From fetus to older age: A review of brain metabolic changes across the lifespan

IntroductionThe knowledge of metabolic changes across the lifespan is poorly understood. Thus we systematically reviewed the available literature to determine the changes in brain biochemical composition from fetus to older age and tried to explain them in the context of neural, cognitive, and behavioural changes.MethodsThe search identified 1262 articles regarding proton magnetic resonance spectroscopy (1H MRS) examinations through December 2017. The following data was extracted: age range of the subjects, number of subjects studied, brain regions studied, MRS sequence used, echo time, MR system, method of statistical analysis, metabolites analyzed, significant differences in metabolites concentrations with age as well as the way of presentation of the results.Results82 studies that described brain metabolite changes with age were identified. Reports on metabolic changes related to healthy aging were analyzed and discussed among six basic age groups: fetuses, infants, children, adolescents, adults, and the elderly as well as between groups and during the whole lifetime.DiscussionThe results presented in the reviewed papers provide evidence that normal aging is associated with a number of metabolic changes characteristic for every period of life. Therefore, it can be concluded that the age matching is essential for comparative studies of disease states using 1H MRS.     

Managing urinary incontinence across the lifespan

In the 1996 baseline surveysoftheAustralianLongitudinal StudyofWomen’s Health (ALSWH), 36.1% of mid-age women (45–50) and 35% of older women (70–75) reported leaking urine. This study aimed to investigate (a) the range of self-management strategies used to deal with urinary incontinence (UI); (b) the reasons why many women who report leaking urine do not seek help for UI; and (c) the types of health professionals consulted and treatment provided, and perceptions of satisfaction with these, among a sample of women in each age group who reported leaking urine “often” at baseline. Five hundred participants were randomly selected from women in each of the mid-age and older cohorts of the ALSWH who had reported leaking urine “often” ina previous survey. Details about UI (frequency, severity, and situations), self-management behaviors and help-seeking for UI, types of health professional consulted, recommended treatment for the problem, and satisfaction with the service provided by health care professionals and the outcomes of recommended treatments were sought through a self-report mailed follow-up survey. Most respondents had leaked urineinthe last month (94% and 91% of mid-age and older women, respectively), and 72.2% and 73.1% of mid-aged and older women, respectively, had sought help or advice about their UI. In both age groups, the likelihood of having sought help significantly increased with severity of incontinence. The most common reasons for not seeking help were that the women felt they could manage the problem themselves or they did not consider it to be a problem. Many women in both cohorts had employed avoidance techniques in an attempt to prevent leaking urine, including reducing their liquid consumption, going to the toilet “just in case,” and rushing to the toilet the minute they felt the need to. Strategies are needed to inform women who experience UI of more effective management techniques and the possible health risks associated with commonly used avoidance behaviors. There may be a need to better publicize existing incontinence services and improve access to these services for women of all ages.     

Stability of physical activity across the lifespan

Physical activity is associated with various health-relevant psychosocial and physiological processes, but activity stability across extended time periods is inadequately understood. This lifespan longitudinal cohort study examined activity levels of 723 males and 554 females. Associations across time were computed and structural equation modeling compared a one factor model and a simplex model. Results showed activity levels are somewhat stable from childhood through middle and late adulthood. Further, a simplex model provided a better fit than a one factor model. Successful models and interventions to improve health will likely require a more nuanced, pattern-sensitive understanding of physical activity across time.     

Quantification of the spatiotemporal microstructural organization of the human brain association, projection and commissural pathways across the lifespan using diffusion tensor tractography

Using diffusion tensor tractography, we quantified the microstructural changes in the association, projection, and commissural compact white matter pathways of the human brain over the lifespan in a cohort of healthy right-handed children and adults aged 6–68 years. In both males and females, the diffusion tensor radial diffusivity of the bilateral arcuate fasciculus, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, uncinate fasciculus, corticospinal, somatosensory tracts, and the corpus callosum followed a U-curve with advancing age; fractional anisotropy in the same pathways followed an inverted U-curve. Our study provides useful baseline data for the interpretation of data collected from patients.     

Epigenetic influence of social experiences across the lifespan

The critical role of social interactions in driving phenotypic variation has long been inferred from the association between early social deprivation and adverse neurodevelopmental outcomes. Recent evidence has implicated molecular pathways involved in the regulation of gene expression as one possible route through which these long‐term outcomes are achieved. These epigenetic effects, though not exclusive to social experiences, may be a mechanism through which the quality of the social environment becomes embedded at a biological level. Moreover, there is increasing evidence for the transgenerational impact of these early experiences mediated through changes in social and reproductive behavior exhibited in adulthood. In this review, recent studies which highlight the epigenetic effects of parent–offspring, peer and adult social interactions both with and across generations will be discussed and the implications of this research for understanding the developmental origins of individual differences in brain and behavior will be explored. © 2010 Wiley Periodicals, Inc. Dev Psychobiol 52: 299–311, 2010.     

Diffusion tensor quantification of the macrostructure and microstructure of human midsagittal corpus callosum across the lifespan

The midsagittal cross-sectional area of the human corpus callosum (CC) has been used by many researchers as a marker of development, natural aging, and neurodegenerative and acquired pathologies. The availability of non-invasive MRI methods for quantifying the macrostructural and microstructural organization of the CC would help to clarify the CC contribution to behavior and cognition in both health and disease. In this report, we extended and validated the ability of a recently described semi-automated diffusion tensor imaging tissue segmentation method to utilize the high orientation contrast of the CC on diffusion tensor imaging. Using a cohort of healthy right-handed children and adults aged 7-59 years, we show gender-independent non-linear (quadratic) and strongly correlated growth trends in the CC area and the corresponding diffusion tensor fractional anisotropy (r = 0.67; P < 1 x 10(-10)). Our results provide preliminary evidence that diffusion tensor anisotropy in the living CC may be related to the number of small myelinated fibers.     

Turner syndrome: four challenges across the lifespan

Turner syndrome (TS) is a sex chromosome condition that occurs in approximately 1/2,500 live female births. Despite the prevalence of this chromosomal condition, the challenges these women face throughout their lives are not fully understood. This qualitative research study aimed to characterize the subjective experiences of individuals with TS throughout their lifespan, to investigate their concerns and obstacles, and to offer insight into the strengths and weaknesses of health care delivery, as they perceived them. Ninety-seven girls and women with TS and 21 parents consented to participate in this interview study. Interviews were semi-structured and open-ended in design. Questions sought to elicit responses relating to existing concerns associated with their condition and positive and negative health care experiences. Participants were divided into four age categories (childhood, adolescence, adulthood, and mature adulthood) to facilitate a comparative analysis across the age spectrum. Regardless of age, infertility was the most frequently cited concern followed closely by short stature. Sexual development and function and general health were also viewed as challenges by a number of participants in each age group. Although the relative weight of these four concerns tended to shift based upon the individual's age and life experiences, all four issues remained significant throughout the lifespan. Enhanced awareness of the evolving physical and psychological challenges faced by girls and women with TS may help health care providers (HCPs) improve the quality of life for these individuals.     

Rehabilitation across the lifespan for individuals with arthrogryposis

Arthrogryposis multiplex congenita (AMC) can be a perplexing diagnosis that consists of limited range of motion (ROM) and decreased muscle strength in multiple joints. The person with AMC often possesses a certain tenacity and “spunk” that assists them with adjusting and adapting to the realities of daily life. The rehabilitation process assists the individual with AMC in achieving and maintaining the maximal active and passive range of motion and strength in order to participate in activities of daily living (ADL) throughout the developmental stages. The result of this life‐long process is greatly impacted by collaboration among the multidisciplinary teams. Ultimately, rehabilitation should focus on three levels of treatment: (a) body structure, (b) activity, and (c) participation. This article describes rehabilitation across the lifespan—focusing on the therapeutic needs in the infant, toddler, school age and teenage/adult years—while also highlighting opportunities for improvement.     

Modeling hippocampal neurogenesis across the lifespan in seven species

The aim of this study was to estimate the number of new cells and neurons added to the dentate gyrus across the lifespan, and to compare the rate of age-associated decline in neurogenesis across species. Data from mice (Mus musculus), rats (Rattus norvegicus), lesser hedgehog tenrecs (Echinops telfairi), macaques (Macaca mulatta), marmosets (Callithrix jacchus), tree shrews (Tupaia belangeri), and humans (Homo sapiens) were extracted from 21 data sets published in 14 different reports. Analysis of variance (ANOVA), exponential, Weibull, and power models were fit to the data to determine which best described the relationship between age and neurogenesis. Exponential models provided a suitable fit and were used to estimate the relevant parameters. The rate of decrease of neurogenesis correlated with species longevity (r = 0.769, p = 0.043), but not body mass or basal metabolic rate. Of all the cells added postnatally to the mouse dentate gyrus, only 8.5% (95% confidence interval [CI], 1.0% to 14.7%) of these will be added after middle age. In addition, only 5.7% (95% CI 0.7% to 9.9%) of the existing cell population turns over from middle age and onward. Thus, relatively few new cells are added for much of an animal's life, and only a proportion of these will mature into functional neurons.     

Neuropsychological functioning in people with ADHD across the lifespan

ADHD is defined by behavioral characteristics similar to neuropsychological disorders of executive dysfunction. This paper is a literature review of the neurocognitive characteristics of ADHD from early childhood through adulthood. The author addresses the development of the concept of attention and executive function (EF) deficits in ADHD, clinical neuropsychological studies of pre-teenage children, teenagers and adults with ADHD, gender and the role of psychiatric co-morbidity including the relationship of learning disabilities to ADHD, heterogeneity of neuropsychological dysfunctions, experimental neuropsychological studies, the relationship of brain structure to function, psychopharmacology of ADHD, and clinical neuropsychological assessment. The group data clearly supports the hypothesis that executive dysfunctions are correlates of ADHD regardless of gender and age, and these EF deficits are exacerbated by co-morbidity with learning disabilities such as dyslexia. However, there is limited data on children under the age of 5, teenagers from age 13-18, and adults with ADHD over the age of 40. Studies of individual classification of people with ADHD compared to healthy, non-psychiatric controls do not support the use of neuropsychological tests for the clinical diagnosis of ADHD, and indicate that not all persons with ADHD have EF deficits. Some persons with ADHD may have deficits in brain reward systems that are relatively independent of EF impairments. Future research should clarify the multiple sources of ADHD impairments, continue to refine neuropsychological tools optimized for assessment, and incorporate longitudinal, developmental designs to understand ADHD across the lifespan.     

Rest-activity rhythms and white matter microstructure across the lifespan

Study ObjectivesThe purpose of this study was to examine how rest-activity (RA) rhythm stability may be associated with white matter microstructure across the lifespan in healthy adults free of significant cardiovascular risk.MethodsWe analyzed multi-shell diffusion tensor images from 103 healthy young and older adults using tract-based spatial statistics (TBSS) to examine relationships between white matter microstructure and RA rhythm stability. RA measures were computed using both cosinor and non-parametric methods derived from 7 days of actigraphy data. Fractional anisotropy (FA) and mean diffusivity (MD) were examined in this analysis. Because prior studies have suggested that the corpus callosum (CC) is sensitive to sleep physiology and RA rhythms, we also conducted a focused region of interest analysis on the CC.ResultsGreater rest-activity rhythm stability was associated with greater FA across both young and older adults, primarily in the CC and anterior corona radiata. This effect was not moderated by age group. While RA measures were associated with sleep metrics, RA rhythm measures uniquely accounted for the variance in white matter integrity.ConclusionsThis study strengthens existing evidence for a relationship between brain white matter structure and RA rhythm stability in the absence of health risk factors. While there are differences in RA stability between age groups, the relationship with brain white matter was present across both young and older adults. RA rhythms may be a useful biomarker of brain health across both periods of adult development.     

Meta-analysis of age and actigraphy-assessed sleep characteristics across the lifespan

Study ObjectivesSleep quantity and continuity vary across the lifespan. Actigraphy is a reliable and widely used behavioral measure of sleep in research and personal health monitoring. This meta-analysis provides a novel examination of whether age (in years) is associated with actigraphy-assessed sleep across the lifespan.MethodsA systematic search of PubMed, Embase.com, Cochrane CENTRAL, and PsycINFO using “actigraphy” and “sleep” terms provided 7079 titles/abstracts; studies of individuals with known psychiatric or medical comorbidities were excluded. Ninety-one articles (N = 23 365) provided data for six meta-analyses examining sleep duration (k = 89), sleep efficiency (k = 58), bedtime (k = 19) and waketime (k = 9) for individuals ages 6–21, and bedtime (k = 7) and waketime (k = 7) for individuals ages 22 and older.ResultsAt older ages, sleep duration was shorter (r = −0.12) and sleep efficiency was lower (r = −0.05). Older age was associated with later bedtime (r = 0.37) and wake-up time (r = 0.24) from ages 6–21, whereas older age was associated with earlier bedtime (r = −0.66) and wake-up time (r = −0.59) for ages 22 and above. The strength of these associations was modified by study continent, but not by any other moderator.ConclusionsAge was negatively associated with actigraphy-assessed sleep duration and efficiency, but the effects were small in magnitude. On the other hand, large associations were observed between age and sleep timing, despite a smaller literature and the absence of analyzable data for ages 30–60. Changes in sleep timing, rather than changes in sleep duration or continuity, may better characterize the effects of age on human sleep.     

Ethnicity‐related skeletal muscle differences across the lifespan

Despite research and clinical significance, limited information is available on the relations between skeletal muscle (SM) and age in adults, specifically among Hispanics, African Americans (AA), and Asians. The aim was to investigate possible sex and ethnic SM differences in adults over an age range of 60 years. Subjects were 468 male and 1280 female adults (≥18 years). SM was estimated based on DXA‐measured appendicular lean‐soft tissue using a previously reported prediction equation. Locally weighted regression smoothing lines were fit to examine SM trends and to localize age cutoffs; piecewise multiple linear regression models were then applied, controlling for weight and height, to identify age cutoffs for sex‐specific changes in SM among the ethnic groups. The age of 27 years was identified for women and men as the cut‐off after which SM starts to show a negative association with age. Both sexes had a similar ethnic pattern for expected mean SM at the age cutoff, with AA presenting the highest SM values, followed by Whites, Hispanics, and Asians. After the age cutoffs, the lowering of SM differed by ethnicity and sex: AA women showed the greatest SM lowering whereas Hispanic women had the least. Hispanic men tended to show a higher negative association of SM with age followed by AA and Whites. To conclude, significant sex and ethnic differences exist in the magnitude of negative associations of SM with age >27 years. Further studies using a longitudinal design are needed to explore the associations of ethnicity‐related decline of SM with health risks. Am. J. Hum. Biol. 2010. © 2009 Wiley‐Liss, Inc.     

Pregnancy and multiple sclerosis: Clinical effects across the lifespan

Multiple sclerosis (MS) is commonly diagnosed in women of childbearing age. Having a greater understanding of the effects of pregnancy on the course of MS will lead to improved family-planning counselling for women. We found well-established evidence for a protective effect of pregnancy on relapse occurrence in historical cohorts. More recent studies suggest that the protective effect of pregnancy against relapse may be lost in those women with more active disease treated with high efficacy therapies. Furthermore, a strong body of evidence suggests that gravidity after diagnosis of MS does not lead to worse long-term outcomes. More contentious however, is whether pregnancy can delay a first episode of demyelination or a confirmed diagnosis of MS. This review provides a detailed analysis of the literature relating to the clinical effects of pregnancy on MS outcomes across a woman's reproductive lifespan.     

Evidence for differential human slow-wave activity regulation across the brain

The regulation of the timing of sleep is thought to be linked to the temporal dynamics of slow‐wave activity [SWA, electroencephalogram (EEG) spectral power in the ～0.75–4.5 Hz range] in the cortical non‐rapid eye movement (NREM) sleep EEG. In the two‐process model of sleep regulation, SWA was used as a direct indication of sleep debt, or Process S. Originally, estimation of the latter was performed in a gross way, by measuring average SWA across NREM–REM sleep cycles, fitting an exponential curve to the values thus obtained and estimating its time constant. In later studies, SWA was assumed to be proportional to the instantaneous decay rate of Process S, rather than taken as a direct reflection of S. Following up on this, we extended the existing model of SWA dynamics in which the effects of intrusions of REM sleep and wakefulness were incorporated. For each subject, a ‘gain constant’ can be estimated that quantifies the efficiency of SWA in dissipating S. As the course of SWA is variable across cortical locations, local differences are likely to exist in the rate of discharge of S, eventually leading to different levels of S in different cortical regions. In this study, we estimate the extent of local differences of SWA regulation on the basis of the extended model of SWA dynamics, for 26 locations on the scalp. We observed higher efficiency of SWA in dissipation of S in frontal EEG derivations, suggesting that SWA regulation has a clear local aspect. This result further suggests that the process involved in (local) SWA regulation cannot be identical to the Process S involved (with Process C) in effectual determination of sleep timing – a single behaviour that cannot vary between locations on the scalp. We therefore propose to distinguish these two representations and characterize the former, purely SWA‐related, as ‘Process Z’, which then is different for different locations on the scalp. To demonstrate those differences, we compare the gain constants derived for the medial EEG derivations (Fz, Cz, Pz, Oz) with each other and with the decay rate derived from SWA values per NREM–REM sleep cycle.     

Short- and long-term spatial delayed response performance across the lifespan

Delayed response paradigms have been used to examine the neural basis of short and long-term memory in humans. However, limited information exists on how delayed response performance changes across the lifespan. Using a well-validated spatial delayed response (SDR) task, we examined performance at short and long delays in over 300 control participants, 7 to 80 years old. We found a significant nonlinear relation between age and short delay performance (children and older adults worse than young adults) and a significant effect of delay length across the entire lifespan (long worse than short; largest in the youngest children, diminishing nonlinearly with age). This study compares short and long-term spatial memory and suggests that the relation between these systems may alter across the lifespan.