Claudia Jacova

Effects of long-term blood pressure lowering and dual antiplatelet treatment on cognitive function in patients with recent lacunar stroke: a secondary analysis from the SPS3 randomised trial

BACKGROUND The primary outcome results for the SPS3 trial suggested that a lower systolic target blood pressure (<130 mm Hg) might be beneficial for reducing the risk of recurrent stroke compared with a higher target (130-149 mm Hg), but that the addition of clopidogrel to aspirin was not beneficial compared with aspirin plus placebo. In this prespecified secondary outcome analysis of the SPS3 trial, we aimed to assess whether blood pressure reduction and dual antiplatelet treatment affect changes in cognitive function over time in patients with cerebral small vessel disease. METHODS In the SPS3 trial, patients with recent (within 6 months) symptomatic lacunar infarcts from 81 centres in North America, Latin America, and Spain were randomly assigned, in a two-by-two factorial design, to target levels of systolic blood pressure (1:1; 130-149 mm Hg vs <130 mm Hg; open-label) and to a once-daily antiplatelet treatment (1:1; aspirin 325 mg plus clopidogrel 75 mg vs aspirin 325 mg plus placebo; double-blind). For this analysis, the main cognitive outcome was change in Cognitive Abilities Screening Instrument (CASI) during follow-up. Patients were tested annually for up to 5 years, during which time the mean difference in systolic blood pressure was 11 mm Hg (SD 16) between the two targets (138 mm Hg vs 127 mm Hg at 1 year). We used linear mixed models to compare changes in CASI Z scores over time. The SPS3 trial is registered with ClinicalTrials.gov, number NCT00059306. FINDINGS The study took place between March 23, 2003, and April 30, 2012. 2916 of 3020 SPS3 participants (mean age 63 years [SD 11]) with CASI scores at study entry were included in the analysis, with a median follow-up of 3·0 years (IQR 1·0-4·9). Mean changes in CASI Z scores from study entry to assessment at years 1 (n=2472), 2 (n=1968), 3 (n=1521), 4 (n=1135), and 5 (n=803) were 0·12 (SD 0·83), 0·15 (0·84), 0·16 (0·95), 0·19 (0·99), and 0·14 (1·09), respectively. Changes in CASI Z scores over time did not differ between assigned antiplatelet groups (p=0·858) or between assigned blood pressure target groups (p=0·520). There was no interaction between assigned antiplatelet groups and assigned blood pressure target groups and change over time (p=0·196). INTERPRETATION Cognitive function is not affected by short-term dual antiplatelet treatment or blood pressure reduction in fairly young patients with recent lacunar stroke. Future studies of cognitive function after stroke should be of longer duration or focus on patients with higher rates of cognitive decline. FUNDING US National Institute of Neurological Disorders and Stroke.

Gray matter changes in asymptomatic C9orf72 and GRN mutation carriers

Frontotemporal dementia (FTD) is a neurodegenerative disease with a strong genetic basis. Understanding the structural brain changes during pre-symptomatic stages may allow for earlier diagnosis of patients suffering from FTD; therefore, we investigated asymptomatic members of FTD families with mutations in C9orf72 and granulin (GRN) genes. Clinically asymptomatic subjects from families with C9orf72 mutation (15 mutation carriers, C9orf72+; and 23 non-carriers, C9orf72−) and GRN mutations (9 mutation carriers, GRN+; and 15 non-carriers, GRN−) underwent structural neuroimaging (MRI). Cortical thickness and subcortical gray matter volumes were calculated using FreeSurfer. Group differences were evaluated, correcting for age, sex and years to mean age of disease onset within the subjects family. Mean age of C9orf72+ and C9orf72− were 42.6 ± 11.3 and 49.7 ± 15.5 years, respectively; while GRN+ and GRN− groups were 50.1 ± 8.7 and 53.2 ± 11.2 years respectively. The C9orf72+ group exhibited cortical thinning in the temporal, parietal and frontal regions, as well as reduced volumes of bilateral thalamus and left caudate compared to the entire group of mutation non-carriers (NC: C9orf72− and GRN− combined). In contrast, the GRN+ group did not show any significant differences compared to NC. C9orf72 mutation carriers demonstrate a pattern of reduced gray matter on MRI prior to symptom onset compared to GRN mutation carriers. These findings suggest that the preclinical course of FTD differs depending on the genetic basis and that the choice of neuroimaging biomarkers for FTD may need to take into account the specific genes involved in causing the disease.

A randomized controlled trial of music therapy in managing behavioral symptoms in Alzheimer disease

respectively, and the mean CDR-global was 0.67 6 0.24 and 0.68 6 0.24, respectively. Mean CDR-sum of boxes was 3.95 6 1.67 at screen and 3.93 6 1.67 at baseline. There were no significant changes in mean total ADAS-Cog or CDR scores. ADAS-Cog-11 total score changes from screen to baseline ranged from a decrease of 10 points to an increase of 7 points; only 6 (14.3%) were unchanged. Additional analyses revealed that ADAS-Cog Word Recognition was poorly correlated between screen and baseline (r1⁄4 0.26) whereas Word Recall was strongly correlated (r1⁄40.62). Screen and baseline CDRglobal and CDR-sum of boxes scores also were strongly correlated (r1⁄40.67 and r1⁄40.68, respectively) with modest to high correlations for individual CDR items. Conclusions:Results suggest stability in total ADAS-Cog scores between screen and baseline with some individual ADAS-Cog items less stable compared to others. Stability also was noted between screen and baseline on functional neurobehavioral measures. These analyses demonstrated stability between the screen and baseline measures for key outcome measures in this clinical trial, which is a fundamental necessity when examining intervention and treatment effects.

Aerobic exercise increases cortical white matter volume in older adults with vascular cognitive impairment: A 6-month randomized controlled trial

Age at Baseline M 1⁄4 23.67 M 1⁄4 24.43 M 1⁄4 22.97 Estimated IQ (WTAR) M 1⁄4 110.19 M 1⁄4 110.73 M 1⁄4 109.69 MMSE Score M 1⁄4 29.48 M 1⁄4 29.50 M 1⁄4 29.45 Gender % (n) % (n) % (n) Male 44.4 (28) 46.7 (14) 42.4 (14) Female 55.6 (35) 53.3 (16) 57.6 (19) Level of Education Less then High School 3.2 (2) 6.7 (2) 0.0 (0) High School 19.0 (12) 20.0 (6) 18.2 (6) Associates Degree 7.9 (5) 13.3 (4) 3.0 (1) Current College Student 50.8 (32) 40.0 (12) 60.6 (20) Bachelors Degree 15.9 (2) 20.0 (6) 12.1 (4) Graduate Degree 3.2 (2) 0.0 (0) 2(6.1) Race / Ethnicity White (Not Hispanic) 69.8 (44) 63.3 (19) 75.8 (25) Black / African American 4.8 (3) 6.7 (2) 3.0 (1) Hispanic 11.1 (7) 6.7 (2) 15.2 (5) Asian / Pacific Islander 7.9 (5) 10.0 (3) 6.1 (2) American Indian 1.6 (1) 3.3 (1) 0.0 (0) Mixed / Multiple 4.8 (3) 10.0 (3) 0.0 (0)

Neuropsychological Performance Patterns of Adult ADHD Subtypes

Objective: Neuropsychological performance patterns associated with adult ADHD subtypes are unknown. The aim of the current systematic review was to identify and synthesize available literature regarding neuropsychological performance associated with adult ADHD subtypes. Method: Searches were completed using the databases PsycINFO and PubMed for studies published before March 2017 addressing adult ADHD subtypes and neuropsychological performance. Data characterizing the neuropsychological tests utilized in each study were obtained and sorted into eight domains. To summarize the results of all comparisons (ADHD subtype compared with control, or to each other), we counted the proportion of tests within each domain with significant group differences. Results/Conclusion: We deemed four domains informative in differentiating ADHD subtypes from controls. Of these, memory was the only domain that held promise in distinguishing ADHD-Inattentive and ADHD-Combined. Limitations of the available literature are highlighted and recommendations for future research are provided.

Erratum to: Exploring the effects of coexisting amyloid in subcortical vascular cognitive impairment.

Background: Mixed pathology, particularly Alzheimer’s disease with cerebrovascular lesions, is reported as the second most common cause of dementia. Research on mixed dementia typically includes people with a primary AD diagnosis and hence, little is known about the effects of co-existing amyloid pathology in people with vascular cognitive impairment (VCI). The purpose of this study was to understand whether individual differences in amyloid pathology might explain variations in cognitive impairment among individuals with clinical subcortical VCI (SVCI). Methods: Twenty-two participants with SVCI completed an C Pittsburgh compound B (PIB) position emission tomography (PET) scan to quantify global amyloid deposition. Cognitive function was measured using: 1) MOCA; 2) ADAS-Cog; 3) EXIT-25; and 4) specific executive processes including a) Digits Forward and Backwards Test, b) Stroop-Colour Word Test, and c) Trail Making Test. To assess the effect of amyloid deposition on cognitive function we conducted Pearson bivariate correlations to determine which cognitive measures to include in our regression models. Cognitive variables that were significantly correlated with PIB retention values were entered in a hierarchical multiple linear regression analysis to determine the unique effect of amyloid on cognitive function. We controlled for age, education, and ApoE ε4 status. Results: Bivariate correlation results showed that PIB binding was significantly correlated with ADAS-Cog (p < 0.01) and MOCA (p < 0.01); increased PIB binding was associated with worse cognitive function on both cognitive measures. PIB binding was not significantly correlated with the EXIT-25 or with specific executive processes (p > 0.05). Regression analyses controlling for age, education, and ApoE ε4 status indicated an independent association between PIB retention and the ADAS-Cog (adjusted R-square change of 15.0 %, Sig F Change = 0.03). PIB retention was also independently associated with MOCA scores (adjusted R-Square Change of 27.0 %, Sig F Change = 0.02). Conclusion: We found that increased global amyloid deposition was significantly associated with greater memory and executive dysfunctions as measured by the ADAS-Cog and MOCA. Our findings point to the important role of co-existing amyloid deposition for cognitive function in those with a primary SVCI diagnosis. As such, therapeutic approaches targeting SVCI must consider the potential role of amyloid for the optimal care of those with mixed dementia. Trial registration: NCT01027858

Cognitive performance following lacunar stroke in Spanish-speaking patients: results from the SPS3 trial

Background Cognitive impairment is frequent in lacunar stroke patients. The prevalence and pattern among Spanish-speaking patients are unknown and have not been compared across regions or with English-speaking patients. Aims The aim of this study was to characterize cognitive impairment in Spanish-speaking patients and compare it with English-speaking patients. Methods The baseline neuropsychological test performance and the prevalence of mild cognitive impairment, defined as a z-score ≤ -1·5 on memory and/or non-memory tests, were evaluated in Spanish-speaking patients in the Secondary Prevention of Small Subcortical Strokes trial. Results Out of 3020 participants, 1177 were Spanish-speaking patients residing in Latin America (n = 693), the United States (n = 121), and Spain (n = 363). Low education (zero- to eight-years) was frequent in Spanish-speaking patients (49–57%). Latin American Spanish-speaking patients had frequent post-stroke upper extremity motor impairment (83%). Compared with English-speaking patients, all Spanish-speaking patient groups had smaller memory deficits and larger non-memory/motor deficits, with Latin American Spanish-speaking patients showing the largest deficits median z-score -1·3 to −0·6 non-memory tests; ≤5·0 for Grooved Pegboard; −0·7 to −0·3 for memory tests). The prevalence of mild cognitive impairment was high and comparable with English-speaking patients in the United States and Latin American Spanish-speaking patients but not the Spanish group: English-speaking patients = 47%, Latin American Spanish-speaking patients = 51%, US Spanish-speaking patients = 40%, Spanish Spanish-speaking patients = 29%, with >50% characterized as non-amnestic in Spanish-speaking patient groups. Older age [odds ratio per 10 years =1·52, confidence interval = 1·35–1·71), lower education (odds ratio 0–4 years = 1·23, confidence interval = 0·90–1·67), being a Latin American resident (odds ratio = 1·31, confidence interval = 0·87–1·98), and post-stroke disability (odds ratio Barthel Index <95=1·89, confidence interval = 1·43–2·50) were independently associated with mild cognitive impairment. Conclusions Mild cognitive impairment in Secondary Prevention of Small Subcortical Strokes Spanish-speaking patients with recent lacunar stroke is highly prevalent but has a different pattern to that observed in English-speaking patients. A combination of socio-demographics, stroke biology, and stroke care may account for these differences.

Patients with Alzheimer disease respond differently to familiar and unfamiliar music: An fMRI study

(p1⁄40.003 for sumscore ofWMHbyone-wayANOVAwithLSDmultiple comparison). The WMH showed a significant correlation with age (r1⁄4 0.453, p<0.001), UPDRS total (r1⁄40.259, p1⁄40.017), MMSE (r1⁄40.558, p1⁄40.000), SOB of CDR (r1⁄40.580, p<0.001), andmanyof the cognitive domains. Themultivariate linear regression model revealed that the WMH was independently associated with cognitive impairment in patientswithDLBandDLB-MCI, regardless of age, gender, education status, andvascular risk factors (p1⁄40.037 for MMSE, p1⁄40.023 for CDR and p1⁄40.035 for SOB of CDR). Conclusions: Our results demonstrated that WMH in DLB group seems more intense than that in DLB-MCI group. These findings reflect that WMH might be associated with cognitive decline in patients with DLB, regardless of age, gender, education status and vascular risk factors. Also this study suggests that other nonvascular factors contribute to the progression of cognitive decline in patients with DLB. The special attentions should be paid on WMH in DLB although the exact pahtophysiologic mechanisms are unclear.