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Sample records for impairs later-life cortical

  1. Prenatal Exposure to Benzo(a)pyrene Impairs Later-Life Cortical Neuronal Function

    PubMed Central

    McCallister, Monique M.; Maguire, Mark; Ramesh, Aramandla; Aimin, Qiao; Liu, Sheng; Khoshbouei, Habibeh; Aschner, Michael; Ebner, Ford F.; Hood, Darryl B.

    2009-01-01

    Prenatal exposure to environmental contaminants, such as Benzo(a)pyrene [B(a)P] has been shown to impair brain development. The overarching hypothesis of our work is that glutamate receptor subunit expression is crucial for cortical evoked responses and that prenatal B(a)P exposure modulates the temporal developmental expression of glutamatergic receptor subunits in the somatosensory cortex. To characterize prenatal B(a)P exposure on the development of cortical function, pregnant Long Evans rats were exposed to low-level B(a)P (300μg/kg BW) by oral gavage on gestational days 14 to 17. At this exposure dose, there was no significant effect of B(a)P on 1) the number of pups born per litter, 2) the pre-weaning growth curves and 3) initial and final brain to body weight ratios. Control and B(a)P-exposed offspring were profiled for B(a)P metabolites in plasma and whole brain during the pre-weaning period. No detectable levels of metabolites were found in the control offspring. However, a time-dependent decrease in total metabolite concentration was observed in B(a)P-exposed offspring. On PND100-120, cerebrocortical mRNA expression was determined for the glutamatergic NMDA receptor subunit (NR2B) in control and B(a)P-exposed offspring. Neural activity was also recorded from neurons in primary somatic sensory (barrel) cortex. Semiquantitative PCR from B(a)P-exposed offspring revealed a significant 50% reduction in NR2B mRNA expression in B(a)P-exposed offspring relative to controls. Recordings from B(a)P-exposed offspring revealed that N-methyl-D-aspartate (NMDA) receptor -dependent neuronal activity in barrel cortex evoked by whisker stimulation was also significantly reduced (70%) as compared to controls. Analysis showed that the greatest deficit in cortical neuronal responses occurred in the shorter latency epochs from 5-20ms post-stimulus. The results suggest that in utero exposure to benzo(a)pyrene results in diminished mRNA expression of the NMDA NR2B receptor

  2. Cortical Visual Impairment

    MedlinePlus

    ... Frequently Asked Questions Español Condiciones Chinese Conditions Cortical Visual Impairment En Español Read in Chinese What is cortical visual impairment? Cortical visual impairment (CVI) is a decreased ...

  3. Age of first exposure to football and later-life cognitive impairment in former NFL players.

    PubMed

    Stamm, Julie M; Bourlas, Alexandra P; Baugh, Christine M; Fritts, Nathan G; Daneshvar, Daniel H; Martin, Brett M; McClean, Michael D; Tripodis, Yorghos; Stern, Robert A

    2015-03-17

    To determine the relationship between exposure to repeated head impacts through tackle football prior to age 12, during a key period of brain development, and later-life executive function, memory, and estimated verbal IQ. Forty-two former National Football League (NFL) players ages 40-69 from the Diagnosing and Evaluating Traumatic Encephalopathy using Clinical Tests (DETECT) study were matched by age and divided into 2 groups based on their age of first exposure (AFE) to tackle football: AFE <12 and AFE ≥12. Participants completed the Wisconsin Card Sort Test (WCST), Neuropsychological Assessment Battery List Learning test (NAB-LL), and Wide Range Achievement Test, 4th edition (WRAT-4) Reading subtest as part of a larger neuropsychological testing battery. Former NFL players in the AFE <12 group performed significantly worse than the AFE ≥12 group on all measures of the WCST, NAB-LL, and WRAT-4 Reading tests after controlling for total number of years of football played and age at the time of evaluation, indicating executive dysfunction, memory impairment, and lower estimated verbal IQ. There is an association between participation in tackle football prior to age 12 and greater later-life cognitive impairment measured using objective neuropsychological tests. These findings suggest that incurring repeated head impacts during a critical neurodevelopmental period may increase the risk of later-life cognitive impairment. If replicated with larger samples and longitudinal designs, these findings may have implications for safety recommendations for youth sports. © 2015 American Academy of Neurology.

  4. Age of first exposure to football and later-life cognitive impairment in former NFL players

    PubMed Central

    Stamm, Julie M.; Bourlas, Alexandra P.; Baugh, Christine M.; Fritts, Nathan G.; Daneshvar, Daniel H.; Martin, Brett M.; McClean, Michael D.; Tripodis, Yorghos

    2015-01-01

    Objective: To determine the relationship between exposure to repeated head impacts through tackle football prior to age 12, during a key period of brain development, and later-life executive function, memory, and estimated verbal IQ. Methods: Forty-two former National Football League (NFL) players ages 40–69 from the Diagnosing and Evaluating Traumatic Encephalopathy using Clinical Tests (DETECT) study were matched by age and divided into 2 groups based on their age of first exposure (AFE) to tackle football: AFE <12 and AFE ≥12. Participants completed the Wisconsin Card Sort Test (WCST), Neuropsychological Assessment Battery List Learning test (NAB-LL), and Wide Range Achievement Test, 4th edition (WRAT-4) Reading subtest as part of a larger neuropsychological testing battery. Results: Former NFL players in the AFE <12 group performed significantly worse than the AFE ≥12 group on all measures of the WCST, NAB-LL, and WRAT-4 Reading tests after controlling for total number of years of football played and age at the time of evaluation, indicating executive dysfunction, memory impairment, and lower estimated verbal IQ. Conclusions: There is an association between participation in tackle football prior to age 12 and greater later-life cognitive impairment measured using objective neuropsychological tests. These findings suggest that incurring repeated head impacts during a critical neurodevelopmental period may increase the risk of later-life cognitive impairment. If replicated with larger samples and longitudinal designs, these findings may have implications for safety recommendations for youth sports. PMID:25632088

  5. Stress, gender, cognitive impairment, and outpatient physician use in later life.

    PubMed

    Krause, N

    1996-01-01

    The purpose of this study was to look at the interface between stressful life events, gender, cognitive impairment, and the use of outpatient physician services among older adults. A theoretical rationale is presented, suggesting that older men who are suffering from either mild or moderate levels of cognitive impairment are especially likely to use outpatient physician services when they are confronted by undesirable stressful events. Analyses with data provided by a nationwide sample of elderly people provide support for this complex three-way interaction.

  6. Community environment, cognitive impairment and dementia in later life: results from the Cognitive Function and Ageing Study

    PubMed Central

    Wu, Yu-Tzu; Prina, A. Matthew; Jones, Andrew P.; Barnes, Linda E.; Matthews, Fiona E.; Brayne, Carol

    2015-01-01

    Background: few studies have investigated the impact of the community environment, as distinct from area deprivation, on cognition in later life. This study explores cross-sectional associations between cognitive impairment and dementia and environmental features at the community level in older people. Method: the postcodes of the 2,424 participants in the year-10 interview of the Cognitive Function and Ageing Study in England were mapped into small area level geographical units (Lower-layer Super Output Areas) and linked to environmental data in government statistics. Multilevel logistic regression was conducted to investigate associations between cognitive impairment (defined as MMSE ≤ 25), dementia (organicity level ≥3 in GMS-AGECAT) and community level measurements including area deprivation, natural environment, land use mix and crime. Sensitivity analyses tested the impact of people moving residence within the last two years. Results: higher levels of area deprivation and crime were not significantly associated with cognitive impairment and dementia after accounting for individual level factors. Living in areas with high land use mix was significantly associated with a nearly 60% reduced odds of dementia (OR: 0.4; 95% CI: 0.2, 0.8) after adjusting for individual level factors and area deprivation, but there was no linear trend for cognitive impairment. Increased odds of dementia (OR: 2.2, 95% CI: 1.2, 4.2) and cognitive impairment (OR: 1.4, 95% CI: 1.0, 2.0) were found in the highest quartile of natural environment availability. Findings were robust to exclusion of the recently relocated. Conclusion: features of land use have complex associations with cognitive impairment and dementia. Further investigations should focus on environmental influences on cognition to inform health and social policies. PMID:26464419

  7. Cumulative Head Impact Exposure Predicts Later-Life Depression, Apathy, Executive Dysfunction, and Cognitive Impairment in Former High School and College Football Players.

    PubMed

    Montenigro, Philip H; Alosco, Michael L; Martin, Brett M; Daneshvar, Daniel H; Mez, Jesse; Chaisson, Christine E; Nowinski, Christopher J; Au, Rhoda; McKee, Ann C; Cantu, Robert C; McClean, Michael D; Stern, Robert A; Tripodis, Yorghos

    2017-01-15

    The term "repetitive head impacts" (RHI) refers to the cumulative exposure to concussive and subconcussive events. Although RHI are believed to increase risk for later-life neurological consequences (including chronic traumatic encephalopathy), quantitative analysis of this relationship has not yet been examined because of the lack of validated tools to quantify lifetime RHI exposure. The objectives of this study were: 1) to develop a metric to quantify cumulative RHI exposure from football, which we term the "cumulative head impact index" (CHII); 2) to use the CHII to examine the association between RHI exposure and long-term clinical outcomes; and 3) to evaluate its predictive properties relative to other exposure metrics (i.e., duration of play, age of first exposure, concussion history). Participants included 93 former high school and collegiate football players who completed objective cognitive and self-reported behavioral/mood tests as part of a larger ongoing longitudinal study. Using established cutoff scores, we transformed continuous outcomes into dichotomous variables (normal vs. impaired). The CHII was computed for each participant and derived from a combination of self-reported athletic history (i.e., number of seasons, position[s], levels played), and impact frequencies reported in helmet accelerometer studies. A bivariate probit, instrumental variable model revealed a threshold dose-response relationship between the CHII and risk for later-life cognitive impairment (p < 0.0001), self-reported executive dysfunction (p < 0.0001), depression (p < 0.0001), apathy (p = 0.0161), and behavioral dysregulation (p < 0.0001). Ultimately, the CHII demonstrated greater predictive validity than other individual exposure metrics.

  8. Creativity in later life.

    PubMed

    Price, K A; Tinker, A M

    2014-08-01

    The ageing population presents significant challenges for the provision of social and health services. Strategies are needed to enable older people to cope within a society ill prepared for the impacts of these demographic changes. The ability to be creative may be one such strategy. This review outlines the relevant literature and examines current public health policy related to creativity in old age with the aim of highlighting some important issues. As well as looking at the benefits and negative aspects of creative activity in later life they are considered in the context of the theory of "successful ageing". Creative activity plays an important role in the lives of older people promoting social interaction, providing cognitive stimulation and giving a sense of self-worth. Furthermore, it is shown to be useful as a tool in the multi-disciplinary treatment of health problems common in later life such as depression and dementia. There are a number of initiatives to encourage older people to participate in creative activities such as arts-based projects which may range from visual arts to dance to music to intergenerational initiatives. However, participation shows geographical variation and often the responsibility of provision falls to voluntary organisations. Overall, the literature presented suggests that creative activity could be a useful tool for individuals and society. However, further research is needed to establish the key factors which contribute to patterns of improved health and well-being, as well as to explore ways to improve access to services.

  9. Reflexive Planning for Later Life

    ERIC Educational Resources Information Center

    Denton, Margaret A.; Kemp, Candace L.; French, Susan; Gafni, Amiram; Joshi, Anju; Rosenthal, Carolyn J.; Davies, Sharon

    2004-01-01

    Informed by Giddens' (1991) concept of "reflexive life" planning and the notion of later life as a time of increasing social and financial risk, this research explores the idea of "reflexive planning for later life". We utilize a conceptual model that incorporates three types of planning for later life: public protection, self-insurance, and…

  10. Discontinuity of cortical gradients reflects sensory impairment

    PubMed Central

    Saadon-Grosman, Noam; Tal, Zohar; Itshayek, Eyal; Amedi, Amir; Arzy, Shahar

    2015-01-01

    Topographic maps and their continuity constitute a fundamental principle of brain organization. In the somatosensory system, whole-body sensory impairment may be reflected either in cortical signal reduction or disorganization of the somatotopic map, such as disturbed continuity. Here we investigated the role of continuity in pathological states. We studied whole-body cortical representations in response to continuous sensory stimulation under functional MRI (fMRI) in two unique patient populations—patients with cervical sensory Brown-Séquard syndrome (injury to one side of the spinal cord) and patients before and after surgical repair of cervical disk protrusion—enabling us to compare whole-body representations in the same study subjects. We quantified the spatial gradient of cortical activation and evaluated the divergence from a continuous pattern. Gradient continuity was found to be disturbed at the primary somatosensory cortex (S1) and the supplementary motor area (SMA), in both patient populations: contralateral to the disturbed body side in the Brown-Séquard group and before repair in the surgical group, which was further improved after intervention. Results corresponding to the nondisturbed body side and after surgical repair were comparable with control subjects. No difference was found in the fMRI signal power between the different conditions in the two groups, as well as with respect to control subjects. These results suggest that decreased sensation in our patients is related to gradient discontinuity rather than signal reduction. Gradient continuity may be crucial for somatotopic and other topographical organization, and its disruption may characterize pathological processing. PMID:26655739

  11. Flourishing in later life.

    PubMed

    Momtaz, Yadollah Abolfathi; Hamid, Tengku Aizan; Haron, Sharifah Azizah; Bagat, Mohamad Fazdillah

    2016-01-01

    Flourishing is a relatively new concept in positive psychology that considers hedonic and eudaimonic aspects of well-being. The current study aims to identify the prevalence and socio-demographic and health factors associated with flourishing among older Malaysians. The sample for this study consisting of 2202 community-dwelling older Malaysians was obtained from a national survey entitled "Identifying Psychosocial and Identifying Economic Risk Factor of Cognitive Impairment among Elderly", conducted from May 2013 to April 2014. Data analyses were conducted using the IBM SPSS Version 22.0 and AMOS Version 22.0. The average age of the respondents was 69.05 (SD=6.24) years. Descriptive results showed that 50.1% of the respondents were flourishing in life, 36.3% were languishing, 8.4% were struggling, and 5.2% were floundering in life. The results of Multiple logistic regression analysis revealed that gender, employment status, level of education, having living children, and chronic medical conditions are significantly associated with flourishing. However, age, marital status, living alone, and economic status did not have much impact on flourishing. To the best of our knowledge, the current study is one of the first studies that conceptualizes and assesses flourishing among older adults in Malaysia. The findings from the present study make important contributions to the existing literature on well-being. It is suggested that health and social care professionals working with older adults adopt a comprehensive approach to identify and propel non-flourishing people toward flourishing in life. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  12. Depressive symptoms in later life: differential impact of social support and motivational processes on depression in individuals with and without cognitive impairment.

    PubMed

    Fankhauser, Sonja; Drobetz, Reinhard; Mortby, Moyra; Maercker, Andreas; Forstmeier, Simon

    2014-12-01

    This study investigates the role of a motivational process based on a composite of four subcomponents (self-efficacy, decision regulation, activation regulation and motivation regulation), as a mediator of the relationship between social support and depression assessed with the Geriatric Depression Scale in cognitively impaired and unimpaired individuals. Participants were 229 adults with a mean age of 74 years (range: 52-94 years). The sample comprised 64 participants diagnosed with mild cognitive impairment (MCI), 47 participants diagnosed with early-stage Alzheimer's disease (AD), and a group of 118 participants without any cognitive impairment. In this cross-sectional study, bivariate correlations and linear regression models were used to assess the association between the predictor variables and depression. Linear regression models were controlled for age, gender, education, cognitive status, cognitive impairment and activities. In the total sample, social support (β = -0.15, p < 0.05) and motivational processes (β = -0.41, p < 0.001) were significantly associated with depression; the impact of social support was mediated by motivational processes. While motivational processes were associated with depression in all three groups (no impairment: β = -0.61, p < 0.001; MCI: β = -0.28, p < 0.05; early AD: β = -0.30, p < 0.06), social support lost significance (no impairment: β = -0.36, p < 0.001; MCI: β = 0.07, p = 0.59; early AD: β = -0.08, p = 0.62). Based on these findings, it can be argued that the impact of social support on depressive symptoms is attenuated by cerebral deterioration in cognitively impaired individuals, while motivational processes remain relevant.

  13. Sexual behavior in later life.

    PubMed

    DeLamater, John; Moorman, Sara M

    2007-12-01

    This research tests the influences of age, biological, and psychosocial factors on sexual expression in later life. The American Association of Retired Persons Modern Maturity Sexuality Survey collected data on diagnosed illnesses, treated illnesses, sexual desire, sexual attitudes, partner circumstances, and sexual behavior from 1,384 persons ages 45 and older. Ordered logistic regression models estimate the associations of age, biological, and psychosocial factors with the frequency of five sexual behaviors. Diagnosed illnesses and treatments are generally unrelated to frequency of sexual activity. Sexual attitudes are related to frequency of partnered behavior and sexual desire is related to frequency of masturbation among both women and men. Satisfaction with the physical relationship with a partner is strongly related to behavior. Age remains significant after all other factors are controlled. The authors conclude that the nature of sexual expression in later life reflects the interplay of body, mind, and social context.

  14. Preserving Dignity in Later Life.

    PubMed

    São José, José Manuel

    2016-09-01

    This article examines how elders who receive social care in the community experience loss of dignity and how they preserve their dignity. Qualitative research revealed that loss of dignity is a major concern for these elders and that they preserve their dignity differently, ranging from actively engaging with life to detaching themselves from life. We conclude that, in later life, preserving dignity while receiving social care differs from preserving dignity in the context of health care, especially health care provided in institutional settings. Furthermore, preserving dignity in later life, while receiving social care, is a complex process, depending not only on performing activities and individual action and responsibility, but also on other actions, some of them involving a certain inactivity/passivity, and interactions with others, especially caregivers. This article offers some insights to developing better policies and care practices for promoting dignity in the context of community-based social care.

  15. Neural-Based Visual Stimulation with Infants with Cortical Impairment.

    ERIC Educational Resources Information Center

    Powell, S. A.

    1996-01-01

    In order to shed light on the needs of children with cortical visual impairments, normal visual development of infants is described. Infant preferences for motion, faces, and black-and-white patterns are explained. Colors useful in stimulating vision development and the time needed for exposure to visual stimuli are discussed. (CR)

  16. Observations on the Habilitation of Children with Cortical Visual Impairment.

    ERIC Educational Resources Information Center

    Groenveld, M.; And Others

    1990-01-01

    This article discusses the increasing incidence of cortical visual impairments, resulting from medical advancements making possible the survival of critically ill children with severe brain damage. Discussed are the prevalence of multiple handicaps, formation of visual concepts, foreground/background distinction, potential for mainstreaming, use…

  17. Neural-Based Visual Stimulation with Infants with Cortical Impairment.

    ERIC Educational Resources Information Center

    Powell, S. A.

    1996-01-01

    In order to shed light on the needs of children with cortical visual impairments, normal visual development of infants is described. Infant preferences for motion, faces, and black-and-white patterns are explained. Colors useful in stimulating vision development and the time needed for exposure to visual stimuli are discussed. (CR)

  18. Observations on the Habilitation of Children with Cortical Visual Impairment.

    ERIC Educational Resources Information Center

    Groenveld, M.; And Others

    1990-01-01

    This article discusses the increasing incidence of cortical visual impairments, resulting from medical advancements making possible the survival of critically ill children with severe brain damage. Discussed are the prevalence of multiple handicaps, formation of visual concepts, foreground/background distinction, potential for mainstreaming, use…

  19. Impaired cortical mitochondrial function following TBI precedes behavioral changes

    PubMed Central

    Watson, William D.; Buonora, John E.; Yarnell, Angela M.; Lucky, Jessica J.; D’Acchille, Michaela I.; McMullen, David C.; Boston, Andrew G.; Kuczmarski, Andrew V.; Kean, William S.; Verma, Ajay; Grunberg, Neil E.; Cole, Jeffrey T.

    2014-01-01

    Traumatic brain injury (TBI) pathophysiology can be attributed to either the immediate, primary physical injury, or the delayed, secondary injury which begins minutes to hours after the initial injury and can persist for several months or longer. Because these secondary cascades are delayed and last for a significant time period post-TBI, they are primary research targets for new therapeutics. To investigate changes in mitochondrial function after a brain injury, both the cortical impact site and ipsilateral hippocampus of adult male rats 7 and 17 days after a controlled cortical impact (CCI) injury were examined. State 3, state 4, and uncoupler-stimulated rates of oxygen consumption, respiratory control ratios (RCRs) were measured and membrane potential quantified, and all were significantly decreased in 7 day post-TBI cortical mitochondria. By contrast, hippocampal mitochondria at 7 days showed only non-significant decreases in rates of oxygen consumption and membrane potential. NADH oxidase activities measured in disrupted mitochondria were normal in both injured cortex and hippocampus at 7 days post-CCI. Respiratory and phosphorylation capacities at 17 days post-CCI were comparable to naïve animals for both cortical and hippocampus mitochondria. However, unlike oxidative phosphorylation, membrane potential of mitochondria in the cortical lining of the impact site did not recover at 17 days, suggesting that while diminished cortical membrane potential at 17 days does not adversely affect mitochondrial capacity to synthesize ATP, it may negatively impact other membrane potential-sensitive mitochondrial functions. Memory status, as assessed by a passive avoidance paradigm, was not significantly impaired until 17 days after injury. These results indicate pronounced disturbances in cortical mitochondrial function 7 days after CCI which precede the behavioral impairment observed at 17 days. PMID:24550822

  20. Gender and Marital Happiness in Later Life

    ERIC Educational Resources Information Center

    Kaufman, Gayle; Taniguchi, Hiromi

    2006-01-01

    In this study, the authors examine the effect of gender ideology on marital happiness in later life. Studies of marital satisfaction in later life have tended to neglect such attitudes, although they have received increasing attention in the literature on younger marriages. The authors use data from married individuals who range in age from 51 to…

  1. Later Life: A Time to Learn

    ERIC Educational Resources Information Center

    Russell, Helen

    2008-01-01

    In this article, an emerging framework for investigating and interpreting the experiences of learning in later life is presented. This framework is contextualized by a study in which the lived experiences of later-life computer learners were investigated. Significant ontological and existential interpretations from the study provided insights into…

  2. Toward Optimizing Cognitive Competence In Later Life

    ERIC Educational Resources Information Center

    Labouvie-Vief, Gisela

    1976-01-01

    Reviews evidence showing the view of pervasive decrement in later life is being challenged. Evidence is accumulated that the intellectual performance of the older adult responds favorably to a variety of ecological, training, and motivational conditions, and that intellectual development in later life is characterized by plasticity not universal…

  3. Discriminant analysis of multiple cortical changes in mild cognitive impairment

    NASA Astrophysics Data System (ADS)

    Wu, Congling; Guo, Shengwen; Lai, Chunren; Wu, Yupeng; Zhao, Di; Jiang, Xingjun

    2017-02-01

    To reveal the differences in brain structures and morphological changes between the mild cognitive impairment (MCI) and the normal control (NC), analyze and predict the risk of MCI conversion. First, the baseline and 2-year longitudinal follow-up magnetic resonance (MR) images of 73 NC, 46 patients with stable MCI (sMCI) and 40 patients with converted MCI (cMCI) were selected. Second, the FreeSurfer was used to extract the cortical features, including the cortical thickness, surface area, gray matter volume and mean curvature. Third, the support vector machine-recursive feature elimination method (SVM-RFE) were adopted to determine salient features for effective discrimination. Finally, the distribution and importance of essential brain regions were described. The experimental results showed that the cortical thickness and gray matter volume exhibited prominent capability in discrimination, and surface area and mean curvature behaved relatively weak. Furthermore, the combination of different morphological features, especially the baseline combined with the longitudinal changes, can be used to evidently improve the performance of classification. In addition, brain regions with high weights predominately located in the temporal lobe and the frontal lobe, which were relative to emotional control and memory functions. It suggests that there were significant different patterns in the brain structure and changes between the compared group, which could not only be effectively applied for classification, but also be used to evaluate and predict the conversion of the patients with MCI.

  4. Motor cortical plasticity is impaired in Unverricht-Lundborg disease.

    PubMed

    Danner, Nils; Säisänen, Laura; Määttä, Sara; Julkunen, Petro; Hukkanen, Taina; Könönen, Mervi; Hyppönen, Jelena; Kälviäinen, Reetta; Mervaala, Esa

    2011-09-01

    Patients with Unverricht-Lundborg disease, also referred to as progressive myoclonus epilepsy type 1, exhibit widespread motor symptoms and signs in addition to epileptic seizures, which suggest abnormal excitability of the primary motor pathways. To explore the plasticity of the sensory-motor cortex, we employed a modern neurophysiological method, the paired associative stimulation protocol, which resembles the concept of long-term potentiation of experimental studies. Seven patients with genetically verified Unverricht-Lundborg disease and 13 healthy control subjects were enrolled in the study to characterize cortical sensory-motor plasticity. In the study protocol, peripheral electric median nerve stimulation preceded navigated transcranial magnetic stimulation targeted to the representation area of thenar musculature on the contralateral primary motor cortex. The protocol consisted of 132 transcranial magnetic stimulation trials at 0.2 Hz, preceded by peripheral sensory stimulation at 25 ms. Motor-evoked potential amplitudes were analyzed at baseline and after the paired associative stimulation protocol at an intensity of 130% of the individual motor threshold. The patients with Unverricht-Lundborg disease exhibited an average decrease of 15% in motor-evoked potential amplitudes 30 minutes after paired associative stimulation, whereas in the control subjects, a significant increase (101%) was observed (P < .05), as expected. The results indicate a lack of normal cortical plasticity in Unverricht-Lundborg disease, which stresses the role of abnormal motor cortical functions or sensorimotor integration as possible pathophysiological contributors to the motor symptoms. The impaired cortical plasticity may be associated with the previously reported structural and physiological abnormalities of the primary motor cortex.

  5. Memory Impairment at Initial Clinical Presentation in Posterior Cortical Atrophy.

    PubMed

    Ahmed, Samrah; Baker, Ian; Husain, Masud; Thompson, Sian; Kipps, Christopher; Hornberger, Michael; Hodges, John R; Butler, Christopher R

    2016-04-23

    Posterior cortical atrophy (PCA) is characterized by core visuospatial and visuoperceptual deficits, and predominant atrophy in the parieto-occipital cortex. The most common underlying pathology is Alzheimer's disease (AD). Existing diagnostic criteria suggest that episodic memory is relatively preserved. The aim of this study was to examine memory performance at initial clinical presentation in PCA, compared to early-onset AD patients (EOAD). 15 PCA patients and 32 EOAD patients, and 34 healthy controls were entered into the study. Patients were tested on the Addenbrooke's Cognitive Examination (ACE-R), consisting of subscales in memory and visuospatial skills. PCA and EOAD patients were significantly impaired compared to controls on the ACE total score (p < 0.001), visuospatial skills (p < 0.001), and memory (p < 0.001). Consistent with the salient diagnostic deficits, PCA patients were significantly more impaired on visuospatial skills compared to EOAD patients (p < 0.001). However, there was no significant difference between patient groups in memory. Further analysis of learning, recall, and recognition components of the memory subscale showed that EOAD and PCA patients were significantly impaired compared to controls on all three components (p < 0.001), however, there was no significant difference between EOAD and PCA patients. The results of this study show that memory is impaired in the majority of PCA patients at clinical presentation. The findings suggest that memory impairment must be considered in assessment and management of PCA. Further study into memory in PCA is warranted, since the ACE-R is a brief screening tool and is likely to underestimate the presence of memory impairment.

  6. Cortical asymmetries in normal, mild cognitive impairment, and Alzheimer's disease.

    PubMed

    Kim, Jong Hun; Lee, Jong Weon; Kim, Geon Ha; Roh, Jee Hoon; Kim, Min-Jeong; Seo, Sang Won; Kim, Sung Tae; Jeon, Seun; Lee, Jong-Min; Heilman, Kenneth M; Na, Duk L

    2012-09-01

    There are functional and structural neocortical hemispheric asymmetries in people with normal cognition. These asymmetries may be altered in patients with Alzheimer's disease (AD) because there is a loss of neuronal connectivity in the heteromodal cortex. The purpose of this study is to test the hypothesis that individuals with amnestic mild cognitive impairment (aMCI), mild AD, and moderate to severe AD have progressive reductions in thickness asymmetries of the heteromodal neocortex. Right-handed elderly volunteers including normal cognition (NC), aMCI, and AD underwent 3-D volume imaging for cortical thickness. Although the cortical asymmetry pattern observed in normal cognition brains was generally maintained in aMCI and AD, there was a progressive decrease in the degree of asymmetry, especially in the inferior parietal lobule. A reduction of neocortical asymmetries may be a characteristic sign that occurs in patients with AD. Future studies are needed to evaluate whether this loss is specific to AD and if measurements of asymmetry can be used as diagnostic markers and for monitoring disease progression.

  7. Prevalence of cortical superficial siderosis in patients with cognitive impairment.

    PubMed

    Wollenweber, Frank Arne; Buerger, Katharina; Mueller, Claudia; Ertl-Wagner, Birgit; Malik, Rainer; Dichgans, Martin; Linn, Jennifer; Opherk, Christian

    2014-02-01

    Cortical superficial siderosis (cSS) is a magnetic resonance imaging marker of cerebral amyloid angiopathy (CAA) and can be its sole imaging sign. cSS has further been identified as a risk marker for future intracranial hemorrhage. Although uncommon in the general population, cSS may be much more prevalent in high risk populations for amyloid pathology. We aimed to determine the frequency of cSS in patients with cognitive impairment presenting to a memory clinic. We prospectively evaluated consecutive patients presenting to our memory clinic between April 2011 and April 2013. Subjects received neuropsychological testing using the Consortium to Establish a Registry for Alzheimer's Disease battery (CERAD-NP). Two hundred and twelve patients with documented cognitive impairment further underwent a standardized 3T-MR-imaging protocol with T2*-weighted gradient-echo sequences for detection of cSS. Thirteen of 212 patients (6.1 %) displayed cSS. In seven of them (54 %) cSS was the only imaging sign of CAA. Patients with cSS did not differ from patients without cSS with regard to medical history, age or cardiovascular risk profile. Subjects with cSS performed worse in the mini-mental state examination (p = 0.001), showed more white matter hyperintensities (p = 0.005) and more often had microbleeds (p = 0.001) compared to those without cSS. cSS is common in patients with cognitive impairment. It is associated with lower cognitive scores, white matter hyperintensities and microbleeds and can be the only imaging sign for CAA in this patient group.

  8. Defining Mental Health in Later Life.

    ERIC Educational Resources Information Center

    Qualls, Sara Honn

    2002-01-01

    Traditional models for defining mental health have used statistical definitions and symptom-based definitions. In a lifespan psychological approach, mental health in later life is defined as acceptance of the aging self as an active being who creates meaning, maintains maximum autonomy, and sustains positive relationships. (Contains 12…

  9. Religious Attendance and Loneliness in Later Life

    ERIC Educational Resources Information Center

    Rote, Sunshine; Hill, Terrence D.; Ellison, Christopher G.

    2013-01-01

    Purpose of the Study: Studies show that loneliness is a major risk factor for health issues in later life. Although research suggests that religious involvement can protect against loneliness, explanations for this general pattern are underdeveloped and undertested. In this paper, we propose and test a theoretical model, which suggests that social…

  10. Depression in Later Life: Recognition and Treatment.

    ERIC Educational Resources Information Center

    Schmall, Vicki L.; And Others

    This guide is designed to help readers understand depression and factors related to its onset in later life; recognize signs of depression and potential suicide; and know actions they can take if they suspect an older family member or friend may be depressed or contemplating suicide. Following a brief introduction, a chapter on depression…

  11. The Sedating Antidepressant Trazodone Impairs Sleep-Dependent Cortical Plasticity

    PubMed Central

    Dumoulin, Michelle C.; Coleman, Tammi; Shiraishi, Mia; Frank, Marcos G.

    2009-01-01

    Background Recent findings indicate that certain classes of hypnotics that target GABAA receptors impair sleep-dependent brain plasticity. However, the effects of hypnotics acting at monoamine receptors (e.g., the antidepressant trazodone) on this process are unknown. We therefore assessed the effects of commonly-prescribed medications for the treatment of insomnia (trazodone and the non-benzodiazepine GABAA receptor agonists zaleplon and eszopiclone) in a canonical model of sleep-dependent, in vivo synaptic plasticity in the primary visual cortex (V1) known as ocular dominance plasticity. Methodology/Principal Findings After a 6-h baseline period of sleep/wake polysomnographic recording, cats underwent 6 h of continuous waking combined with monocular deprivation (MD) to trigger synaptic remodeling. Cats subsequently received an i.p. injection of either vehicle, trazodone (10 mg/kg), zaleplon (10 mg/kg), or eszopiclone (1–10 mg/kg), and were allowed an 8-h period of post-MD sleep before ocular dominance plasticity was assessed. We found that while zaleplon and eszopiclone had profound effects on sleeping cortical electroencephalographic (EEG) activity, only trazodone (which did not alter EEG activity) significantly impaired sleep-dependent consolidation of ocular dominance plasticity. This was associated with deficits in both the normal depression of V1 neuronal responses to deprived-eye stimulation, and potentiation of responses to non-deprived eye stimulation, which accompany ocular dominance plasticity. Conclusions/Significance Taken together, our data suggest that the monoamine receptors targeted by trazodone play an important role in sleep-dependent consolidation of synaptic plasticity. They also demonstrate that changes in sleep architecture are not necessarily reliable predictors of how hypnotics affect sleep-dependent neural functions. PMID:19568418

  12. Cortical visual impairment in children: identification, evaluation and diagnosis.

    PubMed

    Lehman, Sharon S

    2012-09-01

    Cortical visual impairment (CVI) is a major cause of visual loss in children worldwide. The definition of this condition is constantly evolving with respect to definition, identifying those at risk and technology for diagnosis. These advances can be used for early diagnosis, design of accommodations and services, as well as future therapies and prevention strategies. Clinical questionnaires are being developed and tested for reliability in an attempt to identify those at risk for CVI. The definition is constantly being modified and now includes deficits in vision-guided motor planning and higher level executive functions. Neuroimaging techniques, such as MRI, functional MRI, and diffusion tensor imaging; electrophysiologic testing, such as sweep visual-evoked potentials; and perceptual testing, allow for further refinements in correlating structural defects and deficits in function. Recent developments will allow identification of those children at risk for CVI and earlier interventions for specific deficits. A child's performance is built on previously mastered skills, making timely prediction of deficits and intervention essential.

  13. The Reliability of the CVI Range: A Functional Vision Assessment for Children with Cortical Visual Impairment

    ERIC Educational Resources Information Center

    Newcomb, Sandra

    2010-01-01

    Children who are identified as visually impaired frequently have a functional vision assessment as one way to determine how their visual impairment affects their educational performance. The CVI Range is a functional vision assessment for children with cortical visual impairment. The purpose of the study presented here was to examine the…

  14. The Reliability of the CVI Range: A Functional Vision Assessment for Children with Cortical Visual Impairment

    ERIC Educational Resources Information Center

    Newcomb, Sandra

    2010-01-01

    Children who are identified as visually impaired frequently have a functional vision assessment as one way to determine how their visual impairment affects their educational performance. The CVI Range is a functional vision assessment for children with cortical visual impairment. The purpose of the study presented here was to examine the…

  15. Neural correlates of cognitive impairment in posterior cortical atrophy.

    PubMed

    Kas, Aurélie; de Souza, Leonardo Cruz; Samri, Dalila; Bartolomeo, Paolo; Lacomblez, Lucette; Kalafat, Michel; Migliaccio, Raffaella; Thiebaut de Schotten, Michel; Cohen, Laurent; Dubois, Bruno; Habert, Marie-Odile; Sarazin, Marie

    2011-05-01

    With the prospect of disease-modifying drugs that will target the physiopathological process of Alzheimer's disease, it is now crucial to increase the understanding of the atypical focal presentations of Alzheimer's disease, such as posterior cortical atrophy. This study aimed to (i) characterize the brain perfusion profile in posterior cortical atrophy using regions of interest and a voxel-based approach; (ii) study the influence of the disease duration on the clinical and imaging profiles; and (iii) explore the correlations between brain perfusion and cognitive deficits. Thirty-nine patients with posterior cortical atrophy underwent a specific battery of neuropsychological tests, mainly targeting visuospatial functions, and a brain perfusion scintigraphy with 99mTc-ethyl cysteinate dimer. The imaging analysis included a comparison with a group of 24 patients with Alzheimer's disease, matched for age, disease duration and Mini-Mental State Examination, and 24 healthy controls. The single-photon emission computed tomography profile in patients with posterior cortical atrophy was characterized by extensive and severe hypoperfusion in the occipital, parietal, posterior temporal cortices and in a smaller cortical area corresponding to the frontal eye fields (Brodmann areas 6/8). Compared with patients with Alzheimer's disease, the group with posterior cortical atrophy showed more severe occipitoparietal hypoperfusion and higher perfusion in the frontal, anterior cingulate and mesiotemporal regions. When considering the disease duration, the functional changes began and remained centred on the posterior lobes, even in the late stage. Correlation analyses of brain perfusion and neuropsychological scores in posterior cortical atrophy highlighted the prominent role of left inferior parietal damage in acalculia, Gerstmann's syndrome, left-right indistinction and limb apraxia, whereas damage to the bilateral dorsal occipitoparietal regions appeared to be involved in B

  16. Protein Kinase C Overactivity Impairs Prefrontal Cortical Regulation of Working Memory

    NASA Astrophysics Data System (ADS)

    Birnbaum, S. G.; Yuan, P. X.; Wang, M.; Vijayraghavan, S.; Bloom, A. K.; Davis, D. J.; Gobeske, K. T.; Sweatt, J. D.; Manji, H. K.; Arnsten, A. F. T.

    2004-10-01

    The prefrontal cortex is a higher brain region that regulates thought, behavior, and emotion using representational knowledge, operations often referred to as working memory. We tested the influence of protein kinase C (PKC) intracellular signaling on prefrontal cortical cognitive function and showed that high levels of PKC activity in prefrontal cortex, as seen for example during stress exposure, markedly impair behavioral and electrophysiological measures of working memory. These data suggest that excessive PKC activation can disrupt prefrontal cortical regulation of behavior and thought, possibly contributing to signs of prefrontal cortical dysfunction such as distractibility, impaired judgment, impulsivity, and thought disorder.

  17. Confronting the Material Convoy in Later Life

    PubMed Central

    Smith, Gabriella V.; Ekerdt, David J.

    2011-01-01

    We adapt a metaphor from life course studies to designate the whole of one’s possessions, across time, as a convoy of material support. This dynamic collection of things supports daily life and the self, but it can also present difficulty in later life. To alleviate the purported burdens of the material convoy, a discourse has arisen that urges elders and their family members to reduce the volume of possessions. An analysis of 11 such possession management texts shows authors addressing two distinct audiences about elders’ need to downsize: family members and elders themselves. Authors who speak to family members do so with an urgent, unsentimental tone that echoes mainstream clutter-control advice about disorderly, overfull households. In texts for elders, the standard critique about consumption and unruly lives is gentler, more sensitive to the meaning of things, and underplays the emotions of divestment. There is stress on the responsibility to spare the next generation and control one’s legacy. These latter texts seem to respect that downsizing in later life symbolizes a narrowing of the life world. PMID:21822336

  18. Regional impairments of cortical folding in premature infants

    PubMed Central

    Engelhardt, Erin; Inder, Terrie E; Alexopoulos, Dimitrios; Dierker, Donna L; Hill, Jason; Van Essen, David; Neil, Jeffrey J

    2015-01-01

    Objective This study was undertaken to evaluate the influence of preterm birth and other factors on cerebral cortical maturation. Methods We have evaluated the effects of preterm birth on cortical folding by applying cortical cartography methods to a cohort of 52 preterm infants (<31 weeks gestation, mild or no injury on conventional magnetic resonance imaging) and 12 term-born control infants. All infants were evaluated at term-equivalent postmenstrual age. Results Preterm infants had lower values for the global measures of gyrification index (GI; 2.06 ± 0.07 vs 1.80 ± 0.12, p < 0.001; control vs preterm) and cortical surface area (CSA; 316 ± 24 cm2 vs 257 ± 40 cm2, p < 0.001). Regional analysis of sulcal depth and cortical shape showed the greatest impact of preterm birth on the insula, superior temporal sulcus, and ventral portions of the pre- and postcentral sulci in both hemispheres. Although CSA and GI are related, CSA was more sensitive to antenatal and postnatal factors than GI. Both measures were lower in preterm infants of lower birth weight standard deviation scores and smaller occipitofrontal circumference at time of scan, whereas CSA alone was lower in association with smaller occipitofrontal circumference at birth. CSA was also lower in infants with higher critical illness in the first 24 hours of life, exposure to postnatal steroids, and prolonged endotracheal intubation. Interpretation Preterm birth disrupts cortical development in a regionally specific fashion with abnormalities evident by term-equivalent postmenstrual age. This disruption is influenced by both antenatal growth and postnatal course. PMID:25425403

  19. Predicting Later-Life Outcomes of Early-Life Exposures

    EPA Science Inventory

    Background: In utero exposure of the fetus to a stressor can lead to disease in later life. Epigenetic mechanisms are likely mediators of later-life expression of early-life events.Objectives: We examined the current state of understanding of later-life diseases resulting from ea...

  20. Predicting Later-Life Outcomes of Early-Life Exposures

    EPA Science Inventory

    Background: In utero exposure of the fetus to a stressor can lead to disease in later life. Epigenetic mechanisms are likely mediators of later-life expression of early-life events.Objectives: We examined the current state of understanding of later-life diseases resulting from ea...

  1. Cortical spreading depression impairs oxygen delivery and metabolism in mice.

    PubMed

    Yuzawa, Izumi; Sakadžić, Sava; Srinivasan, Vivek J; Shin, Hwa Kyoung; Eikermann-Haerter, Katharina; Boas, David A; Ayata, Cenk

    2012-02-01

    Cortical spreading depression (CSD) is associated with severe hypoperfusion in mice. Using minimally invasive multimodal optical imaging, we show that severe flow reductions during and after spreading depression are associated with a steep decline in cerebral metabolic rate of oxygen. Concurrent severe hemoglobin desaturation suggests that the oxygen metabolism becomes at least in part supply limited, and the decrease in cortical blood volume implicates vasoconstriction as the mechanism. In support of oxygen supply-demand mismatch, cortical nicotinamide adenine dinucleotide (NADH) fluorescence increases during spreading depression for at least 5 minutes, particularly away from parenchymal arterioles. However, modeling of tissue oxygen delivery shows that cerebral metabolic rate of oxygen drops more than predicted by a purely supply-limited model, raising the possibility of a concurrent reduction in oxygen demand during spreading depression. Importantly, a subsequent spreading depression triggered within 15 minutes evokes a monophasic flow increase superimposed on the oligemic baseline, which markedly differs from the response to the preceding spreading depression triggered in naive cortex. Altogether, these data suggest that CSD is associated with long-lasting oxygen supply-demand mismatch linked to severe vasoconstriction in mice.

  2. Possession Divestment by Sales in Later Life

    PubMed Central

    Ekerdt, David J.; Addington, Aislinn

    2015-01-01

    Residential relocation in later life is almost always a downsizing, with many possessions to be divested in a short period of time. This article examines older movers’ capacities for selling things, and ways that selling attenuates people's ties to those things, thus accomplishing the human dis-possession of the material convoy. In qualitative interviews in 79 households in the Midwestern United States, older adults reported their experience with possession sales associated with residential relocation. Among this group, three-quarters of the households downsized by selling some belongings. Informal sales seemed the least fraught of all strategies, estate sales had mixed reviews, and garage sales were recalled as laborious. Sellers’ efforts were eased by social relations and social networks as helpers and buyers came forward. As selling proceeded, sentiment about possessions waned as their materiality and economic value came to the fore, easing their detachment from the household. Possession selling is challenging because older adults are limited in the knowledge, skills, and efforts that they can apply to the recommodification of their belongings. Selling can nonetheless be encouraged as a divestment strategy as long as the frustrations and drawbacks are transparent, and the goal of ridding is kept in view. PMID:26162722

  3. Modelling suicide risk in later life.

    PubMed

    Lo, C F; Kwok, Cordelia M Y

    2006-08-01

    Affective disorder is generally regarded as the prominent risk factor for suicide in the old age population. Despite the large number of empirical studies available in the literature, there is no attempt in modelling the dynamics of an individual's level of suicide risk theoretically yet. In particular, a dynamic model which can simulate the time evolution of an individual's level of risk for suicide and provide quantitative estimates of the probability of suicide risk is still lacking. In the present study we apply the contingent claims analysis of credit risk modelling in the field of quantitative finance to derive a theoretical stochastic model for estimation of the probability of suicide risk in later life in terms of a signalling index of affective disorder. Our model is based upon the hypothesis that the current state of affective disorder of a patient can be represented by a signalling index and exhibits stochastic movement and that a threshold of affective disorder, which signifies the occurrence of suicide, exists. According to the numerical results, the implications of our model are consistent with the clinical findings. Hence, we believe that such a dynamic model will be essential to the design of effective suicide prevention strategies in the target population of older adults, especially in the primary care setting.

  4. Possession divestment by sales in later life.

    PubMed

    Ekerdt, David J; Addington, Aislinn

    2015-08-01

    Residential relocation in later life is almost always a downsizing, with many possessions to be divested in a short period of time. This article examines older movers' capacities for selling things, and ways that selling attenuates people's ties to those things, thus accomplishing the human dis-possession of the material convoy. In qualitative interviews in 79 households in the Midwestern United States, older adults reported their experience with possession sales associated with residential relocation. Among this group, three-quarters of the households downsized by selling some belongings. Informal sales seemed the least fraught of all strategies, estate sales had mixed reviews, and garage sales were recalled as laborious. Sellers' efforts were eased by social relations and social networks as helpers and buyers came forward. As selling proceeded, sentiment about possessions waned as their materiality and economic value came to the fore, easing their detachment from the household. Possession selling is challenging because older adults are limited in the knowledge, skills, and efforts that they can apply to the recommodification of their belongings. Selling can nonetheless be encouraged as a divestment strategy as long as the frustrations and drawbacks are transparent, and the goal of ridding is kept in view.

  5. Cortical peroxynitration of nerve growth factor in aged and cognitively impaired rats.

    PubMed

    Bruno, Martin A; Cuello, A Claudio

    2012-09-01

    Basal forebrain cholinergic neurons (BFCN), a system involved in learning and memory processes, are highly dependent on a continuous supply of biologically active nerve growth factor (NGF). Age-related cholinergic atrophy and cell loss in normal brains is apparently not complemented by reductions in the levels of NGF as could be expected. In the present work, cortical proNGF/NGF were immunoprecipitated from cortical brain homogenates from young and aged and behaviorally characterized rats and resolved with antinitrotyrosine antibodies to reveal nitration of tyrosine residues in proteins. Cortical proNGF in aged and cognitively impaired rats was found to be a target for peroxynitrite-mediated oxidative damage with correlative impact on decrease in choline acetyltransferase activity. These studies provide evidence for oxidative stress damage of NGF molecules in the cerebral cortex of cognitively impaired aged rats as previously shown in AD human brains. Copyright © 2012 Elsevier Inc. All rights reserved.

  6. Visual Behaviors and Adaptations Associated with Cortical and Ocular Impairment in Children.

    ERIC Educational Resources Information Center

    Jan, J. E.; Groenveld, M.

    1993-01-01

    This article shows the usefulness of understanding visual behaviors in the diagnosis of various types of visual impairments that are due to ocular and cortical disorders. Behaviors discussed include nystagmus, ocular motor dyspraxia, head position, close viewing, field loss adaptations, mannerisms, photophobia, and abnormal color perception. (JDD)

  7. Visual Attention to Movement and Color in Children with Cortical Visual Impairment

    ERIC Educational Resources Information Center

    Cohen-Maitre, Stacey Ann; Haerich, Paul

    2005-01-01

    This study investigated the ability of color and motion to elicit and maintain visual attention in a sample of children with cortical visual impairment (CVI). It found that colorful and moving objects may be used to engage children with CVI, increase their motivation to use their residual vision, and promote visual learning.

  8. The Effects of Training on a Young Child with Cortical Visual Impairment: An Exploratory Study.

    ERIC Educational Resources Information Center

    Lueck, Amanda Hall; Dornbusch, Helen; Hart, Jeri

    1999-01-01

    This exploratory study investigated the effects of the components of visual environmental management, visual skills training, and visually dependent task training on the performance of visual behaviors of a toddler with multiple disabilities including cortical visual impairment. Training components were implemented by the mother during daily…

  9. Visual Behaviors and Adaptations Associated with Cortical and Ocular Impairment in Children.

    ERIC Educational Resources Information Center

    Jan, J. E.; Groenveld, M.

    1993-01-01

    This article shows the usefulness of understanding visual behaviors in the diagnosis of various types of visual impairments that are due to ocular and cortical disorders. Behaviors discussed include nystagmus, ocular motor dyspraxia, head position, close viewing, field loss adaptations, mannerisms, photophobia, and abnormal color perception. (JDD)

  10. Outcomes and Opportunities: A Study of Children with Cortical Visual Impairment

    ERIC Educational Resources Information Center

    Roman Lantzy, Christine A.; Lantzy, Alan

    2010-01-01

    Pediatric View is an evaluation project that began in 1999 and is located at Western Pennsylvania Hospital in Pittsburgh. The purpose of Pediatric View is to provide developmental and functional vision evaluations to children who have ocular or cortical visual impairments. The evaluations are generally two hours in length, and a detailed report…

  11. A Survey of Parents of Children with Cortical or Cerebral Visual Impairment

    ERIC Educational Resources Information Center

    Jackel, Bernadette; Wilson, Michelle; Hartmann, Elizabeth

    2010-01-01

    Cortical or cerebral visual impairment (CVI) can result when the visual pathways and visual processing areas of the brain have been damaged. Children with CVI may have difficulty finding an object among other objects, viewing in the distance, orienting themselves in space, going from grass to pavement or other changes in surface, and copying…

  12. Outcomes and Opportunities: A Study of Children with Cortical Visual Impairment

    ERIC Educational Resources Information Center

    Roman Lantzy, Christine A.; Lantzy, Alan

    2010-01-01

    Pediatric View is an evaluation project that began in 1999 and is located at Western Pennsylvania Hospital in Pittsburgh. The purpose of Pediatric View is to provide developmental and functional vision evaluations to children who have ocular or cortical visual impairments. The evaluations are generally two hours in length, and a detailed report…

  13. Depression and frailty in later life: a synthetic review

    PubMed Central

    Briana, Mezuk; Lauren, Edwards; Matt, Lohman; Moon, Choi; Kate, Lapane

    2011-01-01

    Background Many of the symptoms, consequences, and risk factors for frailty are shared with late-life depression. However, thus far, few studies have addressed the conceptual and empirical interrelationships between these conditions. This review synthesizes existing studies that examined depression and frailty among older adults and provides suggestions for future research. Methods A search was conducted using PubMed for publications through 2010. Reviewers assessed the eligibility of each report and abstracted information on study design, sample characteristics, and key findings, including how depression and frailty were conceptualized and treated in the analysis. Results Of 133 abstracted articles, 39 full-text publications met inclusion criteria. Overall, both cross-sectional (n = 16) and cohort studies (n = 23) indicate that frailty, its components, and functional impairment are risk factors for depression. Although cross-sectional studies indicate a positive association between depression and frailty, findings from cohort studies are less consistent. The majority of studies included only women and non-Hispanic Whites. None used diagnostic measures of depression or considered antidepressant use in the design or analysis of the studies. Conclusions A number of empirical studies support for a bidirectional association between depression and frailty in later life. Extant studies have not adequately examined this relationship among men or racial/ethnic minorities, nor has the potential role of antidepressant medications been explored. An interdisciplinary approach to the study of geriatric syndromes such as late-life depression and frailty may promote cross-fertilization of ideas leading to novel conceptualization of intervention strategies to promote health and functioning in later life. PMID:21984056

  14. Diagnostic Significance of Cortical Superficial Siderosis for Alzheimer Disease in Patients with Cognitive Impairment.

    PubMed

    Inoue, Y; Nakajima, M; Uetani, H; Hirai, T; Ueda, M; Kitajima, M; Utsunomiya, D; Watanabe, M; Hashimoto, M; Ikeda, M; Yamashita, Y; Ando, Y

    2016-02-01

    Because the diagnostic significance of cortical superficial siderosis for Alzheimer disease and the association between cortical superficial siderosis and the topographic distribution of cerebral microbleeds have been unclear, we investigated the association between cortical superficial siderosis and clinicoradiologic characteristics of patients with cognitive impairment. We studied 347 patients (217 women, 130 men; mean age, 74 ± 9 years) who visited our memory clinic and underwent MR imaging (3T SWI). We analyzed the association between cortical superficial siderosis and the topographic distribution of cerebral microbleeds plus clinical characteristics including types of dementia. We used multivariate logistic regression analysis to determine the diagnostic significance of cortical superficial siderosis for Alzheimer disease. Twelve patients (3.5%) manifested cortical superficial siderosis. They were older (P = .026) and had strictly lobar cerebral microbleeds significantly more often than did patients without cortical superficial siderosis (50.0% versus 19.4%, P = .02); the occurrence of strictly deep and mixed cerebral microbleeds, however, did not differ in the 2 groups. Alzheimer disease was diagnosed in 162 (46.7%) patients. Of these, 8 patients (4.9%) had cortical superficial siderosis. In the multivariate logistic regression analysis for the diagnosis of Alzheimer disease, lacunar infarcts were negatively and independently associated with Alzheimer disease (P = .007). Although cortical superficial siderosis was associated with a strictly lobar cerebral microbleed location, it was not independently associated with Alzheimer disease in a memory clinic setting. Additional studies are required to investigate the temporal changes of these cerebral amyloid angiopathy-related MR imaging findings. © 2016 by American Journal of Neuroradiology.

  15. Life skills, wealth, health, and wellbeing in later life

    PubMed Central

    Wardle, Jane

    2017-01-01

    Life skills play a key role in promoting educational and occupational success in early life, but their relevance at older ages is uncertain. Here we measured five life skills—conscientiousness, emotional stability, determination, control, and optimism—in 8,119 men and women aged 52 and older (mean 66.7 y). We show that the number of skills is associated with wealth, income, subjective wellbeing, less depression, low social isolation and loneliness, more close relationships, better self-rated health, fewer chronic diseases and impaired activities of daily living, faster walking speed, and favorable objective biomarkers (concentration of high-density lipoprotein cholesterol, vitamin D and C-reactive protein, and less central obesity). Life skills also predicted sustained psychological wellbeing, less loneliness, and a lower incidence of new chronic disease and physical impairment over a 4-y period. These analyses took account of age, sex, parental socioeconomic background, education, and cognitive function. No single life skill was responsible for the associations we observed, nor were they driven by factors such as socioeconomic status or health. Despite the vicissitudes of later life, life skills impact a range of outcomes, and the maintenance of these attributes may benefit the older population. PMID:28396407

  16. Depression in later life: an overview with treatment recommendations.

    PubMed

    Ellison, James M; Kyomen, Helen H; Harper, David G

    2012-03-01

    We have already entered a new, more exciting, and hopeful era in the treatment of late-life depression. The increasing numbers of older adults who are surviving to more advanced ages and the greater recognition of late-life depression’s prevalence and impact on quality of life emphasize how important it is to detect and treat this disorder. Our increasing repertoire of evidence-based psychotherapeutic, pharmacologic, and neurotherapeutic treatment interventions offers many treatment alternatives, allowing substantial individualization of treatment approach. Demonstration of the effectiveness of depression treatment in primary care suggests the feasibility of increasing our patients’ access to care. Growing appreciation of the pathophysiology of depression and its interrelationships with cognitive impairment may increase our ability to limit or delay certain aspects of cognitive impairment through more aggressive treatment of depression. Improved recognition and treatment of late-life depression holds great potential for improving physical and mental health in later life, reducing disability in later years, and improving quality of life.

  17. Postnatal Erythropoietin Mitigates Impaired Cerebral Cortical Development Following Subplate Loss from Prenatal Hypoxia–Ischemia

    PubMed Central

    Jantzie, Lauren L.; Corbett, Christopher J.; Firl, Daniel J.; Robinson, Shenandoah

    2015-01-01

    Preterm birth impacts brain development and leads to chronic deficits including cognitive delay, behavioral problems, and epilepsy. Premature loss of the subplate, a transient subcortical layer that guides development of the cerebral cortex and axonal refinement, has been implicated in these neurological disorders. Subplate neurons influence postnatal upregulation of the potassium chloride co-transporter KCC2 and maturation of γ-amino-butyric acid A receptor (GABAAR) subunits. We hypothesized that prenatal transient systemic hypoxia–ischemia (TSHI) in Sprague–Dawley rats that mimic brain injury from extreme prematurity in humans would cause premature subplate loss and affect cortical layer IV development. Further, we predicted that the neuroprotective agent erythropoietin (EPO) could attenuate the injury. Prenatal TSHI induced subplate neuronal loss via apoptosis. TSHI impaired cortical layer IV postnatal upregulation of KCC2 and GABAAR subunits, and postnatal EPO treatment mitigated the loss (n ≥ 8). To specifically address how subplate loss affects cortical development, we used in vitro mechanical subplate ablation in slice cultures (n ≥ 3) and found EPO treatment attenuates KCC2 loss. Together, these results show that subplate loss contributes to impaired cerebral development, and EPO treatment diminishes the damage. Limitation of premature subplate loss and the resultant impaired cortical development may minimize cerebral deficits suffered by extremely preterm infants. PMID:24722771

  18. Postnatal Erythropoietin Mitigates Impaired Cerebral Cortical Development Following Subplate Loss from Prenatal Hypoxia-Ischemia.

    PubMed

    Jantzie, Lauren L; Corbett, Christopher J; Firl, Daniel J; Robinson, Shenandoah

    2015-09-01

    Preterm birth impacts brain development and leads to chronic deficits including cognitive delay, behavioral problems, and epilepsy. Premature loss of the subplate, a transient subcortical layer that guides development of the cerebral cortex and axonal refinement, has been implicated in these neurological disorders. Subplate neurons influence postnatal upregulation of the potassium chloride co-transporter KCC2 and maturation of γ-amino-butyric acid A receptor (GABAAR) subunits. We hypothesized that prenatal transient systemic hypoxia-ischemia (TSHI) in Sprague-Dawley rats that mimic brain injury from extreme prematurity in humans would cause premature subplate loss and affect cortical layer IV development. Further, we predicted that the neuroprotective agent erythropoietin (EPO) could attenuate the injury. Prenatal TSHI induced subplate neuronal loss via apoptosis. TSHI impaired cortical layer IV postnatal upregulation of KCC2 and GABAAR subunits, and postnatal EPO treatment mitigated the loss (n ≥ 8). To specifically address how subplate loss affects cortical development, we used in vitro mechanical subplate ablation in slice cultures (n ≥ 3) and found EPO treatment attenuates KCC2 loss. Together, these results show that subplate loss contributes to impaired cerebral development, and EPO treatment diminishes the damage. Limitation of premature subplate loss and the resultant impaired cortical development may minimize cerebral deficits suffered by extremely preterm infants.

  19. Methamphetamine abuse impairs motor cortical plasticity and function

    PubMed Central

    Huang, X; Chen, Y-Y; Shen, Y; Cao, X; Li, A; Liu, Q; Li, Z; Zhang, L-B; Dai, W; Tan, T; Arias-Carrion, O; Xue, Y-X; Su, H; Yuan, T-F

    2017-01-01

    Exposure to addictive drugs triggers synaptic plasticity in reward-related brain regions, such as the midbrain, nucleus accumbens and the prefrontal cortex. Effects of chronic drug exposure on other brain areas have not been fully investigated. Here, we characterize synaptic plasticity in motor cortex after methamphetamine self-administration in rats. We show that this causes a loss of corticostriatal plasticity in rat brain slices and impaired motor learning in the rotarod task. These findings are paralleled by the observation of a lack of transcranial magnetic stimulation-induced potentiation or depression of motor evoked potentials in human patients with addiction, along with poor performance in rotary pursuit task. Taken together, our results suggest that chronic methamphetamine use can affect behavioral performance via drug-evoked synaptic plasticity occluding physiological motor learning. PMID:28831198

  20. Methamphetamine abuse impairs motor cortical plasticity and function.

    PubMed

    Huang, X; Chen, Y-Y; Shen, Y; Cao, X; Li, A; Liu, Q; Li, Z; Zhang, L-B; Dai, W; Tan, T; Arias-Carrion, O; Xue, Y-X; Su, H; Yuan, T-F

    2017-09-01

    Exposure to addictive drugs triggers synaptic plasticity in reward-related brain regions, such as the midbrain, nucleus accumbens and the prefrontal cortex. Effects of chronic drug exposure on other brain areas have not been fully investigated. Here, we characterize synaptic plasticity in motor cortex after methamphetamine self-administration in rats. We show that this causes a loss of corticostriatal plasticity in rat brain slices and impaired motor learning in the rotarod task. These findings are paralleled by the observation of a lack of transcranial magnetic stimulation-induced potentiation or depression of motor evoked potentials in human patients with addiction, along with poor performance in rotary pursuit task. Taken together, our results suggest that chronic methamphetamine use can affect behavioral performance via drug-evoked synaptic plasticity occluding physiological motor learning.

  1. Impaired consciousness in temporal lobe seizures: role of cortical slow activity

    PubMed Central

    Englot, Dario J.; Yang, Li; Hamid, Hamada; Danielson, Nathan; Bai, Xiaoxiao; Marfeo, Anthony; Yu, Lissa; Gordon, Aliza; Purcaro, Michael J.; Motelow, Joshua E.; Agarwal, Ravi; Ellens, Damien J.; Golomb, Julie D.; Shamy, Michel C. F.; Zhang, Heping; Carlson, Chad; Doyle, Werner; Devinsky, Orrin; Vives, Kenneth; Spencer, Dennis D.; Spencer, Susan S.; Schevon, Catherine; Zaveri, Hitten P.

    2010-01-01

    Impaired consciousness requires altered cortical function. This can occur either directly from disorders that impair widespread bilateral regions of the cortex or indirectly through effects on subcortical arousal systems. It has therefore long been puzzling why focal temporal lobe seizures so often impair consciousness. Early work suggested that altered consciousness may occur with bilateral or dominant temporal lobe seizure involvement. However, other bilateral temporal lobe disorders do not impair consciousness. More recent work supports a ‘network inhibition hypothesis’ in which temporal lobe seizures disrupt brainstem–diencephalic arousal systems, leading indirectly to depressed cortical function and impaired consciousness. Indeed, prior studies show subcortical involvement in temporal lobe seizures and bilateral frontoparietal slow wave activity on intracranial electroencephalography. However, the relationships between frontoparietal slow waves and impaired consciousness and between cortical slowing and fast seizure activity have not been directly investigated. We analysed intracranial electroencephalography recordings during 63 partial seizures in 26 patients with surgically confirmed mesial temporal lobe epilepsy. Behavioural responsiveness was determined based on blinded review of video during seizures and classified as impaired (complex-partial seizures) or unimpaired (simple-partial seizures). We observed significantly increased delta-range 1–2 Hz slow wave activity in the bilateral frontal and parietal neocortices during complex-partial compared with simple-partial seizures. In addition, we confirmed prior work suggesting that propagation of unilateral mesial temporal fast seizure activity to the bilateral temporal lobes was significantly greater in complex-partial than in simple-partial seizures. Interestingly, we found that the signal power of frontoparietal slow wave activity was significantly correlated with the temporal lobe fast seizure

  2. Disentangling How the Brain is "Wired" in Cortical (Cerebral) Visual Impairment.

    PubMed

    Merabet, Lotfi B; Mayer, D Luisa; Bauer, Corinna M; Wright, Darick; Kran, Barry S

    2017-05-01

    Cortical (cerebral) visual impairment (CVI) results from perinatal injury to visual processing structures and pathways of the brain and is the most common cause of severe visual impairment or blindness in children in developed countries. Children with CVI display a wide range of visual deficits including decreased visual acuity, impaired visual field function, as well as impairments in higher-order visual processing and attention. Together, these visual impairments can dramatically influence a child's development and well-being. Given the complex neurologic underpinnings of this condition, CVI is often undiagnosed by eye care practitioners. Furthermore, the neurophysiological basis of CVI in relation to observed visual processing deficits remains poorly understood. Here, we present some of the challenges associated with the clinical assessment and management of individuals with CVI. We discuss how advances in brain imaging are likely to help uncover the underlying neurophysiology of this condition. In particular, we demonstrate how structural and functional neuroimaging approaches can help gain insight into abnormalities of white matter connectivity and cortical activation patterns, respectively. Establishing a connection between how changes within the brain relate to visual impairments in CVI will be important for developing effective rehabilitative and education strategies for individuals living with this condition. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. White matter integrity of cerebellar-cortical tracts in reading impaired children: A probabilistic tractography study

    PubMed Central

    Fernandez, Vindia G.; Juranek, Jenifer; Romanowska-Pawliczek, Anna; Stuebing, Karla; Williams, Victoria J.; Fletcher, Jack M.

    2016-01-01

    Little is known about the white matter integrity of cerebellar-cortical pathways in individuals with dyslexia. Building on previous findings of decreased volume in the anterior lobe of the cerebellum, we utilized novel cerebellar segmentation procedures and probabilistic tractography to examine tracts that connect the anterior lobe of the cerebellum and cortical regions typically associated with reading: the temporoparietal (TP), occipitotemporal (OT), and inferior frontal (IF) regions. The sample included 29 reading impaired children and 27 typical readers. We found greater fractional anisotropy (FA) for the poor readers in tracts connecting the cerebellum with TP and IF regions relative to typical readers. In the OT region, FA was greater for the older poor readers, but smaller for the younger ones. This study provides evidence for discrete, regionally-bound functions of the cerebellum and suggests that projections from the anterior cerebellum appear to have a regulatory effect on cortical pathways important for reading. PMID:26307492

  4. The Non-Benzodiazepine Hypnotic Zolpidem Impairs Sleep-Dependent Cortical Plasticity

    PubMed Central

    Seibt, Julie; Aton, Sara J.; Jha, Sushil K.; Coleman, Tammi; Dumoulin, Michelle C.; Frank, Marcos G.

    2008-01-01

    Study Objectives: The effects of hypnotics on sleep-dependent brain plasticity are unknown. We have shown that sleep enhances a canonical model of in vivo cortical plasticity, known as ocular dominance plasticity (ODP). We investigated the effects of 3 different classes of hypnotics on ODP. Design: Polysomnographic recordings were performed during the entire experiment (20 h). After a baseline sleep/wake recording (6 h), cats received 6 h of monocular deprivation (MD) followed by an i.p. injection of triazolam (1–10 mg/kg i.p.), zolpidem (10 mg/kg i.p.), ramelteon (0.1–1 mg/kg i.p.), or vehicle (DMSO i.p.). They were then allowed to sleep ad lib for 8 h, after which they were prepared for optical imaging of intrinsic cortical signals and single-unit electrophysiology. Setting: Basic neurophysiology laboratory Patients or Participants: Cats (male and female) in the critical period of visual development (postnatal days 28–41) Interventions: N/A Measurements and Results: Zolpidem reduced cortical plasticity by ∼50% as assessed with optical imaging of intrinsic cortical signals. This was not due to abnormal sleep architecture because triazolam, which perturbed sleep architecture and sleep EEGs more profoundly than zolpidem, had no effect on plasticity. Ramelteon minimally altered sleep and had no effect on ODP. Conclusions: Our findings demonstrate that alterations in sleep architecture do not necessarily lead to impairments in sleep function. Conversely, hypnotics that produce more “physiological” sleep based on polysomnography may impair critical brain processes, depending on their pharmacology. Citation: Seibt J; Aton SJ; Jha SK; Coleman T; Dumoulin MC; Frank MG. The non-benzodiazepine hypnotic zolpidem impairs sleep-dependent cortical plasticity. SLEEP 2008;31(10):1381–1391. PMID:18853935

  5. Pronounced impairment of everyday skills and self-care in posterior cortical atrophy.

    PubMed

    Shakespeare, Timothy J; Yong, Keir X X; Foxe, David; Hodges, John; Crutch, Sebastian J

    2015-01-01

    Posterior cortical atrophy (PCA) is a neurodegenerative syndrome characterized by progressive visual dysfunction and parietal, occipital, and occipitotemporal atrophy. The aim of this study was to compare the impact of PCA and typical Alzheimer's disease (tAD) on everyday functional abilities and neuropsychiatric status. The Cambridge Behavioural Inventory-Revised was given to carers of 32 PCA and 71 tAD patients. PCA patients showed significantly greater impairment in everyday skills and self-care while the tAD group showed greater impairment in aspects of memory and orientation, and motivation. We suggest that PCA poses specific challenges for those caring for people affected by the condition.

  6. Cortical Amyloid β Deposition and Current Depressive Symptoms in Alzheimer Disease and Mild Cognitive Impairment.

    PubMed

    Chung, Jun Ku; Plitman, Eric; Nakajima, Shinichiro; Chakravarty, M Mallar; Caravaggio, Fernando; Gerretsen, Philip; Iwata, Yusuke; Graff-Guerrero, Ariel

    2016-05-01

    Depressive symptoms are frequently seen in patients with dementia and mild cognitive impairment (MCI). Evidence suggests that there may be a link between current depressive symptoms and Alzheimer disease (AD)-associated pathological changes, such as an increase in cortical amyloid-β (Aβ). However, limited in vivo studies have explored the relationship between current depressive symptoms and cortical Aβ in patients with MCI and AD. Our study, using a large sample of 455 patients with MCI and 153 patients with AD from the Alzheimer's disease Neuroimaging Initiatives, investigated whether current depressive symptoms are related to cortical Aβ deposition. Depressive symptoms were assessed using the Geriatric Depression Scale and Neuropsychiatric Inventory-depression/dysphoria. Cortical Aβ was quantified using positron emission tomography with the Aβ probe(18)F-florbetapir (AV-45).(18)F-florbetapir standardized uptake value ratio (AV-45 SUVR) from the frontal, cingulate, parietal, and temporal regions was estimated. A global AV-45 SUVR, defined as the average of frontal, cingulate, precuneus, and parietal cortex, was also used. We observed that current depressive symptoms were not related to cortical Aβ, after controlling for potential confounds, including history of major depression. We also observed that there was no difference in cortical Aβ between matched participants with high and low depressive symptoms, as well as no difference between matched participants with the presence and absence of depressive symptoms. The association between depression and cortical Aβ deposition does not exist, but the relationship is highly influenced by stressful events in the past, such as previous depressive episodes, and complex interactions of different pathways underlying both depression and dementia. © The Author(s) 2015.

  7. Improved Cardiorespiratory Fitness Is Associated with Increased Cortical Thickness in Mild Cognitive Impairment.

    PubMed

    Reiter, Katherine; Nielson, Kristy A; Smith, Theresa J; Weiss, Lauren R; Alfini, Alfonso J; Smith, J Carson

    2015-11-01

    Cortical atrophy is a biomarker of Alzheimer's disease (AD) that correlates with clinical symptoms. This study examined changes in cortical thickness from before to after an exercise intervention in mild cognitive impairment (MCI) and healthy elders. Thirty physically inactive older adults (14 MCI, 16 healthy controls) underwent MRI before and after participating in a 12-week moderate intensity walking intervention. Participants were between the ages of 61 and 88. Change in cardiorespiratory fitness was assessed using residualized scores of the peak rate of oxygen consumption (V̇O2peak) from pre- to post-intervention. Structural magnetic resonance images were processed using FreeSurfer v5.1.0. V̇O2peak increased an average of 8.49%, which was comparable between MCI and healthy elders. Overall, cortical thickness was stable except for a significant decrease in the right fusiform gyrus in both groups. However, improvement in cardiorespiratory fitness due to the intervention (V̇O2peak) was positively correlated with cortical thickness change in the bilateral insula, precentral gyri, precuneus, posterior cingulate, and inferior and superior frontal cortices. Moreover, MCI participants exhibited stronger positive correlations compared to healthy elders in the left insula and superior temporal gyrus. A 12-week moderate intensity walking intervention led to significantly improved fitness in both MCI and healthy elders. Improved V̇O2peak was associated with widespread increased cortical thickness, which was similar between MCI and healthy elders. Thus, regular exercise may be an especially beneficial intervention to counteract cortical atrophy in all risk groups, and may provide protection against future cognitive decline in both healthy elders and MCI.

  8. Cortical Amyloid β Deposition and Current Depressive Symptoms in Alzheimer Disease and Mild Cognitive Impairment

    PubMed Central

    Chung, Jun Ku; Plitman, Eric; Nakajima, Shinichiro; Chakravarty, M. Mallar; Caravaggio, Fernando; Gerretsen, Philip; Iwata, Yusuke; Graff-Guerrero, Ariel

    2016-01-01

    Depressive symptoms are frequently seen in patients with dementia and mild cognitive impairment (MCI). Evidence suggests that there may be a link between current depressive symptoms and Alzheimer disease (AD)-associated pathological changes, such as an increase in cortical amyloid-β (Aβ). However, limited in vivo studies have explored the relationship between current depressive symptoms and cortical Aβ in patients with MCI and AD. Our study, using a large sample of 455 patients with MCI and 153 patients with AD from the Alzheimer’s disease Neuroimaging Initiatives, investigated whether current depressive symptoms are related to cortical Aβ deposition. Depressive symptoms were assessed using the Geriatric Depression Scale and Neuropsychiatric Inventory-depression/dysphoria. Cortical Aβ was quantified using positron emission tomography with the Aβ probe 18F-florbetapir (AV-45). 18F-florbetapir standardized uptake value ratio (AV-45 SUVR) from the frontal, cingulate, parietal, and temporal regions was estimated. A global AV-45 SUVR, defined as the average of frontal, cingulate, precuneus, and parietal cortex, was also used. We observed that current depressive symptoms were not related to cortical Aβ, after controlling for potential confounds, including history of major depression. We also observed that there was no difference in cortical Aβ between matched participants with high and low depressive symptoms, as well as no difference between matched participants with the presence and absence of depressive symptoms. The association between depression and cortical Aβ deposition does not exist, but the relationship is highly influenced by stressful events in the past, such as previous depressive episodes, and complex interactions of different pathways underlying both depression and dementia. PMID:26400248

  9. Mild Cognitive Impairment Is Characterized by Deficient Brainstem and Cortical Representations of Speech.

    PubMed

    Bidelman, Gavin M; Lowther, Jill E; Tak, Sunghee H; Alain, Claude

    2017-03-29

    Mild cognitive impairment (MCI) is recognized as a transitional phase in the progression toward more severe forms of dementia and is an early precursor to Alzheimer's disease. Previous neuroimaging studies reveal that MCI is associated with aberrant sensory-perceptual processing in cortical brain regions subserving auditory and language function. However, whether the pathophysiology of MCI extends to speech processing before conscious awareness (brainstem) is unknown. Using a novel electrophysiological approach, we recorded both brainstem and cortical speech-evoked brain event-related potentials (ERPs) in older, hearing-matched human listeners who did and did not present with subtle cognitive impairment revealed through behavioral neuropsychological testing. We found that MCI was associated with changes in neural speech processing characterized as hypersensitivity (larger) brainstem and cortical speech encoding in MCI compared with controls in the absence of any perceptual speech deficits. Group differences also interacted with age differentially across the auditory pathway; brainstem responses became larger and cortical ERPs smaller with advancing age. Multivariate classification revealed that dual brainstem-cortical speech activity correctly identified MCI listeners with 80% accuracy, suggesting its application as a biomarker of early cognitive decline. Brainstem responses were also a more robust predictor of individuals' MCI severity than cortical activity. Our findings suggest that MCI is associated with poorer encoding and transfer of speech signals between functional levels of the auditory system and advance the pathophysiological understanding of cognitive aging by identifying subcortical deficits in auditory sensory processing mere milliseconds (<10 ms) after sound onset and before the emergence of perceptual speech deficits.SIGNIFICANCE STATEMENT Mild cognitive impairment (MCI) is a precursor to dementia marked by declines in communication skills. Whether

  10. Cortical GABAergic neurons are more severely impaired by alkalosis than acidosis

    PubMed Central

    2013-01-01

    Background Acid–base imbalance in various metabolic disturbances leads to human brain dysfunction. Compared with acidosis, the patients suffered from alkalosis demonstrate more severe neurological signs that are difficultly corrected. We hypothesize a causative process that the nerve cells in the brain are more vulnerable to alkalosis than acidosis. Methods The vulnerability of GABAergic neurons to alkalosis versus acidosis was compared by analyzing their functional changes in response to the extracellular high pH and low pH. The neuronal and synaptic functions were recorded by whole-cell recordings in the cortical slices. Results The elevation or attenuation of extracellular pH impaired these GABAergic neurons in terms of their capability to produce spikes, their responsiveness to excitatory synaptic inputs and their outputs via inhibitory synapses. Importantly, the dysfunction of these active properties appeared severer in alkalosis than acidosis. Conclusions The severer impairment of cortical GABAergic neurons in alkalosis patients leads to more critical neural excitotoxicity, so that alkalosis-induced brain dysfunction is difficultly corrected, compared to acidosis. The vulnerability of cortical GABAergic neurons to high pH is likely a basis of severe clinical outcomes in alkalosis versus acidosis. PMID:24314112

  11. Location of cerebrovascular and degenerative changes, depressive symptoms and cognitive functioning in later life: the SMART-Medea study.

    PubMed

    Grool, Anne M; van der Graaf, Yolanda; Mali, Willem P T M; Geerlings, Mirjam I

    2011-10-01

    Depression and cognitive impairment are highly prevalent in later life and frequently co-occur. Structural changes in critical brain regions may underlie both conditions. The authors examined associations of infarcts, white-matter lesions (WML) and atrophy at different locations with depressive symptoms and cognitive functioning. Within the Second Manifestations of Arterial Disease-Memory, Depression and Aging (SMART-Medea) study, cross-sectional analyses were performed in 585 non-demented patients aged ≥50 years with symptomatic atherosclerotic disease. Volumetric measures of WML and atrophy were obtained with 1.5 T MRI; infarcts were rated visually. Depressive symptoms were assessed with the Patient Health Questionnaire-9 (score ≥6). z Scores of executive functioning, memory and processing speed were calculated. Analyses were adjusted for age, sex, education, intelligence, vascular disease, physical functioning and co-occurring brain changes. Depressive symptoms were present in 102 (17%) patients and were associated with poorer memory (B=-0.26, 95% CI -0.47 to -0.06). Large subcortical infarcts and lacunar infarcts in deep white-matter tracts were both associated with depressive symptoms (RR=2.66, 95% CI 1.28 to 5.54; RR=2.02, 95% CI 1.14 to 3.59) and poorer executive functioning and memory. Periventricular WML volume was associated with poorer executive functioning; cortical infarcts in the left hemisphere and media flow region, ventricular volume and cortical atrophy were associated with a slower processing speed. In this sample of non-demented older persons, subcortical infarcts contributed to an increased risk of depressive symptoms as well as cognitive impairment. This depended on location in projecting white-matter tracts, and not on infarct size.

  12. Progressive Cortical Neuronal Damage and Chronic Hemodynamic Impairment in Atherosclerotic Major Cerebral Artery Disease.

    PubMed

    Yamauchi, Hiroshi; Kagawa, Shinya; Kishibe, Yoshihiko; Takahashi, Masaaki; Higashi, Tatsuya

    2016-06-01

    Cross-sectional studies suggest that chronic hemodynamic impairment may cause selective cortical neuronal damage in patients with atherosclerotic internal carotid artery or middle cerebral artery occlusive disease. The purpose of this longitudinal study was to determine whether the progression of cortical neuronal damage, evaluated as a decrease in central benzodiazepine receptors (BZRs), is associated with hemodynamic impairment at baseline or hemodynamic deterioration during follow-up. We evaluated the distribution of BZRs twice using positron emission tomography and (11)C-flumazenil over time in 80 medically treated patients with atherosclerotic internal carotid artery or middle cerebral artery occlusive disease that had no ischemic episodes during follow-up. Using 3D stereotactic surface projections, we quantified abnormal decreases in the BZRs in the cerebral cortex within the middle cerebral artery distribution and correlated changes in the BZR index with the mean hemispheric values of hemodynamic parameters obtained from (15)O gas positron emission tomography. In the hemisphere affected by arterial disease, the BZR index in 40 patients (50%) was increased during follow-up (mean 26±20 months). In multivariable logistic regression analyses, increases in the BZR index were associated with the decreased cerebral blood flow at baseline and an increased oxygen extraction fraction during follow-up. Increases in the oxygen extraction fraction during follow-up were associated with a lack of statin use. In patients with atherosclerotic internal carotid artery or middle cerebral artery disease, the progression of cortical neuronal damage was associated with hemodynamic impairment at baseline and hemodynamic deterioration during follow-up. Statin use may be beneficial against hemodynamic deterioration and therefore neuroprotective. © 2016 American Heart Association, Inc.

  13. Prenatal Exposure to Arsenic Impairs Behavioral Flexibility and Cortical Structure in Mice

    PubMed Central

    Aung, Kyaw H.; Kyi-Tha-Thu, Chaw; Sano, Kazuhiro; Nakamura, Kazuaki; Tanoue, Akito; Nohara, Keiko; Kakeyama, Masaki; Tohyama, Chiharu; Tsukahara, Shinji; Maekawa, Fumihiko

    2016-01-01

    Exposure to arsenic from well water in developing countries is suspected to cause developmental neurotoxicity. Although, it has been demonstrated that exposure to sodium arsenite (NaAsO2) suppresses neurite outgrowth of cortical neurons in vitro, it is largely unknown how developmental exposure to NaAsO2 impairs higher brain function and affects cortical histology. Here, we investigated the effect of prenatal NaAsO2 exposure on the behavior of mice in adulthood, and evaluated histological changes in the prelimbic cortex (PrL), which is a part of the medial prefrontal cortex that is critically involved in cognition. Drinking water with or without NaAsO2 (85 ppm) was provided to pregnant C3H mice from gestational days 8 to 18, and offspring of both sexes were subjected to cognitive behavioral analyses at 60 weeks of age. The brains of female offspring were subsequently harvested and used for morphometrical analyses. We found that both male and female mice prenatally exposed to NaAsO2 displayed an impaired adaptation to repetitive reversal tasks. In morphometrical analyses of Nissl- or Golgi-stained tissue sections, we found that NaAsO2 exposure was associated with a significant increase in the number of pyramidal neurons in layers V and VI of the PrL, but not other layers of the PrL. More strikingly, prenatal NaAsO2 exposure was associated with a significant decrease in neurite length but not dendrite spine density in all layers of the PrL. Taken together, our results indicate that prenatal exposure to NaAsO2 leads to behavioral inflexibility in adulthood and cortical disarrangement in the PrL might contribute to this behavioral impairment. PMID:27064386

  14. The association of cognitive impairment with gray matter atrophy and cortical lesion load in clinically isolated syndrome.

    PubMed

    Diker, Sevda; Has, Arzu Ceylan; Kurne, Aslı; Göçmen, Rahşan; Oğuz, Kader Karlı; Karabudak, Rana

    2016-11-01

    Multiple sclerosis can impair cognition from the early stages and has been shown to be associated with gray matter damage in addition to white matter pathology. To investigate the profile of cognitive impairment in clinically isolated syndrome (CIS), and the contribution of cortical inflammation, cortical and deep gray matter atrophy, and white matter lesions to cognitive decline. Thirty patients with clinically isolated syndrome and twenty demographically- matched healthy controls underwent neuropsychologic assessment through the Rao Brief Repeatable Battery, and brain magnetic resonance imaging with double inversion recovery using a 3T scanner. Patients with clinically isolated syndrome performed significantly worse than healthy controls on tests that evaluated verbal memory, visuospatial learning and memory, and verbal fluency. Significant deep gray matter atrophy was found in the patients but cortical volume was not lower than the controls. Visual memory tests correlated with the volume of the hippocampus, cerebral white matter and deep gray matter structures and with cerebellar cortical atrophy. Cortical or white matter lesion load did not affect cognitive test results. In our patients with CIS, it was shown that cognitive impairment was mainly related to cerebral white matter, cerebellar cortical and deep gray matter atrophy, but not with cortical inflammation, at least in the early stage of disease. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Task-specific impairment of motor cortical excitation and inhibition in patients with writer's cramp.

    PubMed

    Tinazzi, Michele; Farina, Simona; Edwards, Mark; Moretto, Giuseppe; Restivo, Domenico; Fiaschi, Antonio; Berardelli, Alfredo

    2005-04-11

    Abnormalities in motor cortical excitation and inhibition have been reported in patients with writer's cramp, at rest and during muscle activation. We were interested in whether such abnormalities might be task-specific and depended on the type of movement task used to activate the dystonic hand. We therefore assessed motor-evoked potentials (facilitation/rest MEP amplitude ratio) and duration of the cortical silent period (CSP) from the right first dorsal interosseus (FDI) muscle to transcranial magnetic stimulation (TMS) in 10 patients with writer's cramp and in 10 healthy volunteers performing pincer and power gripping tasks. The mean facilitation/rest MEP amplitude ratio measured during the pincer grip task was significantly larger in dystonic subjects than in controls, but in the power grip condition was similar in the two groups. The CSP measured in the power grip condition was of similar length in normal controls and dystonic subjects, but in the pincer grip condition was significantly shorter in patients than in controls. These results indicate a task-specific impairment of motor cortical excitation and inhibition in writer's cramp.

  16. Paternal programming of offspring cardiometabolic diseases in later life

    PubMed Central

    Li, Jian; Tsuprykov, Oleg; Yang, Xiaoping; Hocher, Berthold

    2016-01-01

    Early – intrauterine – environmental factors are linked to the development of cardiovascular disease in later life. Traditionally, these factors are considered to be maternal factors such as maternal under and overnutrition, exposure to toxins, lack of micronutrients, and stress during pregnancy. However, in the recent years, it became obvious that also paternal environmental factors before conception and during sperm development determine the health of the offspring in later life. We will first describe clinical observational studies providing evidence for paternal programming of adulthood diseases in progeny. Next, we describe key animal studies proving this relationship, followed by a detailed analysis of our current understanding of the underlying molecular mechanisms of paternal programming. Alterations of noncoding sperm micro-RNAs, histone acetylation, and targeted as well as global DNA methylation seem to be in particular involved in paternal programming of offspring's diseases in later life. PMID:27457668

  17. Cortical Structure Alterations and Social Behavior Impairment in p50-Deficient Mice.

    PubMed

    Bonini, Sara Anna; Mastinu, Andrea; Maccarinelli, Giuseppina; Mitola, Stefania; Premoli, Marika; La Rosa, Luca Rosario; Ferrari-Toninelli, Giulia; Grilli, Mariagrazia; Memo, Maurizio

    2016-06-01

    Alterations in genes that regulate neurodevelopment can lead to cortical malformations, resulting in malfunction during postnatal life. The NF-κB pathway has a key role during neurodevelopment by regulating the maintenance of the neural progenitor cell pool and inhibiting neuronal differentiation. In this study, we evaluated whether mice lacking the NF-κB p50 subunit (KO) present alterations in cortical structure and associated behavioral impairment. We found that, compared with wild type (WT), KO mice at postnatal day 2 present an increase in radial glial cells, an increase in Reelin protein expression levels, in addition to an increase of specific layer thickness. Moreover, adult KO mice display abnormal columnar organization in the somatosensory cortex, a specific decrease in somatostatin- and parvalbumin-expressing interneurons, altered neurite orientation, and a decrease in Synapsin I protein levels. Concerning behavior, KO mice, in addition to an increase in locomotor and exploratory activity, display impairment in social behaviors, with a reduction in social interaction. Finally, we found that risperidone treatment decreased hyperactivity of KO mice, but had no effect on defective social interaction. Altogether, these data add complexity to a growing body of data, suggesting a link between dysregulation of the NF-κB pathway and neurodevelopmental disorders pathogenesis.

  18. Cortical Structure Alterations and Social Behavior Impairment in p50-Deficient Mice

    PubMed Central

    Bonini, Sara Anna; Mastinu, Andrea; Maccarinelli, Giuseppina; Mitola, Stefania; Premoli, Marika; La Rosa, Luca Rosario; Ferrari-Toninelli, Giulia; Grilli, Mariagrazia; Memo, Maurizio

    2016-01-01

    Alterations in genes that regulate neurodevelopment can lead to cortical malformations, resulting in malfunction during postnatal life. The NF-κB pathway has a key role during neurodevelopment by regulating the maintenance of the neural progenitor cell pool and inhibiting neuronal differentiation. In this study, we evaluated whether mice lacking the NF-κB p50 subunit (KO) present alterations in cortical structure and associated behavioral impairment. We found that, compared with wild type (WT), KO mice at postnatal day 2 present an increase in radial glial cells, an increase in Reelin protein expression levels, in addition to an increase of specific layer thickness. Moreover, adult KO mice display abnormal columnar organization in the somatosensory cortex, a specific decrease in somatostatin- and parvalbumin-expressing interneurons, altered neurite orientation, and a decrease in Synapsin I protein levels. Concerning behavior, KO mice, in addition to an increase in locomotor and exploratory activity, display impairment in social behaviors, with a reduction in social interaction. Finally, we found that risperidone treatment decreased hyperactivity of KO mice, but had no effect on defective social interaction. Altogether, these data add complexity to a growing body of data, suggesting a link between dysregulation of the NF-κB pathway and neurodevelopmental disorders pathogenesis. PMID:26946128

  19. Parkinson's disease with mild cognitive impairment: severe cortical thinning antedates dementia.

    PubMed

    Gasca-Salas, Carmen; García-Lorenzo, Daniel; Garcia-Garcia, David; Clavero, Pedro; Obeso, José A; Lehericy, Stephane; Rodríguez-Oroz, María C

    2017-07-14

    Mild cognitive impairment (MCI) in Parkinson's disease (PD) is a risk factor for dementia and thus, it is of interest to elucidate if specific patterns of atrophy in PD-MCI patients are associated with a higher risk of developing dementia. We aim to define pattern(s) of regional atrophy in PD-MCI patients who developed dementia during 31 months of follow-up using cortical thickness analysis Twenty-three PD-MCI patients and 18 controls underwent brain MRI and completed a neuropsychological examination at baseline, PD-MCI patients were followed after a 31 month follow-up in order to assess their progression to dementia. At follow up, 8 PD-MCI patients had converted to dementia (PD-MCI converters) whereas 15 remained as PD-MCI (PD-MCI non-converters). All patients were at least 60 years old and suffered PD ≥ 10 years. There were no baseline differences between the two groups of patients in clinical and neuropsychological variables. The cortex of PD-MCI converters was thinner than that of PD-MCI non-converters, bilaterally in the frontal, insula and the left middle temporal areas, also displaying a more widespread pattern of cortical thinning relative to the controls. This study shows that aged and long-term PD patients with MCI who convert to dementia in the short-mid term suffer a thinning of the cortex in several areas (frontal cortex, and middle temporal lobe and insula), even when their cognitive impairment was similar to that of PD-MCI non-converters. Thus, MRI analysis of cortical thickness may represent a useful measure to identify PD-MCI patients at a higher risk of developing dementia.

  20. Conversion Discriminative Analysis on Mild Cognitive Impairment Using Multiple Cortical Features from MR Images.

    PubMed

    Guo, Shengwen; Lai, Chunren; Wu, Congling; Cen, Guiyin

    2017-01-01

    Neuroimaging measurements derived from magnetic resonance imaging provide important information required for detecting changes related to the progression of mild cognitive impairment (MCI). Cortical features and changes play a crucial role in revealing unique anatomical patterns of brain regions, and further differentiate MCI patients from normal states. Four cortical features, namely, gray matter volume, cortical thickness, surface area, and mean curvature, were explored for discriminative analysis among three groups including the stable MCI (sMCI), the converted MCI (cMCI), and the normal control (NC) groups. In this study, 158 subjects (72 NC, 46 sMCI, and 40 cMCI) were selected from the Alzheimer's Disease Neuroimaging Initiative. A sparse-constrained regression model based on the l2-1-norm was introduced to reduce the feature dimensionality and retrieve essential features for the discrimination of the three groups by using a support vector machine (SVM). An optimized strategy of feature addition based on the weight of each feature was adopted for the SVM classifier in order to achieve the best classification performance. The baseline cortical features combined with the longitudinal measurements for 2 years of follow-up data yielded prominent classification results. In particular, the cortical thickness produced a classification with 98.84% accuracy, 97.5% sensitivity, and 100% specificity for the sMCI-cMCI comparison; 92.37% accuracy, 84.78% sensitivity, and 97.22% specificity for the cMCI-NC comparison; and 93.75% accuracy, 92.5% sensitivity, and 94.44% specificity for the sMCI-NC comparison. The best performances obtained by the SVM classifier using the essential features were 5-40% more than those using all of the retained features. The feasibility of the cortical features for the recognition of anatomical patterns was certified; thus, the proposed method has the potential to improve the clinical diagnosis of sub-types of MCI and predict the risk of its

  1. Lesions to Primary Sensory and Posterior Parietal Cortices Impair Recovery from Hand Paresis after Stroke

    PubMed Central

    Abela, Eugenio; Missimer, John; Wiest, Roland; Federspiel, Andrea; Hess, Christian; Sturzenegger, Matthias; Weder, Bruno

    2012-01-01

    Background Neuroanatomical determinants of motor skill recovery after stroke are still poorly understood. Although lesion load onto the corticospinal tract is known to affect recovery, less is known about the effect of lesions to cortical sensorimotor areas. Here, we test the hypothesis that lesions of somatosensory cortices interfere with the capacity to recover motor skills after stroke. Methods Standardized tests of motor skill and somatosensory functions were acquired longitudinally over nine months in 29 patients with stroke to the pre- and postcentral gyrus, including adjacent areas of the frontal, parietal and insular cortices. We derived the recovery trajectories of each patient for five motor subtest using least-squares curve fitting and objective model selection procedures for linear and exponential models. Patients were classified into subgroups based on their motor recovery models. Lesions were mapped onto diffusion weighted imaging scans and normalized into stereotaxic space using cost-function masking. To identify critical neuranatomical regions, voxel-wise subtractions were calculated between subgroup lesion maps. A probabilistic cytoarchitectonic atlas was used to quantify of lesion extent and location. Results Twenty-three patients with moderate to severe initial deficits showed exponential recovery trajectories for motor subtests that relied on precise distal movements. Those that retained a chronic motor deficit had lesions that extended to the center of the somatosensory cortex (area 2) and the intraparietal sulcus (areas hIP1, hIP2). Impaired recovery outcome correlated with lesion extent on this areas and somatosensory performance. The rate of recovery, however, depended on the lesion load onto the primary motor cortex (areas 4a, 4p). Conclusions Our findings support a critical role of uni-and multimodal somatosensory cortices in motor skill recovery. Whereas lesions to these areas influence recovery outcome, lesions to the primary motor

  2. Effects of experimental traumatic brain injury and impaired glutamate transport on cortical spreading depression.

    PubMed

    Hosseini-Zare, Mahshid Sadat; Gu, Feng; Abdulla, Ahmad; Powell, Simon; Žiburkus, Jokūbas

    2017-09-01

    Cortical spreading depression (CSD) is associated with traumatic brain injury (TBI), stroke, migraines, and seizures. Typically, following TBIs and other insults, neuronal excitability in and around the area of the injury is affected, with reported increases in local glutamate signaling. Astrocytic glutamate transporters are critical for precise regulation of the extracellular glutamate availability. However, it remains unclear how impaired astrocytic glutamate transport or an acute TBI affect characteristics of the CSD. We quantified the properties of CSD using whole-cell and extracellular electrophysiological recordings, and voltage-sensitive dye imaging (VSDI) in rat visual cortex in vitro. To model impaired astrocytic glutamate transport, we used astrocytic glutamate transporter blocker (2S, 3S)-3-[3-[4-(trifluoromethyl) benzoylamino] benzyloxy] aspartate (TFB-TBOA). In addition, an acute incision through the superficial cortical layers was used to model the effects of acute traumatic brain injury (TBI) on CSD characteristics. Both manipulations; impaired glutamate cycling and acute cut profoundly affected the physiological properties of cell firing, latency to CSD formation, and its frequency of occurrence. VSD imaging analysis revealed significant changes in spatiotemporal dynamics and propagation of the CSD, suggesting that the cut itself may not initiate CSD depolarizing waves, but rather attract them. Blockade of GLT-1 caused significant reduction in whole-cell sodium currents and changes in CSD wave spatiotemporal characteristics as well, slowing it or even 'trapping' its propagation. Our results reveal new information about CSD properties in these pathological conditions and demonstrate an important role of GLT-1 in regulation of CSD. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Transitions into and out of Cohabitation in Later Life

    ERIC Educational Resources Information Center

    Brown, Susan L.; Bulanda, Jennifer Roebuck; Lee, Gary R.

    2012-01-01

    Cohabitation among adults over age 50 is rising rapidly, more than doubling from 1.2 million in 2000 to 2.75 million in 2010. A small literature provides a descriptive portrait of older cohabitors, but no study has investigated transitions into and out of cohabitation during later life. Drawing on demographic and life course perspectives, the…

  4. Families in Later Life: A Burgeoning Research Area.

    ERIC Educational Resources Information Center

    Brubaker, Timothy H.

    1990-01-01

    Reviews research from 1980s focusing on families who are beyond child-rearing years. Sees later-life families as characterized by continuity and changes as they experience marriage, divorce, widowhood, remarriage, childlessness, grandparenthood, sibling relationships, and family caregiving. Suggests areas for future research focusing on…

  5. Transitions into and out of Cohabitation in Later Life

    ERIC Educational Resources Information Center

    Brown, Susan L.; Bulanda, Jennifer Roebuck; Lee, Gary R.

    2012-01-01

    Cohabitation among adults over age 50 is rising rapidly, more than doubling from 1.2 million in 2000 to 2.75 million in 2010. A small literature provides a descriptive portrait of older cohabitors, but no study has investigated transitions into and out of cohabitation during later life. Drawing on demographic and life course perspectives, the…

  6. Neighborhood Deterioration and Social Isolation in Later Life.

    ERIC Educational Resources Information Center

    Krause, Neal

    1993-01-01

    Tested conceptual model relating neighborhood characteristics to social isolation in later life. Data from nationwide survey supported theoretical sequence of older adults with low levels of educational attainment being more likely to experience financial problems, of elderly people confronted by financial difficulties being more likely to reside…

  7. The Company of Others: Generating Knowhow in Later Life

    ERIC Educational Resources Information Center

    Kimberley, Helen; Golding, Barry; Simons, Bonnie

    2016-01-01

    This paper explores some important aspects of the generation of practical knowledge through later life. It is about the relationship between knowledge generation, agency and capability, developed informally through the life experiences in and through the Company of Others. It emphasises how the everyday processes of socialisation create invaluable…

  8. The Company of Others: Generating Knowhow in Later Life

    ERIC Educational Resources Information Center

    Kimberley, Helen; Golding, Barry; Simons, Bonnie

    2016-01-01

    This paper explores some important aspects of the generation of practical knowledge through later life. It is about the relationship between knowledge generation, agency and capability, developed informally through the life experiences in and through the Company of Others. It emphasises how the everyday processes of socialisation create invaluable…

  9. Network Type and Mortality Risk in Later Life

    ERIC Educational Resources Information Center

    Litwin, Howard; Shiovitz-Ezra, Sharon

    2006-01-01

    Purpose: The purpose of this study was to examine the association of baseline network type and 7-year mortality risk in later life. Design and Methods: We executed secondary analysis of all-cause mortality in Israel using data from a 1997 national survey of adults aged 60 and older (N = 5,055) that was linked to records from the National Death…

  10. Later Life Learning Experience among Chinese Elderly in Hong Kong

    ERIC Educational Resources Information Center

    Leung, Angela; Lui, Yu-Hon; Chi, Iris

    2005-01-01

    In a world with increasing numbers of older adults and a worldwide emphasis placed on lifelong learning, it is crucial to examine and formulate appropriate policy for learning in later life (LLL). Hong Kong has a rapidly aging population, which is projected to double within the next 25 years. However, lifelong learning for the elderly has yet to…

  11. Family Size and Mother-Child Relations in Later Life.

    ERIC Educational Resources Information Center

    Uhlenberg, Peter; Cooney, Teresa M.

    1990-01-01

    Examined effects of family size on mother-child relationships in later life. Subjects were taken from national probability sample which included adults aged 35-55 (n=3,083) who had a living mother and women aged 60-79 (n=1,101) with at least one living child. Found generally positive relationship between number of siblings and favorable…

  12. Engaging Later-Life Learners through Portfolio Writing

    ERIC Educational Resources Information Center

    Clarke, Egerton; Hornyak, Christine

    2012-01-01

    The ever increasing enrollment of later-life students in institutions of higher learning warrants innovative teaching strategies to promote successful learning outcomes. This article discusses the academic challenges that instructors face and argues in support of an important assessment method, that is, portfolio writing. This novel strategy was…

  13. Chronic post-stroke oropharyngeal dysphagia is associated with impaired cortical activation to pharyngeal sensory inputs.

    PubMed

    Cabib, C; Ortega, O; Vilardell, N; Mundet, L; Clavé, P; Rofes, L

    2017-09-05

    The role of afferent sensory pathways in the pathophysiology of post-stroke oropharyngeal dysphagia is not known. We hypothesized that patients with chronic post-stroke dysphagia (PSD) would show impaired sensory cortical activation in the ipsilesional hemisphere. We studied 28 chronic unilateral post-stroke patients [17 PSD and 11 post-stroke non-dysphagic patients (PSnD)] and 11 age-matched healthy volunteers. Event-related sensory-evoked potentials to pharyngeal stimulation (pSEP) and sensory thresholds were assessed. We analyzed pSEP peak latency and amplitude (N1, P1, N2 and P2), and neurotopographic stroke characteristics from brain magnetic resonance imaging. Healthy volunteers presented a highly symmetric bihemispheric cortical pattern of brain activation at centroparietal areas (N1-P1 and N2-P2) to pharyngeal stimuli. In contrast, an asymmetric pattern of reduced ipsilesional activation was found in PSD (N2-P2; P = 0.026) but not in PSnD. PSD presented impaired safety of swallow (penetration-aspiration score: 4.3 ± 1.6), delayed laryngeal vestibule closure (360.0 ± 70.0 ms) and higher National Institute of Health Stroke Scale (7.0 ± 6.2 vs. 1.9 ± 1.4, P = 0.001) and Fazekas scores (3.0 ± 1.4 vs. 2.0 ± 1.1; P < 0.05) than PSnD. pSEP showed a unilateral delay at stroke site exclusively for PSD (peak-latency interhemispheric difference vs. PSnD: N1, 6.5 ± 6.7 vs. 1.1 ± 1.0 ms; N2, 32.0 ± 15.8 vs. 4.5 ± 4.9 ms; P < 0.05). Chronic post-stroke oropharyngeal dysphagia is associated with stroke severity and degree of leukoaraoisis. Impaired conduction and cortical integration of pharyngeal sensory inputs at stroke site are key features of chronic PSD. These findings highlight the role of sensory pathways in the pathophysiology of post-stroke oropharyngeal dysphagia and offer a potential target for future treatments. © 2017 EAN.

  14. Reactivity of cortical alpha rhythms to eye opening in mild cognitive impairment and Alzheimer's disease: an EEG study.

    PubMed

    Babiloni, Claudio; Lizio, Roberta; Vecchio, Fabrizio; Frisoni, Giovanni B; Pievani, Michela; Geroldi, Cristina; Claudia, Fracassi; Ferri, Raffaele; Lanuzza, Bartolo; Rossini, Paolo M

    2010-01-01

    Cortical sources of resting eyes-closed alpha rhythms are typically abnormal in mild cognitive impairment (MCI) and Alzheimer's disease (AD) subjects. Here we tested the hypothesis of a progressive impairment of cortical alpha reactivity to eye-opening across amnesic MCI and mild AD subjects, reflecting another aspect of the impairment of cortical neural synchronization. Resting electroencephalography (EEG) data were recorded in 36 normal elderly subjects (Nold), 91 amnesic MCI, and 31 mild AD subjects during eyes-closed and -open conditions. EEG sources were estimated by LORETA software. In the eye-closed condition, posterior alpha 1 (8-10.5 Hz) sources were lower in MCI and AD than Nold subjects. The opposite was true for occipital delta sources (2-4 Hz). Reactivity to the eyes-open condition showed posterior alpha 1 and alpha 2 (10.5-13 Hz) sources was high in the Nold, intermediate in the MCI, and low in the AD subjects. Furthermore, occipital alpha 1 reactivity across MCI and AD subjects was correlated to the cognitive impairment as revealed by Mini-Mental State Examination score. In conclusion, at least at group level, the continuum across amnesic MCI and mild AD status is related to an impaired reactivity of cortical neuronal synchronization to eyes opening at alpha rhythms.

  15. Mechanisms of cortical neural synchronization related to healthy and impaired consciousness: evidence by quantitative electroencephalographic studies.

    PubMed

    Babiloni, Claudio; Vecchio, Fabrizio; Buffo, Paola; Iacoboni, Marco; Pistoia, Francesca; Sacco, Simona; Sara, Marco; Rossini, Paolo Maria

    2014-01-01

    In this paper, we review the contribution of our research group to the study of human consciousness by quantitative electroencephalographic (EEG) techniques. We posit that EEG techniques can be extremely useful for a direct measurement of brain electrophysiological activity related to human consciousness for their unsurpassable high temporal resolution (milliseconds). This activity can be expressed in terms of event-related potentials as well as changes of EEG rhythms of interest, for example the dominant alpha rhythms (about 8-12 Hz). The results of our studies, and those of several independent groups, lead support to the hypothesis that these techniques provide important insights about the neurophysiologic mechanisms underlying cortical neural synchronization/desynchronization and the regulation of neuromodulatory systems (e.g. dopaminergic, noradrenergic, cholinergic, etc.) at the basis of brain arousal and consciousness in healthy subjects and in patients with impairment of the consciousness. A possible interaction of these mechanisms and the drugs administered to patients with consciousness disorders is discussed.

  16. Ultramicroscopy Reveals Axonal Transport Impairments in Cortical Motor Neurons at Prion Disease

    PubMed Central

    Ermolayev, Vladimir; Friedrich, Mike; Nozadze, Revaz; Cathomen, Toni; Klein, Michael A.; Harms, Gregory S.; Flechsig, Eckhard

    2009-01-01

    Abstract The functional imaging of neuronal circuits of the central nervous system is crucial for phenotype screenings or investigations of defects in neurodegenerative disorders. Current techniques yield either low penetration depth, yield poor resolution, or are restricted by the age of the animals. Here, we present a novel ultramicroscopy protocol for fluorescence imaging and three-dimensional reconstruction in the central nervous system of adult mice. In combination with tracing as a functional assay for axonal transport, retrogradely labeled descending motor neurons were visualized with >4 mm penetration depth. The analysis of the motor cortex shortly before the onset of clinical prion disease revealed that >80% neurons have functional impairments in axonal transport. Our study provides evidence that prion disease is associated with severe axonal transport defects in the cortical motor neurons and suggests a novel mechanism for prion-mediated neurodegeneration. PMID:19383482

  17. Boy with cortical visual impairment and unilateral hemiparesis in Jeff Huntington's "Slip" (2011).

    PubMed

    Bianucci, R; Perciaccante, A; Appenzeller, O

    2016-11-15

    Face recognition is strongly associated with the human face and face perception is an important part in identifying health qualities of a person and is an integral part of so called spot diagnosis in clinical neurology. Neurology depends in part on observation, description and interpretation of visual information. Similar skills are required in visual art. Here we report a case of eye cortical visual impairment (CVI) and unilateral facial weakness in a boy depicted by the painter Jeff Huntington (2011). The corollary of this is that art serves medical clinical exercise. Art interpretation helps neurology students to apply the same skills they will use in clinical experience and to develop their observational and interpretive skills in non-clinical settings. Furthermore, the development of an increased awareness of emotional and character expression in the human face may facilitate successful doctor-patient relationships.

  18. Olanzapine Treatment of Adolescent Rats Causes Enduring Specific Memory Impairments and Alters Cortical Development and Function

    PubMed Central

    Swanson, Thomas; Enos, Jennifer K.; Bailey, Aileen M.; Kolb, Bryan; Frost, Douglas O.

    2013-01-01

    Antipsychotic drugs are increasingly used in children and adolescents to treat a variety of psychiatric disorders. However, little is known about the long-term effects of early life antipsychotic drug treatment. Most antipsychotic drugs are potent antagonists or partial agonists of dopamine D2 receptors; atypical antipsychotic drugs also antagonize type 2A serotonin receptors. Dopamine and serotonin regulate many neurodevelopmental processes. Thus, early life antipsychotic drug treatment can, potentially, perturb these processes, causing long-term behavioral- and neurobiological impairments. Here, we treated adolescent, male rats with olanzapine on post-natal days 28–49. As adults, they exhibited impaired working memory, but normal spatial memory, as compared to vehicle-treated control rats. They also showed a deficit in extinction of fear conditioning. Measures of motor activity and skill, habituation to an open field, and affect were normal. In the orbital- and medial prefrontal cortices, parietal cortex, nucleus accumbens core and dentate gyrus, adolescent olanzapine treatment altered the developmental dynamics and mature values of dendritic spine density in a region-specific manner. Measures of motor activity and skill, habituation to an open field, and affect were normal. In the orbital- and medial prefrontal cortices, D1 binding was reduced and binding of GABAA receptors with open Cl− channels was increased. In medial prefrontal cortex, D2 binding was also increased. The persistence of these changes underscores the importance of improved understanding of the enduring sequelae of pediatric APD treatment as a basis for weighing the benefits and risks of adolescent antipsychotic drug therapy, especially prophylactic treatment in high risk, asymptomatic patients. The long-term changes in neurotransmitter receptor binding and neural circuitry induced by adolescent APD treatment may also cause enduring changes in behavioral- and neurobiological responses to

  19. Change in Perceived Age in Middle and Later Life

    ERIC Educational Resources Information Center

    Ward, Russell A.

    2013-01-01

    Analyses examine change in the age people "feel" ("felt age") and "would like to be" ("ideal age") (relative to current age) in middle and later life. Data are from 1,815 respondents in two waves (1995-96, 2004-06) of the Midlife in the United States Survey (MIDUS) who were age 40+ at Wave 1. In aggregate, people feel about the same amount younger…

  20. Change in Perceived Age in Middle and Later Life

    ERIC Educational Resources Information Center

    Ward, Russell A.

    2013-01-01

    Analyses examine change in the age people "feel" ("felt age") and "would like to be" ("ideal age") (relative to current age) in middle and later life. Data are from 1,815 respondents in two waves (1995-96, 2004-06) of the Midlife in the United States Survey (MIDUS) who were age 40+ at Wave 1. In aggregate, people feel about the same amount younger…

  1. Transitions Into and Out of Cohabitation in Later Life

    PubMed Central

    Brown, Susan L.; Bulanda, Jennifer Roebuck; Lee, Gary R.

    2012-01-01

    Cohabitation among adults over age 50 is rising rapidly, more than doubling from 1.2 million in 2000 to 2.75 million in 2010. A small literature provides a descriptive portrait of older cohabitors, but no study has investigated transitions into and out of cohabitation during later life. Drawing on demographic and life course perspectives, the authors developed a framework for conceptualizing later life union behaviors. Using data from the 1998 – 2006 Health and Retirement Study, they estimated discrete -time event-history models predicting union formation (i.e., cohabitation or marriage) among older unmarried individuals (N = 3,736) as well as transitions to either marriage or separation among older cohabitors (N = 377). Those who formed a union were as likely to be in a cohabiting relationship as a marriage. Older adult cohabiting unions were quite stable and unlikely to culminate in either marriage or separation. During later life, cohabitation appears to operate as a long-term alternative to marriage. PMID:23226875

  2. Cortical Auditory Evoked Potentials in (Un)aided Normal-Hearing and Hearing-Impaired Adults

    PubMed Central

    Van Dun, Bram; Kania, Anna; Dillon, Harvey

    2016-01-01

    Cortical auditory evoked potentials (CAEPs) are influenced by the characteristics of the stimulus, including level and hearing aid gain. Previous studies have measured CAEPs aided and unaided in individuals with normal hearing. There is a significant difference between providing amplification to a person with normal hearing and a person with hearing loss. This study investigated this difference and the effects of stimulus signal-to-noise ratio (SNR) and audibility on the CAEP amplitude in a population with hearing loss. Twelve normal-hearing participants and 12 participants with a hearing loss participated in this study. Three speech sounds—/m/, /g/, and /t/—were presented in the free field. Unaided stimuli were presented at 55, 65, and 75 dB sound pressure level (SPL) and aided stimuli at 55 dB SPL with three different gains in steps of 10 dB. CAEPs were recorded and their amplitudes analyzed. Stimulus SNRs and audibility were determined. No significant effect of stimulus level or hearing aid gain was found in normal hearers. Conversely, a significant effect was found in hearing-impaired individuals. Audibility of the signal, which in some cases is determined by the signal level relative to threshold and in other cases by the SNR, is the dominant factor explaining changes in CAEP amplitude. CAEPs can potentially be used to assess the effects of hearing aid gain in hearing-impaired users. PMID:27587919

  3. Prefrontal cortical GABAergic dysfunction contributes to age-related working memory impairment.

    PubMed

    Bañuelos, Cristina; Beas, B Sofia; McQuail, Joseph A; Gilbert, Ryan J; Frazier, Charles J; Setlow, Barry; Bizon, Jennifer L

    2014-03-05

    Working memory functions supported by the prefrontal cortex decline in normal aging. Disruption of corticolimbic GABAergic inhibitory circuits can impair working memory in young subjects; however, relatively little is known regarding how aging impacts prefrontal cortical GABAergic signaling and whether such changes contribute to cognitive deficits. The current study used a rat model to evaluate the effects of aging on expression of prefrontal GABAergic synaptic proteins in relation to working memory decline, and to test whether pharmacological manipulations of prefrontal GABAergic signaling can improve working memory abilities in aged subjects. Results indicate that in aged medial prefrontal cortex (mPFC), expression of the vesicular GABA transporter VGAT was unchanged; however, there was a significant increase in expression of the GABA synthesizing enzyme GAD67, and a significant decrease in the primary neuronal GABA transporter GAT-1 and in both subunits of the GABA(B) receptor (GABA(B)R). Expression of VGAT, GAD67, and GAT-1 was not associated with working memory ability. In contrast, among aged rats, GABA(B)R expression was significantly and negatively associated with working memory performance, such that lower GABA(B)R expression predicted better working memory. Subsequent experiments showed that systemic administration of a GABA(B)R antagonist, CGP55845, dose-dependently enhanced working memory in aged rats. This enhancing effect of systemic CGP55845 was reproduced by direct intra-mPFC administration. Together, these data suggest that age-related dysregulation of GABAergic signaling in prefrontal cortex may play a causal role in impaired working memory and that targeting GABA(B)Rs may provide therapeutic benefit for age-related impairments in executive functions.

  4. Prefrontal Cortical GABAergic Dysfunction Contributes to Age-Related Working Memory Impairment

    PubMed Central

    Bañuelos, Cristina; Beas, B. Sofia; McQuail, Joseph A.; Gilbert, Ryan J.; Frazier, Charles J.; Setlow, Barry

    2014-01-01

    Working memory functions supported by the prefrontal cortex decline in normal aging. Disruption of corticolimbic GABAergic inhibitory circuits can impair working memory in young subjects; however, relatively little is known regarding how aging impacts prefrontal cortical GABAergic signaling and whether such changes contribute to cognitive deficits. The current study used a rat model to evaluate the effects of aging on expression of prefrontal GABAergic synaptic proteins in relation to working memory decline, and to test whether pharmacological manipulations of prefrontal GABAergic signaling can improve working memory abilities in aged subjects. Results indicate that in aged medial prefrontal cortex (mPFC), expression of the vesicular GABA transporter VGAT was unchanged; however, there was a significant increase in expression of the GABA synthesizing enzyme GAD67, and a significant decrease in the primary neuronal GABA transporter GAT-1 and in both subunits of the GABA(B) receptor (GABA(B)R). Expression of VGAT, GAD67, and GAT-1 was not associated with working memory ability. In contrast, among aged rats, GABA(B)R expression was significantly and negatively associated with working memory performance, such that lower GABA(B)R expression predicted better working memory. Subsequent experiments showed that systemic administration of a GABA(B)R antagonist, CGP55845, dose-dependently enhanced working memory in aged rats. This enhancing effect of systemic CGP55845 was reproduced by direct intra-mPFC administration. Together, these data suggest that age-related dysregulation of GABAergic signaling in prefrontal cortex may play a causal role in impaired working memory and that targeting GABA(B)Rs may provide therapeutic benefit for age-related impairments in executive functions. PMID:24599447

  5. Dating for Older Women: Experiences and Meanings of Dating in Later Life

    PubMed Central

    Watson, Wendy K.; Stelle, Charlie

    2013-01-01

    Research over the last 20 years has provided an increased understanding of intimate relationships in later life; however, dating in later life remains largely unexplored. The purpose of this study was to examine the meanings of dating for women in later life. In this study, dating was examined through semistructured, in-depth interviews with 14 women ages 64 to 77 who had all dated in later life. Themes that emerged from an interpretative phenomenological analysis included multiple meanings of dating in later life, how dating in later life compared to earlier points in life, and dating in the future. PMID:21767089

  6. Auditory processing disorder in patients with language-learning impairment and correlation with malformation of cortical development.

    PubMed

    Boscariol, Mirela; Guimarães, Catarina Abraão; Hage, Simone R de Vasconcellos; Garcia, Vera Lucia; Schmutzler, Kátia M R; Cendes, Fernando; Guerreiro, Marilisa Mantovani

    2011-11-01

    Malformations of cortical development have been described in children and families with language-learning impairment. The objective of this study was to assess the auditory processing information in children with language-learning impairment in the presence or absence of a malformation of cortical development in the auditory processing areas. We selected 32 children (19 males), aged eight to 15 years, divided into three groups: Group I comprised 11 children with language-learning impairment and bilateral perisylvian polymicrogyria, Group II comprised 10 children with language-learning impairment and normal MRI, and Group III comprised 11 normal children. Behavioral auditory tests, such as the Random Gap Detection Test and Digits Dichotic Test were performed. Statistical analysis was performed using the Kruskal-Wallis test and Mann-Whitney test, with a level of significance of 0.05. The results revealed a statistically significant difference among the groups. Our data showed abnormalities in auditory processing of children in Groups I and II when compared with the control group, with children in Group I being more affected than children in Group II. Our data showed that the presence of a cortical malformation correlates with a worse performance in some tasks of auditory processing function.

  7. Early Visual Evoked Potential Acuity and Future Behavioral Acuity in Cortical Visual Impairment

    PubMed Central

    Watson, Tonya; Orel-Bixler, Deborah; Haegerstrom-Portnoy, Gunilla

    2014-01-01

    Purpose Cortical Visual Impairment (CVI) is bilateral visual impairment caused by damage to the posterior visual pathway. Both preferential looking (PL) and sweep visual evoked potential (VEP) can be used to measure visual acuity. The purpose of this study was to determine if an early VEP measure of acuity is related to a young patient’s future behavioral acuity. Methods The visual acuity of 33 patients with CVI was assessed using the sweep VEP and a behavioral measure on two occasions. The median age of the patients at the initial visit was 4.8 years (range: 1.3–19.2 years), and they were followed for an average of 6.9 years (SD: 3.5 years). Results The mean initial VEP acuity was 20/135 (0.735 logMAR), and the mean initial behavioral acuity was 20/475 (1.242 logMAR). The average difference between the two initial measures of acuity was 0.55 log unit, with the behavioral measure reporting a poorer visual acuity in all patients. However, the mean final behavioral acuity was 20/150 (0.741 logMAR), and the average difference between the initial VEP acuity and the final behavioral acuity was only 0.01 log unit. Therefore, the initial VEP measure was not statistically different from the final behavioral measure (t=0.11; df=32; p=0.45). Conclusions Even though the initial VEP measure was much better than the initial behavioral measure, the initial VEP measure was similar to the behavioral visual acuity measured approximately 7 years later. Sweep VEP testing can be used as a predictive tool for at least the lower limit of future behavioral acuity in young patients with CVI. PMID:20016393

  8. Impact of Depression, Fatigue, and Global Measure of Cortical Volume on Cognitive Impairment in Multiple Sclerosis

    PubMed Central

    De Cola, Maria Cristina; D'Aleo, Giangaetano; Sessa, Edoardo; Marino, Silvia

    2015-01-01

    Objective. To investigate the influence of demographic and clinical variables, such as depression, fatigue, and quantitative MRI marker on cognitive performances in a sample of patients affected by multiple sclerosis (MS). Methods. 60 MS patients (52 relapsing remitting and 8 primary progressive) underwent neuropsychological assessments using Rao's Brief Repeatable Battery of Neuropsychological Tests (BRB-N), the Beck Depression Inventory-second edition (BDI-II), and the Fatigue Severity Scale (FSS). We performed magnetic resonance imaging to all subjects using a 3 T scanner and obtained tissue-specific volumes (normalized brain volume and cortical brain volume). We used Student's t-test to compare depressed and nondepressed MS patients. Finally, we performed a multivariate regression analysis in order to assess possible predictors of patients' cognitive outcome among demographic and clinical variables. Results. 27.12% of the sample (16/59) was cognitively impaired, especially in tasks requiring attention and information processing speed. From between group comparison, we find that depressed patients had worse performances on BRB-N score, greater disability and disease duration, and brain volume decrease. According to multiple regression analysis, the BDI-II score was a significant predictor for most of the neuropsychological tests. Conclusions. Our findings suggest that the presence of depressive symptoms is an important determinant of cognitive performance in MS patients. PMID:25861633

  9. Herpes Simplex Virus-Type1 (HSV-1) Impairs DNA Repair in Cortical Neurons.

    PubMed

    De Chiara, Giovanna; Racaniello, Mauro; Mollinari, Cristiana; Marcocci, Maria Elena; Aversa, Giorgia; Cardinale, Alessio; Giovanetti, Anna; Garaci, Enrico; Palamara, Anna Teresa; Merlo, Daniela

    2016-01-01

    Several findings suggest that Herpes simplex virus-1 (HSV-1) infection plays a role in the neurodegenerative processes that characterize Alzheimer's disease (AD), but the underlying mechanisms have yet to be fully elucidated. Here we show that HSV-1 productive infection in cortical neurons causes the accumulation of DNA lesions that include both single (SSBs) and double strand breaks (DSBs), which are reported to be implicated in the neuronal loss observed in neurodegenerative diseases. We demonstrate that HSV-1 downregulates the expression level of Ku80, one of the main components of non-homologous end joining (NHEJ), a major pathway for the repair of DSBs. We also provide data suggesting that HSV-1 drives Ku80 for proteasomal degradation and impairs NHEJ activity, leading to DSB accumulation. Since HSV-1 usually causes life-long recurrent infections, it is possible to speculate that cumulating damages, including those occurring on DNA, may contribute to virus induced neurotoxicity and neurodegeneration, further suggesting HSV-1 as a risk factor for neurodegenerative conditions.

  10. Impairment of GABA transporter GAT-1 terminates cortical recurrent network activity via enhanced phasic inhibition

    PubMed Central

    Razik, Daniel S.; Hawellek, David J.; Antkowiak, Bernd; Hentschke, Harald

    2013-01-01

    In the central nervous system, GABA transporters (GATs) very efficiently clear synaptically released GABA from the extracellular space, and thus exert a tight control on GABAergic inhibition. In neocortex, GABAergic inhibition is heavily recruited during recurrent phases of spontaneous action potential activity which alternate with neuronally quiet periods. Therefore, such activity should be quite sensitive to minute alterations of GAT function. Here, we explored the effects of a gradual impairment of GAT-1 and GAT-2/3 on spontaneous recurrent network activity – termed network bursts and silent periods – in organotypic slice cultures of rat neocortex. The GAT-1 specific antagonist NO-711 depressed activity already at nanomolar concentrations (IC50 for depression of spontaneous multiunit firing rate of 42 nM), reaching a level of 80% at 500–1000 nM. By contrast, the GAT-2/3 preferring antagonist SNAP-5114 had weaker and less consistent effects. Several lines of evidence pointed toward an enhancement of phasic GABAergic inhibition as the dominant activity-depressing mechanism: network bursts were drastically shortened, phasic GABAergic currents decayed slower, and neuronal excitability during ongoing activity was diminished. In silent periods, NO-711 had little effect on neuronal excitability or membrane resistance, quite in contrast to the effects of muscimol, a GABA mimetic which activates GABAA receptors tonically. Our results suggest that an enhancement of phasic GABAergic inhibition efficiently curtails cortical recurrent activity and may mediate antiepileptic effects of therapeutically relevant concentrations of GAT-1 antagonists. PMID:24062646

  11. Impairment of GABA transporter GAT-1 terminates cortical recurrent network activity via enhanced phasic inhibition.

    PubMed

    Razik, Daniel S; Hawellek, David J; Antkowiak, Bernd; Hentschke, Harald

    2013-01-01

    In the central nervous system, GABA transporters (GATs) very efficiently clear synaptically released GABA from the extracellular space, and thus exert a tight control on GABAergic inhibition. In neocortex, GABAergic inhibition is heavily recruited during recurrent phases of spontaneous action potential activity which alternate with neuronally quiet periods. Therefore, such activity should be quite sensitive to minute alterations of GAT function. Here, we explored the effects of a gradual impairment of GAT-1 and GAT-2/3 on spontaneous recurrent network activity--termed network bursts and silent periods--in organotypic slice cultures of rat neocortex. The GAT-1 specific antagonist NO-711 depressed activity already at nanomolar concentrations (IC50 for depression of spontaneous multiunit firing rate of 42 nM), reaching a level of 80% at 500-1000 nM. By contrast, the GAT-2/3 preferring antagonist SNAP-5114 had weaker and less consistent effects. Several lines of evidence pointed toward an enhancement of phasic GABAergic inhibition as the dominant activity-depressing mechanism: network bursts were drastically shortened, phasic GABAergic currents decayed slower, and neuronal excitability during ongoing activity was diminished. In silent periods, NO-711 had little effect on neuronal excitability or membrane resistance, quite in contrast to the effects of muscimol, a GABA mimetic which activates GABAA receptors tonically. Our results suggest that an enhancement of phasic GABAergic inhibition efficiently curtails cortical recurrent activity and may mediate antiepileptic effects of therapeutically relevant concentrations of GAT-1 antagonists.

  12. Herpes Simplex Virus-Type1 (HSV-1) Impairs DNA Repair in Cortical Neurons

    PubMed Central

    De Chiara, Giovanna; Racaniello, Mauro; Mollinari, Cristiana; Marcocci, Maria Elena; Aversa, Giorgia; Cardinale, Alessio; Giovanetti, Anna; Garaci, Enrico; Palamara, Anna Teresa; Merlo, Daniela

    2016-01-01

    Several findings suggest that Herpes simplex virus-1 (HSV-1) infection plays a role in the neurodegenerative processes that characterize Alzheimer’s disease (AD), but the underlying mechanisms have yet to be fully elucidated. Here we show that HSV-1 productive infection in cortical neurons causes the accumulation of DNA lesions that include both single (SSBs) and double strand breaks (DSBs), which are reported to be implicated in the neuronal loss observed in neurodegenerative diseases. We demonstrate that HSV-1 downregulates the expression level of Ku80, one of the main components of non-homologous end joining (NHEJ), a major pathway for the repair of DSBs. We also provide data suggesting that HSV-1 drives Ku80 for proteasomal degradation and impairs NHEJ activity, leading to DSB accumulation. Since HSV-1 usually causes life-long recurrent infections, it is possible to speculate that cumulating damages, including those occurring on DNA, may contribute to virus induced neurotoxicity and neurodegeneration, further suggesting HSV-1 as a risk factor for neurodegenerative conditions. PMID:27803664

  13. Chronic cortical visual impairment in children: aetiology, prognosis, and associated neurological deficits

    PubMed Central

    Huo, R.; Burden, S.; Hoyt, C.; Good, W.

    1999-01-01

    BACKGROUND/AIMS—To evaluate prevalence, aetiology, prognosis, and associated neurological and ophthalmological problems in children with cortical visual impairment (CVI).
METHODS—The records of 7200 outpatients seen in the paediatric ophthalmology practice over the past 15 years were reviewed in order to compile data concerning CVI. In addition, the authors devised and applied a system for grading visual recovery in order to assess prognosis.
RESULTS—CVI occurred in 2.4% of all patients examined. The four most common causes of CVI were perinatal hypoxia (22%), cerebral vascular accident (14%), meningitis (12%), and acquired hypoxia (10%). Most children with CVI had associated neurological abnormalities. The most common were seizures (53%), cerebral palsy (26%) hemiparesis (12%), and hypotonia (5%). Associated ophthalmological problems were esotropia (19%), exotropia (18%), optic nerve atrophy (16%), ocular motor apraxia (15%), nystagmus (11%), and retinal disease (3%). On average, CVI patients improved by two levels as measured by the authors' scale.
CONCLUSION—The majority of children with CVI showed at least some recovery. In this group of children, CVI is often accompanied by additional ophthalmological problems and is nearly always associated with other, serious neurological abnormalities.

 PMID:10340973

  14. Psychosis in Later Life: A Review and Update.

    PubMed

    Colijn, Mark A; Nitta, Bradley H; Grossberg, George T

    2015-01-01

    Psychosis is relatively common in later life and can present in a wide variety of contexts, including early-onset and late-onset schizophrenia, delusional disorder, mood disorders, and various dementias. It can also occur as the result of numerous medical and neurological diseases and from the use of certain medications. Although identifying the cause of psychosis in older patients can be challenging, the unique clinical features associated with the different disorders can help in making the diagnosis. Accurate diagnosis of psychosis in older populations is essential, as its treatment varies depending on the context in which it appears. Despite the safety concerns regarding the use of antipsychotics in older patients, certain pharmacological treatments appear to be both efficacious and reasonably safe in treating psychosis in older populations. Additionally, although research is limited, numerous psychosocial therapies appear promising. This review summarizes the literature on the epidemiology, clinical characteristics, neuroimaging, and treatment of psychosis in later life, and serves as an update to past reviews on this topic.

  15. Successful transition to later life: strategies used by baby boomers.

    PubMed

    Wilhelm, Kay; Geerligs, Liesbeth; Peisah, Carmelle

    2014-06-01

    We sought to understand strategies employed by baby boomers to maintain well-being and facilitate transition to later life. A non-clinical cohort (n = 139) provided qualitative data about well-being strategies. Thematic data analysis provided insights for those with high and low life satisfaction (based on Satisfaction with Life Scale) and quantitative data from previous waves provided predictors of life satisfaction decades later. Longitudinal predictors were depression history (cognitive trait and repeated episodes) and quality of partner's care. 'Highly satisfied older people' reported proactive strategies, contrasted with lack of planning by 'dissatisfied older people'. 'Resilient older people', with high life satisfaction despite repeated depressive episodes, reported benefit from strategies dealing with adversity, including depression. Strategies of 'satisfied older people' support theories of proactive coping and demonstrate the importance of developing adaptational skills to support later life satisfaction. In 'resilient older people' adaptive strategies can lead to achievement of life satisfaction despite repeated depressive episodes. © 2013 The Authors. Australasian Journal on Ageing © 2013 ACOTA.

  16. Aging and Subjective Well-Being in Later Life

    PubMed Central

    Nazroo, James; Vanhoutte, Bram; Chandola, Tarani

    2014-01-01

    Objectives. This paper examines age-related changes in subjective well-being (SWB) in later life using multiple measures that cover eudemonic, evaluative, and affective dimensions of well-being. Method. Using data from 5 waves of respondents aged 50 and older from the English Longitudinal Study of Ageing (2002–11), we fit multilevel linear growth curve models to examine the cohort differences and individual aging effects on quality of life, depressive symptomatology, and life satisfaction. Results. Older cohorts are shown to have equivalent or better SWB than younger cohorts for each well-being measure. Nonetheless, individual aging effects for each well-being measure were observed with deterioration in well-being being greatest in older cohorts, even when adjusting for age-related changes in later life, including widowhood, retirement, and declining health. Discussion. The results suggest that although older cohorts enjoy higher levels of SWB than their younger counterparts when under similar circumstances, they experience sharper declines, especially in the very oldest cohorts. The findings demonstrate the importance of separating out cohort differences and aging effects and also of taking into account the multidimensionality of SWB to determine the point at which age deterioration begins to occur across different measures. PMID:24569002

  17. Early growth and development of later life metabolic disorders.

    PubMed

    Foo, Joo-Pin; Mantzoros, Christos

    2013-01-01

    Growth is effected via a complex interaction of genetic, nutritional, environmental and growth factors. Hormonal factors such as the growth hormone (GH) and insulin-like growth factor (IGF) signaling system, the human placental lactogen, and insulin play an integral role in early growth. Genetic factors affecting the GH-IGF system and insulin secretion and actions, and epigenetic mechanisms including DNA methylation have been further implicated as contributory factors. These hormonal systems, on a background of genetic susceptibility, together with other factors including maternal nutrition, placental and environmental factors, regulate not only early growth but also development. These interactions may impact on later health consequences in adult life. Accumulating data in the last few decades on developmental programming and later life metabolic disorders has provided a novel perspective on the possible pathogenesis of metabolic dysregulation. Despite postulations put forward to elucidate the mechanism underlying the association between early growth and later life metabolic disorders, it remains unclear what the dominant factor(s) would be, how any underlying mechanisms interact, or whether these mechanisms are truly causal.

  18. The impact of experienced stress on aged spatial discrimination: Cortical overreliance as a result of hippocampal impairment.

    PubMed

    Marshall, Amanda C; Cooper, Nicholas R; Geeraert, Nicolas

    2016-03-01

    A large body of neuroscientific work indicates that exposure to experienced stress causes damage to both cortical and hippocampal cells and results in impairments to cognitive abilities associated with these structures. Similarly, work within the domain of cognitive aging demonstrates that elderly participants who report experiencing greater amounts of stress show reduced levels of cognitive functioning. The present article attempted to combine both findings by collecting data from elderly and young participants who completed a spatial discrimination paradigm developed by Reagh and colleagues [Reagh et al. (2013) Hippocampus 24:303-314] to measure hippocampal-mediated cognitive processes. In order to investigate the effect of stress on the cortex and, indirectly, the hippocampus, it paired the paradigm with electroencephalographic recordings of the theta frequency band, which is thought to reflect cortical/hippocampal interactions. Findings revealed that elderly participants with high levels of experienced stress performed significantly worse on target recognition and lure discrimination and demonstrated heightened levels of cortical theta synchronization compared with young and elderly low stress counterparts. Results therefore provided further evidence for the adverse effect of stress on cognitive aging and indicate that impaired behavioral performance among high stress elderly may coincide with an overreliance on cortical cognitive processing strategies as a result of early damage to the hippocampus.

  19. Intensity of recreational physical activity throughout life and later life cognitive functioning in women.

    PubMed

    Tierney, Mary C; Moineddin, Rahim; Morra, Angela; Manson, Judith; Blake, Jennifer

    2010-01-01

    Long-term physical activity may affect risk of cognitive impairment but few studies have examined later life cognition in relation to intensity of life-long physical activity. We examined the associations between the intensity of long-term recreational physical activity and neuropsychological functioning in 90 healthy postmenopausal women on tests found to be useful in the early identification of dementia. Information was collected about their participation in strenuous and moderate activities between high school and menopause. Summary measures of long-term strenuous and moderate activity were constructed for each participant. All analyses were adjusted for relevant covariates. The six linear regression analyses showed significant positive associations between moderate activity and Wechsler Adult Intelligence Scale Revised (WAIS-R), Digit Span backward, WAIS-R Digit Symbol, and Trail Making Test Part B. Significant negative relationships were found between strenuous activity and Rey Auditory Verbal Learning Test delayed verbal recall, Complex Figure Test delayed visual memory, WAIS-R Digit Span backward, category fluency, and WAIS-R Digit Symbol. The associations found in the present study suggest that while moderate activity may be protective, long-term strenuous activity before menopause may lower cognitive performance later in life. These results support further investigation of the effects of life-long exercise intensity on cognition in later life.

  20. Municipality and Neighborhood Influences on Volunteering in Later Life.

    PubMed

    Dury, Sarah; Willems, Jurgen; De Witte, Nico; De Donder, Liesbeth; Buffel, Tine; Verté, Dominique

    2016-06-01

    This article explores the relationships between municipality features and volunteering by older adults. In the literature, strong evidence exists of the influence of place on older people's health. However, the question how neighborhoods and municipalities promote or hinder volunteer participation remains under-explored. Data for the research are derived from the Belgian Aging Studies. We estimate logistic multilevel models for older individuals' engagement in volunteering across 141 municipalities in Belgium (N = 67,144). Analysis shows that neighborhood connectedness, neighborhood satisfaction, home ownership, and presence of services predict voluntary engagement at older ages. The findings support that perceptions and quality of social resources that relate to neighborhoods may be important factors to explain volunteering among older adults. Moreover, the findings suggest that volunteering in later life must be considered within a broader framework. © The Author(s) 2014.

  1. Expectations of later life support among lesbian and gay Queenslanders.

    PubMed

    Hughes, Mark

    2010-12-01

      To examine lesbian and gay people's expectations of support, socialising and cohabitation in older age.   The study involved secondary data analysis of a subsample of 371 lesbian and gay people taken from a survey conducted by the Queensland Association for Healthy Communities.   Lesbian and gay people expected to receive support from diverse sources, including same-sex partners, lesbian, gay, bisexual and transgender friends and heterosexual friends. Women were more likely to expect to receive support from others than men, and men were more likely to expect to live alone in later life.   Aged care providers need to be responsive to the different sources of support that may be provided to older lesbian and gay people. Services that are lesbian- and gay-friendly may facilitate service uptake and reduce pressures on lesbian and gay people's informal networks of support. © 2010 The Author. Journal compilation © 2010 ACOTA.

  2. Self-realization and cultural narratives about later life.

    PubMed

    Laceulle, Hanne; Baars, Jan

    2014-12-01

    In late modern circumstances, aging individuals are confronted with the task of creating a meaningful individual life trajectory. However, these personal narratives are situated in the context of broader cultural narratives. It is argued that current cultural narratives about aging are often stereotyping and demeaning, being based on either a decline ideology or an age-defying ideology. This complicates the ascription of meaning to later life. We argue that narrative gerontology could profit from integrating a more cultural critical stance in its investigations. Dominant cultural narratives need to be challenged by viable counter narratives aimed at repairing and strengthening the moral agency of aging individuals. We discuss the criteria such counter narratives have to answer to and consider how the moral discourse on self-realization can provide an ideological foundation for meaning-generating cultural counter narratives on aging.

  3. Dyslexia and language impairment associated genetic markers influence cortical thickness and white matter in typically developing children.

    PubMed

    Eicher, John D; Montgomery, Angela M; Akshoomoff, Natacha; Amaral, David G; Bloss, Cinnamon S; Libiger, Ondrej; Schork, Nicholas J; Darst, Burcu F; Casey, B J; Chang, Linda; Ernst, Thomas; Frazier, Jean; Kaufmann, Walter E; Keating, Brian; Kenet, Tal; Kennedy, David; Mostofsky, Stewart; Murray, Sarah S; Sowell, Elizabeth R; Bartsch, Hauke; Kuperman, Joshua M; Brown, Timothy T; Hagler, Donald J; Dale, Anders M; Jernigan, Terry L; Gruen, Jeffrey R

    2016-03-01

    Dyslexia and language impairment (LI) are complex traits with substantial genetic components. We recently completed an association scan of the DYX2 locus, where we observed associations of markers in DCDC2, KIAA0319, ACOT13, and FAM65B with reading-, language-, and IQ-related traits. Additionally, the effects of reading-associated DYX3 markers were recently characterized using structural neuroimaging techniques. Here, we assessed the neuroimaging implications of associated DYX2 and DYX3 markers, using cortical volume, cortical thickness, and fractional anisotropy. To accomplish this, we examined eight DYX2 and three DYX3 markers in 332 subjects in the Pediatrics Imaging Neurocognition Genetics study. Imaging-genetic associations were examined by multiple linear regression, testing for influence of genotype on neuroimaging. Markers in DYX2 genes KIAA0319 and FAM65B were associated with cortical thickness in the left orbitofrontal region and global fractional anisotropy, respectively. KIAA0319 and ACOT13 were suggestively associated with overall fractional anisotropy and left pars opercularis cortical thickness, respectively. DYX3 markers showed suggestive associations with cortical thickness and volume measures in temporal regions. Notably, we did not replicate association of DYX3 markers with hippocampal measures. In summary, we performed a neuroimaging follow-up of reading-, language-, and IQ-associated DYX2 and DYX3 markers. DYX2 associations with cortical thickness may reflect variations in their role in neuronal migration. Furthermore, our findings complement gene expression and imaging studies implicating DYX3 markers in temporal regions. These studies offer insight into where and how DYX2 and DYX3 risk variants may influence neuroimaging traits. Future studies should further connect the pathways to risk variants associated with neuroimaging/neurocognitive outcomes.

  4. Cortical phase changes measured using 7-T MRI in subjects with subjective cognitive impairment, and their association with cognitive function.

    PubMed

    van Rooden, Sanneke; Buijs, Mathijs; van Vliet, Marjolein E; Versluis, Maarten J; Webb, Andrew G; Oleksik, Ania M; van de Wiel, Lotte; Middelkoop, Huub A M; Blauw, Gerard Jan; Weverling-Rynsburger, Annelies W E; Goos, Jeroen D C; van der Flier, Wiesje M; Koene, Ted; Scheltens, Philip; Barkhof, Frederik; van de Rest, Ondine; Slagboom, P Eline; van Buchem, Mark A; van der Grond, Jeroen

    2016-09-01

    Studies have suggested that, in subjects with subjective cognitive impairment (SCI), Alzheimer's disease (AD)-like changes may occur in the brain. Recently, an in vivo study has indicated the potential of ultra-high-field MRI to visualize amyloid-beta (Aβ)-associated changes in the cortex in patients with AD, manifested by a phase shift on T2 *-weighted MRI scans. The main aim of this study was to investigate whether cortical phase shifts on T2 *-weighted images at 7 T in subjects with SCI can be detected, possibly implicating the deposition of Aβ plaques and associated iron. Cognitive tests and T2 *-weighted scans using a 7-T MRI system were performed in 28 patients with AD, 18 subjects with SCI and 27 healthy controls (HCs). Cortical phase shifts were measured. Univariate general linear modeling and linear regression analysis were used to assess the association between diagnosis and cortical phase shift, and between cortical phase shift and the different neuropsychological tests, adjusted for age and gender. The phase shift (mean, 1.19; range, 1.00-1.35) of the entire cortex in AD was higher than in both SCI (mean, 0.85; range, 0.73-0.99; p < 0.001) and HC (mean, 0.94; range, 0.79-1.10; p < 0.001). No AD-like changes, e.g. increased cortical phase shifts, were found in subjects with SCI compared with HCs. In SCI, a significant association was found between memory function (Wechsler Memory Scale, WMS) and cortical phase shift (β = -0.544, p = 0.007). The major finding of this study is that, in subjects with SCI, an increased cortical phase shift measured at high field is associated with a poorer memory performance, although, as a group, subjects with SCI do not show an increased phase shift compared with HCs. This increased cortical phase shift related to memory performance may contribute to the understanding of SCI as it is still unclear whether SCI is a sign of pre-clinical AD. Copyright © 2014 John Wiley & Sons, Ltd. Copyright © 2014

  5. Neurophysiological mechanisms of cortical plasticity impairments in schizophrenia and modulation by the NMDA receptor agonist D-serine.

    PubMed

    Kantrowitz, Joshua T; Epstein, Michael L; Beggel, Odeta; Rohrig, Stephanie; Lehrfeld, Jonathan M; Revheim, Nadine; Lehrfeld, Nayla P; Reep, Jacob; Parker, Emily; Silipo, Gail; Ahissar, Merav; Javitt, Daniel C

    2016-12-01

    Schizophrenia is associated with deficits in cortical plasticity that affect sensory brain regions and lead to impaired cognitive performance. Here we examined underlying neural mechanisms of auditory plasticity deficits using combined behavioural and neurophysiological assessment, along with neuropharmacological manipulation targeted at the N-methyl-D-aspartate type glutamate receptor (NMDAR). Cortical plasticity was assessed in a cohort of 40 schizophrenia/schizoaffective patients relative to 42 healthy control subjects using a fixed reference tone auditory plasticity task. In a second cohort (n = 21 schizophrenia/schizoaffective patients, n = 13 healthy controls), event-related potential and event-related time-frequency measures of auditory dysfunction were assessed during administration of the NMDAR agonist d-serine. Mismatch negativity was used as a functional read-out of auditory-level function. Clinical trials registration numbers were NCT01474395/NCT02156908 Schizophrenia/schizoaffective patients showed significantly reduced auditory plasticity versus healthy controls (P = 0.001) that correlated with measures of cognitive, occupational and social dysfunction. In event-related potential/time-frequency analyses, patients showed highly significant reductions in sensory N1 that reflected underlying impairments in θ responses (P < 0.001), along with reduced θ and β-power modulation during retention and motor-preparation intervals. Repeated administration of d-serine led to intercorrelated improvements in (i) auditory plasticity (P < 0.001); (ii) θ-frequency response (P < 0.05); and (iii) mismatch negativity generation to trained versus untrained tones (P = 0.02). Schizophrenia/schizoaffective patients show highly significant deficits in auditory plasticity that contribute to cognitive, occupational and social dysfunction. d-serine studies suggest first that NMDAR dysfunction may contribute to underlying cortical plasticity deficits and, second, that repeated

  6. Social Support and Attitudes to Aging in Later Life.

    PubMed

    Lamont, Ruth A; Nelis, Sharon M; Quinn, Catherine; Clare, Linda

    2017-01-01

    Negative attitudes to aging are a risk factor for poor health and well-being. The current study sought to examine satisfaction with social support as a potentially modifiable factor that might facilitate the development of more positive attitudes to aging. A convenience sample of 501 older respondents (Mage = 72.06) reported on frequency of social support and their satisfaction with it, as well as completing a rating of attachment (model of the self and others), a measure of attitudes to aging, and a number of background measures. Results indicated that better subjective health, younger age, and greater satisfaction with social support were all significant predictors of more positive attitudes to aging, while frequency of social support was not. Model of the self accounted for some variation in satisfaction with social support. Interventions to increase satisfaction with social support in later life, recognizing individual differences and attachment styles, may improve attitudes to aging and further support health and well-being. © The Author(s) 2016.

  7. Poverty and transitions in health in later life.

    PubMed

    Adena, Maja; Myck, Michal

    2014-09-01

    Using a sample of Europeans aged 50+ from 12 countries in the Survey of Health, Ageing and Retirement in Europe (SHARE), we analyse the role of poor material conditions as a determinant of changes in health over a four- to five-year period. We find that poverty defined with respect to relative income has no effect on changes in health. However, broader measures of poor material conditions, such as subjective poverty or low wealth, significantly increase the probability of transition to poor health among the healthy and reduce the chance of recovery from poor health over the time interval analysed. In addition to this, the subjective measure of poverty has a significant effect on mortality, increasing it by 65% among men and by 68% among those aged 50-64. Material conditions affect health among older people. We suggest that if attempts to reduce poverty in later life and corresponding policy targets are to focus on the relevant measures, they should take into account broader definitions of poverty than those based only on relative incomes.

  8. Later life learning experience among Chinese elderly in Hong Kong.

    PubMed

    Leung, Angela; Lui, Yu-Hon; Chi, Iris

    2005-01-01

    In a world with increasing numbers of older adults and a world wide emphasis placed on lifelong learning, it is crucial to examine and formulate appropriate policy for learning in later life (LLL). Hong Kong has a rapidly aging population, which is projected to double within the next 25 years. However, lifelong learning for the elderly has yet to be fully developed. This article reports the findings of 2 surveys: one on the LLL experience among 190 Chinese elderly in Hong Kong and another on the experiences of 9 center directors in running courses for the elderly. We found that Chinese older persons generally learn for expressive motivation rather than instrumental motivation, although those with higher educational attainment take LLL for both instrumental and expressive motivation. This finding is consistent with those obtained with American populations. Practical courses such as languages and health-related topics were found to be the most popular; and Nearly a quarter (27%) of the respondents (in particular those who are well educated) expressed interest in peer teaching. The findings are important to understand LLL in the Chinese population and assist in the formulation of an appropriate LLL policy in Hong Kong. These findings also serve as a comparison for other countries trying to provide continuing education opportunities for its older citizens.

  9. The role of food shopping in later life.

    PubMed

    Pettigrew, Simone; Worrall, Caitlin; Biagioni, Nicole; Talati, Zenobia; Jongenelis, Michelle

    2017-04-01

    By the time they reach retirement, individuals are typically highly experienced in sourcing food products and they have strong familiarity with food retailing environments. To investigate the ongoing role of food shopping in later life, the present study explored seniors' attitudes to food shopping and their food-selection behaviours through the lens of their broader lifestyles. The aim was to provide insights of relevance to the development of future efforts to optimise seniors' food shopping experiences and nutrition-related outcomes. Interviews were conducted with 75 Western Australians aged 60 + years to discuss food shopping in the context of their day-to-day lives. The sample was comprised mainly of women (n = 64) and the average age was 74 years. In general, food shopping was perceived to be a manageable but mundane part of life. The findings suggest that there has been an improvement in food retailing practices because many of the numerous areas of concern identified in previous research conducted in this geographical location a decade ago were not nominated as relevant by the interviewees. Instead, food-related issues reported to be most problematic included the difficulties associated with sourcing affordable food products that had been produced locally and that did not contain unacceptable food additives. Seniors' food shopping concerns thus appear to have changed from functional aspects of the physical store environment to product attributes that reflect the increasing industrialisation of the food industry. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. MEC-17 deficiency leads to reduced α-tubulin acetylation and impaired migration of cortical neurons.

    PubMed

    Li, Lei; Wei, Dan; Wang, Qiong; Pan, Jing; Liu, Rong; Zhang, Xu; Bao, Lan

    2012-09-12

    Neuronal migration is a fundamental process during the development of the cerebral cortex and is regulated by cytoskeletal components. Microtubule dynamics can be modulated by posttranslational modifications to tubulin subunits. Acetylation of α-tubulin at lysine 40 is important in regulating microtubule properties, and this process is controlled by acetyltransferase and deacetylase. MEC-17 is a newly discovered α-tubulin acetyltransferase that has been found to play a major role in the acetylation of α-tubulin in different species in vivo. However, the physiological function of MEC-17 during neural development is largely unknown. Here, we report that MEC-17 is critical for the migration of cortical neurons in the rat. MEC-17 was strongly expressed in the cerebral cortex during development. MEC-17 deficiency caused migratory defects in the cortical projection neurons and interneurons, and perturbed the transition of projection neurons from the multipolar stage to the unipolar/bipolar stage in the intermediate zone of the cortex. Furthermore, knockdown of α-tubulin deacetylase HDAC6 or overexpression of tubulin(K40Q) to mimic acetylated α-tubulin could reduce the migratory and morphological defects caused by MEC-17 deficiency in cortical projection neurons. Thus, MEC-17, which regulates the acetylation of α-tubulin, appears to control the migration and morphological transition of cortical neurons. This finding reveals the importance of MEC-17 and α-tubulin acetylation in cortical development.

  11. A Qualitative Study of Alcohol, Health and Identities among UK Adults in Later Life

    PubMed Central

    Wilson, Graeme B.; Kaner, Eileen F. S.; Crosland, Ann; Ling, Jonathan; McCabe, Karen; Haighton, Catherine A.

    2013-01-01

    Increasing alcohol consumption among older individuals is a public health concern. Lay understandings of health risks and stigma around alcohol problems may explain why public health messages have not reduced rates of heavy drinking in this sector. A qualitative study aimed to elucidate older people's reasoning about drinking in later life and how this interacted with health concerns, in order to inform future, targeted, prevention in this group. In 2010 a diverse sample of older adults in North East England (ages 50–95) participated in interviews (n = 24, 12 male, 12 female) and three focus groups (participants n = 27, 6 male, 21 female). Data were analysed using grounded theory and discursive psychology methods. When talking about alcohol use older people oriented strongly towards opposed identities of normal or problematic drinker, defined by propriety rather than health considerations. Each of these identities could be applied in older people's accounts of either moderate or heavy drinking. Older adults portrayed drinking less alcohol as an appropriate response if one experienced impaired health. However continued heavy drinking was also presented as normal behaviour for someone experiencing relative wellbeing in later life, or if ill health was construed as unrelated to alcohol consumption. Older people displayed scepticism about health advice on alcohol when avoiding stigmatised identity as a drinker. Drinking patterns did not appear to be strongly defined by gender, although some gendered expectations of drinking were described. Identities offer a useful theoretical concept to explain the rises in heavy drinking among older populations, and can inform preventive approaches to tackle this. Interventions should engage and foster positive identities to sustain healthier drinking and encourage at the community level the identification of heavy drinking as neither healthy nor synonymous with dependence. Future research should test and assess such

  12. Parturition events and risk of urinary incontinence in later life.

    PubMed

    Thom, David H; Brown, Jeanette S; Schembri, Michael; Ragins, Arona I; Creasman, Jennifer M; Van Den Eeden, Stephen K

    2011-11-01

    To examine the association between specific events during vaginal deliveries and urinary incontinence later in life. A retrospective cohort study of 1,521 middle-aged and older women with at least one vaginal delivery who were long-term members of an integrated health delivery system. Age, race/ethnicity, current incontinence status, medical, surgical history, pregnancy and parturition history, menopausal status, hormone replacement, health habits, and general health were obtained by questionnaire. Labor and delivery records, archived since 1948, were abstracted by professional medical record abstractors to obtain parturition events including induction, length of labor stages, type of anesthesia, episiotomy, instrumental delivery, and birth weight. The primary dependent variable was current weekly urinary incontinence (once per week or more often) versus urinary incontinence less than monthly (including no incontinence) in past 12 months. Associations of parturition events and later incontinence were assessed in multivariate analysis with logistic regression. The mean age of participants was 56 years. After adjustment for multiple risk factors, weekly urinary incontinence significantly associated with age at first birth (P = 0.036), greatest birth weight (P = 0.005), and ever having been induced for labor (OR = 1.51; 95%CI = 1.06-2.16, P = 0.02). Risk of incontinence increased from OR = 1.35 (95%CI = 0.92-1.97, P = 0.12) for women with one induction to OR = 2.67 (95%CI = 1.25-5.71, P = 0.01) for women with two or more inductions (P = 0.01 for trend). No other parturition factors were associated with incontinence. Younger age at first birth, greatest birth weight, and induction of labor were associated with an increased risk of incontinence in later life. Copyright © 2011 Wiley Periodicals, Inc.

  13. Parturition Events and Risk of Urinary Incontinence in Later Life

    PubMed Central

    Thom, David H.; Brown, Jeanette S.; Schembri, Michael; Ragins, Arona I.; Creasman, Jennifer M.; Van Den Eeden, Stephen K.

    2011-01-01

    Aims To examine the association between specific events during vaginal deliveries and urinary incontinence later in life. Methods A retrospective cohort study of 1521 middle-aged and older women with at least 1 vaginal delivery who were long-term members of an integrated health delivery system. Age, race/ethnicity, current incontinence status, medical, surgical history, pregnancy and parturition history, menopausal status, hormone replacement, health habits, and general health were obtained by questionnaire. Labor and delivery records, archived since 1948, were abstracted by professional medical record abstractors to obtain parturition events including induction, length of labor stages, type of anesthesia, episiotomy, instrumental delivery, and birth weight. The primary dependent variable was current weekly urinary incontinence (once per week or more often) vs urinary incontinence less than monthly (including no incontinence) in past 12 months. Associations of parturition events and later incontinence were assessed in multivariate analysis with logistic regression. Results The mean age of participants was 56 years. After adjustment for multiple risk factors, weekly urinary incontinence significantly associated with age at first birth (p=.036), greatest birth weight (p=.005), and ever having been induced for labor (OR=1.51; 95% CI=1.06–2.16, p=.02). Risk of incontinence increased from OR=1.35 (95% CI=0.92–1.97, p=0.12) for women with one induction to OR=2.67 (95% CI= 1.25–5.71, p=.01) for women with 2 or more inductions (p=0.01 for trend). No other parturition factors were associated with incontinence. Conclusions Younger age at first birth, greatest birth weight, and induction of labor were associated with an increased risk of incontinence in later life. PMID:21780171

  14. Early Life Nutrition, Epigenetics and Programming of Later Life Disease

    PubMed Central

    Vickers, Mark H.

    2014-01-01

    The global pandemic of obesity and type 2 diabetes is often causally linked to marked changes in diet and lifestyle; namely marked increases in dietary intakes of high energy diets and concomitant reductions in physical activity levels. However, less attention has been paid to the role of developmental plasticity and alterations in phenotypic outcomes resulting from altered environmental conditions during the early life period. Human and experimental animal studies have highlighted the link between alterations in the early life environment and increased risk of obesity and metabolic disorders in later life. This link is conceptualised as the developmental programming hypothesis whereby environmental influences during critical periods of developmental plasticity can elicit lifelong effects on the health and well-being of the offspring. In particular, the nutritional environment in which the fetus or infant develops influences the risk of metabolic disorders in offspring. The late onset of such diseases in response to earlier transient experiences has led to the suggestion that developmental programming may have an epigenetic component, as epigenetic marks such as DNA methylation or histone tail modifications could provide a persistent memory of earlier nutritional states. Moreover, evidence exists, at least from animal models, that such epigenetic programming should be viewed as a transgenerational phenomenon. However, the mechanisms by which early environmental insults can have long-term effects on offspring are relatively unclear. Thus far, these mechanisms include permanent structural changes to the organ caused by suboptimal levels of an important factor during a critical developmental period, changes in gene expression caused by epigenetic modifications (including DNA methylation, histone modification, and microRNA) and permanent changes in cellular ageing. A better understanding of the epigenetic basis of developmental programming and how these effects may be

  15. Is loneliness in later life a self-fulfilling prophecy?

    PubMed Central

    Pikhartova, Jitka; Bowling, Ann; Victor, Christina

    2016-01-01

    Objectives: There are many stereotypes about ageing and later life. We looked at the association between expectations and stereotyping of loneliness in old age and actual self-reported loneliness status 8 years later in English Longitudinal Study of Ageing (ELSA). Method: Data from 4465 ELSA core members aged over 50 who responded to Waves 2 (2004) did not report loneliness in Wave 2, and responded to loneliness questions at least once between Waves 3 and 6 (2006–2012) were used in multivariable repeated measures logit regression analysis to estimate relationship between perceived stereotypes and expectation of loneliness in older age and actual loneliness reported within 8 years of follow-up. Results: Twenty-four per cent of respondents from the analytical sample agreed at Wave 2 that old age is time of loneliness and 33% expected to be lonely in old age. Loneliness was reported by 11.5% of respondents at Waves 3–6. Both stereotypes and expectation were significantly associated with later reported loneliness (OR 2.65 (95% CI 2.05–3.42) for stereotypes and 2.98 (95% CI 2.33–3.75) for expectations in age-sex adjusted analysis). Both variables significantly predicted future loneliness even when socio-demographic circumstances were taken into account and both variables were mutually adjusted although the effect was reduced (OR's 1.53 (95% CI 1.16–2.01) for stereotypes and 2.38 (95% CI 1.84–3.07) for expectations). Conclusions: Stereotypes and expectations related to loneliness in the old age were significantly associated with reported loneliness 8 years later. Interventions aimed at changing age-related stereotypes in population may have more impact on reducing loneliness than individually based services. PMID:25806794

  16. Early life nutrition, epigenetics and programming of later life disease.

    PubMed

    Vickers, Mark H

    2014-06-02

    The global pandemic of obesity and type 2 diabetes is often causally linked to marked changes in diet and lifestyle; namely marked increases in dietary intakes of high energy diets and concomitant reductions in physical activity levels. However, less attention has been paid to the role of developmental plasticity and alterations in phenotypic outcomes resulting from altered environmental conditions during the early life period. Human and experimental animal studies have highlighted the link between alterations in the early life environment and increased risk of obesity and metabolic disorders in later life. This link is conceptualised as the developmental programming hypothesis whereby environmental influences during critical periods of developmental plasticity can elicit lifelong effects on the health and well-being of the offspring. In particular, the nutritional environment in which the fetus or infant develops influences the risk of metabolic disorders in offspring. The late onset of such diseases in response to earlier transient experiences has led to the suggestion that developmental programming may have an epigenetic component, as epigenetic marks such as DNA methylation or histone tail modifications could provide a persistent memory of earlier nutritional states. Moreover, evidence exists, at least from animal models, that such epigenetic programming should be viewed as a transgenerational phenomenon. However, the mechanisms by which early environmental insults can have long-term effects on offspring are relatively unclear. Thus far, these mechanisms include permanent structural changes to the organ caused by suboptimal levels of an important factor during a critical developmental period, changes in gene expression caused by epigenetic modifications (including DNA methylation, histone modification, and microRNA) and permanent changes in cellular ageing. A better understanding of the epigenetic basis of developmental programming and how these effects may be

  17. Changes in body mass in later life and incident dementia.

    PubMed

    Power, Brian D; Alfonso, Helman; Flicker, Leon; Hankey, Graeme J; Yeap, Bu B; Almeida, Osvaldo P

    2013-03-01

    There is ongoing debate about whether a decline in body mass represents a true risk factor for dementia, whether it is a phenotypic marker of incipient dementia, or perhaps a marker of another process that increases dementia risk. This study was designed to determine if changes in body mass index (BMI) in later life are associated with hazard of incident dementia over a follow-up period of up to eight years. Method followed was a prospective cohort study of 4,181 men aged 65-84 years, resident in Perth, Australia. The exposure of interest was change in BMI measured between 1996-1998 and 2001-2004. The outcome was incident dementia, established using the Western Australia Data Linkage System until 2009. We used Cox regression models to establish crude and adjusted hazard of dementia for change in BMI. Compared with men with a stable BMI, those with a decrease in BMI >1 kg/m2 had a higher adjusted hazard of dementia (hazard ratio (HR) = 1.89, 95% CI = 1.32-2.70). The cumulative hazard of dementia over follow-up for changes in BMI was greatest for men with a decrease in BMI >1 kg/m2; this trend was apparent for men in all BMI categories (underweight, normal, overweight, obese). A reverse "J-shaped" association between BMI change and incident dementia was observed, with the lowest dementia rate being for men whose BMI remained stable. Men who maintained a stable body mass had the lowest incidence of dementia. Further studies are needed to clarify causality and assess feasibility of interventional studies to preserve body mass in aging men.

  18. Listening to Religious Music and Mental Health in Later Life.

    PubMed

    Bradshaw, Matt; Ellison, Christopher G; Fang, Qijuan; Mueller, Collin

    2015-12-01

    Research has linked several aspects of religion--including service attendance, prayer, meditation, religious coping strategies, congregational support systems, and relations with God, among others--with positive mental health outcomes among older U.S. adults. This study examines a neglected dimension of religious life: listening to religious music. Two waves of nationally representative data on older U.S. adults were analyzed (n = 1,024). Findings suggest that the frequency of listening to religious music is associated with a decrease in death anxiety and increases in life satisfaction, self-esteem, and a sense of control across the 2 waves of data. In addition, the frequency of listening to gospel music (a specific type of religious music) is associated with a decrease in death anxiety and an increase in a sense of control. These associations are similar for blacks and whites, women and men, and low- and high-socioeconomic status individuals. Religion is an important socioemotional resource that has been linked with desirable mental health outcomes among older U.S. adults. This study shows that listening to religious music may promote psychological well-being in later life. Given that religious music is available to most individuals--even those with health problems or physical limitations that might preclude participation in more formal aspects of religious life--it might be a valuable resource for promoting mental health later in the life course. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  19. Differential microstructural and morphological abnormalities in mild cognitive impairment and Alzheimer's disease: Evidence from cortical and deep gray matter.

    PubMed

    Gong, Nan-Jie; Chan, Chun-Chung; Leung, Lam-Ming; Wong, Chun-Sing; Dibb, Russell; Liu, Chunlei

    2017-05-01

    One aim of this study is to use non-Gaussian diffusion kurtosis imaging (DKI) for capturing microstructural abnormalities in gray matter of Alzheimer's disease (AD). The other aim is to compare DKI metrics against thickness of cortical gray matter and volume of deep gray matter, respectively. A cohort of 18 patients with AD, 18 patients with amnestic mild cognitive impairment (MCI), and 18 normal controls underwent morphological and DKI MR imaging. Images were investigated using regions-of-interest-based analyses for deep gray matter and vertex-wise analyses for cortical gray matter. In deep gray matter, more regions showed DKI parametric abnormalities than atrophies at the early MCI stage. Mean kurtosis (MK) exhibited the largest number of significant abnormalities among all DKI metrics. At the later AD stage, diffusional abnormalities were observed in fewer regions than atrophies. In cortical gray matter, abnormalities in thickness were mainly in the medial and lateral temporal lobes, which fit the locations of known early pathological changes. Microstructural abnormalities were predominantly in the parietal and even frontal lobes, which fit the locations of known late pathological changes. In conclusion, MK can complement conventional diffusion metrics for detecting microstructural changes, especially in deep gray matter. This study also provides evidence supporting the notion that microstructural changes predate morphological changes. Hum Brain Mapp 38:2495-2508, 2017. © 2017 Wiley Periodicals, Inc.

  20. High Insulin Levels in KK-Ay Diabetic Mice Cause Increased Cortical Bone Mass and Impaired Trabecular Micro-Structure

    PubMed Central

    Fu, Cen; Zhang, Xiaolin; Ye, Fei; Yang, Jianhong

    2015-01-01

    Type 2 diabetes mellitus (T2DM) is a chronic disease characterized by hyperglycemia, hyperinsulinemia and complications, including obesity and osteoporosis. Rodents have been widely used to model human T2DM and investigate its effect on the skeleton. We aimed to investigate skeletal alterations in Yellow Kuo Kondo (KK-Ay) diabetic mice displaying high insulin and glucose levels. Bone mineral density (BMD), micro-architecture and bone metabolism-related genes were analyzed. The total femoral areal BMD (aBMD), cortical volumetric BMD (vBMD) and thickness were significantly increased in KK-Ay mice, while the trabecular vBMD and mineralized bone volume/tissue volume (BV/TV), trabecular thickness and number were decreased compared to C57BL mice. The expression of both osteoblast-related genes, such as osteocalcin (OC), bone sialoprotein, Type I Collagen, osteonectin, RUNX2 and OSX, and osteoclast-related genes, such as TRAP and TCIRG, were up-regulated in KK-Ay mice. Correlation analyses showed that serum insulin levels were positively associated with aBMD, cortical vBMD and thickness and negatively associated with trabecular vBMD and micro-architecture. In addition, serum insulin levels were positively related to osteoblast-related and osteoclast-related gene expression. Our data suggest that high insulin levels in KK-Ay diabetic mice may increase cortical bone mass and impair trabecular micro-structure by up-regulating osteoblast-and osteoclast-related gene expression. PMID:25872143

  1. High insulin levels in KK-Ay diabetic mice cause increased cortical bone mass and impaired trabecular micro-structure.

    PubMed

    Fu, Cen; Zhang, Xiaolin; Ye, Fei; Yang, Jianhong

    2015-04-13

    Type 2 diabetes mellitus (T2DM) is a chronic disease characterized by hyperglycemia, hyperinsulinemia and complications, including obesity and osteoporosis. Rodents have been widely used to model human T2DM and investigate its effect on the skeleton. We aimed to investigate skeletal alterations in Yellow Kuo Kondo (KK-Ay) diabetic mice displaying high insulin and glucose levels. Bone mineral density (BMD), micro-architecture and bone metabolism-related genes were analyzed. The total femoral areal BMD (aBMD), cortical volumetric BMD (vBMD) and thickness were significantly increased in KK-Ay mice, while the trabecular vBMD and mineralized bone volume/tissue volume (BV/TV), trabecular thickness and number were decreased compared to C57BL mice. The expression of both osteoblast-related genes, such as osteocalcin (OC), bone sialoprotein, Type I Collagen, osteonectin, RUNX2 and OSX, and osteoclast-related genes, such as TRAP and TCIRG, were up-regulated in KK-Ay mice. Correlation analyses showed that serum insulin levels were positively associated with aBMD, cortical vBMD and thickness and negatively associated with trabecular vBMD and micro-architecture. In addition, serum insulin levels were positively related to osteoblast-related and osteoclast-related gene expression. Our data suggest that high insulin levels in KK-Ay diabetic mice may increase cortical bone mass and impair trabecular micro-structure by up-regulating osteoblast-and osteoclast-related gene expression.

  2. Loss of cortical actin filaments in insulin-resistant skeletal muscle cells impairs GLUT4 vesicle trafficking and glucose transport

    PubMed Central

    McCarthy, Alicia M.; Spisak, Kristen O.; Brozinick, Joseph T.; Elmendorf, Jeffrey S.

    2008-01-01

    Study has demonstrated an essential role of cortical filamentous actin (F-actin) in insulin-regulated glucose uptake by skeletal muscle. Here, we tested whether perturbations in F-actin contributed to impaired insulin responsiveness provoked by hyperinsulinemia. In L6 myo-tubes stably expressing GLUT4 that carries an exofacial myc-epitope tag, acute insulin stimulation (20 min, 100 nM) increased GLUT4myc translocation and glucose uptake by ~2-fold. In contrast, a hyperinsulinemic state, induced by inclusion of 5 nM insulin in the medium for 12 h decreased the ability of insulin to stimulate these processes. Defects in insulin signaling did not readily account for the observed disruption. In contrast, hyperinsulinemia reduced cortical F-actin. This occurred concomitant with a loss of plasma membrane phosphatidylinositol 4,5-bisphosphate (PIP2), a lipid involved in cytoskeletal regulation. Restoration of plasma membrane PIP2 in hyperinsulinemic cells restored F-actin and insulin responsiveness. Consistent with these in vitro observations suggesting that the hyperinsulinemic state negatively affects cortical F-actin structure, epitrochlearis skeletal muscle from insulin-resistant hyperinsulinemic Zucker fatty rats displayed a similar loss of F-actin structure compared with that in muscle from lean insulin-sensitive littermates. We propose that a component of insulin-induced insulin resistance in skeletal muscle involves defects in PIP2/F-actin structure essential for insulin-regulated glucose transport. PMID:16774991

  3. Loss of cortical actin filaments in insulin-resistant skeletal muscle cells impairs GLUT4 vesicle trafficking and glucose transport.

    PubMed

    McCarthy, Alicia M; Spisak, Kristen O; Brozinick, Joseph T; Elmendorf, Jeffrey S

    2006-11-01

    Study has demonstrated an essential role of cortical filamentous actin (F-actin) in insulin-regulated glucose uptake by skeletal muscle. Here, we tested whether perturbations in F-actin contributed to impaired insulin responsiveness provoked by hyperinsulinemia. In L6 myotubes stably expressing GLUT4 that carries an exofacial myc-epitope tag, acute insulin stimulation (20 min, 100 nM) increased GLUT4myc translocation and glucose uptake by approximately 2-fold. In contrast, a hyperinsulinemic state, induced by inclusion of 5 nM insulin in the medium for 12 h decreased the ability of insulin to stimulate these processes. Defects in insulin signaling did not readily account for the observed disruption. In contrast, hyperinsulinemia reduced cortical F-actin. This occurred concomitant with a loss of plasma membrane phosphatidylinositol 4,5-bisphosphate (PIP(2)), a lipid involved in cytoskeletal regulation. Restoration of plasma membrane PIP(2) in hyperinsulinemic cells restored F-actin and insulin responsiveness. Consistent with these in vitro observations suggesting that the hyperinsulinemic state negatively affects cortical F-actin structure, epitrochlearis skeletal muscle from insulin-resistant hyperinsulinemic Zucker fatty rats displayed a similar loss of F-actin structure compared with that in muscle from lean insulin-sensitive littermates. We propose that a component of insulin-induced insulin resistance in skeletal muscle involves defects in PIP(2)/F-actin structure essential for insulin-regulated glucose transport.

  4. Development of later life spontaneous seizures in a rodent model of hypoxia induced neonatal seizures

    PubMed Central

    Rakhade, Sanjay N; Klein, Peter; Huynh, Thanthao; Hilario-Gomez, Cristina; Kosaras, Bela; Rotenberg, Alexander; Jensen, Frances E.

    2011-01-01

    Summary Purpose To study the development of epilepsy following hypoxia-induced neonatal seizures in Long Evans rats and to establish the presence of spontaneous seizures in this model of early life seizures. Methods Long-Evans rat pups were subjected to hypoxia-induced neonatal seizures at postnatal day 10 (P10). Epidural cortical electroencephalography (EEG) and hippocampal depth electrodes were used to detect the presence of seizures in later adulthood (>P60). In addition, subdermal wire electrode recordings were used to monitor age at onset and progression of seizures in the juvenile period, at intervals between P10–P60. Timm staining was performed to evaluate mossy fiber sprouting in the hippocampi of P100 adult rats that had experienced neonatal seizures. Key Findings In recordings made from adult rats (P60–P180), the prevalence of epilepsy in cortical and hippocampal EEG recordings was 94.4% following early life hypoxic seizures. These spontaneous seizures were identified by characteristic spike and wave activity on EEG accompanied by behavioral arrest and facial automatisms (electroclinical seizures). Phenobarbital injection transiently abolished spontaneous seizures. EEG in the juvenile period (P10–60) showed that spontaneous seizures first occurred approximately 2 weeks after the initial episode of hypoxic seizures. Following this period, spontaneous seizure frequency and duration progressively increased with time. Furthermore, significantly increased sprouting of mossy fibers was observed in the CA3 pyramidal cell layer of the hippocampus in adult animals following hypoxia-induced neonatal seizures. Notably, Fluoro-Jade B staining confirmed that hypoxic seizures at P10 did not induce acute neuronal death. Significance The rodent model of hypoxia-induced neonatal seizures leads to the development of epilepsy in later life, accompanied by increased mossy fiber sprouting. In addition, this model appears to exhibit a seizure-free latent period

  5. Anosognosia in mild cognitive impairment: Relationship to activation of cortical midline structures involved in self-appraisal

    PubMed Central

    Ries, Michele L.; Jabbar, Britta M.; Schmitz, Taylor W.; Trivedi, Mehul A.; Gleason, Carey E.; Carlsson, Cynthia M.; Rowley, Howard A.; Asthana, Sanjay; Johnson, Sterling C.

    2009-01-01

    Awareness of cognitive dysfunction shown by individuals with Mild Cognitive Impairment (MCI), a condition conferring risk for Alzheimer’s disease (AD), is variable. Anosognosia, or unawareness of loss of function, is beginning to be recognized as an important clinical symptom of MCI. However, little is known about the brain substrates underlying this symptom. We hypothesized that MCI participants’ activation of cortical midline structures (CMS) during self-appraisal would covary with level of insight into cognitive difficulties (indexed by a discrepancy score between patient and informant ratings of cognitive decline in each MCI participant). To address this hypothesis, we first compared 16 MCI participants and 16 age-matched controls, examining brain regions showing conjoint or differential BOLD response during self-appraisal. Second, we used regression to investigate the relationship between awareness of deficit in MCI and BOLD activity during self-appraisal, controlling for extent of memory impairment. Between-group comparisons indicated that MCI participants show subtly attenuated CMS activity during self-appraisal. Regression analysis revealed a highly-significant relationship between BOLD response during self-appraisal and self-awareness of deficit in MCI. This finding highlights the level of anosognosia in MCI as an important predictor of response to self-appraisal in cortical midline structures, brain regions vulnerable to changes in early AD. PMID:17445294

  6. DISC1 knockdown impairs the tangential migration of cortical interneurons by affecting the actin cytoskeleton

    PubMed Central

    Steinecke, André; Gampe, Christin; Nitzsche, Falk; Bolz, Jürgen

    2014-01-01

    Disrupted-in-Schizophrenia 1 (DISC1) is a risk gene for a spectrum of major mental disorders. It has been shown to regulate radial migration as well as dendritic arborization during neurodevelopment and corticogenesis. In a previous study we demonstrated through in vitro experiments that DISC1 also controls the tangential migration of cortical interneurons originating from the medial ganglionic eminence (MGE). Here we first show that DISC1 is necessary for the proper tangential migration of cortical interneurons in the intact brain. Expression of EGFP under the Lhx6 promotor allowed us to analyze exclusively interneurons transfected in the MGE after in utero electroporation. After 3 days in utero, DISC1 deficient interneurons displayed prolonged leading processes and, compared to control, fewer neurons reached the cortex. Time-lapse video microscopy of cortical feeder-layers revealed a decreased migration velocity due to a reduction of soma translocations. Immunostainings indicated that DISC1 is co-localized with F-actin in the growth cone-like structure of the leading process. DISC1 knockdown reduced F-actin levels whereas the overall actin level was not altered. Moreover, DISC1 knockdown also decreased levels of phosphorylated Girdin, which cross-links F-actin, as well as the Girdin-activator pAkt. In contrast, using time-lapse video microscopy of fluorescence-tagged tubulin and EB3 in fibroblasts, we found no effects on microtubule polymerization when DISC1 was reduced. However, DISC1 affected the acetylation of microtubules in the leading processes of MGE-derived cortical interneurons. Together, our results provide a mechanism how DISC1 might contribute to interneuron migration thereby explaining the reduced number of specific classes of cortical interneurons in some DISC1 mouse models. PMID:25071449

  7. Gendered emotion work around physical health problems in mid- and later-life marriages.

    PubMed

    Thomeer, Mieke Beth; Reczek, Corinne; Umberson, Debra

    2015-01-01

    The provision and receipt of emotion work-defined as intentional activities done to promote another's emotional well-being-are central dimensions of marriage. However, emotion work in response to physical health problems is a largely unexplored, yet likely important, aspect of the marital experience. We analyze dyadic in-depth interviews with husbands and wives in 21 mid- to later-life couples to examine the ways that health-impaired people and their spouses provide, interpret, and explain emotion work. Because physical health problems, emotion work, and marital dynamics are gendered, we consider how these processes differ for women and men. We find that wives provide emotion work regardless of their own health status. Husbands provide emotion work less consistently, typically only when the husbands see themselves as their wife's primary source of stability or when the husbands view their marriage as balanced. Notions of traditional masculinity preclude some husbands from providing emotion work even when their wife is health-impaired. This study articulates emotion work around physical health problems as one factor that sustains and exacerbates gender inequalities in marriage with implications for emotional and physical well-being.

  8. Gendered emotion work around physical health problems in mid- and later-life marriages☆

    PubMed Central

    Thomeer, Mieke Beth; Reczek, Corinne; Umberson, Debra

    2015-01-01

    The provision and receipt of emotion work—defined as intentional activities done to promote another’s emotional well-being—are central dimensions of marriage. However, emotion work in response to physical health problems is a largely unexplored, yet likely important, aspect of the marital experience. We analyze dyadic in-depth interviews with husbands and wives in 21 mid-to later-life couples to examine the ways that health-impaired people and their spouses provide, interpret, and explain emotion work. Because physical health problems, emotion work, and marital dynamics are gendered, we consider how these processes differ for women and men. We find that wives provide emotion work regardless of their own health status. Husbands provide emotion work less consistently, typically only when the husbands see themselves as their wife’s primary source of stability or when the husbands view their marriage as balanced. Notions of traditional masculinity preclude some husbands from providing emotion work even when their wife is health-impaired. This study articulates emotion work around physical health problems as one factor that sustains and exacerbates gender inequalities in marriage with implications for emotional and physical well-being. PMID:25661852

  9. Impaired Cognition in Rats with Cortical Dysplasia: Additional Impact of Early-Life Seizures

    ERIC Educational Resources Information Center

    Lucas, Marcella M.; Lenck-Santini, Pierre-Pascal; Holmes, Gregory L.; Scott, Rod C.

    2011-01-01

    One of the most common and serious co-morbidities in patients with epilepsy is cognitive impairment. While early-life seizures are considered a major cause for cognitive impairment, it is not known whether it is the seizures, the underlying neurological substrate or a combination that has the largest impact on eventual learning and memory. Teasing…

  10. Impaired Cognition in Rats with Cortical Dysplasia: Additional Impact of Early-Life Seizures

    ERIC Educational Resources Information Center

    Lucas, Marcella M.; Lenck-Santini, Pierre-Pascal; Holmes, Gregory L.; Scott, Rod C.

    2011-01-01

    One of the most common and serious co-morbidities in patients with epilepsy is cognitive impairment. While early-life seizures are considered a major cause for cognitive impairment, it is not known whether it is the seizures, the underlying neurological substrate or a combination that has the largest impact on eventual learning and memory. Teasing…

  11. Regional Cortical Thickness and Subcortical Volume Changes Are Associated with Cognitive Impairments in the Drug-Naive Patients with Late-Onset Depression

    PubMed Central

    Lim, Hyun Kook; Jung, Won Sang; Ahn, Kook Jin; Won, Wang Youn; Hahn, Changtae; Lee, Seung Yup; Kim, InSeong; Lee, Chang Uk

    2012-01-01

    Previous studies have shown an association between late-onset depression (LOD) and cognitive impairment in older adults. However, the neural correlates of this relationship are not yet clear. The aim of this study was to investigate the differences in both cortical thickness and subcortical volumes between drug-naive LOD patients and healthy controls and explore the relationship between LOD and cognitive impairments. A total of 48 elderly, drug-naive patients with LOD and 47 group-matched healthy control subjects underwent 3T MRI scanning, and the cortical thickness was compared between the groups in multiple locations, across the continuous cortical surface. The subcortical volumes were also compared on a structure-by-structure basis. Subjects with LOD exhibited significantly decreased cortical thickness in the rostral anterior cingulate cortex, the medial orbitofrontal cortex, dorsolateral prefrontal cortex, the superior and middle temporal cortex, and the posterior cingulate cortex when compared with healthy subjects (all p<0.05, false discovery rate corrected). Reduced volumes of the right hippocampus was also observed in LOD patients when compared with healthy controls (p<0.001). There were significant correlations between memory functions and cortical thickness of medial temporal, isthmus cingulate, and precuneus (p<0.001). This study was the first study to explore the relationships between the cortical thickness/subcortical volumes and cognitive impairments of drug-naive patients with LOD. These structural changes might explain the neurobiological mechanism of LOD as a risk factor of dementia. PMID:22048467

  12. Later Life Parental Divorce and Widowhood: Impact on Young Adults' Assessment of Parent-Child Relations.

    ERIC Educational Resources Information Center

    Aquilino, William S.

    1994-01-01

    Explored implications of later life parental divorce and widowhood for relationship between parents and young adult children among 3,281 young adults who grew up in intact families. Family disruption that occurred after children were grown had sizable effects on parent-adult child relations, with later life divorce lowering relationship quality…

  13. The association between intra- and juxta-cortical pathology and cognitive impairment in multiple sclerosis by quantitative T2* mapping at 7 T MRI.

    PubMed

    Louapre, Céline; Govindarajan, Sindhuja T; Giannì, Costanza; Madigan, Nancy; Nielsen, A Scott; Sloane, Jacob A; Kinkel, Revere P; Mainero, Caterina

    2016-01-01

    Using quantitative T2* at 7 Tesla (T) magnetic resonance imaging, we investigated whether impairment in selective cognitive functions in multiple sclerosis (MS) can be explained by pathology in specific areas and/or layers of the cortex. Thirty-one MS patients underwent neuropsychological evaluation, acquisition of 7 T multi-echo T2* gradient-echo sequences, and 3 T anatomical images for cortical surfaces reconstruction. Seventeen age-matched healthy subjects served as controls. Cortical T2* maps were sampled at various depths throughout the cortex and juxtacortex. Relation between T2*, neuropsychological scores and a cognitive index (CI), calculated from a principal component analysis on the whole battery, was tested by a general linear model. Cognitive impairment correlated with T2* increase, independently from white matter lesions and cortical thickness, in cortical areas highly relevant for cognition belonging to the default-mode network (p < 0.05 corrected). Dysfunction in different cognitive functions correlated with longer T2* in selective cortical regions, most of which showed longer T2* relative to controls. For most tests, this association was strongest in deeper cortical layers. Executive dysfunction, however, was mainly related with pathology in juxtameningeal cortex. T2* explained up to 20% of the variance of the CI, independently of conventional imaging metrics (adjusted-R(2): 52-67%, p < 5.10(- 4)). Location of pathology across the cortical width and mantle showed selective correlation with impairment in differing cognitive domains. These findings may guide studies at lower field strength designed to develop surrogate markers of cognitive impairment in MS.

  14. Resting state cortical rhythms in mild cognitive impairment and Alzheimer's disease: electroencephalographic evidence.

    PubMed

    Babiloni, Claudio; Vecchio, Fabrizio; Lizio, Roberta; Ferri, Raffaele; Rodriguez, Guido; Marzano, Nicola; Frisoni, Giovanni B; Rossini, Paolo M

    2011-01-01

    Physiological brain aging is characterized by a combination of synaptic pruning, loss of cortico-cortical connections and neuronal apoptosis that provoke age-dependent decline of cognitive functions. Neural/synaptic redundancy and plastic remodeling of brain networking, also secondary to mental and physical training, promotes maintenance of brain activity in healthy elderly for everyday life and fully productive affective and intellectual capabilities. Unfortunately, in pathological situations, aging triggers neurodegenerative processes that impact on cognition, like Alzheimer's disease (AD). Oscillatory electromagnetic brain activity is a hallmark of neuronal network function in various brain regions. Modern neurophysiological techniques including digital electroencephalography (EEG) allow non-invasive analysis of cortico-cortical connectivity and neuronal synchronization of firing, and coherence of brain rhythmic oscillations at various frequencies. The present review of field EEG literature suggests that discrimination between physiological and pathological brain aging clearly emerges at the group level, with some promising result on the informative value of EEG markers at the individual level. Integrated approaches utilizing neurophysiological techniques together with biological markers and structural and functional imaging are promising for large-scale, low-cost, widely available on the territory and non-invasive screening of at-risk populations.

  15. Impaired ideomotor limb apraxia in cortical and subcortical dementia: a comparison of Alzheimer's and Huntington's disease.

    PubMed

    Holl, Anna K; Ille, Rottraut; Wilkinson, Leonora; Otti, Daniela V; Hödl, Elfriede; Herranhof, Brigitte; Reisinger, Karin M; Müller, Nicole; Painold, Annamaria; Holl, Etienne M; Letmaier, Martin; Bonelli, Raphael M

    2011-01-01

    Although ideomotor limb apraxia is often considered to occur only in dementia with cortical involvement like Alzheimer's disease (AD), it is also frequently seen in dementia with subcortical degeneration like Huntington's disease (HD). To assess the occurrence of ideomotor limb apraxia, 46 patients with HD (27 men) and 37 patients with AD (16 men), matched for cognitive performance, were assessed with an apraxia test battery containing tests of the imitation of meaningless hand and finger gestures, the performance of meaningful gestures and of pantomimic movements. There was a high frequency of ideomotor limb apraxia in both AD and HD patients. For the assessment of hands' imitation 13.5% of the AD patients and 41.3% of the HD patients were apraxic, for fingers' imitation 21.6% (AD) and 41.3% (HD) were apraxic, for gestures 27.0% (AD) and 32.6% (HD), and for the assessment of pantomimic movements 24.3% (AD) and 52.2% (HD) showed apraxia. In the AD patients, disease severity was related to the occurrence of apraxia. Ideomotor limb apraxia is a common sign in both groups of patients, occurring in a high percentage. For particular neuropsychological deficits, including ideomotor limb apraxia, a division of dementia in a subcortical and cortical subtype seems to be clinically not meaningful. Copyright © 2011 S. Karger AG, Basel.

  16. AMPA Receptor antagonist NBQX attenuates later-life epileptic seizures and autistic-like social deficits following neonatal seizures

    PubMed Central

    Lippman-Bell, Jocelyn J.; Rakhade, Sanjay N.; Klein, Peter M.; Obeid, Makram; Jackson, Michele C.; Joseph, Annelise; Jensen, Frances E.

    2013-01-01

    Summary Purpose To determine whether AMPA receptor (AMPAR) antagonist NBQX can prevent early mTOR pathway activation and long-term sequelae following neonatal seizures in rats, including later-life spontaneous recurrent seizures, CA3 mossy fiber sprouting, and autistic-like social deficits. Methods Long-Evans rats experienced hypoxia-induced neonatal seizures (HS) at postnatal day (P)10. NBQX (20 mg/kg) was administered immediately following HS (every 12h x 4 doses). 12h post-HS, we assessed mTOR activation marker phosphorylated p70-S6 kinase (p-p70S6K) in hippocampus and cortex of vehicle (HS+V) or NBQX-treated post-HS rats (HS+N) versus littermate controls (C+V). Spontaneous seizure activity was compared between groups by epidural cortical electroencephalography (EEG) at P70-100. Aberrant mossy fiber sprouting was measured using Timm staining. Finally, we assessed behavior between P30-38. Key findings Post-seizure NBQX treatment significantly attenuated seizure-induced increases in p-P70S6K in the hippocampus (p<0.01) and cortex (p<0.001). While spontaneous recurrent seizures increased in adulthood in HS+V rats compared to controls (3.22±1seizures/hour; p=0.03), NBQX significantly attenuated later-life seizures (0.14±0.1 seizures/hour; p=0.046). HS+N rats showed less aberrant mossy fiber sprouting (115±8.0%) than vehicle-treated post-HS rats (174±10%, p=0.004), compared to controls (normalized to 100%). Finally, NBQX treatment prevented alterations in later-life social behavior; post-HS rats showed significantly decreased preference for a novel over a familiar rat (71.0±12 sec) compared to controls (99.0±15.6 sec; p<0.01), while HS+N rats showed social novelty preference similar to controls (114.3±14.1 sec). Significance Brief NBQX administration during the 48 hours post-seizure in P10 Long-Evans rats suppresses transient mTOR pathway activation and attenuates spontaneous recurrent seizures, social preference deficits and mossy fiber sprouting observed in

  17. Subcortical atrophy is associated with cognitive impairment in mild Parkinson disease: a combined investigation of volumetric changes, cortical thickness, and vertex-based shape analysis.

    PubMed

    Mak, E; Bergsland, N; Dwyer, M G; Zivadinov, R; Kandiah, N

    2014-12-01

    The involvement of subcortical deep gray matter and cortical thinning associated with mild Parkinson disease remains poorly understood. We assessed cortical thickness and subcortical volumes in patients with Parkinson disease without dementia and evaluated their associations with cognitive dysfunction. The study included 90 patients with mild Parkinson disease without dementia. Neuropsychological assessments classified the sample into patients with mild cognitive impairment (n = 25) and patients without cognitive impairment (n = 65). Volumetric data for subcortical structures were obtained by using the FMRIB Integrated Registration and Segmentation Tool while whole-brain, gray and white matter volumes were estimated by using Structural Image Evaluation, with Normalization of Atrophy. Vertex-based shape analyses were performed to investigate shape differences in subcortical structures. Vertex-wise group differences in cortical thickness were also assessed. Volumetric comparisons between Parkinson disease with mild cognitive impairment and Parkinson disease with no cognitive impairment were performed by using ANCOVA. Associations of subcortical structures with both cognitive function and disease severity were assessed by using linear regression models. Compared with Parkinson disease with no cognitive impairment, Parkinson disease with mild cognitive impairment demonstrated reduced volumes of the thalamus (P = .03) and the nucleus accumbens (P = .04). Significant associations were found for the nucleus accumbens and putamen with performances on the attention/working memory domains (P < .05) and nucleus accumbens and language domains (P = .04). The 2 groups did not differ in measures of subcortical shape or in cortical thickness. Patients with Parkinson disease with mild cognitive impairment demonstrated reduced subcortical volumes, which were associated with cognitive deficits. The thalamus, nucleus accumbens, and putamen may serve as potential biomarkers for

  18. Colour identification and colour constancy are impaired in a patient with incomplete achromatopsia associated with prestriate cortical lesions.

    PubMed

    Kennard, C; Lawden, M; Morland, A B; Ruddock, K H

    1995-05-22

    We have examined visual functions, including colour vision, in a patient with bilateral cortical lesions involving mainly the fusiform and lingual gyri, areas known to be involved in the central processing of chromatic stimuli. The patient has near normal (6/9) acuity, and his responses to tests of binocular function and spatial vision are normal, as are his discrimination of changes in target speed and surface lightness. He does, however, exhibit minor losses in the upper visual field, mild prosopagnosia and topographical agnosia, all conditions commonly associated with cerebral achromatopsia. Colour matches and spectral response data establish that his cone photoreceptors have normal spectral characteristics and his spectral sensitivity measured against a white background reveals normal postreceptoral chromatic function. The patient's colour discrimination for differences in wavelength, hue or saturation is, however, impaired and his colour naming is significantly disturbed, particularly for blues and greens. We have determined the areas of the chromaticity chart that correspond to his naming categories for surface colours, and show that changes in illuminant cause him to alter the names of surface colours in a manner consistent with the changes in their chromaticities. Other subjects with normal or congenital red-green deficient colour vision make many fewer name changes under changes in illuminant. We conclude that the patient's colour constancy is impaired as a consequence of abnormal central processing of colour vision.

  19. Persistent impairments in hippocampal, dorsal striatal, and prefrontal cortical function following repeated photoperiod shifts in rats.

    PubMed

    Zelinski, Erin L; Tyndall, Amanda V; Hong, Nancy S; McDonald, Robert J

    2013-01-01

    Cognitive impairments are observed when learned associations are being acquired or retrieved during a period of circadian disruption. However, the extent of the functional impacts on previously acquired associations following circadian rhythm re-entrainment is unknown. The impacts of repeated photoperiod shifts on learning and memory in male and female rats were examined. For these experiments, rats were trained on a spatial version of the Morris water task (MWT) and a visual discrimination task designed for the 8-arm radial maze. Following asymptotic performance on these tasks, rats experienced a repeating photoperiod shift procedure and were then re-entrained. Following circadian re-entrainment, retention of pre-photoperiod-shift-acquired associations was tested. In addition, an extra-dimensional set shift was performed using the 8-arm radial maze. Impaired retention of the MWT platform location was observed in photoperiod-shifted subjects relative to subjects with stable, unmanipulated photoperiods. Repeated photoperiod shifts negatively impacted retention in males and females compared with subjects with stable photoperiods. Retention and the ability to detect extra-dimensional shifts on the visual discrimination task were also impaired, though not consistently by sex or photoperiod condition. Running wheel availability was also included in the analyses to determine whether exercise influenced the effects of photoperiod shifting. The absence of a running wheel produced significant declines in memory retention on both MWT and the visual discrimination task, but only for male rats. The observed impairments indicate that multiple neural systems supporting different learning and memory functions are susceptible to circadian disruption, even if the association is acquired prior to rhythm fragmentation and tested following rhythm re-entrainment.

  20. Cortical afferent inhibition reflects cognitive impairment in obstructive sleep apnea syndrome: a TMS study.

    PubMed

    Nardone, Raffaele; Bergmann, Jürgen; Brigo, Francesco; Höller, Yvonne; Schwenker, Kerstin; Florea, Cristina; Kunz, Alexander B; Golaszewski, Stefan; Trinka, Eugen

    2016-08-01

    Patients with obstructive sleep apnea syndrome (OSAS) show neurocognitive impairment, but the exact mechanisms that cause cognitive dysfunctions remain unknown. The cholinergic system is known to play a key role in all attentional processes and cognitive functions. A transcranial magnetic stimulation (TMS) protocol may give direct information about the function of some cholinergic circuits in the human brain; this technique relies on short latency afferent inhibition (SAI) of the motor cortex. The objective of this exploratory study was to test the hypothesis that impaired cognitive performances in OSAS patients are associated with a dysfunction of the cholinergic system, as assessed by SAI. We applied SAI technique in a group of 13 patients with OSAS and compared the data with those from a group of 13 age-matched healthy subjects. All the patients underwent a sleep study, an extensive neuropsychological evaluation, and TMS examination. Mean SAI was significantly reduced in our OSAS patients when compared with controls. The neuropsychological evaluation showed impairments in most cognitive areas in the OSAS patients. SAI values were strongly correlated with the neuropsychological test scores. These findings suggest that the cognitive deficits in OSAS may be, at least in part, secondary to alterations in cholinergic neurotransmission, presumably caused by nocturnal hypoxemia. TMS studies may shed light on the pathophysiological mechanisms of the cognitive disturbances in OSAS patients. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. A Course on Humanistic Creativity in Later Life: Literature Review, Case Histories, and Recommendations.

    ERIC Educational Resources Information Center

    Nuessel, Frank; Van Stewart, Arthur; Cedeno, Aristofanes

    2001-01-01

    Presents case histories of late-life creativity in literature (May Sarton), painting (Marcel Duchamp), music (Leos Janacek), dance (Martha Graham), and theatre (Jessica Tandy). Offers suggestions for a course on humanistic creativity in later life. (Contains 74 references.) (SK)

  2. A Course on Humanistic Creativity in Later Life: Literature Review, Case Histories, and Recommendations.

    ERIC Educational Resources Information Center

    Nuessel, Frank; Van Stewart, Arthur; Cedeno, Aristofanes

    2001-01-01

    Presents case histories of late-life creativity in literature (May Sarton), painting (Marcel Duchamp), music (Leos Janacek), dance (Martha Graham), and theatre (Jessica Tandy). Offers suggestions for a course on humanistic creativity in later life. (Contains 74 references.) (SK)

  3. Role of hippocampal and prefrontal cortical signaling pathways in dextromethorphan effect on morphine-induced memory impairment in rats.

    PubMed

    Ghasemzadeh, Zahra; Rezayof, Ameneh

    2016-02-01

    Evidence suggests that dextromethorphan (DM), an NMDA receptor antagonist, induces memory impairment. Considering that DM is widely used in cough-treating medications, and the co-abuse of DM with morphine has recently been reported, the aims of the present study was (1) to investigate whether there is a functional interaction between morphine and DM in passive avoidance learning and (2) to assess the possible role of the hippocampal and prefrontal cortical (PFC) signaling pathways in the effects of the drugs on memory formation. Our findings indicated that post-training or pre-test administration of morphine (2 and 6 mg/kg) or DM (10-30 mg/kg) impaired memory consolidation and retrieval which was associated with the attenuation of the levels of phosphorylated Ca(2+)/calmodulin-dependent protein kinase II (p-CAMKII) and cAMP responsive element-binding protein (p-CREB) in the targeted sites. Moreover, the memory impairment induced by post-training administration of morphine was reversed by pre-test administration of the same dose of morphine or DM (30 mg/kg), indicating state-dependent learning (SDL) and a cross-SDL between the drugs. It is important to note that the levels of p-CAMKII/CAMKII and p-CREB/CREB in the hippocampus and the PFC increased in drugs-induced SDL. In addition, DM administration potentiated morphine-induced SDL which was related to the enhanced levels of hippocampal and PFC CAMKII-CREB signaling pathways. It can be concluded that there is a relationship between the hippocampus and the PFC in the effect of DM and/or morphine on memory retrieval. Moreover, a cross SDL can be induced between the co-administration of DM and morphine. Interestingly, CAMKII-CREB signaling pathways also mediate the drugs-induced SDL.

  4. Minocycline mitigates motor impairments and cortical neuronal loss induced by focal ischemia in rats chronically exposed to ethanol during adolescence.

    PubMed

    Oliveira, Gedeão Batista; Fontes, Enéas de Andrade; de Carvalho, Sabrina; da Silva, Josiane Batista; Fernandes, Luanna Melo Pereira; Oliveira, Maria Cristina Souza Pereira; Prediger, Rui Daniel; Gomes-Leal, Walace; Lima, Rafael Rodrigues; Maia, Cristiane Socorro Ferraz

    2014-05-02

    Ethanol is an important risk factor for the occurrence of cerebral ischemia contributing to poor prognosis and inefficacy of drug treatments for stroke-related symptoms. Females have a higher lifetime risk for stroke than males. Moreover, female gender has been associated with increased ethanol consumption during adolescence. In the present study, we investigated whether chronic ethanol exposure during adolescence may potentiate the motor impairments and cortical damage induced by focal ischemia in female rats. We also addressed whether these effects can be mitigated by minocycline, which has been shown to be neuroprotective against different insults in the CNS. Female rats were treated with distilled water or ethanol (6.5 g/kg/day, 22.5% w/v) for 55 days by gavage. Focal ischemia was induced by microinjections of endothelin-1 (ET-1) into the motor cortex. Animals of both groups were treated daily with minocycline (25-50 mg/kg, i.p.) or sterile saline (i.p.) for 5 days, and motor function was assessed using open field, inclined plane and rotarod tests. Chronic ethanol exposure exacerbated locomotor activity and motor coordination impairments induced by focal ischemia in rats. Moreover, histological analysis revealed that microinjections of ET-1 induced pyramidal neuron loss and microglial activation in the motor cortex. Minocycline reversed the observed motor impairments, microglial activation and pyramidal neuron loss in the motor cortex of ischemic rats even in those exposed to ethanol. These results suggest that minocycline induces neuroprotection and functional recovery in ischemic female rats intoxicated with ethanol during adolescence. Furthermore, the mechanism underlying this protective effect may be related to the modulation of neuroinflammation.

  5. Depression and communication processes in later life marriages.

    PubMed

    Harper, James M; Sandberg, Jonathan G

    2009-07-01

    About six hundred and fourteen elderly people married to each other, average ages 66 and 63 respectively, in long term, mature marriages, lasting on the average 36 years, completed the Marital Satisfaction Inventory, Revised-MSIr (Snyder, D.K. 1999) and the short version of the Center for Epidemiological Studies Depression Scale (Kohout, F.J., Berkman, L.F., Evans, D.A., & Cornoni-Huntley, J. (1993). The purpose of this study was to determine whether depression in one or both spouses and poor affective and problem solving communication occur together. Husbands and wives were divided into nine groups based on their levels of depression (hlow/wlow, hmed/wmed, hhigh/whigh, hhigh/wlow, hhigh/wmed, wlow/hhigh, and wlow/hmed, hmed/wlow, and hmed/whigh). Analysis of Variance was used to examine the difference in couple affective communication and problem solving scores from the MSIr (1999). The findings indicated that when husbands or wives are more depressed, both affective communication and problem solving processes are impaired for the couple. When both are depressed, affective communication and problem solving are worse than when only one is depressed, and both husband and wife communication scores are worse when one or both partners is depressed than when neither husband nor wife is depressed. While these findings do not point to cause, implications for providing mental health services (including marital therapy) or couple based education groups as supports to the depressed elderly and their spouses are recommended.

  6. Motor and premotor cortices in subcortical stroke: proton magnetic resonance spectroscopy measures and arm motor impairment.

    PubMed

    Craciunas, Sorin C; Brooks, William M; Nudo, Randolph J; Popescu, Elena A; Choi, In-Young; Lee, Phil; Yeh, Hung-Wen; Savage, Cary R; Cirstea, Carmen M

    2013-06-01

    Although functional imaging and neurophysiological approaches reveal alterations in motor and premotor areas after stroke, insights into neurobiological events underlying these alterations are limited in human studies. We tested whether cerebral metabolites related to neuronal and glial compartments are altered in the hand representation in bilateral motor and premotor areas and correlated with distal and proximal arm motor impairment in hemiparetic persons. In 20 participants at >6 months postonset of a subcortical ischemic stroke and 16 age- and sex-matched healthy controls, the concentrations of N-acetylaspartate and myo-inositol were quantified by proton magnetic resonance spectroscopy. Regions of interest identified by functional magnetic resonance imaging included primary (M1), dorsal premotor (PMd), and supplementary (SMA) motor areas. Relationships between metabolite concentrations and distal (hand) and proximal (shoulder/elbow) motor impairment using Fugl-Meyer Upper Extremity (FMUE) subscores were explored. N-Acetylaspartate was lower in M1 (P = .04) and SMA (P = .004) and myo-inositol was higher in M1 (P = .003) and PMd (P = .03) in the injured (ipsilesional) hemisphere after stroke compared with the left hemisphere in controls. N-Acetylaspartate in ipsilesional M1 was positively correlated with hand FMUE subscores (P = .04). Significant positive correlations were also found between N-acetylaspartate in ipsilesional M1, PMd, and SMA and in contralesional M1 and shoulder/elbow FMUE subscores (P = .02, .01, .02, and .02, respectively). Our preliminary results demonstrated that proton magnetic resonance spectroscopy is a sensitive method to quantify relevant neuronal changes in spared motor cortex after stroke and consequently increase our knowledge of the factors leading from these changes to arm motor impairment.

  7. Depression and frailty in later life: a systematic review

    PubMed Central

    Vaughan, Leslie; Corbin, Akeesha L; Goveas, Joseph S

    2015-01-01

    Frailty and depression are important issues affecting older adults. Depressive syndrome may be difficult to clinically disambiguate from frailty in advanced old age. Current reviews on the topic include studies with wide methodological variation. This review examined the published literature on cross-sectional and longitudinal associations between frailty and depressive symptomatology with either syndrome as the outcome, moderators of this relationship, construct overlap, and related medical and behavioral interventions. Prevalence of both was reported. A systematic review of studies published from 2000 to 2015 was conducted in PubMed, the Cochrane Database of Systematic Reviews, and PsychInfo. Key search terms were “frailty”, “frail”, “frail elderly”, “depressive”, “depressive disorder”, and “depression”. Participants of included studies were ≥55 years old and community dwelling. Included studies used an explicit biological definition of frailty based on Fried et al’s criteria and a screening measure to identify depressive symptomatology. Fourteen studies met the inclusion/exclusion criteria. The prevalence of depressive symptomatology, frailty, or their co-occurrence was greater than 10% in older adults ≥55 years old, and these rates varied widely, but less in large epidemiological studies of incident frailty. The prospective relationship between depressive symptomatology and increased risk of incident frailty was robust, while the opposite relationship was less conclusive. The presence of comorbidities that interact with depressive symptomatology increased incident frailty risk. Measurement variability of depressive symptomatology and inclusion of older adults who are severely depressed, have cognitive impairment or dementia, or stroke may confound the frailty syndrome with single disease outcomes, accounting for a substantial proportion of shared variance in the syndromes. Further study is needed to identify medical and behavioral

  8. Rewriting age to overcome misaligned age and gender norms in later life.

    PubMed

    Morelock, Jeremiah C; Stokes, Jeffrey E; Moorman, Sara M

    2017-01-01

    In this paper we suggest that older adults undergo a misalignment between societal age norms and personal lived experience, and attempt reconciliation through discursive strategies: They rewrite how they frame chronological age as well as their subjective relations to it. Using a sample of 4041 midlife and older adults from the 2004-2006 wave of the National Survey of Midlife Development in the United States (MIDUS II), we explore associations of age and gender with subjective age and at what age respondents felt people enter later life. Our results confirm that as men and women age, they push up the age at which they think people enter later life, and slow down subjective aging (there is a growing gap between subjective and chronological age). Relations between a person's age and at what age they think people enter later life were stronger for men than for women. For every year they get older get older, men push up when they think people enter later life by 0.24years, women by 0.16years. Age norms surrounding the transition to later life may be more prominent for men than for women, and the difference in their tendencies to push up when they mark entry into later life may be a reflection of this greater prominence.

  9. Later life disability status following incarceration as a prisoner of war.

    PubMed

    Hunt, Stephen C; Orsborn, Mack; Checkoway, Harvey; Biggs, Mary L; McFall, Miles; Takaro, Tim K

    2008-07-01

    Incarceration-related predictors of later life disability in former prisoners of war (POWs) have not been previously described. The objective of this project was to identify aspects of POW incarceration which are associated with later life disability status. Cross-sectional retrospective study of 328 former U.S. military personnel held as POWs (World War II and Korean and Vietnam Wars) who presented for evaluations at a Veterans Affairs medical center between January 1, 1997 and December 31, 2004 outcome measures were: (1) total number of later life disability conditions attributable to incarceration and (2) cumulative percentage later life disability attributable to these conditions. We found significant associations between later life disability and POW experiences, including experiencing or witnessing torture, solitary confinement, forced marches, dysentry, pellagra, vitamin deficiencies, scabies, depression, and suicidal thoughts. Conditions of captivity and health concerns or emotional distress during captivity may contribute to long-term adverse health outcomes as measured by later life disabilities in individuals incarcerated as POWs.

  10. Impaired excitability of somatostatin- and parvalbumin-expressing cortical interneurons in a mouse model of Dravet syndrome.

    PubMed

    Tai, Chao; Abe, Yasuyuki; Westenbroek, Ruth E; Scheuer, Todd; Catterall, William A

    2014-07-29

    Haploinsufficiency of the voltage-gated sodium channel NaV1.1 causes Dravet syndrome, an intractable developmental epilepsy syndrome with seizure onset in the first year of life. Specific heterozygous deletion of NaV1.1 in forebrain GABAergic-inhibitory neurons is sufficient to cause all the manifestations of Dravet syndrome in mice, but the physiological roles of specific subtypes of GABAergic interneurons in the cerebral cortex in this disease are unknown. Voltage-clamp studies of dissociated interneurons from cerebral cortex did not detect a significant effect of the Dravet syndrome mutation on sodium currents in cell bodies. However, current-clamp recordings of intact interneurons in layer V of neocortical slices from mice with haploinsufficiency in the gene encoding the NaV1.1 sodium channel, Scn1a, revealed substantial reduction of excitability in fast-spiking, parvalbumin-expressing interneurons and somatostatin-expressing interneurons. The threshold and rheobase for action potential generation were increased, the frequency of action potentials within trains was decreased, and action-potential firing within trains failed more frequently. Furthermore, the deficit in excitability of somatostatin-expressing interneurons caused significant reduction in frequency-dependent disynaptic inhibition between neighboring layer V pyramidal neurons mediated by somatostatin-expressing Martinotti cells, which would lead to substantial disinhibition of the output of cortical circuits. In contrast to these deficits in interneurons, pyramidal cells showed no differences in excitability. These results reveal that the two major subtypes of interneurons in layer V of the neocortex, parvalbumin-expressing and somatostatin-expressing, both have impaired excitability, resulting in disinhibition of the cortical network. These major functional deficits are likely to contribute synergistically to the pathophysiology of Dravet syndrome.

  11. Automated volumetry and regional thickness analysis of hippocampal subfields and medial temporal cortical structures in mild cognitive impairment.

    PubMed

    Yushkevich, Paul A; Pluta, John B; Wang, Hongzhi; Xie, Long; Ding, Song-Lin; Gertje, Eske C; Mancuso, Lauren; Kliot, Daria; Das, Sandhitsu R; Wolk, David A

    2015-01-01

    We evaluate a fully automatic technique for labeling hippocampal subfields and cortical subregions in the medial temporal lobe in in vivo 3 Tesla MRI. The method performs segmentation on a T2-weighted MRI scan with 0.4 × 0.4 × 2.0 mm(3) resolution, partial brain coverage, and oblique orientation. Hippocampal subfields, entorhinal cortex, and perirhinal cortex are labeled using a pipeline that combines multi-atlas label fusion and learning-based error correction. In contrast to earlier work on automatic subfield segmentation in T2-weighted MRI [Yushkevich et al., 2010], our approach requires no manual initialization, labels hippocampal subfields over a greater anterior-posterior extent, and labels the perirhinal cortex, which is further subdivided into Brodmann areas 35 and 36. The accuracy of the automatic segmentation relative to manual segmentation is measured using cross-validation in 29 subjects from a study of amnestic mild cognitive impairment (aMCI) and is highest for the dentate gyrus (Dice coefficient is 0.823), CA1 (0.803), perirhinal cortex (0.797), and entorhinal cortex (0.786) labels. A larger cohort of 83 subjects is used to examine the effects of aMCI in the hippocampal region using both subfield volume and regional subfield thickness maps. Most significant differences between aMCI and healthy aging are observed bilaterally in the CA1 subfield and in the left Brodmann area 35. Thickness analysis results are consistent with volumetry, but provide additional regional specificity and suggest nonuniformity in the effects of aMCI on hippocampal subfields and MTL cortical subregions. © 2014 Wiley Periodicals, Inc.

  12. Automated Volumetry and Regional Thickness Analysis of Hippocampal Subfields and Medial Temporal Cortical Structures in Mild Cognitive Impairment

    PubMed Central

    Yushkevich, Paul A.; Pluta, John B.; Wang, Hongzhi; Xie, Long; Ding, Song-Lin; Gertje, E. C.; Mancuso, Lauren; Kliot, Daria; Das, Sandhitsu R.; Wolk, David A.

    2014-01-01

    We evaluate a fully automatic technique for labeling hippocampal subfields and cortical subregions in the medial temporal lobe (MTL) in in vivo 3 Tesla MRI. The method performs segmentation on a T2-weighted MRI scan with 0.4 × 0.4 × 2.0 mm3 resolution, partial brain coverage, and oblique orientation. Hippocampal subfields, entorhinal cortex, and perirhinal cortex are labeled using a pipeline that combines multi-atlas label fusion and learning-based error correction. In contrast to earlier work on automatic subfield segmentation in T2-weighted MRI (Yushkevich et al., 2010), our approach requires no manual initialization, labels hippocampal subfields over a greater anterior-posterior extent, and labels the perirhinal cortex, which is further subdivided into Brodmann areas 35 and 36. The accuracy of the automatic segmentation relative to manual segmentation is measured using cross-validation in 29 subjects from a study of amnestic Mild Cognitive Impairment (aMCI), and is highest for the dentate gyrus (Dice coefficient is 0.823), CA1 (0.803), perirhinal cortex (0.797) and entorhinal cortex (0.786) labels. A larger cohort of 83 subjects is used to examine the effects of aMCI in the hippocampal region using both subfield volume and regional subfield thickness maps. Most significant differences between aMCI and healthy aging are observed bilaterally in the CA1 subfield and in the left Brodmann area 35. Thickness analysis results are consistent with volumetry, but provide additional regional specificity and suggest non-uniformity in the effects of aMCI on hippocampal subfields and MTL cortical subregions. PMID:25181316

  13. Increased Water Diffusion in the Parcellated Cortical Regions from the Patients with Amnestic Mild Cognitive Impairment and Alzheimer's Disease.

    PubMed

    Lin, Sung-Han; Hsu, Wen-Chuin; Ng, Shu-Hang; Cheng, Jur-Shan; Khegai, Oleksandr; Huang, Chin-Chang; Chen, Yao-Liang; Chen, Yi-Chun; Wang, Jiun-Jie

    2016-01-01

    Background: The loss of cortical neuron environment integrity is the hallmark of neurodegeneration diseases such as Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI). To reveal the microenvironment changes in cerebral cortex, the current study aimed to examine the changes of mean diffusivity (MD) in parcellated brain among AD, aMCI patients and normal controls (NC). Methods: Diffusion tensor imaging data with the whole brain coverage were acquired from 28 AD (aged 69.4 ± 8.2 year old), 41 aMCI patients (aged 68.2 ± 6.4 year old) and 40 NC subjects (aged 65.7 ± 6.4 year old). Subsequently, the MD values were parcellated according to the standard automatic anatomic labeling (AAL) template. Only the 90 regions located in the cerebral cortex were used in the final analysis. The mean values of MD from each brain region were extracted and compared among the participant groups. The integrity of the white matter tracts and gray matter atrophy was analyzed using the track-based spatial statistics and voxel-based morphometry approaches, respectively. Results: Significant differences of MD were noticed both in aMCI and AD patients, in terms of the affected regions and the amount of increase. The hippocampus, parahippocampal gyrus and cingulum were the most significantly affected regions in AD patients. From all the 90 cerebral cortex regions, significant increase of MD in the AD patients was found in 40 regions, compared to only one (fusiform gyrus on the right) in aMCI patients. In the disease affected regions, the MD from aMCI patients is in state between NC and AD patients. Conclusions: Increased MD in the specific regions of the brain shows the feasibility of MD as an indicator of the early stage cortical degeneration in aMCI and AD patients.

  14. Increased Water Diffusion in the Parcellated Cortical Regions from the Patients with Amnestic Mild Cognitive Impairment and Alzheimer's Disease

    PubMed Central

    Lin, Sung-Han; Hsu, Wen-Chuin; Ng, Shu-Hang; Cheng, Jur-Shan; Khegai, Oleksandr; Huang, Chin-Chang; Chen, Yao-Liang; Chen, Yi-Chun; Wang, Jiun-Jie

    2017-01-01

    Background: The loss of cortical neuron environment integrity is the hallmark of neurodegeneration diseases such as Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI). To reveal the microenvironment changes in cerebral cortex, the current study aimed to examine the changes of mean diffusivity (MD) in parcellated brain among AD, aMCI patients and normal controls (NC). Methods: Diffusion tensor imaging data with the whole brain coverage were acquired from 28 AD (aged 69.4 ± 8.2 year old), 41 aMCI patients (aged 68.2 ± 6.4 year old) and 40 NC subjects (aged 65.7 ± 6.4 year old). Subsequently, the MD values were parcellated according to the standard automatic anatomic labeling (AAL) template. Only the 90 regions located in the cerebral cortex were used in the final analysis. The mean values of MD from each brain region were extracted and compared among the participant groups. The integrity of the white matter tracts and gray matter atrophy was analyzed using the track-based spatial statistics and voxel-based morphometry approaches, respectively. Results: Significant differences of MD were noticed both in aMCI and AD patients, in terms of the affected regions and the amount of increase. The hippocampus, parahippocampal gyrus and cingulum were the most significantly affected regions in AD patients. From all the 90 cerebral cortex regions, significant increase of MD in the AD patients was found in 40 regions, compared to only one (fusiform gyrus on the right) in aMCI patients. In the disease affected regions, the MD from aMCI patients is in state between NC and AD patients. Conclusions: Increased MD in the specific regions of the brain shows the feasibility of MD as an indicator of the early stage cortical degeneration in aMCI and AD patients. PMID:28123367

  15. Plasticity of cortical inhibition in dystonia is impaired after motor learning and Paired-Associative Stimulation

    PubMed Central

    Meunier, Sabine; Russmann, Heike; Shamim, Ejaz; Lamy, Jean-Charles; Hallett, Mark

    2012-01-01

    Summary Artificial induction of plasticity by paired associative stimulation (PAS) in healthy subjects (HV) demonstrates Hebbian-like plasticity in selected inhibitory networks as well as excitatory ones. In a group of 17 patients with focal hand dystonia and a group of 19 HV, we evaluated how PAS and the learning of a simple motor task influence the circuits supporting long interval intracortical inhibition (LICI, reflecting activity of GABAB interneurons) and long latency afferent inhibition (LAI, reflecting activity of somatosensory inputs to the motor cortex). In HV, PAS and motor learning induced LTP-like plasticity of excitatory networks and a lasting decrease of LAI and LICI in the motor representation of the targeted or trained muscle. The better the motor performance, the larger was the decrease of LAI. Although motor performance in the patient group was similar to that of the control group, LAI did not decrease during the motor learning as it did in the control group. In contrast, LICI was normally modulated. In patients the results after PAS did not match those obtained after motor learning: LAI was paradoxically increased and LICI did not exhibit any change. In the normal situation, decreased excitability in inhibitory circuits after induction of LTP-like plasticity may help to shape the cortical maps according to the new sensorimotor task. In patients, the abnormal or absent modulation of afferent and intracortical long-interval inhibition might indicate maladaptive plasticity that possibly contributes to the difficulty that they have to learn a new sensorimotor task.“ PMID:22429246

  16. Neonatal exposure to lipopolysaccharide enhances vulnerability of nigrostriatal dopaminergic neurons to rotenone neurotoxicity in later life

    PubMed Central

    Fan, Lir-Wan; Tien, Lu-Tai; Lin, Rick C. S.; Simpson, Kimberly L.; Rhodes, Philip G.; Cai, Zhengwei

    2011-01-01

    Brain inflammation in early life has been proposed to play important roles in the development of neurodegenerative disorders in adult life. To test this hypothesis, we used a neonatal rat model of lipopolysaccharide (LPS) exposure (1,000 EU/g body weight, intracerebral injection on P5) to produce brain inflammation. By P70, when LPS-induced behavioral deficits were spontaneously recovered, animals were challenged with rotenone, a commonly used pesticide, through subcutaneous mini-pump infusion at a dose of 1.25 mg/kg per day for 14 days. This rotenone treatment regimen ordinarily does not produce toxic effects on behaviors in normal adult rats. Our results show that neonatal LPS exposure enhanced vulnerability of nigrostriatal dopaminergic neurons to rotenone neurotoxicity in later life. Rotenone treatment resulted in motor neurobehavioral impairments in rats with the neonatal LPS exposure, but not in those without the neonatal LPS exposure. Rotenone induced losses of tyrosine hydroxylase immunoreactive neurons in the substantia nigra and decreased mitochondrial complex I activity in the striatum of rats with neonatal LPS exposure, but not in those without this exposure. Neonatal LPS exposure with later exposure to rotenone decreased retrogradely labeled nigrostriatal dopaminergic projecting neurons. The current study suggests that perinatal brain inflammation may enhance adult susceptibility to the development of neurodegenerative disorders triggered later on by environmental toxins at an ordinarily non-toxic or sub-toxic dose. Our model may be useful for studying mechanisms involved in the pathogenesis of nonfamilial Parkinson’s disease and the development of potential therapeutic treatments. PMID:21798348

  17. Nutrition and neurodevelopment: mechanisms of developmental dysfunction and disease in later life.

    PubMed

    Dauncey, M J; Bicknell, R J

    1999-12-01

    Nutrition plays a central role in linking the fields of developmental neurobiology and cognitive neuroscience. It has a profound impact on the development of brain structure and function and malnutrition can result in developmental dysfunction and disease in later life. A number of diseases, including schizophrenia, may be related to neurodevelopmental insults such as malnutrition, hypoxia, viruses or in utero drug exposure. Some of the most significant findings on nutrition and neurodevelopment during the last three decades, and especially during the last few years, are discussed in this review. Attention is focused on the underlying cellular and molecular mechanisms by which diet exerts its effects. Randomized intervention studies have revealed important effects of early nutrition on later cognitive development, and recent epidemiological findings show that both genetics and environment are risk factors for schizophrenia. Particularly important is the effect of early nutrition on development of the hippocampus, a brain structure important in establishing learning and memory, and hence for cognitive performance. A major aim of future research should be to elucidate the molecular mechanisms underlying nutritionally-induced impairment of neurodevelopment and specifically to determine the mechanisms by which early nutritional experience affects later cognitive performance. Key research objectives should include: (1) increased understanding of mechanisms underlying the normal processes of ageing and neurodegenerative disorders; (2) assessment of the role of susceptibility genes in modulating the effects of early nutrition on neurodevelopment; and (3) development of nutritional and pharmaceutical strategies for preventing and/or ameliorating the adverse effects of early malnutrition on long-term programming.

  18. Neonatal exposure to lipopolysaccharide enhances vulnerability of nigrostriatal dopaminergic neurons to rotenone neurotoxicity in later life.

    PubMed

    Fan, Lir-Wan; Tien, Lu-Tai; Lin, Rick C S; Simpson, Kimberly L; Rhodes, Philip G; Cai, Zhengwei

    2011-12-01

    Brain inflammation in early life has been proposed to play important roles in the development of neurodegenerative disorders in adult life. To test this hypothesis, we used a neonatal rat model of lipopolysaccharide (LPS) exposure (1000 EU/g body weight, intracerebral injection on P5) to produce brain inflammation. By P70, when LPS-induced behavioral deficits were spontaneously recovered, animals were challenged with rotenone, a commonly used pesticide, through subcutaneous mini-pump infusion at a dose of 1.25 mg/kg per day for 14 days. This rotenone treatment regimen ordinarily does not produce toxic effects on behaviors in normal adult rats. Our results show that neonatal LPS exposure enhanced the vulnerability of nigrostriatal dopaminergic neurons to rotenone neurotoxicity in later life. Rotenone treatment resulted in motor neurobehavioral impairments in rats with the neonatal LPS exposure, but not in those without the neonatal LPS exposure. Rotenone induced losses of tyrosine hydroxylase immunoreactive neurons in the substantia nigra and decreased mitochondrial complex I activity in the striatum of rats with neonatal LPS exposure, but not in those without this exposure. Neonatal LPS exposure with later exposure to rotenone decreased retrogradely labeled nigrostriatal dopaminergic projecting neurons. The current study suggests that perinatal brain inflammation may enhance adult susceptibility to the development of neurodegenerative disorders triggered later on by environmental toxins at an ordinarily non-toxic or sub-toxic dose. Our model may be useful for studying mechanisms involved in the pathogenesis of nonfamilial Parkinson's disease and the development of potential therapeutic treatments. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. Midlife Work-Related Stress Increases Dementia Risk in Later Life: The CAIDE 30-Year Study.

    PubMed

    Sindi, Shireen; Hagman, Göran; Håkansson, Krister; Kulmala, Jenni; Nilsen, Charlotta; Kåreholt, Ingemar; Soininen, Hilkka; Solomon, Alina; Kivipelto, Miia

    2016-04-08

    To investigate the associations between midlife work-related stress and mild cognitive impairment (MCI), dementia, and Alzheimer's disease later in life, in a large representative population. Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study participants were randomly selected from independent population-based surveys (mean age 50 years). A random sample of 2,000 individuals was invited for two reexaminations including cognitive tests (at mean age 71 and mean age 78), and 1,511 subjects participated in at least one reexamination (mean follow-up 28.5 years). Work-related stress was measured using two questions on work demands that were administered in midlife. Analyses adjusted for important confounders. Higher levels of midlife work-related stress were associated with higher risk of MCI (odds ratio [OR], 1.38; 95% confidence interval [CI], 1.08-1.76), dementia (OR, 1.53; CI, 1.13-2.07), and Alzheimer's disease (OR, 1.55; CI, 1.19-2.36) at the first follow-up among the CAIDE participants. Results remained significant after adjusting for several possible confounders. Work-related stress was not associated with MCI and dementia during the extended follow-up. Midlife work-related stress increases the risk for MCI, dementia, and Alzheimer's disease in later life. The association was not seen after the extended follow-up possibly reflecting selective survival/participation, heterogeneity in dementia among the oldest old, and a critical time window for the effects of midlife stress. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. Cortical activation during word reading and picture naming in dyslexic and non-reading-impaired children.

    PubMed

    Trauzettel-Klosinski, Susanne; Dürrwächter, Ute; Klosinski, Gunther; Braun, Christoph

    2006-05-01

    In a recent study on picture naming and word reading in dyslexics and control children we found a combination of normal picture retrieval times and severe reading impairments in dyslexics. Therefore, we hypothesize that brain response patterns differ between patients and controls during word reading, but are similar in picture naming as a non-letter mediated task. Time course of brain activation was investigated by magnetoencephalography during word reading and picture naming in 9 dyslexic children and 13 age-matched controls (aged 9-10 years). We found 5 consecutive activations spreading from occipito-parietal to temporo-frontal sites. Group differences occurred only during reading: a delayed response in temporal superior and angular gyri at 235-285 ms and absence of activation in anterior temporal and inferior frontal regions at 430-530 ms for dyslexics. Problems in phonological processing are reflected in delay of early activity and absence of late activity in language related brain regions. From the lack of group differences during picture naming, we conclude the presence of two pathways: a phonological/orthographic one for word reading, which is disturbed in dyslexics, and a visual one for picture naming, which can be unaffected in dyslexics. Evidence is provided for different pathways for the processing of letter-mediated and visual-eidetic information. This knowledge may be important for dyslexics in the context of coping with everyday demands and for training of relevant skills.

  1. Association between olfaction and higher cortical functions in Alzheimer's disease, mild cognitive impairment, and healthy older adults.

    PubMed

    Ward, Amanda M; Calamia, Matthew; Thiemann, Erin; Dunlap, Jamie; Tranel, Daniel

    2017-09-01

    Neural regions important for smell are proximal and closely connected to cortical areas that have been strongly implicated in higher order functions of value-based decision making and emotional memory. The integrity of these neural regions are affected in aging and neurodegenerative conditions. Two specific predictions follow from these neuroanatomical arrangements-namely, that olfaction would be associated with value-based decision making and with emotional memory. To test these predictions, we measured these different capacities in participants with presumed varying degrees of integrity of the relevant brain structures: specifically, 13 patients with Alzheimer's disease, 8 patients with mild cognitive impairment, and 20 healthy older adults. The participants completed detailed tests of olfaction, value-based decision making, emotional memory, and general cognitive ability. Olfactory functioning was significantly associated with emotional and nonemotional memory. The association was especially strong and consistent for memory recall with olfaction, explaining as much as 10% additional variance over and above general cognition. Olfactory functioning was not strongly or consistently associated with decision making over and above general cognition. Olfaction is a strong predictor of memory recall. These findings may contribute to a better understanding of olfaction and specific cognitive domains known to be affected by aging and implicated in neurodegenerative disease.

  2. Diisopropylfluorophosphate Impairs the Transport of Membrane-Bound Organelles in Rat Cortical Axons.

    PubMed

    Gao, Jie; Naughton, Sean X; Wulff, Heike; Singh, Vikrant; Beck, Wayne D; Magrane, Jordi; Thomas, Bobby; Kaidery, Navneet Ammal; Hernandez, Caterina M; Terry, Alvin V

    2016-03-01

    The extensive use of organophosphates (OPs) is an ongoing environmental health concern due to multiple reports of OP-related neurologic abnormalities. The mechanism of the acute toxicity of OPs has been attributed to inhibition of acetylcholinesterase (AChE), but there is growing evidence that this may not account for all the long-term neurotoxic effects of OPs. In previous experiments (using ex vivo and in vitro model systems) we observed that the insecticide OP chlorpyrifos impaired the movements of vesicles and mitochondria in axons. Here, using a time-lapse imaging technique, we evaluated the OP-nerve agent diisopropylfluorophosphate (DFP) across a wide range of concentrations (subnanomolar to micromolar) for effects on fast axonal transport of membrane-bound organelles (MBOs) that contain the amyloid precursor protein (APP) tagged with the fluorescent marker Dendra2 (APPDendra2). Both 1 and 24 hours of exposure to DFP and a positive control compound, colchicine, resulted in a decrease in the velocity of anterograde and retrograde movements of MBOs and an increase in the number of stationary MBOs. These effects occurred at picomolar (100 pM) to low nanomolar (0.1 nM) concentrations that were not associated with compromised cell viability or cytoskeletal damage. Moreover, the effects of DFP on axonal transport occurred at concentrations that did not inhibit AChE activity, and they were not blocked by cholinergic receptor antagonists. Given the fundamental importance of axonal transport to neuronal function, these observations may explain some of the long-term neurologic deficits that have been observed in humans who have been exposed to OPs. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  3. Diisopropylfluorophosphate Impairs the Transport of Membrane-Bound Organelles in Rat Cortical Axons

    PubMed Central

    Gao, Jie; Naughton, Sean X.; Wulff, Heike; Singh, Vikrant; Beck, Wayne D.; Magrane, Jordi; Thomas, Bobby; Kaidery, Navneet Ammal; Hernandez, Caterina M.

    2016-01-01

    The extensive use of organophosphates (OPs) is an ongoing environmental health concern due to multiple reports of OP-related neurologic abnormalities. The mechanism of the acute toxicity of OPs has been attributed to inhibition of acetylcholinesterase (AChE), but there is growing evidence that this may not account for all the long-term neurotoxic effects of OPs. In previous experiments (using ex vivo and in vitro model systems) we observed that the insecticide OP chlorpyrifos impaired the movements of vesicles and mitochondria in axons. Here, using a time-lapse imaging technique, we evaluated the OP-nerve agent diisopropylfluorophosphate (DFP) across a wide range of concentrations (subnanomolar to micromolar) for effects on fast axonal transport of membrane-bound organelles (MBOs) that contain the amyloid precursor protein (APP) tagged with the fluorescent marker Dendra2 (APPDendra2). Both 1 and 24 hours of exposure to DFP and a positive control compound, colchicine, resulted in a decrease in the velocity of anterograde and retrograde movements of MBOs and an increase in the number of stationary MBOs. These effects occurred at picomolar (100 pM) to low nanomolar (0.1 nM) concentrations that were not associated with compromised cell viability or cytoskeletal damage. Moreover, the effects of DFP on axonal transport occurred at concentrations that did not inhibit AChE activity, and they were not blocked by cholinergic receptor antagonists. Given the fundamental importance of axonal transport to neuronal function, these observations may explain some of the long-term neurologic deficits that have been observed in humans who have been exposed to OPs. PMID:26718240

  4. Do early life factors affect the development of knee osteoarthritis in later life: a narrative review.

    PubMed

    Antony, Benny; Jones, Graeme; Jin, Xingzhong; Ding, Changhai

    2016-09-13

    Osteoarthritis (OA) mainly affects older populations; however, it is possible that early life factors contribute to the development of OA in later life. The aim of this review is to describe the association between childhood or early adulthood risk factors and knee pain, structural imaging markers and development of knee OA in later life. A narrative overview of the literature synthesising the findings of literature retrieved from searches of computerised databases and manual searches was conducted. We found that only a few studies have explored the long-term effect of childhood or early adulthood risk factors on the markers of joint health that predispose people to OA or joint symptoms. High body mass index (BMI) and/or overweight status from childhood to adulthood were independently related to knee pain and OA in later life. The findings regarding the association between strenuous physical activity and knee structures in young adults are still conflicting. However, a favourable effect of moderate physical activity and fitness on knee structures is reported. Childhood physical activity and performance measures had independent beneficial effects on knee structures including knee cartilage in children and young adults. Anterior knee pain syndrome in adolescence could lead to the development of patellofemoral knee OA in the late 40s. Furthermore, weak evidence suggests that childhood malalignment, socioeconomic status and physical abuse are associated with OA in later life. The available evidence suggests that early life intervention may prevent OA in later life.

  5. Lifelong Socio Economic Position and biomarkers of later life health: testing the contribution of competing hypotheses.

    PubMed

    Ploubidis, George B; Benova, Lenka; Grundy, Emily; Laydon, Daniel; DeStavola, Bianca

    2014-10-01

    The relative contribution of early or later life Socio Economic Position (SEP) to later life health is not fully understood and there are alternative hypotheses about the pathways through which they may influence health. We used data from the English Longitudinal Study of Ageing with a formal approach for the identification of mediating factors in order to investigate alternative hypotheses about life course influences on biomarkers of later life health. We found that early life SEP predicts physical health at least 65 years later. However, a more complicated pattern of associations than that implied by previous findings was also observed. Age group specific effects emerged, with current SEP dominating the effect on later life physical health and fibrinogen levels in participants under 65, while early life SEP had a more prominent role in explaining inequalities in physical health for men and women over 75. We extend previous findings on mid adulthood and early old age, to old age and the beginnings of late old age. The complexity of our findings highlights the need for further research on the mechanisms that underlie the association between SEP and later life health.

  6. Later-Life Preparation Patterns on Depression Among Korean Baby Boom Generations.

    PubMed

    Nam, Seok In; Kim, Junpyo; Shin, Jimin; Yim, Arram

    2017-01-01

    The aim of this study was to examine the later-life preparation pattern of Korean baby boomers and its effect on depression. Using the fourth wave of Korean Retirement and Income Study, later-life preparation was measured by economic, physical, and psychological preparation, and leisure, and family relationship satisfaction. The data analysis included latent class analysis, correlations, multiple logistic regression, and analysis of variance. Later-life patterns of Korean baby boomers were classified as high-level (35.7%), low-level (31.1%), and health and family relationship (33.2%) preparation patterns. For depression, the low-level pattern was associated with significantly higher level of depression; however, no differences were found in other two patterns. Researchers recommended a postretirement program to reflect the unique characteristics of Korean baby boomers. Moreover, findings regarding the importance of health and family relationships can be applied to other countries that have historical and cultural backgrounds similar to Korea.

  7. Revisiting widowhood in later life: changes in patterns and profiles, advances in research and understanding.

    PubMed

    Martin-Matthews, Anne

    2011-09-01

    This analysis reviews the ways in which both the experience of widowhood in old age and the nature of research on widowhood have changed since the publication of the book Widowhood in Later Life in 1991. Patterns of decline in widowhood in both its duration and incidence in later life are examined. Widowhood research has advanced conceptually by moving beyond understanding widowhood solely in terms of role loss. Life course perspectives, and concepts of multiple narratives and of resilience, have also contributed to the field. New methodologies, including prospective and longitudinal designs involving larger data sets, and more in-depth qualitative studies, have advanced our understanding of complexities and variations in widowhood. These include issues of gender and ethnocultural diversity, as well as the intersection of wealth, health, and class. This article also examines how patterns of labour force affiliation, social policy, and the changing nature of marriage shape widowhood in later life.

  8. Living in the doldrums: The lived experience of dispiritedness in later life.

    PubMed

    Butcher, Howard Karl; McGonigal-Kenney, Meghan L

    2010-07-01

    This phenomenological investigation sought to enhance understanding of the experience of dispiritedness by providing a rich and vivid description of the essential structure of the experience in later life. van Manen's hermeneutic-phenomenological method was used to analyze the transcribed texts of 11 individuals who identified themselves as being in "later life" (mean age = 73, age range = 52 to 93) and who participated in phenomenological interviews focusing on describing the experience of dispiritedness. Statements describing the experience of dispiritedness were sorted into 21 thematic categories that were synthesized into 7 essential themes that described the structure of the lived experience of dispiritedness in later life as Arising From Life's Trying Transitions, Feeling Disengaged From Meaning, Experiencing a Restricting Loss of Vigor and Animation, Feeling Forlorn Bewilderment, Moving Between Engagement and Disengagement, Remaining Faithful to Enduring Connections, and Engaging in Day-to-Day Living. Copyright 2010, SLACK Incorporated.

  9. The Implications of Unintended Pregnancies for Mental Health in Later Life

    PubMed Central

    Higgins, Jenny; Sicinski, Kamil; Merkurieva, Irina

    2016-01-01

    Despite decades of research on unintended pregnancies, we know little about the health implications for the women who experience them. Moreover, no study has examined the implications for women whose pregnancies occurred before Roe v. Wade was decided—nor whether the mental health consequences of these unintended pregnancies continue into later life. Using the Wisconsin Longitudinal Study, a 60-year ongoing survey, we examined associations between unwanted and mistimed pregnancies and mental health in later life, controlling for factors such as early life socioeconomic conditions, adolescent IQ, and personality. We found that in this cohort of mostly married and White women, who completed their pregnancies before the legalization of abortion, unwanted pregnancies were strongly associated with poorer mental health outcomes in later life. PMID:26691118

  10. Gender Transitions in Later Life: The Significance of Time in Queer Aging

    PubMed Central

    Fabbre, Vanessa D.

    2014-01-01

    Concepts of time are ubiquitous in studies of aging. This article integrates an existential perspective on time with a notion of queer time based on the experiences of older transgender persons who contemplate or pursue a gender transition in later life. Interviews were conducted with male-to-female identified persons aged 50 years or older (N=22), along with participant observation at three national transgender conferences (N=170 hours). Interpretive analyses suggest that an awareness of “time left to live” and a feeling of “time served” play a significant role in later life development and help expand gerontological perspectives on time and queer aging. PMID:24798691

  11. Decreased prefrontal cortical sensitivity to monetary reward is associated with impaired motivation and self-control in cocaine addiction

    PubMed Central

    Goldstein, Rita Z.; Alia-Klein, Nelly; Tomasi, Dardo; Zhang, Lei; Cottone, Lisa A.; Maloney, Thomas; Telang, Frank; Caparelli, Elisabeth C.; Chang, Linda; Ernst, Thomas; Samaras, Dimitris; Squires, Nancy K.; Volkow, Nora D.

    2008-01-01

    Objective To examine the brain’s sensitivity to monetary rewards of different magnitudes in cocaine abusers and to study its association with motivation and self-control. Method Sixteen cocaine abusers and 13 matched healthy comparison subjects performed a forced-choice task under three monetary value conditions while brain activation was measured with functional magnetic resonance imaging. Objective measures of state motivation were assessed by reaction time and accuracy, and subjective measures were assessed by self-reports of task engagement. Measures of trait motivation and self-control were assessed with the Multidimensional Personality Questionnaire. Results The cocaine abusers demonstrated an overall reduced regional brain responsivity to differences between the monetary value conditions. Also, in comparison subjects but not in cocaine abusers reward-induced improvements in performance were associated with self-reports of task engagement, and money-induced activations in the lateral prefrontal cortex were associated with activations in the orbitofrontal cortex. For cocaine subjects, prefrontal cortex sensitivity to money was instead associated with motivation and self-control. Conclusions These findings suggest that in cocaine addiction (1) activation of the corticolimbic reward circuit to gradations of money is altered; (2) lack of a correlation between objective and subjective measures of state motivation may be indicative of disrupted perception of motivational drive, which could contribute to impairments in self-control; and (3) the lateral prefrontal cortex modulates trait motivation and deficits in self-control, and a possible underlying mechanism may encompass a breakdown in prefrontal-orbitofrontal cortical communication. PMID:17202543

  12. Impairment of a cortical event-related desynchronisation during a bimanual load-lifting task in children with autistic disorder.

    PubMed

    Martineau, Joëlle; Schmitz, Christina; Assaiante, Christine; Blanc, Romuald; Barthélémy, Catherine

    2004-09-09

    In autism, the abilities of communication are affected, associated with abnormalities of cognitive, sensorial and motor development. In a previous study based on a load-lifting task, we showed impairment of anticipation in children with autism as evidenced by kinematics and eletromyographic recordings [Neurosci. Lett. 348 (2003) 17]. In the present study, we assessed the cortical counterparts of the use of anticipatory postural adjustments in a group of control children and in a group of children with autism. The tasks required maintaining a stable forearm position despite imposed or voluntary lifting of an object placed either on the controlateral forearm or on a support. We investigated the differences between the two groups of children on the Event-Related Desynchronisation (ERD) which precedes movement onset in adults [Electroencephalogr. Clin. Neurophysiol. 46 (1979) 138]. Electroencephalogram (EEG) power evolution of a 6-8-Hz frequency band was averaged before and after imposed or voluntary movement onset. EEG reactivity of control and autistic children did not differ during the imposed unloading condition, but significant differences appeared in the voluntary unloading situations. Before lifting the object, control children showed an ERD above the left motor areas. An ERD also occurred above the right motor areas when the object was placed on their forearm. This indicates that the ERD can also translate the use of anticipatory postural adjustments. By contrast, children with autism did not show an ERD in the two voluntary situations. This suggests a central deficit of anticipation in both postural and motor control in children with autism.

  13. Chronic Underactivity of Medial Frontal Cortical β2-Containing Nicotinic Receptors Increases Clozapine-Induced Working Memory Impairment in Female Rats

    PubMed Central

    Levin, Edward D.; Perkins, Abigail; Brotherton, Terrell; Qazi, Melissa; Berez, Chantal; Montalvo-Ortiz, Janitza; Davis, Kasey; Williams, Paul; Christopher, N. Channelle

    2009-01-01

    Nicotinic receptor decreases in the frontal cortex and hippocampus are important mediators of cognitive impairment in both schizophrenia and Alzheimer's disease. Drug treatments for these diseases should take into account the impacts of compromised brain function on drug response. This study investigated the impact of compromised nicotinic receptor activity in the frontal cortex in rats on memory function. Since both Alzheimer's disease and schizophrenia can involve psychosis, antipsychotic drugs are often given. The impacts of antipsychotic drugs on cognitive function have been found to be quite variable. It is the hypothesis of this and previous studies that the cognitive effects of antispychotic drugs on cognitive function depend on the integrity of brain systems involved in cognition. Previously in studies of the hippocampus, we found that chronic inhibition of β2-containing nicotinic receptors with dihydro-β-erythrodine (DHβE) impaired working memory and that this effect was attenuated by the antipsychotic drug clozapine. In contrast, chronic hippocampal α7 nicotinic receptor blockade with methyllycaconitine (MLA) potentiated the clozapine-induced memory impairment which is seen in rats without compromised nicotinic receptor activity. The current study determined medial frontal cortical α7 and β2-containing nicotinic receptor involvement in memory and the interactions with antipsychotic drug therapy with clozapine. Chronic DHβE and MLA infusion effects and interactions with systemic clozapine were assessed in female rats tested for memory on the radial-arm maze. Antipsychotic drug interactions with chronic systemic nicotine were investigated because nicotinic procognitive treatment has been proposed. The same local infusion DHβE dose that impaired memory with hippocampal infusion did not impair memory when infused in the medial frontal cortex. Frontal DHβE infusion potentiated clozapine-induced memory impairment, whereas previously the memory

  14. Selective depletion of cortical noradrenaline by anti-dopamine beta-hydroxylase–saporin impairs attentional function and enhances the effects of guanfacine in the rat

    PubMed Central

    2007-01-01

    Rationale Previous data indicate that depletion of cortical noradrenaline (NA) impairs performance of an attentional five-choice serial reaction time task (5CSRT) under certain conditions. This study employed a novel immunotoxin, anti-dopamine-beta hydroylase (DβH)–saporin, to make relatively selective lesions of the noradrenergic projections to the prefrontal cortex (PFC) in rats trained to perform the 5CSRT. Objectives The aim of this work is to examine (1) the effect of cortical noradrenaline depletion on sustained attentional performance in the 5CSRT under a variety of test conditions and (2) the effects of guanfacine, a selective α-2 adrenoceptor agonist on attentional performance in sham and NA-depleted rats. Materials and methods Animals received either intramedial prefrontal anti-DβH–saporin or vehicle and were tested on the baseline task with a variety of additional manipulations including (1) decreasing target duration, (2) increasing rate and (3) temporal unpredictability of target presentation and (4) systemic guanfacine. Results Anti-DβH-saporin infused into the PFC produced a substantial loss of DβH-positive fibers in that region and in other adjacent cortical areas. There was no significant depletion of DA or 5-HT. NA-depleted animals were not impaired on the baseline task, but were slower to respond correctly under high event rate conditions, and their discriminative accuracy was reduced when stimulus predictability decreased. Guanfacine significantly reduced discriminative accuracy in NA-depleted animals only. Conclusion Selective cortical NA depletion produced deficits on the 5CSRT test of sustained attention, especially when the attentional load was increased and in response to systemic guanfacine. These results are consistent with a role of coeruleo-cortical NA in the regulation of effortful attentional processes. PMID:17096085

  15. Impaired fast-spiking, suppressed cortical inhibition, and increased susceptibility to seizures in mice lacking Kv3.2 K+ channel proteins.

    PubMed

    Lau, D; Vega-Saenz de Miera, E C; Contreras, D; Ozaita, A; Harvey, M; Chow, A; Noebels, J L; Paylor, R; Morgan, J I; Leonard, C S; Rudy, B

    2000-12-15

    Voltage-gated K(+) channels of the Kv3 subfamily have unusual electrophysiological properties, including activation at very depolarized voltages (positive to -10 mV) and very fast deactivation rates, suggesting special roles in neuronal excitability. In the brain, Kv3 channels are prominently expressed in select neuronal populations, which include fast-spiking (FS) GABAergic interneurons of the neocortex, hippocampus, and caudate, as well as other high-frequency firing neurons. Although evidence points to a key role in high-frequency firing, a definitive understanding of the function of these channels has been hampered by a lack of selective pharmacological tools. We therefore generated mouse lines in which one of the Kv3 genes, Kv3.2, was disrupted by gene-targeting methods. Whole-cell electrophysiological recording showed that the ability to fire spikes at high frequencies was impaired in immunocytochemically identified FS interneurons of deep cortical layers (5-6) in which Kv3.2 proteins are normally prominent. No such impairment was found for FS neurons of superficial layers (2-4) in which Kv3.2 proteins are normally only weakly expressed. These data directly support the hypothesis that Kv3 channels are necessary for high-frequency firing. Moreover, we found that Kv3.2 -/- mice showed specific alterations in their cortical EEG patterns and an increased susceptibility to epileptic seizures consistent with an impairment of cortical inhibitory mechanisms. This implies that, rather than producing hyperexcitability of the inhibitory interneurons, Kv3.2 channel elimination suppresses their activity. These data suggest that normal cortical operations depend on the ability of inhibitory interneurons to generate high-frequency firing.

  16. Cholinergic-associated loss of hnRNP-A/B in Alzheimer's disease impairs cortical splicing and cognitive function in mice

    PubMed Central

    Berson, Amit; Barbash, Shahar; Shaltiel, Galit; Goll, Yael; Hanin, Geula; Greenberg, David S; Ketzef, Maya; Becker, Albert J; Friedman, Alon; Soreq, Hermona

    2012-01-01

    Genetic studies link inherited errors in RNA metabolism to familial neurodegenerative disease. Here, we report such errors and the underlying mechanism in sporadic Alzheimer's disease (AD). AD entorhinal cortices presented globally impaired exon exclusions and selective loss of the hnRNP A/B splicing factors. Supporting functional relevance, hnRNP A/B knockdown induced alternative splicing impairments and dendrite loss in primary neurons, and memory and electrocorticographic impairments in mice. Transgenic mice with disease-associated mutations in APP or Tau displayed no alterations in hnRNP A/B suggesting that its loss in AD is independent of Aβ and Tau toxicity. However, cholinergic excitation increased hnRNP A/B levels while in vivo neurotoxin-mediated destruction of cholinergic neurons caused cortical AD-like decrease in hnRNP A/B and recapitulated the alternative splicing pattern of AD patients. Our findings present cholinergic-mediated hnRNP A/B loss and impaired RNA metabolism as important mechanisms involved in AD. PMID:22628224

  17. Learning in Later Life: A Bicultural Perspective from Aotearoa/New Zealand

    ERIC Educational Resources Information Center

    Findsen, Brian

    2016-01-01

    This article is concerned with how learning in later life has been constructed and practised by the two most numerous ethnic groups in Aotearoa/New Zealand, "Pakeha" (Europeans) and "Maori" (Indigenous people). It is argued that learning is heavily influenced by historic features of interaction between these two groups; Pakeha…

  18. The Interplay between Women's Life Course Work Patterns and Financial Planning for Later Life

    ERIC Educational Resources Information Center

    Berger, Ellie D.; Denton, Margaret A.

    2004-01-01

    In order to gain a comprehensive understanding of the interplay between women's life course work patterns and their financial planning for later life, we examined data from semi-structured interviews with retired women (n = 28) aged 59 to 92. The majority of women disrupted their careers at some point in time, for an average of 14 years, primarily…

  19. Learning in Later Life: A Bicultural Perspective from Aotearoa/New Zealand

    ERIC Educational Resources Information Center

    Findsen, Brian

    2016-01-01

    This article is concerned with how learning in later life has been constructed and practised by the two most numerous ethnic groups in Aotearoa/New Zealand, "Pakeha" (Europeans) and "Maori" (Indigenous people). It is argued that learning is heavily influenced by historic features of interaction between these two groups; Pakeha…

  20. The Role of Musical Possible Selves in Supporting Subjective Well-Being in Later Life

    ERIC Educational Resources Information Center

    Creech, Andrea; Hallam, Susan; Varvarigou, Maria; Gaunt, Helena; McQueen, Hilary; Pincas, Anita

    2014-01-01

    There is now an accepted need for initiatives that support older people's well-being. There is increasing evidence that active engagement with music has the potential to contribute to this. This paper explores the relationship between musical possible selves and subjective well-being in later life. The research reported here formed part of a…

  1. Early-Life Characteristics, Psychiatric History, and Cognition Trajectories in Later Life

    ERIC Educational Resources Information Center

    Brown, Maria Teresa

    2010-01-01

    Purpose of the Study: Although considerable attention has been paid to the relationship between later-life depression and cognitive function, the relationship between a history of psychiatric problems and cognitive function is not very well documented. Few studies of relationships between childhood health, childhood disadvantage, and cognitive…

  2. Later Life Learning Experiences: Listening to the Voices of Chinese Elders in Hong Kong

    ERIC Educational Resources Information Center

    Tam, Maureen

    2016-01-01

    Governments' anxieties about ageing populations are mostly concerned with the costs of welfare, care and health provision which all have to be paid for by an ever dwindling working population. However, research in later life learning indicates the significant role that lifelong learning can play in promoting mental well-being and resilience, and…

  3. Learning about Sex in Later Life: Sources of Education and Older Australian Adults

    ERIC Educational Resources Information Center

    Fileborn, Bianca; Lyons, Anthony; Hinchliff, Sharron; Brown, Graham; Heywood, Wendy; Minichiello, Victor

    2017-01-01

    This paper examines the preferred sexuality education sources of older Australian adults in later life. Drawing on findings from qualitative interviews with 30 men and 23 women aged 60 years and older, we consider the sources that participants currently use, or would like to use, in seeking information about sex. Where relevant, we examine…

  4. Later Life Learning Experiences: Listening to the Voices of Chinese Elders in Hong Kong

    ERIC Educational Resources Information Center

    Tam, Maureen

    2016-01-01

    Governments' anxieties about ageing populations are mostly concerned with the costs of welfare, care and health provision which all have to be paid for by an ever dwindling working population. However, research in later life learning indicates the significant role that lifelong learning can play in promoting mental well-being and resilience, and…

  5. The Role of Musical Possible Selves in Supporting Subjective Well-Being in Later Life

    ERIC Educational Resources Information Center

    Creech, Andrea; Hallam, Susan; Varvarigou, Maria; Gaunt, Helena; McQueen, Hilary; Pincas, Anita

    2014-01-01

    There is now an accepted need for initiatives that support older people's well-being. There is increasing evidence that active engagement with music has the potential to contribute to this. This paper explores the relationship between musical possible selves and subjective well-being in later life. The research reported here formed part of a…

  6. Sexuality in later life: examining beliefs and perceptions of undergraduate students.

    PubMed

    Freeman, Shannon; Sousa, Sarah; Neufeld, Eva

    2014-01-01

    Understanding students' beliefs and perceptions of sex/sexuality in later life can reduce and prevent ageist myths and stereotypes. The objective of this study was to gauge undergraduate students' knowledge of several myths, stereotypes, and facts regarding sex/sexuality in later life, including lesbian, gay, bisexual, and transgendered (LGBT) older adults. More than 85% of students held a positive view of sex/sexuality in later life with 65% believing that they would engage in sexual activity past age 80 (N=125). Correct responses to true/false questions were higher for those with a positive perspective on aging, and recognizing that sexual behavior does not cease to be important with aging was the strongest predictor of holding a positive view on sexuality in later life. No significant differences were observed from responses regarding LGBT older adults or constraints to sexuality in long term care facilities. The positive perceptions among students in the current study suggest an increased acceptance of sexuality and diversity that should be maintained in university curricula.

  7. Early-Life Characteristics, Psychiatric History, and Cognition Trajectories in Later Life

    ERIC Educational Resources Information Center

    Brown, Maria Teresa

    2010-01-01

    Purpose of the Study: Although considerable attention has been paid to the relationship between later-life depression and cognitive function, the relationship between a history of psychiatric problems and cognitive function is not very well documented. Few studies of relationships between childhood health, childhood disadvantage, and cognitive…

  8. Living Arrangements, Social Integration, and Loneliness in Later Life: The Case of Physical Disability

    ERIC Educational Resources Information Center

    Russell, David

    2009-01-01

    Despite the theoretical linkages between household composition and social integration, relatively limited research has considered how living arrangements affect risk for loneliness in later life. Prior work has also failed to consider whether physical disability moderates this potentially important relationship. Using data from a sample of older…

  9. Learning about Sex in Later Life: Sources of Education and Older Australian Adults

    ERIC Educational Resources Information Center

    Fileborn, Bianca; Lyons, Anthony; Hinchliff, Sharron; Brown, Graham; Heywood, Wendy; Minichiello, Victor

    2017-01-01

    This paper examines the preferred sexuality education sources of older Australian adults in later life. Drawing on findings from qualitative interviews with 30 men and 23 women aged 60 years and older, we consider the sources that participants currently use, or would like to use, in seeking information about sex. Where relevant, we examine…

  10. Women's Later Life Career Development: Looking through the Lens of the Kaleidoscope Career Model

    ERIC Educational Resources Information Center

    August, Rachel A.

    2011-01-01

    This study explores the relevance of the Kaleidoscope Career Model (KCM) to women's later life career development. Qualitative interview data were gathered from 14 women in both the "truly" late career and bridge employment periods using a longitudinal design. The relevance of authenticity, balance, and challenge--central parameters in the KCM--is…

  11. Sensory Changes in Later Life. A Pacific Northwest Extension Publication. PNW 196. Revised.

    ERIC Educational Resources Information Center

    Schmall, Vicki L.

    This booklet is designed to help persons who have elderly family members or who work with older adults understand and help compensate for the sensory changes that occur in later life. It contains sections on vision, hearing, taste and smell, and touch. Discussed in the section on vision are the following: common age-related changes, eye diseases…

  12. How Old Am I? Perceived Age in Middle and Later Life

    ERIC Educational Resources Information Center

    Ward, Russell A.

    2010-01-01

    Literatures on perceived age and developmental issues in middle and later life are joined in analyzing perceived age and its implications for well-being. Respondents aged 40-74 (N = 2,696) are drawn from the national MIDUS survey, containing developmental variables such as personal growth and insight into past. People generally "feel" ("felt age")…

  13. Deconstructing Positive Affect in Later Life: A Differential Functionalist Analysis of Joy and Interest

    ERIC Educational Resources Information Center

    Consedine, Nathan S.; Magai, Carol; King, Arlene R.

    2004-01-01

    Positive affect, an index of psychological well-being, is a known predictor of functionality and health in later life. Measures typically studied include joy, happiness, and subjective well-being, but less often interest--a positive emotion with functional properties that differ from joy or happiness. Following differential emotions theory, the…

  14. Constructions of sexuality in later life: analyses of Canadian magazine and newspaper portrayals of online dating.

    PubMed

    Wada, Mineko; Hurd Clarke, Laura; Rozanova, Julia

    2015-01-01

    Advertisements as well as contemporary literature and films often depict older adults as sexually undesirable and unattractive, which reinforces the stereotype that they are nonsexual. However, the evolving discourses of successful aging emphasize that active engagement in life is a key element of healthy aging and as such, have been influencing the ways that older adults' sexuality is represented. This paper explores how popular newspapers and magazines in Canada construct and portray later life sexuality within the context of online dating. We retrieved 144 newspaper and magazine articles about later life online dating that were published between 2009 and 2011. Our thematic and discursive analyses of the articles generated six themes. Of 144 articles, 13% idealized sexuality (sexual attractiveness and optimal sexual engagement) for older adults. The articles portrayed sexual interests and functioning as declining in later life (19%) more often than sustaining (15%). Approximately 15% of the articles suggested that older adults should explore new techniques to boost sexual pleasure, thereby medicalizing and ameliorating sexual decline. In addition, the articles challenged the stereotype of older adults as non-sexual and claimed that sexual engagement in later life was valuable as it contributed to successful aging. We address the paradox in the articles' positive portrayals of older adults' sexuality and the tensions that arise between the two distinct ideals of sexuality that they advance.

  15. A multidimensional risk factor model for suicide attempts in later life.

    PubMed

    Chan, Sau Man Sandra; Chiu, Fung Kum Helen; Lam, Chiu Wa Linda; Wong, Sau Man Corine; Conwell, Yeates

    2014-01-01

    Elderly suicide is a public health problem worldwide, and the risk factors are multidimensional. Chronic mental health problems, personality traits, stressful life events, comorbid medical conditions, social isolation, unemployment, and poverty are associated with higher risk for suicide in later life. There was a relative paucity of data on the neurobiological markers of elderly suicide. This study examines the conjoint roles of cerebrovascular risk factors (CVRFs) and other established biopsychosocial risk factors in older adults who had made a recent suicide attempt. A cross-sectional, case-controlled study. A tertiary care setting in a public sector and a community setting. Cases (N=77) were nondemented Chinese adults aged ≥65 years, enrolled in a regional psychogeriatric service following a suicide attempt; comparison subjects (N=99) were community-dwelling nondemented older adults with no lifetime history of suicide. Measures of sociodemographic profile, life events, suicidal behavior, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) Axis I psychopathology, personality traits, functional status, physical health, CVRFs, and executive cognitive functions were administered. WEIGHTED SUM OF CVRF SCORE WAS SIGNIFICANTLY HIGHER IN OLDER WOMEN WHO HAD MADE A RECENT SUICIDE ATTEMPT (MEAN: 10.56; standard deviation [SD]: 5.46) than comparison subjects (mean: 7.24; SD: 4.04) (t=3.52, P=0.001; df=99). Logistic regression showed that CVRF score (Exp[B]: 1.289, P=0.033), DSM-IV depressive disorders (current) (Exp[B]: 348, P<0.001), number of life events in the past 12 weeks (Exp[B]: 10.4; P<0.001), and being married (Exp[B]: 12.2, P<0.048) significantly increased odds for suicide attempt status in older women (Nagelkerke R (2): 0.844). Association of CVRF score and suicide attempt status was not observed in older men for whom number of life events in the past 12 weeks (Exp[B]: 9.164; P<0.001), higher neuroticism (Exp[B]: 1.028; P=0

  16. Reorganization of motor cortex and impairment of motor performance induced by hindlimb unloading are partially reversed by cortical IGF-1 administration.

    PubMed

    Mysoet, Julien; Canu, Marie-Hélène; Gillet, Christophe; Fourneau, Julie; Garnier, Cyril; Bastide, Bruno; Dupont, Erwan

    2017-01-15

    Immobilization, bed rest, or sedentary lifestyle, are known to induce a profound impairment in sensorimotor performance. These alterations are due to a combination of peripheral and central factors. Previous data conducted on a rat model of disuse (hindlimb unloading, HU) have shown a profound reorganization of motor cortex and an impairment of motor performance. Recently, our interest was turned towards the role of insulin-like growth factor 1 (IGF-1) in cerebral plasticity since this growth factor is considered as the mediator of beneficial effects of exercise on the central nervous system, and its cortical level is decreased after a 14-day period of HU. In the present study, we attempted to determine whether a chronic subdural administration of IGF-1 in HU rats could prevent deleterious effects of HU on the motor cortex and on motor activity. We demonstrated that HU induces a shrinkage of hindlimb cortical representation and an increase in current threshold to elicit a movement. Administration of IGF-1 in HU rats partially reversed these changes. The functional evaluation revealed that IGF-1 prevents the decrease in spontaneous activity found in HU rats and the changes in hip kinematics during overground locomotion, but had no effect of challenged locomotion (ladder rung walking test). Taken together, these data clearly indicate the implication of IGF-1 in cortical plastic mechanisms and in behavioral alteration induced by a decreased in sensorimotor activity. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Resveratrol Attenuates Behavioral Impairments and Reduces Cortical and Hippocampal Loss in a Rat Controlled Cortical Impact Model of Traumatic Brain Injury

    PubMed Central

    Singleton, Richard H.; Yan, Hong Q.; Fellows-Mayle, Wendy

    2010-01-01

    Abstract Resveratrol (3,5,4′-trihydroxystilbene) is a plant-derived small molecule that is protective against multiple neurological and systemic insults. To date, no studies have explored the potential for resveratrol to provide behavioral protection in adult animals in the setting of traumatic brain injury (TBI). Using 50 male Sprague-Dawley rats, we employed the controlled cortical impact (CCI) model to ascertain whether post-injury administration of resveratrol would reduce the severity of the well-described cognitive and motor deficits associated with the model. Contusion volumes and hippocampal neuronal numbers were also measured to characterize the tissue and neuronal-sparing properties, respectively, of resveratrol. We found that 100 mg/kg, but not 10 mg/kg, of intraperitoneal resveratrol administered after injury provides significant behavioral protection in rats sustaining CCI. Specifically, rodents treated with 100 mg/kg of resveratrol showed improvements in motor performance (beam balance and beam walking) and testing of visuospatial memory (Morris water maze). Behavioral protection was correlated with significantly reduced contusion volumes, preservation of CA1 and CA3 hippocampal neurons, and protection from overt hippocampal loss as a result of incorporation into the overlying cortical contusion in resveratrol-treated animals. Although the mechanisms by which resveratrol mediates its neuroprotection is unclear, the current study adds to the growing literature identifying resveratrol as a potential therapy for human brain injury. PMID:20560755

  18. Disconnection of the Perirhinal and Postrhinal Cortices Impairs Recognition of Objects in Context But Not Contextual Fear Conditioning.

    PubMed

    Heimer-McGinn, Victoria R; Poeta, Devon L; Aghi, Krishan; Udawatta, Methma; Burwell, Rebecca D

    2017-05-03

    The perirhinal cortex (PER) is known to process object information, whereas the rodent postrhinal cortex (POR), homolog to the parahippocampal cortex in primates, is thought to process spatial information. A number of studies, however, provide evidence that both areas are involved in processing contextual information. In this study, we tested the hypothesis that the rat POR relies on object information received from the PER to form complex representations of context. Using three fear-conditioning (FC) paradigms (signaled, unsignaled, and renewal) and two context-guided object recognition tasks (with 3D and 2D objects), we examined the effects of crossed excitotoxic lesions to the POR and the contralateral PER. Performance of rats with crossed lesions was compared with that of rats with ipsilateral POR plus PER lesions and sham-operated rats. We found that rats with contralateral PER-POR lesions were impaired in object-context recognition but not in contextual FC. Therefore, interaction between the POR and PER is necessary for context-guided exploratory behavior but not for associating fear with context. Our results provide evidence for the hypothesis that the POR relies on object and pattern information from the PER to encode representations of context. The association of fear with a context, however, may be supported by alternate cortical and/or subcortical pathways when PER-POR interaction is not available. Our results suggest that contextual FC may represent a special case of context-guided behavior.SIGNIFICANCE STATEMENT Representations of context are important for perception, memory, decision making, and other cognitive processes. Moreover, there is extensive evidence that the use of contextual representations to guide appropriate behavior is disrupted in neuropsychiatric and neurological disorders including developmental disorders, schizophrenia, affective disorders, and Alzheimer's disease. Many of these disorders are accompanied by changes in

  19. Higher Education is Not Associated with Greater Cortical Thickness in Brain Areas Related to Literacy or Intelligence in Normal Aging or Mild Cognitive Impairment

    PubMed Central

    Pillai, Jagan A.; McEvoy, Linda K.; Hagler, Donald J.; Holland, Dominic; Dale, Anders M.; Salmon, David P.; Galasko, Douglas; Fennema-Notestine, Christine

    2012-01-01

    Education may reduce risk of dementia through passive reserve, by increasing neural substrate. We tested the hypotheses that education is associated with thicker cortex and reduced rates of atrophy in brain regions related to literacy and intellectual ability. Healthy older adults and those with mild cognitive impairment were categorized into High (≥18 yrs) and Low (≤13 yrs) education groups. Higher education was associated with thinner cortices in several areas, but one-year atrophy rates in these areas did not differ by education group. These results do not support a passive reserve model in which early life education protects against dementia by increasing cortical thickness. Connectivity and synaptic efficiency, or other lifestyle factors may more directly reflect cognitive reserve. PMID:22905705

  20. Higher education is not associated with greater cortical thickness in brain areas related to literacy or intelligence in normal aging or mild cognitive impairment.

    PubMed

    Pillai, Jagan A; McEvoy, Linda K; Hagler, Donald J; Holland, Dominic; Dale, Anders M; Salmon, David P; Galasko, Douglas; Fennema-Notestine, Christine

    2012-01-01

    Education may reduce risk of dementia through passive reserve, by increasing neural substrate. We tested the hypotheses that education is associated with thicker cortex and reduced rates of atrophy in brain regions related to literacy and intellectual ability. Healthy older adults and those with mild cognitive impairment were categorized into high (≥18 years) and low (≤13 years) education groups. Higher education was associated with thinner cortices in several areas, but one-year atrophy rates in these areas did not differ by education group. These results do not support a passive reserve model in which early-life education protects against dementia by increasing cortical thickness. Connectivity and synaptic efficiency or other lifestyle factors may more directly reflect cognitive reserve.

  1. Enhanced limbic/impaired cortical-loop connection onto the hippocampus of NHE rats: Application of resting-state functional connectivity in a preclinical ADHD model.

    PubMed

    Zoratto, F; Palombelli, G M; Ruocco, L A; Carboni, E; Laviola, G; Sadile, A G; Adriani, W; Canese, R

    2017-08-30

    Due to a hyperfunctioning mesocorticolimbic system, Naples-High-Excitability (NHE) rats have been proposed to model for the meso-cortical variant of attention deficit/hyperactivity disorder (ADHD). Compared to Naples Random-Bred (NRB) controls, NHE rats show hyperactivity, impaired non-selective attention (Aspide et al., 1998), and impaired selective spatial attention (Ruocco et al., 2009a, 2014). Alteration in limbic functions has been proposed; however, resulting unbalance among forebrain areas has not been assessed yet. By resting-state functional Magnetic-Resonance Imaging (fMRI) in vivo, we investigated the connectivity of neuronal networks belonging to limbic vs. cortical loops in NHE and NRB rats (n=10 each). Notably, resting-state fMRI was applied using a multi-slice sagittal, gradient-echo sequence. Voxel-wise connectivity maps at rest, based on temporal correlation among fMRI time-series, were computed by seeding the hippocampus (Hip), nucleus accumbens (NAcc), dorsal striatum (dStr), amygdala (Amy) and dorsal/medial prefrontal cortex (PFC), both hemispheres. To summarize patterns of altered connection, clearly directional connectivity was evident within the cortical loop: bilaterally and specularly, from orbital and dorsal PFCs through dStr and hence towards Hip. Such network communication was reduced in NHE rats (also, with less mesencephalic/pontine innervation). Conversely, enhanced network activity emerged within the limbic loop of NHE rats: from left PFC, both through the NAcc and directly, to the Hip (all of which received greater ventral tegmental innervation, likely dopamine). Together with tuned-down cortical loop, this potentiated limbic loop may serve a major role in controlling ADHD-like behavioral symptoms in NHE rats. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Relationship between herpes simplex virus-1-specific antibody titers and cortical brain damage in Alzheimer’s disease and amnestic mild cognitive impairment

    PubMed Central

    Baglio, Francesca; Agostini, Simone; Agostini, Monia Cabinio; Laganà, Maria M.; Hernis, Ambra; Margaritella, Nicolò; Guerini, Franca R.; Zanzottera, Milena; Nemni, Raffaello; Clerici, Mario

    2014-01-01

    Alzheimer’s disease (AD) is a multifactorial disease with a still barely understood etiology. Herpes simplex virus 1 (HSV-1) has long been suspected to play a role in the pathogenesis of AD because of its neurotropism, high rate of infection in the general population, and life-long persistence in neuronal cells, particularly in the same brain regions that are usually altered in AD. The goal of this study was to evaluate HSV-1-specific humoral immune responses in patients with a diagnosis of either AD or amnestic mild cognitive impairment (aMCI), and to verify the possible relation between HSV-1-specific antibody (Ab) titers and cortical damage; results were compared to those obtained in a group of healthy controls (HC). HSV-1 serum IgG titers were measured in 225 subjects (83 AD, 68 aMCI, and 74 HC). HSV-specific Ab avidity and cortical gray matter volumes analyzed by magnetic resonance imaging (MRI) were evaluated as well in a subgroup of these individuals (44 AD, 23 aMCI, and 26 HC). Results showed that, whereas HSV-1 seroprevalence and IgG avidity were comparable in the three groups, increased Ab titers (p < 0.001) were detected in AD and aMCI compared to HC. Positive significant correlations were detected in AD patients alone between HSV-1 IgG titers and cortical volumes in orbitofrontal (region of interest, ROI1 RSp0.56; p = 0.0001) and bilateral temporal cortices (ROI2 RSp0.57; p < 0.0001; ROI3 RSp0.48; p = 0.001); no correlations could be detected between IgG avidity and MRI parameters. Results herein suggest that a strong HSV-1-specific humoral response could be protective toward AD-associated cortical damage. PMID:25360113

  3. Cortical selective neuronal loss, impaired behavior, and normal magnetic resonance imaging in a new rat model of true transient ischemic attacks.

    PubMed

    Ejaz, Sohail; Emmrich, Julius V; Sawiak, Stephen J; Williamson, David J; Baron, Jean-Claude

    2015-04-01

    New-definition transient ischemic attacks (TIAs) are frequent but difficult to diagnose because magnetic resonance imaging (MRI)-negative by definition. However, hidden underlying cell damage might be present and account for the reported long-lasting cognitive impairment after TIAs. Most prior rodent models of true TIA targeted the striatum or have not been fully characterized. Here we present the MRI, behavioral, and quantitative cell changes characterizing a new rodent model of true TIA targeting the more behaviorally relevant cerebral cortex. Fifteen-minute distal middle cerebral artery occlusion was performed in 29 spontaneously hypertensive rats allowed to survive for 7 to 60 days. Behavior was assessed serially using both global neurological and fine sensorimotor tests. Diffusion- and T2-weighted MRI was obtained 20 min postreperfusion and again 7 to 60 days later, and then changes in neurons and microglia were quantified across the middle cerebral artery territory using immunohistochemistry. No MRI changes or pan-necrosis were observed at any time point, but patchy cortical selective neuronal loss affected 28/29 rats, regardless of survival interval, together with topographically congruent microglial activation that gradually declined over time. The Neuroscore was unchanged, but there was marked contralateral sensorimotor impairment, still recovering by day 28. Our new rodent model mimicking true cortical TIA is characterized by normal MRI, but consistent cortical selective neuronal loss and microglial activation and long-lasting sensorimotor deficits. By causing selective neuronal loss, TIAs and silent microemboli might affect neuronal reserve, thereby increasing long-term cognitive impairment risk. Selective neuronal loss and microglial activation might represent novel therapeutic targets that could be detectable in vivo after TIAs using appropriate imaging tracers. © 2015 American Heart Association, Inc.

  4. Women narrate later life remarriage: Negotiating the cultural to create the personal.

    PubMed

    Watson, Wendy K; Bell, Nancy J; Stelle, Charlie

    2010-12-01

    Narrative provides a window to experience in a way that is different from traditional research methods. In this study, narrative affords both a holistic vantage point on later life relationships, and at the same time, a "view from the inside"-older women's own accounts of single life, relationship development, and remarriage. The narratives were obtained in interviews with eight recently remarried women between the ages of sixty-five and eighty. A two-stage analysis addresses, first, the narrative content-the phenomenology of remarriage for these older women. The second stage focuses on process, analyzing how cultural-level narratives are drawn upon in the creation of the women's personal stories. Based upon these analyses, we discuss the ways that a narrative approach can inform our understanding of later life relationships, and we comment on the potential of narratives such as these to rewrite a script for older women's relationships.

  5. Union formation in later life: economic determinants of cohabitation and remarriage among older adults.

    PubMed

    Vespa, Jonathan

    2012-08-01

    This study builds on Becker's and Oppenheimer's theories of union formation to examine the economic determinants of marriage and cohabitation during older adulthood. Based on the 1998-2006 Health and Retirement Study and a sample of previously married Americans who are at least 50 years old, results show that wealthier older adults, regardless of gender, are more likely to repartner than stay single. Wealth has no discernable effect on the likelihood of remarrying versus cohabiting. Among the oldest men, the positive associations between wealth and repartnering are entirely due to housing assets. Results suggest that Oppenheimer's theory of marriage timing may be more applicable to later-life union formation than Becker's independence hypothesis. Further, economic disadvantage does not appear to characterize later-life cohabitation, unlike cohabitation during young adulthood. These findings help illuminate the union formation process during older adulthood and are timely considering demographic changes reshaping the American population.

  6. All Shook Up: Sexuality of Mid- to Later Life Married Couples

    PubMed Central

    Lodge, Amy C.; Umberson, Debra

    2012-01-01

    The authors integrate theoretical work on the performance of gender with a life course perspective to frame an analysis of in-depth interviews with 17 long-term married couples. The findings indicated that couples’ sexual experiences are characterized by change over time, yet that change is shaped by the intersection of gender and age. Midlife couples (ages 50 – 69) were distressed by changes in their sex lives likely because they impede couples from performing gendered sexuality. The source of this distress stems from age-related physical changes; however, it manifests in different ways for husbands and wives. In contrast, later life couples (ages 70 – 86) were more likely to emphasize the importance of emotional intimacy over sex as they age. Marital sex is a source of conflict for many midlife couples because of husbands’ and wives’ incongruent experiences, but later life husbands and wives tend to have more congruent experiences of marital sex. PMID:22904574

  7. The interplay between women's life course work patterns and financial planning for later life.

    PubMed

    Berger, Ellie D; Denton, Margaret A

    2004-01-01

    In order to gain a comprehensive understanding of the interplay between women's life course work patterns and their financial planning for later life, we examined data from semi-structured interviews with retired women (n = 28) aged 59 to 92. The majority of women disrupted their careers at some point in time, for an average of 14 years, primarily for child-rearing responsibilities. We found that financial preparedness and income security in later life are structured by women's life course work patterns. However, individuals also have the ability to shape their own lives and many of the women took the initiative to acquire financial knowledge irrespective of their work situation. Financial-planning advice that participants gave to future generations of older women was also explored and centred on the importance of saving, avoiding debt, maintaining financial independence, and planning ahead.

  8. Later-life Employment Preferences and Outcomes: The Role of Mid-life Work Experiences

    PubMed Central

    Raymo, James M.; Warren, John R.; Sweeney, Megan M.; Hauser, Robert M.; Ho, Jeong-Hwa

    2010-01-01

    In this paper, we evaluate relationships between mid-life work experiences and the realization of preferences for full-time employment, part-time employment, and complete retirement at age 63–64. Using rich data from the Wisconsin Longitudinal Study, we demonstrate that the likelihood of achieving one's preferred employment status is related to earlier work experiences including employment stability in mid-life and self-employment, part-time employment, and private pension coverage across the life course. Despite large gender differences in work experiences across the life course, relationships between earlier work experiences and the likelihood of realizing later-life employment preferences are generally similar for men and women. We also find that these relationships are only partially mediated by economic and employment circumstances in late mid-life, suggesting the need for further evaluation of the cumulative pathways linking mid-life work experiences to the realization of later-life employment preferences. PMID:20824202

  9. Personality Disorders in Later Life: Questions about the Measurement, Course, and Impact of Disorders

    PubMed Central

    Oltmanns, Thomas F.; Balsis, Steve

    2011-01-01

    Lifespan perspectives have played a crucial role in shaping our understanding of many forms of psychopathology. Unfortunately, little attention has been given to personality disorders in middle adulthood and later life. Several issues are responsible for this deficiency, including difficulty applying the diagnostic criteria for personality disorders to older people and challenges in identifying appropriate samples of older participants. The goal of this review is to explore the benefits of considering older adults in the study of personality disorders. Later life offers a unique opportunity for investigators to consider links between personality pathology and consequential outcomes in people’s lives. Many domains are relevant, including health, longevity, social adjustment, marital relationships, and the experience of major life events. We review each domain and consider ways in which the study of middle-aged and older adults challenges researchers to evaluate how personality disorders in general are defined and measured. PMID:21219195

  10. Women narrate later life remarriage: Negotiating the cultural to create the personal

    PubMed Central

    Watson, Wendy K.; Bell, Nancy J.; Stelle, Charlie

    2013-01-01

    Narrative provides a window to experience in a way that is different from traditional research methods. In this study, narrative affords both a holistic vantage point on later life relationships, and at the same time, a “view from the inside”—older women's own accounts of single life, relationship development, and remarriage. The narratives were obtained in interviews with eight recently remarried women between the ages of sixty-five and eighty. A two-stage analysis addresses, first, the narrative content—the phenomenology of remarriage for these older women. The second stage focuses on process, analyzing how cultural-level narratives are drawn upon in the creation of the women's personal stories. Based upon these analyses, we discuss the ways that a narrative approach can inform our understanding of later life relationships, and we comment on the potential of narratives such as these to rewrite a script for older women's relationships. PMID:25197160

  11. Early health-related behaviours and their impact on later life chances: evidence from the US.

    PubMed

    Burgess, S M; Propper, C

    1998-08-01

    This paper uses evidence from the US to examine the impact of adolescent illegal consumption and violent behaviour on later life chances. Specifically, we look at the effect of such behaviour by young men in late adolescence on productivity and household formation 10 years on. We find that alcohol and soft drug consumption have no harmful effects on economic prospects in later life. In contrast, hard drug consumption and violent behaviour in adolescence are both associated with lower productivity even by the time the individuals are in their late twenties. These effects are substantial and affect earnings levels and earnings growth. These results are robust to the inclusion of a rich set of additional controls measuring aspects of the individuals' backgrounds. However, we find no evidence of any of these behaviours significantly affecting household formation.

  12. Later-life Employment Preferences and Outcomes: The Role of Mid-life Work Experiences.

    PubMed

    Raymo, James M; Warren, John R; Sweeney, Megan M; Hauser, Robert M; Ho, Jeong-Hwa

    2010-07-01

    In this paper, we evaluate relationships between mid-life work experiences and the realization of preferences for full-time employment, part-time employment, and complete retirement at age 63-64. Using rich data from the Wisconsin Longitudinal Study, we demonstrate that the likelihood of achieving one's preferred employment status is related to earlier work experiences including employment stability in mid-life and self-employment, part-time employment, and private pension coverage across the life course. Despite large gender differences in work experiences across the life course, relationships between earlier work experiences and the likelihood of realizing later-life employment preferences are generally similar for men and women. We also find that these relationships are only partially mediated by economic and employment circumstances in late mid-life, suggesting the need for further evaluation of the cumulative pathways linking mid-life work experiences to the realization of later-life employment preferences.

  13. Older Women in New Romantic Relationships: Understanding the Meaning and Importance of Sex in Later Life.

    PubMed

    Watson, Wendy K; Stelle, Charlie; Bell, Nancy

    2016-12-02

    Although research has found that sexual activity declines with age, most of this literature examines people in long-term marriages. Little is known about the initiation of new sexual relationships in later life. In-depth interviews with 14 women aged 64 to 77 years were conducted to examine their personal and collective narratives regarding sexuality in later life. In contrast to common perceptions, none of the participants felt that aging had negatively impacted their own sexuality. For many, this was a time in their lives when they were experiencing renewed sexual desire and enjoyment. Even though sex might not have held the same priority as when they were younger, it held a place of importance in their romantic relationships. The discussion focuses on understanding women's sexual relationships and behaviors within the context of their cohort and lives.

  14. Sex and the (older) single girl: experiences of sex and dating in later life.

    PubMed

    Fileborn, Bianca; Thorpe, Rachel; Hawkes, Gail; Minichiello, Victor; Pitts, Marian

    2015-04-01

    This study explored the sexual subjectivities of older Australian women. In this article we present findings from 15 qualitative interviews with Australian women aged 55-81 who were single at the time of interview. The majority of these women were single following divorce or separation, with a smaller number of women who were widowed or never in a long-term relationship. We found that these women's sexual desire and sexual activity were fluid and diverse across their life course. Although some participants desired a romantic or sexual relationship, they were also protective of their independence and reluctant to re-enter into a relationship in later life. Our findings indicate that these women's sexual subjectivities were shaped by dominant norms of ageing, sex, and gender. At the same time, older women are challenging and resisting these norms, and beginning to renegotiate sexuality in later life. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. The Enduring Impact of Maladaptive Personality Traits on Relationship Quality and Health in Later Life

    PubMed Central

    Gleason, Marci E. J.; Weinstein, Yana; Balsis, Steve; Oltmanns, Thomas F.

    2013-01-01

    Over the past five years, the St. Louis Personality and Aging Network (SPAN) has been collecting data on personality in later life with an emphasis on maladaptive personality, social integration, and health outcomes in a representative sample of 1630 adults aged 55–64 living in the St. Louis area. This program has confirmed the importance of considering both the normal range of personality and in particular the role of maladaptive traits in order to understand individuals’ relationships, life events, and health outcomes. In the current paper we discuss the explanatory benefits of considering maladaptive traits or traits associated with personality disorders when discussing the role of personality on social and health outcomes with an emphasis on adults in middle to later life, and integrate these findings into the greater literature. PMID:23998798

  16. The enduring impact of maladaptive personality traits on relationship quality and health in later life.

    PubMed

    Gleason, Marci E J; Weinstein, Yana; Balsis, Steve; Oltmanns, Thomas F

    2014-12-01

    Over the past 5 years, the St. Louis Personality and Aging Network (SPAN) has been collecting data on personality in later life with an emphasis on maladaptive personality, social integration, and health outcomes in a representative sample of 1,630 adults aged 55-64 living in the St. Louis area. This program has confirmed the importance of considering both the normal range of personality and in particular the role of maladaptive traits in order to understand individuals' relationships, life events, and health outcomes. In the current article, we discuss the explanatory benefits of considering maladaptive traits or traits associated with personality disorders when discussing the role of personality in social and health outcomes, with an emphasis on adults in middle to later life, and integrate these findings into the greater literature. © 2013 Wiley Periodicals, Inc.

  17. Dependence on place: A source of autonomy in later life for older Māori.

    PubMed

    Butcher, Elizabeth; Breheny, Mary

    2016-04-01

    Attachment to place is an important component of ageing. Although the importance of place for older people's well-being is known, the ways in which different conceptions of place and expectations for what later life may hold depend upon cultural beliefs, values, and expectations is underexplored. This study examined the ways that place influences experiences of ageing for older Māori in New Zealand. Eight interviews with older Māori were analysed thematically alongside field notes from a research visit. Attachment to place provided the foundation for experiences of ageing for older Māori. Through their connection to place, the participants drew on a comforting and comfortable dependence on land and family to enable autonomy in later life. Rather than seeking to maintain independence in terms of avoiding reliance on others, older Māori conceptualised older age through autonomy and freedom to live in accordance with Māori values encapsulated by whakawhanaungatanga. A good old age depended on balancing competing demands of living in wider society with attachment to place and Māori identity in later life. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Effects of prenatal exposure to the Dutch famine on adult disease in later life: an overview.

    PubMed

    Roseboom, T J; van der Meulen, J H; Ravelli, A C; Osmond, C; Barker, D J; Bleker, O P

    2001-12-20

    Chronic diseases are the main public health problem in Western countries. There are indications that these diseases originate in the womb. It is thought that undernutrition of the fetus during critical periods of development would lead to adaptations in the structure and physiology of the fetal body, and thereby increase the risk of diseases in later life. The Dutch famine--though a historical disaster--provides a unique opportunity to study effects of undernutrition during gestation in humans. This thesis describes the effects of prenatal exposure to the Dutch famine on health in later life. We found indications that undernutrition during gestation affects health in later life. The effects on undernutrition, however, depend upon its timing during gestation and the organs and systems developing during that critical time window. Furthermore, our findings suggest that maternal malnutrition during gestation may permanently affect adult health without affecting the size of the baby at birth. This may imply that adaptations that enable the fetus to continue to grow may nevertheless have adverse consequences of improved nutrition of pregnant women will be underestimated if these are solely based on the size of the baby at birth. Little is known about what an adequate diet for pregnant women might be. In general, women are especially receptive to advice about diet and lifestyle before and during a pregnancy. This should be exploited to improve the health of future generations.

  19. Maternal nutrition, low nephron number and arterial hypertension in later life.

    PubMed

    Benz, Kerstin; Amann, Kerstin

    2010-12-01

    A potential role of the intrauterine environment in the development of low nephron number and hypertension in later life has been recently recognized in experimental studies and is also postulated in certain conditions in human beings. Nephrogenesis is influenced by genetic as well as by environmental and in particular maternal factors. In man nephrogenesis, i.e. the formation of nephrons during embryogenesis, takes place from weeks 5 to 36 of gestation with the most rapid phase of nephrogenesis occurring from the mid-2nd trimester until 36 weeks. This 16 week period is a very vulnerable phase where genetic and environmental factors such as maternal diet or medication could influence and disturb nephron formation leading to lower nephron number. Given a constant rise in body mass until adulthood lower nephron number may become "nephron underdosing" and result in maladaptive glomerular changes, i.e. glomerular hyperfiltration and glomerular enlargement. These maladaptive changes may then eventually lead to the development of glomerular and systemic hypertension and renal disease in later life. It is the purpose of this review to discuss the currently available experimental and clinical evidence for factors and mechanisms that could interfere with nephrogenesis with particular emphasis on maternal nutrition. In addition, we discuss the emerging concept of low nephron number being a new cardiovascular risk factor in particular for essential hypertension in later life. Copyright © 2010 Elsevier B.V. All rights reserved.

  20. Dopaminergic neurotransmission dysfunction induced by amyloid-β transforms cortical long-term potentiation into long-term depression and produces memory impairment.

    PubMed

    Moreno-Castilla, Perla; Rodriguez-Duran, Luis F; Guzman-Ramos, Kioko; Barcenas-Femat, Alejandro; Escobar, Martha L; Bermudez-Rattoni, Federico

    2016-05-01

    Alzheimer's disease (AD) is a neurodegenerative condition manifested by synaptic dysfunction and memory loss, but the mechanisms underlying synaptic failure are not entirely understood. Although dopamine is a key modulator of synaptic plasticity, dopaminergic neurotransmission dysfunction in AD has mostly been associated to noncognitive symptoms. Thus, we aimed to study the relationship between dopaminergic neurotransmission and synaptic plasticity in AD models. We used a transgenic model of AD (triple-transgenic mouse model of AD) and the administration of exogenous amyloid-β (Aβ) oligomers into wild type mice. We found that Aβ decreased cortical dopamine levels and converted in vivo long-term potentiation (LTP) into long-term depression (LTD) after high-frequency stimulation delivered at basolateral amygdaloid nucleus-insular cortex projection, which led to impaired recognition memory. Remarkably, increasing cortical dopamine and norepinephrine levels rescued both high-frequency stimulation -induced LTP and memory, whereas depletion of catecholaminergic levels mimicked the Aβ-induced shift from LTP to LTD. Our results suggest that Aβ-induced dopamine depletion is a core mechanism underlying the early synaptopathy and memory alterations observed in AD models and acts by modifying the threshold for the induction of cortical LTP and/or LTD. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Cortical disconnection of the ipsilesional primary motor cortex is associated with gait speed and upper extremity motor impairment in chronic left hemispheric stroke.

    PubMed

    Peters, Denise M; Fridriksson, Julius; Stewart, Jill C; Richardson, Jessica D; Rorden, Chris; Bonilha, Leonardo; Middleton, Addie; Gleichgerrcht, Ezequiel; Fritz, Stacy L

    2017-10-05

    Advances in neuroimaging have enabled the mapping of white matter connections across the entire brain, allowing for a more thorough examination of the extent of white matter disconnection after stroke. To assess how cortical disconnection contributes to motor impairments, we examined the relationship between structural brain connectivity and upper and lower extremity motor function in individuals with chronic stroke. Forty-three participants [mean age: 59.7 (±11.2) years; time poststroke: 64.4 (±58.8) months] underwent clinical motor assessments and MRI scanning. Nonparametric correlation analyses were performed to examine the relationship between structural connectivity amid a subsection of the motor network and upper/lower extremity motor function. Standard multiple linear regression analyses were performed to examine the relationship between cortical necrosis and disconnection of three main cortical areas of motor control [primary motor cortex (M1), premotor cortex (PMC), and supplementary motor area (SMA)] and motor function. Anatomical connectivity between ipsilesional M1/SMA and the (1) cerebral peduncle, (2) thalamus, and (3) red nucleus were significantly correlated with upper and lower extremity motor performance (P ≤ 0.003). M1-M1 interhemispheric connectivity was also significantly correlated with gross manual dexterity of the affected upper extremity (P = 0.001). Regression models with M1 lesion load and M1 disconnection (adjusted for time poststroke) explained a significant amount of variance in upper extremity motor performance (R(2)  = 0.36-0.46) and gait speed (R(2)  = 0.46), with M1 disconnection an independent predictor of motor performance. Cortical disconnection, especially of ipsilesional M1, could significantly contribute to variability seen in locomotor and upper extremity motor function and recovery in chronic stroke. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  2. Cortical thickness in de novo patients with Parkinson disease and mild cognitive impairment with consideration of clinical phenotype and motor laterality.

    PubMed

    Danti, S; Toschi, N; Diciotti, S; Tessa, C; Poletti, M; Del Dotto, P; Lucetti, C

    2015-12-01

    Parkinson's disease (PD) is a progressive neurodegenerative disorder with motor and non-motor symptoms, including cognitive deficits. Several magnetic resonance imaging approaches have been applied to investigate brain atrophy in PD. The aim of this study was to detect early structural cortical and subcortical changes in de novo PD whilst distinguishing cognitive status, clinical phenotype and motor laterality. Eighteen de novo PD with mild cognitive impairment (PD-MCI), 18 de novo PD without MCI (PD-NC) and 18 healthy control subjects were evaluated. In the PD-MCI group, nine were tremor dominant and nine were postural instability gait disorder (PIGD) phenotype; 11 had right-sided symptom dominance and seven had left-sided symptom dominance. FreeSurfer was used to measure cortical thickness/folding, subcortical structures and to study group differences as well as the association with clinical and neuropsychological data. Parkinson's disease with MCI showed regional thinning in the right frontal, right middle temporal areas and left insula compared to PD-NC. A reduction of the volume of the left and right thalamus and left hippocampus was found in PD-MCI compared to PD-NC. PD-MCI PIGD showed regional thinning in the right inferior parietal area compared to healthy controls. A decreased volume of the left thalamus was reported in PD-MCI with right-sided symptom dominance compared to PD-NC and PD-MCI with left-sided symptom dominance. When MCI was present, PD patients showed a fronto-temporo-parietal pattern of cortical thinning. This cortical pattern does not appear to be influenced by motor laterality, although one-sided symptom dominance may contribute to volumetric reduction of specific subcortical structures. © 2015 EAN.

  3. Impairment of preoperative language mapping by lesion location: a functional magnetic resonance imaging, navigated transcranial magnetic stimulation, and direct cortical stimulation study.

    PubMed

    Ille, Sebastian; Sollmann, Nico; Hauck, Theresa; Maurer, Stefanie; Tanigawa, Noriko; Obermueller, Thomas; Negwer, Chiara; Droese, Doris; Boeckh-Behrens, Tobias; Meyer, Bernhard; Ringel, Florian; Krieg, Sandro M

    2015-08-01

    Language mapping by repetitive navigated transcranial magnetic stimulation (rTMS) is increasingly used and has already replaced functional MRI (fMRI) in some institutions for preoperative mapping of neurosurgical patients. Yet some factors affect the concordance of both methods with direct cortical stimulation (DCS), most likely by lesions affecting cortical oxygenation levels. Therefore, the impairment of the accuracy of rTMS and fMRI was analyzed and compared with DCS during awake surgery in patients with intraparenchymal lesions. Language mapping was performed by DCS, rTMS, and fMRI using an object-naming task in 27 patients with left-sided perisylvian lesions, and the induced language errors of each method were assigned to the cortical parcellation system. Subsequently, the receiver operating characteristics were calculated for rTMS and fMRI and compared with DCS as ground truth for regions with (w/) and without (w/o) the lesion in the mapped regions. The w/ subgroup revealed a sensitivity of 100% (w/o 100%), a specificity of 8% (w/o 5%), a positive predictive value of 34% (w/o: 53%), and a negative predictive value (NPV) of 100% (w/o: 100%) for the comparison of rTMS versus DCS. Findings for the comparison of fMRI versus DCS within the w/ subgroup revealed a sensitivity of 32% (w/o: 62%), a specificity of 88% (w/o: 60%), a positive predictive value of 56% (w/o: 62%), and a NPV of 73% (w/o: 60%). Although strengths and weaknesses exist for both rTMS and fMRI, the results show that rTMS is less affected by a brain lesion than fMRI, especially when performing mapping of language-negative cortical regions based on sensitivity and NPV.

  4. Breast-feeding and cardiovascular risk factors and outcomes in later life: evidence from epidemiological studies.

    PubMed

    Owen, Christopher G; Whincup, Peter H; Cook, Derek G

    2011-11-01

    This paper considers the body of observational evidence examining the association of being breast-fed to cardiovascular risk factors and outcomes in later life, and whether any potentially advantageous findings are causal. Early cardiovascular consequences/correlates of breast-feeding, compared to being formula fed, include markedly higher levels of total blood cholesterol, lower levels of pre-prandial blood glucose and insulin and lower levels of adiposity. However, a key issue is whether these early differences at a period of rapid development programme/influence cardiovascular risk factors and outcomes in later life. Evidence of long-term effects of early feeding, largely from observational studies, has shown that those breast-fed have lower levels of blood total cholesterol, lower risk of type-2 diabetes and marginally lower levels of adiposity and blood pressure in adult life. There is no strong evidence to suggest effects of early feeding on adult levels of blood glucose, blood insulin and CHD outcomes, although further data are needed. However, the influence of confounding factors, such as maternal body size, maternal smoking and socio-demographic factors, and exclusivity of early feeding on these potentially beneficial associations needs to be considered before inferring any causal effects. Moreover, fewer studies have examined whether duration of exclusive breast-feeding has a graded influence on these risk factors and outcomes; such data would help further in deciding upon causal associations. While strong observational evidence suggests nutritional programming of adult cholesterol levels, associations with other markers of cardiometabolic risk and their consequences in later life need to be confirmed in well-conducted observational and experimental studies.

  5. Survival of offspring who experience early parental death: Early life conditions and later-life mortality

    PubMed Central

    Smith, Ken R.; Hanson, Heidi A.; Norton, Maria C.; Hollingshaus, Michael S.; Mineau, Geraldine P.

    2014-01-01

    We examine the influences of a set of early life conditions (ELCs) on all-cause and cause-specific mortality among elderly individuals, with special attention to one of the most dramatic early events in a child’s, adolescent’s, or even young adult’s life, the death of a parent. The foremost question is, once controlling for prevailing (and potentially confounding) conditions early in life (family history of longevity, paternal characteristics (SES, age at time of birth, sibship size, and religious affiliation)), is a parental death associated with enduring mortality risks after age 65? The years following parental death may initiate new circumstances through which the adverse effects of paternal death operate. Here we consider the offspring’s marital status (whether married; whether and when widowed), adult socioeconomic status, fertility, and later life health status. Adult health status is based on the Charlson Co-Morbidity Index, a construct that summarizes nearly all serious illnesses afflicting older individuals that relies on Medicare data. The data are based on linkages between the Utah Population Database and Medicare claims that hold medical diagnoses data. We show that offspring whose parents died when they were children, but especially when they were adolescents/young adults, have modest but significant mortality risks after age 65. What are striking are the weak mediating influences of later-life comorbidities, marital status, fertility and adult socioeconomic status since controls for these do little to alter the overall association. No beneficial effects of the surviving parent’s remarriage were detected. Overall, we show the persistence of the effects of early life loss on later-life mortality and indicate the difficulties in addressing challenges at young ages. PMID:24530028

  6. Exploring the later life relationship between adults with cerebral palsy and their non-disabled siblings.

    PubMed

    Dew, Angela; Llewellyn, Gwynnyth; Balandin, Susan

    2014-01-01

    Adults with moderate or severe cerebral palsy often require significant lifetime support from family and formal services. The aim of this study was to use a life course approach to explore how previous life experiences impact on the later life relationships of people with moderate to severe cerebral palsy aged 40 years and over and their non-disabled siblings. Twelve adults with moderate to severe cerebral palsy and 16 of their non-disabled siblings were interviewed twice to explore their relationships. Constructivist grounded theory method was used to analyse the data. Four themes were identified as important in understanding these later life sibling relationships: sharing childhood experiences, contact in adulthood, diminishing parental role and increasing support needs. The life course approach indicated that siblings' growing up together was important for the development and maintenance of emotional closeness later in life. Emotional closeness and familial obligation were important factors in motivating siblings with and without cerebral palsy to maintain or re-establish contact with each other in adulthood. Maintenance of sibling relationships in later life is dependent on health, proximity and the ability to keep in contact with each other. Implications for Rehabilitation As adults with severe cerebral palsy live longer, their relationships with non-disabled siblings often take on increased importance and particularly as their parents may be no longer able to provide support. Service providers have a role in helping ageing siblings with and without disability to maintain and build their relationships, for example, by supporting geographically distant siblings to keep in touch. Service providers have a role in supporting the person with a disability and their siblings to make plans for the future.

  7. Survival of offspring who experience early parental death: early life conditions and later-life mortality.

    PubMed

    Smith, Ken R; Hanson, Heidi A; Norton, Maria C; Hollingshaus, Michael S; Mineau, Geraldine P

    2014-10-01

    We examine the influences of a set of early life conditions (ELCs) on all-cause and cause-specific mortality among elderly individuals, with special attention to one of the most dramatic early events in a child's, adolescent's, or even young adult's life, the death of a parent. The foremost question is, once controlling for prevailing (and potentially confounding) conditions early in life (family history of longevity, paternal characteristics (SES, age at time of birth, sibship size, and religious affiliation)), is a parental death associated with enduring mortality risks after age 65? The years following parental death may initiate new circumstances through which the adverse effects of paternal death operate. Here we consider the offspring's marital status (whether married; whether and when widowed), adult socioeconomic status, fertility, and later life health status. Adult health status is based on the Charlson Co-Morbidity Index, a construct that summarizes nearly all serious illnesses afflicting older individuals that relies on Medicare data. The data are based on linkages between the Utah Population Database and Medicare claims that hold medical diagnoses data. We show that offspring whose parents died when they were children, but especially when they were adolescents/young adults, have modest but significant mortality risks after age 65. What are striking are the weak mediating influences of later-life comorbidities, marital status, fertility and adult socioeconomic status since controls for these do little to alter the overall association. No beneficial effects of the surviving parent's remarriage were detected. Overall, we show the persistence of the effects of early life loss on later-life mortality and indicate the difficulties in addressing challenges at young ages. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Learning impaired children exhibit timing deficits and training-related improvements in auditory cortical responses to speech in noise.

    PubMed

    Warrier, Catherine M; Johnson, Krista L; Hayes, Erin A; Nicol, Trent; Kraus, Nina

    2004-08-01

    The physiological mechanisms that contribute to abnormal encoding of speech in children with learning problems are yet to be well understood. Furthermore, speech perception problems appear to be particularly exacerbated by background noise in this population. This study compared speech-evoked cortical responses recorded in a noisy background to those recorded in quiet in normal children (NL) and children with learning problems (LP). Timing differences between responses recorded in quiet and in background noise were assessed by cross-correlating the responses with each other. Overall response magnitude was measured with root-mean-square (RMS) amplitude. Cross-correlation scores indicated that 23% of LP children exhibited cortical neural timing abnormalities such that their neurophysiological representation of speech sounds became distorted in the presence of background noise. The latency of the N2 response in noise was isolated as being the root of this distortion. RMS amplitudes in these children did not differ from NL children, indicating that this result was not due to a difference in response magnitude. LP children who participated in a commercial auditory training program and exhibited improved cortical timing also showed improvements in phonological perception. Consequently, auditory pathway timing deficits can be objectively observed in LP children, and auditory training can diminish these deficits.

  9. Aging parents of adults with disabilities: the gratifications and frustrations of later-life caregiving.

    PubMed

    Greenberg, J S; Seltzer, M M; Greenley, J R

    1993-08-01

    Using a stress process model, we investigated the impact of later-life caregiving on 105 mothers of adult children with mental illness and 208 mothers of adult children with mental retardation. As hypothesized, mothers of persons with mental illness reported higher levels of frustrations and lower levels of gratifications. Whereas the adult child's behavior problems were the strongest predictor of maternal gratifications, the adult child's diagnosis was the strongest predictor of maternal frustrations once all other factors were controlled. In addition, the size of the mother's social network, the family social climate, and the child's participation in an out-of-home program were associated with the effect of caregiver stress.

  10. The Political Economy of Longevity: Developing New Forms of Solidarity for Later Life.

    PubMed

    Phillipson, Chris

    2015-01-01

    Aging populations now exert influence on all aspects of social life. This article examines changes to major social and economic institutions linked with old age, taking the period from the mid-20th century to the opening decades of the 21st century. These developments are set within the context of the influence of globalization as well as the impact of the 2008 financial crisis, these restructuring debates around the longevity revolution. The article examines how the basis for a new framework for accommodating longevity can be built, outlining ways of securing new forms of solidarity in later life.

  11. Effects of prenatal exposure to the Dutch famine on adult disease in later life: an overview.

    PubMed

    Roseboom, T J; van der Meulen, J H; Ravelli, A C; Osmond, C; Barker, D J; Bleker, O P

    2001-10-01

    People who were small at birth have been shown to have an increased risk of CHD and chronic bronchitis in later life. These findings have led to the fetal origins hypothesis that proposes that the fetus adapts to a limited supply of nutrients, and in doing so it permanently alters its physiology and metabolism, which could increase its risk of disease in later life. The Dutch famine--though a historical disaster--provides a unique opportunity to study effects of undernutrition during gestation in humans. People who had been exposed to famine in late or mid gestation had reduced glucose tolerance. Whereas people exposed to famine in early gestation had a more atherogenic lipid profile, somewhat higher fibrinogen concentrations and reduced plasma concentrations of factor VII, a higher BMI and they appeared to have a higher risk of CHD. Though the latter was based on small numbers, as could be expected from the relatively young age of the cohort. Nevertheless, this is the first evidence in humans that maternal undernutrition during gestation is linked with the risk of CHD in later life. Our findings broadly support the hypothesis that chronic diseases originate through adaptations made by the fetus in response to undernutrition. The long-term effects of intrauterine undernutrition, however, depend upon its timing during gestation and on the tissues and systems undergoing critical periods of development at that time. Furthermore, our findings suggest that maternal malnutrition during gestation may permanently affect adult health without affecting the size of the baby at birth. This gives the fetal origins hypothesis a new dimension. It may imply that adaptations that enable the fetus to continue to grow may nevertheless have adverse consequences for health in later life. CHD may be viewed as the price paid for successful adaptations to an adverse intra-uterine environment. It also implies that the long-term consequences of improved nutrition of pregnant women will be

  12. The Political Economy of Longevity: Developing New Forms of Solidarity for Later Life

    PubMed Central

    Phillipson, Chris

    2015-01-01

    Aging populations now exert influence on all aspects of social life. This article examines changes to major social and economic institutions linked with old age, taking the period from the mid-20th century to the opening decades of the 21st century. These developments are set within the context of the influence of globalization as well as the impact of the 2008 financial crisis, these restructuring debates around the longevity revolution. The article examines how the basis for a new framework for accommodating longevity can be built, outlining ways of securing new forms of solidarity in later life. PMID:25678722

  13. The effects of weight and physical activity change over 20 years on later-life objective and self-reported disability

    PubMed Central

    Williams, Emily D; Eastwood, Sophie V; Tillin, Therese; Hughes, Alun D; Chaturvedi, Nishi

    2014-01-01

    Background: Weight and health behaviours are known to affect physical disability; however the evidence exploring the impact of changes to these lifestyle factors over the life course on disability is inconsistent. We aimed to explore the roles of weight and activity change between mid and later life on physical disability. Methods: Baseline and 20-year clinical follow-up data were collected from1418 men and women, aged 58–88 years at follow-up, as part of a population-based observational study based in north-west London. At clinic, behavioural data were collected by questionnaire and anthropometry measured. Disability was assessed using a performance-based locomotor function test and self-reported questionnaires on functional limitation and basic activities of daily living (ADLs). Results: At follow-up, 39% experienced a locomotor dysfunction, 24% a functional limitation and 17% an impairment of ADLs. Weight gain of 10–20% or >20% of baseline, but not weight loss, were associated with increased odds of a functional limitation [odds ratio (OR) 1.69, 95% confidence interval (CI) 1.14-2.49 and OR 2.74, 1.55-4.83, respectively], after full adjustment for covariates. The same patterns were seen for the other disability outcomes. Increased physical activity reduced, and decreased physical activity enhanced the likelihood of disability, independent of baseline behaviours and adiposity. The adverse effects of weight gain appeared to be lessened in the presence of increased later-life physical activity. Conclusion: Weight and activity changes between mid and later life have strong implications for physical functioning in older groups. These findings reinforce the importance of the maintenance of healthy weight and behaviour throughout the life course, and the need to promote healthy lifestyles across population groups. PMID:24562419

  14. Impaired gamma-band activity during perceptual organization in adults with autism spectrum disorders: evidence for dysfunctional network activity in frontal-posterior cortices.

    PubMed

    Sun, Limin; Grützner, Christine; Bölte, Sven; Wibral, Michael; Tozman, Tahmine; Schlitt, Sabine; Poustka, Fritz; Singer, Wolf; Freitag, Christine M; Uhlhaas, Peter J

    2012-07-11

    Current theories of the pathophysiology of autism spectrum disorders (ASD) have focused on abnormal temporal coordination of neural activity in cortical circuits as a core impairment of the disorder. In the current study, we examined the possibility that gamma-band activity may be crucially involved in aberrant brain functioning in ASD. Magneto-encephalographic (MEG) data were recorded from 13 adult human participants with ASD and 16 controls during the presentation of Mooney faces. MEG data were analyzed in the 25-150 Hz frequency range and a beamforming approach was used to identify the sources of spectral power. Participants with ASD showed elevated reaction times and reduced detection rates during the perception of upright Mooney faces, while responses to inverted stimuli were in the normal range. Impaired perceptual organization in the ASD group was accompanied by a reduction in both the amplitude and phase locking of gamma-band activity. A beamforming approach identified distinct networks during perceptual organization in controls and participants with ASD. In controls, perceptual organization of Mooney faces involved increased 60-120 Hz activity in a frontoparietal network, while in the ASD group stronger activation was found in visual regions. These findings highlight the contribution of impaired gamma-band activity toward complex visual processing in ASD, suggesting atypical modulation of high-frequency power in frontoposterior networks.

  15. Subjective financial well-being, income and health inequalities in mid and later life in Britain.

    PubMed

    Arber, Sara; Fenn, Kirsty; Meadows, Robert

    2014-01-01

    The relationship between health and income is well established, but the link between subjective financial well-being and self-reported health has been relatively ignored. This study investigates the relationship between income, subjective financial well-being and health in mid-life and later life in Britain. Analysis of the General Household Survey for 2006 examined these relationships at ages 45-64 (n = 4639) and 65 and over (n = 3104). Logistic regression analysis was used to adjust for income and other socio-economic factors associated with self-reported health. Both income and subjective financial well-being are independently associated with health in mid-life; those with lower incomes and greater subjective financial difficulties had higher risk of reporting 'less than good' health. In contrast in later life, subjective financial well-being was associated with health, but the effect of income on health was mediated entirely through subjective financial well-being. The poorer health of the divorced/separated was also entirely mediated by differences in subjective financial well-being. Research on health inequalities should pay greater attention to the link between subjective financial hardship and ill-health, especially during periods of greater economic difficulties and financial austerity.

  16. Evidence for the intra-uterine programming of adiposity in later life

    PubMed Central

    Fall, Caroline HD

    2012-01-01

    Research in animals has shown that altering fetal nutrition by under-nourishing or over-nourishing the mother or rendering her diabetic, or fetal exposure to glucocorticoids and toxins, can programme obesity in later life. The increased adiposity is mediated by permanent changes in appetite, food choices, physical activity and energy metabolism. In humans, increased adiposity has been shown in people who experienced fetal under-nutrition due to maternal famine, or over-nutrition due to maternal diabetes. Lower birth weight (a proxy for fetal under-nutrition) is associated with a reduced adult lean mass and increased intra-abdominal fat. Higher birthweight caused by maternal diabetes is associated with increased total fat mass and obesity in later life. There is growing evidence that maternal obesity, without diabetes, is also a risk factor for obesity in the child, due to fetal over-nutrition effects. Maternal smoking is associated with an increased risk of obesity in the children, though a causal link has not been proven. Other fetal exposures associated with increased adiposity in animals include glucocorticoids and endocrine disruptors. Reversing the current obesity epidemic will require greater attention to, and better understanding of, these inter-generational (mother-offspring) factors that programme body composition during early development. PMID:21682572

  17. Forever productive: the discursive shaping of later life workers in contemporary Canadian newspapers.

    PubMed

    Rudman, Debbie Laliberte; Molke, Daniel

    2009-01-01

    Increasingly, ;productive aging' is promoted within government policies and reports in several Western nations, as well as those of international organizations. The ways in which ;productive aging' comes to be shaped within texts, that is, its discursive shaping, influences what aging individuals view as possible and ideal ways to be and do in later life, as well as what collectivities view as required services and programs to support such identities and occupations. Drawing on governmentality theory, in concert with occupational science, a critical discourse analysis of 72 Canadian newspaper articles pertaining to work and retirement published in 2006 was conducted to examine how 'productive aging' is shaped within such print media texts and the possibilities for identity and occupation promoted. This work critically analyzes ways 'later life workers' have come to be discursively shaped within neoliberal sociopolitical contexts, characterized by emphases on fostering individual responsibility, decreasing state dependency, and increasing privatization. The authors raises concerns related to occupational injustice, arguing for continuing vigilance regarding the ways 'productive aging' discourses might be drawn on to justify further state and workplace retreat from policies and programs that support those who face challenges to continued engagement in work or who cannot, or chose not to, be 'forever productive'.

  18. Living arrangements, social integration, and loneliness in later life: the case of physical disability.

    PubMed

    Russell, David

    2009-12-01

    Despite the theoretical linkages between household composition and social integration, relatively limited research has considered how living arrangements affect risk for loneliness in later life. Prior work has also failed to consider whether physical disability moderates this potentially important relationship. Using data from a sample of older adults with and without a physical disability (N = 868), this study aims to (1) document variations in loneliness across living arrangements, (2) assess whether any observed association varies by physical disability status, and (3) evaluate the mediating role of social integration and social support. Results reveal that those living alone or with people other than a spouse (children, extended family members) report greater loneliness than those living with a spouse. However the magnitude of these differences is greater for older adults with a physical disability. Measures of social integration and social support attenuated, but did not fully explain, inter-household variations in loneliness. These findings point to the independent significance of living arrangements for experiences of loneliness in later life among both disabled and nondisabled adults.

  19. Predictive timing functions of cortical beta oscillations are impaired in Parkinson's disease and influenced by L-DOPA and deep brain stimulation of the subthalamic nucleus

    PubMed Central

    Gulberti, A.; Moll, C.K.E.; Hamel, W.; Buhmann, C.; Koeppen, J.A.; Boelmans, K.; Zittel, S.; Gerloff, C.; Westphal, M.; Schneider, T.R.; Engel, A.K.

    2015-01-01

    Cortex-basal ganglia circuits participate in motor timing and temporal perception, and are important for the dynamic configuration of sensorimotor networks in response to exogenous demands. In Parkinson's disease (PD) patients, rhythmic auditory stimulation (RAS) induces motor performance benefits. Hitherto, little is known concerning contributions of the basal ganglia to sensory facilitation and cortical responses to RAS in PD. Therefore, we conducted an EEG study in 12 PD patients before and after surgery for subthalamic nucleus deep brain stimulation (STN-DBS) and in 12 age-matched controls. Here we investigated the effects of levodopa and STN-DBS on resting-state EEG and on the cortical-response profile to slow and fast RAS in a passive-listening paradigm focusing on beta-band oscillations, which are important for auditory–motor coupling. The beta-modulation profile to RAS in healthy participants was characterized by local peaks preceding and following auditory stimuli. In PD patients RAS failed to induce pre-stimulus beta increases. The absence of pre-stimulus beta-band modulation may contribute to impaired rhythm perception in PD. Moreover, post-stimulus beta-band responses were highly abnormal during fast RAS in PD patients. Treatment with levodopa and STN-DBS reinstated a post-stimulus beta-modulation profile similar to controls, while STN-DBS reduced beta-band power in the resting-state. The treatment-sensitivity of beta oscillations suggests that STN-DBS may specifically improve timekeeping functions of cortical beta oscillations during fast auditory pacing. PMID:26594626

  20. Altered intracellular distribution of PrPC and impairment of proteasome activity in tau overexpressing cortical neurons.

    PubMed

    Canu, Nadia; Filesi, Ilaria; Pristerà, Andrea; Ciotti, Maria Teresa; Biocca, Silvia

    2011-01-01

    The microtubule associated protein tau plays a crucial role in Alzheimer's disease and in many neurodegenerative disorders collectively known as tauopathies. Recently, tau pathology has been also documented in prion diseases although the possible molecular events linking these two proteins are still unknown. We have investigated the fate of normal cellular prion protein (PrP(C)) in primary cortical neurons overexpressing tau protein. We found that overexpression of tau reduces PrP(C) expression at the cell surface and causes its accumulation and aggregation in the cell body but does not affect its maturation and glycosylation. Trapped PrP(C) forms detergent-insoluble aggregates, mainly composed of un-glycosylated and mono-glycosylated forms of prion protein. Interestingly, co-transfection of tau gene in cortical neurons with a proteasome activity reporter, consisting of a short peptide degron fused to the carboxyl-terminus of green fluorescent protein (GFP-CL1), results in down-regulation of the proteasome system, suggesting a possible mechanism that contributes to intracellular PrP(C) accumulation. These findings open a new perspective for the possible crosstalk between tau and prion proteins in the pathogenesis of tau induced-neurodegeneration.

  1. Linking Microcircuit Dysfunction to Cognitive Impairment: Effects of Disinhibition Associated with Schizophrenia in a Cortical Working Memory Model

    PubMed Central

    Murray, John D.; Anticevic, Alan; Gancsos, Mark; Ichinose, Megan; Corlett, Philip R.; Krystal, John H.; Wang, Xiao-Jing

    2014-01-01

    Excitation–inhibition balance (E/I balance) is a fundamental property of cortical microcircuitry. Disruption of E/I balance in prefrontal cortex is hypothesized to underlie cognitive deficits observed in neuropsychiatric illnesses such as schizophrenia. To elucidate the link between these phenomena, we incorporated synaptic disinhibition, via N-methyl-D-aspartate receptor perturbation on interneurons, into a network model of spatial working memory (WM). At the neural level, disinhibition broadens the tuning of WM-related, stimulus-selective persistent activity patterns. The model predicts that this change at the neural level leads to 2 primary behavioral deficits: 1) increased behavioral variability that degrades the precision of stored information and 2) decreased ability to filter out distractors during WM maintenance. We specifically tested the main model prediction, broadened WM representation under disinhibition, using behavioral data from human subjects performing a spatial WM task combined with ketamine infusion, a pharmacological model of schizophrenia hypothesized to induce disinhibition. Ketamine increased errors in a pattern predicted by the model. Finally, as proof-of-principle, we demonstrate that WM deteriorations in the model can be ameliorated by compensations that restore E/I balance. Our findings identify specific ways by which cortical disinhibition affects WM, suggesting new experimental designs for probing the brain mechanisms of WM deficits in schizophrenia. PMID:23203979

  2. Linking microcircuit dysfunction to cognitive impairment: effects of disinhibition associated with schizophrenia in a cortical working memory model.

    PubMed

    Murray, John D; Anticevic, Alan; Gancsos, Mark; Ichinose, Megan; Corlett, Philip R; Krystal, John H; Wang, Xiao-Jing

    2014-04-01

    Excitation-inhibition balance (E/I balance) is a fundamental property of cortical microcircuitry. Disruption of E/I balance in prefrontal cortex is hypothesized to underlie cognitive deficits observed in neuropsychiatric illnesses such as schizophrenia. To elucidate the link between these phenomena, we incorporated synaptic disinhibition, via N-methyl-D-aspartate receptor perturbation on interneurons, into a network model of spatial working memory (WM). At the neural level, disinhibition broadens the tuning of WM-related, stimulus-selective persistent activity patterns. The model predicts that this change at the neural level leads to 2 primary behavioral deficits: 1) increased behavioral variability that degrades the precision of stored information and 2) decreased ability to filter out distractors during WM maintenance. We specifically tested the main model prediction, broadened WM representation under disinhibition, using behavioral data from human subjects performing a spatial WM task combined with ketamine infusion, a pharmacological model of schizophrenia hypothesized to induce disinhibition. Ketamine increased errors in a pattern predicted by the model. Finally, as proof-of-principle, we demonstrate that WM deteriorations in the model can be ameliorated by compensations that restore E/I balance. Our findings identify specific ways by which cortical disinhibition affects WM, suggesting new experimental designs for probing the brain mechanisms of WM deficits in schizophrenia.

  3. Repeated mild lateral fluid percussion brain injury in the rat causes cumulative long-term behavioral impairments, neuroinflammation, and cortical loss in an animal model of repeated concussion.

    PubMed

    Shultz, Sandy R; Bao, Feng; Omana, Vanessa; Chiu, Charlotte; Brown, Arthur; Cain, Donald Peter

    2012-01-20

    There is growing evidence that repeated brain concussion can result in cumulative and long-term behavioral symptoms, neuropathological changes, and neurodegeneration. Little is known about the factors and mechanisms that contribute to these effects. The current study addresses the need to investigate and better understand the effects of repeated concussion through the development of an animal model. Male Long-Evans rats received 1, 3, or 5 mild lateral fluid percussion injuries or sham injuries spaced 5 days apart. After the final injury, rats received either a short (24 h) or long (8 weeks) post-injury recovery period, followed by a detailed behavioral analysis consisting of tests for rodent anxiety-like behavior, cognition, social behavior, sensorimotor function, and depression-like behavior. Brains were examined immunohistochemically to assess neuroinflammation and cortical damage. Rats given 1, 3, or 5 mild percussion injuries displayed significant short-term cognitive impairments. Rats given repeated mild percussion injuries displayed significantly worse short- and long-term cognitive impairments. Rats given 5 mild percussion injuries also displayed increased anxiety- and depression-like behaviors. Neuropathological analysis revealed short-term neuroinflammation in 3-injury rats, and both short- and long-term neuroinflammation in 5-injury rats. There was also evidence that repeated injuries induced short- and long-term cortical damage. These cumulative and long-term changes are consistent with findings in human patients suffering repeated brain concussion, provide support for the use of repeated mild lateral fluid percussion injuries to study repeated concussion in the rat, and suggest that neuroinflammation may be important for understanding the cumulative and chronic effects of repeated concussion.

  4. Immature Cortical Responses to Auditory Stimuli in Specific Language Impairment: Evidence from ERPS to Rapid Tone Sequences

    ERIC Educational Resources Information Center

    Bishop, D. V. M.; McArthur, G. M.

    2004-01-01

    Event-related potentials (ERPs) to tone pairs and single tones were measured for 16 participants with specific language impairment (SLI) and 16 age-matched controls aged from 10 to 19 years. The tone pairs were separated by an inter-stimulus interval (ISI) of 20, 50 or 150 ms. The intraclass correlation (ICC) was computed for each participant…

  5. Immature Cortical Responses to Auditory Stimuli in Specific Language Impairment: Evidence from ERPS to Rapid Tone Sequences

    ERIC Educational Resources Information Center

    Bishop, D. V. M.; McArthur, G. M.

    2004-01-01

    Event-related potentials (ERPs) to tone pairs and single tones were measured for 16 participants with specific language impairment (SLI) and 16 age-matched controls aged from 10 to 19 years. The tone pairs were separated by an inter-stimulus interval (ISI) of 20, 50 or 150 ms. The intraclass correlation (ICC) was computed for each participant…

  6. Vascular cognitive impairment and dementia

    PubMed Central

    Gorelick, Philip B.; Counts, Scott E.; Nyenhuis, David

    2016-01-01

    Vascular contributions to cognitive impairment are receiving heightened attention as potentially modifiable factors for dementias of later life. These factors have now been linked not only to vascular cognitive disorders but also Alzheimer’s disease. In this chapter we review 3 related topics that address vascular contributions to cognitive impairment: 1. vascular pathogenesis and mechanisms; 2. neuropsychological and neuroimaging phenotypic manifestations of cerebrovascular disease; and 3. prospects for prevention of cognitive impairment of later life based on cardiovascular and stroke risk modification.1 PMID:26704177

  7. Permanent impairment of birth and survival of cortical and hippocampal proliferating cells following excessive drinking during alcohol dependence

    PubMed Central

    Richardson, Heather N.; Chan, Stephanie H.; Crawford, Elena F.; Lee, Youn Kyung; Funk, Cindy K.; Koob, George F.; Mandyam, Chitra D.

    2009-01-01

    Experimenter-delivered alcohol decreases adult hippocampal neurogenesis, and hippocampal-dependent learning and memory. The present study used clinically relevant rodent models of nondependent limited access alcohol self-administration and excessive drinking during alcohol dependence (alcohol self-administration followed by intermittent exposure to alcohol vapors over several weeks) to compare alcohol-induced effects on cortical gliogenesis and hippocampal neurogenesis. Alcohol dependence, but not nondependent drinking, reduced proliferation and survival in the medial prefrontal cortex (mPFC). Apoptosis was reduced in both alcohol groups within the mPFC, which may reflect an initiation of a reparative environment following alcohol exposure as decreased proliferation was abolished after prolonged dependence. Reduced proliferation, differentiation, and neurogenesis was observed in the hippocampus of both alcohol groups, and prolonged dependence worsened the effects. Increased hippocampal apoptosis and neuronal degeneration following alcohol exposure suggests a loss in neuronal turnover and indicates that the hippocampal neurogenic niche is highly vulnerable to alcohol. PMID:19501165

  8. White Matter Damage Impairs Adaptive Recovery More than Cortical Damage in an in silico Model of Activity-Dependent Plasticity

    PubMed Central

    Follett, Pamela L.; Roth, Cassandra; Follett, David; Dammann, Olaf

    2013-01-01

    Little is understood of how damaged white matter interacts with developmental plasticity. We propose that computational neuroscience methods are underutilized in this problem. In this paper we present a non-deterministic, in silico model of activity-dependent plasticity. Using this model we compared the impact of neuronal cell loss or axonal dysfunction on the ability of the system to generate, maintain, and recover synapses. The results suggest the axonal dysfunction seen in white matter injury is a greater burden to adaptive plasticity and recovery than is the neuronal loss of cortical injury. Better understanding of the interaction between features of preterm brain injury and developmental plasticity is an essential component for improving recovery. PMID:19745092

  9. Feelings of Hopelessness in Midlife and Cognitive Health in Later Life: A Prospective Population-Based Cohort Study

    PubMed Central

    Håkansson, Krister; Soininen, Hilkka; Winblad, Bengt; Kivipelto, Miia

    2015-01-01

    .37 (1.05–1.78) for Alzheimer’s disease. These associations remained significant also after the final adjustments for depressive feelings and for hopelessness at follow-up. The individual changes in hopelessness scores between midlife and follow-up were not systematically related to cognitive health at the follow-up. Conclusion Our results suggest that feelings of hopelessness already in midlife may have long-term implications for cognitive health and increase the risk of Alzheimer’s disease in later life. PMID:26460971

  10. The relative effects of shocks in early- and later-life conditions on mortality.

    PubMed

    Myrskylä, Mikko

    2010-01-01

    The relative importance of cohorts' early-life conditions, compared to later period conditions, on adult and old-age mortality is not known. This article studies how cohort-level mortality depends on shocks in cohorts' early- and later-life (period) conditions. I use cohorts' own mortality as a proxy for the early-life conditions, and define shocks as deviations from trend. Using historical data for five European Countries i find that shocks in early-life conditions are only weakly associated with cohorts' later mortality. This may be because individual-level health is robust to early-life conditions, or because at the cohort level scarring, selection, and immunity cancel each other. Shocks in period conditions, measured as deviations from trend in period child mortality, are strongly and positively correlated with mortality at all older ages. The results suggest that at the cohort level changing period conditions drive mortality variation and change.

  11. The reproduction of gender norms through downsizing in later life residential relocation.

    PubMed

    Addington, Aislinn; Ekerdt, David J

    2014-01-01

    Using data collected from qualitative interviews in 36 households, this article examines people's use of social relations based on gender to perform tasks associated with residential relocation in later life. Without prompting, our respondents addressed the social relations of gender in the meanings of things, in the persons of gift recipients, and in the persons of actors accomplishing the tasks. They matched gender-typed objects to same-sex recipients, reproducing circumstances of possession and passing on expectations for gender identity. The accounts of our respondents also depicted a gendered division of household labor between husbands and wives and a gendered division of care work by daughters and sons. These strategies economized a big task by shaping decisions about who should get what and who will do what. In turn, these practices affirmed the gendered nature of possession and care work into another generation.

  12. Education is associated with higher later life IQ scores, but not with faster cognitive processing speed.

    PubMed

    Ritchie, Stuart J; Bates, Timothy C; Der, Geoff; Starr, John M; Deary, Ian J

    2013-06-01

    Recent reports suggest a causal relationship between education and IQ, which has implications for cognitive development and aging-education may improve cognitive reserve. In two longitudinal cohorts, we tested the association between education and lifetime cognitive change. We then tested whether education is linked to improved scores on processing-speed variables such as reaction time, which are associated with both IQ and longevity. Controlling for childhood IQ score, we found that education was positively associated with IQ at ages 79 (Sample 1) and 70 (Sample 2), and more strongly for participants with lower initial IQ scores. Education, however, showed no significant association with processing speed, measured at ages 83 and 70. Increased education may enhance important later life cognitive capacities, but does not appear to improve more fundamental aspects of cognitive processing.

  13. Gaps in Social Support Resources in Later Life: An Adaptational Challenge in Need of Further Research.

    PubMed

    Rook, Karen S

    2009-02-01

    Gaps in social support resources in later life may arise when older adults lose social network members due to illness, death, or residential relocation. Gaps also may arise when social networks remain intact but are not well suited to meet older adults' intensifying support needs, such as needs for extended or highly personal instrumental support. Significant gaps in support resources are likely to require adaptive responses by older adults. This discussion highlights theoretical perspectives and illustrates empirical findings regarding the nature and effectiveness of older adults' responses to gaps in their social support resources. The literature examining these issues is relatively small and, as a result, is ripe for further development. Promising directions for future research are suggested.

  14. Complex Households and the Distribution of Multiple Resources in Later Life: Findings from A National Survey

    PubMed Central

    Kim, Juyeon; Link, Arts; Waite, Linda

    2016-01-01

    The availability of social and financial resources has profound implications for health and well-being in later life. Older adults often share resources with others who live with them, sometimes in households including relatives or friends. We examine differences in social support, social connections, money, and the household environment across types of living arrangements, develop hypotheses from two theoretical perspectives, one focusing on obligations toward kin, and one focused on social exchange within households, and test them using data from the National Social Life, Health, and Aging Project. We find that availability of resources is not consistently associated with the presence of grandchildren and other young relatives, but often differs with presence of other adults. These findings suggest that a single type of resource tells us little about the distribution of the resources of older adults, and call on us to examine multiple resources simultaneously. PMID:25904682

  15. Unpacking the Relation between Extraversion and Volunteering in Later Life: The Role of Social Capital

    PubMed Central

    Okun, Morris A.; Pugliese, John; Rook, Karen S.

    2009-01-01

    This study tested the hypothesis that the relation between extraversion and volunteering by older adults is fully mediated by social capital (participation in clubs and organizations, church attendance, and contact with friends). Data for this study come from 888 adults between the ages of 65–90 years old who participated in the Later Life Study of Social Exchanges (LLSSE). In support of our hypothesis, structural equation modeling revealed that extraversion exerted (a) a significant total effect on volunteering (.122), (b) significant indirect effects on volunteering via contact with friends (.042), church attendance (.034), and clubs and organizations (females only: .042), and (c) a non-significant direct effect on volunteering (.010). These findings suggest that social capital provides a viable explanation for the association between extraversion and volunteering. PMID:19710946

  16. [Setting the course early: relevance of childhood and adolescence for health in later life].

    PubMed

    Lampert, T

    2010-05-01

    The article examines the importance of childhood and adolescence for health in later life against the background of the population-aging process and the debate on the social challenges expected to result from this process. In this context, it describes the findings of life course epidemiology, which suggest (among other things) that there is a connection between early organic damage and the risk of illness in middle and old age, that risks and resources accumulate throughout a person's lifespan, and that living conditions and opportunities in life influence the development of health. The article also describes the health situation of children and adolescents based on the data available in Germany, in order to draw attention to existing problems and to identify possible ways of preventing them and taking action.

  17. Prayer, Attachment to God, and Changes in Psychological Well-Being in Later Life.

    PubMed

    Bradshaw, Matt; Kent, Blake Victor

    2017-01-01

    The aim of this study was to investigate the effects of prayer and attachment to God on psychological well-being (PWB) in later life. Using data from two waves of the nationwide Religion, Aging, and Health Survey, we estimate the associations between frequency of prayer and attachment to God at baseline with cross-wave changes in three measures of PWB: self-esteem, optimism, and life satisfaction. Prayer does not have a main effect on PWB. Secure attachment to God is associated with improvements in optimism but not self-esteem or life satisfaction. The relationship between prayer and PWB is moderated by attachment to God; prayer is associated with improvements in PWB among securely attached individuals but not those who are insecurely attached to God. These findings shed light on the complex relationship between prayer and PWB by showing that the effects of prayer are contingent upon one's perceived relationship with God.

  18. Life Course Trajectories of Later-Life Cognitive Functions: Does Social Engagement in Old Age Matter?

    PubMed

    Park, Sojung; Kwon, Eunsun; Lee, Hyunjoo

    2017-04-07

    This study identified differential patterns of later-life cognitive function trajectories and examined to what extent life course factors and social engagement are associated with group trajectories. Data came from seven waves of the Health and Retirement Study (HRS 1998-2010; n = 7374; Observations = 41,051). Latent class growth analysis identified cognitive function trajectory groups, and multinomial logistic regression was used to examine the factors associated with group trajectories. Five heterogeneous trajectories were identified: stable high, stable moderate, stable low, high-to-moderate, and moderate-to-low. Findings suggest that, after adjusting for life course factors, individuals who became volunteers were more likely to belong to one of the two least vulnerable trajectories, stable high or high-to-moderate. Our findings suggest that, despite the cumulative life course factors evident in cognitive decline, social engagement in old age may serve as a potential protective resource.

  19. Early Life Adversity as a Risk Factor for Fibromyalgia in Later Life

    PubMed Central

    Low, Lucie A.; Schweinhardt, Petra

    2012-01-01

    The impact of early life events is increasingly becoming apparent, as studies investigate how early childhood can shape long-term physiology and behaviour. Fibromyalgia (FM), which is characterised by increased pain sensitivity and a number of affective co-morbidities, has an unclear etiology. This paper discusses risk factors from early life that may increase the occurrence or severity of FM in later life: pain experience during neonatal life causes long-lasting changes in nociceptive circuitry and increases pain sensitivity in the older organism; premature birth and related stressor exposure cause lasting changes in stress responsivity; maternal deprivation affects anxiety-like behaviours that may be partially mediated by epigenetic modulation of the genome—all these adult phenotypes are strikingly similar to symptoms displayed by FM sufferers. In addition, childhood trauma and exposure to substances of abuse may cause lasting changes in developing neurotransmitter and endocrine circuits that are linked to anxiety and stress responses. PMID:22110940

  20. Impairments in brain-derived neurotrophic factor-induced glutamate release in cultured cortical neurons derived from rats with intrauterine growth retardation: possible involvement of suppression of TrkB/phospholipase C-γ activation.

    PubMed

    Numakawa, Tadahiro; Matsumoto, Tomoya; Ooshima, Yoshiko; Chiba, Shuichi; Furuta, Miyako; Izumi, Aiko; Ninomiya-Baba, Midori; Odaka, Haruki; Hashido, Kazuo; Adachi, Naoki; Kunugi, Hiroshi

    2014-04-01

    Low birth weight due to intrauterine growth retardation (IUGR) is suggested to be a risk factor for various psychiatric disorders such as schizophrenia. It has been reported that developmental cortical dysfunction and neurocognitive deficits are observed in individuals with IUGR, however, the underlying molecular mechanisms have yet to be elucidated. Brain-derived neurotrophic factor (BDNF) and its receptor TrkB are associated with schizophrenia and play a role in cortical development. We previously demonstrated that BDNF induced glutamate release through activation of the TrkB/phospholipase C-γ (PLC-γ) pathway in developing cultured cortical neurons, and that, using a rat model for IUGR caused by maternal administration of thromboxane A2, cortical levels of TrkB were significantly reduced in IUGR rats at birth. These studies prompted us to hypothesize that TrkB reduction in IUGR cortex led to impairment of BDNF-dependent glutamatergic neurotransmission. In the present study, we found that BDNF-induced glutamate release was strongly impaired in cultured IUGR cortical neurons where TrkB reduction was maintained. Impairment of BDNF-induced glutamate release in IUGR neurons was ameliorated by transfection of human TrkB (hTrkB). Although BDNF-stimulated phosphorylation of TrkB and of PLC-γ was decreased in IUGR neurons, the hTrkB transfection recovered the deficits in their phosphorylation. These results suggest that TrkB reduction causes impairment of BDNF-stimulated glutamatergic function via suppression of TrkB/PLC-γ activation in IUGR cortical neurons. Our findings provide molecular insights into how IUGR links to downregulation of BDNF function in the cortex, which might be involved in the development of IUGR-related diseases such as schizophrenia.

  1. Does food insufficiency in childhood contribute to dementia in later life?

    PubMed

    Momtaz, Yadollah Abolfathi; Haron, Sharifah Azizah; Hamid, Tengku Aizan; Ibrahim, Rahimah; Masud, Jariah

    2015-01-01

    Despite several studies attempting to identify the risk factors for dementia, little is known about the impact of childhood living conditions on cognitive function in later life. The present study aims to examine the unique contribution of food insufficiency in childhood to dementia in old age. Data for this study of 2,745 older Malaysians aged 60 years and older was obtained from a national survey entitled "Mental Health and Quality of Life of Older Malaysians" conducted from 2003 through 2005 using a cross-sectional design. The Geriatric Mental State-Automated Geriatric Examination for Computer Assisted Taxonomy was used to measure dementia. A multiple binary logistic regression using Statistical Package for Social Sciences version 21 was conducted to assess the unique effect of food insufficiency in childhood on developing dementia in old age. A notably higher prevalence of dementia was found in respondents who indicated they had experienced food insufficiency in childhood than in their food-sufficient counterparts (23.5% versus 14.3%). The findings from multiple logistic regression analysis revealed that food insufficiency in childhood would independently increase the risk of developing dementia in old age by 81%, after adjusting for sociodemographic factors (odds ratio =1.81, 95% confidence interval 1.13-2.92, P<0.01). Findings from the present study showing that food insufficiency in early life significantly contributes to dementia in later life highlight the importance of childhood living conditions in maintaining cognitive function in old age. It is, therefore, suggested that older adults with childhood food insufficiency might be targeted for programs designed to prevent dementia.

  2. Gender Transitions in Later Life: A Queer Perspective on Successful Aging

    PubMed Central

    Fabbre, Vanessa D.

    2015-01-01

    Purpose of the Study: Most understandings of successful aging are developed within a heteronormative cultural framework, leading to a dearth of theoretical and empirical scholarship relevant to lesbian, gay, bisexual, transgender, and queer (LGBTQ) older adults. This study explores the experiences of transgender persons who contemplate or pursue a gender transition in later life in order to develop culturally diverse conceptualizations of health and wellness in older age. Design and Methods: Using the extended case method, in-depth interviews were conducted with male-to-female-identified persons (N = 22) who have seriously contemplated or pursued a gender transition past the age of 50. In addition, 170hr of participant observation was carried out at 3 national transgender conferences generating ethnographic field notes on the topics of aging and gender transitions in later life. Results: Interpretive analyses suggest that many transgender older adults experience challenges to their gender identities that put their emotional and physical well-being at risk. Contemporary queer theory is used to understand these experiences and argue that greater attention to experiences of queer “failure” and negotiating “success on new terms” may be integral aspects of growth and development for transgender older adults. Implications: The Baby Boom generation is aging in a post-Stonewall, LGBTQ civil rights era, yet gerontology’s approach to gender and sexual identity has largely been formulated from a heteronormative perspective. A framework for understanding older transgender persons’ experiences informed by queer theory offers a new orientation for conceptualizing successful aging in the lives of marginalized gender and sexual minorities. PMID:25161264

  3. Work-related psychosocial stress and the risk of type 2 diabetes in later life.

    PubMed

    Pan, K-Y; Xu, W; Mangialasche, F; Fratiglioni, L; Wang, H-X

    2017-06-01

    Although work-related psychosocial stress and type 2 diabetes mellitus (T2DM) have been investigated, the association between lifelong work stress and T2DM in later life remains unclear. This study examined whether high work stress increased the risk of T2DM risk in later life, accounting also for other sources of stress outside work, such as burden from household chores. From the population-based prospective study SNAC-K, 2719 diabetes-free participants aged ≥60 years were identified and followed up for 6 years. T2DM was ascertained by glycated haemoglobin level, self-report, hypoglycaemic medication use and clinical records. Levels of job control and demands over the whole working life were assessed by a validated matrix. Household chores load was assessed by hours spent on such chores. Multivariate logistic regression models were used to estimate the association between job strain and T2DM. During the 6-year follow-up, 154 incident cases of T2DM were identified. High job strain was associated with T2DM occurrence amongst the 60-year-old cohort (OR = 3.14, 95% CI: 1.27-7.77), and only amongst women (OR = 6.18, 95% CI: 1.22-31.26), but not in men. When taking into account household chores load, a more pronounced risk of T2DM was associated with high job strain in combination with heavy household chores load in women aged 60 years at baseline (OR = 9.45, 95% CI: 1.17-76.53). Work-related psychosocial stress may increase the risk of T2DM only amongst women in their early 60s. The risk can be amplified by high household chores load. © 2017 The Association for the Publication of the Journal of Internal Medicine.

  4. Does food insufficiency in childhood contribute to dementia in later life?

    PubMed Central

    Momtaz, Yadollah Abolfathi; Haron, Sharifah Azizah; Hamid, Tengku Aizan; Ibrahim, Rahimah; Masud, Jariah

    2015-01-01

    Background Despite several studies attempting to identify the risk factors for dementia, little is known about the impact of childhood living conditions on cognitive function in later life. The present study aims to examine the unique contribution of food insufficiency in childhood to dementia in old age. Methods Data for this study of 2,745 older Malaysians aged 60 years and older was obtained from a national survey entitled “Mental Health and Quality of Life of Older Malaysians” conducted from 2003 through 2005 using a cross-sectional design. The Geriatric Mental State-Automated Geriatric Examination for Computer Assisted Taxonomy was used to measure dementia. A multiple binary logistic regression using Statistical Package for Social Sciences version 21 was conducted to assess the unique effect of food insufficiency in childhood on developing dementia in old age. Results A notably higher prevalence of dementia was found in respondents who indicated they had experienced food insufficiency in childhood than in their food-sufficient counterparts (23.5% versus 14.3%). The findings from multiple logistic regression analysis revealed that food insufficiency in childhood would independently increase the risk of developing dementia in old age by 81%, after adjusting for sociodemographic factors (odds ratio =1.81, 95% confidence interval 1.13–2.92, P<0.01). Conclusion Findings from the present study showing that food insufficiency in early life significantly contributes to dementia in later life highlight the importance of childhood living conditions in maintaining cognitive function in old age. It is, therefore, suggested that older adults with childhood food insufficiency might be targeted for programs designed to prevent dementia. PMID:25565786

  5. Diet and cognitive function in later life: a challenge for nutrition epidemiology.

    PubMed

    McNeill, G; Winter, J; Jia, X

    2009-02-01

    As the proportion of old and very old people in the population increases, new research on the influence of diet on health and nutritional needs in later life will be needed. Dietary assessment methods that rely on short-term memory or lengthy interviews, such as the 24-h recall and diet history methods, could have some limitations in this age group. There is some support for the use of food frequency questionnaires (FFQs) in older people, although their validity in the older old and in those with more advanced cognitive decline has not been extensively assessed. In a study designed to assess the validity of a modified FFQ in men and women over 65 years, 50 men and 47 women completed two FFQs, and 42 men and 41 women completed one FFQ followed by a 4-day weighed diet diary. Digit span forward (a test of short-term memory) and verbal fluency (a test of executive function) tests were used to assess the possible influence of cognitive function on repeatability and validity of the FFQ. The FFQ was found to have good repeatability for most nutrients and reasonable validity for some but not all nutrients. Cognitive function assessed prior to the dietary assessment showed no relationship with repeatability, but there was some evidence that validity was lower in those with lower executive function. Dietary assessment in healthy older people without overt cognitive decline can be achieved, but development and testing of methods of data collection for each target population and nutrient of interest are particularly important in this age group to ensure valid results. The possibility that cognitive decline influences dietary assessment needs to be borne in mind in the interpretation of observational studies of the influence of dietary intake on cognition in later life.

  6. How important is sex in later life? The views of older people.

    PubMed

    Gott, Merryn; Hinchliff, Sharron

    2003-04-01

    Stereotypes of an asexual old age remain pervasive, shaping not only popular images of older people, but also research and policy agendas. However, older people's own attitudes towards the role and value of sex in later life remain relatively unexplored. This paper draws on both quantitative and qualitative data to examine how sex is prioritised in middle age and later life. Data collection methods involved completion of two quality of life measures (WHOQOL-100 and WHOQOL Importance Scale), followed by semi-structured interviews. In total the sample comprised 69 individuals recruited from the age/sex register of a general practice in Sheffield in the UK. This paper will focus upon the accounts of 21 men and 23 women aged 50-92 years. Ratings of the importance of sex to participants were gathered from the WHOQOL Importance Scale; the in-depth interviews enabled the basis for this prioritisation to be explored. Analysis identified the following key themes. Participants who did not consider sex to be of any importance to them neither had a current sexual partner, nor felt that they would have another sexual partner in their lifetime. Indeed, all participants who had a current sexual partner attributed at least some importance to sex, with many rating sex as 'very' or 'extremely' important. However, experiencing barriers to being sexually active led them to place less importance on sex; this was particularly apparent when health problems and widowhood were experienced. Age was seen as facilitating coping when sex became less frequent, or stopped altogether. This was explained in terms of sexual desire decreasing with age (for some male participants), the cessation of sex being easier to cope with in a relationship of long duration and the expectation that sex will become less possible with 'normal ageing'. The discussion considers the implications of these findings for this developing field.

  7. Quetiapine attenuates cognitive impairment and decreases seizure susceptibility possibly through promoting myelin development in a rat model of malformations of cortical development.

    PubMed

    Ma, Lei; Yang, Feng; Zhao, Rui; Li, Li; Kang, Xiaogang; Xiao, Lan; Jiang, Wen

    2015-10-05

    Developmental delay, cognitive impairment, and refractory epilepsy are the most frequent consequences found in patients suffering from malformations of cortical development (MCD). However, therapeutic options for these psychiatric and neurological comorbidities are currently limited. The development of white matter undergoes dramatic changes during postnatal brain maturation, thus myelination deficits resulting from MCD contribute to its comorbid diseases. Consequently, drugs specifically targeting white matter are a promising therapeutic option for the treatment of MCD. We have used an in utero irradiation rat model of MCD to investigate the effects of postnatal quetiapine treatment on brain myelination as well as neuropsychological and cognitive performances and seizure susceptibility. Fatally irradiated rats were treated with quetiapine (10mg/kg, i.p.) or saline once daily from postnatal day 0 (P0) to P30. We found that postnatal administration of quetiapine attenuated object recognition memory impairment and improved long-term spatial memory in the irradiated rats. Quetiapine treatment also reduced the susceptibility and severity of pentylenetetrazol-induced seizures. Importantly, quetiapine treatment resulted in an inhibition of irradiation-induced myelin breakdown in the cerebral cortex and corpus callosum. These findings suggest that quetiapine may have beneficial, postnatal effects in the irradiated rats, strongly suggesting that improving MCD-derived white matter pathology is a possible underlying mechanism. Collectively, these results indicate that brain myelination represents an encouraging pharmacological target to improve the prognosis of patients with MCD.

  8. Social capital dynamics and health in mid to later life: findings from Australia.

    PubMed

    Yiengprugsawan, Vasoontara; Welsh, Jennifer; Kendig, Hal

    2017-07-26

    The influence of social capital has been shown to improve health and wellbeing. This study investigates the relationship between changes in social capital and health outcomes during a 6-year follow-up in mid to later life in Australia. Nationally representative data from the Household, Income and Labour Dynamics in Australia (HILDA) survey included participants aged 45 years and over who responded in 2006, 2010 and 2012 (N = 3606). Each of the three components of social capital (connectedness, trust and participation) was measured in Waves 2006 and 2010 and categorised as: 'never low', 'transitioned to low', 'transitioned out of low' and 'consistently low'. Health outcomes in 2012 included self-rated overall health, physical functioning, and mental health based on the Short Form 36-item health survey (SF-36). Multivariable logistic regression assessed changes in social capital (measured in 2006 and 2010) predicted poor health (measured in 2012), adjusting for covariates. Consistently low trust was significantly associated with higher odds of transitions into poor physical functioning (AOR 1.54; 95% Confidence Interval 1.06-1.22), poor mental health (AOR 1.59; 95% CI 1.08-2.36) and poor self-rated health (AOR 1.86; 95% CI 1.27-2.72). Transition into low trust was also a predictor of poor self-rated health after adjusting for covariates (AOR 1.74; 95% CI 1.11-2.73). Changes in social connectedness in both directions (transitioned out of and into low) were statistically associated with poor self-rated health (AORs 1.40; 95% CI 1.00-1.97 and 1.61; 95% CI 1.11-2.34, respectively) after adjusting for confounders as well as other social capital components. Our longitudinal findings reveal social capital dynamics and effects on health in mid to later life. Social trust and connectedness could be important enablers for older persons to be more active in the community and potentially benefit their health and wellbeing over time.

  9. Childhood abuse affects emotional closeness with family in mid- and later life.

    PubMed

    Savla, J Tina; Roberto, Karen A; Jaramillo-Sierra, Ana L; Gambrel, Laura Eubanks; Karimi, Hassan; Butner, L Michelle

    2013-06-01

    Knowledge about the effects of early life adversity on kin relationships in later years is sparse. The purpose of this study was to examine if childhood abuse and adversity negatively influences emotional closeness with family in mid- and later life. A second goal was to determine the role of psychosocial resources and personality traits in buffering the effects of early adversities. Gender and cohort differences were explored to see if men were differentially affected than women and whether middle-aged adults (35-49 years old) were differentially affected than older adults (50-74 years old) by the effects of childhood abuse and adversity. Using retrospective accounts of early family abuse and adversities of 1,266 middle aged adults and 1,219 older adults from a large population-based survey, the National Survey of Midlife Development in United States (MIDUS), separate multiple regression analyses were conducted for the two cohorts to examine the effects of childhood emotional and physical abuse and family adversities on perceived emotional closeness with family. Interaction effects between childhood abuse and adversity (e.g., being expelled from school, death of sibling, parental divorce, losing a home to a natural disaster) with psychosocial resources (perceived control and self acceptance), personality characteristics (extraversion and neuroticism), and gender were examined. Results of OLS regressions suggest emotional and physical abuse predicted family closeness in middle-aged adults. Conversely, only emotional abuse predicted family closeness in older adults. Moderation models revealed that high levels of self acceptance were associated with better maintenance of emotional closeness among middle-aged adults who were emotionally and physically abused as children. Older adults with lower extraversion who experienced emotional abuse or reported greater number of adversities in childhood were found to be at higher risk for lower emotional closeness with family

  10. Gender differences in the relation between depression and social support in later life.

    PubMed

    Sonnenberg, C M; Deeg, D J H; van Tilburg, T G; Vink, D; Stek, M L; Beekman, A T F

    2013-01-01

    Prevalence of depression is twice as high in women as in men, also in older adults. Lack of social support is a risk factor for late-life depression. The relation between depression and social support may be different for men and women. Data from the Longitudinal Aging Study Amsterdam were used to investigate gender differences in the relation between social support and depression in a population-based sample aged 55-85 years, with n = 2,823 at baseline and using the 13-year follow-up data on onset of depression. Respondents without a partner in the household, with a small network, and with low emotional support were more often depressed, with men showing higher rates of depression than women. A high need for affiliation was associated with depression in women but not in men. Lack of a partner in the household and having a small network predicted onset of depression in men but not in women. In respondents with high affiliation need and low social support, depression rates were higher, with men being more often depressed than women. Low social support and a high need for affiliation were related to depression in later life, with men being more vulnerable for depression than women. Considering the serious consequences of depression, especially in older people, it is important to identify the persons with low social support and a high need for affiliation, and to help them to increase their social support or to adjust their needs.

  11. A Global View on the Effects of Work on Health in Later Life.

    PubMed

    Staudinger, Ursula M; Finkelstein, Ruth; Calvo, Esteban; Sivaramakrishnan, Kavita

    2016-04-01

    Work is an important environment shaping the aging processes during the adult years. Therefore, the cumulative and acute effects of work characteristics on late-life health deserve great attention. Given that population aging has become a global trend with ensuing changes in labor markets around the world, increased attention is paid to investigating the effects of the timing of retirement around the world and the macroeconomic benefits often associated with delaying retirement. It will be essential for societies with aging populations to maintain productivity given an aging workforce and for individuals it will be crucial to add healthy and meaningful years rather than just years to their lives. We first describe the available evidence about participation of older workers (65+) in the labor force in high, middle, and low-income countries. Second, we discuss the individual-level and societal influences that might govern labor-force participation of older adults. Thirdly, we review evidence on the association between work on the one and physical, mental, and cognitive health in later life on the other. Globally, both is true: work supports healthy aging and jeopordizes it. We draw implications for policymaking in terms of social protection, HR policies, and older employee employability. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. Refashioning One’s Place in Time: Stories of Household Downsizing in Later Life

    PubMed Central

    Luborsky, Mark R.; Lysack, Catherine L.; Van Nuil, Jennifer

    2011-01-01

    Older adults face a daunting task: while continuing engagements in multiple relationships, investment in their own and others’ futures, and developing life interests and capacities, they also reexamine and sometimes reconfigure the place where their social lives and objects are housed. Some relocate, downsize, to a new smaller place and reducing possessions to ensure an environment supportive of their capacities and desired daily activities. This article examines how key contours of the experiences of place during residential downsizing are infused with unexpectedly heightened awareness and cultivation of one’s sense of place in multiple timeframes. In a discovery mode, the downsizing stories of 40 older adults in southeast Michigan are examined. Findings indicate conflicting temporalities and the natures of cognitions related to decision-making and thinking about being leave-taking and being in place. Findings also highlight in particular how making sense of one’s place is predicated on notions of its time, of being on time and downsizing on time. Further, these characterizations of the lived worlds of older adults’ modes of conceptualizing the nature of downsizing show how an understanding of the meaningfulness of place in later life relocations requires a layered sense of home as places-in multiple timelines. PMID:21765597

  13. Refashioning One's Place in Time: Stories of Household Downsizing in Later Life.

    PubMed

    Luborsky, Mark R; Lysack, Catherine L; Van Nuil, Jennifer

    2011-08-01

    Older adults face a daunting task: while continuing engagements in multiple relationships, investment in their own and others' futures, and developing life interests and capacities, they also reexamine and sometimes reconfigure the place where their social lives and objects are housed. Some relocate, downsize, to a new smaller place and reducing possessions to ensure an environment supportive of their capacities and desired daily activities. This article examines how key contours of the experiences of place during residential downsizing are infused with unexpectedly heightened awareness and cultivation of one's sense of place in multiple timeframes. In a discovery mode, the downsizing stories of 40 older adults in southeast Michigan are examined. Findings indicate conflicting temporalities and the natures of cognitions related to decision-making and thinking about being leave-taking and being in place. Findings also highlight in particular how making sense of one's place is predicated on notions of its time, of being on time and downsizing on time. Further, these characterizations of the lived worlds of older adults' modes of conceptualizing the nature of downsizing show how an understanding of the meaningfulness of place in later life relocations requires a layered sense of home as places-in multiple timelines.

  14. Negotiating a moral identity in the context of later life care.

    PubMed

    Breheny, Mary; Stephens, Christine

    2012-12-01

    Strategies to maintain independence for older people have received considerable attention as a social policy solution to the financial and social impact of the ageing population. Critical scholars in gerontology have also highlighted the negative consequences of promoting independence in this way. Understandings of independence have profound implications for caring relationships as people age. To investigate the ways that older people talk about caring we interviewed 48 people aged 55-70 years. A discourse analysis of these data showed that a dominant discourse of 'independence' was drawn upon to value self-sufficiency and construct dependence on others as burdensome. This construction of care provides a comfortable position for those who can afford to purchase professional care; however, those without resources are unable to accept unpaid help without also accepting a position of dependency. An alternative discourse of 'being there' constructs having others to provide personal care as a virtue and obligations to provide such care as based on family duty and affection. This discourse emphasises connections between people and a moral obligation to care which also creates difficulties for those with fewer material resources. The position for a dependent older subject in these two discourses may seem incompatible but can be reconciled by reframing independence as autonomy. Autonomy for those requiring care alongside a wider recognition of caring as the responsibility of all members of the community rather than with individual family members would support a flexible approach to later life care arrangements. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Later Life Learners: A Significant and Receptive Audience for Introductory Astronomy

    NASA Astrophysics Data System (ADS)

    Percy, J. R.; Krstovic, M.

    2001-05-01

    ``Later life learners" (LLL: generally age 65 or older) are a subset of ``life long learners"; both form a large, influential, and receptive audience for courses in introductory astronomy. This year alone, one of us (JRP) has taught two LLL courses of almost 200 ``students" each. In previous years, he has taught several other such courses (as well as courses for life long learners in general). Each course has its own personality, but the students all tend to be interested and highly interactive, bringing a wealth of life experience to the course. They are also influential in that the students provide a strong link with the community, and they tend to have a very positive and supportive attitude to scholarship and research, and to colleges and universities. Yet these courses are rather neglected in terms of educational research, and resources such as textbooks. In this paper, we discuss the nature of LLL courses, and the motivations for teaching them. We present anecdotal comments on the nature of the learners, and results based on questionnaires about their interests and their reactions to the courses. We encourage other astronomy educators to make contact with LLL groups in their community, with a view to offering a course. Thanks to the Ontario Work-Study Program for supporting this project.

  16. Patterns of intimate partner homicide suicide in later life: Strategies for prevention

    PubMed Central

    Salari, Sonia

    2007-01-01

    Intimate partner homicide suicide (IPHS) constitutes the most violent domestic abuse outcome, devastating individuals, families, neighborhoods and communities. This research used content analysis to analyze 225 murder suicide events (444 deaths) among dyads with at least one member 60 or older. Data were collected from newspaper articles, television news transcripts, police reports and obituaries published between 1999 and 2005. Findings suggest the most dangerous setting was the home and the majority of perpetrators were men. Firearms were most often employed in the violence. Relationship strife was present in some cases, but only slightly higher than the divorce rate for that age group. Illness was cited in just over half of the cases, but 30% of sick elderly couples had only a perpetrator who was ill. Evidence of suicide pacts and mercy killings were very rare and practitioners are encouraged to properly investigate these events. Suicidal men in this age range must be recognized as a potential threat to others, primarily their partner. Homicide was sometimes the primary motive, and the perpetrators in those cases resembled the “intimate terrorist.” Victims in those cases were often terrorized before the murder. Clinicians are educated about the patterns of fatal violence in later life dyads and provided with strategies for prevention. PMID:18044194

  17. Fear of falling from a daily life perspective; narratives from later life.

    PubMed

    Mahler, Marianne; Sarvimäki, Anneli

    2012-03-01

    Fear of falling is a well-known condition in later life. The aim of this study was to illuminate the experiences and the meaning of fear of falling in a daily-life context. The method used was a qualitative study inspired by interpretive phenomenology. In narrative interviews, five community-dwelling women over 80 years of age told about their fear of falling from a daily-life perspective. The overall thematic analysis resulted in three main themes: the meaning of managing daily life necessities; keeping in contact with the outside; living with fear. The findings showed that to live with fear of falling was to discipline daily life, and to learn to live with the challenge of a vulnerable bodily condition and of losing control at different levels: from falling, from incontinence, from dirt and from the stigma of being in a humiliating situation. The women created a perception of independence while they were dependent on help and community care and on news from the outside. At an existential level, they coped with their fear by strengthening their will. The conclusion was that the older women studied accepted the condition of fear of falling. They shared the ability to cope in various ways with the limitations of their bodily capacity and their imbalance. © 2011 The Authors. Scandinavian Journal of Caring Sciences © 2011 Nordic College of Caring Science.

  18. The interaction of family background and personal education on depressive symptoms in later life.

    PubMed

    Schaan, Barbara

    2014-02-01

    This study assesses the interaction between personal education and family background during childhood on depressive symptoms in later life by applying Ross & Mirowsky's resource substitution and structural amplification theory of health and education. OLS regression models are estimated using data from the "Survey of Health, Ageing and Retirement in Europe" (SHARE), which covers information on current social and health status as well as retrospective life histories from 20,716 respondents aged 50 or older from thirteen European countries. Higher education helps to overcome the negative consequences of a poor family background. Since people from poor families are less likely to attain higher educational levels, they lack exactly the resource they need in order to overcome the negative consequences their non-prosperous background has on depressive symptoms. Thus, low family background and low personal education amplify each other. Examining the processes described by theory of resource substitution and structural amplification over different age groups from midlife to old-age suggests that the moderating effect of education remains constant over age among people coming from a poor family background. However, there is some evidence for a decrease with age in the buffering effect of a well-off family background on depressive symptoms among the low educated group. Furthermore, the educational gap in depression diverges with age among individuals originating from a well-off family background. Taken together the results cautiously allude to the conclusion that three processes - cumulative (dis-)advantage, age-as-leveler, and persistent inequalities - might take place.

  19. Patterns of intimate partner homicide suicide in later life: strategies for prevention.

    PubMed

    Salari, Sonia

    2007-01-01

    Intimate partner homicide suicide (IPHS) constitutes the most violent domestic abuse outcome, devastating individuals, families, neighborhoods and communities. This research used content analysis to analyze 225 murder suicide events (444 deaths) among dyads with at least one member 60 or older. Data were collected from newspaper articles, television news transcripts, police reports and obituaries published between 1999 and 2005. Findings suggest the most dangerous setting was the home and the majority of perpetrators were men. Firearms were most often employed in the violence. Relationship strife was present in some cases, but only slightly higher than the divorce rate for that age group. Illness was cited in just over half of the cases, but 30% of sick elderly couples had only a perpetrator who was ill. Evidence of suicide pacts and mercy killings were very rare and practitioners are encouraged to properly investigate these events. Suicidal men in this age range must be recognized as a potential threat to others, primarily their partner. Homicide was sometimes the primary motive, and the perpetrators in those cases resembled the "intimate terrorist." Victims in those cases were often terrorized before the murder. Clinicians are educated about the patterns of fatal violence in later life dyads and provided with strategies for prevention.

  20. Validation of the Cognitive Assessment of Later Life Status (CALLS) instrument: a computerized telephonic measure

    PubMed Central

    Crooks, Valerie C; Parsons, Thomas D; Buckwalter, J Galen

    2007-01-01

    Background Brief screening tests have been developed to measure cognitive performance and dementia, yet they measure limited cognitive domains and often lack construct validity. Neuropsychological assessments, while comprehensive, are too costly and time-consuming for epidemiological studies. This study's aim was to develop a psychometrically valid telephone administered test of cognitive function in aging. Methods Using a sequential hierarchical strategy, each stage of test development did not proceed until specified criteria were met. The 30 minute Cognitive Assessment of Later Life Status (CALLS) measure and a 2.5 hour in-person neuropsychological assessment were conducted with a randomly selected sample of 211 participants 65 years and older that included equivalent distributions of men and women from ethnically diverse populations. Results Overall Cronbach's coefficient alpha for the CALLS test was 0.81. A principal component analysis of the CALLS tests yielded five components. The CALLS total score was significantly correlated with four neuropsychological assessment components. Older age and having a high school education or less was significantly correlated with lower CALLS total scores. Females scored better overall than males. There were no score differences based on race. Conclusion The CALLS test is a valid measure that provides a unique opportunity to reliably and efficiently study cognitive function in large populations. PMID:17517137

  1. Ethnic inequalities in limiting health and self-reported health in later life revisited

    PubMed Central

    Evandrou, Maria; Falkingham, Jane; Feng, Zhixin; Vlachantoni, Athina

    2016-01-01

    Background It is well established that there are ethnic inequalities in health in the UK; however, such inequalities in later life remain a relatively under-researched area. This paper explores ethnic inequalities in health among older people in the UK, controlling for social and economic disadvantages. Methods This paper analyses the first wave (2009–2011) of Understanding Society to examine differentials in the health of older persons aged 60 years and over. 2 health outcomes are explored: the extent to which one's health limits the ability to undertake typical activities and self-rated health. Logistic regression models are used to control for a range of other factors, including income and deprivation. Results After controlling for social and economic disadvantage, black and minority ethnic (BME) elders are still more likely than white British elders to report limiting health and poor self-rated health. The ‘health disadvantage’ appears most marked among BME elders of South Asian origin, with Pakistani elders exhibiting the poorest health outcomes. Length of time resident in the UK does not have a direct impact on health in models for both genders, but is marginally significant for women. Conclusions Older people from ethnic minorities report poorer health outcomes even after controlling for social and economic disadvantages. This result reflects the complexity of health inequalities among different ethnic groups in the UK, and the need to develop health policies which take into account differences in social and economic resources between different ethnic groups. PMID:26787199

  2. Happy Marriage, Happy Life? Marital Quality and Subjective Well-Being in Later Life

    PubMed Central

    Carr, Deborah; Freedman, Vicki A.; Cornman, Jennifer C.; Schwarz, Norbert

    2014-01-01

    The authors examined associations between marital quality and both general life satisfaction and experienced (momentary) well-being among older husbands and wives, the relative importance of own versus spouse’s marital appraisals for well-being, and the extent to which the association between own marital appraisals and well-being is moderated by spouse’s appraisals. Data are from the 2009 Disability and Use of Time daily diary supplement to the Panel Study of Income Dynamics (N = 722). One’s own marital satisfaction is a sizable and significant correlate of life satisfaction and momentary happiness; associations do not differ significantly by gender. The authors did not find a significant association between spouse’s marital appraisals and own well-being. However, the association between husband’s marital quality and life satisfaction is buoyed when his wife also reports a happy marriage, yet flattened when his wife reports low marital quality. Implications for understanding marital dynamics and well-being in later life are discussed. PMID:25221351

  3. Capturing transitions and trajectories: the role of socioeconomic status in later life disability.

    PubMed

    Taylor, Miles G

    2010-11-01

    Disability is conceptualized as a life course process and measured using either transitions or trajectories. Previous research does not simultaneously explore both aspects of disablement, accounting for timing and trajectory. The role of education is noted in disability research, but its independent effects over time have not been fully examined. I investigate the effects of education and income on disability onset and progression over a decade. I use a latent curve modeling approach with four waves of the Duke Established Populations for Epidemiologic Studies of the Elderly data to independently test the preventive and mediating effects education and income provide for disability. Education has a preventive effect for disability onset but no significant effect on progression once income is held constant. Income has both a preventive and mediating effect on disability, although preventive effects are stronger for education. Later life disability is measured here using both onset and trajectory. Findings are consistent with health research suggesting that education and income work through shared and independent mechanisms to affect disability over time. These findings also highlight the importance of modeling timing when studying health trajectories.

  4. Low Birth Weight and Risk of Later-Life Physical Disability in Women.

    PubMed

    Spracklen, Cassandra N; Ryckman, Kelli K; Robinson, Jennifer G; Stefanick, Marcia L; Sarto, Gloria E; Anton, Stephen D; Wallace, Robert B

    2017-04-01

    There is strong evidence that low and high birth weight due to in-utero programming results in elevated risk for adult diseases, though less research has been performed examining the influence of birth weight and physical disability later in life. Baseline data from 76,055 postmenopausal women in the Women's Health Initiative, a large multi-ethnic cohort, were used to examine the association between self-reported birth weight category (<6 lbs, 6-7 lbs 15 oz, 8-9 lbs 15 oz, and ≥10 lbs) and the self-reported physical functioning score on the RAND 36-item Health Survey. Linear regression models were adjusted for age, education, race/ethnicity, body mass index, and a comorbidity score. Unadjusted models indicate that women born in the lowest and highest birth weight categories have significantly lower physical functioning scores as compared to women born in the normal weight category (β = -2.22, p < .0001 and β = -3.56, p < .0001, respectively). After adjustments, the relationship between the lowest birth weight category and physical functioning score remained significant (β = -1.52, p < .0001); however, the association with the highest birth weight category dissipated. Preconception and prenatal interventions aimed at reducing the incidence of low birth weight infants may subsequently reduce the burden of later-life physical disability.

  5. Subjective Age and Health in Later Life: The Role of Posttraumatic Symptoms.

    PubMed

    Avidor, Sharon; Benyamini, Yael; Solomon, Zahava

    2016-05-01

    We examined: (a) long-term effects of war-related trauma and captivity on posttraumatic stress symptoms (PTSS), physical health, and subjective age; and (b) the moderation effect of PTSS and health on subjective age among ex-prisoners of war (ex-POWs) and war veterans. Israeli veterans of the 1973 Yom Kippur War (mean age 57 years), including 111 ex-POWs and 167 matched veterans were assessed for subjective age, war-related PTSS, and health-related measures (physical symptoms, somatization, health-risk behaviors, and self-rated health). Controlling for age, ex-POWs endorsed higher subjective age than controls, and ex-POWs with posttraumatic stress disorder (PTSD) endorsed higher subjective age than ex-POWs and controls without PTSD. PTSS and health measures besides health-risk behaviors predicted subjective age. Significant interactions were found between PTSS and each health measure, suggesting that health only predicts subjective age for those reporting high PTSS. PTSS appear to be implicated in the link between health measures and subjective age in later life, pointing to the long-term effect of captivity and war-induced traumatic distress on aging. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. What contributes to perceived stress in later life? A recursive partitioning approach

    PubMed Central

    Scott, Stacey B.; Jackson, Brenda R.; Bergeman, C. S.

    2011-01-01

    One possible explanation for the individual differences in outcomes of stress is the diversity of inputs that produce perceptions of being stressed. The current study examines how combinations of contextual features (e.g., social isolation, neighborhood quality, health problems, age discrimination, financial concerns, and recent life events) of later life contribute to overall feelings of stress. Recursive partitioning techniques (regression trees and random forests) were used to examine unique interrelations between predictors of perceived stress in a sample of 282 community-dwelling adults. Trees provided possible examples of equifinality (i.e., subsets of people with similar levels of perceived stress but different predictors) as well as for the identification both of contextual combinations that separated participants with very high and very low perceived stress. Random forest analyses aggregated across many trees based on permuted versions of the data and predictors; loneliness, financial strain, neighborhood strain, ageism, and to some extent life events emerged as important predictors. Interviews with a subsample of participants provided both thick description of the complex relationships identified in the trees, as well as additional risks not appearing in the survey results. Together, the analyses highlight what may be missed when stress is used as a simple unidimensional construct and can guide differential intervention efforts. PMID:21604885

  7. Gender differences in approaches to self-management of poor sleep in later life.

    PubMed

    Venn, Susan; Meadows, Robert; Arber, Sara

    2013-02-01

    In this paper we seek to understand the influence of gender on the different approaches to managing poor sleep by older men and women through the conceptual framework of existing theoretical debates on medicalization, healthicization and 'personalization'. In-depth interviews undertaken between January and July 2008 with 62 people aged 65-95 who were experiencing poor sleep, revealed that the majority of older men and women resisted the medicalization of poor sleep, as they perceived sleep problems in later life were an inevitable consequence of ageing. However, older men and women engaged differently with the healthicization of poor sleep, with women far more likely than men to explore a range of alternative sleep remedies, such as herbal supplements, and were also much more likely than men to engage in behavioural practices to promote good sleep, and to avoid practices which prevented sleep. Women situated 'sleep' alongside more abstract discussions of 'diet' and health behaviours and drew on the discourses of the media, friends, family and their own experiences to create 'personalized' strategies, drawn from a paradigm of healthicization. Men, however, solely relied on the 'body' to indicate when sleep was needed and gauged their sleep needs largely by how they felt, and were able to function the following day. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. Technostress: measuring a new threat to well-being in later life.

    PubMed

    Nimrod, Galit

    2017-05-31

    Technostress is stress induced by Information and Communication Technology (ICT) use. Research on the topic has focused primarily on the workforce and tended to overlook senior citizens. This study presents the development of a new scale, which was designed to measure technostress specifically among older adults. The scale explores five constructs: overload, invasion, complexity, privacy and inclusion. The initial 20-item measure was tested in a pilot study and then included in an online survey of 537 Internet users aged 60 years and over. Based on the statistical analysis, the scale was reduced to 14 items. The constructs had good internal homogeneity, significant inter-construct correlations and high loadings on a single latent factor. The scores were well distributed along the range. Concurrent validity was assessed using the Satisfaction with Life Scale. A significant negative association was found between the two scales - a correlation that remained significant even after controlling for background variables. The new scale is useful for measuring technostress in older people, and technostress ought to be considered a particular threat to well-being in later life. Future research should explore its antecedents and consequences and identify interventions useful in alleviating its harmful effect on older ICT users.

  9. Comparing the Relationship Between Stature and Later Life Health in Six Low and Middle Income Countries

    PubMed Central

    McGovern, Mark E.

    2014-01-01

    This paper examines the relationship between stature and later life health in 6 emerging economies, each of which are expected to experience significant increases in the mean age of their populations over the coming decades. Using data from the WHO Study on Global Ageing and Adult Health (SAGE) and pilot data from the Longitudinal Ageing Study in India (LASI), I show that various measures of health are associated with height, a commonly used proxy for childhood environment. In the pooled sample, an additional 10cm increase in height is associated with between a 2 and 3 percentage point increase in the probability of being in very good or good self-reported health, a 3 percentage point increase in the probability of reporting no difficulties with activities of daily living or instrumental activities of daily living, and between a fifth and a quarter of a standard deviation increase in grip strength and lung function. Adopting a methodology previously used in the research on inequality, I also summarise the height-grip strength gradient for each country using the concentration index, and provide a decomposition analysis. PMID:25590021

  10. Preventing Depression in Later Life: Translation From Concept to Experimental Design and Implementation

    PubMed Central

    Sriwattanakomen, Roy; Ford, Angela F.; Thomas, Stephen B.; Miller, Mark D.; Stack, Jacqueline A.; Morse, Jennifer Q.; Kasckow, John; Brown, Charlotte; Reynolds, Charles F.

    2009-01-01

    Objective The authors detail the public health need for depression prevention research and the decisions made in designing an experiment testing problem solving therapy as “indicated” preventive intervention for high-risk older adults with subsyndromal depression. Special attention is given to the recruitment of African Americans because of well-documented inequalities in mental health services and depression treatment outcomes between races. Methods A total of 306 subjects (half white, half African American) with scores of 16 or higher on the Center for Epidemiological Studies of Depression Scale, but with no history of major depressive disorder in the past 12 months, are being recruited and randomly assigned to either problem solving therapy-primary care or to a dietary education control condition. Time to, and rate of, incident episodes of major depressive disorder are to be modeled using survival analysis. Level of depressive symptoms will be analyzed via a mixed models approach. Results Twenty-two subjects have been recruited into the study, and to date eight have completed the randomly assigned intervention and postintervention assessment. Four of 22 have exited after developing major depressive episodes. None have complained about study procedures or demands. Implementation in a variety of community settings is going well. Conclusion The data collected to date support the feasibility of translating from epidemiology to RCT design and implementation of empirical depression prevention research in later life. PMID:18515690

  11. Multilingualism and later life: a sociolinguistic perspective on age and aging.

    PubMed

    Divita, David

    2014-08-01

    In this paper, I contribute to subjective accounts of aging by focusing on a population that has been largely overlooked in social gerontology: individuals in later life who are multilingual. How do such individuals experience and make sense of their multilingualism? What role does language play in the way they experience and make sense of their lives? To answer these questions I take a life story approach to three women who experienced similar sociohistorical circumstances but arrived at different linguistic outcomes: born in Spain around the time of the civil war (1936-1939), they migrated to Paris in the 1960s to pursue social and economic mobility. Although they arrived in France as monolingual Spanish speakers, they have since acquired French and now practice their multilingualism in distinct ways. I juxtapose their life stories to illustrate how the acquisition and use of language are informed by a confluence of personal, social, and historical factors. Focusing on the linguistic dimension of the life course I thus introduce a new perspective on the heterogeneity obtained among individuals at this stage of their biographical trajectories. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. [Early-life stress and vulnerability for disease in later life].

    PubMed

    Entringer, Sonja; Buss, Claudia; Heim, Christine

    2016-10-01

    The rapidly growing research field of developmental programming of health and disease risk investigates the early life origins of individual vulnerability for common, complex disorders that confer a major burden of disease. The present article introduces the concept of developmental programming of disease vulnerability and summarizes studies on the mental and physical health consequences of exposure to childhood trauma and prenatal stress. Biological mechanisms that mediate disease risk after early life stress are discussed. The possibility of transgenerational transmission of effects of childhood trauma in exposed women to their children and potential mechanisms of this transmission are also presented. A substantial number of studies show associations between early life stress and risk for mental and somatic diseases in later life. The underlying mechanisms are currently being studied at the molecular and epigenetic level. Potentially, these findings will allow unprecedented opportunities to improve the precision of current clinical diagnostic tools and the success of interventions. However, there is currently a lack of translation of research findings related to developmental programming to clinical applications.

  13. Ketamine alters cortical integration of GABAergic interneurons and induces long-term sex-dependent impairments in transgenic Gad67-GFP mice

    PubMed Central

    Aligny, C; Roux, C; Dourmap, N; Ramdani, Y; Do-Rego, J-C; Jégou, S; Leroux, P; Leroux-Nicollet, I; Marret, S; Gonzalez, B J

    2014-01-01

    Ketamine, a non-competitive N-methyl-D-aspartate (NMDA) antagonist, widely used as an anesthetic in neonatal pediatrics, is also an illicit drug named Super K or KitKat consumed by teens and young adults. In the immature brain, despite several studies indicating that NMDA antagonists are neuroprotective against excitotoxic injuries, there is more and more evidence indicating that these molecules exert a deleterious effect by suppressing a trophic function of glutamate. In the present study, we show using Gad67-GFP mice that prenatal exposure to ketamine during a time-window in which GABAergic precursors are migrating results in (i) strong apoptotic death in the ganglionic eminences and along the migratory routes of GABAergic interneurons; (ii) long-term deficits in interneuron density, dendrite numbers and spine morphology; (iii) a sex-dependent deregulation of γ-aminobutyric acid (GABA) levels and GABA transporter expression; (iv) sex-dependent changes in the response to glutamate-induced calcium mobilization; and (v) the long-term sex-dependent behavioral impairment of locomotor activity. In conclusion, using a preclinical approach, the present study shows that ketamine exposure during cortical maturation durably affects the integration of GABAergic interneurons by reducing their survival and differentiation. The resulting molecular, morphological and functional modifications are associated with sex-specific behavioral deficits in adults. In light of the present data, it appears that in humans, ketamine could be deleterious for the development of the brain of preterm neonates and fetuses of addicted pregnant women. PMID:24991763

  14. Abnormal white matter tractography of visual pathways detected by high-angular-resolution diffusion imaging (HARDI) corresponds to visual dysfunction in cortical/cerebral visual impairment.

    PubMed

    Bauer, Corinna M; Heidary, Gena; Koo, Bang-Bon; Killiany, Ronald J; Bex, Peter; Merabet, Lotfi B

    2014-08-01

    Cortical (cerebral) visual impairment (CVI) is characterized by visual dysfunction associated with damage to the optic radiations and/or visual cortex. Typically it results from pre- or perinatal hypoxic damage to postchiasmal visual structures and pathways. The neuroanatomical basis of this condition remains poorly understood, particularly with regard to how the resulting maldevelopment of visual processing pathways relates to observations in the clinical setting. We report our investigation of 2 young adults diagnosed with CVI and visual dysfunction characterized by difficulties related to visually guided attention and visuospatial processing. Using high-angular-resolution diffusion imaging (HARDI), we characterized and compared their individual white matter projections of the extrageniculo-striate visual system with a normal-sighted control. Compared to a sighted control, both CVI cases revealed a striking reduction in association fibers, including the inferior frontal-occipital fasciculus as well as superior and inferior longitudinal fasciculi. This reduction in fibers associated with the major pathways implicated in visual processing may provide a neuroanatomical basis for the visual dysfunctions observed in these patients.

  15. Ornithine and Homocitrulline Impair Mitochondrial Function, Decrease Antioxidant Defenses and Induce Cell Death in Menadione-Stressed Rat Cortical Astrocytes: Potential Mechanisms of Neurological Dysfunction in HHH Syndrome.

    PubMed

    Zanatta, Ângela; Rodrigues, Marília Danyelle Nunes; Amaral, Alexandre Umpierrez; Souza, Débora Guerini; Quincozes-Santos, André; Wajner, Moacir

    2016-09-01

    Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is caused by deficiency of ornithine translocase leading to predominant tissue accumulation and high urinary excretion of ornithine (Orn), homocitrulline (Hcit) and ammonia. Although affected patients commonly present neurological dysfunction manifested by cognitive deficit, spastic paraplegia, pyramidal and extrapyramidal signs, stroke-like episodes, hypotonia and ataxia, its pathogenesis is still poorly known. Although astrocytes are necessary for neuronal protection. Therefore, in the present study we investigated the effects of Orn and Hcit on cell viability (propidium iodide incorporation), mitochondrial function (thiazolyl blue tetrazolium bromide-MTT-reduction and mitochondrial membrane potential-ΔΨm), antioxidant defenses (GSH) and pro-inflammatory response (NFkB, IL-1β, IL-6 and TNF-α) in unstimulated and menadione-stressed cortical astrocytes that were previously shown to be susceptible to damage by neurotoxins. We first observed that Orn decreased MTT reduction, whereas both amino acids decreased GSH levels, without altering cell viability and the pro-inflammatory factors in unstimulated astrocytes. Furthermore, Orn and Hcit decreased cell viability and ΔΨm in menadione-treated astrocytes. The present data indicate that the major compounds accumulating in HHH syndrome impair mitochondrial function and reduce cell viability and the antioxidant defenses in cultured astrocytes especially when stressed by menadione. It is presumed that these mechanisms may be involved in the neuropathology of this disease.

  16. Later-Life Career Disruption and Self-Rated Health: An Analysis of General Social Survey Data.

    ERIC Educational Resources Information Center

    He, Y. H.; Colantonio, A.; Marshall, V. W.

    2003-01-01

    A study described situations of later-life career disruption in older workers in Canada (n=2,592); large numbers had experienced job interruption or loss. Disruptions were significantly associated with self-ratings of poor health. However, the causal relationship between unemployment and poor health was complex. (Contains 49 references.) (JOW)

  17. The determinants of transitions into sheltered accommodation in later life in England and Wales.

    PubMed

    Vlachantoni, Athina; Maslovskaya, Olga; Evandrou, Maria; Falkingham, Jane

    2016-08-01

    Population ageing is a global challenge and understanding the dynamics of living arrangements in later life and their implications for the design of appropriate housing and long-term care is a critical policy issue. Existing research has focused on the study of transitions into residential care in the UK. This paper investigates transitions into sheltered accommodation among older people in England and Wales between 1993 and 2008. The study uses longitudinal data constructed from pooled observations across waves 2-18 of the British Household Panel Survey (BHPS) data, focusing on individuals aged 65 and over who lived in private housing at baseline and who were observed for two consecutive time points. A discrete-time logistic regression model was used to examine the association of transitioning into sheltered accommodation with a range of demographic, health and socioeconomic predictors. Demographic (age, region), socioeconomic factors (housing tenure, having a washing machine) and contact with health professionals (number of visits to the general practitioner, start in use of health visitor) were significant determinants of an older person's move into sheltered accommodation. Transitions into sheltered accommodation are associated with a range of demographic and socioeconomic characteristics as well as service use but not with health. Such results indicate that this type of housing option may be accessible by individuals with relatively good health, but may be limited to those who are referred by gatekeepers. Policymakers could consider making such housing option available to everyone, as well as providing incentives for building lifecourse-sensitive housing in the future. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  18. Maternal Obesity During Pregnancy Associates With Premature Mortality and Major Cardiovascular Events in Later Life.

    PubMed

    Lee, Kuan Ken; Raja, Edwin A; Lee, Amanda J; Bhattacharya, Sohinee; Bhattacharya, Siladitya; Norman, Jane E; Reynolds, Rebecca M

    2015-11-01

    One in 5 pregnant women is obese but the impact on later health is unknown. We aimed to determine whether maternal obesity during pregnancy associates with increased premature mortality and later life major cardiovascular events. Maternity records of women who gave birth to their first child between 1950 and 1976 (n=18 873) from the Aberdeen Maternity and Neonatal databank were linked to the National Register of Deaths, Scotland and Scottish Morbidity Record. The effect of maternal obesity at first antenatal visit on death and hospital admissions for cardiovascular events was tested using time-to-event analysis with Cox proportional hazard regression to compare outcomes of mothers in underweight, overweight, or obese body mass index (BMI) categories compared with normal BMI. Median follow-up was at 73 years. All-cause mortality was increased in women who were obese during pregnancy (BMI>30 kg/m(2)) versus normal BMI after adjustment for socioeconomic status, smoking, gestation at BMI measurement, preeclampsia, and low birth weight (hazard ratio, 1.35; 95% confidence interval, 1.02-1.77). In adjusted models, overweight and obese mothers had increased risk of hospital admission for a cardiovascular event (1.16; 1.06-1.27 and 1.26; 1.01-1.57) compared with normal BMI mothers. Adjustment for parity largely unchanged the hazard ratios (mortality: 1.43, 1.09-1.88; cardiovascular events overweight: 1.17, 1.07-1.29; and obese: 1.30, 1.04-1.62). In conclusion, maternal obesity is associated with increased risk of premature death and cardiovascular disease. Pregnancy and early postpartum could represent an opportunity for interventions to identify obesity and reduce its adverse consequences.

  19. Close social ties and health in later life: Strengths and vulnerabilities.

    PubMed

    Rook, Karen S; Charles, Susan T

    2017-09-01

    The world is aging at an unprecedented rate, with older adults representing the fastest-growing segment of the population in most economically developed and developing countries. This demographic shift leaves much uncharted territory for researchers who study social relationships and health. Social relationships exert powerful influences on physical health in later adulthood, a critical consideration given age-related increases in the prevalence of chronic health conditions and physical disability. A large body of research indicates that older adults report greater satisfaction with their social networks than do younger adults, and that they often take measures to minimize their exposure to negative social encounters. These emotionally satisfying and generally positive social ties afford some health protection against a backdrop of mounting physical limitations and play an important role when juxtaposed with the potentially health-damaging frictions that sometimes emerge in older adults' social relationships. Although most older adults report that they are satisfied with their social ties, some older adults experience frequent conflicts or ambivalent exchanges with members of their social networks, and these experiences detract from their health. In addition, many older adults will experience the loss of one or more close relationships during the course of their lives, with ramifications for their health and, often, for the reorganization of their social lives over time. Understanding how both the strengths and vulnerabilities of close social relationships affect health and well-being in later life is an important goal, particularly in view of the accelerating rate of population aging worldwide. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  20. Predicting later life health status and mortality using state-level socioeconomic characteristics in early life.

    PubMed

    Hamad, Rita; Rehkopf, David H; Kuan, Kai Y; Cullen, Mark R

    2016-12-01

    Studies extending across multiple life stages promote an understanding of factors influencing health across the life span. Existing work has largely focused on individual-level rather than area-level early life determinants of health. In this study, we linked multiple data sets to examine whether early life state-level characteristics were predictive of health and mortality decades later. The sample included 143,755 U.S. employees, for whom work life claims and administrative data were linked with early life state-of-residence and mortality. We first created a "state health risk score" (SHRS) and "state mortality risk score" (SMRS) by modeling state-level contextual characteristics with health status and mortality in a randomly selected 30% of the sample (the "training set"). We then examined the association of these scores with objective health status and mortality in later life in the remaining 70% of the sample (the "test set") using multivariate linear and Cox regressions, respectively. The association between the SHRS and adult health status was β=0.14 (95%CI: 0.084, 0.20), while the hazard ratio for the SMRS was 0.96 (95%CI: 0.93, 1.00). The association between the SHRS and health was not statistically significant in older age groups at a p-level of 0.05, and there was a statistically significantly different association for health status among movers compared to stayers. This study uses a life course perspective and supports the idea of "sensitive periods" in early life that have enduring impacts on health. It adds to the literature examining populations in the U.S. where large linked data sets are infrequently available.

  1. Substance use disorders and psychiatric comorbidity in mid and later life: a review

    PubMed Central

    Wu, Li-Tzy; Blazer, Dan G

    2014-01-01

    Background Globally, adults aged 65 years or older will increase from 516 million in 2009 to an estimated 1.53 billion in 2050. Due to substance use at earlier ages that may continue into later life, and ageing-related changes in medical conditions, older substance users are at risk for substance-related consequences. Methods MEDLINE and PsychInfo databases were searched using keywords: alcohol use disorder, drug use disorder, drug misuse, substance use disorder, prescription drug abuse, and substance abuse. Using the related-articles link, additional articles were screened for inclusion. This review focused on original studies published between 2005 and 2013 to reflect recent trends in substance use disorders. Studies on psychiatric comorbidity were also reviewed to inform treatment needs for older adults with a substance use disorder. Results Among community non-institutionalized adults aged 50+ years, about 60% used alcohol, 3% used illicit drugs and 1–2% used nonmedical prescription drugs in the past year. Among adults aged 50+, about 5% of men and 1.4% of women had a past-year alcohol use disorder. Among alcohol users, about one in 14 users aged 50–64 had a past-year alcohol use disorder vs one in 30 elder users aged 65+. Among drug users aged 50+, approximately 10–12% had a drug use disorder. Similar to depressive and anxiety disorders, substance use disorders were among the common psychiatric disorders among older adults. Older drug users in methadone maintenance treatment exhibited multiple psychiatric or medical conditions. There have been increases in treatment admissions for illicit and prescription drug problems in the United States. Conclusions Substance use in late life requires surveillance and research, including tracking substance use in the racial/ethnic populations and developing effective care models to address comorbid medical and mental health problems. PMID:24163278

  2. Association of allostatic load with brain structure and cognitive ability in later life

    PubMed Central

    Booth, Tom; Royle, Natalie A.; Corley, Janie; Gow, Alan J.; Valdés Hernández, Maria del C.; Muñoz Maniega, Susana; Ritchie, Stuart J.; Bastin, Mark E.; Starr, John M.; Wardlaw, Joanna M.; Deary, Ian J.

    2015-01-01

    Allostatic load (AL) has been proposed as a general framework for understanding the cumulative effects of life stress on individuals. Despite growing interest in AL, limited research has been conducted on aging samples. We consider the association of AL (operationalized by a range of inflammatory, cardiovascular, and metabolic measures) with a range of brain volume measurements and cognitive ability in a large cohort sample of older adults (n = 658, mean age = 72.5 years, standard deviation = 0.7) using structural equation modeling. AL was significantly inversely associated with total brain volume (range of standardized β = −0.16 to −0.20) and white-matter volume (−0.35 to −0.36) and positively with hippocampal volume (0.10–0.15) but not gray-matter volume (0.04). AL was also significantly inversely associated with general cognitive ability (range β = −0.13 to −0.20), processing speed (−0.20 to −0.22), and knowledge (−0.18 to −0.20) but not memory or nonverbal reasoning. The associations of AL with cognitive abilities were not mediated by these brain volume measures. AL did not predict cognitive change from age 11 to approximately age 73. The findings suggest a link between AL and later life brain health and cognitive functioning. PMID:25659881

  3. The determinants of transitions into sheltered accommodation in later life in England and Wales

    PubMed Central

    Vlachantoni, Athina; Maslovskaya, Olga; Evandrou, Maria; Falkingham, Jane

    2016-01-01

    Background Population ageing is a global challenge and understanding the dynamics of living arrangements in later life and their implications for the design of appropriate housing and long-term care is a critical policy issue. Existing research has focused on the study of transitions into residential care in the UK. This paper investigates transitions into sheltered accommodation among older people in England and Wales between 1993 and 2008. Methods The study uses longitudinal data constructed from pooled observations across waves 2–18 of the British Household Panel Survey (BHPS) data, focusing on individuals aged 65 and over who lived in private housing at baseline and who were observed for two consecutive time points. A discrete-time logistic regression model was used to examine the association of transitioning into sheltered accommodation with a range of demographic, health and socioeconomic predictors. Results Demographic (age, region), socioeconomic factors (housing tenure, having a washing machine) and contact with health professionals (number of visits to the general practitioner, start in use of health visitor) were significant determinants of an older person's move into sheltered accommodation. Conclusions Transitions into sheltered accommodation are associated with a range of demographic and socioeconomic characteristics as well as service use but not with health. Such results indicate that this type of housing option may be accessible by individuals with relatively good health, but may be limited to those who are referred by gatekeepers. Policymakers could consider making such housing option available to everyone, as well as providing incentives for building lifecourse-sensitive housing in the future. PMID:26896519

  4. Cardiovascular risk, lipids and pregnancy: preeclampsia and the risk of later life cardiovascular disease.

    PubMed

    Charlton, Francesca; Tooher, Jane; Rye, Kerry-Anne; Hennessy, Annemarie

    2014-03-01

    It has been widely thought that the effects of hypertension in pregnancy reversed after delivery and hypertension values returned to their pre-pregnancy level as it was seen as a disease of short duration in otherwise healthy young women. However, recent studies have demonstrated that the principal underlying abnormality, endothelial dysfunction, remains in women who had preeclampsia and that it is this damage that increases the risk of developing cardiovascular disease (CVD) in later life. The contributions of hypertension and dyslipidaemia before and during the pregnancy are also important and contribute to future risk. Serum lipids are complex and change dramatically in pregnancy. In general there is an increase in most plasma lipid components, notably triglycerides, total cholesterol and the major particles of HDL and LDL. Aberrations or exaggerations in this shift (i.e. decrease HDL and a greater increase in LDL) are associated with poor outcomes of pregnancy such as preeclampsia. Long term cardiovascular disease is influenced by preeclampsia and in part potentially by the lipid changes which escalate late in disease. Whether we can influence the risk of preeclampsia by controlling cardiovascular risk factors preceding or during preeclampsia, or cardiovascular disease after preeclampsia is yet to be determined. Ultimately, strategies to control lipid concentrations will only be viable when we understand the safety to the mother at the time of the pregnancy, and to the foetus both immediately and in the very long term. Strategies to control blood pressure are well established in the non-pregnant population, and previous preeclampsia and gestational hypertension should be considered in any cardiovascular risk profile. Whether control of blood pressure in the pregnancy per se is of any longer term benefit is also yet to be determined.

  5. Combined effects of type 2 diabetes and hypertension associated with cortical thinning and impaired cerebrovascular reactivity relative to hypertension alone in older adults

    PubMed Central

    Tchistiakova, Ekaterina; Anderson, Nicole D.; Greenwood, Carol E.; MacIntosh, Bradley J.

    2014-01-01

    Objective Type 2 diabetes mellitus is characterized by metabolic dysregulation in the form of hyperglycemia and insulin resistance and can have a profound impact on brain structure and vasculature. The primary aim of this study was to identify brain regions where the combined effects of type 2 diabetes and hypertension on brain health exceed those of hypertension alone. A secondary objective was to test whether vascular impairment and structural brain measures in this population are associated with cognitive function. Research design and methods We enrolled 18 diabetic participants with hypertension (HTN + T2DM, 7 women, 71.8 ± 5.6 years) and 22 participants with hypertension only (HTN, 12 women, 73.4 ± 6.2 years). Cerebrovascular reactivity (CVR) was assessed using blood oxygenation level dependent (BOLD) MRI during successive breath holds. Gray matter structure was evaluated using cortical thickness (CThk) measures estimated from T1-weighted images. Analyses of cognitive and blood data were also performed. Results Compared to HTN, HTN + T2DM had decreased CVR and CThk in a spatially overlapping region of the right occipital lobe (P < 0.025); CVR group differences were more expansive and included bilateral occipito-parietal areas (P < 0.025). Whereas CVR showed no significant associations with measures of cognitive function (P > 0.05), CThk in the right lingual gyrus ROI and regions resulting from a vertex-wise analysis (including posterior cingulate, precuneus, superior and middle frontal, and middle and inferior temporal regions (P < 0.025) were associated with executive function. Conclusions Individuals with T2DM and HTN showed decreased CVR and CThk compared to age-matched HTN controls. This study identifies brain regions that are impacted by the combined effects of comorbid T2DM and HTN conditions, with new evidence that the corresponding cortical thinning may contribute to cognitive decline. PMID:24967157

  6. Developmental cuprizone exposure impairs oligodendrocyte lineages differentially in cortical and white matter tissues and suppresses glutamatergic neurogenesis signals and synaptic plasticity in the hippocampal dentate gyrus of rats.

    PubMed

    Abe, Hajime; Saito, Fumiyo; Tanaka, Takeshi; Mizukami, Sayaka; Hasegawa-Baba, Yasuko; Imatanaka, Nobuya; Akahori, Yumi; Yoshida, Toshinori; Shibutani, Makoto

    2016-01-01

    Developmental cuprizone (CPZ) exposure impairs rat hippocampal neurogenesis. Here, we captured the developmental neurotoxicity profile of CPZ using a region-specific expression microarray analysis in the hippocampal dentate gyrus, corpus callosum, cerebral cortex and cerebellar vermis of rat offspring exposed to 0, 0.1, or 0.4% CPZ in the maternal diet from gestation day 6 to postnatal day (PND) 21. Transcripts of those genes identified as altered were subjected to immunohistochemical analysis on PNDs 21 and 77. Our results showed that transcripts for myelinogenesis-related genes, including Cnp, were selectively downregulated in the cerebral cortex by CPZ at ≥0.1% or 0.4% on PND 21. CPZ at 0.4% decreased immunostaining intensity for 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase) and CNPase(+) and OLIG2(+) oligodendrocyte densities in the cerebral cortex, whereas CNPase immunostaining intensity alone was decreased in the corpus callosum. By contrast, a striking transcript upregulation for Klotho gene and an increased density of Klotho(+) oligodendrocytes were detected in the corpus callosum at ≥0.1%. In the dentate gyrus, CPZ at ≥0.1% or 0.4% decreased the transcript levels for Gria1, Grin2a and Ptgs2, genes related to the synapse and synaptic transmission, and the number of GRIA1(+) and GRIN2A(+) hilar γ-aminobutyric acid (GABA)-ergic interneurons and cyclooxygenase-2(+) granule cells. All changes were reversed at PND 77. Thus, developmental CPZ exposure reversibly decreased mature oligodendrocytes in both cortical and white matter tissues, and Klotho protected white matter oligodendrocyte growth. CPZ also reversibly targeted glutamatergic signals of GABAergic interneuron to affect dentate gyrus neurogenesis and synaptic plasticity in granule cells.

  7. Effects of floor eggs on hatchability and later life performance in broiler chickens.

    PubMed

    van den Brand, H; Sosef, M P; Lourens, A; van Harn, J

    2016-05-01

    Two experiments were conducted in which effects of floor eggs, washed floor eggs, and clean nest eggs were investigated on incubation characteristics and performance in later life of broiler chickens. In both experiments, a young and an older breeder flock were used in a 3×2 factorial design during incubation. In the second experiment, male and female chickens were reared separately until d 35 of age in floor pens. During this grow out trial, an extra group was created in which chickens obtained from clean nest eggs were mixed with chickens obtained from floor eggs, meaning that grow out period was set up as a 4×2×2 factorial design with 4 egg types, 2 breeder ages, and 2 sexes. In both experiments, fertility and hatchability of fertile eggs were lower in floor and washed eggs than in clean nest eggs (hatchability: experiment 1: 74.4 vs. 70.6 vs. 92.6% for floor eggs, washed floor eggs and clean nest eggs, respectively, P<0.001; experiment 2: 78.3 vs. 81.7 vs. 90.2%, respectively, P<0.001). In experiment 2, BW at d 0 of chickens obtained from clean nest eggs was higher than that of chickens from floor eggs and washed floor eggs (41.5 vs. 40.4 and 40.3 g, respectively; P<0.001). This difference disappeared during the grow out period and was absent at slaughter age at d 35 of age. Feed intake (FI), feed conversion ratio (FCR), and mortality during the grow out period were not affected by egg type. Incidence and severity of hock burns and footpad dermatitis were not affected by egg type or breeder age. Litter friability at d 35 of age tended to be lower in pens with chickens obtained from washed floor eggs compared to clean nest eggs. We conclude that incubation of floor eggs or washed floor eggs resulted in lower fertility and hatchability compared to clean nest eggs, but that performance during the grow out period was not affected.

  8. Midlife fitness and the development of chronic conditions in later life.

    PubMed

    Willis, Benjamin L; Gao, Ang; Leonard, David; Defina, Laura F; Berry, Jarett D

    2012-09-24

    BACKGROUND The association between cardiorespiratory fitness (fitness) and mortality is well described. However, the association between midlife fitness and the development of nonfatal chronic conditions in older age has not been studied. METHODS To examine the association between midlife fitness and chronic disease outcomes in later life, participant data from the Cooper Center Longitudinal Study were linked with Medicare claims. We studied 18 670 healthy participants (21.1% women; median age, 49 years) who survived to receive Medicare coverage from January 1, 1999, to December 31, 2009. Fitness estimated by Balke treadmill time was analyzed as a continuous variable (in metabolic equivalents [METs]) and according to age- and sex-specific quintiles. Eight common chronic conditions were defined using validated algorithms, and associations between midlife fitness and the number of conditions were assessed using a modified Cox proportional hazards model that stratified the at-risk population by the number of conditions while adjusting for age, body mass index, blood pressure, cholesterol and glucose levels, alcohol use, and smoking. RESULTS After 120 780 person-years of Medicare exposure with a median follow-up of 26 years, the highest quintile of fitness (quintile 5) was associated with a lower incidence of chronic conditions compared with the lowest quintile (quintile 1) in men (15.6 [95% CI, 15.0-16.2] vs 28.2 [27.4-29.0] per 100 person-years) and women (11.4 [10.5-12.3] vs 20.1 [18.7 vs 21.6] per 100 person-years). After multivariate adjustment, higher fitness (in METs) was associated with a lower risk of developing chronic conditions in men (hazard ratio, 0.95 [95% CI, 0.94-0.96] per MET) and women (0.94 [0.91-0.96] per MET). Among decedents (2406 [12.9%]), higher fitness was associated with lower risk of developing chronic conditions relative to survival (compression hazard ratio, 0.90 [95% CI, 0.88-0.92] per MET), suggesting morbidity compression. CONCLUSIONS

  9. Midlife Fitness and the Development of Chronic Conditions in Later Life

    PubMed Central

    Willis, Benjamin L.; Gao, Ang; Leonard, David; DeFina, Laura F.; Berry, Jarett D.

    2013-01-01

    Background The association between cardiorespiratory fitness (fitness) and mortality is well described. However, the association between midlife fitness and the development of nonfatal chronic conditions in older age has not been studied. Methods To examine the association between midlife fitness and chronic disease outcomes in later life, participant data from the Cooper Center Longitudinal Study were linked with Medicare claims. We studied 18 670 healthy participants (21.1% women; median age, 49 years) who survived to receive Medicare coverage from January 1, 1999, to December 31, 2009. Fitness estimated by Balke treadmill time was analyzed as a continuous variable (in metabolic equivalents [METs]) and according to age- and sex-specific quintiles. Eight common chronic conditions were defined using validated algorithms, and associations between midlife fitness and the number of conditions were assessed using a modified Cox proportional hazards model that stratified the at-risk population by the number of conditions while adjusting for age, body mass index, blood pressure, cholesterol and glucose levels, alcohol use, and smoking. Results After 120 780 person-years of Medicare exposure with a median follow-up of 26 years, the highest quintile of fitness (quintile 5) was associated with a lower incidence of chronic conditions compared with the lowest quintile (quintile 1) in men (15.6 [95% CI, 15.0–16.2] vs 28.2 [27.4–29.0] per 100 person-years) and women (11.4 [10.5–12.3] vs 20.1 [18.7 vs 21.6] per 100 person-years). After multivariate adjustment, higher fitness (in METs) was associated with a lower risk of developing chronic conditions in men (hazard ratio, 0.95 [95% CI, 0.94–0.96] per MET) and women (0.94 [0.91–0.96] per MET). Among decedents (2406 [12.9%]), higher fitness was associated with lower risk of developing chronic conditions relative to survival (compression hazard ratio, 0.90 [95% CI, 0.88–0.92] per MET), suggesting morbidity compression

  10. Social inequalities in later life: the socio-economic position of older people from ethnic minority groups in Britain.

    PubMed

    Evandrou, M

    2000-01-01

    There are now nearly a quarter of a million individuals aged 60 years or over belonging to ethnic minority groups living in Britain. As the ethnic minority groups in Britain continue to age, information regarding their circumstances in later life will be of increasing importance for the development of appropriate services and policy. This article uses data from the General Household Survey (1991-96) to investigate the household living arrangements, lifestyle, socio-economic status, economic resources and experience of multiple deprivation in later life amongst older people from ethnic minority groups in Britain. The findings indicate that there are significant differences both between and within ethnic minority groups in access to material and social resources, which need to be taken into account by policy makers and planners.

  11. Reproductive History and Later-Life Comorbidity Trajectories: A Medicare Linked Cohort Study From the Utah Population Database

    PubMed Central

    Hanson, Heidi A.; Smith, Ken R.; Zimmer, Zachary

    2015-01-01

    Reproductive lives of men and women may provide significant insight into later-life morbidity and mortality. Sociological, biological, and evolutionary theories predict a relationship between reproductive history and later-life health; however, current research is lacking consensus on the direction of the relationship. Parity, early age at first birth and last birth, birth weight of offspring, having a child die as an infant, and having a preterm birth may have long-term effects on health for both men and women. In this study, the relationship between these measures of reproductive history and later-life health is examined using the Utah Population Database (a rich source of longitudinal data), and Medicare claims data from 1992–2009. Later-life health is measured using annual Charlson comorbidity index scores, a construct that summarizes most serious illnesses afflicting older individuals. Group-based trajectory modeling that accounts for nonrandom attrition due to death is used to identify the number and types of morbidity trajectories by sex and age for 52,924 individuals aged 65–84 in 1992. For females, early age at first birth, high parity, and having a preterm or high-birth-weight baby are associated with increased risks of comorbidity; later age at last birth is associated with a decreased risk of comorbidity. For males, early age at first birth and having a child with an abnormal birth weight leads to increased risk of comorbidity. The results suggest that both biological and social factors play important roles in the relationships between fertility and morbidity profiles at older ages. PMID:26527471

  12. Mothering alone: cross-national comparisons of later-life disability and health among women who were single mothers

    PubMed Central

    Berkman, Lisa F.; Zheng, Yuhui; Glymour, M. Maria; Avendano, Mauricio; Supan, Axel Börsch; Sabbath, Erika L.

    2016-01-01

    Background Single motherhood is associated with poorer health, but whether this association varies between countries is not known. We examine associations between single motherhood and poor later-life health in the US, England and 13 European countries. Methods Data came from 25,125 women aged 50+ who participated in the US Health and Retirement Study, the English Longitudinal Study of Ageing, and Survey of Health, Ageing and Retirement in Europe. We tested whether single motherhood at ages 16–49 was associated with increased risk of limitations with activities of daily living (ADL), instrumental ADL (IADL) and fair/poor self-rated health in later life. Results 33% of American mothers had experienced single motherhood before age 50, versus 22% in England, 38% in Scandinavia, 22% in Western Europe and 10% in Southern Europe. Single mothers had higher risk of poorer health and disability in later life than married mothers, but associations varied between countries. For example, risk ratios for ADL limitations were 1.51 (95% CI 1.29, 1.98) in England, 1.50 (1.10, 2.05) in Scandinavia and 1.27 (1.17, 1.40) in the US, versus 1.09 (0.80, 1.47) in Western Europe, 1.13 (0.80, 1.60) in Southern Europe, and 0.93 (0.66, 1.31) in Eastern Europe. Women who were single mothers before age 20, for 8+ years, or resulting from divorce or non-marital childbearing, were at particular risk. Conclusion Single motherhood during early- or mid-adulthood is associated with poorer health in later life. Risks were greatest in England, the US, and Scandinavia. Both selection and causation mechanisms might explain between-country variation. PMID:25977123

  13. Caregiving Networks in Later Life: Does Cognitive Status Make a Difference?

    ERIC Educational Resources Information Center

    Strain, Laurel A.; Blandford, Audrey A.

    2003-01-01

    This study examines the caregiving networks of older adults, with particular emphasis on differences according to cognitive status (n = 303). Individuals with cognitive impairment were significantly more likely than those who were cognitively intact to receive assistance with personal care, linking with the outside world, and mobility. The types…

  14. Gastric suction at birth associated with long-term risk for functional intestinal disorders in later life.

    PubMed

    Anand, K J S; Runeson, Bo; Jacobson, Bertil

    2004-04-01

    To test the hypothesis that noxious stimulation at birth may increase the long-term risk for developing psychosomatic or functional disorders during later life. Matched case-control study using sibling controls. The birth records were retrieved for the offspring of 494 mothers who, after uncomplicated pregnancies, had delivered two or more children with birth weights at least 2500 g, if at least one child was exposed to a perinatal complication or birth asphyxia. Among their offspring (N=1110), the 108 cases hospitalized for functional intestinal symptoms were identified from nationwide hospital discharge records. Of these, 96 cases were compared with 116 unaffected sibling controls. Functional intestinal symptoms occurred more commonly among the 1110 subjects (9.5%) than in the general population (3.4%, chi(2)=124, P<10(-6)). Gastric suction at birth occurred more frequently among the cases compared with their siblings (22.9% vs 11.2%). There were no differences in the number of cases and controls exposed to perinatal trauma or birth asphyxia. Multivariate logistic regression analyses showed that gastric suction at birth was associated with functional intestinal disorders during later life (odds ratio, 2.99; 95% confidence interval, 1.32-6.79; P=.009), whereas maternal, perinatal, or other confounding variables were not significant. Noxious stimulation caused by gastric suction at birth may promote the development of long-term visceral hypersensitivity and cognitive hypervigilance, leading to an increased prevalence of functional intestinal disorders in later life.

  15. Genomic biomarkers of prenatal intrauterine inflammation in umbilical cord tissue predict later life neurological outcomes.

    PubMed

    Tilley, Sloane K; Joseph, Robert M; Kuban, Karl C K; Dammann, Olaf U; O'Shea, T Michael; Fry, Rebecca C

    2017-01-01

    Preterm birth is a major risk factor for neurodevelopmental delays and disorders. This study aimed to identify genomic biomarkers of intrauterine inflammation in umbilical cord tissue in preterm neonates that predict cognitive impairment at 10 years of age. Genome-wide messenger RNA (mRNA) levels from umbilical cord tissue were obtained from 43 neonates born before 28 weeks of gestation. Genes that were differentially expressed across four indicators of intrauterine inflammation were identified and their functions examined. Exact logistic regression was used to test whether expression levels in umbilical cord tissue predicted neurocognitive function at 10 years of age. Placental indicators of inflammation were associated with changes in the mRNA expression of 445 genes in umbilical cord tissue. Transcripts with decreased expression showed significant enrichment for biological signaling processes related to neuronal development and growth. The altered expression of six genes was found to predict neurocognitive impairment when children were 10 years old These genes include two that encode for proteins involved in neuronal development. Prenatal intrauterine inflammation is associated with altered gene expression in umbilical cord tissue. A set of six of the differentially expressed genes predict cognitive impairment later in life, suggesting that the fetal environment is associated with significant adverse effects on neurodevelopment that persist into later childhood.

  16. [How municipalities can plan for later life. Regional challenges of a demography-sensitive social planning for later life as exemplified by the administrative district Vechta (Lower Saxony/Germany)].

    PubMed

    Amrhein, L; Backes, G M

    2012-07-01

    The demographic ageing of the population confronts towns, municipalities and administrative districts with new sociopolitical challenges. The general view of the demographic and social change requires demography-sensitive social planning that is no longer segregated according to age or life stages. Drawing on the example of a demographic evaluation conducted for the administrative district of Vechta in Lower Saxony, Germany, it will be discussed how a life course-orientated municipal social planning for later life can be developed. Furthermore, which practical research and methodical challenges the gerontological policy development municipalities can expect to be confronted with in the future are discussed.

  17. Tracing the origins of successful aging: the role of childhood conditions and social inequality in explaining later life health.

    PubMed

    Brandt, Martina; Deindl, Christian; Hank, Karsten

    2012-05-01

    This study investigates the role of childhood conditions and social inequality in older Europeans' propensity to age successfully, controlling for later life risk factors. Successful aging was assessed following Rowe and Kahn's conceptualization, using baseline interviews from the first two waves of the Survey of Health, Ageing and Retirement in Europe (SHARE). These data were merged with retrospective information on participants from 13 Continental European countries, collected as part of the SHARELIFE project. Our sample consists of 22,464 men and women, who are representative of the non-institutionalized population aged 50 or older (mean age: 63.3) in their respective country. Estimating multilevel logistic models, we controlled for demographics (age, sex), childhood conditions (SES, health, cognition), later life risk factors (various dimensions of SES and health behaviors), as well as social inequality (measured by country-specific Gini coefficients). There is an independent association of childhood living conditions with elders' odds of aging well. Higher parental SES, better math and reading skills, as well as self-reports of good childhood health were positively associated with successful aging, even if contemporary characteristics were controlled for. Later life SES and health behaviors exhibited the expected correlations with our dependent variable. Moreover, lower levels of income inequality were associated with a greater probability of meeting Rowe and Kahn's successful aging criteria. We conclude that unfavorable childhood conditions exhibit a harmful influence on individuals' chances to age well across all European welfare states considered in this study. Policy interventions should thus aim at improving the conditions for successful aging throughout the entire life course. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Potentially modifiable lifestyle factors, cognitive reserve, and cognitive function in later life: A cross-sectional study.

    PubMed

    Clare, Linda; Wu, Yu-Tzu; Teale, Julia C; MacLeod, Catherine; Matthews, Fiona; Brayne, Carol; Woods, Bob

    2017-03-01

    Potentially modifiable lifestyle factors may influence cognitive health in later life and offer potential to reduce the risk of cognitive decline and dementia. The concept of cognitive reserve has been proposed as a mechanism to explain individual differences in rates of cognitive decline, but its potential role as a mediating pathway has seldom been explored using data from large epidemiological studies. We explored the mediating effect of cognitive reserve on the cross-sectional association between lifestyle factors and cognitive function in later life using data from a population-based cohort of healthy older people. We analysed data from 2,315 cognitively healthy participants aged 65 y and over in the Cognitive Function and Ageing Study Wales (CFAS-Wales) cohort collected in 2011-2013. Linear regression modelling was used to investigate the overall associations between five lifestyle factors-cognitive and social activity, physical activity, diet, alcohol consumption, and smoking-and cognition, adjusting for demographic factors and chronic conditions. Mediation analysis tested for indirect effects of the lifestyle factors on cognition via cognitive reserve. After controlling for age, gender, and the presence of chronic conditions, cognitive and social activity, physical activity, healthy diet, and light-to-moderate alcohol consumption were positively associated with cognitive function, together accounting for 20% (95% CI 17%-23%) of variance in cognitive test scores. Cognitive reserve was an important mediator of this association, with indirect effects via cognitive reserve contributing 21% (95% CI 15%-27%) of the overall effect on cognition. The main limitations of the study derive from the cross-sectional nature of the data and the challenges of accurately measuring the latent construct of cognitive reserve. Cross-sectional associations support the view that enhancing cognitive reserve may benefit cognition, and maintenance of cognitive health may be supported

  19. Life-course occupational social class and health in later life: the importance of frequency and timing of measures.

    PubMed

    Stone, Juliet; Netuveli, Gopalakrishnan; Blane, David

    2014-09-01

    Research investigating associations between social class over the life-course and later health relies primarily on secondary analysis of existing data, limiting the number and timing of available measurements. This paper aims to examine the impact of these constraints on the measurement of life-course occupational social class and subsequent explanatory analyses predicting health in later life. Participants of the UK Boyd Orr Lifegrid Subsample (n = 294), aged an average of 68 years, provided retrospective information on their life-course occupational social class, coded at 6-month intervals. This was used to simulate two types of life-course data: (1) Theoretical: Life stage (four data-points at key life stages); (2) A-theoretical: Panel data (data-points at regular intervals of varying length). The percentage of life time in disadvantage and the predictive value for limiting longstanding illness (LLI) in later life using the full life-course and simulated data was compared. The presence of 'critical periods' of exposure and the role of trajectories of social class were also investigated. Compared with the full data, the life stage approach estimated a higher percentage of life time in disadvantage and emphasised 'transient' periods in disadvantage (e.g. labour market entry). With varying intervals using the a-theoretical approach, there was no clear pattern. Percentage of life time in manual class was a significant predictor of LLI only when using the four-point life stage approach. Occupational social class at labour market entry was a predictor of LLI in later life, suggesting a 'critical period'. Comparison of trajectories of social class further emphasised the importance of the sequence and timing of exposures to disadvantage in determining later health. We conclude that producing a valid summary of life-course occupational social class does not necessarily require a large number of data-points, particularly if guided by relevant theory, and that such

  20. Potentially modifiable lifestyle factors, cognitive reserve, and cognitive function in later life: A cross-sectional study

    PubMed Central

    Wu, Yu-Tzu

    2017-01-01

    Background Potentially modifiable lifestyle factors may influence cognitive health in later life and offer potential to reduce the risk of cognitive decline and dementia. The concept of cognitive reserve has been proposed as a mechanism to explain individual differences in rates of cognitive decline, but its potential role as a mediating pathway has seldom been explored using data from large epidemiological studies. We explored the mediating effect of cognitive reserve on the cross-sectional association between lifestyle factors and cognitive function in later life using data from a population-based cohort of healthy older people. Methods and findings We analysed data from 2,315 cognitively healthy participants aged 65 y and over in the Cognitive Function and Ageing Study Wales (CFAS-Wales) cohort collected in 2011–2013. Linear regression modelling was used to investigate the overall associations between five lifestyle factors—cognitive and social activity, physical activity, diet, alcohol consumption, and smoking—and cognition, adjusting for demographic factors and chronic conditions. Mediation analysis tested for indirect effects of the lifestyle factors on cognition via cognitive reserve. After controlling for age, gender, and the presence of chronic conditions, cognitive and social activity, physical activity, healthy diet, and light-to-moderate alcohol consumption were positively associated with cognitive function, together accounting for 20% (95% CI 17%–23%) of variance in cognitive test scores. Cognitive reserve was an important mediator of this association, with indirect effects via cognitive reserve contributing 21% (95% CI 15%–27%) of the overall effect on cognition. The main limitations of the study derive from the cross-sectional nature of the data and the challenges of accurately measuring the latent construct of cognitive reserve. Conclusions Cross-sectional associations support the view that enhancing cognitive reserve may benefit cognition

  1. N-acetylcysteine attenuates lipopolysaccharide-induced impairment in lamination of Ctip2-and Tbr1- expressing cortical neurons in the developing rat fetal brain

    PubMed Central

    Chao, Ming-Wei; Chen, Chie-Pein; Yang, Yu-Hsiu; Chuang, Yu-Chen; Chu, Tzu-Yun; Tseng, Chia-Yi

    2016-01-01

    Oxidative stress and inflammatory insults are the major instigating events of bacterial intrauterine infection that lead to fetal brain injury. The purpose of this study is to investigate the remedial effects of N-acetyl-cysteine (NAC) for inflammation-caused deficits in brain development. We found that lipopolysaccharide (LPS) induced reactive oxygen species (ROS) production by RAW264.7 cells. Macrophage-conditioned medium caused noticeable cortical cell damage, specifically in cortical neurons. LPS at 25 μg/kg caused more than 75% fetal loss in rats. An increase in fetal cortical thickness was noted in the LPS-treated group. In the enlarged fetal cortex, laminar positioning of the early born cortical cells expressing Tbr1 and Ctip2 was disrupted, with a scattered distribution. The effect was similar, but minor, in later born Satb2-expressing cortical cells. NAC protected against LPS-induced neuron toxicity in vitro and counteracted pregnancy loss and alterations in thickness and lamination of the neocortex in vivo. Fetal loss and abnormal fetal brain development were due to LPS-induced ROS production. NAC is an effective protective agent against LPS-induced damage. This finding highlights the key therapeutic impact of NAC in LPS-caused abnormal neuronal laminar distribution during brain development. PMID:27577752

  2. Subjective Well-Being In Later Life: 20 years after the Butterworths monograph series on individual and population aging.

    PubMed

    Stones, Michael; Kozma, Albert; McNeil, Kevin; Worobetz, Sarah

    2011-09-01

    This article discusses developments in theory and research on happiness two decades after publication of Psychological Well-Being in Later Life (Butterworths, 1991) by Albert Kozma, Michael Stones, and Kevin McNeil. Major empirical advances include new knowledge about contributions to happiness resulting from genetically related effects and personality. Personality traits have stronger relationships with happiness than was apparent 20 years ago and contribute to covariance between happiness and some of its predictors. Evolving emphases in research include the ways in which genetically related effects influence how people shape, and react to, their environment.

  3. Mothering alone: cross-national comparisons of later-life disability and health among women who were single mothers.

    PubMed

    Berkman, Lisa F; Zheng, Yuhui; Glymour, M Maria; Avendano, Mauricio; Börsch-Supan, Axel; Sabbath, Erika L

    2015-09-01

    Single motherhood is associated with poorer health, but whether this association varies between countries is not known. We examine associations between single motherhood and poor later-life health in the USA, England and 13 European countries. Data came from 25 125 women aged 50+ who participated in the US Health and Retirement Study, the English Longitudinal Study of Ageing and Survey of Health, Ageing and Retirement in Europe. We tested whether single motherhood at ages 16-49 was associated with increased risk of limitations with activities of daily living (ADL), instrumental ADL and fair/poor self-rated health in later life. 33% of American mothers had experienced single motherhood before age 50, versus 22% in England, 38% in Scandinavia, 22% in Western Europe and 10% in Southern Europe. Single mothers had higher risk of poorer health and disability in later life than married mothers, but associations varied between countries. For example, risk ratios for ADL limitations were 1.51 (95% CI 1.29 to 1.98) in England, 1.50 (1.10 to 2.05) in Scandinavia and 1.27 (1.17 to 1.40) in the USA, versus 1.09 (0.80 to 1.47) in Western Europe, 1.13 (0.80 to 1.60) in Southern Europe and 0.93 (0.66 to 1.31) in Eastern Europe. Women who were single mothers before age 20, for 8+ years, or resulting from divorce or non-marital childbearing, were at particular risk. Single motherhood during early-adulthood or mid-adulthood is associated with poorer health in later life. Risks were greatest in England, the USA and Scandinavia. Selection and causation mechanisms might both explain between-country variation. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  4. Childhood school segregation and later life sense of control and physical performance in the African American Health cohort.

    PubMed

    Wolinsky, Fredric D; Andresen, Elena M; Malmstrom, Theodore K; Miller, J Philip; Schootman, Mario; Miller, Douglas K

    2012-09-27

    The association between childhood school desegregation and later life sense of control and physical performance among African Americans is not clear. We hypothesized that childhood school desegregation adversely affected the sense of control of in later life, and that this reduced sense of control accounts in part for reduced physical performance. In-home follow-up assessments were completed in 2010 with 582 of the 58-74 year old men and women participating in the on-going African American Health cohort. We used these data to examine the relationship between (a) retrospective self-reports of attending segregated schools during one's 1st-to-12th grade education and one's current sense of control, as well as (b) the association between current sense of control and physical performance. Multiple linear regression analysis with propensity score re-weighting was used. Attending segregated schools for at least half of one's 1st-to-12th grade education was significantly associated with higher scores on the sense of control. Adjusting for all covariates and potential confounders, those receiving half or more of their 1st-to-12th grade education in segregated schools had sense of control scores that were .886 points higher (p ≤ .01; standardized effect size = .22). Sense of control scores were independently (all p < .01) associated with better systolic blood pressure, grip strength, peak expiratory flow, chair stands, balance tests, and the Short Portable Physical Battery even after adjusting for all covariates and potential confounders. Moreover, sense of control scores either partially or fully mediated the statistically significant beneficial associations between childhood school segregation and physical performance. Childhood school desegregation was adversely associated with the sense of control of African Americans in later life, and this reduced sense of control appears, in part, to account for their poorer physical performance. The etiologic

  5. Childhood school segregation and later life sense of control and physical performance in the African American Health cohort

    PubMed Central

    2012-01-01

    Background The association between childhood school desegregation and later life sense of control and physical performance among African Americans is not clear. We hypothesized that childhood school desegregation adversely affected the sense of control of in later life, and that this reduced sense of control accounts in part for reduced physical performance. Methods In-home follow-up assessments were completed in 2010 with 582 of the 58–74 year old men and women participating in the on-going African American Health cohort. We used these data to examine the relationship between (a) retrospective self-reports of attending segregated schools during one’s 1st-to-12th grade education and one’s current sense of control, as well as (b) the association between current sense of control and physical performance. Multiple linear regression analysis with propensity score re-weighting was used. Results Attending segregated schools for at least half of one’s 1st-to-12th grade education was significantly associated with higher scores on the sense of control. Adjusting for all covariates and potential confounders, those receiving half or more of their 1st-to-12th grade education in segregated schools had sense of control scores that were .886 points higher (p ≤ .01; standardized effect size = .22). Sense of control scores were independently (all p < .01) associated with better systolic blood pressure, grip strength, peak expiratory flow, chair stands, balance tests, and the Short Portable Physical Battery even after adjusting for all covariates and potential confounders. Moreover, sense of control scores either partially or fully mediated the statistically significant beneficial associations between childhood school segregation and physical performance. Conclusions Childhood school desegregation was adversely associated with the sense of control of African Americans in later life, and this reduced sense of control appears, in part, to account for their

  6. A window of vulnerability: impaired fear extinction in adolescence.

    PubMed

    Baker, Kathryn D; Den, Miriam L; Graham, Bronwyn M; Richardson, Rick

    2014-09-01

    There have been significant advances made towards understanding the processes mediating extinction of learned fear. However, despite being of clear theoretical and clinical significance, very few studies have examined fear extinction in adolescence, which is often described as a developmental window of vulnerability to psychological disorders. This paper reviews the relatively small body of research examining fear extinction in adolescence. A prominent finding of this work is that adolescents, both humans and rodents, exhibit a marked impairment in extinction relative to both younger (e.g., juvenile) and older (e.g., adult) groups. We then review some potential mechanisms that could produce the striking extinction deficit observed in adolescence. For example, one neurobiological candidate mechanism for impaired extinction in adolescence involves changes in the functional connectivity within the fear extinction circuit, particularly between prefrontal cortical regions and the amygdala. In addition, we review research on emotion regulation and attention processes that suggests that developmental changes in attention bias to threatening cues may be a cognitive mechanism that mediates age-related differences in extinction learning. We also examine how a differential reaction to chronic stress in adolescence impacts upon extinction retention during adolescence as well as in later life. Finally, we consider the findings of several studies illustrating promising approaches that overcome the typically-observed extinction impairments in adolescent rodents and that could be translated to human adolescents. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Repetitive head impact exposure and later-life plasma total tau in former National Football League players.

    PubMed

    Alosco, Michael L; Tripodis, Yorghos; Jarnagin, Johnny; Baugh, Christine M; Martin, Brett; Chaisson, Christine E; Estochen, Nate; Song, Linan; Cantu, Robert C; Jeromin, Andreas; Stern, Robert A

    2017-01-01

    Blood protein analysis of total tau (t-tau) may be a practical screening biomarker for chronic traumatic encephalopathy (CTE), a neurodegenerative tauopathy associated with repetitive head impact (RHI) exposure. We examined plasma t-tau in symptomatic former National Football League (NFL) players compared with controls and the relationship between RHI exposure and later-life plasma t-tau. Ninety-six former NFL players (age 40-69) and 25 same-age controls underwent blood draw to determine plasma t-tau levels. The cumulative head impact index (CHII) quantified RHI exposure. Subjects completed measures of clinical function. A higher CHII predicted greater plasma t-tau in the former NFL players (P = .0137). No group differences in plasma t-tau emerged, but a concentration ≥3.56 pg/mL was 100% specific to former NFL players. Plasma t-tau did not predict clinical function. Greater RHI exposure predicted higher later-life plasma t-tau concentrations, and further study on plasma t-tau as a candidate screening biomarker for CTE is warranted.

  8. "Can Breast Feeding Help You in Later Life? Evidence from German Military Heights in the Early 20th Century"*

    PubMed Central

    Haines, Michael R.; Kintner, Hallie J.

    2008-01-01

    Considerable literature exists on the benefits of breast feeding on the health and survival of infants and young children, but there is less on the effects on later life outcomes. One such measure of health and well-being that has received attention in the historical literature is terminal adult stature. Information on height is rather widely available; however, it is much more difficult to obtain data on breast feeding. One country that does have such information is Imperial Germany (1871–1919). A number of physicians and local health officials collected information on the incidence and duration of breast feeding early in the 20th century, particularly because of concern about the unusually high infant mortality rates in parts of Germany. Hallie Kintner has surveyed the published results of these studies. The information on the prevalence of breast feeding for the period 1903/10 has been inputed into a database of demographic and economic variables for the counties (Regierungsbezirke) of Germany (1850–1939) There are also published data on heights of military recruits from the Imperial German military forces in 1906. These can be linked to areas in the database and related to breast feeding practices and infant mortality both contemporaneously and approximately 20 years previous to 1906. Results indicate a significant effect of infant feeding practices on later life outcomes operating through infant health conditions, proxied by the infant mortality rate. PMID:18715833

  9. Perinatal BPA exposure induces hyperglycemia, oxidative stress and decreased adiponectin production in later life of male rat offspring.

    PubMed

    Song, Shunzhe; Zhang, Ling; Zhang, Hongyuan; Wei, Wei; Jia, Lihong

    2014-04-03

    The main object of the present study was to explore the effect of perinatal bisphenol A (BPA) exposure on glucose metabolism in early and later life of male rat offspring, and to establish the potential mechanism of BPA-induced dysglycemia. Pregnant rats were treated with either vehicle or BPA by drinking water at concentrations of 1 and 10 µg/mL BPA from gestation day 6 through the end of lactation. We measured the levels of fasting serum glucose, insulin, adiponectin and parameters of oxidative stress on postnatal day (PND) 50 and PND100 in male offspring, and adiponectin mRNA and protein expression in adipose tissue were also examined. Our results showed that perinatal exposure to 1 or 10 µg/mL BPA induced hyperglycemia with insulin resistance on PND100, but only 10 µg/mL BPA exposure had similar effects as early as PND50. In addition, increased oxidative stress and decreased adiponectin production were also observed in BPA exposed male offspring. Our findings indicated that perinatal exposure to BPA resulted in abnormal glucose metabolism in later life of male offspring, with an earlier and more exacerbated effect at higher doses. Down-regulated expression of adiponectin gene and increased oxidative stress induced by BPA may be associated with insulin resistance.

  10. Early Origins of Later Life Psychological Well-Being? A Novel Application of Causal Mediation Analysis to Life Course Research.

    PubMed

    Bhatta, Tirth R; Albert, Jeffrey M; Kahana, Eva; Lekhak, Nirmala

    2017-03-14

    This study employs a novel approach to mediation analysis to clarify the influence of interrelated indicators of life course socioeconomic status (SES) on later life psychological well-being in India. Contrary to traditional approaches (i.e., use of product and difference-in-coefficients), we recognize the role of confounders in the estimation of total, direct, and indirect effects of parental education on respondents' psychological well-being. Drawing from the first wave (2007-2010) of the Study on Global Ageing and Adult Health (SAGE) and adopting a counterfactual approach, we estimate both natural direct and indirect effects of parental education through individual educational attainment (secondarily, through household assets as an additional mediator) on respondents' life-satisfaction and quality of life (QOL). Findings document a statistically not significant positive total effect of parental education on life satisfaction and QOL. While lower for women, significant indirect effects suggest that the positive influence of parental education operates primarily through the individual's education. Notably, we found negative direct effect of parental education on psychological well-being outcomes. Contrary to prior literature, we found no positive direct influence of parental education on later life psychological well-being, but established its influence through socioeconomic positioning over the life course.

  11. Testing and testing positive: childhood adversities and later life HIV status among Kenyan women and their partners.

    PubMed

    Goodman, Michael L; Raimer-Goodman, Lauren; Chen, Catherine X; Grouls, Astrid; Gitari, Stanley; Keiser, Philip H

    2016-12-02

    Adverse childhood experiences are a critical feature of lifelong health. No research assesses whether childhood adversities predict HIV-testing behaviors, and little research analyzes childhood adversities and later life HIV status in sub-Saharan Africa. We use regression models with cross-sectional data from a representative sample (n = 1974) to analyze whether adverse childhood experiences, separately or as cumulative exposures, predict reports of later life HIV testing and testing HIV+ among semi-rural Kenyan women and their partners. No significant correlation was observed between thirteen cumulative childhood adversities and reporting prior HIV testing for respondent or partner. Separately, childhood sexual abuse and emotional neglect predicted lower odds of reporting having previously been tested for HIV. Witnessing household violence during one's childhood predicted significantly higher odds of reporting HIV+. Sexual abuse predicted higher odds of reporting a partner tested HIV+. Preventing sexual abuse and household violence may improve HIV testing and test outcomes among Kenyan women. More research is required to understand pathways between adverse childhood experiences and partner selection within Kenya and sub-Saharan Africa, and data presented here suggest understanding pathways may help improve HIV outcomes. © The Author 2016. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. Education and male-female differences in later-life cognition: international evidence from Latin America and the Caribbean.

    PubMed

    Maurer, Jürgen

    2011-08-01

    This study explores the role of early-life education for differences in cognitive functioning between men and women aged 60 and older from seven major urban areas in Latin America and the Caribbean. After documenting statistically significant differences in cognitive functioning between men and women for six of the seven study sites, I assess the extent to which these differences can be explained by prevailing male-female differences in education. I decompose predicted male-female differences in cognitive functioning based on various statistical models for later-life cognition and find robust evidence that male-female differences in education are a major driving force behind cognitive functioning differences between older men and women. This study therefore suggests that early-life differences in educational attainment between boys and girls during childhood have a lasting impact on gender inequity in cognitive functioning at older ages. Increases in educational attainment and the closing of the gender gap in education in many countries in Latin America and the Caribbean may thus result in both higher levels and a more gender-equitable distribution of later-life cognition among the future elderly in those countries.

  13. Effect of pregnancy for females born small on later life metabolic disease risk.

    PubMed

    Tran, Melanie; Gallo, Linda A; Wadley, Glenn D; Jefferies, Andrew J; Moritz, Karen M; Wlodek, Mary E

    2012-01-01

    There is a strong inverse relationship between a females own birth weight and her subsequent risk for gestational diabetes with increased risk of developing diabetes later in life. We have shown that growth restricted females develop loss of glucose tolerance during late pregnancy with normal pancreatic function. The aim of this study was to determine whether growth restricted females develop long-term impairment of metabolic control after an adverse pregnancy adaptation. Uteroplacental insufficiency was induced by bilateral uterine vessel ligation (Restricted) or sham surgery (Control) in late pregnancy (E18) in F0 female rats. F1 Control and Restricted female offspring were mated with normal males and allowed to deliver (termed Ex-Pregnant). Age-matched Control and Restricted Virgins were also studied and glucose tolerance and insulin secretion were determined. Pancreatic morphology and hepatic glycogen and triacylglycerol content were quantified respectively. Restricted females were born lighter than Control and remained lighter at all time points studied (p<0.05). Glucose tolerance, first phase insulin secretion and liver glycogen and triacylglycerol content were not different across groups, with no changes in β-cell mass. Second phase insulin secretion was reduced in Restricted Virgins (-34%, p<0.05) compared to Control Virgins, suggestive of enhanced peripheral insulin sensitivity but this was lost after pregnancy. Growth restriction was associated with enhanced basal hepatic insulin sensitivity, which may provide compensatory benefits to prevent adverse metabolic outcomes often associated with being born small. A prior pregnancy was associated with reduced hepatic insulin sensitivity with effects more pronounced in Controls than Restricted. Our data suggests that pregnancy ameliorates the enhanced peripheral insulin sensitivity in growth restricted females and has deleterious effects for hepatic insulin sensitivity, regardless of maternal birth weight.

  14. Effect of Pregnancy for Females Born Small on Later Life Metabolic Disease Risk

    PubMed Central

    Tran, Melanie; Gallo, Linda A.; Wadley, Glenn D.; Jefferies, Andrew J.; Moritz, Karen M.; Wlodek, Mary E.

    2012-01-01

    There is a strong inverse relationship between a females own birth weight and her subsequent risk for gestational diabetes with increased risk of developing diabetes later in life. We have shown that growth restricted females develop loss of glucose tolerance during late pregnancy with normal pancreatic function. The aim of this study was to determine whether growth restricted females develop long-term impairment of metabolic control after an adverse pregnancy adaptation. Uteroplacental insufficiency was induced by bilateral uterine vessel ligation (Restricted) or sham surgery (Control) in late pregnancy (E18) in F0 female rats. F1 Control and Restricted female offspring were mated with normal males and allowed to deliver (termed Ex-Pregnant). Age-matched Control and Restricted Virgins were also studied and glucose tolerance and insulin secretion were determined. Pancreatic morphology and hepatic glycogen and triacylglycerol content were quantified respectively. Restricted females were born lighter than Control and remained lighter at all time points studied (p<0.05). Glucose tolerance, first phase insulin secretion and liver glycogen and triacylglycerol content were not different across groups, with no changes in β-cell mass. Second phase insulin secretion was reduced in Restricted Virgins (−34%, p<0.05) compared to Control Virgins, suggestive of enhanced peripheral insulin sensitivity but this was lost after pregnancy. Growth restriction was associated with enhanced basal hepatic insulin sensitivity, which may provide compensatory benefits to prevent adverse metabolic outcomes often associated with being born small. A prior pregnancy was associated with reduced hepatic insulin sensitivity with effects more pronounced in Controls than Restricted. Our data suggests that pregnancy ameliorates the enhanced peripheral insulin sensitivity in growth restricted females and has deleterious effects for hepatic insulin sensitivity, regardless of maternal birth weight

  15. Inflammation, Depression, and Slow Gait: A High Mortality Phenotype in Later Life

    PubMed Central

    Roose, Steven P.; Zhang, Jun; Wall, Melanie; Rutherford, Bret R.; Ayonayon, Hilsa N.; Butters, Meryl A.; Harris, Tamara; Newman, Anne B.; Satterfield, Suzanne; Simonsick, Eleanor M.; Yaffe, Kristine

    2016-01-01

    Background. Inflammation, slow gait, and depression individually are associated with mortality, yet little is known about the trajectories of these measures, their interrelationships, or their collective impact on mortality. Methods. Longitudinal latent class analysis was used to evaluate trajectories of depression (Center for Epidemiologic Studies Depression ≥ 10), slow gait (<1.0 m/s), and elevated inflammation (interleukin 6 > 3.2 pg/mL) using data from the Health Aging and Body Composition Study. Logistic regression was used to identify their associations with mortality. Results. For each outcome, low-probability (n inflammation = 1,656, n slow gait = 1,471, n depression = 1,458), increasing-probability (n inflammation = 847, n slow gait = 880, n depression = 1,062), and consistently high-probability (n inflammation = 572, n slow gait = 724, n depression = 555) trajectories were identified, with 22% of all participants classified as having increasing or consistently high-probability trajectories on inflammation, slow gait, and depression (meaning probability of impairment on each outcome increased from low to moderate/high or remained high over 10 years). Trajectories of slow gait were associated with inflammation (r = .40, p < .001) and depression (r = .49, p < .001). Although worsening trajectories of inflammation were independently associated with mortality (p < .001), the association between worsening trajectories of slow gait and mortality was only present in participants with worsening depression trajectories (p < .01). Participants with increasing/consistently high trajectories of depression and consistently high trajectories of inflammation and slow gait (n = 247) have an adjusted-morality rate of 85.2%, greater than all other classification permutations. Conclusions. Comprehensive assessment of older adults is warranted for the development of treatment strategies targeting a high-mortality risk phenotype consisting of inflammation, depression, and

  16. Inflammation, Depression, and Slow Gait: A High Mortality Phenotype in Later Life.

    PubMed

    Brown, Patrick J; Roose, Steven P; Zhang, Jun; Wall, Melanie; Rutherford, Bret R; Ayonayon, Hilsa N; Butters, Meryl A; Harris, Tamara; Newman, Anne B; Satterfield, Suzanne; Simonsick, Eleanor M; Yaffe, Kristine

    2016-02-01

    Inflammation, slow gait, and depression individually are associated with mortality, yet little is known about the trajectories of these measures, their interrelationships, or their collective impact on mortality. Longitudinal latent class analysis was used to evaluate trajectories of depression (Center for Epidemiologic Studies Depression ≥ 10), slow gait (<1.0 m/s), and elevated inflammation (interleukin 6 > 3.2 pg/mL) using data from the Health Aging and Body Composition Study. Logistic regression was used to identify their associations with mortality. For each outcome, low-probability (n inflammation = 1,656, n slow gait = 1,471, n depression = 1,458), increasing-probability (n inflammation = 847, n slow gait = 880, n depression = 1,062), and consistently high-probability (n inflammation = 572, n slow gait = 724, n depression = 555) trajectories were identified, with 22% of all participants classified as having increasing or consistently high-probability trajectories on inflammation, slow gait, and depression (meaning probability of impairment on each outcome increased from low to moderate/high or remained high over 10 years). Trajectories of slow gait were associated with inflammation (r = .40, p < .001) and depression (r = .49, p < .001). Although worsening trajectories of inflammation were independently associated with mortality (p < .001), the association between worsening trajectories of slow gait and mortality was only present in participants with worsening depression trajectories (p < .01). Participants with increasing/consistently high trajectories of depression and consistently high trajectories of inflammation and slow gait (n = 247) have an adjusted-morality rate of 85.2%, greater than all other classification permutations. Comprehensive assessment of older adults is warranted for the development of treatment strategies targeting a high-mortality risk phenotype consisting of inflammation, depression, and slow gait speed. © The Author 2015

  17. Taking up physical activity in later life and healthy ageing: the English longitudinal study of ageing.

    PubMed

    Hamer, Mark; Lavoie, Kim L; Bacon, Simon L

    2014-02-01

    Physical activity is associated with improved overall health in those people who survive to older ages, otherwise conceptualised as healthy ageing. Previous studies have examined the effects of mid-life physical activity on healthy ageing, but not the effects of taking up activity later in life. We examined the association between physical activity and healthy ageing over 8 years of follow-up. Participants were 3454 initially disease-free men and women (aged 63.7 ± 8.9 years at baseline) from the English Longitudinal Study of Ageing, a prospective study of community dwelling older adults. Self-reported physical activity was assessed at baseline (2002-2003) and through follow-up. Healthy ageing, assessed at 8 years of follow-up (2010-2011), was defined as those participants who survived without developing major chronic disease, depressive symptoms, physical or cognitive impairment. At follow-up, 19.3% of the sample was defined as healthy ageing. In comparison with inactive participants, moderate (OR, 2.67, 95% CI 1.95 to 3.64), or vigorous activity (3.53, 2.54 to 4.89) at least once a week was associated with healthy ageing, after adjustment for age, sex, smoking, alcohol, marital status and wealth. Becoming active (multivariate adjusted, 3.37, 1.67 to 6.78) or remaining active (7.68, 4.18 to 14.09) was associated with healthy ageing in comparison with remaining inactive over follow-up. Sustained physical activity in older age is associated with improved overall health. Significant health benefits were even seen among participants who became physically active relatively late in life.

  18. Childhood deprivation and later-life cognitive function in a population-based study of older rural South Africans.

    PubMed

    Kobayashi, Lindsay C; Glymour, M Maria; Kahn, Kathleen; Payne, Collin F; Wagner, Ryan G; Montana, Livia; Mateen, Farrah J; Tollman, Stephen M; Berkman, Lisa F

    2017-10-01

    Little research has evaluated the life course drivers of cognitive aging in South Africa. We investigated the relationships of self-rated childhood health and father's occupation during childhood with later-life cognitive function score and whether educational attainment mediated these relationships among older South Africans living in a former region of Apartheid-era racial segregation. Data were from baseline assessments of "Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community" (HAALSI), a population-based study of 5059 men and women aged ≥40 years in 2015 in rural Agincourt sub-district, South Africa. Childhood health, father's occupation during childhood, and years of education were self-reported in study interviews. Cognitive measures assessed time orientation, numeracy, and word recall, which were included in a z-standardized latent cognitive function score variable. Linear regression models adjusted for age, sex, and country of birth were used to estimate the total and direct effects of each childhood risk factor, and the indirect effects mediated by years of education. Poor childhood health predicted lower cognitive scores (total effect = -0.28; 95% CI = -0.35, -0.21, versus good); this effect was not mediated by educational attainment. Having a father in a professional job during childhood, while rare (3% of sample), predicted better cognitive scores (total effect = 0.25; 95% CI = 0.10, 0.40, versus unskilled manual labor, 29% of sample). Half of this effect was mediated by educational attainment. Education was linearly associated with later-life cognitive function score (0.09; 95% CI = 0.09, 0.10 per year achieved). In this post-Apartheid, rural South African context, older adults with poor self-reported childhood health or whose father worked in unskilled manual labor had relatively poor cognitive outcomes. Educational attainment strongly predicted cognitive outcomes, and appeared to be, in part, a mechanism of social

  19. Hypertensive diseases of pregnancy and risk of hypertension and stroke in later life: results from cohort study

    PubMed Central

    Wilson, Brenda J; Watson, M Stuart; Prescott, Gordon J; Sunderland, Sarah; Campbell, Doris M; Hannaford, Philip; Smith, W Cairns S

    2003-01-01

    Objective To examine the association between hypertensive diseases of pregnancy (gestational hypertension and pre-eclampsia) and the development of circulatory diseases in later life. Design Cohort study of women who had pre-eclampsia during their first singleton pregnancy. Two comparison groups were matched for age and year of delivery, one with gestational hypertension and one with no history of raised blood pressure. Setting Maternity services in the Grampian region of Scotland. Participants Women selected from the Aberdeen maternity and neonatal databank who were resident in Aberdeen and who delivered a first, live singleton from 1951 to 1970. Main outcome measures Current vital and cardiovascular health status ascertained through postal questionnaire survey, clinical examination, linkage to hospital discharge, and mortality data. Results There were significant positive associations between pre-eclampsia/eclampsia or gestational hypertension and later hypertension in all measures. The adjusted relative risks varied from 1.13-3.72 for gestational hypertension and 1.40-3.98 for pre-eclampsia or eclampsia. The adjusted incident rate ratio for death from stroke for the pre-eclampsia/eclampsia group was 3.59 (95% confidence interval 1.04 to 12.4). Conclusions Hypertensive diseases of pregnancy seem to be associated in later life with diseases related to hypertension. If greater awareness of this association leads to earlier diagnosis and improved management, there may be scope for reducing a proportion of the morbidity and mortality from such diseases. What is already known on this topicMuch is known about the effect of cardiovascular risks factors that are shared by men and women, but less on those specific to womenRetrospective studies, based on patient recall, suggest that hypertension in pregnancy may be associated with increased risk of cardiovascular diseases in later lifeWhat this study addsProspective recording of blood pressure and proteinuria shows that

  20. Disconnection mechanism and regional cortical atrophy contribute to impaired processing of facial expressions and theory of mind in multiple sclerosis: a structural MRI study.

    PubMed

    Mike, Andrea; Strammer, Erzsebet; Aradi, Mihaly; Orsi, Gergely; Perlaki, Gabor; Hajnal, Andras; Sandor, Janos; Banati, Miklos; Illes, Eniko; Zaitsev, Alexander; Herold, Robert; Guttmann, Charles R G; Illes, Zsolt

    2013-01-01

    Successful socialization requires the ability of understanding of others' mental states. This ability called as mentalization (Theory of Mind) may become deficient and contribute to everyday life difficulties in multiple sclerosis. We aimed to explore the impact of brain pathology on mentalization performance in multiple sclerosis. Mentalization performance of 49 patients with multiple sclerosis was compared to 24 age- and gender matched healthy controls. T1- and T2-weighted three-dimensional brain MRI images were acquired at 3Tesla from patients with multiple sclerosis and 18 gender- and age matched healthy controls. We assessed overall brain cortical thickness in patients with multiple sclerosis and the scanned healthy controls, and measured the total and regional T1 and T2 white matter lesion volumes in patients with multiple sclerosis. Performances in tests of recognition of mental states and emotions from facial expressions and eye gazes correlated with both total T1-lesion load and regional T1-lesion load of association fiber tracts interconnecting cortical regions related to visual and emotion processing (genu and splenium of corpus callosum, right inferior longitudinal fasciculus, right inferior fronto-occipital fasciculus, uncinate fasciculus). Both of these tests showed correlations with specific cortical areas involved in emotion recognition from facial expressions (right and left fusiform face area, frontal eye filed), processing of emotions (right entorhinal cortex) and socially relevant information (left temporal pole). Thus, both disconnection mechanism due to white matter lesions and cortical thinning of specific brain areas may result in cognitive deficit in multiple sclerosis affecting emotion and mental state processing from facial expressions and contributing to everyday and social life difficulties of these patients.

  1. Disconnection Mechanism and Regional Cortical Atrophy Contribute to Impaired Processing of Facial Expressions and Theory of Mind in Multiple Sclerosis: A Structural MRI Study

    PubMed Central

    Mike, Andrea; Strammer, Erzsebet; Aradi, Mihaly; Orsi, Gergely; Perlaki, Gabor; Hajnal, Andras; Sandor, Janos; Banati, Miklos; Illes, Eniko; Zaitsev, Alexander; Herold, Robert; Guttmann, Charles R. G.; Illes, Zsolt

    2013-01-01

    Successful socialization requires the ability of understanding of others’ mental states. This ability called as mentalization (Theory of Mind) may become deficient and contribute to everyday life difficulties in multiple sclerosis. We aimed to explore the impact of brain pathology on mentalization performance in multiple sclerosis. Mentalization performance of 49 patients with multiple sclerosis was compared to 24 age- and gender matched healthy controls. T1- and T2-weighted three-dimensional brain MRI images were acquired at 3Tesla from patients with multiple sclerosis and 18 gender- and age matched healthy controls. We assessed overall brain cortical thickness in patients with multiple sclerosis and the scanned healthy controls, and measured the total and regional T1 and T2 white matter lesion volumes in patients with multiple sclerosis. Performances in tests of recognition of mental states and emotions from facial expressions and eye gazes correlated with both total T1-lesion load and regional T1-lesion load of association fiber tracts interconnecting cortical regions related to visual and emotion processing (genu and splenium of corpus callosum, right inferior longitudinal fasciculus, right inferior fronto-occipital fasciculus, uncinate fasciculus). Both of these tests showed correlations with specific cortical areas involved in emotion recognition from facial expressions (right and left fusiform face area, frontal eye filed), processing of emotions (right entorhinal cortex) and socially relevant information (left temporal pole). Thus, both disconnection mechanism due to white matter lesions and cortical thinning of specific brain areas may result in cognitive deficit in multiple sclerosis affecting emotion and mental state processing from facial expressions and contributing to everyday and social life difficulties of these patients. PMID:24349280

  2. In Sickness and in Health? Physical Illness as a Risk Factor for Marital Dissolution in Later Life.

    PubMed

    Karraker, Amelia; Latham, Kenzie

    2015-09-01

    The health consequences of marital dissolution are well known, but little work has examined the impact of health on the risk of marital dissolution. We use a sample of 2,701 marriages from the Health and Retirement Study to examine the role of serious physical illness onset in subsequent marital dissolution via either divorce or widowhood. We use a series of discrete time event history models with competing risks to estimate the impact of husband's and wife's physical illness onset on risk of divorce and widowhood. We find that only measures of wife's illness onset are associated with elevated risk of divorce, while measures of either spouse's illness onset is associated with elevated risk of widowhood. Further, in the case of heart problems, we find that this gender difference is statistically significant. These findings suggest health as a determinant of marital dissolution in later life via both biological and gendered social pathways.

  3. The role of family social background and inheritance in later life volunteering: evidence from SHARE-Israel.

    PubMed

    Youssim, Iaroslav; Hank, Karsten; Litwin, Howard

    2015-01-01

    Building on a tripartite model of capitals necessary to perform productive activities and on work suggesting that cumulative (dis-)advantage processes are important mechanisms for life course inequalities, our study set out to investigate the potential role of family social background and inheritance in later life volunteering. We hypothesized that older individuals who inherited work-relevant economic and cultural capitals from their family of origin are more likely to be engaged in voluntary activities than their counterparts with a less advantageous family social background. Our main findings from the analysis of a representative sample of community-dwelling Israelis aged 50 and over provide strong support for this hypothesis: the likelihood to volunteer is significantly higher among those who received substantial financial transfers from their family of origin ("inherited economic capital") and among those having a "white collar" parental background ("inherited cultural capital"). We conclude with perspectives for future research. © The Author(s) 2014.

  4. The relationship between childhood poverty, military service, and later life depression among men: Evidence from the Health and Retirement Study.

    PubMed

    Bareis, Natalie; Mezuk, Briana

    2016-12-01

    Childhood poverty has been associated with depression in adulthood, but whether this relationship extends to later life major depression (MD) or is modified by military service is unclear. Data come from the Health and Retirement Study (HRS) 2010 wave, a longitudinal, nationally representative study of older adults. Men with data on military service and childhood poverty were included (N=6330). Childhood poverty was assessed by four indicators (i.e., parental unemployment, residential instability) experienced before age 16. Military service was categorized as veteran versus civilian, and during draft versus all-volunteer (after 1973) eras. Past year MD was defined by the Composite International Diagnostic Inventory. Four in ten men ever served, with 13.7% in the all-volunteer military. Approximately 12% of civilians, 8% draft era and 24% all-volunteer era veterans had MD. Childhood poverty was associated with higher odds of MD (Odds Ratio (OR): 2.38, 95% Confidence Interval (CI): 1.32-4.32) and higher odds of military service (OR: 2.58, 95% CI: 1.58-4.21). Military service was marginally associated with MD (OR: 1.28, 95% CI: 0.98-1.68) and did not moderate the association between childhood poverty and MD. Self-report data is subject to recall bias. The HRS did not assess childhood physical and emotional abuse, or military combat exposure. Men raised in poverty had greater odds of draft and all-volunteer military service. Early-life experiences, independent of military service, appear associated with greater odds of MD. Assessing childhood poverty in service members may identify risk for depression in later life. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Prolonged breast-feeding protects mothers from later-life obesity and related cardio-metabolic disorders.

    PubMed

    Wiklund, Petri; Xu, Leiting; Lyytikäinen, Arja; Saltevo, Juha; Wang, Qin; Völgyi, Eszter; Munukka, Eveliina; Cheng, Shumei; Alen, Markku; Keinänen-Kiukaanniemi, Sirkka; Cheng, Sulin

    2012-01-01

    To investigate the long-term effects of duration of postpartum lactation on maternal body composition and risk for cardio-metabolic disorders in later life. Retrospective study. Body composition was measured using dual-energy X-ray absorptiometry and serum glucose, insulin and lipids were analysed using enzymatic photometric methods 16-20 years after the last pregnancy. Medical history and lifestyle factors were collected via a self-administered questionnaire. Detailed information regarding weight change patterns during each pregnancy was obtained from personal maternity tracking records. City of Jyväskylä and surroundings in Central Finland. Two hundred and twelve women (mean age 48, range 36-60 years). At 16-20 years after their last pregnancy, women who had breast-fed for less than 6 months had higher total body fat mass and fat mass percentage, particularly in the android region (46·5 (sd 8·2) %) than mothers who had breast-fed for longer than 6 months (39·0 (sd 10·2) %) or for longer than 10 months (38·4 (sd 10·9) %, P < 0·01). These differences were independent of pre-pregnancy weight and BMI, menopausal status, smoking status, level of education, participation in past and present leisure-time physical activity, and current dietary energy intake. Higher body fat mass was also associated with higher fasting serum glucose concentration and insulin resistance, TAG, LDL cholesterol and total cholesterol concentrations, as well as higher systolic and diastolic blood pressure (P < 0·05 for all). Short duration of breast-feeding may induce weight retention and fat mass accumulation, resulting in increased risk of cardio-metabolic disorders in later life.

  6. Micro-scale environment and mental health in later life: Results from the Cognitive Function and Ageing Study II (CFAS II).

    PubMed

    Wu, Yu-Tzu; Prina, A Matthew; Jones, Andy; Barnes, Linda E; Matthews, Fiona E; Brayne, Carol

    2017-08-15

    Poor micro-scale environmental features, such as graffiti and broken windows, have been associated with crime and signs of social disorder with a potential impact on mental health. The aim of this study is to investigate the association between micro-scale environment and mental health problems in later life, including cognitive (cognitive impairment and dementia) and common mental disorders (depressive and anxiety symptoms). The method of visual image audits was used to collect micro-scale environmental data for 3590 participants in the Cognitive Function and Ageing Study II, a population-based multicentre cohort of people aged 65 or above in England. Multilevel logistic regression was used to examine the associations between the quality of micro-scale environment and mental health problems taking into account urban/rural difference. Poor quality of micro-scale environment was associated with nearly 20% increased odds of depressive (OR: 1.19; 95% CI: 0.99, 1.44) and anxiety symptoms (OR: 1.17; 95% CI: 0.99, 1.38) while the direction of association for cognitive disorders differed across urban and rural settings. Although higher odds of cognitive disorders were found in rural settings, living in a poor quality environment was associated with nearly twice higher odds of cognitive impairment (OR: 1.88; 95% CI: 1.18, 2.97) in urban conurbations but 20% lower odds in rural areas (OR: 0.80; 95% CI: 0.57, 1.11). The causal direction could not be fully determined due to the cross-sectional nature of the data. The visual nature of the environmental assessment tool means it likely does not fully capture features related to the availability of local support services, or opportunities for social participation and interaction. The quality of micro-scale environment appears to be important to mental health in older people. Interventions may incorporate the environmental aspect to reduce cognitive and common mental disorders. Copyright © 2017 The Authors. Published by

  7. [Posterior cortical atrophy].

    PubMed

    Solyga, Volker Moræus; Western, Elin; Solheim, Hanne; Hassel, Bjørnar; Kerty, Emilia

    2015-06-02

    Posterior cortical atrophy is a neurodegenerative condition with atrophy of posterior parts of the cerebral cortex, including the visual cortex and parts of the parietal and temporal cortices. It presents early, in the 50s or 60s, with nonspecific visual disturbances that are often misinterpreted as ophthalmological, which can delay the diagnosis. The purpose of this article is to present current knowledge about symptoms, diagnostics and treatment of this condition. The review is based on a selection of relevant articles in PubMed and on the authors' own experience with the patient group. Posterior cortical atrophy causes gradually increasing impairment in reading, distance judgement, and the ability to perceive complex images. Examination of higher visual functions, neuropsychological testing, and neuroimaging contribute to diagnosis. In the early stages, patients do not have problems with memory or insight, but cognitive impairment and dementia can develop. It is unclear whether the condition is a variant of Alzheimer's disease, or whether it is a separate disease entity. There is no established treatment, but practical measures such as the aid of social care workers, telephones with large keypads, computers with voice recognition software and audiobooks can be useful. Currently available treatment has very limited effect on the disease itself. Nevertheless it is important to identify and diagnose the condition in its early stages in order to be able to offer patients practical assistance in their daily lives.

  8. Impaired Memory and Evidence of Histopathology in CA1 Pyramidal Neurons through Injection of Aβ1-42 Peptides into the Frontal Cortices of Rat

    PubMed Central

    Eslamizade, Mohammad Javad; Madjd, Zahra; Rasoolijazi, Homa; Saffarzadeh, Fatemeh; Pirhajati, Vahid; Aligholi, Hadi; Janahmadi, Mahyar; Mehdizadeh, Mehdi

    2016-01-01

    Introduction: Alzheimer’s disease (AD) is one of the most common neurodegenerative disorders, which has much benefited from animal models to find the basics of its pathophysiology. In our previous work (Haghani, Shabani, Javan, Motamedi, & Janahmadi, 2012), a non-transgenic rat model of AD was used in electrophysiological studies. However, we did not investigate the histological aspects in the mentioned study. Methods: An AD model was developed through bilateral injection of amyloid-β peptides (Aβ) into the frontal cortices. Behavioral and histological methods were used to assess alterations in the memory and (ultra)structures. Furthermore, melatonin has been administered to assess its efficacy on this AD model. Results: Passive avoidance showed a progressive decline in the memory following Aβ injection. Furthermore, Nissl staining showed that Aβ neurotoxicity caused shrinkage of the CA1 pyramidal neurons. Neurodegeneration was clearly evident from Fluoro-jade labeled neurons in Aβ treated rats. Moreover, higher NF-κB immunoreactive CA1 pyramidal neurons were remarkably observed in Aβ treated rats. Ultrastructural analysis using electron microscopy also showed the evidence of subcellular abnormalities. Melatonin treatment in this model of AD prevented Aβ-induced increased NF-κB from immunoreaction and neurodegeneration. Discussion: This study suggests that injection of Aβ into the frontal cortices results in the memory decline and histochemical disturbances in CA1 pyramidal neurons. Furthermore, melatonin can prevent several histological changes induced by Aβ. PMID:27303597

  9. Empowerment for Later Life.

    ERIC Educational Resources Information Center

    Myers, Jane E.

    This monograph purports that American society limits the behavior of older individuals based on the arbitrary criterion of chronological age and proposes the concept of empowerment--gaining a sense of personal power or control over over's life--as the antidote for older persons who face devalued status as they age and the for the accompanying drop…

  10. Association between the findings on magnetic resonance imaging screening for syringomyelia in asymptomatic Cavalier King Charles spaniels and observation of clinical signs consistent with syringomyelia in later life.

    PubMed

    Ives, E J; Doyle, L; Holmes, M; Williams, T L; Vanhaesebrouck, A E

    2015-01-01

    A questionnaire-based study was used to investigate the association between the findings on magnetic resonance imaging (MRI) screening for syringomyelia (SM) in 79 asymptomatic Cavalier King Charles spaniels (CKCS) and the subsequent development of clinical signs consistent with SM in later life. Owners reported clinical signs consistent with SM in 13/79 (16%) dogs at the time of the questionnaire. A significantly greater proportion of CKCS with a syrinx visible on MRI screening showed clinical signs in later life (9/25, 36%) than dogs without a visible syrinx (4/54, 7%; odds ratio 6.9). Whether the findings of MRI screening can be used to indicate the likelihood of an asymptomatic CKCS developing clinical signs consistent with SM in later life warrants further prospective study in a larger cohort of dogs.

  11. Adverse childhood experiences (ACEs) and later-life depression: perceived social support as a potential protective factor.

    PubMed

    Cheong, E Von; Sinnott, Carol; Dahly, Darren; Kearney, Patricia M

    2017-09-01

    To investigate associations between adverse childhood experiences (ACEs) and later-life depressive symptoms; and to explore whether perceived social support (PSS) moderates these. We analysed baseline data from the Mitchelstown (Ireland) 2010-2011 cohort of 2047 men and women aged 50-69 years. Self-reported measures included ACEs (Centre for Disease Control ACE questionnaire), PSS (Oslo Social Support Scale) and depressive symptoms (CES-D). The primary exposure was self-report of at least one ACE. We also investigated the effects of ACE exposure by ACE scores and ACE subtypes abuse, neglect and household dysfunction. Associations between each of these exposures and depressive symptoms were estimated using logistic regression, adjusted for socio-demographic factors. We tested whether the estimated associations varied across levels of PSS (poor, moderate and strong). 23.7% of participants reported at least one ACE (95% CI 21.9% to 25.6%). ACE exposures (overall, subtype or ACE scores) were associated with a higher odds of depressive symptoms, but only among individuals with poor PSS. Exposure to any ACE (vs none) was associated with almost three times the odds of depressive symptoms (adjusted OR 2.85; 95% CI 1.64 to 4.95) among individuals reporting poor PSS, while among those reporting moderate and strong PSS, the adjusted ORs were 2.21 (95% CI 1.52 to 3.22) and 1.39 (95% CI 0.85 to 2.29), respectively. This pattern of results was similar when exposures were based on ACE subtype and ACE scores, though the interaction was clearly strongest among those reporting abuse. ACEs are common among older adults in Ireland and are associated with higher odds of later-life depressive symptoms, particularly among those with poor PSS. Interventions that enhance social support, or possibly perceptions of social support, may help reduce the burden of depression in older populations with ACE exposure, particularly in those reporting abuse. © Article author(s) (or their employer

  12. Hypertensive disorders during pregnancy and risk of type 2 diabetes in later life: a systematic review and meta-analysis.

    PubMed

    Wang, Zengfang; Wang, Zengyan; Wang, Luang; Qiu, Mingyue; Wang, Yangang; Hou, Xu; Guo, Zhong; Wang, Bin

    2017-03-01

    Many studies assessed the association between hypertensive disorders during pregnancy and risk of type 2 diabetes mellitus in later life, but contradictory findings were reported. A systemic review and meta-analysis was carried out to elucidate type 2 diabetes mellitus risk in women with hypertensive disorders during pregnancy. Pubmed, Embase, and Web of Science were searched for cohort or case-control studies on the association between hypertensive disorders during pregnancy and subsequent type 2 diabetes mellitus. Random-effect model was used to pool risk estimates. Bayesian meta-analysis was carried out to further estimate the type 2 diabetes mellitus risk associated with hypertensive disorders during pregnancy. Seventeen cohort or prospective matched case-control studies were finally included. Those 17 studies involved 2,984,634 women and 46,732 type 2 diabetes mellitus cases. Overall, hypertensive disorders during pregnancy were significantly correlated with type 2 diabetes mellitus risk (relative risk = 1.56, 95 % confidence interval 1.21-2.01, P = 0.001). Preeclampsia was significantly and independently correlated with type 2 diabetes mellitus risk (relative risk = 2.25, 95 % confidence interval 1.73-2.90, P < 0.001). In addition, gestational hypertension was also significantly and independently correlated with subsequent type 2 diabetes mellitus risk (relative risk = 2.06, 95 % confidence interval 1.57-2.69, P < 0.001). The pooled estimates were not significantly altered in the subgroup analyses of studies on preeclampsia or gestational hypertension. Bayesian meta-analysis showed the relative risks of type 2 diabetes mellitus risk for individuals with hypertensive disorders during pregnancy, preeclampsia, and gestational hypertension were 1.59 (95 % credibility interval: 1.11-2.32), 2.27 (95 % credibility interval: 1.67-2.97), and 2.06 (95 % credibility interval: 1.41-2.84), respectively. Publication bias was not evident

  13. Altered patterns of heartbeat-evoked potentials in depersonalization/derealization disorder: neurophysiological evidence for impaired cortical representation of bodily signals.

    PubMed

    Schulz, André; Köster, Susann; Beutel, Manfred E; Schächinger, Hartmut; Vögele, Claus; Rost, Silke; Rauh, Manfred; Michal, Matthias

    2015-06-01

    Core features of depersonalization/derealization disorder (DPD) are emotional numbing and feelings of disembodiment. Although there are several neurophysiological findings supporting subjective emotional numbing, the psychobiology of disembodiment remains unclear. Heartbeat-evoked potentials (HEPs), which are considered psychophysiological indicators for the cortical representation of afferent signals originating from the cardiovascular system, were assessed in 23 patients with DPD and 24 healthy control individuals during rest and while performing a heartbeat perception task. Absolute HEP amplitudes did not differ between groups. Nevertheless, healthy individuals showed higher HEPs during the heartbeat perception task than during rest, whereas no such effect was found in patients with DPD (p = .031). Patients with DPD had higher total levels of salivary α-amylase than did healthy individuals (9626.6 [8200.0] versus 5344.3 [3745.8] kU min/l; p = .029), but there were no group differences in cardiovascular measures (heart rate = 76.2 [10.1] versus 74.3 [7.5] beats/min, p = .60; normalized low-frequency heart rate variability = 0.63 [0.15] versus 0.56 [0.15] normalized units, p = .099; low frequency/high frequency ratio = 249.3 [242.7] versus 164.8 [108.8], p = .10), salivary cortisol (57.5 [46.7] versus 55.1 [43.6] nmol min/l, p = .86), or cortisone levels (593.2 [260.3] versus 543.8 [257.1] nmol min/l, p = .52). These results suggest altered cortical representation of afferent signals originating from the cardiovascular system in patients with DPD, which may be associated with higher sympathetic tone. These findings may reflect difficulties of patients with DPD to attend to their actual bodily experiences.

  14. Poor Health and Loneliness in Later Life: The Role of Depressive Symptoms, Social Resources, and Rural Environments

    PubMed Central

    2014-01-01

    Objectives. We draw on cognitive discrepancy theory to hypothesize and test a pathway from poor health to loneliness in later life. We hypothesize that poor health will have a negative influence on social participation and social resources, and these factors will mediate between health and loneliness. We hypothesize that rural environments will amplify any difficulties associated with social participation or accessing social resources and that depression will moderate how intensely people react to levels of social contact and support. Methods. We conceptualize a mediation model and a moderated-mediation model. Nationally representative data on older people living in the Republic of Ireland are used to validate the hypothesized pathways. Results. In the mediation model, health has a significant indirect effect on loneliness through the mediating variables social resources and social participation. In the moderated-mediation model, rurality moderates the pathway between health and social resources but not social participation. Depressive symptoms moderate the effect of social resources on loneliness but not social participation. Discussion. The results provide further credence to cognitive discrepancy theory, suggesting that depressive symptoms influence cognitive processes, interfering with judgments about the adequacy of social interaction. The theory is extended by demonstrating the impact of the environment on loneliness. PMID:24326076

  15. In Sickness and in Health? Physical Illness as a Risk Factor for Marital Dissolution in Later Life

    PubMed Central

    Karraker, Amelia; Latham, Kenzie

    2016-01-01

    The health consequences of marital dissolution are well-known, but little work has examined the impact of health on the risk of marital dissolution. In this study we use a sample of 2,701 marriages from the Health and Retirement Study (HRS; 1992–2010) to examine the role of serious physical illness onset (i.e., cancer, heart problems, lung disease, and/or stroke) in subsequent marital dissolution due to either divorce or widowhood. We use a series of discrete-time event history models with competing risks to estimate the impact of husband’s and wife’s physical illness onset on risk of divorce and widowhood. We find that only wife’s illness onset is associated with elevated risk of divorce, while either husband’s or wife’s illness onset is associated with elevated risk of widowhood. These findings suggest the importance of health as a determinant of marital dissolution in later life via both biological and gendered social pathways. PMID:26315504

  16. Religiosity is negatively associated with later-life intelligence, but not with age-related cognitive decline☆

    PubMed Central

    Ritchie, Stuart J.; Gow, Alan J.; Deary, Ian J.

    2014-01-01

    A well-replicated finding in the psychological literature is the negative correlation between religiosity and intelligence. However, several studies also conclude that one form of religiosity, church attendance, is protective against later-life cognitive decline. No effects of religious belief per se on cognitive decline have been found, potentially due to the restricted measures of belief used in previous studies. Here, we examined the associations between religiosity, intelligence, and cognitive change in a cohort of individuals (initial n = 550) with high-quality measures of religious belief taken at age 83 and multiple cognitive measures taken in childhood and at four waves between age 79 and 90. We found that religious belief, but not attendance, was negatively related to intelligence. The effect size was smaller than in previous studies of younger participants. Longitudinal analyses showed no effect of either religious belief or attendance on cognitive change either from childhood to old age, or across the ninth decade of life. We discuss differences between our cohort and those in previous studies – including in age and location – that may have led to our non-replication of the association between religious attendance and cognitive decline. PMID:25278639

  17. Fetal Hematopoietic Stem Cells Are the Canaries in the Coal Mine That Portend Later Life Immune Deficiency

    PubMed Central

    Tate, Everett R.

    2015-01-01

    Disorders of the blood system are a significant and growing global health concern and include a spectrum of diseases ranging from aplastic anemia and leukemias to immune suppression. This array of hematological disorders is attributed to the fact that the blood system undergoes a perpetual cycle of turn over with aged and exhausted red and white blood cells undergoing daily replacement. The foundational cells of this replenishment process are comprised of rare hematopoietic stem cells (HSCs) located in the bone marrow that possess the dual function of long-term self-renewal and multilineage differentiation. This constant turnover makes the hematopoietic system uniquely vulnerable to changes in the environment that impact multilineage differentiation, self-renewal, or both. Notably, environmental endocrine-disrupting exposures occurring during development, when HSCs are first emerging, can lead to alterations in HSC programming that impacts the blood and immune systems throughout life. In this review, we describe the process of fetal hematopoiesis and provide an overview of the intrauterine environmental and endocrine-disrupting compounds that disrupt this process. Finally, we describe research opportunities for fetal HSCs as potential sentinels of later-life blood and immune system disorders. PMID:26241066

  18. Quality of care after early childhood trauma and well-being in later life: child Holocaust survivors reaching old age.

    PubMed

    van der Hal-Van Raalte, Elisheva; Van Ijzendoorn, Marinus H; Bakermans-Kranenburg, Marian J

    2007-10-01

    The link between deprivation and trauma during earliest childhood and psychosocial functioning and health in later life was investigated in a group of child Holocaust survivors. In a nonconvenience sample 203 survivors, born between 1935 and 1944, completed questionnaires on Holocaust survival experience and several inventories on current health, depression, posttraumatic stress, loneliness, and attachment style. Quality of postwar care arrangements and current physical health independently predicted lack of well-being in old age. Loss of parents during the persecution, year of birth of the survivors (being born before or during the war), and memories of the Holocaust did not significantly affect present well-being. Lack of adequate care after the end of World War II is associated with lower well-being of the youngest Holocaust child survivors, even after an intervening period of 60 years. Our study validates Keilson's (1992) concept of "sequential traumatization," and points to the importance of aftertrauma care in decreasing the impact of early childhood trauma.

  19. Early-Life State-of-Residence Characteristics and Later Life Hypertension, Diabetes, and Ischemic Heart Disease.

    PubMed

    Rehkopf, David H; Eisen, Ellen A; Modrek, Sepideh; Mokyr Horner, Elizabeth; Goldstein, Benjamin; Costello, Sadie; Cantley, Linda F; Slade, Martin D; Cullen, Mark R

    2015-08-01

    We examined how state characteristics in early life are associated with individual chronic disease later in life. We assessed early-life state of residence using the first 3 digits of social security numbers from blue- and white-collar workers from a US manufacturing company. Longitudinal data were available from 1997 to 2012, with 305 936 person-years of observation. Disease was assessed using medical claims. We modeled associations using pooled logistic regression with inverse probability of censoring weights. We found small but statistically significant associations between early-state-of-residence characteristics and later life hypertension, diabetes, and ischemic heart disease. The most consistent associations were with income inequality, percentage non-White, and education. These associations were similar after statistically controlling for individual socioeconomic and demographic characteristics and current state characteristics. Characteristics of the state in which an individual lives early in life are associated with prevalence of chronic disease later in life, with a strength of association equivalent to genetic associations found for these same health outcomes.

  20. Differential impact of multiple levels of productive activity engagement on psychological well-being in middle and later life.

    PubMed

    Matz-Costa, Christina; Besen, Elyssa; Boone James, Jacquelyn; Pitt-Catsouphes, Marcie

    2014-04-01

    This study tested the effect of multiple levels of engagement in the productive roles of paid work, volunteering, and caregiving on midlife and older adults' psychological well-being. Using cross-sectional data from a sample of 330 adults aged 50 and older (largely white, women, and educated), a treatment effects model was employed to test the impact of four levels of engagement (not involved and low, medium, and high engagement) on psychological well-being. Those involved in work or volunteer activities who were high in engagement reported greater psychological well-being than those who were not involved, whereas those who were low or medium in engagement reported lower well-being than those not involved. A different pattern emerged for caregiving; midlevels of engagement were associated with higher well-being compared with the noninvolved, whereas low and high levels of engagement were associated with lower well-being. Findings suggest that one's experience of an activity plays an important role in the extent to which involvement is associated with positive outcomes. Recommendations for enhancing role quality to promote psychological well-being in middle and later life are discussed.

  1. Cognitive behavioral therapy for somatic symptom disorders in later life: a prospective comparative explorative pilot study in two clinical populations.

    PubMed

    Verdurmen, Michelle Jh; Videler, Arjan C; Kamperman, Astrid M; Khasho, David; van der Feltz-Cornelis, Christina M

    2017-01-01

    Elderly patients with somatic symptom disorder (SSD) put a great burden on the health care delivery system. Cognitive behavioral therapy (CBT) is effective in adults with SSD. However, no studies have been conducted yet into CBT for SSD in later life. We explored the feasibility of CBT for SSD in the elderly. This is a prospective pilot study comparing two outpatient specialty mental health settings for adults (<60 years; n=13) and for elderly patients (≥60 years; n=9) with SSD. Intervention was 18 structured, protocoled, and supervised CBT sessions. Outcomes were somatic symptoms, pain intensity, pain disability, quality of life, depressive symptoms, and generalized anxiety symptoms. Feasibility of the CBT intervention was explored with self-developed questions, both for the therapists and the patients. Both therapists and elderly patients evaluated the treatment as positive. Somatic symptoms improved significantly in the adult group but not in the elderly group. There was a large, significant decrease in pain intensity and pain disability in elderly patients compared to the adults. Social functioning, vitality, and anxiety symptoms improved significantly in the adults. Presence of chronic medical conditions did not influence these results. This study shows that CBT is feasible as a treatment for SSD in older adults and has encouraging results. Replication in an RCT is warranted.

  2. Continuity and Change in Relationships with Neighbors: Implications for Psychological Well-being in Middle and Later Life

    PubMed Central

    Reyes, Laurent

    2015-01-01

    Objectives. There is growing enthusiasm for community initiatives that aim to strengthen neighbor relationships to promote well-being in later life. Nevertheless, few studies have examined the extent to which relationships with neighbors are associated with better psychological well-being among midlife and older adults. Methods. We used data from 1,071 noninstitutionalized, English-speaking adults, aged 40–70 years, who participated in both waves of the 1995–2005 National Survey of Midlife Development in the United States. Lagged dependent regression models were estimated to examine associations between changes in two dimensions of neighbor relationships (contact and perceived support) and psychological well-being. Results. Few associations were found between relationships with neighbors and negative or positive affect. In contrast, having continuously low levels of contact with neighbors, or losing contact with neighbors over the 10-year study period, was associated with declining levels of eudaimonic well-being. Associations between contact and this aspect of well-being were explained, in part, by less perceived support from neighbors. Discussion. Results suggest that continuity and change in relationships with neighbors is especially important for more developmental aspects of psychological well-being. Implications for future research on the meaning of neighbor relationships and aging in community are discussed. PMID:25106785

  3. Mid and later life care work migration: Patterns of re-organising informal care obligations in Central and Eastern Europe.

    PubMed

    Bauer, Gudrun; Österle, August

    2016-04-01

    Many women in mid or later life from Central and Eastern Europe commute for live-in 24-hour care work to Austria. In addition to paid care work abroad, the majority of women in this age group is confronted with informal (family) care obligations towards children, towards older relatives or towards grandchildren. This study aims to explore the patterns of re-organising these informal care obligations (childcare, long-term care and domestic work) in the respective home country and to analyse the factors that determine the re-organisation. The study builds on qualitative interviews with 20 migrant care workers aged 40years and over, 9 Romanian and 11 Slovakian women providing 24-hour care work in Austria. All interviewees commute in 2- to 4-weekly shifts between the home country and Austria and report multiple informal care obligations towards family members in the respective home country. In most cases, members of the nuclear and extended family, and in many cases husbands or partners of migrant care workers, act as the main substitute caregivers. Institutional care provision plays a more important role for child care as against for older people in need of care for whom care services are hardly available or accessible in the countries observed. While re-organisation depends much on the specific family constellations, strong assumptions towards family care, the limitations in (monetary) resources and the lack of public welfare provisions strongly co-determine the arrangements. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Mother's nutritional miRNA legacy: Nutrition during pregnancy and its possible implications to develop cardiometabolic disease in later life.

    PubMed

    Casas-Agustench, Patricia; Iglesias-Gutiérrez, Eduardo; Dávalos, Alberto

    2015-10-01

    Maternal nutrition during pregnancy and lactation influences the offspring's health in the long-term. Indeed, human epidemiological studies and animal model experiments suggest that either an excess or a deficit in maternal nutrition influence offspring development and susceptibility to metabolic disorders. Different epigenetic mechanisms may explain in part the way by which dietary factors in early critical developmental steps might be able to affect the susceptibility to develop metabolic diseases in adulthood. microRNAs are versatile regulators of gene expression and play a major role during tissue homeostasis and disease. Dietary factors have also been shown to modify microRNA expression. However, the role of microRNAs in fetal programming remains largely unstudied. This review evaluates in vivo studies conducted to analyze the effect of maternal diet on the modulation of the microRNA expression in the offspring and their influence to develop metabolic and cardiovascular disease in later life. In overall, the available evidence suggests that nutritional status during pregnancy influence offspring susceptibility to the development of cardiometabolic risk factors, partly through microRNA action. Thus, therapeutic modulation of microRNAs can open up new strategies to combat - later in life - the effects of nutritional insult during critical points of development.

  5. Childhood Maltreatment and Psychological Well-Being in Later Life: The Mediating Effect of Contemporary Relationships with the Abusive Parent.

    PubMed

    Kong, Jooyoung

    2017-04-26

    Parental childhood maltreatment has a negative impact on psychological well-being in adulthood. However, little is known about whether and how contemporary relationships with an abusive parent might explain the long-term harmful effects. Thus, this study aims to examine the mediating effect of later-life relationships with an abusive parent on the association between parental childhood maltreatment and psychological well-being. Using the 2004-2005 Wisconsin Longitudinal Study, this study analyzed a total of 1,696 adults aged 65 years. A series of ordinary least squares regression and mediational analyses were performed. Key findings showed that maternal childhood neglect and abuse were associated with decreased emotional closeness with mothers, which was, in turn, associated with diminished psychological well-being. In addition, childhood neglect was associated with less frequent exchanges of social support with mothers, which was, in turn, associated with diminished psychological well-being. This study suggests that, despite childhood maltreatment, parent-child relationships persist throughout life, and the continuing relationship with an abusive parent may undermine adult victims' psychological well-being. When intervening with mental health issues of adults who have experienced childhood maltreatment, their unresolved issues with the parent should be properly addressed.

  6. Fetal Hematopoietic Stem Cells Are the Canaries in the Coal Mine That Portend Later Life Immune Deficiency.

    PubMed

    Laiosa, Michael D; Tate, Everett R

    2015-10-01

    Disorders of the blood system are a significant and growing global health concern and include a spectrum of diseases ranging from aplastic anemia and leukemias to immune suppression. This array of hematological disorders is attributed to the fact that the blood system undergoes a perpetual cycle of turn over with aged and exhausted red and white blood cells undergoing daily replacement. The foundational cells of this replenishment process are comprised of rare hematopoietic stem cells (HSCs) located in the bone marrow that possess the dual function of long-term self-renewal and multilineage differentiation. This constant turnover makes the hematopoietic system uniquely vulnerable to changes in the environment that impact multilineage differentiation, self-renewal, or both. Notably, environmental endocrine-disrupting exposures occurring during development, when HSCs are first emerging, can lead to alterations in HSC programming that impacts the blood and immune systems throughout life. In this review, we describe the process of fetal hematopoiesis and provide an overview of the intrauterine environmental and endocrine-disrupting compounds that disrupt this process. Finally, we describe research opportunities for fetal HSCs as potential sentinels of later-life blood and immune system disorders.

  7. Early-Life State-of-Residence Characteristics and Later Life Hypertension, Diabetes, and Ischemic Heart Disease

    PubMed Central

    Eisen, Ellen A.; Modrek, Sepideh; Mokyr Horner, Elizabeth; Goldstein, Benjamin; Costello, Sadie; Cantley, Linda F.; Slade, Martin D.; Cullen, Mark R.

    2015-01-01

    Objectives. We examined how state characteristics in early life are associated with individual chronic disease later in life. Methods. We assessed early-life state of residence using the first 3 digits of social security numbers from blue- and white-collar workers from a US manufacturing company. Longitudinal data were available from 1997 to 2012, with 305 936 person-years of observation. Disease was assessed using medical claims. We modeled associations using pooled logistic regression with inverse probability of censoring weights. Results. We found small but statistically significant associations between early-state-of-residence characteristics and later life hypertension, diabetes, and ischemic heart disease. The most consistent associations were with income inequality, percentage non-White, and education. These associations were similar after statistically controlling for individual socioeconomic and demographic characteristics and current state characteristics. Conclusions. Characteristics of the state in which an individual lives early in life are associated with prevalence of chronic disease later in life, with a strength of association equivalent to genetic associations found for these same health outcomes. PMID:26066927

  8. Diabetes Risk and Disease Management in Later Life: A National Longitudinal Study of the Role of Marital Quality.

    PubMed

    Liu, Hui; Waite, Linda; Shen, Shannon

    2016-11-01

    We assess the association between marital quality and both the risk of developing diabetes and the management of diabetes after its onset in later life. We use data from the first two waves of the National Social Life, Health, and Aging Project to estimate regression models with lagged dependent variables. The sample includes 1,228 married respondents, among whom 389 were diabetic. Those with either a reported diagnosis or with HbA1c ≥ 6.5% are identified diabetic. We categorize diabetic respondents into three groups: controlled, undiagnosed, and uncontrolled diabetes. We conduct factor analysis to construct positive and negative marital quality scales. For women, an increase in positive marital quality between Waves 1 and 2 is related to a lower risk of being diabetic at Wave 2, net of diabetes status at Wave 1; surprisingly, for men, an increase in negative marital quality between Waves 1 and 2 is related to both a lower risk of being diabetic at Wave 2 and a higher chance of controlling diabetes at Wave 2 after its onset. Our results challenge the traditional assumption that negative marital quality is always detrimental to health and encourage family scholars to distinguish different sources and types of negative marital quality. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  9. Holding On and Letting Go: The Perspectives of Pre-Seniors and Seniors on Driving Self-Regulation in Later Life

    ERIC Educational Resources Information Center

    Rudman, Deborah Laliberte; Friedland, Judith; Chipman, Mary; Sciortino, Paola

    2006-01-01

    Although decisions related to driving are vital to well-being in later life, little is known about how aging drivers who do not experience a medical condition that requires driving cessation regulate their driving. This exploratory, qualitative study used focus groups with 79 such community-dwelling individuals to examine driving self-regulation…

  10. The impact of involuntary exit from employment in later life on the risk of major depression and being prescribed anti-depressant medication.

    PubMed

    Hyde, Martin; Hanson, Linda Magnusson; Chungkham, Holendro Singh; Leineweber, Constanze; Westerlund, Hugo

    2015-01-01

    Involuntary employment exit in later life has been shown to be a risk factor for poor physical and mental health. This study aims to examine the relationship between involuntary employment exit in later life and subsequent risk of reporting major depression or being prescribed anti-depressant medication (ADM). Data were drawn from four waves of the Swedish Longitudinal Occupational Survey of Health (SLOSH). This is a nationally representative longitudinal cohort survey of persons employed in Sweden in 2003 and 2005. The sample was restricted to respondents who had exited the labour market aged 50+ years between 2006 and 2012 (N = 1433). Major depression was measured using the Symptom Checklist Core Depression Scale (SCL-CD6). Prescription ADM redeemed from a pharmacy was based on the National Prescribed Drug Register. After controlling for socio-demographic variables, health, health behaviours, and baseline depression, involuntary employment exit was associated with an increased risk of reporting major depression (OR 3.16; CI 1.32-7.61) and becoming newly prescribed ADM (HR 2.08; CI 1.03-4.21) compared to voluntary employment exit. Involuntary employment exit represents a risk for subsequent depression in later life. Mental health and social services ought to consider identifying these individuals for possible intervention programs to reduce the burden of depression in later life.

  11. Cortical auditory disorders: clinical and psychoacoustic features.

    PubMed Central

    Mendez, M F; Geehan, G R

    1988-01-01

    The symptoms of two patients with bilateral cortical auditory lesions evolved from cortical deafness to other auditory syndromes: generalised auditory agnosia, amusia and/or pure word deafness, and a residual impairment of temporal sequencing. On investigation, both had dysacusis, absent middle latency evoked responses, acoustic errors in sound recognition and matching, inconsistent auditory behaviours, and similarly disturbed psychoacoustic discrimination tasks. These findings indicate that the different clinical syndromes caused by cortical auditory lesions form a spectrum of related auditory processing disorders. Differences between syndromes may depend on the degree of involvement of a primary cortical processing system, the more diffuse accessory system, and possibly the efferent auditory system. Images PMID:2450968

  12. Overexpressed neuroglobin raises threshold for nitric oxide-induced impairment of mitochondrial respiratory activities and stress signaling in primary cortical neurons

    PubMed Central

    Singh, Shilpee; Zhuo, Ming; Gorgun, Murat; Englander, Ella W.

    2013-01-01

    Surges of nitric oxide compromise mitochondrial respiration primarily by competitive inhibition of oxygen binding to cytochrome c oxidase (complex IV) and are particularly injurious in neurons, which rely on oxidative phosphorylation for all their energy needs. Here, we show that transgenic overexpression of the neuronal globin protein, neuroglobin, helps diminish protein nitration, preserve mitochondrial function and sustain ATP content of primary cortical neurons challenged by extended nitric oxide exposure. Specifically, in transgenic neurons, elevated neuroglobin curtailed nitric oxide-induced alterations in mitochondrial oxygen consumption rates, including baseline oxygen consumption, consumption coupled with ATP synthesis, proton leak and spare respiratory capacity. Concomitantly, activation of genes involved in sensing and responding to oxidative/nitrosative stress, including the early-immediate c-Fos gene and the phase II antioxidant enzyme, heme oxygenase-1, was diminished in neuroglobin-overexpressing compared to wild-type neurons. Taken together, these differences reflect a lesser insult produced by similar concentrations of nitric oxide in neuroglobin-overexpressing compared to wild-type neurons, suggesting that abundant neuroglobin buffers nitric oxide and raises the threshold of nitric oxide-mediated injury in neurons. PMID:23587847

  13. In utero exposure to benzo(a)pyrene predisposes offspring to cardiovascular dysfunction in later-life

    PubMed Central

    G.E., Jules; Pratap, S.; Ramesh, A.; Hood, D.B.

    2013-01-01

    In utero exposure of the fetus to benzo(a)pyrene [B(a)P], a polycyclic aromatic hydrocarbon, is thought to dysregulate cardiovascular development. To investigate the effects of in utero B(a)P exposure on cardiovascular development, timed-pregnant Long Evans Hooded (LEH) rats were exposed to diluent or B(a)P (150, 300, 600 and 1200 μg/kg/BW) by oral gavage on embryonic (E) days E14 (the metamorphosing embryo stage) through E17 (the 1st fetal stage). There were no significant effects of in utero exposure to B(a)P on the number of pups born per litter or in pre-weaning growth curves. Pre-weaning profiles for B(a)P metabolite generation from cardiovascular tissue were shown to be dose-dependent and elimination of these metabolites was shown to be time-dependent in exposed offspring. Systolic blood pressure on postnatal day P53 in the middle and high exposure groups of offspring were significantly elevated as compared to controls. Microarray and quantitative real-time PCR results were directly relevant to a biological process pathway in animal models for “regulation of blood pressure”. Microarray and quantitative real-time PCR analysis revealed upregulation of mRNA expression for angiotensin (AngII), angiotensinogen (AGT) and endothelial nitric oxide synthase (eNOS) in exposed offspring. Biological network analysis and gene set enrichment analysis subsequently identified potential signaling mechanisms and molecular pathways that might explain the elevated systolic blood pressures observed in B(a)P-exposed offspring. Our findings suggest that in utero exposure to B(a)P predispose offspring to functional deficits in cardiovascular development that may contribute to cardiovascular dysfunction in later life. PMID:22374506

  14. Obesity and excess weight in early adulthood and high risks of arsenic-related cancer in later life.

    PubMed

    Steinmaus, Craig; Castriota, Felicia; Ferreccio, Catterina; Smith, Allan H; Yuan, Yan; Liaw, Jane; Acevedo, Johanna; Pérez, Liliana; Meza, Rodrigo; Calcagno, Sergio; Uauy, Ricardo; Smith, Martyn T

    2015-10-01

    Elevated body mass index (BMI) is a risk factor for cardiovascular disease, diabetes, cancer, and other diseases. Inflammation or oxidative stress induced by high BMI may explain some of these effects. Millions of people drink arsenic-contaminated water worldwide, and ingested arsenic has also been associated with inflammation, oxidative stress, and cancer. To assess the unique situation of people living in northern Chile exposed to high arsenic concentrations in drinking water and investigate interactions between arsenic and BMI, and associations with lung and bladder cancer risks. Information on self-reported body mass index (BMI) at various life stages, smoking, diet, and lifetime arsenic exposure was collected from 532 cancer cases and 634 population-based controls. In subjects with BMIs <90th percentile in early adulthood (27.7 and 28.6 kg/m(2) in males and females, respectively), odds ratios (OR) for lung and bladder cancer combined for arsenic concentrations of <100, 100-800 and >800 µg/L were 1.00, 1.64 (95% CI, 1.19-2.27), and 3.12 (2.30-4.22). In subjects with BMIs ≥90th percentile in early adulthood, the corresponding ORs were higher: 1.00, 1.84 (0.75-4.52), and 9.37 (2.88-30.53), respectively (synergy index=4.05, 95% CI, 1.27-12.88). Arsenic-related cancer ORs >20 were seen in those with elevated BMIs in both early adulthood and in later life. Adjustments for smoking, diet, and other factors had little impact. These findings provide novel preliminary evidence supporting the notion that environmentally-related cancer risks may be markedly increased in people with elevated BMIs, especially in those with an elevated BMI in early-life. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Obesity and excess weight in early adulthood and high risks of arsenic-related cancer in later life

    PubMed Central

    Steinmaus, C; Castriota, F; Ferreccio, C; Smith, AH; Yuan, Y; Liaw, J; Acevedo, J; Perez, L; Meza, R; Calcagno, S; Uauy, R; Smith, MT

    2015-01-01

    Background Elevated body mass index (BMI) is a risk factor for cardiovascular disease, diabetes, cancer, and other diseases. Inflammation or oxidative stress induced by high BMI may explain some of these effects. Millions of people drink arsenic-contaminated water worldwide, and ingested arsenic has also been associated with inflammation, oxidative stress, and cancer. Objectives To assess the unique situation of people living in northern Chile exposed to high arsenic concentrations in drinking water and investigate interactions between arsenic and BMI, and associations with lung and bladder cancer risks. Methods Information on self-reported body mass index (BMI) at various life stages, smoking, diet, and lifetime arsenic exposure was collected from 532 cancer cases and 634 population-based controls. Results In subjects with BMIs <90th percentile in early adulthood (27.7 and 28.6 kg/m2 in males and females, respectively), odds ratios (OR) for lung and bladder cancer combined for arsenic concentrations of <100, 100–800 and >800 μg/L were 1.00, 1.64 (95% CI, 1.19–2.27), and 3.12 (2.30–4.22). In subjects with BMIs ≥90th percentile in early adulthood, the corresponding ORs were higher: 1.00, 1.84 (0.75–4.52), and 9.37 (2.88–30.53), respectively (synergy index=4.05, 95% CI, 1.27–12.88). Arsenic-related cancer ORs >20 were seen in those with elevated BMIs in both early adulthood and in later life. Adjustments for smoking, diet, and other factors had little impact. Conclusion These findings provide novel preliminary evidence supporting the notion that environmentally-related cancer risks may be markedly increased in people with elevated BMIs, especially in those with an elevated BMI in early-life. PMID:26301739

  16. Reasons Why People Change Their Alcohol Consumption in Later Life: Findings from the Whitehall II Cohort Study

    PubMed Central

    Britton, Annie; Bell, Steven

    2015-01-01

    Purpose Harmful alcohol consumption among the ageing population is an important public health issue. Very few studies ask drinkers why they change their consumption in later life. The aim of this paper was to determine whether a group of people aged over 60 years increased or decreased their alcohol consumption over the past decade and to determine the reasons for their change. We also examined whether the responses varied by age, sex and socio-economic position (SEP). Subjects and Methods Data were taken from 6,011 participants (4,310 men, 1,701 women, age range 61 to 85 years) who completed questionnaires at phase 11 (2012-2013) of the Whitehall II Cohort Study. Results Over half the study members reported a change in alcohol consumption over the past decade (40% decreased, 11% increased). The most common reasons given for decreases were as a health precaution and fewer social occasions. Common reasons for increases were more social occasions and fewer responsibilities. The lowest SEP group was less likely to increase consumption compared to high SEP (RR 0.57, 95% CI 0.40 to 0.81). Women were more likely to increase consumption in response to stress/depression than men (RR1.53, 95% CI 1.04 to 2.25). Compared to high SEP, the lowest SEP group was less likely to reduce as a health precaution (RR 0.61, 95% CI 0.38 to 0.76). Conclusions Alcohol consumption in late life is not fixed. Reasons for change vary by age, sex and SEP. Such information could be used to tailor intervention strategies to reduce harmful consumption. PMID:25756213

  17. Relationship between employment histories and frailty trajectories in later life: evidence from the English Longitudinal Study of Ageing

    PubMed Central

    Lu, Wentian; Benson, Rebecca; Glaser, Karen; Corna, Laurie M; Worts, Diana; McDonough, Peggy; Price, Debora; Sacker, Amanda

    2017-01-01

    Background Given the acceleration of population ageing and policy changes to extend working lives, evidence is needed on the ability of older adults to work for longer. To understand more about the health impacts of work, this study examined the relationship between employment histories before retirement and trajectories of frailty thereafter. Methods The sample comprised 2765 women and 1621 men from the English Longitudinal Study of Ageing. We used gendered typologies of life-time employment and a frailty index (FI). Multilevel growth curve models were used to predict frailty trajectories by employment histories. Results Women who had a short break for family care, then did part-time work till 59 years had a lower FI after 60 years than those who undertook full-time work until 59 years. Women who were largely family carers or non-employed throughout adulthood, had higher levels of frailty at 60 years but experienced a slower decline with age. Men who worked full-time but early exited at either 49 or 60 years had a higher FI at 65 years than those who worked full-time up to 65 years. Interaction between employment histories and age indicated that men in full-time work who experienced an early exit at 49 tended to report slower declines. Conclusions For women, experiencing distinct periods throughout the lifecourse of either work or family care may be advantageous for lessening frailty risk in later life. For men, leaving paid employment before 65 years seems to be beneficial for decelerating increases in frailty thereafter. Continuous full-time work until retirement age conferred no long-term health benefits. PMID:27913614

  18. 8-Oxoguanine accumulation in mitochondrial DNA causes mitochondrial dysfunction and impairs neuritogenesis in cultured adult mouse cortical neurons under oxidative conditions

    PubMed Central

    Leon, Julio; Sakumi, Kunihiko; Castillo, Erika; Sheng, Zijing; Oka, Sugako; Nakabeppu, Yusaku

    2016-01-01

    Oxidative stress and mitochondrial dysfunction are implicated in aging-related neurodegenerative disorders. 8-Oxoguanine (8-oxoG), a common oxidised base lesion, is often highly accumulated in brains from patients with neurodegenerative disorders. MTH1 hydrolyses 8-oxo-2′-deoxyguanosine triphosphate (8-oxo-dGTP) to 8-oxo-dGMP and pyrophosphate in nucleotide pools, while OGG1 excises 8-oxoG paired with cytosine in DNA, thereby minimising the accumulation of 8-oxoG in DNA. Mth1/Ogg1-double knockout (TO-DKO) mice are highly susceptible to neurodegeneration under oxidative conditions and show increased accumulation of 8-oxoG in mitochondrial DNA (mtDNA) in neurons, suggesting that 8-oxoG accumulation in mtDNA causes mitochondrial dysfunction. Here, we evaluated the contribution of MTH1 and OGG1 to the prevention of mitochondrial dysfunction during neuritogenesis in vitro. We isolated cortical neurons from adult wild-type and TO-DKO mice and maintained them with or without antioxidants for 2 to 5 days and then examined neuritogenesis. In the presence of antioxidants, both TO-DKO and wild-type neurons exhibited efficient neurite extension and arborisation. However, in the absence of antioxidants, the accumulation of 8-oxoG in mtDNA of TO-DKO neurons was increased resulting in mitochondrial dysfunction. Cells also exhibited poor neurite outgrowth with decreased complexity of neuritic arborisation, indicating that MTH1 and OGG1 are essential for neuritogenesis under oxidative conditions. PMID:26912170

  19. A selective allosteric potentiator of the M1 muscarinic acetylcholine receptor increases activity of medial prefrontal cortical neurons and restores impairments in reversal learning.

    PubMed

    Shirey, Jana K; Brady, Ashley E; Jones, Paulianda J; Davis, Albert A; Bridges, Thomas M; Kennedy, J Phillip; Jadhav, Satyawan B; Menon, Usha N; Xiang, Zixiu; Watson, Mona L; Christian, Edward P; Doherty, James J; Quirk, Michael C; Snyder, Dean H; Lah, James J; Levey, Allan I; Nicolle, Michelle M; Lindsley, Craig W; Conn, P Jeffrey

    2009-11-11

    M(1) muscarinic acetylcholine receptors (mAChRs) may represent a viable target for treatment of disorders involving impaired cognitive function. However, a major limitation to testing this hypothesis has been a lack of highly selective ligands for individual mAChR subtypes. We now report the rigorous molecular characterization of a novel compound, benzylquinolone carboxylic acid (BQCA), which acts as a potent, highly selective positive allosteric modulator (PAM) of the rat M(1) receptor. This compound does not directly activate the receptor, but acts at an allosteric site to increase functional responses to orthosteric agonists. Radioligand binding studies revealed that BQCA increases M(1) receptor affinity for acetylcholine. We found that activation of the M(1) receptor by BQCA induces a robust inward current and increases spontaneous EPSCs in medial prefrontal cortex (mPFC) pyramidal cells, effects which are absent in acute slices from M(1) receptor knock-out mice. Furthermore, to determine the effect of BQCA on intact and functioning brain circuits, multiple single-unit recordings were obtained from the mPFC of rats that showed BQCA increases firing of mPFC pyramidal cells in vivo. BQCA also restored discrimination reversal learning in a transgenic mouse model of Alzheimer's disease and was found to regulate non-amyloidogenic APP processing in vitro, suggesting that M(1) receptor PAMs have the potential to provide both symptomatic and disease modifying effects in Alzheimer's disease patients. Together, these studies provide compelling evidence that M(1) receptor activation induces a dramatic excitation of PFC neurons and suggest that selectively activating the M(1) mAChR subtype may ameliorate impairments in cognitive function.

  20. Excessive alcohol consumption increases mortality in later life: a genetic analysis of the health in men cohort study.

    PubMed

    Almeida, Osvaldo P; McCaul, Kieran; Hankey, Graeme J; Yeap, Bu B; Golledge, Jonathan; Flicker, Leon

    2017-03-01

    We designed this cohort study of men aged 70-89 years to determine if excessive alcohol use increases mortality. They reported history of alcohol use (never, past, ≤ two daily drinks, two to four daily drinks, four to six daily drinks, > six daily drinks) and donated a blood sample in 2001-2004. We determined the ADH1B rs1229984 G>A polymorphism and retrieved mortality data from the Western Australian Data Linkage System. Other study measures included age, education, body mass index, smoking, and history of hypertension, diabetes, chronic respiratory diseases, coronary heart disease and stroke. Of the 3496 participants, 225 (6.4 percent) carried the ADH1B rs1229984 G>A polymorphism. Carriers consumed significantly less alcohol than non-carriers. The adjusted mortality hazard ratio (MHR, 95 percent confidence interval-95%CI) over 8.0 years (range: 10 weeks to 11.2 years) relative to never drinkers was 1.15 (95%CI = 0.86, 1.55) for past drinkers, 0.98 (95%CI = 0.76, 1.25) for men consuming ≤ two daily drinks, 1.13 (95%CI = 0.85, 1.49) for two to four drinks, 1.18 (95%CI = 0.81, 1.71) for four to six drinks and 1.87 (95%CI = 1.11, 3.12) for those consuming more than six daily drinks on a regular basis. The MHR associated with the ADH1B rs1229984 G>A polymorphism was 0.68 (95%CI = 0.54, 0.87). Excessive alcohol use in later life is associated with increased mortality, and this association is likely to be causal. We found no evidence that light to moderate alcohol use decreases the mortality of older men. Health messages regarding the safe use of alcohol in older age may benefit from taking these findings into account. © 2015 Society for the Study of Addiction.

  1. Cognitive, affective and eudemonic well-being in later life: Measurement equivalence over gender and life stage.

    PubMed

    Vanhoutte, Bram; Nazroo, James

    2014-05-31

    The hedonic view on well-being, consisting of both cognitive and affective aspects, assumes that through maximizing pleasurable experiences, and minimizing suffering, the highest levels of well-being can be achieved. The eudemonic approach departs from the concept of a good life that is not just about pleasure and happiness, but involves developing one-self, being autonomous and realizing one's potential. While these approaches are often positioned against each other on theoretical grounds, this paper investigates the empirical plausibility of this two dimensional view on subjective well-being. The interrelations between common measures such as the General Health Questionnaire, the CES-D inventory of depressive symptoms, the satisfaction with life scale and the eudemonic CASP scale are examined in a confirmatory factor analysis framework using the third wave of the English Longitudinal Study of Ageing (ELSA). A multidimensional structure of well-being, distinguishing cognitive, affective and eudemonic well-being, is shown to be the best fitting empirical solution. This three dimensional second order structure is neutral to gender in its measurement. A lower influence of feeling energetic on self-actualisation, and of somatic symptoms of depression on affective well-being was noted for respondents in the fourth age in comparison to respondents in the third age. These small measurement artefacts underline that somatic symptoms of later life depression should be distinguished from mood symptoms. Two main social facts are confirmed when we compare the different forms of well-being over gender and life stage: men tend to have a higher level of well-being than women, and well-being is lower in the fourth age than in the third age. Although the three measures are very closely related, with high correlations between .74 and .88, they each have their specific meaning. While affective and cognitive well-being emphasize the use of an internal yardstick to measure well

  2. Duration of diabetes and its association with depression in later life: The Health In Men Study (HIMS).

    PubMed

    Almeida, Osvaldo P; McCaul, Kieran; Hankey, Graeme J; Yeap, Bu B; Golledge, Jonathan; Norman, Paul E; Flicker, Leon

    2016-04-01

    To examine if diabetes and duration of diabetes are direct or indirect causes of depression in later life. Cross-sectional study of a community-derived sample of 5462 men aged 70-89 years. Men with 'current depression' scored 7 or more on the abbreviated Geriatric Depression Scale (GDS-15), whereas men with 'ever depression' were either currently depressed or reported history or treatment for past depression. The presence of diabetes was established by self-reported history, fasting glucose ≥7 mmol/L (126 mg/dL), or use of insulin or hypoglycemic drugs. Duration of diabetes relied on self-report. Other measured factors included age, place of birth, education, smoking history, and the FRAIL scale. Diabetes was associated with increased odds ratio (OR) of ever (OR=1.49, 95%CI=1.25, 1.76) and current depression (OR=1.94, 95%CI=1.15, 2.48). The association between duration of diabetes and risk of current depression was 'J-shaped' with odds ratios of 1.92 (95%CI=1.44, 2.54), 1.56 (95%CI=0.89, 2.75), 2.49 (95%CI=1.16, 5.32) and 3.13 (95%CI=1.28, 7.63) for <10, 10-19.9, 20-29.9 and ≥30 years of diabetes history compared with older men without diabetes. The strength of these associations was attenuated after the analyses were adjusted for other measured factors, but the shape of the curve did not change. Structural equation modeling showed that frailty mediated some of the association between diabetes duration and depression (about 15%) and was a strong predictor of depression in the sample. In older men, the association between time lived with the diagnosis of diabetes and the risk of depression is 'J-shaped'. Frailty mediates some of the association between diabetes and depression, although other unmeasured factors are also likely to play a role. The introduction of strategies that are effective at decreasing diabetes-related complications may also contribute to decrease the risk of depression among older men. Copyright © 2016 Elsevier Ireland Ltd. All rights

  3. Impaired maturation of dendritic spines without disorganization of cortical cell layers in mice lacking NRG1/ErbB signaling in the central nervous system

    PubMed Central

    Barros, Claudia S.; Calabrese, Barbara; Chamero, Pablo; Roberts, Amanda J.; Korzus, Ed; Lloyd, Kent; Stowers, Lisa; Mayford, Mark; Halpain, Shelley; Müller, Ulrich

    2009-01-01

    Neuregulin-1 (NRG1) and its ErbB2/B4 receptors are encoded by candidate susceptibility genes for schizophrenia, yet the essential functions of NRG1 signaling in the CNS are still unclear. Using CRE/LOX technology, we have inactivated ErbB2/B4-mediated NRG1 signaling specifically in the CNS. In contrast to expectations, cell layers in the cerebral cortex, hippocampus, and cerebellum develop normally in the mutant mice. Instead, loss of ErbB2/B4 impairs dendritic spine maturation and perturbs interactions of postsynaptic scaffold proteins with glutamate receptors. Conversely, increased NRG1 levels promote spine maturation. ErbB2/B4-deficient mice show increased aggression and reduced prepulse inhibition. Treatment with the antipsychotic drug clozapine reverses the behavioral and spine defects. We conclude that ErbB2/B4-mediated NRG1 signaling modulates dendritic spine maturation, and that defects at glutamatergic synapses likely contribute to the behavioral abnormalities in ErbB2/B4-deficient mice. PMID:19240213

  4. Maternal obesity mediated predisposition to respiratory complications at birth and in later life: understanding the implications of the obesogenic intrauterine environment.

    PubMed

    McGillick, Erin V; Lock, Mitchell C; Orgeig, Sandra; Morrison, Janna L

    2017-01-01

    More women than not are entering pregnancy either overweight or obese. This presents a significant health care burden with respect to maternal morbidities and offspring complications at birth and in later life. In recent years it has also become clear that maternal obesity is an even greater global health problem than anticipated, because the effects are not limited to the mother but are also programmed in the fetus, known as the 'intergenerational cycle of obestiy'. Despite a large body of epidemiological evidence reporting outcomes of obese pregnancies, including offspring respiratory complications, much less is known about the molecular effects of maternal obesity on fetal lung development. This review focuses on the influence of altered substrate supply associated with the obesogenic intrauterine environment on fetal lung development. Understanding the molecular mechanisms contributing to altered fetal lung development will lead to improved respiratory outcomes for offspring at birth and in later life.

  5. Cortical and Subcortical Grey and White Matter Atrophy in Myotonic Dystrophies Type 1 and 2 Is Associated with Cognitive Impairment, Depression and Daytime Sleepiness

    PubMed Central

    Prehn, Christian; Krogias, Christos; Schneider, Ruth; Klein, Jan; Gold, Ralf; Lukas, Carsten

    2015-01-01

    to cognitive impairment, depression and daytime sleepiness, partly indicating involvement of complex neuronal networks. PMID:26114298

  6. Neonatal repetitive pain in rats leads to impaired spatial learning and dysregulated hypothalamic-pituitary-adrenal axis function in later life

    PubMed Central

    Chen, Mengying; Xia, Dongqing; Min, Cuiting; Zhao, Xiaoke; Chen, Yinhua; Liu, Li; Li, Xiaonan

    2016-01-01

    Preterm birth is a major health issue. As part of their life-saving care, most preterm infants require hospitalization and are inevitably exposed to repetitive skin-breaking procedures. The long-term effects of neonatal repetitive pain on cognitive and emotional behaviors involving hypothalamic-pituitary-adrenal (HPA) axis function in young and adult rats are unknown. From P8 to P85, mechanical hypersensitivity of the bilateral hindpaws was observed in the Needle group (P < 0.001). Compared with the Tactile group, the Needle group took longer to find the platform on P30 than on P29 (P = 0.03), with a decreased number of original platform site crossings during the probe trial of the Morris water maze test (P = 0.026). Moreover, the Needle group spent more time and took longer distances in the central area than the Tactile group in the Open-field test, both in prepubertal and adult rats (P < 0.05). The HPA axis function in the Needle group differed from the Tactile group (P < 0.05), with decreased stress responsiveness in prepuberty and puberty (P < 0.05) and increased stress responsiveness in adulthood (P < 0.05). This study indicates that repetitive pain that occurs during a critical period may cause severe consequences, with behavioral and neuroendocrine disturbances developing through prepuberty to adult life. PMID:27966656

  7. Emotional well-being and adjustment to vision loss in later life: a meta-synthesis of qualitative studies.

    PubMed

    Nyman, Samuel Robert; Dibb, Bridget; Victor, Christina Rita; Gosney, Margot Ann

    2012-01-01

    To review perceived emotional well-being in older people with visual impairment and perceived factors that inhibit/facilitate psychosocial adjustment to vision loss. The databases of MEDLINE, EMBASE, PsycINFO and CINAHL were searched for studies published from January 1980 to December 2010, which recruited older people with irreversible vision loss, and used qualitative methods for both data collection and analysis. Results sections of the papers were synthesised using a thematic-style analysis to identify the emergent and dominant themes. Seventeen qualitative papers were included in the review, and five main themes emerged from the synthesis: 1) the trauma of an ophthalmic diagnosis, 2) impact of vision loss on daily life, 3) negative impact of visual impairment on psychosocial well-being, 4) factors that inhibit social well-being, and 5) factors that facilitate psychological well-being. We found the response shift model useful for explaining our synthesis. Acquired visual impairment can have a significant impact on older people's well-being and make psychosocial adjustment to the condition a major challenge. Acceptance of the condition and a positive attitude facilitate successful psychosocial adjustment to vision loss as well as social support from family, friends and peers who have successfully adjusted to the condition.

  8. Deficient social and play behavior in juvenile and adult rats after neonatal cortical lesion: effects of chronic pubertal cannabinoid treatment.

    PubMed

    Schneider, Miriam; Koch, Michael

    2005-05-01

    The aim of the present study was to investigate the effects of neonatal excitotoxic lesions of the medial prefrontal cortex (mPFC) on social play, social behavior unrelated to play, and self-grooming in juvenile and adult rats. We additionally examined the behavioral effects of chronic pubertal treatment with the cannabinoid agonist WIN 55,212-2 (WIN) in order to test the hypothesis that early lesions render the brain vulnerable to cannabinoid intake in later life. Neonatal mPFC lesions and pubertal WIN treatment disrupted social play, social behavior, and self-grooming in juvenile and adult rats. Additionally, we observed more social play behaviors during light cycle in WIN-treated than in vehicle-treated rats. Notably, the combination of surgery and WIN treatment disrupted social behavior in lesioned and sham-lesioned rats. The present data indicate that the mPFC is important for adequate juvenile response selection in the context of social play and might be involved in the development of adult social and nonsocial behavior. Moreover, our data add further evidence for an involvement of the cannabinoid system in anxiety and social behavior. Additive effects of neonatal surgery-induced stress or cortical lesions in combination with pubertal cannabinoid administration are also shown. The disturbances of social and nonsocial behavior in rats are comparable to symptoms of early frontal cortex damage, as well as neurodevelopmental disorders in humans, such as schizophrenia and autism. Therefore, we propose the combination of neonatal cortical lesions with chronic cannabinoid administration during puberty as an animal model for studying neuronal mechanisms of impaired social functioning in neuropsychiatric disorders.

  9. Low birthweight or rapid catch-up growth: which is more associated with cardiovascular disease and its risk factors in later life? A systematic review and cryptanalysis.

    PubMed

    Kelishadi, Roya; Haghdoost, Ali Akbar; Jamshidi, Fahimeh; Aliramezany, Maryam; Moosazadeh, Mahmood

    2015-05-01

    The effects of birthweight (the Barker hypothesis) and growth trajectory in early life on the incidence of cardiovascular disease (CVD) and its risk factors in later life have been investigated in a number of studies. To undertake a systematic review and cryptanalysis of the association of low birthweight (LBW) and the postnatal growth trajectory with CVD and its risk factors. English-language publications in PubMed, ISI Web of Science and Scopus were searched. Initially, two independent reviewers identified relevant papers in several steps and the quality of papers was then determined by a validated quality-appraisal checklist. By applying maximum sensitivity, 7259 paper were identified, 382 of which were duplicates and 1273 were considered to be relevant to the topic. Then, after title and abstract review, 628 irrelevant papers were excluded; 26 papers were added after reference-checking. Then, 250 other papers were deleted after full text review. Finally, 39 relevant papers remained and were entered into the systematic review. Overall, 79·6% of all CVD risk factors reported in primary studies of the rapid catch-up growth hypothesis were statistically significant, whereas the corresponding figure was 58·5% for the effects of LBW (Barker hypothesis). This systematic review highlights the importance of low birthweight in increasing the risk of CVD and its risk factors in later life. The results support rapid postnatal catch-up growth of LBW neonates as a more important factor than LBW alone in CVD and its risk factors.

  10. Can volunteering in later life reduce the risk of dementia? A 5-year longitudinal study among volunteering and non-volunteering retired seniors

    PubMed Central

    Hanson, Linda Magnusson; Vantilborgh, Tim; Janssens, Laurens; Jones, Samantha K.; Hyde, Martin

    2017-01-01

    We propose that voluntary work, characterized by social, physical and cognitive activity in later life is associated with fewer cognitive problems and lower dementia rates. We test these assumptions using 3-wave, self-reported, and registry data from the 2010, 2012, and 2014 Swedish National Prescribed Drug Register. We had three groups of seniors in our data: 1) no volunteering (N = 531), 2) discontinuous volunteering (N = 220), and 3) continuous volunteering (N = 250). We conducted a path analysis in Mplus to investigate the effect of voluntary work (discontinuously and continuously) on self-reported cognitive complaints and the likelihood of being prescribed an anti-dementia treatment after controlling for baseline and relevant background variables. Our results indicated that seniors, who continuously volunteered, reported a decrease in their cognitive complaints over time, whereas no such associations were found for the other groups. In addition, they were 2.44 (95%CI [1.86; 3.21]) and 2.46 (95%CI [1,89; 3.24]) times less likely to be prescribed an anti-dementia treatment in 2012 and 2014, respectively. Our results largely support the assumptions that voluntary work in later life is associated with lower self-reported cognitive complaints and a lower risk for dementia, relative to those who do not engage, or only engage episodically in voluntary work. PMID:28301554

  11. ‘You learn to live with all the things that are wrong with you’: gender and the experience of multiple chronic conditions in later life

    PubMed Central

    CLARKE, LAURA HURD; BENNETT, ERICA

    2014-01-01

    This article examines how older adults experience the physical and social realities of having multiple chronic conditions in later life. Drawing on data from in-depth interviews with 16 men and 19 women aged 73+ who had between three and 14 chronic conditions, we address the following research questions: (a) What is it like to have multiple chronic conditions in later life? (b) How do older men and women ‘learn to live’ with the physical and social realities of multiple morbidities? (c) How are older adults’ experiences of illness influenced by age and gender norms? Our participants experienced their physical symptoms and the concomitant limitations to their activities to be a source of personal disruption. However, they normalised their illnesses and made social comparisons in order to achieve a sense of biographical flow in distinctly gendered ways. Forthright in their frustration over their loss of autonomy and physicality but resigned and stoic, the men’s stories reflected masculine norms of control, invulnerability, physical prowess, self-reliance and toughness. The women were dismayed by their bodies’ altered appearances and concerned about how their illnesses might affect their significant others, thereby responding to feminine norms of selflessness, sensitivity to others and nurturance. We discuss the findings in relation to the competing concepts of biographical disruption and biographical flow, as well as successful ageing discourses. PMID:24976658

  12. A Life-span Perspective on Combat Exposure and PTSD Symptoms in Later Life: Findings From the VA Normative Aging Study

    PubMed Central

    Kang, Sungrok; Aldwin, Carolyn M.; Choun, Soyoung; Spiro, Avron

    2016-01-01

    Purpose of the Study: We tested a life-span model of combat exposure on posttraumatic stress disorder (PTSD) symptoms in later life, examining the direct and indirect effects of prewar, warzone, and postwar factors. Design and Methods: The sample included 947 male World War II and Korean War veterans from the VA Normative Aging Study (Mage = 65, SD = 7). They completed mail surveys on childhood family environment, military service and postwar experience, stressful life events, and PTSD symptoms (response rates > 80%). Results: We constructed an initial path model testing cumulative advantage and disadvantage pathways. Although all hypothesized relationships were significant, the model was not a good fit to the data. Subsequent models showed that all three life-span periods had both direct and indirect effects on PTSD symptoms and that there were interesting cross-links between the two sets of pathways. Implications: The life-span perspective provides a useful heuristic to model various developmental effects on later-life outcomes. A supportive childhood family environment can have lifelong protective effects, whereas a conflictual one can set up lifelong patterns of pessimistic appraisals. PMID:26324040

  13. Proposing interactions between maternal phospholipids and the one carbon cycle: A novel mechanism influencing the risk for cardiovascular diseases in the offspring in later life.

    PubMed

    Khot, Vinita; Chavan-Gautam, Preeti; Joshi, Sadhana

    2015-05-15

    Studies have adequately demonstrated the importance of maternal nutrition, particularly, micronutrients (folic acid, vitamin B12) and long chain polyunsaturated fatty acids (LCPUFAs) in determining pregnancy outcome. Reports indicate that children born preterm or to mothers with preeclampsia are at increased risk of developing cardiovascular diseases (CVD) in later life although mechanisms are unclear. Our earlier studies have established that micronutrients (folic acid, vitamin B12) and LCPUFAs are interlinked in the one carbon cycle and influence methylation reactions. Here, we propose a novel hypothesis that altered phospholipid metabolism and dysregulation in the one carbon cycle will result in altered epigenetic programming of placental genes leading to an adverse pregnancy outcome with increased risk of adult diseases in the offspring. Folic acid and vitamin B12 are involved in S-adenosylmethionine (SAM) synthesis, the major methyl donor for most methyl acceptors. Inadequacy of LCPUFA containing phospholipids, one of the major methyl group acceptors in the one carbon metabolic pathway, may cause diversion of methyl groups toward deoxyribonucleic acid (DNA) eventually resulting in aberrant DNA methylation patterns. These modified DNA methylation patterns lead to alterations in the expression of vital genes e.g. angiogenic factor genes thereby contributing to the dysregulation of angiogenesis/vasculogenesis further affecting placental development. This consequently would adversely "program" the fetus for increased risk of CVD in later life.

  14. A Life-span Perspective on Combat Exposure and PTSD Symptoms in Later Life: Findings From the VA Normative Aging Study.

    PubMed

    Kang, Sungrok; Aldwin, Carolyn M; Choun, Soyoung; Spiro, Avron

    2016-02-01

    We tested a life-span model of combat exposure on posttraumatic stress disorder (PTSD) symptoms in later life, examining the direct and indirect effects of prewar, warzone, and postwar factors. The sample included 947 male World War II and Korean War veterans from the VA Normative Aging Study (Mage = 65, SD = 7). They completed mail surveys on childhood family environment, military service and postwar experience, stressful life events, and PTSD symptoms (response rates > 80%). We constructed an initial path model testing cumulative advantage and disadvantage pathways. Although all hypothesized relationships were significant, the model was not a good fit to the data. Subsequent models showed that all three life-span periods had both direct and indirect effects on PTSD symptoms and that there were interesting cross-links between the two sets of pathways. The life-span perspective provides a useful heuristic to model various developmental effects on later-life outcomes. A supportive childhood family environment can have lifelong protective effects, whereas a conflictual one can set up lifelong patterns of pessimistic appraisals. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  15. 'You learn to live with all the things that are wrong with you': gender and the experience of multiple chronic conditions in later life.

    PubMed

    Clarke, Laura Hurd; Bennett, Erica

    2013-02-01

    This article examines how older adults experience the physical and social realities of having multiple chronic conditions in later life. Drawing on data from in-depth interviews with 16 men and 19 women aged 73+ who had between three and 14 chronic conditions, we address the following research questions: (a) What is it like to have multiple chronic conditions in later life? (b) How do older men and women 'learn to live' with the physical and social realities of multiple morbidities? (c) How are older adults' experiences of illness influenced by age and gender norms? Our participants experienced their physical symptoms and the concomitant limitations to their activities to be a source of personal disruption. However, they normalised their illnesses and made social comparisons in order to achieve a sense of biographical flow in distinctly gendered ways. Forthright in their frustration over their loss of autonomy and physicality but resigned and stoic, the men's stories reflected masculine norms of control, invulnerability, physical prowess, self-reliance and toughness. The women were dismayed by their bodies' altered appearances and concerned about how their illnesses might affect their significant others, thereby responding to feminine norms of selflessness, sensitivity to others and nurturance. We discuss the findings in relation to the competing concepts of biographical disruption and biographical flow, as well as successful ageing discourses.

  16. Reduced Cortical Thickness in Mental Retardation

    PubMed Central

    Wang, Chao; Wang, Jiaojian; Zhang, Yun; Yu, Chunshui; Jiang, Tianzi

    2011-01-01

    Mental retardation is a developmental disorder associated with impaired cognitive functioning and deficits in adaptive behaviors. Many studies have addressed white matter abnormalities in patients with mental retardation, while the changes of the cerebral cortex have been studied to a lesser extent. Quantitative analysis of cortical integrity using cortical thickness measurement may provide new insights into the gray matter pathology. In this study, cortical thickness was compared between 13 patients with mental retardation and 26 demographically matched healthy controls. We found that patients with mental retardation had significantly reduced cortical thickness in multiple brain regions compared with healthy controls. These regions include the bilateral lingual gyrus, the bilateral fusiform gyrus, the bilateral parahippocampal gyrus, the bilateral temporal pole, the left inferior temporal gyrus, the right lateral orbitofrontal cortex and the right precentral gyrus. The observed cortical thickness reductions might be the anatomical substrates for the impaired cognitive functioning and deficits in adaptive behaviors in patients with mental retardation. Cortical thickness measurement might provide a sensitive prospective surrogate marker for clinical trials of neuroprotective medications. PMID:22216343

  17. Prenatal exposure to the CB1 receptor agonist WIN 55,212-2 causes learning disruption associated with impaired cortical NMDA receptor function and emotional reactivity changes in rat offspring.

    PubMed

    Antonelli, Tiziana; Tomasini, Maria Cristina; Tattoli, Maria; Cassano, Tommaso; Tanganelli, Sergio; Finetti, Simone; Mazzoni, Elisa; Trabace, Luigia; Steardo, Luca; Cuomo, Vincenzo; Ferraro, Luca

    2005-12-01

    The aim of this study was to investigate whether prenatal exposure to the cannabinoid CB1 receptor agonist WIN 55,212-2 (WIN) at a daily dose devoid of overt signs of toxicity and/or gross malformations (0.5 mg/kg, gestation days 5-20), influences cortical glutamatergic neurotransmission, learning and emotional reactivity in rat offspring. Basal and K+-evoked extracellular glutamate levels were significantly lower in cortical cell cultures obtained from pups exposed to WIN during gestation with respect to those measured in cultures obtained from neonates born from vehicle-treated dams. The addition of NMDA to cortical cell cultures from neonates born from vehicle-treated dams concentration-dependently increased glutamate levels, and this was absent in cell cultures obtained from WIN-exposed pups. WIN-exposed rats also revealed a poorer performance in homing (10-12 days of age) and active avoidance tests (80 days of age) as well as a decrease in the rate of separation-induced ultrasonic emission (10 days of age). Finally, prenatal exposure to WIN induced a reduction in the number of cortical neuronal population. These findings (i) provide evidence for a deficit in cortical glutamatergic neurotransmission and behaviour in the rat neonate following prenatal exposure to WIN; and (ii) suggest that the reduction in cortical glutamatergic neurotransmission, NMDA receptor activity and alterations in neuronal development might underlie, at least in part, the learning deficit and decreased emotional reactivity observed in the offspring.

  18. Neonatal systemic exposure to lipopolysaccharide enhances susceptibility of nigrostriatal dopaminergic neurons to rotenone neurotoxicity in later life

    PubMed Central

    Cai, Zhengwei; Fan, Lir-Wan; Kaizaki, Asuka; Tien, Lu-Tai; Ma, Tangeng; Pang, Yi; Lin, Shuying; Lin, Rick C. S.; Simpson, Kimberly L.

    2013-01-01

    Brain inflammation via intracerebral injection with lipopolysaccharide (LPS) in early life has been shown to increase risks for the development of neurodegenerative disorders in adult rats. To determine if neonatal systemic LPS exposure has the same effects on enhancement of adult dopaminergic neuron susceptibility to rotenone neurotoxicity as centrally-injected LPS does, LPS (2 μg/g body weight) was administered intraperitoneally into post-natal day 5 (P5) rats and when grown to P70, rats were challenged with rotenone, a commonly used pesticide, through subcutaneous mini-pump infusion at a dose of 1.25 mg/kg per day for 14 days. Systemically administered LPS can penetrate into the neonatal rat brain and cause acute and chronic brain inflammation, as evidenced by persistent increases in IL-1β levels, cyclooxygenase-2 expression and microglial activation in the substantia nigra (SN) of P70 rats. Neonatal LPS exposure resulted in suppression of tyrosine hydroxylase (TH) expression, but not actual death of dopaminergic neurons in the SN, as indicated by the reduced number of TH+ cells and unchanged total number of neurons (NeuN+) in the SN. Neonatal LPS exposure also caused motor function deficits, which were spontaneously recoverable by P70. A small dose of rotenone at P70 induced loss of dopaminergic neurons, as indicated by reduced numbers of both TH+ and NeuN+ cells in the SN, and Parkinson’s disease (PD)-like motor impairment in P98 rats that had experienced neonatal LPS exposure, but not in those without the LPS exposure. These results indicate that although neonatal systemic LPS exposure may not necessarily lead to death of dopaminergic neurons in the SN, such an exposure could cause persistent functional alterations in the dopaminergic system and indirectly predispose the nigrostriatal system in the adult brain more vulnerable to be damaged by environmental toxins at an ordinarily non-toxic or sub-toxic dose to develop PD-like pathological features and

  19. Cortical thickness abnormalities in late adolescence with online gaming addiction.

    PubMed

    Yuan, Kai; Cheng, Ping; Dong, Tao; Bi, Yanzhi; Xing, Lihong; Yu, Dahua; Zhao, Limei; Dong, Minghao; von Deneen, Karen M; Liu, Yijun; Qin, Wei; Tian, Jie

    2013-01-01

    Online gaming addiction, as the most popular subtype of Internet addiction, had gained more and more attention from the whole world. However, the structural differences in cortical thickness of the brain between adolescents with online gaming addiction and healthy controls are not well unknown; neither was its association with the impaired cognitive control ability. High-resolution magnetic resonance imaging scans from late adolescence with online gaming addiction (n = 18) and age-, education- and gender-matched controls (n = 18) were acquired. The cortical thickness measurement method was employed to investigate alterations of cortical thickness in individuals with online gaming addiction. The color-word Stroop task was employed to investigate the functional implications of the cortical thickness abnormalities. Imaging data revealed increased cortical thickness in the left precentral cortex, precuneus, middle frontal cortex, inferior temporal and middle temporal cortices in late adolescence with online gaming addiction; meanwhile, the cortical thicknesses of the left lateral orbitofrontal cortex (OFC), insula, lingual gyrus, the right postcentral gyrus, entorhinal cortex and inferior parietal cortex were decreased. Correlation analysis demonstrated that the cortical thicknesses of the left precentral cortex, precuneus and lingual gyrus correlated with duration of online gaming addiction and the cortical thickness of the OFC correlated with the impaired task performance during the color-word Stroop task in adolescents with online gaming addiction. The findings in the current study suggested that the cortical thickness abnormalities of these regions may be implicated in the underlying pathophysiology of online gaming addiction.

  20. Cortical Thickness Abnormalities in Late Adolescence with Online Gaming Addiction

    PubMed Central

    Yuan, Kai; Cheng, Ping; Dong, Tao; Bi, Yanzhi; Xing, Lihong; Yu, Dahua; Zhao, Limei; Dong, Minghao; von Deneen, Karen M.; Liu, Yijun; Qin, Wei; Tian, Jie

    2013-01-01

    Online gaming addiction, as the most popular subtype of Internet addiction, had gained more and more attention from the whole world. However, the structural differences in cortical thickness of the brain between adolescents with online gaming addiction and healthy controls are not well unknown; neither was its association with the impaired cognitive control ability. High-resolution magnetic resonance imaging scans from late adolescence with online gaming addiction (n = 18) and age-, education- and gender-matched controls (n = 18) were acquired. The cortical thickness measurement method was employed to investigate alterations of cortical thickness in individuals with online gaming addiction. The color-word Stroop task was employed to investigate the functional implications of the cortical thickness abnormalities. Imaging data revealed increased cortical thickness in the left precentral cortex, precuneus, middle frontal cortex, inferior temporal and middle temporal cortices in late adolescence with online gaming addiction; meanwhile, the cortical thicknesses of the left lateral orbitofrontal cortex (OFC), insula, lingual gyrus, the right postcentral gyrus, entorhinal cortex and inferior parietal cortex were decreased. Correlation analysis demonstrated that the cortical thicknesses of the left precentral cortex, precuneus and lingual gyrus correlated with duration of online gaming addiction and the cortical thickness of the OFC correlated with the impaired task performance during the color-word Stroop task in adolescents with online gaming addiction. The findings in the current study suggested that the cortical thickness abnormalities of these regions may be implicated in the underlying pathophysiology of online gaming addiction. PMID:23326379

  1. Developmental exposure to 2,3,7,8 tetrachlorodibenzo-p-dioxin attenuates later-life Notch1-mediated T cell development and leukemogenesis

    SciTech Connect

    Ahrenhoerster, Lori S.; Leuthner, Tess C.; Tate, Everett R.; Lakatos, Peter A.; Laiosa, Michael D.

    2015-03-01

    Over half of T cell acute lymphoblastic leukemia (T-ALL) patients have activating mutations in the Notch gene. Moreover, the contaminant 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) is a known carcinogen that mediates its toxicity through the aryl hydrocarbon receptor (AHR), and crosstalk between activated AHR and Notch signaling pathways has previously been observed. Given the importance of Notch signaling in thymocyte development and T-ALL disease progression, we hypothesized that the activated AHR potentiates disease initiation and progression in an in vivo model of Notch1-induced thymoma. This hypothesis was tested utilizing adult and developmental exposure paradigms to TCDD in mice expressing a constitutively active Notch1 transgene (Notch{sup ICN-TG}). Following exposure of adult Notch{sup ICN-TG} mice to a single high dose of TCDD, we observed a significant increase in the efficiency of CD8 thymocyte generation. We next exposed pregnant mice to 3 μg/kg of TCDD throughout gestation and lactation to elucidate effects of developmental AHR activation on later-life T cell development and T-ALL-like thymoma susceptibility induced by Notch1. We found that the vehicle-exposed Notch{sup ICN-TG} offspring have a peripheral T cell pool heavily biased toward the CD4 lineage, while TCDD-exposed Notch{sup ICN-TG} offspring were biased toward the CD8 lineage. Furthermore, while the vehicle-exposed NotchICN-TG mice showed increased splenomegaly and B to T cell ratios indicative of disease, mice developmentally exposed to TCDD were largely protected from disease. These studies support a model where developmental AHR activation attenuates later-life Notch1-dependent impacts on thymocyte development and disease progression. - Highlights: • Adult mice exposed to 30 μg/kg TCDD have higher efficiency of CD8 thymocyte generation. • Mice carrying a constitutively active Notch transgene were exposed to 3 μg/kg TCDD throughout development. • Progression of Notch

  2. Felt Obligation to Help Others as a Protective Factor Against Losses in Psychological Well-being Following Functional Decline in Middle and Later Life

    PubMed Central

    2009-01-01

    This study examined felt obligation to help others in two domains (close others and society) as protective factors against losses in psychological well-being following functional decline. Lagged-dependent regression models were estimated using data from 849 respondents aged 35–74 years and without any functional limitations at baseline in the 1995–2005 National Survey of Midlife in the United States. Greater felt obligation to help close others protected against declining self-acceptance in the face of more severe functional decline, and greater felt obligation to help society protected against declining personal growth and self-acceptance. Greater felt obligation to help close others and society protected against increasing depressive symptoms at younger ages in adulthood. Findings suggest the importance for additional research on how aspects of altruism can promote psychological adaptation to declining functional health in middle and later life. PMID:19825942

  3. THE ROLE OF PERCEIVED RELIGIOUS SIMILARITY IN THE QUALITY OF MOTHER-CHILD RELATIONS IN LATER-LIFE: DIFFERENCES WITHIN FAMILIES AND BETWEEN RACES

    PubMed Central

    Sechrist, Jori; Suitor, J. Jill; Vargas, Nicholas; Pillemer, Karl

    2010-01-01

    Despite evidence of the importance of value similarity in predicting parent-adult child relations, little attention has been given to the unique role of religious similarity. Using 1,407 dyads nested within 390 families, we examine whether religious similarity predicts the quality of mother-child relations in later life, and whether the strength of this association differs by race. Consistent with our hypotheses, religious similarity was found to be an important factor in predicting both closeness and conflict, particularly in Black families. These findings suggest that it may be important to give greater attention to religion when studying patterns of interaction and support in the later years, especially among Black families. PMID:21221411

  4. Patterns of Shelter Use Among Men New to Homelessness in Later Life: Duration of Stay and Psychosocial Factors Related to Departure.

    PubMed

    Rothwell, David W; Sussman, Tamara; Grenier, Amanda; Mott, Sebastian; Bourgeois-Guérin, Valérie

    2017-01-01

    People who become homeless for the first time in late life are a growing but understudied population. This study draws on administrative data from one shelter (N = 1,214 first-time homeless) to assess the extent to which age is related to shelter stay and, to examine psychosocial factors that may be associated with shelter departure. Our bivariate and survival analysis results suggest that older homeless men stay in the shelter 2 weeks longer than younger clients. Older men with pending legal issues and mobility concerns were more likely to leave the shelter than those without such concerns. Findings highlight the impact of age and other psychosocial variables on shelter stay, and provide direction from which to address homelessness among men who are new to homelessness in later life.

  5. Revising the personality disorder diagnostic criteria for the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-V): consider the later life context.

    PubMed

    Balsis, Steve; Segal, Daniel L; Donahue, Cailin

    2009-10-01

    The categorical measurement approach implemented by the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) personality disorder (PD) diagnostic system is theoretically and pragmatically limited. As a result, many prominent psychologists now advocate for a shift away from this approach in favor of more conceptually sound dimensional measurement. This shift is expected to improve the psychometric properties of the personality disorder (PD) diagnostic system and make it more useful for clinicians and researchers. The current article suggests that despite the probable benefits of such a change, several limitations will remain if the new diagnostic system does not closely consider the context of later life. A failure to address the unique challenges associated with the assessment of personality in older adults likely will result in the continued limited validity, reliability, and utility of the Diagnostic and Statistical Manual of Mental Disorders (DSM) system for this growing population. This article discusses these limitations and their possible implications.

  6. Developmental Programming of Nonalcoholic Fatty Liver Disease: The Effect of Early Life Nutrition on Susceptibility and Disease Severity in Later Life.

    PubMed

    Li, Minglan; Reynolds, Clare M; Segovia, Stephanie A; Gray, Clint; Vickers, Mark H

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is fast becoming the most common liver disease globally and parallels rising obesity rates. The developmental origins of health and disease hypothesis have linked alterations in the early life environment to an increased risk of metabolic disorders in later life. Altered early life nutrition, in addition to increasing risk for the development of obesity, type 2 diabetes, and cardiovascular disease in offspring, is now associated with an increased risk for the development of NAFLD. This review summarizes emerging research on the developmental programming of NAFLD by both maternal obesity and undernutrition with a particular focus on the possible mechanisms underlying the development of hepatic dysfunction and potential strategies for intervention.

  7. Developmental Programming of Nonalcoholic Fatty Liver Disease: The Effect of Early Life Nutrition on Susceptibility and Disease Severity in Later Life

    PubMed Central

    Li, Minglan; Reynolds, Clare M.; Segovia, Stephanie A.; Vickers, Mark H.

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is fast becoming the most common liver disease globally and parallels rising obesity rates. The developmental origins of health and disease hypothesis have linked alterations in the early life environment to an increased risk of metabolic disorders in later life. Altered early life nutrition, in addition to increasing risk for the development of obesity, type 2 diabetes, and cardiovascular disease in offspring, is now associated with an increased risk for the development of NAFLD. This review summarizes emerging research on the developmental programming of NAFLD by both maternal obesity and undernutrition with a particular focus on the possible mechanisms underlying the development of hepatic dysfunction and potential strategies for intervention. PMID:26090409

  8. Cultural identity and belonging in later life: is extra care housing an attractive concept to older Jewish people living in Britain?

    PubMed

    Holland, Caroline A; Katz, Jeanne S

    2010-03-01

    The extra care housing concept of supported independence within a caring community is one that may offer much to minority communities, particularly those with changing patterns of family care. The context for this study is a UK population which is ageing, with a relatively small but growing number of older people within religious and ethnic minority groups who have needs specific to their cultural identity in addition to those in common with the majority. In considering its need for new forms of later life accommodation, the British Jewish community is looking for models that are acceptable both in terms of specifically Jewish cultural requirements and with respect to 'mainstream' middle class expectations of amenity, service, and social inclusion. This article presents findings of sixteen focus groups with middle-aged and older members of Jewish communities in London and the south east of England, and reflects on their attitudes to specificity in cultural provision in extra care.

  9. Felt obligation to help others as a protective factor against losses in psychological well-being following functional decline in middle and later life.

    PubMed

    Greenfield, Emily A

    2009-11-01

    This study examined felt obligation to help others in two domains (close others and society) as protective factors against losses in psychological well-being following functional decline. Lagged-dependent regression models were estimated using data from 849 respondents aged 35-74 years and without any functional limitations at baseline in the 1995-2005 National Survey of Midlife in the United States. Greater felt obligation to help close others protected against declining self-acceptance in the face of more severe functional decline, and greater felt obligation to help society protected against declining personal growth and self-acceptance. Greater felt obligation to help close others and society protected against increasing depressive symptoms at younger ages in adulthood. Findings suggest the importance for additional research on how aspects of altruism can promote psychological adaptation to declining functional health in middle and later life.

  10. Long-term Excessive Body Weight and Adult Left Ventricular Hypertrophy Are Linked Through Later Life Body Size and Blood Pressure: The Bogalusa Heart Study.

    PubMed

    Zhang, Huijie; Zhang, Tao; Li, Shengxu; Guo, Yajun; Shen, Wei; Fernandez, Camilo; Harville, Emily W; Bazzano, Lydia A; Urbina, Elaine M; He, Jiang; Chen, Wei

    2017-02-23

    Rationale: Childhood adiposity is associated with cardiac structure in later life, but little is known regarding to what extent childhood body weight affects adult left ventricular geometric patterns through adult body size and blood pressure (BP). Objective: Determine quantitatively the mediation effect of adult body weight and BP on the association of childhood BMI with adult left ventricular hypertrophy (LVH). Methods and Results: This longitudinal study consisted of 710 adults, age 26 to 48 years, who had been examined for BMI and BP measured 4 or more times during childhood and 2 or more times during adulthood, with a mean follow-up period of 28.0 years. After adjusting for age, race and sex, adult BMI had a significant mediation effect (76.4%, p<0.01) on the childhood BMI-adult LV mass index (LVMI) association. The mediation effects of adult systolic BP (SBP, 15.2%), long-term burden (12.1%) and increasing trends of SBP (7.9%) were all significant (p<0.01). Furthermore, these mediators also had significant mediation effects on the association of childhood BMI with adult LVH, eccentric and concentric hypertrophy. Importantly, the mediation effects of adult BMI were all significantly stronger than those of adult SBP on LVMI, LVH and LV remodeling patterns (p<0.01). Additionally, the mediation effect of SBP on concentric hypertrophy was significantly stronger than on eccentric hypertrophy (p<0.01). Conclusions: These findings suggest that increased childhood BMI has long-term adverse impact on subclinical changes in adult cardiac structure, and early life excessive body weight and adult LVH are linked through later life excessive body weight and elevated BP.

  11. Developmental Exposure To 2,3,7,8 Tetrachlorodibenzo-p-Dioxin Attenuates Later-Life Notch1-Mediated T Cell Development and Leukemogenesis

    PubMed Central

    Ahrenhoerster, Lori S.; Leuthner, Tess C.; Tate, Everett R.; Lakatos, Peter A.; Laiosa, Michael D.

    2015-01-01

    Over half of T-cell acute lymphoblastic leukemia (T-ALL) patients have activating mutations in the Notch gene. Moreover, the contaminant 2,3,7,8 Tetrachlorodibenzo-p-dioxin (TCDD) is a known carcinogen that mediates its toxicity through the aryl hydrocarbon receptor (AHR), and crosstalk between activated AHR and Notch signaling pathways has previously been observed. Given the importance of Notch signaling in thymocyte development and T-ALL disease progression, we hypothesized that the activated AHR potentiates disease initiation and progression in an in vivo model of Notch1-induced thymoma. This hypothesis was tested utilizing adult and developmental exposure paradigms to TCDD in mice expressing a constitutively active Notch1 transgene (NotchICN-TG). Following exposure of adult NotchICN-TG mice to a single high dose of TCDD, we observed a significant increase in the efficiency of CD8 thymocyte generation. We next exposed pregnant mice to 3μg/kg of TCDD throughout gestation and lactation to elucidate effects of developmental AHR activation on later-life T cell development and T-ALL-like thymoma susceptibility induced by Notch1. We found that the vehicle-exposed NotchICN-TG offspring have a peripheral T-cell pool heavily biased toward the CD4 lineage, while TCDD-exposed NotchICN-TG offspring were biased toward the CD8 lineage. Furthermore, while the vehicle-exposed NotchICN-TG mice showed increased splenomegaly and B to T cell ratios indicative of disease, mice developmentally exposed to TCDD were largely protected from disease. These studies support a model where developmental AHR activation attenuates later-life Notch1-dependent impacts on thymocyte development and disease progression. PMID:25585350

  12. Decreased prefrontal cortical dopamine transmission in alcoholism.

    PubMed

    Narendran, Rajesh; Mason, Neale Scott; Paris, Jennifer; Himes, Michael L; Douaihy, Antoine B; Frankle, W Gordon

    2014-08-01

    Basic studies have demonstrated that optimal levels of prefrontal cortical dopamine are critical to various executive functions such as working memory, attention, inhibitory control, and risk/reward decisions, all of which are impaired in addictive disorders such as alcoholism. Based on this and imaging studies of alcoholism that have demonstrated less dopamine in the striatum, the authors hypothesized decreased dopamine transmission in the prefrontal cortex in persons with alcohol dependence. To test this hypothesis, amphetamine and [11C]FLB 457 positron emission tomography were used to measure cortical dopamine transmission in 21 recently abstinent persons with alcohol dependence and 21 matched healthy comparison subjects. [11C]FLB 457 binding potential, specific compared to nondisplaceable uptake (BPND), was measured in subjects with kinetic analysis using the arterial input function both before and after 0.5 mg kg-1 of d-amphetamine. Amphetamine-induced displacement of [11C]FLB 457 binding potential (ΔBPND) was significantly smaller in the cortical regions in the alcohol-dependent group compared with the healthy comparison group. Cortical regions that demonstrated lower dopamine transmission in the alcohol-dependent group included the dorsolateral prefrontal cortex, medial prefrontal cortex, orbital frontal cortex, temporal cortex, and medial temporal lobe. The results of this study, for the first time, unambiguously demonstrate decreased dopamine transmission in the cortex in alcoholism. Further research is necessary to understand the clinical relevance of decreased cortical dopamine as to whether it is related to impaired executive function, relapse, and outcome in alcoholism.

  13. Cortical thinning in former professional soccer players.

    PubMed

    Koerte, Inga K; Mayinger, Michael; Muehlmann, Marc; Kaufmann, David; Lin, Alexander P; Steffinger, Denise; Fisch, Barbara; Rauchmann, Boris-Stephan; Immler, Stefanie; Karch, Susanne; Heinen, Florian R; Ertl-Wagner, Birgit; Reiser, Maximilian; Stern, Robert A; Zafonte, Ross; Shenton, Martha E

    2016-09-01

    Soccer is the most popular sport in the world. Soccer players are at high risk for repetitive subconcussive head impact when heading the ball. Whether this leads to long-term alterations of the brain's structure associated with cognitive decline remains unknown. The aim of this study was to evaluate cortical thickness in former professional soccer players using high-resolution structural MR imaging. Fifteen former male professional soccer players (mean age 49.3 [SD 5.1] years) underwent high-resolution structural 3 T MR imaging, as well as cognitive testing. Fifteen male, age-matched former professional non-contact sport athletes (mean age 49.6 [SD 6.4] years) served as controls. Group analyses of cortical thickness were performed using voxel-based statistics. Soccer players demonstrated greater cortical thinning with increasing age compared to controls in the right inferolateral-parietal, temporal, and occipital cortex. Cortical thinning was associated with lower cognitive performance as well as with estimated exposure to repetitive subconcussive head impact. Neurocognitive evaluation revealed decreased memory performance in the soccer players compared to controls. The association of cortical thinning and decreased cognitive performance, as well as exposure to repetitive subconcussive head impact, further supports the hypothesis that repetitive subconcussive head impact may play a role in early cognitive decline in soccer players. Future studies are needed to elucidate the time course of changes in cortical thickness as well as their association with impaired cognitive function and possible underlying neurodegenerative process.

  14. Household Disbandment in Later Life

    PubMed Central

    Sergeant, Julie F.; Dingel, Molly; Bowen, Mary Elizabeth

    2005-01-01

    Objectives. This study described activities that older people undertake to reduce the volume of their possessions in the course of a residential move to smaller quarters, a process with practical, cognitive, emotional, and social dimensions. Methods. Qualitative interviews were conducted with members of 30 households who had moved in the prior year. The disbandment period, typically lasting about 2 months, was a particular focus of the interview. Results. The interviews suggested nine reasons why people had accumulated and kept things, which now became problematic for the impending move. The initial steps of disbandment entailed decisions about major furniture and meaningful gifts to family and friends, followed by evaluation of the remaining belongings for retention, sale, further gifts, donation, or discard. Things not divested by one means were reassigned to another strategy. People took pleasure in dispositions that saw their things used, cared for, and valued as they had done, thus fulfilling a responsibility to their belongings. Discussion. Disbandment is an acute episode of a more general, lifelong process of possession management. It is an encounter with things that are meaningful to the self, but as it unfolds, it also makes new meaning for things. PMID:15358801

  15. Future talk in later life.

    PubMed

    Paoletti, Isabella; Gomes, Sandra

    2014-04-01

    This article focuses on the relevance that the dimension of the future has for promoting healthy and active aging. Older people generally have difficulties in talking about the future and when they do they generally express very negative perspectives on it. The data analyzed in this paper are part of an on-going interdisciplinary research project: "Aging, poverty and social exclusion: an interdisciplinary study on innovative support services" (https://apseclunl.wordpress.com/). The project aims at documenting good practices in social intervention with older people who are at risk of exclusion. This study describes and critically discusses an activity carried out in Portugal among older women in a poor area in the suburb of Lisbon entitled "self-awareness workshop on the future". Through a detailed discourse analysis within an ethnomethodological framework the study shows age membership categorizations in use and categorization processes, examining the workshop interaction. In particular, the article describes how the psychologist works at deconstructing and problematizing the negative connotations related to age membership categories. Taking into consideration the interactionally constructed nature of aging and the material consequences that different attitudes towards aging can imply is very important in particular in relation to the provision of services to older people.

  16. Basic visual function and cortical thickness patterns in posterior cortical atrophy.

    PubMed

    Lehmann, Manja; Barnes, Josephine; Ridgway, Gerard R; Wattam-Bell, John; Warrington, Elizabeth K; Fox, Nick C; Crutch, Sebastian J

    2011-09-01

    Posterior cortical atrophy (PCA) is characterized by a progressive decline in higher-visual object and space processing, but the extent to which these deficits are underpinned by basic visual impairments is unknown. This study aimed to assess basic and higher-order visual deficits in 21 PCA patients. Basic visual skills including form detection and discrimination, color discrimination, motion coherence, and point localization were measured, and associations and dissociations between specific basic visual functions and measures of higher-order object and space perception were identified. All participants showed impairment in at least one aspect of basic visual processing. However, a number of dissociations between basic visual skills indicated a heterogeneous pattern of visual impairment among the PCA patients. Furthermore, basic visual impairments were associated with particular higher-order object and space perception deficits, but not with nonvisual parietal tasks, suggesting the specific involvement of visual networks in PCA. Cortical thickness analysis revealed trends toward lower cortical thickness in occipitotemporal (ventral) and occipitoparietal (dorsal) regions in patients with visuoperceptual and visuospatial deficits, respectively. However, there was also a lot of overlap in their patterns of cortical thinning. These findings suggest that different presentations of PCA represent points in a continuum of phenotypical variation.

  17. With a little help from my friends?: racial and gender differences in the role of social support in later-life depression medication adherence.

    PubMed

    Gerlach, Lauren B; Kavanagh, Janet; Watkins, Daphne; Chiang, Claire; Kim, Hyungjin M; Kales, Helen C

    2017-09-01

    Social support has been shown to be an important factor in improving depression symptom outcomes, yet less is known regarding its impact on antidepressant medication adherence. This study sought to evaluate the role of perceived social support on adherence to new antidepressant medication prescriptions in later-life depression. Data from two prospective observational studies of participants ≥60 years old, diagnosed with depression, and recently prescribed a new antidepressant (N = 452). Perceived social support was measured using a subscale of the Duke Social Support Index and medication adherence was assessed using a validated self-report measure. At four-month follow up, 68% of patients reported that they were adherent to antidepressant medication. Examining the overall sample, logistic regression analysis demonstrated no significant relationship between perceived social support and medication adherence. However, when stratifying the sample by social support, race, and gender, adherence significantly differed by race and gender in those with inadequate social support: Among those with low social support, African-American females were significantly less likely to adhere to depression treatment than white females (OR = 4.82, 95% CI = 1.14-20.28, p = 0.032) and white males (OR = 3.50, 95% CI = 1.03-11.92, p = 0.045). There is a significant difference in antidepressant medication adherence by race and gender in those with inadequate social support. Tailored treatment interventions for low social support should be sensitive to racial and gender differences.

  18. Race/Ethnic and Nativity Disparities in Later Life Physical Performance: The Role of Health and Socioeconomic Status Over the Life Course

    PubMed Central

    Krueger, Patrick M.; Rohlfsen, Leah

    2012-01-01

    Objectives. We examine race/ethnic and nativity differences in objective measures of physical performance (i.e., peak expiratory flow, grip strength, and gait speed) in a nationally representative sample of older Whites, Blacks, and Hispanics. We also examine whether detailed measures of childhood and adult health and socioeconomic status (SES) mediate race/ethnic differences in physical performance. Method. We use data from the Health and Retirement Study, a population-based sample of older Americans born before 1947, and 3 measures of physical performance. Nested ordinary least squares models examine whether childhood and adult health and SES mediate race/ethnic differences in performance. Results. We find large and significant race/ethnic and nativity differences in lung function, grip strength, and gait speed. Adjusting for childhood and current adult health and SES reduces race/ethnic differences in physical performance but does not eliminate them entirely. Childhood health and SES as well as more proximal levels of SES are important determinants of race/ethnic disparities in later life physical performance. Discussion. The analysis highlights that a large proportion of race/ethnic and nativity disparities result from health and socioeconomic disadvantages in both early life and adulthood and thus suggests multiple intervention points at which disparities can be reduced. PMID:22391749

  19. Maternal obesity induced by a high fat diet causes altered cellular development in fetal brains suggestive of a predisposition of offspring to neurological disorders in later life.

    PubMed

    Stachowiak, Ewa K; Srinivasan, Malathi; Stachowiak, Michal K; Patel, Mulchand S

    2013-12-01

    Fetal development in an obese maternal intrauterine environment has been shown to predispose the offspring for a number of metabolic disorders in later life. The observation that a large percentage of women of child-bearing age in the US are overweight/obese during pregnancy is therefore a source of concern. A high fat (HF) diet-induced obesity in female rats has been used as a model for maternal obesity. The objective of this study was to determine cellular development in brains of term fetuses of obese rats fed a HF diet from the time of weaning. Fetal brains were dissected out on gestational day 21 and processed for immunohistochemical analysis in the hypothalamic as well as extra-hypothalamic regions. The major observation of this study is that fetal development in the obese HF female rat induced several alterations in the HF fetal brain. Marked increases were observed in orexigenic signaling and a significant decrease was observed for anorexigenic signaling in the vicinity of the 3rd ventricle in HF brains. Additionally, our results indicated diminished migration and maturation of stem-like cells in the 3rd ventricular region as well as in the brain cortex. The results from the present study indicate developmental alterations in the hypothalamic and extra-hypothalamic regions in the HF fetal brain suggestive of a predisposition for the development of obesity and possibly neurodevelopmental abnormalities in the offspring.

  20. Type and Timing of Menopause and Later Life Mortality Among Women in the Iowa Established Populations for the Epidemiological Study of the Elderly Cohort

    PubMed Central

    Cooper, Rachel; Wallace, Robert B.; Guralnik, Jack M.

    2012-01-01

    Abstract Background The relationship between menopausal characteristics and later life mortality is unclear. We tested the hypotheses that women with surgical menopause would have increased all-cause and cardiovascular mortality compared with women with natural menopause, and that women with earlier ages at natural or surgical menopause would have greater all-cause and cardiovascular mortality than women with later ages at menopause. Methods Women who participated in the Iowa cohort of the Established Populations for the Epidemiologic Study of the Elderly (n=1684) reported menopausal characteristics and potential confounding variables at baseline and were followed up for up to 24 years. Participants were aged 65 years or older at baseline and lived in rural areas. We used survival analysis to examine the relationships between menopausal characteristics and all-cause and cardiovascular mortality. Results A total of 1477 women (87.7% of respondents) died during the study interval. Women with an age at natural menopause ≥55 years had increased all-cause and cardiovascular disease mortality compared with women who had natural menopause at younger ages. Type of menopause and age at surgical menopause were not related to mortality. These patterns persisted after adjustment for potential confounding variables. Conclusions Among an older group of women from a rural area of the United States, later age at natural menopause was related to increased all-cause and cardiovascular mortality. Monitoring the cardiovascular health of this group of older women may contribute to improved survival times. PMID:21970557

  1. Early-life social origins of later-life body weight: the role of socioeconomic status and health behaviors over the life course.

    PubMed

    Pudrovska, Tetyana; Logan, Ellis Scott; Richman, Aliza

    2014-07-01

    Using the 1957-2004 data from the Wisconsin Longitudinal Study, we apply structural equation modeling to examine gender-specific effects of family socioeconomic status (SES) at age 18 on body weight at age 65. We further explore SES and health behaviors over the life course as mechanisms linking family background and later-life body weight. We find that early-life socioeconomic disadvantage is related to higher body weight at age 65 and a steeper weight increase between midlife and late life. These adverse effects are stronger among women than men. Significant mediators of the effect of parents' SES include adolescent body mass (especially among women) as well as exercise and SES in midlife. Yet, consistent with the critical period mechanism, the effect of early-life SES on late-life body weight persists net of all mediating variables. This study expands current understanding of life-course mechanisms that contribute to obesity and increase biological vulnerability to social disadvantage.

  2. Life Course Pathways to Later Life Wellbeing: A Comparative Study of the Role of Socio-Economic Position in England and the U.S.

    PubMed

    Vanhoutte, Bram; Nazroo, James

    The influence of early life, accumulation and social mobility on wellbeing in later life in the U.S. and England is investigated. Using cross-sectional data from the Health and Retirement Study (HRS) and the English Longitudinal Study of Ageing (ELSA), we estimate multivariate regressions of hedonic and eudemonic measures of wellbeing on these life course mechanisms, controlling for age, gender, ethnic background, partnership status, health and wealth. On the level of the life course mechanisms, there is mixed evidence regarding the critical impact of early life, strong evidence for an association between accumulation and eudemonic wellbeing and a moderate negative effect of downward social mobility. While the relation between hedonic wellbeing and life course mechanisms is unclear or in a different direction than anticipated, eudemonic wellbeing is clearly related to accumulation and mobility in both countries and to early life in the U.S. On the societal level, the major observation is that the life course has a larger influence in the U.S. than in England.

  3. Early-Life Social Origins of Later-Life Body Weight: The Role of Socioeconomic Status and Health Behaviors over the Life Course

    PubMed Central

    Logan, Ellis Scott; Richman, Aliza

    2014-01-01

    Using the 1957-2004 data from the Wisconsin Longitudinal Study, we apply structural equation modeling to examine gender-specific effects of family socioeconomic status (SES) at age 18 on body weight at age 65. We further explore SES and health behaviors over the life course as mechanisms linking family background and later-life body weight. We find that early-life socioeconomic disadvantage is related to higher body weight at age 65 and a steeper weight increase between midlife and late life. These adverse effects are stronger among women than men. Significant mediators of the effect of parents' SES include adolescent body mass (especially among women) as well as exercise and SES in midlife. Yet, consistent with the critical period mechanism, the effect of early-life SES on late-life body weight persists net of all mediating variables. This study expands current understanding of life-course mechanisms that contribute to obesity and increase biological vulnerability to social disadvantage. PMID:24767590

  4. Oral antigen exposure in extreme early life in lambs influences the magnitude of the immune response which can be generated in later life.

    PubMed

    Buchanan, Rachelle M; Mertins, Sonja; Wilson, Heather L

    2013-08-12

    Previous investigations in newborn lambs determined that adenovirus-mediated expression of antigen to a localized region of the gut induced antigen-specific mucosal and systemic immunity. These experiments were limited in that the localized region of the gut to which antigen was introduced was sterile and the influence of colostrum on the antigen was not assessed but they do suggest that mucosal vaccines may be an effective vaccination strategy to protect neonatal lambs. We propose that persistent oral antigen exposure introduced in extreme early life can induce immunity in lambs, despite the presence of commensal bacteria and colostrum. To test this hypothesis, conventionally raised newborn lambs (n = 4 per group) were gavaged with ovalbumin (OVA) starting the day after birth for either a single day (2.27 g), every day for 3 days (0.23 g/day), or every day for 3 days then every second day until nine days of age (0.023 g/day). Lambs gavaged with OVA for 3 to 9 days developed significant serum anti-OVA IgG titres (p < 0.05), but not IgA titres, relative to control lambs (n = 4) after 3 and 4 weeks. At 4 weeks of age, lambs were immunized with OVA in Incomplete Freund's Adjuvant via intraperitoneal (i.p.) injection then lambs were euthanized at 7 weeks. Serum anti-OVA IgG titres were further augmented after i.p. immunization indicating immunity persisted and tolerance was not induced. Serum IgA titres remained low regardless of treatment. It is known that i.p. priming of sheep with antigen in Freund's complete adjuvant leads to an enhanced number of IgA and IgG antibody containing cells in the respiratory mucosa (Immunology 53(2):375-384, 1984). Lambs gavaged with a single bolus of 2.27 g OVA prior to i.p. immunization showed very low titres of anti-OVA IgA in the lung lavage. These data suggest that a single, high dose exposure to OVA can promote tolerance which impacts response to systemic vaccination in later life. Lambs gavaged with 0.023

  5. Neonatal exposure to lipopolysaccharide enhances accumulation of α-synuclein aggregation and dopamine transporter protein expression in the substantia nigra in responses to rotenone challenge in later life

    PubMed Central

    Tien, Lu-Tai; Kaizaki, Asuka; Pang, Yi; Cai, Zhengwei; Bhatt, Abhay J; Fan, Lir-Wan

    2013-01-01

    Brain inflammation in early life may enhance adult susceptibility to develop neurodegenerative disorders triggered by environmental toxins. Our previous studies show that perinatal lipopolysaccharide (LPS) exposure enhances adult susceptibility to rotenone-induced injury to the dopaminergic system in the substantia nigra (SN) of the adult rat brain. To further investigate the enhanced adult susceptibility by neonatal LPS exposure to rotenone neurotoxicity, we used our neonatal rat model of LPS exposure (1 mg/kg, intracerebral injection in postnatal day 5, P5, neonatal rats) to examine the protein levels of α-synuclein and dopamine transporters (DAT) in the adult rat. By P70, rats from the saline- or LPS-exposed group were challenged with rotenone, a commonly used pesticide, through subcutaneous mini-pump infusion at a dose of 1.25 mg/kg per day for 14 days. The accumulation of α-synuclein aggregation and increment of DAT protein content were found in the SN of LPS-exposed rats. Neonatal LPS exposure enhanced rotenone-stimulated accumulation of α-synuclein aggregation and increment in DAT protein expression in the cytoplasmic compartment of the SN, and in the synaptosomal compartment of the striatum of adult rats. Rotenone treatment also resulted in reduction of [3H]dopamine uptake and mitochondrial complex I activity in the striatum of rats with neonatal LPS exposure, but not in those without this exposure. The current study suggests possible roles of α-synuclein aggregate and DAT distribution in the cytoplasm and synaptosome triggered by environmental toxins in later life in the development of neurodegenerative disorders. Our model may be useful in studying mechanisms involved in the pathogenesis of nonfamilial Parkinson's disease and for developing potential therapeutic treatments for this disease. PMID:23567316

  6. Behavioural Risk Factors in Mid-Life Associated with Successful Ageing, Disability, Dementia and Frailty in Later Life: A Rapid Systematic Review

    PubMed Central

    Lafortune, Louise; Martin, Steven; Kelly, Sarah; Kuhn, Isla; Remes, Olivia; Cowan, Andy; Brayne, Carol

    2016-01-01

    Background Smoking, alcohol consumption, poor diet and low levels of physical activity significantly contribute to the burden of illness in developed countries. Whilst the links between specific and multiple risk behaviours and individual chronic conditions are well documented, the impact of these behaviours in mid-life across a range of later life outcomes has yet to be comprehensively assessed. This review aimed to provide an overview of behavioural risk factors in mid-life that are associated with successful ageing and the primary prevention or delay of disability, dementia, frailty and non-communicable chronic conditions. Methods A literature search was conducted to identify cohort studies published in English since 2000 up to Dec 2014. Multivariate analyses and a minimum follow-up of five years were required for inclusion. Two reviewers screened titles, abstracts and papers independently. Studies were assessed for quality. Evidence was synthesised by mid-life behavioural risk for a range of late life outcomes. Findings This search located 10,338 individual references, of which 164 are included in this review. Follow-up data ranged from five years to 36 years. Outcomes include dementia, frailty, disability and cardiovascular disease. There is consistent evidence of beneficial associations between mid-life physical activity, healthy ageing and disease outcomes. Across all populations studied there is consistent evidence that mid-life smoking has a detrimental effect on health. Evidence specific to alcohol consumption was mixed. Limited, but supportive, evidence was available relating specifically to mid-life diet, leisure and social activities or health inequalities. Conclusions There is consistent evidence of associations between mid-life behaviours and a range of late life outcomes. The promotion of physical activity, healthy diet and smoking cessation in all mid-life populations should be encouraged for successful ageing and the prevention of disability and

  7. Programme and policy issues related to promoting positive early nutritional influences to prevent obesity, diabetes and cardiovascular disease in later life: a developing countries view.

    PubMed

    Solomons, Noel W

    2005-07-01

    Public health policy differs from programme insofar as the former is the expression of goals at a higher decision-making level (international, regional, national or provincial) and the latter involves the execution of intervention measures at the community or individual level. It has recently become fashionable to speak of "evidence-based" policy. There is now ample evidence to suggest that early nutritional influences on chronic disease risk in later life are contributing to the acceleration of the overall worldwide epidemic of obesity and non-transmissible diseases. In developing countries, in which 80% of the world's population resides, the opportunities for preventive policy must be balanced against needs, cost and effectiveness considerations and the intrinsic limitations of policy execution. Not everyone in the population is at risk of suffering from any given negative condition of interest, nor will everyone at risk benefit from any given intervention. Hence, decisions must be made between universal or targeted policies, seeking maximal cost-efficiency, but without sowing the seeds of either discrimination or stigmatization with a non-universal application of benefits. Moreover, although large segments of the covered population may benefit from a public health measure, it may produce adverse and harmful effects on another segment. It is ethically incumbent on policy makers to minimize unintended consequences of public health measures. With respect to the particular case of mothers, fetuses and infants and long-term health, only a limited number of processes are amenable to intervention measures that could be codified in policy and executed as programmes.

  8. Individual Variations in Maternal Care Early in Life Correlate with Later Life Decision-Making and c-Fos Expression in Prefrontal Subregions of Rats

    PubMed Central

    van Hasselt, Felisa N.; de Visser, Leonie; Tieskens, Jacintha M.; Cornelisse, Sandra; Baars, Annemarie M.; Lavrijsen, Marla; Krugers, Harm J.; van den Bos, Ruud; Joëls, Marian

    2012-01-01

    Early life adversity affects hypothalamus-pituitary-adrenal axis activity, alters cognitive functioning and in humans is thought to increase the vulnerability to psychopathology–e.g. depression, anxiety and schizophrenia- later in life. Here we investigated whether subtle natural variations among individual rat pups in the amount of maternal care received, i.e. differences in the amount of licking and grooming (LG), correlate with anxiety and prefrontal cortex-dependent behavior in young adulthood. Therefore, we examined the correlation between LG received during the first postnatal week and later behavior in the elevated plus maze and in decision-making processes using a rodent version of the Iowa Gambling Task (rIGT). In our cohort of male and female animals a high degree of LG correlated with less anxiety in the elevated plus maze and more advantageous choices during the last 10 trials of the rIGT. In tissue collected 2 hrs after completion of the task, the correlation between LG and c-fos expression (a marker of neuronal activity) was established in structures important for IGT performance. Negative correlations existed between rIGT performance and c-fos expression in the lateral orbitofrontal cortex, prelimbic cortex, infralimbic cortex and insular cortex. The insular cortex correlations between c-fos expression and decision-making performance depended on LG background; this was also true for the lateral orbitofrontal cortex in female rats. Dendritic complexity of insular or infralimbic pyramidal neurons did not or weakly correlate with LG background. We conclude that natural variations in maternal care received by pups may significantly contribute to later-life decision-making and activity of underlying brain structures. PMID:22693577

  9. Socio-demographic and health-related factors affecting depression of the Greek population in later life: an analysis using SHARE data.

    PubMed

    Verropoulou, Georgia; Tsimbos, Cleon

    2007-09-01

    Depression in later life is one of the most prevalent conditions forecasted to rise to the second most burdensome health condition worldwide by 2020. Using data from the 2004 Study of Health Ageing and Retirement in Europe (SHARE: release 1) on 857 Greek males and 1,032 females aged 50 or higher this study explores, firstly, associations of socio-demographic and health related indicators with depressive symptoms (EURO-D) and, secondly, attempts to identify patterns and structures among them. To achieve the first objective, the 12-item summated EURO-D scale is used in binary form with a cut-off point clinically validated by the EURODEP. Use of logistic regression pinpoints strong associations with gender, years of education, co-morbidity, disability, cognitive function and past depression. Women, less educated persons, those with poor physical health, declining cognitive function and a history of depression are significantly more at risk of scoring higher than three at the EURO-D scale. The role of age is not as clear. To achieve the second objective, multiple correspondence analysis is used in the first instance and factor analysis for binary data subsequently; two components are identified within EURO-D and continuous factor scores are produced. These factors are called "affective suffering" and "motivation". Linear regression models reveal that the first component is responsible for the gender while the second for the age differentials in EURO-D; additionally we find that, apart from physical health indicators which are strongly related to both factors, other associations differ. Further exploration of this differentiation seems of interest, particularly as there is an indication that "motivation" may be an affectively neutral condition.

  10. Evolution of cortical neurogenesis.

    PubMed

    Abdel-Mannan, Omar; Cheung, Amanda F P; Molnár, Zoltán

    2008-03-18

    The neurons of the mammalian neocortex are organised into six layers. By contrast, the reptilian and avian dorsal cortices only have three layers which are thought to be equivalent to layers I, V and VI of mammals. Increased repertoire of mammalian higher cognitive functions is likely a result of an expanded cortical surface area. The majority of cortical cell proliferation in mammals occurs in the ventricular zone (VZ) and subventricular zone (SVZ), with a small number of scattered divisions outside the germinal zone. Comparative developmental studies suggest that the appearance of SVZ coincides with the laminar expansion of the cortex to six layers, as well as the tangential expansion of the cortical sheet seen within mammals. In spite of great variation and further compartmentalisation in the mitotic compartments, the number of neurons in an arbitrary cortical column appears to be remarkably constant within mammals. The current challenge is to understand how the emergence and elaboration of the SVZ has contributed to increased cortical cell diversity, tangential expansion and gyrus formation of the mammalian neocortex. This review discusses neurogenic processes that are believed to underlie these major changes in cortical dimensions in vertebrates.

  11. Induction of bilateral plasticity in sensory cortical maps by small unilateral cortical infarcts in rats.

    PubMed

    Reinecke, S; Dinse, H R; Reinke, H; Witte, O W

    2003-02-01

    Behavioural impairments caused by brain lesions show a considerable, though often incomplete, recovery. It is hypothesized that cortical and subcortical plasticity of sensory representations contribute to this recovery. In the hindpaw representation of somatosensory cortex of adult rats we investigated the effects of focal unilateral cortical lesions on remote areas. Cortical lesions with a diameter of approximately 2 mm were induced in the parietal cortex by photothrombosis with the photosensitive dye Rose Bengal. Subsequently, animals were kept in standard cages for 7 days. On day seven, animals were anaesthetized and cutaneous receptive fields in the cortical hindpaw representations ipsi- and contralateral to the lesion were constructed from extracellular recordings of neurons in layer IV using glass microelectrodes. Receptive fields in the lesioned animals were compared to receptive fields measured in nonlesioned animals serving as controls. Quantitative analysis of receptive fields revealed a significant increase in size in the lesioned animals. This doubling in receptive field size was observed equally in the hemispheres ipsi- and contralateral to the lesion. The results indicate that the functional consequences of restricted cortical lesions are not limited to the area surrounding the lesion, but affect the cortical maps on the contralateral, nonlesioned hemisphere.

  12. Cortical Stimulation Concurrent With Skilled Motor Training Improves Forelimb Function and Enhances Motor Cortical Reorganization Following Controlled Cortical Impact.

    PubMed

    Jefferson, Stephanie C; Clayton, Elyse Renee; Donlan, Nicole A; Kozlowski, Dorothy Annette; Jones, Theresa A; Adkins, DeAnna Lynn

    2016-02-01

    Electrical and magnetic brain stimulation can improve motor function following stroke in humans, rats, and nonhuman primates, especially when paired with rehabilitative training (RT). Previously, we found in rodent stroke models that epidural electrical cortical stimulation (CS) of the ipsilesional motor cortex (MC) combined with motor RT enhances motor function and motor cortical plasticity. It was unknown whether CS following experimental traumatic brain injury (TBI) would have similar effects. To test the effects of CS combined with motor training after moderate/severe TBI on behavioral outcome and motor cortical organization. Following unilateral controlled cortical impact (CCI) over the caudal forelimb area of the MC in adult male rats, forelimb reach training was administered daily for 9 weeks concurrently with subthreshold, 100-Hz monopolar CS or no-stimulation control procedures. The rate and magnitude of behavioral improvements and changes in forelimb movement representations in the injured MC as revealed by intracortical microstimulation were measured. CCI resulted in severe motor impairments persisting throughout the 9 weeks of training in both groups, but CS-treated animals had significantly greater behavioral improvements. CS also increased wrist motor cortical representation, one of the main movements used in the training task, when compared with RT alone. However, the overall recovery level was modest, leaving animals still extremely impaired. These data suggest that CS may be useful for improving rehabilitation efficacy after TBI but also raise the possibility that the CS parameters that are highly effective following stroke are suboptimal after moderate/severe TBI. © The Author(s) 2015.

  13. Relation of Childhood Home Environment to Cortical Thickness in Late Adolescence: Specificity of Experience and Timing.

    PubMed

    Avants, Brian B; Hackman, Daniel A; Betancourt, Laura M; Lawson, Gwendolyn M; Hurt, Hallam; Farah, Martha J

    2015-01-01

    What are the long-term effects of childhood experience on brain development? Research with animals shows that the quality of environmental stimulation and parental nurturance both play important roles in shaping lifelong brain structure and function. Human research has so far been limited to the effects of abnormal experience and pathological development. Using a unique longitudinal dataset of in-home measures of childhood experience at ages 4 and 8 and MRI acquired in late adolescence, we were able to relate normal variation in childhood experience to later life cortical thickness. Environmental stimulation at age 4 predicted cortical thickness in a set of automatically derived regions in temporal and prefrontal cortex. In contrast, age 8 experience was not predictive. Parental nurturance was not predictive at either age. This work reveals an association between childhood experience and later brain structure that is specific relative to aspects of experience, regions of brain, and timing.

  14. Relation of Childhood Home Environment to Cortical Thickness in Late Adolescence: Specificity of Experience and Timing

    PubMed Central

    Avants, Brian B.; Hackman, Daniel A.; Betancourt, Laura M.; Lawson, Gwendolyn M.; Hurt, Hallam; Farah, Martha J.

    2015-01-01

    What are the long-term effects of childhood experience on brain development? Research with animals shows that the quality of environmental stimulation and parental nurturance both play important roles in shaping lifelong brain structure and function. Human research has so far been limited to the effects of abnormal experience and pathological development. Using a unique longitudinal dataset of in-home measures of childhood experience at ages 4 and 8 and MRI acquired in late adolescence, we were able to relate normal variation in childhood experience to later life cortical thickness. Environmental stimulation at age 4 predicted cortical thickness in a set of automatically derived regions in temporal and prefrontal cortex. In contrast, age 8 experience was not predictive. Parental nurturance was not predictive at either age. This work reveals an association between childhood experience and later brain structure that is specific relative to aspects of experience, regions of brain, and timing. PMID:26509809

  15. Posterior neocortical (visual cortex) lesions in the rat impair matching-to-place navigation in a swimming pool: a reevaluation of cortical contributions to spatial behavior using a new assessment of spatial versus nonspatial behavior.

    PubMed

    Whishaw, Ian Q

    2004-11-05

    In the face of contradictory findings on the role of visual cortex contributions to spatial behavior, the present study evaluated the ability of rats with primary visual cortex (area 17) lesions to learn spatial problems in a swimming pool. Because the solution to any spatial learning problem consists of acquiring at least two primary elements of a task, task procedures and spatial learning, the study, in addition to assessing spatial ability on a place task, used two training/testing methods to identify the nature of the spatial impairment associated with visual cortex lesions. Non-spatial training consisted of learning to find a platform in the dark and spatial training consisted of a series of matching-to-place problems. The results confirmed that although rats with visual cortex lesions were impaired on place learning, the deficit was partially ameliorated by non-spatial training given following the lesion, and completely ameliorated by non-spatial training given before the lesion. Nevertheless, all visual cortex groups failed to show a quadrant preference on a probe trial and displayed a profound impairment in matching-to-place learning. This definitive demonstration that appropriate testing methods can reveal a failure in spatial behavior following visual cortex lesions is consistent with the idea that primary visual cortex is required in spatial navigation.

  16. Posterior neocortical (visual cortex) lesions in the rat impair matching-to-place navigation in a swimming pool: a reevaluation of cortical contributions to spatial behavior using a new assessment of spatial versus non-spatial behavior.

    PubMed

    Whishaw, Ian Q

    2004-12-06

    In the face of contradictory findings on the role of visual cortex contributions to spatial behavior, the present study evaluated the ability of rats with primary visual cortex (Area 17) lesions to learn spatial problems in a swimming pool. Because the solution to any spatial learning problem consists of acquiring at least two primary elements of a task, task procedures and spatial learning, the study, in addition to assessing spatial ability on a place task, used two training/testing methods to identify the nature of the spatial impairment associated with visual cortex lesions. Non-spatial training consisted of learning to find a platform in the dark and spatial training consisted of a series of matching-to-place problems. The results confirmed that although rats with visual cortex lesions were impaired on place learning, the deficit was partially ameliorated by non-spatial training given following the lesion, and completely ameliorated by non-spatial training given before the lesion. Nevertheless, all visual cortex groups failed to show a quadrant preference on a probe trial and displayed a profound impairment in matching-to-place learning. This definitive demonstration that appropriate testing methods can reveal a failure in spatial behavior following visual cortex lesions is consistent with the idea that primary visual cortex is required in spatial navigation.

  17. Reduced Regional Brain Cortical Thickness in Patients with Heart Failure

    PubMed Central

    Kumar, Rajesh; Yadav, Santosh K.; Palomares, Jose A.; Park, Bumhee; Joshi, Shantanu H.; Ogren, Jennifer A.; Macey, Paul M.; Fonarow, Gregg C.; Harper, Ronald M.; Woo, Mary A.

    2015-01-01

    Aims Autonomic, cognitive, and neuropsychologic deficits appear in heart failure (HF) subjects, and these compromised functions depend on cerebral cortex integrity in addition to that of subcortical and brainstem sites. Impaired autoregulation, low cardiac output, sleep-disordered-breathing, hypertension, and diabetic conditions in HF offer considerable potential to affect cortical areas by loss of neurons and glia, which would be expressed as reduced cortical thicknesses. However, except for gross descriptions of cortical volume loss/injury, regional cortical thickness integrity in HF is unknown. Our goal was to assess regional cortical thicknesses across the brain in HF, compared to control subjects. Methods and Results We examined localized cortical thicknesses in 35 HF and 61 control subjects with high-resolution T1-weighted images (3.0-Tesla MRI) using FreeSurfer software, and assessed group differences with analysis-of-covariance (covariates; age, gender; p<0.05; FDR). Significantly-reduced cortical thicknesses appeared in HF over controls in multiple areas, including the frontal, parietal, temporal, and occipital lobes, more markedly on the left side, within areas that control autonomic, cognitive, affective, language, and visual functions. Conclusion Heart failure subjects show reduced regional cortical thicknesses in sites that control autonomic, cognitive, affective, language, and visual functions that are deficient in the condition. The findings suggest chronic tissue alterations, with regional changes reflecting loss of neurons and glia, and presumably are related to earlier-described axonal changes. The pathological mechanisms contributing to reduced cortical thicknesses likely include hypoxia/ischemia, accompanying impaired cerebral perfusion from reduced cardiac output and sleep-disordered-breathing and other comorbidities in HF. PMID:25962164

  18. Cortical areas involved in Arabic number reading.

    PubMed

    Roux, F-E; Lubrano, V; Lauwers-Cances, V; Giussani, C; Démonet, J-F

    2008-01-15

    Distinct functional pathways for processing words and numbers have been hypothesized from the observation of dissociated impairments of these categories in brain-damaged patients. We aimed to identify the cortical areas involved in Arabic number reading process in patients operated on for various brain lesions. Direct cortical electrostimulation was prospectively used in 60 brain mappings. We used object naming and two reading tasks: alphabetic script (sentences and number words) and Arabic number reading. Cortical areas involved in Arabic number reading were identified according to location, type of interference, and distinctness from areas associated with other language tasks. Arabic number reading was sustained by small cortical areas, often extremely well localized (<1 cm(2)). Over 259 language sites detected, 43 (17%) were exclusively involved in Arabic number reading (no sentence or word number reading interference detected in these sites). Specific Arabic number reading interferences were mainly found in three regions: the Broca area (Brodmann area 45), the anterior part of the dominant supramarginal gyrus (Brodmann area 40; p < 0.0001), and the temporal-basal area (Brodmann area 37; p < 0.05). Diverse types of interferences were observed (reading arrest, phonemic or semantic paraphasia). Error patterns were fairly similar across temporal, parietal, and frontal stimulation sites, except for phonemic paraphasias, which were found only in supramarginal gyrus. Our findings strongly support the fact that the acquisition through education of specific symbolic entities, such as Arabic numbers, could result in the segregation and the specialization of anatomically distinct brain areas.

  19. Mechanisms of Hierarchical Cortical Maturation

    PubMed Central

    Chomiak, Taylor; Hu, Bin

    2017-01-01

    Cortical information processing is structurally and functionally organized into hierarchical pathways, with primary sensory cortical regions providing modality specific information and associative cortical regions playing a more integrative role. Historically, there has been debate as to whether primary cortical regions mature earlier than associative cortical regions, or whether both primary and associative cortical regions mature simultaneously. Identifying whether primary and associative cortical regions mature hierarchically or simultaneously will not only deepen our understanding of the mechanisms that regulate brain maturation, but it will also provide fundamental insight into aspects of adolescent behavior, learning, neurodevelopmental disorders and computational models of neural processing. This mini-review article summarizes the current evidence supporting the sequential and hierarchical nature of cortical maturation, and then proposes a new cellular model underlying this process. Finally, unresolved issues associated with hierarchical cortical maturation are also addressed. PMID:28959187

  20. Abnormalities of fixation, saccade and pursuit in posterior cortical atrophy

    PubMed Central

    Kaski, Diego; Yong, Keir X. X.; Paterson, Ross W.; Slattery, Catherine F.; Ryan, Natalie S.; Schott, Jonathan M.; Crutch, Sebastian J.

    2015-01-01

    saccadic intrusions whose frequency correlated significantly with generalized reductions in cortical thickness. Patients with both posterior cortical atrophy and typical Alzheimer’s disease showed lower gain in smooth pursuit compared to controls. The current study establishes that eye movement abnormalities are near-ubiquitous in posterior cortical atrophy, and highlights multiple aspects of saccadic performance which distinguish posterior cortical atrophy from typical Alzheimer’s disease. We suggest the posterior cortical atrophy oculomotor profile (e.g. exacerbation of the saccadic gap/overlap effect, preserved saccadic velocity) reflects weak input from degraded occipito-parietal spatial representations of stimulus location into a superior collicular spatial map for eye movement regulation. This may indicate greater impairment of identification of oculomotor targets rather than generation of oculomotor movements. The results highlight the critical role of spatial attention and object identification but also precise stimulus localization in explaining the complex real world perception deficits observed in posterior cortical atrophy and many other patients with dementia-related visual impairment. PMID:25895507

  1. Abnormalities of fixation, saccade and pursuit in posterior cortical atrophy.

    PubMed

    Shakespeare, Timothy J; Kaski, Diego; Yong, Keir X X; Paterson, Ross W; Slattery, Catherine F; Ryan, Natalie S; Schott, Jonathan M; Crutch, Sebastian J

    2015-07-01

    whose frequency correlated significantly with generalized reductions in cortical thickness. Patients with both posterior cortical atrophy and typical Alzheimer's disease showed lower gain in smooth pursuit compared to controls. The current study establishes that eye movement abnormalities are near-ubiquitous in posterior cortical atrophy, and highlights multiple aspects of saccadic performance which distinguish posterior cortical atrophy from typical Alzheimer's disease. We suggest the posterior cortical atrophy oculomotor profile (e.g. exacerbation of the saccadic gap/overlap effect, preserved saccadic velocity) reflects weak input from degraded occipito-parietal spatial representations of stimulus location into a superior collicular spatial map for eye movement regulation. This may indicate greater impairment of identification of oculomotor targets rather than generation of oculomotor movements. The results highlight the critical role of spatial attention and object identification but also precise stimulus localization in explaining the complex real world perception deficits observed in posterior cortical atrophy and many other patients with dementia-related visual impairment.

  2. Locus coeruleus stimulation recruits a broad cortical neuronal network and increases cortical perfusion.

    PubMed

    Toussay, Xavier; Basu, Kaustuv; Lacoste, Baptiste; Hamel, Edith

    2013-02-20

    The locus coeruleus (LC), the main source of brain noradrenalin (NA), modulates cortical activity, cerebral blood flow (CBF), glucose metabolism, and blood-brain barrier permeability. However, the role of the LC-NA system in the regulation of cortical CBF has remained elusive. This rat study shows that similar proportions (∼20%) of cortical pyramidal cells and GABA interneurons are contacted by LC-NA afferents on their cell soma or proximal dendrites. LC stimulation induced ipsilateral activation (c-Fos upregulation) of pyramidal cells and of a larger proportion (>36%) of interneurons that colocalize parvalbumin, somatostatin, or nitric oxide synthase compared with pyramidal cells expressing cyclooxygenase-2 (22%, p < 0.05) or vasoactive intestinal polypeptide-containing interneurons (16%, p < 0.01). Concurrently, LC stimulation elicited larger ipsilateral compared with contralateral increases in cortical CBF (52 vs 31%, p < 0.01). These CBF responses were almost abolished (-70%, p < 0.001) by cortical NA denervation with DSP-4 [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride] and were significantly reduced by α- and β-adrenoceptor antagonists (-40%, p < 0.001 and -30%, p < 0.05, respectively). Blockade of glutamatergic or GABAergic neurotransmission with NMDA or GABA(A) receptor antagonists potently reduced the LC-induced hyperemic response (-56%, p < 0.001 or -47%, p < 0.05). Moreover, inhibition of astroglial metabolism (-35%, p < 0.01), vasoactive epoxyeicosatrienoic acids (EETs; -60%, p < 0.001) synthesis, large-conductance, calcium-operated (BK, -52%, p < 0.05), and inward-rectifier (Kir, -40%, p < 0.05) K+ channels primarily impaired the hyperemic response. The data demonstrate that LC stimulation recruits a broad network of cortical excitatory and inhibitory neurons resulting in increased cortical activity and that K+ fluxes and EET signaling mediate a large part of the hemodynamic response.

  3. Optogenetic stimulation of cholinergic brainstem neurons during focal limbic seizures: Effects on cortical physiology.

    PubMed

    Furman, Moran; Zhan, Qiong; McCafferty, Cian; Lerner, Benjamin A; Motelow, Joshua E; Meng, Jin; Ma, Chanthia; Buchanan, Gordon F; Witten, Ilana B; Deisseroth, Karl; Cardin, Jessica A; Blumenfeld, Hal

    2015-12-01

    Focal temporal lobe seizures often cause impaired cortical function and loss of consciousness. Recent work suggests that the mechanism for depressed cortical function during focal seizures may depend on decreased subcortical cholinergic arousal, which leads to a sleep-like state of cortical slow-wave activity. To test this hypothesis, we sought to directly activate subcortical cholinergic neurons during focal limbic seizures to determine the effects on cortical function. Here we used an optogenetic approach to selectively stimulate cholinergic brainstem neurons in the pedunculopontine tegmental nucleus during focal limbic seizures induced in a lightly anesthetized rat model. We found an increase in cortical gamma activity and a decrease in delta activity in response to cholinergic stimulation. These findings support the mechanistic role of reduced subcortical cholinergic arousal in causing cortical dysfunction during seizures. Through further work, electrical or optogenetic stimulation of subcortical arousal networks may ultimately lead to new treatments aimed at preventing cortical dysfunction during seizures.

  4. Visual Dysfunction in Posterior Cortical Atrophy

    PubMed Central

    da Silva, Mari N. Maia; Millington, Rebecca S.; Bridge, Holly; James-Galton, Merle; Plant, Gordon T.

    2017-01-01

    Posterior cortical atrophy (PCA) is a syndromic diagnosis. It is characterized by progressive impairment of higher (cortical) visual function with imaging evidence of degeneration affecting the occipital, parietal, and posterior temporal lobes bilaterally. Most cases will prove to have Alzheimer pathology. The aim of this review is to summarize the development of the concept of this disorder since it was first introduced. A critical discussion of the evolving diagnostic criteria is presented and the differential diagnosis with regard to the underlying pathology is reviewed. Emphasis is given to the visual dysfunction that defines the disorder, and the classical deficits, such as simultanagnosia and visual agnosia, as well as the more recently recognized visual field defects, are reviewed, along with the evidence on their neural correlates. The latest developments on the imaging of PCA are summarized, with special attention to its role on the differential diagnosis with related conditions. PMID:28861031

  5. Mapping cortical mesoscopic networks of single spiking cortical or sub-cortical neurons.

    PubMed

    Xiao, Dongsheng; Vanni, Matthieu P; Mitelut, Catalin C; Chan, Allen W; LeDue, Jeffrey M; Xie, Yicheng; Chen, Andrew Cn; Swindale, Nicholas V; Murphy, Timothy H

    2017-02-04

    Understanding the basis of brain function requires knowledge of cortical operations over wide-spatial scales, but also within the context of single neurons. In vivo, wide-field GCaMP imaging and sub-cortical/cortical cellular electrophysiology were used in mice to investigate relationships between spontaneous single neuron spiking and mesoscopic cortical activity. We make use of a rich set of cortical activity motifs that are present in spontaneous activity in anesthetized and awake animals. A mesoscale spike-triggered averaging procedure allowed the identification of motifs that are preferentially linked to individual spiking neurons by employing genetically targeted indicators of neuronal activity