Age-related Decline In Cognitive Function Research Articles

Prefrontal activity and heart rate variability during cognitive tasks may show different changes in young and older adults with and without mild cognitive impairment.

Age-related decline in cognitive function is often linked to changed prefrontal cortex (PFC) activity and heart rate variability (HRV). Mild cognitive impairment (MCI), a transitional stage between normal aging and dementia, might have further degeneration beyond aging. This study aimed to investigate the differences between young and older adults with or without MCI in cognitive functions, task-induced PFC activation and HRV changes. Thirty-one healthy young adults (YA), 44 older adults (OA), and 28 older adults with MCI (OA-MCI) were enrolled and compared in this cross-sectional study. Each participant received a one-time assessment including cognitive and executive functions, as well as the simultaneous recording of PFC activity and HRV during a cognitive task paradigm. We observed age-related decrease in global cognitive functions, executive functions, HRV, and increase in PFC activity. The MCI further deteriorated the global cognitive and executive performances, but not the HRV or the prefrontal activation. Older people showed lower performances in general cognitive function and executive function, compensatory increase of PFC activity, and reduced HRV. Older people with MCI had further deterioration in cognitive performance, but not in PFC activation and HRV.

Is Quantifying Iron in the Putamen Important in Neurodegenerative Diseases?

Iron is crucial for the functioning of neurons. However, the accumulation of iron in subcortical structures, particularly in the putamen, has been linked to age-related decline in cognitive function and neurodegeneration. This accumulation leads to oxidative stress, which damages cellular components and contributes to the development of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Quantitative Susceptibility Mapping (QSM) has provided insights into the paramagnetic properties of iron, enabling the non-invasive measurement of iron deposits in brain structures. Studies have shown a significant correlation between increased iron levels in the putamen and the severity of neurodegenerative diseases, highlighting the vulnerability of the putamen to iron-induced toxicity. QSM holds promise as an imaging biomarker for understanding disease mechanisms, assessing disease severity, and monitoring treatment. However, further longitudinal studies are needed to evaluate the progression of iron deposition and its implications for disease pathology.

Age differences in routine formation: the role of automatization, motivation, and executive functions.

Medication adherence can be vital for one's health, especially in older adults. However, previous research has demonstrated that medication adherence is negatively affected by age-related cognitive decline. In the current study we investigated whether older adults are able to compensate for this decline by relying more on the formation of efficient, automatized routines. To this end, we directly compared daily (placebo) medication adherence in a healthy sample of 68 younger (18-29 years) and 63 older adults (65-86 years) over a period of 4 weeks. We show that despite an age-related decline in cognitive functions (i.e., poorer working memory, prospective memory, task switching, and goal-directed control), older adults adhered better to a daily pill intake routine than younger adults did and, in line with our hypothesis about increased routine formation, reported higher subjective automaticity of pill intake. Across age groups, automatization of pill intake was related to intake regularity and conscientiousness, but not to individual differences in habit tendency as measured in the lab nor to explicit strategic planning. Crucially, the age-related increase in pill intake adherence was mediated by experienced automatization as well as motivation. These findings demonstrate that intact habitual processes and high motivation aid older adults in successfully forming daily routines.

An attempt to model the causal structure behind white matter aging and cognitive decline

In this diffusion tension imaging study, voxel wise structural equation modeling was used to unravel the relation between white matter, cognition, and age. Four neurocognitive ageing models describing the interplay between age, white matter integrity, and cognition were investigated but only two models survived an Akaike information criterion-based model selection procedure. The independent factor model predicts that there is no relation between white matter integrity and cognition although both systems are affected by age. The cognitive mediation model predicts that the relation between age and white matter integrity is mediated through cognition. Roughly 60% of the observed voxels were in agreement with the independent factor model while 16% of the observed voxels were in agreement with the cognitive mediation model. Imaging results of the latter model suggest that the deterioration of fibers—that connect the two hemispheres with each other—is partly caused by an age-related decline in cognitive functioning.

Polarized Anti-Inflammatory Mesenchymal Stem Cells Increase Hippocampal Neurogenesis and Improve Cognitive Function in Aged Mice.

Age-related decline in cognitive functions is associated with reduced hippocampal neurogenesis caused by changes in the systemic inflammatory milieu. Mesenchymal stem cells (MSC) are known for their immunomodulatory properties. Accordingly, MSC are a leading candidate for cell therapy and can be applied to alleviate inflammatory diseases as well as aging frailty via systemic delivery. Akin to immune cells, MSC can also polarize into pro-inflammatory MSC (MSC1) and anti-inflammatory MSC (MSC2) following activation of Toll-like receptor 4 (TLR4) and TLR3, respectively. In the present study, we apply pituitary adenylate cyclase-activating peptide (PACAP) to polarize bone-marrow-derived MSC towards an MSC2 phenotype. Indeed, we found that polarized anti-inflammatory MSC were able to reduce the plasma levels of aging related chemokines in aged mice (18-months old) and increased hippocampal neurogenesis following systemic administration. Similarly, aged mice treated with polarized MSC displayed improved cognitive function in the Morris water maze and Y-maze assays compared with vehicle- and naïve-MSC-treated mice. Changes in neurogenesis and Y-maze performance were negatively and significantly correlated with sICAM, CCL2 and CCL12 serum levels. We conclude that polarized PACAP-treated MSC present anti-inflammatory properties that can mitigate age-related changes in the systemic inflammatory milieu and, as a result, ameliorate age related cognitive decline.

MODE EFFECTS ON COGNITIVE FUNCTIONING ASSESSMENTS IN THE HEALTH AND RETIREMENT STUDY

Abstract As the population of the US ages, there is interest in assessing health conditions associated with age and longevity, such as age-related decline in cognitive functioning. As a result, there is an increased focus on measuring cognitive functioning in surveys of older populations. One challenge relates to conducting comparable measurement across survey modes (e.g., phone vs. web). Compounding this is that mode of survey administration is often not assigned randomly making inter-group comparison more difficult. This paper addresses these issues using a novel experiment embedded within the Health and Retirement Study (HRS). The HRS, a US-based cohort of people over 50, has measured cognition since its inception using both in-person and telephone modes. In 2018, a sample of approximately 3700 respondents was identified as web-eligible based on a prior report of internet access along with other selection criteria. Of these, 60% were randomly selected for the web sample with the remainder serving as controls, assigned to telephone mode for comparison purposes. We deploy techniques from item response theory (IRT) and differential item functioning (DIF) to estimate the difference in cognitive functioning between web and phone respondents in 2018 based on longitudinal cognition data collected prior to 2018. Second, we estimate the overall effect of taking the survey via the web as compared to the phone. Third, we examine item-level variation in the magnitude of the mode effect and suggest possible methods for adjustment to support longitudinal consistency. These results are important in guiding future research that utilizes web-based cognitive measures.

Evaluating the causal effect of tobacco smoking on white matter brain aging: a two-sample Mendelian randomization analysis in UK Biobank.

Tobacco smoking is a risk factor for impaired brain function, but its causal effect on white matter brain aging remains unclear. This study aimed to measure the causal effect of tobacco smoking on white matter brain aging. Mendelian randomization (MR) analysis using two non-overlapping data sets (with and without neuroimaging data) from UK Biobank (UKB). The group exposed to smoking and control group consisted of current smokers and never smokers, respectively. Our main method was generalized weighted linear regression with other methods also included as sensitivity analysis. United Kingdom. The study cohort included 23 624 subjects [10 665 males and 12 959 females with a mean age of 54.18 years, 95% confidence interval (CI) = 54.08, 54.28]. Genetic variants were selected as instrumental variables under the MR analysis assumptions: (1) associated with the exposure; (2) influenced outcome only via exposure; and (3) not associated with confounders. The exposure smoking status (current versus never smokers) was measured by questionnaires at the initial visit (2006-10). The other exposure, cigarettes per day (CPD), measured the average number of cigarettes smoked per day for current tobacco users over the life-time. The outcome was the 'brain age gap' (BAG), the difference between predicted brain age and chronological age, computed by training machine learning model on a non-overlapping set of never smokers. The estimated BAG had a mean of 0.10 (95% CI = 0.06, 0.14) years. The MR analysis showed evidence of positive causal effect of smoking behaviors on BAG: the effect of smoking is 0.21 (in years, 95% CI = 6.5 × 10-3 , 0.41; P-value = 0.04), and the effect of CPD is 0.16 year/cigarette (UKB: 95% CI = 0.06, 0.26; P-value = 1.3 × 10-3 ; GSCAN: 95% CI = 0.02, 0.31; P-value = 0.03). The sensitivity analyses showed consistent results. There appears to be a significant causal effect of smoking on the brain age gap, which suggests that smoking prevention can be an effective intervention for accelerated brain aging and the age-related decline in cognitive function.

Do older adults make more risky decisions in the Hungry Donkey Task or in the Iowa Gambling Task?

ABSTRACT The Iowa Gambling Task (IGT) and the Hungry Donkey Task (HDT) are well-known tasks employed to assess decisions under ambiguity. Although the two tasks are equal in terms of wins and losses, they differ in terms of the recipient: while in the IGT participants make decisions for themselves, in the HDT decisions are made to help a hungry donkey. Decisions for themselves versus another one in a situation of ambiguity are particularly important in the field of aging because of older adults’ changes in motivational and other-oriented behavior. The present study aimed to test whether older adults make different decisions under ambiguity for themselves than for another one (i.e., the hungry donkey) as compared to younger adults. Forty-five young adults (M = 23.31; SD = 1.58) and 45 older adults (M = 72.47; SD = 5.49) performed the IGT and the HDT. In addition, participants performed tasks on working memory, set-shifting, and inhibition. Results showed age-related differences in the HDT but not in the IGT. Older adults, compared to younger adults, made disadvantageous decisions to help the hungry donkey as compared to themselves. Interestingly, this pattern of results is not explained by the age-related decline in cognitive functioning. The findings seem to suggest that older adults’ decisions made under the condition of ambiguity are affected by motivational and emotional changes associated with aging.

Epigenetic GrimAge acceleration and cognitive impairment in bipolar disorder

Bipolar disorder (BD) has been previously associated with clinical signs of premature aging, including accelerated epigenetic aging in blood and brain, and a steeper age-related decline in cognitive function. However, the clinical drivers and cognitive correlates of epigenetic aging in BD are still unknown. We aimed to investigate the relationship between multiple measures of epigenetic aging acceleration with clinical, functioning, and cognitive outcomes in patients with BD and controls. Blood genome-wide DNA methylation levels were measured in BD patients (n = 153) and matched healthy controls (n = 50) with the Infinium MethylationEPIC BeadChip (Illumina). Epigenetic age estimates were calculated using an online tool, including the recently developed lifespan predictor GrimAge, and analyzed with generalized linear models controlling for demographic variables and blood cell proportions. BD was significantly associated with greater GrimAge acceleration (AgeAccelGrim, β=0.197, p = 0.009), and significant group-dependent interactions were found between AgeAccelGrim and blood cell proportions (CD4+ T-lymphocytes, monocytes, granulocytes, and B-cells). Within patients, higher AgeAccelGrim was associated with worse cognitive function in multiple domains (short-term affective memory (β=-0.078, p = 0.030), short-term non-affective memory (β=-0.088, p = 0.018), inhibition (β=0.064, p = 0.046), and problem solving (β=-0.067, p = 0.034)), age of first diagnosis with any mood disorder (β=-0.076, p = 0.039) or BD (β=-0.102, p = 0.016), as well as with current non-smoking status (β=-0.392, p < 0.001). Overall, our findings support the contribution of epigenetic factors to the aging-related cognitive decline and premature mortality reported in BD patients, with an important driving effect of smoking in this population.

Cognitive Functioning among Older Adults in Japan and Other Selected Asian Countries: In Search of a Better Way to Remeasure Population Aging

Japan is the oldest society in the world. It has the highest proportion of the population aged 65 and over, a demographic indicator that has been used by demographers for more than a century. One of the main objectives of this study is to apply a new indicator—the cognition-adjusted dependency ratio (CADR)—to remeasure the level of population aging from an innovative point of view. To compute this new index, we apply the mean age-group-specific immediate recall scores for Japan and four other Asian countries, and we compare the results with those derived from the United States and various developed nations in Europe. Our analysis shows that Japan’s pattern and level of age-related decline in cognitive functioning are highly comparable to those of many other developed nations, particularly in Continental Europe. Among the other Asian countries, Malaysia shows a pattern of change similar to countries in Southern Europe, although Malaysia has slightly lower scores than Southern Europe in all age groups. More importantly, these comparative results based on CADR are astonishingly different from the corresponding results obtained from conventional old-age dependency ratios. The Japanese case is the most salient example.

Aging Effect on Visuomotor Adaptation: Mediated by Cognitive Decline.

The question of whether and how aging affects humans’ visuomotor adaptation remains controversial. This study investigates how the effect of aging on visuomotor adaptation is related to age-related cognitive declines. We compared the performance of 100 older people (age: 55–82 years) and 20 young adults (age: 18–27 years) on a visuomotor adaptation task and three cognition tasks. A decline in visuomotor adaptation of older people was well observed. However, this decline was not strongly correlated with chronological age increase but was associated to the age-related declines of cognitive functions and speed of motor planning. We then constructed a structural mediation model in which the declined cognitive resources mediated the effect of age increase on the decline in visuomotor adaptation. The data from the present study was well-explained by the mediation model. These findings indicate that the aging effect on visuomotor adaptation mainly reflects the age-related decline of cognitive functions, which results in insufficient explicit processing on visual perturbation during visuomotor control.

Aged Brains Express Less Melanocortin Receptors, Which Correlates with Age-Related Decline of Cognitive Functions.

Brain G-protein coupled receptors have been hypothesized to be potential targets for maintaining or restoring cognitive function in normal aged individuals or in patients with neurodegenerative disease. A number of recent reports suggest that activation of melanocortin receptors (MCRs) in the brain can significantly improve cognitive functions of normal rodents and of different rodent models of the Alzheimer’s disease. However, the potential impact of normative aging on the expression of MCRs and their potential roles for modulating cognitive function remains to be elucidated. In the present study, we first investigated the expression of these receptors in six different brain regions of young (6 months) and aged (23 months) rats following assessment of their cognitive status. Correlation analysis was further performed to reveal potential contributions of MCR subtypes to spatial learning and memory. Our results revealed statistically significant correlations between the expression of several MCR subtypes in the frontal cortex/hypothalamus and the hippocampus regions and the rats’ performance in spatial learning and memory only in the aged rats. These findings support the hypothesis that aging has a direct impact on the expression and function of MCRs, establishing MCRs as potential drug targets to alleviate aging-induced decline of cognitive function.

Increased Endogenous GDNF in Mice Protects Against Age-Related Decline in Neuronal Cholinergic Markers.

Gradual decline in cholinergic transmission and cognitive function occurs during normal aging, whereas pathological loss of cholinergic function is a hallmark of different types of dementia, including Alzheimer’s disease (AD), Lewy body dementia (LBD), and Parkinson’s disease dementia (PDD). Glial cell line-derived neurotrophic factor (GDNF) is known to modulate and enhance the dopamine system. However, how endogenous GDNF influences brain cholinergic transmission has remained elusive. In this study, we explored the effect of a twofold increase in endogenous GDNF (Gdnf hypermorphic mice, Gdnfwt/hyper) on cholinergic markers and cognitive function upon aging. We found that Gdnfwt/hyper mice resisted an overall age-associated decline in the cholinergic index observed in the brain of Gdnfwt/wt animals. Biochemical analysis revealed that the level of nerve growth factor (NGF), which is important for survival and function of central cholinergic neurons, was significantly increased in several brain areas of old Gdnfwt/hyper mice. Analysis of expression of genes involved in cholinergic transmission in the cortex and striatum confirmed modulation of cholinergic pathways by GDNF upon aging. In line with these findings, Gdnfwt/hyper mice did not undergo an age-related decline in cognitive function in the Y-maze test, as observed in the wild type littermates. Our results identify endogenous GDNF as a potential modulator of cholinergic transmission and call for future studies on endogenous GDNF function in neurodegenerative disorders characterized by cognitive impairments, including AD, LBD, and PDD.

More Teeth and Posterior Balanced Occlusion Are a Key Determinant for Cognitive Function in the Elderly.

Age-related decline in cognitive function is a major challenge in geriatric healthcare. A possible explanation is that the tooth loss or low chewing ability is at cause of cognitive impairment or dementia. The study aimed to investigate the potential relationship between chewing ability and cognitive function in the elderly. A total of 563 participants aged 65 years or over residing in urban and rural areas of South Korea were surveyed. The chewing ability was measured by objectively measurable indications such as the number of remaining teeth, denture status, color-changeable gum, and occlusal balance using T-Scan III®. The cognitive function was measured by the Korean version of Mini-Mental State Examination-Dementia Screening (MMSE-DS) and a score of 24 or more (out of 30) indicates a normal cognition, below 23 indicates cognitive impairment. The association between socio-demographic factors, chewing ability factors, and cognitive function demonstrated statistically significant results. When comparing the denture status and chewing ability, the proportion of need denture group had fewer remaining teeth and anterior balanced occlusion. The average number of remaining teeth in anterior balanced occlusion with cognitive impairment was 11.2 compared to posterior balanced occlusion with the normal cognition 19.2. A multiple linear regression analysis declared a significant correlation between number of remaining teeth, denture status, occlusal balance, and cognitive function. Results of the present study revealed objectively measurable indications are suitable for chewing ability assessment and correlated with cognitive function.

Interleukin 6 reduces allopregnanolone synthesis in the brain and contributes to age-related cognitive decline in mice

Cognitive decline with age is a harmful process that can reduce quality of life. Multiple factors have been established to contribute to cognitive decline, but the overall etiology remains unknown. Here, we hypothesized that cognitive dysfunction is mediated, in part, by increased levels of inflammatory cytokines that alter allopregnanolone (AlloP) levels, an important neurosteroid in the brain. We assessed the levels and regulation of AlloP and the effects of AlloP supplementation on cognitive function in 4-month-old and 24-month-old male C57BL/6 mice. With age, the expression of enzymes involved in the AlloP synthetic pathway was decreased and corticosterone (CORT) synthesis increased. Supplementation of AlloP improved cognitive function. Interestingly, interleukin 6 (IL-6) infusion in young animals significantly reduced the production of AlloP compared with controls. It is notable that inhibition of IL-6 with its natural inhibitor, soluble membrane glycoprotein 130, significantly improved spatial memory in aged mice. These findings were supported by in vitro experiments in primary murine astrocyte cultures, indicating that IL-6 decreases production of AlloP and increases CORT levels. Our results indicate that age-related increases in IL-6 levels reduce progesterone substrate availability, resulting in a decline in AlloP levels and an increase in CORT. Furthermore, our results indicate that AlloP is a critical link between inflammatory cytokines and the age-related decline in cognitive function.

Memory and Learning Deficits Are Associated With Ca2+ Dyshomeostasis in Normal Aging.

Neuronal intracellular Ca2+ homeostasis is critical to the normal physiological functions of neurons and neuronal Ca2+ dyshomeostasis has been associated with the age-related decline of cognitive functions. Accumulated evidence indicates that the underlying mechanism for this is that abnormal intracellular Ca2+ levels stimulate the dysregulation of intracellular signaling, which subsequently induces neuronal cell death. We examined intracellular Ca2+ homeostasis in cortical (in vivo) and hippocampal (in vitro) neurons from young (3-months), middle-age (12-months), and aged (24-months) wild type C57BL6J mice. We found a progressive age-related elevation of intracellular resting calcium ([Ca2+]r) in cortical (in vivo) and hippocampal (in vitro) neurons associated with increased hippocampal neuronal calpain activity and reduced cell viability. In vitro, removal of extracellular Ca2+ or treatment with SAR7334 or dantrolene reduced [Ca2+]r in all age groups and dantrolene treatment lowered calpain activity and increased cell viability. In vivo, both middle-aged and aged mice showed cognitive deficits compared to young mice, which improved after dantrolene treatment. These findings support the hypothesis that intracellular Ca2+ dyshomeostasis is a major mechanism underlying the cognitive deficits seen in both normal aging and degenerative neurologic diseases.

The role of cognitive reserve on prefrontal and premotor cortical activity in visuo-motor response tasks in healthy old adults

Cognitive reserve (CR) is a key factor to mitigate the cognitive decline during the aging process. Here, we used event-related potentials to target the preparatory brain activities associated with different levels of CR during visuo-motor simple response tasks (SRTs) and discriminative response tasks (DRTs). EEG was recorded from 28 healthy old (Age: 72.2 ± 4.7 years) and 14 young (Age: 22.2 ± 2.4 years) individuals during an SRT and a DRT. Depending on the CR median score, old participants were divided into either a high (High-CR) or a low CR (Low-CR) group. Behavioral performance and electrophysiological data were compared across the 3 groups. Compared with the Low-CR, the High-CR group showed larger prestimulus prefrontal (prefrontal negativity) and premotor activity (Bereitschaftspotential–BP), in the SRT, and increased premotor readiness (BP), in the DRT. The High-CR was faster and more accurate than the Low-CR group in the DRT and SRT, respectively. The High-CR group revealed enhanced brain preparatory activities that, paralleled to their behavioral performance, might reflect neural compensation and maintenance effects possibly counteracting the age-related decline in cognitive functioning.

Greater lifestyle engagement is associated with better age-adjusted cognitive abilities.

Previous evidence suggests that modifiable lifestyle factors, such as engagement in leisure activities, might slow the age-related decline of cognitive functions. Less is known, however, about which aspects of lifestyle might be particularly beneficial to healthy cognitive ageing, and whether they are associated with distinct cognitive domains (e.g. fluid and crystallized abilities) differentially. We investigated these questions in the cross-sectional Cambridge Centre for Ageing and Neuroscience (Cam-CAN) data (N = 708, age 18–88), using data-driven exploratory structural equation modelling, confirmatory factor analyses, and age-residualized measures of cognitive differences across the lifespan. Specifically, we assessed the relative associations of the following five lifestyle factors on age-related differences of fluid and crystallized age-adjusted abilities: education/SES, physical health, mental health, social engagement, and intellectual engagement. We found that higher education, better physical and mental health, more social engagement and a greater degree of intellectual engagement were each individually correlated with better fluid and crystallized cognitive age-adjusted abilities. A joint path model of all lifestyle factors on crystallized and fluid abilities, which allowed a simultaneous assessment of the lifestyle domains, showed that physical health, social and intellectual engagement and education/SES explained unique, complementary variance, but mental health did not make significant contributions above and beyond the other four lifestyle factors and age. The total variance explained for fluid abilities was 14% and 16% for crystallized abilities. Our results are compatible with the hypothesis that intellectually and physically challenging as well as socially engaging activities are associated with better crystallized and fluid performance across the lifespan.

OR02-05 Effect of Testosterone Replacement Therapy Added to Intensive Lifestyle Intervention on Cognitive Functions in Frail, Older Veterans with Hypogonadism and Obesity: A Randomized Clinical Trial

Background: Both hypogonadism and obesity are common in older men which might additively exacerbate their age-related decline in cognitive functions. We tested the hypothesis that the addition of testosterone replacement therapy to intensive lifestyle intervention would enhance the benefits of intensive lifestyle intervention on cognition in older men with hypogonadism and obesity. Methods: Eighty-three older (age≥65 years) male veterans with obesity (BMI≥30 kg/m2) and evidence of persistently low AM testosterone (<300 ng/dl) associated with frailty (modified Physical Performance Test score <31) were randomized to six months of: 1) lifestyle therapy (diet-induced weight loss and supervised aerobic and resistance exercise training) + testosterone replacement therapy (LT+Test) or 2) lifestyle therapy + placebo (LT+Pbo). In this secondary analyses, outcomes were changes in cognition as assessed through comprehensive cognitive test battery (Modified Mini-Mental State Exam, Word Fluency Test, Trail Making Test Parts A and B Rey Auditory Verbal Learning Test, Stroop Color and Word Test, and Symbol Digit Modalities Test). We used z scores of changes in the cognitive tests to assess changes in attention, memory, executive function, language, global, and composite cognitive functions in response to the lifestyle and hormonal interventions. Results: After 6 months, body weight decreased similarly in the LT+Test group and LT+Pbo group (decrease of 9.7 kg vs. 10.3 kg, respectively; P=0.91) whereas testosterone levels increased more in the LT+Test than in the LT+Pbo group (increase of 324 ng/dl vs 88 ng/dl, respectively; P<0.001). Memory z-score increased more in the LT+Test group than in the LT+Pbo group (0.73 vs. 0.39, respectively; P=0.03). Moreover, attention z-score increased more in the LT+Test group than in the LT+Pbo group (0.89 vs. 0.38, respectively; P=0.01). On the other hand, changes in executive function z-score, language z-score, and global z-score did not significantly differ between the LT+Test group and LT+Pbo group (0.45 vs 0.37, 0.34 vs 0.07, and 0.55 vs 0.29, respectively; P=0.13 to 0.56). More importantly, the composite cognitive z-score obtained by averaging all z-scores from each domain increased more in the LT+Test group than in the LT+Pbo group (0.56 vs 0.27; P=0.003). Conclusion: These findings suggest that in the specific population of older men with hypogonadism and obesity associated with frailty, testosterone replacement therapy can augment the positive effects on cognition from intensive lifestyle intervention by diet-induced weight loss and combined aerobic and resistance exercise.

Biochips for Physical Exercise Studies

In early 1990s, microfluidics technology was mainly aiming at the manipulation of fluids in micro-scale and nanoscale. At present, with the development of microfluidics, it has been widely used in the life science and medical researches with significant achievements. The microfluidics technology can be used in single cell capture, cell screening, and synthesis of biomacromolecules. Some microfluidic chips have already been commercialized and applied in disease detection, drug delivery and bioscience. However, the physical index oriented wearable technology ignored another part of the most important indications in health monitoring i.e. the body fluid. The body fluid in this review refers to the blood, sweat, interstitial fluid, saliva, tears, and urine. The current medical procedures for the testing of body fluid involve using highly sophisticated instrument such as atomic absorption spectrometry, ion chromatography and gas chromatograph for the detection of specific targets in body fluid. For correct detection of changes in body fluids, it is necessary to intervene in body fluids naturally. Physical fatigue is known to have a direct effect on body fluids. For this reason, microfluidic chips are used in experiments after exercise. Also exercise; diabetes, cancer, cardiovascular disease, muscle, immune, and age-related decline in cognitive function have been documented against the protect. In addition, regular physical exercise is the most powerful initiative known to have positive effects on health and aging.