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Effect of Early High-Dose Vitamin D3 Repletion on Cognitive Outcomes in Critically Ill Adults.
Han, JH, Ginde, AA, Brown, SM, Baughman, A, Collar, EM, Ely, EW, Gong, MN, Hope, AA, Hou, PC, Hough, CL, et al
Chest. 2021;(3):909-918
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BACKGROUND Long-term cognitive impairment frequently occurs after critical illness; no treatments are known to improve long-term cognition. RESEARCH QUESTION Does a single high-dose (540,000 International Units) enteral treatment of vitamin D3 given shortly after hospital admission in critically ill patients who are vitamin D deficient improve long-term global cognition or executive function? STUDY DESIGN AND METHODS This study evaluated long-term cognitive outcomes among patients enrolled in a multicenter, blinded, randomized clinical trial comparing vitamin D3 treatment vs placebo in critically ill adults with vitamin D deficiency. Global cognition was measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Executive function was measured with a composite score derived from three Delis-Kaplan Executive Function System subscales. Outcomes were assessed at a median of 443 days (interquartile range, 390-482 days) after randomization and were compared using multivariate proportional odds regression. Adjusted ORs of > 1.0 would indicate better outcomes in the vitamin D3 group compared with the placebo group. RESULTS Ninety-five patients were enrolled, including 47 patients randomized to vitamin D3 treatment and 48 patients randomized to placebo. The adjusted median RBANS score at follow-up was 79.6 (95% CI, 73.0-84.0) in the vitamin D3 group and 82.1 (95% CI, 74.7-84.6) in the placebo group (adjusted OR, 0.83; 95% CI, 0.50-1.38). The adjusted median executive function composite scores were 8.1 (95% CI, 6.8-9.0) and 8.7 (95% CI, 7.4-9.3), respectively (adjusted OR, 0.72; 95% CI, 0.36-1.42). INTERPRETATION In vitamin D-deficient, critically-ill adults, a large dose of enteral vitamin D3 did not improve long-term global cognition or executive function. TRIAL REGISTRY ClinicalTrials.gov; No.: NCT03733418; URL: www.clinicaltrials.gov.
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Efficacy and Safety of Divaza for the Correction of Oxidative Disturbances in Patients with Cerebral Atherosclerosis: A Randomized Controlled Trial.
Lashch, NU, Kamchatnov, PR, Fedorova, TN, Muzychuk, OA, Khacheva, KK, Pizova, NV, Malygin, AU, Shavlovskaya, OA, Fateeva, VV, Nikulina, KV, et al
Cerebrovascular diseases (Basel, Switzerland). 2021;(4):472-482
Abstract
OBJECTIVE The objective of this study was to determine if Divaza, a drug with nootropic and antioxidant effects, was safe and effective for the correction of oxidative disturbances and to stabilize cognitive impairment in patients with cerebral atherosclerosis. STUDY DESIGN The study design consisted of a 12-week multicenter, randomized, double-blind, placebo-controlled, prospective trial in parallel groups. SETTING The setting in which the study was conducted comprised 10 clinical centers across the Russian Federation. INTERVENTIONS Patients were randomized into 2 groups and instructed to take either 2 tablets of the study drug or a placebo 3 times per day in conjunction with basic therapy. OUTCOMES The primary outcome was a change in the average endogenous antioxidant potential after the completion of the study. The blood indicators of the oxidative stress (OS) were analyzed at the baseline and then after 12 weeks of therapy using iron-induced chemiluminescence analysis. The Montreal cognitive assessment test was used as a secondary outcome measure to evaluate cognitive impairment at the end of the study. RESULTS 124 outpatients with a mean age of 60.7 ± 7.6 years were enrolled and randomly assigned to receive Divaza (n = 65) or a placebo (n = 59). An improvement of cognitive function was observed in all patients of the Divaza group at the end of the treatment; this was significantly better than the placebo group (100 [100] vs. 89.5 [89.1]%, respectively, p = 0.0272 [p = 0.0128]). The administration of Divaza restored the activity of the endogenous antioxidant system. The change in the average level of lipoprotein resistance to oxidation after 12 weeks of therapy, compared to the baseline, was significantly higher in the Divaza group (14.8 ± 14.7 [14.8 ± 14.7] seconds latent period vs. 6.4 ± 16.9 [6.9 ± 16.7] seconds in the placebo group (p = 0.007 [p = 0.0107]). CONCLUSIONS Divaza is a safe and effective therapeutic option for attenuating OS and recovery of cognitive impairment in patients with cerebral atherosclerosis.
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Conventional chemotherapy for acute myeloid leukemia in older adults: Impact on nutritional, cognitive, and functional status.
Jouzier, C, Hamel, JF, Dumas, PY, Delaunay, J, Bonmati, C, Guièze, R, Hunault, M, Banos, A, Lioure, B, Béné, MC, et al
European journal of haematology. 2021;(6):859-867
Abstract
OBJECTIVES The impact of conventional treatment for acute myeloid leukemia (AML) on the nutritional, cognitive, and functional status of elderly patients is seldom studied. This assessment was performed in the context of the LAMSA 2007 trial. METHODS The trial enrolled 424 patients with de novo AML. Among them, 316 benefited from geriatric assessment (GA) including nutritional, cognitive, and functional status and were scored according to Eastern Cooperative Oncology Group (ECOG) and sorror for the prediction of treatment toxicity, morbidity, and mortality. Patients were investigated at diagnosis for three times during follow-up. RESULTS This study showed that AML and its treatment have no impact on cognitive (P = .554) nor functional status (P = .842 for Activity of Daily Living and P = .087 for Instrumental Activities of Daily Living). The nutritional status improved over time (P = .041). None of these three parameters at baseline, associated or not with ECOG and sorror scores, impacted survivals or toxicities. CONCLUSIONS The cognitive, functional, and nutritional status had no impact in this cohort of fit elderly AML patients without unfavorable cytogenetics. The GA tools used provided no additional information compared with ECOG and sorror scores, to predict toxicity, morbidity, or mortality due to intensive chemotherapy.
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Consequences of using chronological age versus corrected age when testing cognitive and motor development in infancy and intelligence quotient at school age for children born preterm.
Gould, JF, Fuss, BG, Roberts, RM, Collins, CT, Makrides, M
PloS one. 2021;(9):e0256824
Abstract
BACKGROUND Children born preterm (<37 weeks' gestation) have an increased risk of poor neurodevelopment, including lower intelligence quotient (IQ) scores compared with their term-born counterparts. OBJECTIVE To explore the differences in psychometric scores for cognition and motor skills when they are age-standardized according to chronological age instead of corrected age for children born preterm. METHODS We assessed = 554 children born <33 weeks' gestation with the Bayley Scales of Infant Development, 2nd edition (mental and motor scores) at 18 months and the Weschler Abbreviated Scale of Intelligence (IQ score) at seven years of age. Scores were standardized according to chronological age and corrected age and differences between mean chronological and corrected scores were compared, along with the proportion of children whose scores could be classified as impaired. RESULTS When scores were standardized according to chronological age instead of corrected age there was a large significant difference of 17.3 points on the mental scale (79.5 vs. 96.8, respectively) and 11.8 points on the motor scale (84.8 vs. 96.6, respectively) at 18 months. By seven years, the difference in IQ scores remained, although of a smaller magnitude at 1.9 points between mean chronological and corrected age scoring (97.2 vs. 99.1, respectively). CONCLUSION Consistent with previous literature, outcome assessments for preterm infants consistently differed according to use of chronological or corrected age to standardized scores. Cognitive scores were impacted more severely than motor scores, and differences were more substantial in early childhood than later in childhood. For clinical purposes, correction for preterm birth is only likely to have an impact during early childhood, however assessments for research purposes should continue to correct into childhood to account for the persistent bias due to preterm birth.
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The Japan-Multimodal Intervention Trial for Prevention of Dementia (J-MINT): The Study Protocol for an 18-Month, Multicenter, Randomized, Controlled Trial.
Sugimoto, T, Sakurai, T, Akatsu, H, Doi, T, Fujiwara, Y, Hirakawa, A, Kinoshita, F, Kuzuya, M, Lee, S, Matsuo, K, et al
The journal of prevention of Alzheimer's disease. 2021;(4):465-476
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BACKGROUND/OBJECTIVES The Japan-multimodal intervention trial for prevention of dementia (J-MINT) is intended to verify the effectiveness of multi-domain interventions and to clarify the mechanism of cognitive improvement and deterioration by carrying out assessment of dementia-related biomarkers, omics analysis and brain imaging analysis among older adults at high risk of dementia. Moreover, the J-MINT trial collaborates with partnering private enterprises in the implementation of relevant interventional measures. This manuscript describes the study protocol. DESIGN/SETTING Eighteen-month, multi-centered, randomized controlled trial. PARTICIPANTS We plan to recruit 500 older adults aged 65-85 years with mild cognitive impairment. Subjects will be centrally randomized into intervention and control groups at a 1:1 allocation ratio using the dynamic allocation method with all subjects stratified by age, sex, and cognition. INTERVENTION The multi-domain intervention program includes: (1) management of vascular risk factors; (2) group-based physical exercise and self-monitoring of physical activity; (3) nutritional counseling; and (4) cognitive training. Health-related information will be provided to the control group every two months. MEASUREMENTS The primary and secondary outcomes will be assessed at baseline, 6-, 12-, and 18-month follow-up. The primary outcome is the change from baseline to 18 months in a global composite score combining several neuropsychological domains. Secondary outcomes include: cognitive change in each neuropsychological test, incident dementia, changes in blood and dementia-related biomarkers, changes in geriatric assessment including activities of daily living, frailty status and neuroimaging, and number of medications taken. CONCLUSIONS This trial that enlist the support of private enterprises will lead to the creation of new services for dementia prevention as well as to verify the effectiveness of multi-domain interventions for dementia prevention.
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Physical fitness and physical activity association with cognitive function and quality of life: baseline cross-sectional analysis of the PREDIMED-Plus trial.
Daimiel, L, Martínez-González, MA, Corella, D, Salas-Salvadó, J, Schröder, H, Vioque, J, Romaguera, D, Martínez, JA, Wärnberg, J, Lopez-Miranda, J, et al
Scientific reports. 2020;(1):3472
Abstract
Physical activity (PA) has been hypothesized to be effective to maintaining cognitive function and delay cognitive decline in the elderly, but physical fitness (PF) could be a better predictor of cognitive function. We aimed to study the association between PA and PF with cognitive function and quality of life using cross-sectional data from 6874 participants of the PREDIMED-Plus trial (64.9 ± 4.9 years, 48.5% female). PF and PA were measured with a Chair Stand Test, the REGICOR and Rapid Assessment Physical Activity questionnaires. Cognitive function was measured with Mini-mental State Examination, Control Oral Word Association Test, Trail Making Test and Digit Span tests; whereas health-related quality of life was assessed with the SF36-HRQL test. Cognitive and quality of life scores were compared among PF quartiles and PA levels (low, moderate and high) with ANCOVA and with Chair Stand repetitions and energy expenditure from total PA with multivariable linear regression adjusted for confounding factors. PF associated with higher scores in phonemic and semantic verbal fluency tests and with lower TMT A time. However, PA was not associated with the neurocognitive parameters evaluated. Both PF and PA levels were strongly associated with a better quality of life. We concluded that PF, but not PA, is associated with a better cognitive function. This trial was retrospectively registered at the International Standard Randomized Controlled Trial (ISRCTN89898870, https://www.isrctn.com/ISRCTN89898870?q=ISRCTN89898870&filters=&sort=&offset=1&totalResults=1&page=1&pageSize=10&searchType=basic-search) on 07/24/2014.
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Cognitive Function Following Diabetic Ketoacidosis in Children With New-Onset or Previously Diagnosed Type 1 Diabetes.
Ghetti, S, Kuppermann, N, Rewers, A, Myers, SR, Schunk, JE, Stoner, MJ, Garro, A, Quayle, KS, Brown, KM, Trainor, JL, et al
Diabetes care. 2020;(11):2768-2775
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OBJECTIVE This study assessed whether a single diabetic ketoacidosis (DKA) episode is associated with cognitive declines in children with newly diagnosed type 1 diabetes and whether the same is true in children who had previously been diagnosed after accounting for variations in glycemic control and other relevant factors. RESEARCH DESIGN AND METHODS We prospectively enrolled 758 children, 6-18 years old, who presented with DKA in a randomized multisite clinical trial evaluating intravenous fluid protocols for DKA treatment. DKA was moderate/severe in 430 children and mild in 328 children. A total of 392 children with DKA had new onset of type 1 diabetes, and the rest were previously diagnosed. Neurocognitive assessment occurred 2-6 months after the DKA episode. A comparison group of 376 children with type 1 diabetes, but no DKA exposure, was also enrolled. RESULTS Among all patients, moderate/severe DKA was associated with lower intelligence quotient (IQ) (β = -0.12, P < 0.001), item-color recall (β = -0.08, P = 0.010), and forward digit span (β = -0.06, P = 0.04). Among newly diagnosed patients, moderate/severe DKA was associated with lower item-color recall (β = -0.08, P = 0.04). Among previously diagnosed patients, repeated DKA exposure and higher HbA1c were independently associated with lower IQ (β = -0.10 and β = -0.09, respectively, P < 0.01) and higher HbA1c was associated with lower item-color recall (β = -0.10, P = 0.007) after hypoglycemia, diabetes duration, and socioeconomic status were accounted for. CONCLUSIONS A single DKA episode is associated with subtle memory declines soon after type 1 diabetes diagnosis. Sizable IQ declines are detectable in children with known diabetes, suggesting that DKA effects may be exacerbated in children with chronic exposure to hyperglycemia.
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Long-term Change in Physiological Markers and Cognitive Performance in Type 2 Diabetes: The Look AHEAD Study.
Carmichael, OT, Neiberg, RH, Dutton, GR, Hayden, KM, Horton, E, Pi-Sunyer, FX, Johnson, KC, Rapp, SR, Spira, AP, Espeland, MA
The Journal of clinical endocrinology and metabolism. 2020;(12):e4778-91
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CONTEXT The effects of physiological improvements on cognitive function among persons with type 2 diabetes mellitus (T2DM) are not fully understood. OBJECTIVE To determine whether improvements in physiological markers (body weight, blood sugar control, and physical activity) during intensive lifestyle intervention (ILI) are associated with enhancements in cognitive function in older adults with T2DM. DESIGN Multisite randomized controlled trial. SETTING Academic research centers. PATIENTS OR OTHER PARTICIPANTS Participants were aged 45-76 years, with T2DM. INTERVENTION The Action for Health in Diabetes (Look AHEAD) study, a randomized, controlled clinical trial of ILI. MAIN OUTCOME MEASURE Two to 3 cognitive assessments were collected from 1089 participants, the first and last occurring a mean (standard deviation) of 8.6 (1.0) and 11.5 (0.7) years after enrollment. RESULTS Greater improvement in blood sugar control was associated with better cognitive scores (fasting glucose and Rey Auditory Verbal Learning Test [AVLT]: P = 0.0148; fasting glucose and Digit Symbol Coding (DSC): P = 0.0360; HbA1C and DSC: P = 0.0477); but weight loss had mixed associations with cognitive scores (greater body mass index [BMI] reduction and worse AVLT overall: P = 0.0053; and greater BMI reduction and better DSC scores among those overweight but not obese at baseline: P = 0.010). Associations were strongest among those who were overweight (not obese) at baseline, and among those with a history of cardiovascular disease (CVD) at baseline. CONCLUSIONS Improvements in glycemic control, but not necessarily weight status, during ILI may be associated with better subsequent cognitive performance. These associations may differ by adiposity and CVD history.
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Early Life Experiences and Trajectories of Cognitive Development.
McCormick, BJJ, Caulfield, LE, Richard, SA, Pendergast, L, Seidman, JC, Maphula, A, Koshy, B, Blacy, L, Roshan, R, Nahar, B, et al
Pediatrics. 2020;(3)
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BACKGROUND Multiple factors constrain the trajectories of child cognitive development, but the drivers that differentiate the trajectories are unknown. We examine how multiple early life experiences differentiate patterns of cognitive development over the first 5 years of life in low-and middle-income settings. METHODS Cognitive development of 835 children from the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) multisite observational cohort study was assessed at 6, 15, 24 (Bayley Scales of Infant and Toddler Development), and 60 months (Wechsler Preschool and Primary Scale of Intelligence). Markers of socioeconomic status, infection, illness, dietary intake and status, anthropometry, and maternal factors were also assessed. Trajectories of development were determined by latent class-mixed models, and factors associated with class membership were examined by discriminant analysis. RESULTS Five trajectory groups of cognitive development are described. The variables that best discriminated between trajectories included presence of stimulating and learning resources in the home, emotional or verbal responsivity of caregiver and the safety of the home environment (especially at 24 and 60 months), proportion of days (0-24 months) for which the child had diarrhea, acute lower respiratory infection, fever or vomiting, maternal reasoning ability, mean nutrient densities of zinc and phytate, and total energy from complementary foods (9-24 months). CONCLUSIONS A supporting and nurturing environment was the variable most strongly differentiating the most and least preferable trajectories of cognitive development. In addition, a higher quality diet promoted cognitive development while prolonged illness was indicative of less favorable patterns of development.
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Volume Analysis of Brain Cognitive Areas in Alzheimer's Disease: Interim 3-Year Results from the ASCOMALVA Trial.
Traini, E, Carotenuto, A, Fasanaro, AM, Amenta, F
Journal of Alzheimer's disease : JAD. 2020;(1):317-329
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BACKGROUND Cerebral atrophy is a common feature of several neurodegenerative disorders, including Alzheimer's disease (AD). In AD, brain atrophy is associated with loss of gyri and sulci in the temporal and parietal lobes, and in parts of the frontal cortex and cingulate gyrus. OBJECTIVE The ASCOMALVA trial has assessed, in addition to neuropsychological analysis, whether the addition of the cholinergic precursor choline alphoscerate to treatment with donepezil has an effect on brain volume loss in patients affected by AD associated with cerebrovascular injury. METHODS 56 participants to the randomized, placebo-controlled, double-blind ASCOMALVA trial were assigned to donepezil + placebo (D + P) or donepezil + choline alphoscerate (D + CA) treatments and underwent brain magnetic resonance imaging and neuropsychological tests every year for 4 years. An interim analysis of 3-year MRI data was performed by voxel morphometry techniques. RESULTS The D + P group (n = 27) developed atrophy of the gray and white matter with concomitant increase in ventricular space volume. In the D + CA group (n = 29) the gray matter atrophy was less pronounced compared to the D + P group in frontal and temporal lobes, hippocampus, and amygdala. These morphological data are consistent with the results of the neuropsychological tests. CONCLUSION Our findings indicate that the addition of choline alphoscerate to standard treatment with the cholinesterase inhibitor donepezil counters to some extent the loss in volume occurring in some brain areas of AD patients. The observation of parallel less pronounced decrease in cognitive and functional tests in patients with the same treatment suggests that the morphological changes observed may have functional relevance.