Profile reliability of cognitive ability subscores in a referred sample.

Galantamine (Reminyl^®), a novel agent with a dual mode of action, modulates nicotinic acetylcholine receptors and inhibits acetylcholinesterase. Galantamine has consistently demonstrated a broad range of beneficial effects and has shown sustained benefits in cognitive and functional abilities for at least 12 months in patients with mild-to-moderate Alzheimer’s disease (AD). As pivotal studies demonstrating the efficacy of cholinergic drugs were designed to exclude patients with severer AD, many patients with the advanced stage of this condition are currently not treated due to the lack of demonstrated efficacy in clinical trials. We aimed to investigate whether there was any evidence for the benefits of galantamine in patients with severer disease, by performing a post hoc analysis using data extracted from the population of the two long-term galantamine studies. We evaluated the efficacy of galantamine in patients with ‘advanced moderate’ AD. ‘Advanced moderate’ patients were those with baseline Mini Mental State Examination (MMSE) scores ≤14 or Alzheimer’s Disease Assessment Scale – cognitive subscale (ADAS-cog) scores >30. These patients were compared with matched controls who received placebo in a different historical study. Cognitive abilities (assessed using the ADAS-cog scale) of ‘advanced moderate’ AD patients receiving galantamine for 12 months were maintained at baseline levels after 12 months, and significantly improved over those of placebo patients (p < 0.001). Of the ‘advanced moderate’ patients receiving galantamine, 51% with baseline ADAS-cog of >30 maintained or improved their ADAS-cog scores over baseline values, compared with 13% receiving placebo (p < 0.001). In the subgroup of ‘advanced moderate’ patients with baseline MMSE ≤14, 48% of those receiving galantamine and 4% of those receiving placebo maintained or improved their ADAS-cog scores at 12 months (p = 0.001). In both subgroups, the treatment difference (galantamine vs. historical placebo) amounted to approximately 10 points on the ADAS-cog scale. Functional abilities, as assessed using the Disability Assessment for Dementia scale, remained significantly superior in galantamine-treated patients compared with historical placebo-treated patients at 12 months (p < 0.001). In conclusion, galantamine offered sustained efficacy to patients with ‘advanced moderate’ AD, confirming the benefits seen in published studies of patients with mild-to-moderate AD. This drug has potential for broader use in clinical practice.

The Medical Outcomes Study HIV (MOS-HIV) Health Survey is a widely used instrument to assess quality of life in HIV-1-infected individuals. Its cognitive functional status subscale measures functional status owing to neuropsychological (NP) impairment. To determine the concurrent validity of the Dutch four-item MOS-HIV cognitive functional status subscale and its clinical significance in predicting NP test performance. Cross-sectional analysis of baseline data collected between October, 1994, and March, 1997, in the Netherlands and in Flanders, Belgium. A total of 85 HIV-1-infected homosexual men who participated in an ongoing longitudinal research project designed to study the effects of a support group. The MOS-HIV cognitive functional status subscale showed significant associations with NP test performance overall and, specifically, with the domains of abstraction, language and visuospatial abilities, controlling for CD4 cell count and Centers for Disease Control and Prevention (CDC) clinical disease stage. A trend toward significance was also found in the memory domain. To our knowledge, this is the first report of a cognitive functional status subscale used with HIV-1-infected subjects in a language other than English. The MOS-HIV cognitive functional status subscale seems particularly sensitive to changes in NP test performance in early HIV-1 infection. These results suggest the potential for clinical utility of a brief functional status self-report measure related to cognitive abilities in early HIV-1 infection for the screening and diagnosis of HIV-1 associated cognitive-motor disorders.

Family empowerment in families of young children with cerebral palsy (CP) is an important consideration because the first few years of life can be overwhelming for parents. The purpose of this research was to investigate the relationship between family empowerment, fine motor (FM), gross motor (GM) and cognitive development in children with CP who were under 3 years of age. Forty-one children with a mean age of 23.8 months participated in this study. The Family Empowerment Scale (FES) was completed by the participants' parents, whereas the FM, GM and cognitive subscales of the Bayley Scales of Infant and Toddler Development Third edition (B-III) were administered by physical therapists. Statistically significant positive correlations were found between the FES total and B-III raw scores for FM, GM and cognitive subscales with coefficients ranging from 0.35 to 0.41. Significant relationships were also found between the FES Community subscale and the B-III FM, GM and cognitive subscales. This study provides evidence of a relationship between family empowerment and FM, GM and cognitive abilities in young children with CP, with a greater severity of impairments related to lower levels of caregiver empowerment.

Pilot Randomized Controlled Trial of Self-Regulation in Promoting Function in Acute Poststroke Patients

IntroductionPatients with Alzheimer's disease (AD) are currently treated with cholinesterase inhibitors, such as galantamine, without actual knowledge of its concentration in plasma. Our objective was to analyse potential relationships between galantamine concentration, galantamine dose, socio-demographic characteristics, body weight, body mass index (BMI), and treatment response.MethodsEighty-four patients with AD recruited from the Memory Clinic, Malmö, Sweden, and treated with galantamine were included in the study. Efficacy measures, including cognition (Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-cog)) and instrumental activities of daily living (IADL), were evaluated at baseline, 2 months after treatment initiation (MMSE only) and semi-annually over 3 years. At these assessments, blood samples were obtained for the analysis of the galantamine concentration, and body weight, BMI, drug dose and time from drug intake were recorded.ResultsAll patients had a measurable concentration of galantamine at all assessments. The mean plasma concentration of the drug exhibited a positive linear association with dose (r = 0.513, P < 0.001). The dose did not differ between sexes. Negative linear associations between the galantamine plasma concentration and BMI (r = -0.454, P = 0.001) or body weight (r = -0.310, P = 0.034) were found exclusively in the male group. When mixed-effects models were used, the dose of galantamine (P < 0.001), time from drug intake (P < 0.001), and BMI (P = 0.021) or weight (P = 0.002) were factors that predicted the concentration, whereas sex, age, and cognitive and functional changes were not.ConclusionsHigh compliance to galantamine treatment was found among all patients in this naturalistic AD study. The impact of BMI or body weight on the plasma concentration of galantamine was important only among males. No relationship was observed between concentration and short-term treatment response or progression rate in terms of cognitive and functional abilities.

Alzheimer's disease (AD) is characterized by amyloid-β plaques, neurofibrillary tangles, and regional cerebral glucose hypometabolism. Providing an alternative metabolic substrate, such as ketone bodies, may be a viable therapeutic option. The objective was to determine the efficacy and safety of the AC-1204 formulation of caprylic triglyceride administered daily for 26 weeks in APOE4 non-carrier participants with mild-to-moderate AD. In a double-blind, placebo-controlled, randomized study (AC-12-010, NOURISH AD, NCT01741194), 413 patients with mild-to-moderate probable AD were stratified by APOE genotype and randomized (1 : 1) to receive either placebo or AC-1204 for 26 weeks. The primary outcome was the change from baseline to week 26 on the 11-item Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-Cog11) among APOE4 non-carriers. The key secondary outcome was the change from baseline to week 26 in the Alzheimer's Disease Cooperative Study - Clinician's Global Impression of Change scale. Administration of AC-1204 was safe and well-tolerated. Mean changes from baseline in the primary outcome at 26 weeks in ADAS-Cog11 for placebo (n = 138) was 0.0 and for AC-1204 (n = 137) was 0.6 (LS differences of mean - 0.761, p = 0.2458) and secondary outcome measures failed to detect any drug effects. The AC-1204 formulation of caprylic triglyceride failed to improve cognition or functional ability in subjects with mild-to-moderate AD. The lack of efficacy observed in this study may have several contributing factors including a lower ketone body formation from AC-1204 than expected and a lack of decline in the patients receiving placebo.

BackgroundRepetitive transcranial magnetic stimulation (rTMS) may improve cognition in patients with Alzheimer’s disease (AD). rTMS therapy is currently limited by the relative short duration and the uncertainty on the most appropriate brain target area. AD patients primarily show alterations of the default mode network (DMN), a brain functional network for which the precuneus (PC) is a key node.MethodWe hypothesized that a long‐term 6 month course of rTMS applied over the precuneus could modify cognitive functions in patients with mild‐to‐moderate AD, by restoring cortical activity in the target network. To test this hypothesis we performed a randomized, double‐blind, sham‐controlled, phase II, 24‐weeks trial (NCT03778151). The primary outcome measure was change from baseline to week 24 of the Clinical Dementia Rating Scale–Sum of Boxes (CDR‐SOB). Secondary outcomes included score changes in the Alzheimer’s Disease Assessment Scale– Cognitive Subscale (ADAS‐Cog)11, Mini Mental State Examination (MMSE) and Alzheimer’s Disease Cooperative Study–Activities of Daily Living scale (ADCS‐ADL).Personalization of treatment and monitoring of cortical activity changes were refined by combining TMS and electroencephalography (TMS‐EEG).ResultWe found that AD patients treated with PC‐rTMS showed almost no decline in the CDR‐SB score, showing a clear advantage in terms of cognitive functions and functional abilities as compared to the sham group. rTMS induced in parallel remarkable changes in cortical activity, as demonstrated by TMS‐EEG recordings.Conclusion24 weeks of PC‐ rTMS may slow down cognitive and functional decline in AD patients by enhancing brain plasticity. Non‐invasive brain stimulation of the DMN could represent a novel therapeutic approach in AD patients.

Intro: Results from several epidemiologic studies suggest that prenatal air pollution exposure, particularly from traffic sources, increases risk for autism spectrum disorder (ASD). We examined the relationship of prenatal diesel exhaust exposure with measurements of cognitive ability and early autistic traits in Early Autism Risk Longitudinal Investigation (EARLI). Methods: EARLI is an enriched-for-high-familial-ASD-risk pregnancy cohort with longitudinal follow-up of infants through 36 months. Cognitive ability was assessed at 6 and 12 months using the Mullen Scales of Early Learning (MSEL). The Autism Observational Scales for Infants (AOSI) was administered at 6 and 12 months to assess the presence of early autistic traits. We quantified hemoglobin (Hb) adducts of 1-nitropyrene (a diesel exhaust specific compound) in 235 mid-pregnancy maternal blood samples using HPLC-MS-MS. The relationship between the adduct and outcome was examined using linear regression. Analyses were adjusted for season of sample collection and study site (Philadelphia, Baltimore, Sacramento, San Francisco). Results: Level of the Hb adduct was not associated with MSEL composite or cognitive scores at 6 months. At 12 months, a 2 standard deviation (SD) increase in adduct level was associated with poorer performance on the MSEL overall (beta= -4.19, p=0.05) and on the cognitive subscale (-8.73, 0.05). When stratified by study site, increasing adduct level was associated with poorer MSEL overall only in the San Francisco site (-7.16, 0.03) after adjusting for season. No associations were found between the adduct and AOSI score. Conclusion: Preliminary results suggest that increasing diesel exhaust exposure during pregnancy may result in decreased overall cognitive ability at 12 months of age. Further analyses of adduct measures with additional longitudinal outcome data are needed to understand if associations with ASD may be present.

This retrospective analysis assessed the efficacy of metrifonate in the treatment of mild to moderate Alzheimer’s disease (AD). Those four studies meeting Food and Drug Administration guidelines for establishing the efficacy of an AD therapeutic agent were pooled for further analysis. Data were included from all patients valid for the intent-to-treat analyses (last observation carried forward). Patients received once daily placebo (n = 550), metrifonate 30–60 mg (by weight, n = 769) or 60/80 mg (by weight, n = 197). Metrifonate 60/80 mg significantly improved the cognitive abilities [AD Assessment Scale – Cognitive Subscale (ADAS-Cog), p = 0.0001; Mini Mental State Examination (MMSE), p = 0.0001], psychiatric and behavioral disturbances (Neuropsychiatric Inventory, p = 0.039; ADAS – Noncognitive Subscale, p = 0.0001), performance of instrumental and basic activities of daily living (Disability Assessment for Dementia, p = 0.0002) and global status (Clinician’s Interview-Based Impression of Change with Caregiver Input, p = 0.0001) of AD patients when compared with placebo. Metrifonate effects across these domains were dose related. Metrifonate 60/80 mg significantly improved the cognitive performance relative to both placebo and to baseline as evaluated by both the ADAS-Cog and the MMSE. Metrifonate is the first cholinesterase inhibitor consistently shown under prospective, placebo-controlled conditions to improve significantly behavior in addition to cognition, function in activities of daily living and global functional status of patients with mild to moderate AD.

Total Daily Activity is Associated With Cognition in Older Persons

P4-333: Cogtest is more sensitive than the ADAS-Cog in detecting change in clinical trials of early Alzheimer's disease

Objective:General cognitive ability (g), a latent variable derived from cognitive data, can predict life outcomes (e.g., educational attainment and occupational success) among neurologically healthy individuals. The value of g for predicting post-stroke functional outcomes is unknown. We addressed this gap here.Method:We derived g using exploratory structural equation modeling of 15 neuropsychological tests administered to 112 patients with stroke, 69 of whom also had functional outcome data (42 men; mean age = 53.23 years (SD = 10.54)). We used logistic regressions to compare g and individual tests in terms of their ability to predict the Functional Assessment Measure (FAM) and the Functional Independence Measure (FIM; motor and cognitive subscales) at 12 months post-stroke.Results:g was a statistically significant predictor of FAM (X2 = 6.86, p = 0.013) and the cognitive (X2 = 11.48, p = 0.002) but not motor FIM subscale (X2 = 0.93, p = 0.154). Individual tests varied widely in terms of predictive utility (X2 range: 0.07–21.03), with the most robust predictors being measures of visuospatial functions.Conclusions:Acute measures of cognition, including g, can predict functional independence 12 months after stroke. g and visuospatial ability measures were the most robust predictors.

Background: Many South African learners seem unprepared for formal education, and a need for intervention during early childhood has been identified. Aim: The present study explored the effect of infant exposure to an early childhood development programme aimed at the sensory developmental stage of the infant’s brain. Setting: Participants were recruited through local baby clinics and nursery schools in the Western Cape. Participants were from the middle-income sector and the sample consisted of 63 infants between the ages of 3 and 12 months – gender representation was approximately equal and 17% of the infants were of mixed race, 8% black and 75% white. Methods: A pretest–posttest design was used involving an intervention group (N = 29) and a control group (N = 34) of infants. There was no known bias in group allocation. Intervention was provided in the form of the Numbers in Nappies programme and cognitive performance was assessed with the BSID (III) before and after the intervention for both groups. Results: The intervention group showed theory expectant increases, most notably on the Cognitive Scale and the Social-Emotional Scale of the BSID (III). The performance of the intervention and the control group on the cognitive subscales (Cognitive, Language and Motor) was compared before and after the intervention. The only significant difference was on the Cognitive Scale after the intervention. Conclusion: The findings indicate that appropriate intervention taps into the cognitive processing potential of infants, thus increasing their cognitive ability and enhancing their social–emotional functioning. The stimulation provided by parents and primary caregivers is essential in enhancing this experience-dependent development and the Numbers in Nappies programme provides a cost-effective intervention suitable for a home environment.

Music Therapy for Motor and Nonmotor Symptoms of Parkinson's Disease: A Prospective, Randomized, Controlled, Single-Blinded Study.

Functional independence measure predicts the outcome of clean intermittent catheterization training in patients with multiple sclerosis.