ABSTRACT: Interventions to improve the cognitive health of older adults are of critical importance. In the current study, we conducted a double-blind, placebo-controlled clinical trial using a pill-based nutraceutical (NT-020) that contained a proprietary formulation of blueberry, carnosine, green tea, vitamin D3, and Biovin to evaluate the impact on changes in multiple domains of cognitive functioning. One hundred and five cognitively intact adults aged 65-85 years of age (M=73.6 years) were randomized to receive NT-020 (n=52) or a placebo (n=53). Participants were tested with a battery of cognitive performance tests that were classified into six broad domains--episodic memory, processing speed, verbal ability, working memory, executive functioning, and complex speed at baseline and 2 months later. The results indicated that persons taking NT-020 improved significantly on two measures of processing speed across the 2-month test period in contrast to persons on the placebo whose performance did not change. None of the other cognitive ability measures were related to intervention group. The results also indicated that the NT-020 was well tolerated by older adults, and the presence of adverse events or symptoms did not differ between the NT-020 and placebo groups. Overall, the results of the current study were promising and suggest the potential for interventions like these to improve the cognitive health of older adults.
Project description:Aging is associated with many pathophysiological changes that could lead to the onset of degenerative disease. Some of the physiological changes that occur with aging include increased inflammation and decreased stem cell proliferation, leading to decreased capacity for tissue regeneration and loss of function. In previous studies, we and others have found nutraceutical intervention to ameliorate some of the deleterious effects associated with aging. In particular, we have previously shown that NT-020, a supplement composed of a proprietary blend of blueberries, green tea, vitamin D3, and carnosine, is able to rescue age-related cognitive deficits, impaired neurogenesis, and inflammation in rats. We have also previously demonstrated that stem cells cultured with old serum showed decreased proliferation; however, when stem cells were cultured in serum from old rats given a diet supplemented with NT-020, proliferation did not differ from that of cells cultured with serum from young rats. While it is clear that NT-020 is exerting a therapeutic, anti-aging effect, the mechanisms of action were yet to be fully elucidated.To that end, in the present study, we conducted a bioinformatics experiment to examine the rat proteome of serum from young and old control rats and young and old rats given a diet supplemented with NT-020. Serum from old rats showed an increase in some inflammatory and pro-aging factors while serum from old rats given a diet supplemented with NT-020 showed an increase in some anti-aging factors, most notably proteins associated with the complement system and autophagy. A number of immune functions that increase with age were shown to be downregulated with NT-020 treatment.
Project description:Cognitive decline is common in older adults and more than 5 million Americans suffer from Alzheimer's disease (AD). A number of physiological processes including systemic inflammation, excess adiposity, and impaired glucoregulation arise from a combination of genetic and behavioral factors and increase risk for developing AD or other forms of dementia. Recent research suggests that the gut microbiome may moderate these pathological processes and possibly influence cognitive outcomes. This paper reviews the methodology for a double-blind, randomized clinical trial examining the influence of Lactobacillus GG (LGG) probiotic supplementation on mood and cognitive functioning in middle-aged and older adults. Our two primary hypotheses include: 1) Participants randomized to the probiotic group will show greater improvements in psychological status compared to participants in the placebo group; 2) Participants randomized to the probiotic group will show greater improvements in executive functioning and processing speed, as evidenced through performance on neuropsychological testing, than participants in the placebo group. We anticipate these results will inform future efforts on the feasibility of LGG probiotic supplementation as an intervention for psychological status and cognitive functioning and further elucidate the link between the gut microbiome and cognitive health.
Project description:Purpose:The gut microbiome has been linked to cognitive function and appears to worsen with aging. Probiotic supplementation has been found to improve the health of the gut microbiome. As such, it is possible that probiotic supplementation may protect the aging brain. The current study examined the cognitive benefits of probiotic supplementation (Lactobacillus rhamnosus GG) in healthy middle-aged and older adults. Materials and Methods:The study was a double-blind, placebo-controlled, randomized clinical trial. Two hundred community-dwelling adults aged 52-75 were enrolled (mean age=64.3, SD=5.52). A three-month intervention involved daily consumption of probiotic or placebo. Independent sample t-tests, chi-squared tests, and repeated measure ANOVAs compared groups and examined changes over time. Primary outcome was change in NIH Toolbox Total Cognition Score from baseline to follow-up. Results:A total of 145 participants were examined in primary analyses (probiotic=77, placebo=68) and excluded persons due to discontinuation, low adherence, missing data, or outlier values. Established criteria (ie ?1 subtest t-scores ?35; n=19, n=23) were used to operationally define cognitive impairment. Repeated measures ANOVAs revealed that persons with cognitive impairment who consumed probiotics exhibited a greater total cognition score improvement than persons with cognitive impairment in the placebo group and cognitively intact persons in probiotic or placebo groups. Conclusion:Lactobacillus rhamnosus GG probiotic supplementation was associated with improved cognitive performance in middle-aged and older adults with cognitive impairment. Probiotic supplementation may be a novel method for protecting cognitive health in aging.
Project description:Aging is associated with changes in lower-body functioning. The extent to which lower-body function is associated with cognitive changes over time is unclear, especially among older Hispanics, a high-risk population for declines in physical and cognitive functioning. We sought to determine if the association between lower-body functioning and cognitive decline over 9-years differentially varied with respect to balance, gait speed, lower-body strength (chair stands), or a summary score of the three measures. This retrospective cohort study used clinical performance data from the Hispanic Established Populations for the Epidemiologic Study of the Elderly (H-EPESE). Cognitive function was measured using the Mini-Mental Status Exam. Linear mixed modeling was used to investigate the association between lower-body function and cognitive decline, controlling for patients' demographic and health characteristics. We found that gait speed and timed chair stands but not balance were associated with accelerated cognitive decline in Mexican-Americans age 75?years and older. These parameters of lower-body function can be feasibly measured in any clinic. As limitations in lower-body functioning may be an early marker of cognitive decline, this suggests an opportunity for the development of interventions to slow cognitive and physical disablement and promote successful aging among persons older than 75?years.
Project description:BACKGROUND:Depressive symptoms and impaired physical functioning are prevalent among older adults. Supplementation with vitamin D might improve both conditions, particularly in persons with low vitamin D status. OBJECTIVE:The D-Vitaal study primarily aimed to investigate the effect of vitamin D supplementation on depressive symptoms, functional limitations, and physical performance in a high-risk older population with low vitamin D status. Secondary aims included examining the effect of vitamin D supplementation on anxiety symptoms, cognitive functioning, mobility, handgrip strength, and health-related quality of life. METHODS:This study was a randomized placebo-controlled trial with 155 participants aged 60-80 y who had clinically relevant depressive symptoms, ≥1 functional limitations, and serum 25-hydroxyvitamin D [25(OH)D] concentrations of 15-50/70 nmol/L (depending on season). Participants received 1200 IU/d vitamin D3 (n = 77) or placebo tablets (n = 78) for 12 mo. Serum 25(OH)D was measured at baseline and 6 mo; outcomes were assessed at baseline, 6 mo, and 12 mo. Linear mixed-models analyses were conducted to assess the effect of the intervention. RESULTS:The supplementation increased serum 25(OH)D concentrations in the intervention group to a mean ± SD of 85 ± 16 nmol/L compared with 43 ± 18 nmol/L in the placebo group after 6 mo (P < 0.001). No relevant differences between the treatment groups were observed regarding depressive symptoms, functional limitations, physical performance, or any of the secondary outcomes. CONCLUSIONS:Supplementation with 1200 IU/d vitamin D for 12 mo had no effect on depressive symptoms and physical functioning in older persons with relatively low vitamin D status, clinically relevant depressive symptoms, and poor physical functioning. This trial is registered with the Netherlands Trial Register (www.trialregister.nl) under NTR3845.
Project description:We investigated the associations of morning and evening salivary cortisol levels with regional brain volumes and cognitive functioning in community-dwelling older persons without dementia.From the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study, we included 4,244 persons without dementia (age 76 ± 5 years, 58% women) who had 1.5T brain MRI, assessment of cognitive functioning, and saliva collected at home 45 minutes after awakening and at night. Linear regression analysis was used to estimate the cross-sectional relationship among cortisol levels, brain volumes, and cognitive functioning, adjusting for covariates.Higher evening cortisol was associated with smaller total brain volume (highest vs lowest tertile -16.0 mL; 95% confidence interval -19.7 to -12.2 mL, adjusted for age, sex, education, intracranial volume, smoking, steroid use, white matter lesions, and brain infarcts on MRI). The smaller volumes were observed in all brain regions, but were significantly smaller in gray matter than in white matter regions. Poorer cognitive functioning across all domains was also associated with higher evening cortisol. Higher levels of morning cortisol were associated with slightly greater normal white matter volume and better processing speed and executive functioning, but not with gray matter volume or with memory performance.In older persons, evening and morning cortisol levels may be differentially associated with tissue volume in gray and white matter structures and cognitive function. Understanding these differential associations may aid in developing strategies to reduce the effects of hypothalamic-pituitary-adrenal axis dysfunction on late-life cognitive impairment.
Project description:To investigate the independent association of serum N-terminal fragment of the prohormone natriuretic peptide (NT-proBNP) with structural and functional features of abnormal brain aging in older individuals.In this cross-sectional study based on the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study, we included 4,029 older community-dwelling individuals (born 1907 to 1935) with a measured serum level of NT-proBNP. Outcomes included parenchymal brain volumes estimated from brain MRI, cognitive function measured by tests of memory, processing speed, and executive functioning, and presence of depressive symptoms measured using the Geriatric Depression Scale. In a substudy, cardiac output of 857 participants was assessed using cardiac MRI.In multivariate analyses, adjusted for sociodemographic and cardiovascular factors, higher levels of NT-proBNP were independently associated with lower total (p < 0.001), gray matter (p < 0.001), and white matter (p = 0.001) brain volumes. Likewise, in multivariate analyses, higher levels of NT-proBNP were associated with worse scores in memory (p = 0.005), processing speed (p = 0.001), executive functioning (p < 0.001), and more depressive symptoms (p = 0.002). In the substudy, the associations of higher NT-proBNP with lower brain parenchymal volumes, impaired executive function and processing speed, and higher depressive symptoms were independent of the level of cardiac output.Higher serum levels of NT-proBNP, independent of cardiovascular risk factors and a measure of cardiac function, are linked with alterations in brain structure and function. Roles of natriuretic peptides in the process of brain aging need to be further elucidated.
Project description:The current population of older Americans has accumulated substantial lifetime lead doses, which raises concern about the possibility of adverse cognitive outcomes. We evaluated whether cumulative lead dose from environmental exposures is associated with cognitive function and decline, and whether such effects are persistent, reversible, or progressive.We used longitudinal linear modeling to evaluate associations of tibia lead concentration with cognitive function and decline in sociodemographically diverse, community-dwelling adults aged 50-70 years who were randomly selected from neighborhoods in Baltimore. Six summary measures of cognitive function were created from standard tests in the following domains: language, processing speed, eye-hand coordination, executive functioning, verbal memory and learning, and visual memory.The mean (SD) tibia lead level was 18.8 (11.6) microg/g. In models adjusted for demographic characteristics, socioeconomic status (SES), and race/ethnicity, higher tibia lead was associated with a progressive decline in eye-hand coordination. Tibia lead was associated with persistently impaired cognitive function in all 6 domains, although these associations weakened after increasing covariate control. In fully adjusted stratified analysis among white persons, persistent effects were apparent in eye-hand coordination, executive functioning, and verbal memory and learning.The study presents the strongest evidence to date of the effects of cumulative lead dose on adult cognitive function independent of SES. The study population was relatively young and the average total duration of follow-up short (<30 months); these findings may represent the lower bound of the impact of cumulative lead dose on cognitive function of older adults.
Project description:The delineation of the interrelationships between cognitive and physical functioning in older adults is critical to determining pathways to disability. By using longitudinal data from 395 initially high-functioning, community-dwelling older women in Baltimore, Maryland, from the Women's Health and Aging Study II (from 1994 to 2006), we simultaneously assessed associations of cognition with later physical functioning and associations of physical functioning with later cognition. The analysis included measures of global cognition and 2 cognitive domains (executive functioning and memory), as well as 2 measures of physical functioning (a Short Physical Performance Battery and a 4-meter test of usual walking speed). We found the strongest bidirectional associations of memory with physical functioning and less evidence of associations of physical functioning with executive functioning and global cognition. For a 1-standard deviation increase in walking speed, subsequent memory increased by 0.08 standard deviations (95% confidence interval: (0.03, 0.13)). For a 1-standard deviation increase in memory, subsequent walking speed increased by 0.07 standard deviations (95% confidence interval: 0.03, 0.10). Associations were similar in magnitude for models using a Short Physical Performance Battery. We did not find evidence that associations between cognitive and physical functioning varied over time. Our results suggest that cognition, and particularly memory, is associated with subsequent physical functioning and vice versa.
Project description:Increasing age is associated with deficits in a wide range of cognitive domains as well as with structural brain changes. Recent studies using diffusion tensor imaging (DTI) have shown that microstructural integrity of white matter is associated with cognitive performance in elderly persons, especially on tests that rely on perceptual speed. We used structural equation modeling to investigate associations between white matter microstructure and cognitive functions in a population-based sample of elderly persons (age ? 60 years), free of dementia, stroke, and neurological disorders (n = 253). Participants underwent a magnetic resonance imaging scan, from which mean fractional anisotropy (FA) and mean diffusivity (MD) of seven white matter tracts were quantified. Cognitive functioning was analyzed according to performance in five task domains (perceptual speed, episodic memory, semantic memory, letter fluency, and category fluency). After controlling for age, FA and MD were exclusively related to perceptual speed. When further stratifying the sample into two age groups, the associations were reliable in the old-old (? 78 years) only. This relationship between white matter microstructure and perceptual speed remained significant after excluding persons in a preclinical dementia phase. The observed pattern of results suggests that microstructural white matter integrity may be especially important to perceptual speed among very old adults.