiagnosed for 6 years despite seeing 8 specialists. Results of her MRI scans, genetic testing, and computerized speech analysis are provided. AOS is an underdiagnosed clinical syndrome causing great distress to patients and families. Using acoustic analysis of speech may lead to improved diagnostic accuracy. AOS is a complex entity with an expanding phenotype, and quantitative clinical measures will be critical for detection and to assess progression.

%B J Alzheimers Dis %V 53 %P 79-83 %8 2016 Apr 19 %G eng %N 1 %1 http://www.ncbi.nlm.nih.gov/pubmed/27104903?dopt=Abstract %R 10.3233/JAD-160069 %0 Journal Article %J J Alzheimers Dis %D 2016 %T A Phase IIa Randomized Control Trial of VEL015 (Sodium Selenate) in Mild-Moderate Alzheimer's Disease. %A Malpas, Charles B %A Vivash, Lucy %A Genc, Sila %A Saling, Michael M %A Desmond, Patricia %A Steward, Christopher %A Hicks, Rodney J %A Callahan, Jason %A Brodtmann, Amy %A Collins, Steven %A Macfarlane, Stephen %A Corcoran, Niall M %A Hovens, Christopher M %A Velakoulis, Dennis %A O'Brien, Terence J %X

BACKGROUND: There is increasing interest in targeting hyperphosphorylated tau (h-tau) as a disease modifying approach for Alzheimer's disease (AD). Sodium selenate directly stimulates the activity of PP2A, the main enzyme responsible for h-tau dephosphorylation in the brain.

OBJECTIVE: This study assessed the safety and tolerability of 24-week treatment with VEL015 (sodium selenate) in AD. Investigating the effects of VEL015 on cognitive, CSF, and neuroimaging biomarkers of AD were secondary, exploratory objectives. Data were used to identify biomarkers showing most promise for use in subsequent efficacy trials.

METHODS: A 24-week, multicenter, Phase IIa, double-blinded randomized controlled trial. Forty patients aged ≥55 y with mild-moderate AD (MMSE 14-26) were randomized to supranutritional (VEL015 10 mg tds [n = 20]) and control (VEL015 320μg tds [n = 10] or placebo [n = 10]) groups. Patients were regularly monitored for safety, adverse events (AEs), and protocol compliance. Exploratory biomarkers included cognitive tests, neuroimaging (diffusion MR), and CSF (p-tau, t-tau, and Aβ1-42).

RESULTS: Thirty-six (90%; [supranutritional n = 18, control/placebo n = 18]) patients completed the trial. There were no differences in the incidence of specific AEs between groups. Only one secondary biomarker, diffusion MR measures, showed group differences, with less deterioration in the supranutritional group (p < 0.05).

CONCLUSION: Treatment with VEL015 at doses up to 30 mg per day for 24 weeks was safe and well-tolerated in patients with AD. Diffusion MR measures appear to be the most sensitive biomarkers to assess disease progression over 24 weeks.

%B J Alzheimers Dis %V 54 %P 223-32 %8 2016 Jul 22 %G eng %N 1 %1 http://www.ncbi.nlm.nih.gov/pubmed/27447428?dopt=Abstract %R 10.3233/JAD-160544