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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. 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

  3. 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

  4. Cortical Visual Impairment: New Directions

    PubMed Central

    Good, William V.

    2009-01-01

    Cortical visual impairment is the leading cause of bilateral low vision in children in the U.S., yet very little research is being done to find new diagnostic measures and treatments. Dr. Velma Dobson's pioneering work on visual assessments of developmentally delayed children stands out as highly significant in this field. Future research will assess new diagnostic measures, including advanced imaging techniques. In addition, research will evaluate methods to prevent, treat, and rehabilitate infants and children afflicted with this condition. PMID:19417710

  5. Photophobia and cortical visual impairment.

    PubMed

    Jan, J E; Groenveld, M; Anderson, D P

    1993-06-01

    Photophobia, or intolerance of light, is not completely understood as a symptom. It has been divided into ocular and central types. This study shows that persistent, usually mild, photophobia occurs in about one-third of children with cortical visual impairment (CVI). When the CVI is congenital the photophobia is present from birth, and when it is acquired the sensitivity to light appears immediately after the brain insult. The intensity of photophobia tends to diminish with time and occasionally it may even disappear. The pathophysiology is unclear, as in all other neurological disorders associated with photophobia. PMID:8504889

  6. 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. PMID:24974278

  7. 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

  8. Discontinuity of cortical gradients reflects sensory impairment.

    PubMed

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

    2015-12-29

    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

  9. Focal cortical damage parallels cognitive impairment in minimal hepatic encephalopathy.

    PubMed

    Montoliu, Carmina; Gonzalez-Escamilla, Gabriel; Atienza, Mercedes; Urios, Amparo; Gonzalez, Olga; Wassel, Abdallah; Aliaga, Roberto; Giner-Duran, Remedios; Serra, Miguel A; Rodrigo, Jose M; Belloch, Vicente; Felipo, Vicente; Cantero, Jose L

    2012-07-16

    Little attention has been paid to cortical integrity in patients with minimal hepatic encephalopathy (MHE), although cognitive functions affected in early stages of liver disease are mainly allocated in different neocortical structures. Here we used cortical surface-based analysis techniques to investigate if patterns of cortical thinning accompany the mildest form of HE. To aim this goal, cortical thickness obtained from high-resolution 3T magnetic resonance imaging (MRI) was measured in patients with no MHE (NMHE), MHE, and healthy controls. Further correlation analyses were performed to examine whether scores in the critical flicker frequency (CFF) test, and blood ammonia levels accounted for the loss of cortical integrity in different stages of liver disease. Finally, we assessed group differences in volume of different subcortical regions and their potential relationships with CFF scores/blood ammonia levels. Results showed a focal thinning of the superior temporal cortex and precuneus in MHE patients when compared with NMHE and controls. Relationships between blood ammonia levels and cortical thickness of the calcarine sulcus accounted for impaired visual judgment in patients with MHE when compared to NMHE. Regression analyses between cortical thickness and CFF predicted differences between controls and the two groups of HE patients, but failed to discriminate between patients with NMHE and MHE. Taking together, these findings provide the first report of cortical thinning in MHE patients, and they yield novel insights into the neurobiological basis of cognitive impairment associated with early stages of liver diseases. PMID:22465844

  10. 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. PMID:27456751

  11. Verbal memory impairments in schizophrenia associated with cortical thinning

    PubMed Central

    Guimond, S.; Chakravarty, M.M.; Bergeron-Gagnon, L.; Patel, R.; Lepage, M.

    2015-01-01

    Verbal memory (VM) represents one of the most affected cognitive domains in schizophrenia. Multiple studies have shown that schizophrenia is associated with cortical abnormalities, but it remains unclear whether these are related to VM impairments. Considering the vast literature demonstrating the role of the frontal cortex, the parahippocampal cortex, and the hippocampus in VM, we examined the cortical thickness/volume of these regions. We used a categorical approach whereby 27 schizophrenia patients with ‘moderate to severe’ VM impairments were compared to 23 patients with ‘low to mild’ VM impairments and 23 healthy controls. A series of between-group vertex-wise GLM on cortical thickness were performed for specific regions of interest defining the parahippocampal gyrus and the frontal cortex. When compared to healthy controls, patients with ‘moderate to severe’ VM impairments revealed significantly thinner cortex in the left frontal lobe, and the parahippocampal gyri. When compared to patients with ‘low to mild’ VM impairments, patients with ‘moderate to severe’ VM impairments showed a trend of thinner cortex in similar regions. Virtually no differences were observed in the frontal area of patients with ‘low to mild’ VM impairments relative to controls. No significant group differences were observed in the hippocampus. Our results indicate that patients with greater VM impairments demonstrate significant cortical thinning in regions known to be important in VM performance. Treating VM deficits in schizophrenia could have a positive effect on the brain; thus, subgroups of patients with more severe VM deficits should be a prioritized target in the development of new cognitive treatments. PMID:26909322

  12. Antisaccade task reflects cortical involvement in mild cognitive impairment

    PubMed Central

    Mirsky, Jacob B.; Kong, Erwin L.; Dickerson, Bradford C.; Miller, Bruce L.; Kramer, Joel H.; Boxer, Adam L.

    2013-01-01

    Objective: The aims of this study were to examine executive dysfunction using an antisaccade (AS) task in normal elderly (NE) and patients with mild cognitive impairment (MCI) and Alzheimer disease (AD) as well as to evaluate the relationship between AS performance and cortical thinning within AD-associated regions. Methods: We recorded eye movements in 182 subjects (NE: 118; MCI: 36; AD: 28) during an AS task. We also performed neuropsychological measures of executive function for comparison. Brain MRI scans were collected on most subjects, and cortical thickness was determined in 9 regions known to exhibit atrophy in AD dementia (“AD signature”). We investigated the relationships between AS and neuropsychological performance, as well as possible correlations between AS performance and cortical thickness. Results: AS performance in MCI resembled that in NE; subjects with AD were impaired relative to both MCI and NE. In all subjects, AS performance correlated with neuropsychological measures of executive function, even after controlling for disease severity. In the subjects with MCI but not in NE, cortical thickness in frontoparietal AD signature regions correlated with AS performance. Conclusions: The AS task is a useful measure of executive function across the AD spectrum. In MCI, AS performance may reflect disease burden within cortical brain regions involved in oculomotor control; however, AS impairments in NE may have etiologies other than incipient AD. PMID:23986300

  13. Immobilization impairs tactile perception and shrinks somatosensory cortical maps.

    PubMed

    Lissek, Silke; Wilimzig, Claudia; Stude, Philipp; Pleger, Burkhard; Kalisch, Tobias; Maier, Christoph; Peters, Sören A; Nicolas, Volkmar; Tegenthoff, Martin; Dinse, Hubert R

    2009-05-26

    Use is a major factor driving plasticity of cortical processing and cortical maps. As demonstrated of blind Braille readers and musicians, long-lasting and exceptional usage of the fingers results in the development of outstanding sensorimotor skills and in expansions of the cortical finger representations. However, how periods of disuse affect cortical representations and perception in humans remains elusive. Here, we report that a few weeks of hand and arm immobilization by cast wearing significantly reduced hand use and impaired tactile acuity, associated with reduced activation of the respective finger representations in the somatosensory cortex (SI), measured by functional magnetic resonance imaging. Hemodynamic responses in the SI correlated positively with hand-use frequency and negatively with discrimination thresholds, indicating that reduced activation was most prominent in subjects with severe perceptual impairment. We found, strikingly, compensatory effects on the contralateral, healthy hand consisting of improved perceptual performance compared to healthy controls. Two to three weeks after cast removal, perceptual and cortical changes recovered, whereas tactile acuity on the healthy side remained superior to that on the formerly immobilized side. These findings suggest that brief periods of reduced use of a limb have overt consequences and thus constitute a significant driving force of brain organization equivalent to enhanced use. PMID:19398335

  14. 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

  15. 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…

  16. Cortical thinning in individuals with subjective memory impairment.

    PubMed

    Meiberth, Dix; Scheef, Lukas; Wolfsgruber, Steffen; Boecker, Henning; Block, Wolfgang; Träber, Frank; Erk, Susanne; Heneka, Michael T; Jacobi, Heike; Spottke, Annika; Walter, Henrik; Wagner, Michael; Hu, Xiaochen; Jessen, Frank

    2015-01-01

    Elderly individuals with subjective memory impairment (SMI) report memory decline, but perform within the age-, gender-, and education- adjusted normal range on neuropsychological tests. Longitudinal studies indicate SMI as a risk factor or early sign of Alzheimer's disease (AD). There is increasing evidence from neuroimaging that at the group level, subjects with SMI display evidence of AD related pathology. This study aimed to determine differences in cortical thickness between individuals with SMI and healthy control subjects (CO) using the FreeSurfer environment. 110 participants (41 SMI/69 CO) underwent structural 3D-T1 MR imaging. Cortical thickness values were compared between groups in predefined AD-related brain regions of the medial temporal lobe, namely the bilateral entorhinal cortex and bilateral parahippocampal cortex. Cortical thickness reduction was observed in the SMI group compared to controls in the left entorhinal cortex (p = 0.003). We interpret our findings as evidence of early AD-related brain changes in persons with SMI. PMID:25471190

  17. 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. PMID:27128371

  18. Cognitive impairment in paediatric multiple sclerosis patients is not related to cortical lesions.

    PubMed

    Rocca, Maria A; De Meo, Ermelinda; Amato, Maria P; Copetti, Massimiliano; Moiola, Lucia; Ghezzi, Angelo; Veggiotti, Pierangelo; Capra, Ruggero; Fiorino, Agnese; Pippolo, Lorena; Pera, Maria C; Falini, Andrea; Comi, Giancarlo; Filippi, Massimo

    2015-06-01

    We investigated the contribution of cortical lesions to cognitive impairment in 41 paediatric MS patients. Thirteen (32%) paediatric MS patients were considered as cognitively impaired. T2-hyperintense and T1-hypointense white matter lesion volumes did not differ between cognitively impaired and cognitively preserved MS patients. Cortical lesions number, cortical lesions volume and grey matter volume did not differ between cognitively impaired and cognitively preserved patients, whereas white matter volume was significantly lower in cognitively impaired versus cognitively preserved MS patients (p=0.01). Contrary to adult MS, cortical lesions do not seem to contribute to cognitive impairment in paediatric MS patients, which is likely driven by white matter damage. PMID:25392332

  19. 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…

  20. 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…

  1. 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…

  2. The Never-Married in Later Life.

    ERIC Educational Resources Information Center

    Ward, Russell A.

    1979-01-01

    Consequences of singlehood are analyzed for never-married persons. Highly-educated older women are most likely to remain single. Family background is not a predictor. Although the never-married find life more exciting than other marital statuses among younger respondents, this reverses in later life. Never-marrieds are also less happy than the…

  3. 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.

  4. Transnational connections of later-life migrants.

    PubMed

    Heikkinen, Sari Johanna; Lumme-Sandt, Kirsi

    2013-04-01

    In this paper a transnational perspective is used to explain whether and how older migrants construct and sustain their social networks. The paper uses a transnational viewpoint on older migrants' lives by analysing their engagement with their former homeland, and the intensity and habitualness of those engagements in old age. The aim of this article is to study the transnational connections of later-life migrants'. Attention is especially paid to the features of old age while maintaining these connections. These considerations are based on analyses of transnational networks in the everyday lives of later-life migrants from the former Soviet Union residing in Finland. The data were collected from 11 later-life migrants. It is found that transnational relationships are a vital part of the everyday lives of older migrants, and that they are sustained in varied ways. These connections mean a concrete source of help, family affiliations, the sharing of emotions, and a larger social network. Economic limitations affect the frequency and type of communication, and various physical limitations may also cause inability to maintain contacts across borders. In these circumstances, family members or other close relatives or friends are needed to deliver messages on the older person's behalf. Old age and immigration status affect the amount and direction of communication across borders, thereby shaping these networks. PMID:23561285

  5. Greater cortical thinning in normal older adults predicts later cognitive impairment.

    PubMed

    Pacheco, Jennifer; Goh, Joshua O; Kraut, Michael A; Ferrucci, Luigi; Resnick, Susan M

    2015-02-01

    Cross-sectional studies have shown regional differences in cortical thickness between healthy older adults and patients with Alzheimer's disease (AD) or mild cognitive impairment (MCI). We now demonstrate that participants who subsequently develop cognitive impairment leading to a diagnosis of MCI or AD (n = 25) experience greater cortical thinning in specific neuroanatomic regions compared with control participants who remained cognitively normal (n = 96). Based on 8 years of annual magnetic resonance imaging scans beginning an average of 11 years before onset of cognitive impairment, participants who developed cognitive impairment subsequent to the scanning period had greater longitudinal cortical thinning in the temporal poles and left medial temporal lobe compared with controls. No significant regional cortical thickness differences were found at baseline between the 2 study groups indicating that we are capturing a critical time when brain changes occur before behavioral manifestations of impairment are detectable. Our findings suggest that early events of the pathway that leads to cognitive impairment may involve the temporal lobe and that this increased atrophy could be considered an early biomarker of neurodegeneration predictive of cognitive impairment years later. PMID:25311277

  6. 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...

  7. Apathy is associated with lower inferior temporal cortical thickness in mild cognitive impairment and normal elderly individuals.

    PubMed

    Guercio, Brendan J; Donovan, Nancy J; Ward, Andrew; Schultz, Aaron; Lorius, Natacha; Amariglio, Rebecca E; Rentz, Dorene M; Johnson, Keith A; Sperling, Reisa A; Marshall, Gad A

    2015-01-01

    Apathy is a common neuropsychiatric symptom in Alzheimer's disease dementia and amnestic mild cognitive impairment and is associated with cortical atrophy in Alzheimer's disease dementia. This study investigated possible correlations between apathy and cortical atrophy in 47 individuals with mild cognitive impairment and 19 clinically normal elderly. Backward elimination multivariate linear regression was used to evaluate the cross-sectional relationship between scores on the Apathy Evaluation Scale and thickness of several cortical regions and covariates. Lower inferior temporal cortical thickness was predictive of greater apathy. Greater anterior cingulate cortical thickness was also predictive of greater apathy, suggesting an underlying reactive process. PMID:25716491

  8. Cognitive Correlates of Basal Forebrain Atrophy and Associated Cortical Hypometabolism in Mild Cognitive Impairment.

    PubMed

    Grothe, Michel J; Heinsen, Helmut; Amaro, Edson; Grinberg, Lea T; Teipel, Stefan J

    2016-06-01

    Degeneration of basal forebrain (BF) cholinergic nuclei is associated with cognitive decline, and this effect is believed to be mediated by neuronal dysfunction in the denervated cortical areas. MRI-based measurements of BF atrophy are increasingly being used as in vivo surrogate markers for cholinergic degeneration, but the functional implications of reductions in BF volume are not well understood. We used high-resolution MRI, fluorodeoxyglucose-positron emission tomography (PET), and neuropsychological test data of 132 subjects with mild cognitive impairment (MCI) and 177 cognitively normal controls to determine associations between BF atrophy, cortical hypometabolism, and cognitive deficits. BF atrophy in MCI correlated with both impaired memory function and attentional control deficits, whereas hippocampus volume was more specifically associated with memory deficits. BF atrophy was also associated with widespread cortical hypometabolism, and path analytic models indicated that hypometabolism in domain-specific cortical networks mediated the association between BF volume and cognitive dysfunction. The presence of cortical amyloid pathology, as assessed using AV45-PET, did not significantly interact with the observed associations. These data underline the potential of multimodal imaging markers to study structure-function-cognition relationships in the living human brain and provide important in vivo evidence for an involvement of the human BF in cortical activity and cognitive function. PMID:25840425

  9. 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.

  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. 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)

  12. Increasing a Functional Skill for an Adolescent with Cortical Visual Impairment.

    ERIC Educational Resources Information Center

    Farrenkopf, C.; McGregor, D.; Nes, S. L.; Koenig, A. J.

    1997-01-01

    The effectiveness of two treatment strategies (verbal prompts and a physical prompt) on the independent drinking skills of a 17-year-old girl with cortical visual impairment was investigated. Results found that the physical prompt was highly effective in promoting the target behavior, whereas verbal prompts were less effective. (Author/CR)

  13. 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…

  14. Cortical Visual Impairment in Children: Presentation Intervention, and Prognosis in Educational Settings

    ERIC Educational Resources Information Center

    Swift, Suzanne H.; Davidson, Roseanna C.; Weems, Linda J.

    2008-01-01

    Children with cortical visual impairment (CVI) exhibit distinct visual behaviors which are often misinterpreted. As the incidence of CVI is on the rise, this has subsequently caused an increased need for identification and intervention with these children from teaching and therapy service providers. Distinguishing children with CVI from children…

  15. Cortical Contributions to Impaired Contour Integration in Schizophrenia

    PubMed Central

    Silverstein, Steven M.; Harms, Michael P.; Carter, Cameron S.; Gold, James M.; Keane, Brian P.; MacDonald, Angus; Ragland, J. Daniel; Barch, Deanna M.

    2015-01-01

    Objectives Visual perceptual organization impairments in schizophrenia (SCZ) are well established, but their neurobiological bases are not. The current study used the previously validated Jittered Orientation Visual Integration (JOVI) task, along with fMRI, to examine the neural basis of contour integration (CI), and its impairment in SCZ. CI is an aspect of perceptual organization in which multiple distinct oriented elements are grouped into a single continuous boundary or shape. Methods On the JOVI, five levels of orientational jitter were added to non-contiguous closed contour elements embedded in background noise to progressively increase the difficulty in perceiving contour elements as left- or right-pointing ovals. Multi-site fMRI data were analyzed for 56 healthy control subjects and 47 people with SCZ. Results SCZ patients demonstrated poorer CI, and this was associated with increased activation in regions involved in global shape processing and visual attention, namely the lateral occipital complex and superior parietal lobules. There were no brain regions where controls demonstrated more activation than patients. Conclusions CI impairment in this sample of outpatients with SCZ was related to excessive activation in regions associated with object processing and allocation of visual-spatial attention. There was no evidence for basic impairments in contour element linking in the fMRI data. The latter may be limited to poor outcome patients, where more extensive structural and functional changes in the occipital lobe have been observed. PMID:26160288

  16. 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

  17. 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. PMID:26162722

  18. 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. PMID:16797044

  19. Acidosis and alkalosis impair brain functions through weakening spike encoding at cortical GABAergic neurons.

    PubMed

    Song, Rongrong; Zhang, Liming; Yang, Zichao; Tian, Xiaoyan

    2011-05-15

    Acidosis and alkalosis, associated with metabolic disorders, lead to the pathological changes of cognition and behaviors in clinical practices of neurology and psychology. Cellular mechanisms for these functional disorders in the central nervous system remain unclear. We have investigated the influences of acidosis and alkalosis on the functions of cortical GABAergic neurons. Both acidosis and alkalosis impair the ability of encoding sequential spikes at these GABAergic neurons. The impairments of their spiking are associated with the increases of refractory periods, threshold potential and afterhyperpolarization. Our studies reveal that acidosis and alkalosis impair cortical GABAergic neurons and in turn deteriorate brain functions, in which their final targets may be voltage-gated channels of sodium and potassium. PMID:21353681

  20. Coping with anxiety in later life.

    PubMed

    Frazier, Leslie D; Waid, Lisa D; Fincke, Candy

    2002-12-01

    The goal of this study was to determine how older adults cope with three forms of anxiety, and potential avenues for applied interventions. Although the findings shed light on some interesting findings with potential psychosocial applications, several limitations need to be noted. First, this study was based on two assumptions. The assumption, based on earlier work (Carver et al., 1989; Lazarus & Folkman, 1984; Zeidner & Saklofske, 1996), that certain coping strategies are more effective than others, and an assumption of the direction of influence in which anxiety is a precursor of coping strategies. Because this was an exploratory study, the research questions did not directly test these assumptions. Second, this study is correlational in nature. Therefore, conclusions cannot be drawn about the causality of these associations. Third, as with any self-report data and self-selected sample, one needs to interpret the findings with caution. Similarly, for the purposes of the study, a non-clinical sample of older adults was examined using three distinct conceptualizations of anxiety. Suggestions for future research include: Replication of this study using a multidimensional measure of anxiety appropriate for clinical samples. A longitudinal replication of this study identifying patterns of coping that facilitate adjustment over time. Finally, a more general purpose of this study was to focus attention on a neglected issue in gerontology--the experience of anxietY in later life (Frazier & Waid, 1999; Gatz, 1995; Rabins, 1992; Shamoian, 1991; Sheikh, 1992; Smyer, 1995; Stanley & Beck, 1998), and, most importantly, the role of gerontological nurses in early assessment and intervention for successful treatment of anxiety in older adults. PMID:12567825

  1. Mild cognitive impairment in patients with Parkinson's disease is associated with increased cortical degeneration.

    PubMed

    Hanganu, Alexandru; Bedetti, Christophe; Jubault, Thomas; Gagnon, Jean-Francois; Mejia-Constain, Béatriz; Degroot, Clotilde; Lafontaine, Anne-Louise; Chouinard, Sylvain; Monchi, Oury

    2013-09-01

    Mild cognitive impairment (MCI) can occur early in the course of Parkinson's disease (PD), and its presence increases the risk of developing dementia. Determining the cortical changes associated with MCI in PD, thus, may be useful in predicting the future development of dementia. To address this objective, 37 patients with PD, divided into 2 groups according to the presence or absence MCI (18 with and 19 without) and 16 matched controls, underwent anatomic magnetic resonance imaging. Corticometry analyses were performed to measure the changes in cortical thickness and surface area as well as their correlation with disease duration. Compared with healthy controls, the PD-MCI group exhibited increased atrophy and changes of local surface area in the bilateral occipital, left temporal, and frontal cortices; whereas the PD non-MCI group exhibited only unilateral thinning and decreased surface area in the occipital lobe and in the frontal cortex. In addition, a comparison between the PD-MCI and PD non-MCI groups revealed increased local surface area in the occipital lobe, temporal lobe, and postcentral gyrus for the cognitively impaired patients. It is noteworthy that, in the PD-MCI group, cortical thickness had a significant negative correlation with disease duration in the precentral, supramarginal, occipital, and superior temporal cortices; whereas, in the PD non-MCI group, such a correlation was absent. The findings from this study reveal that, at the same stage of PD evolution, the presence of MCI is associated with a higher level of cortical changes, suggesting that cortical degeneration is increased in patients with PD because of the presence of MCI. PMID:23801590

  2. 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

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

    PubMed

    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; Blumenfeld, Hal

    2010-12-01

    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 activity in

  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. PMID:25096622

  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. PMID:26400248

  7. Anhedonia in the psychosis risk syndrome: associations with social impairment and basal orbitofrontal cortical activity

    PubMed Central

    Cressman, Victoria L; Schobel, Scott A; Steinfeld, Sara; Ben-David, Shelly; Thompson, Judy L; Small, Scott A; Moore, Holly; Corcoran, Cheryl M

    2015-01-01

    Background/Objectives: Anhedonia is associated with poor social function in schizophrenia. Here, we examined this association in individuals at clinical high risk (CHR) for schizophrenia and related psychotic disorders, taking into account social anxiety. We then explored correlations between anhedonia and basal metabolic activity in selected forebrain regions implicated in reward processing. Methods: In 62 CHR individuals and 37 healthy controls, we measured social adjustment (Social Adjustment Self-Report Scale), social and physical anhedonia (Chapman Revised Anhedonia Scales), and social anxiety (Social Anxiety Scale for Adolescents) in cross-section. In a subgroup of 25 CHR individuals for whom high-spatial-resolution basal-state functional magnetic resonance imaging data were available, we also assessed correlations of these socio-affective constructs with basal cerebral blood volume in orbitofrontal cortex and related regions involved in reward processing. Results: Relative to controls, CHR individuals reported social impairment, greater social and physical anhedonia, and more social anxiety, exhibiting impairments comparable to schizophrenia. Regression analyses showed that anhedonia predicted social impairment and correlated negatively with basal cerebral blood volume within the orbitofrontal cortex (all P’s<0.05). Conclusions: Anhedonia and social anxiety are prominent in CHR individuals. Trait-like anhedonia may be a core phenotype related to orbitofrontal cortical function that, independent of symptoms, predicts social impairment. These data provide a rationale for interventions that target anhedonia and related activity in orbitofrontal cortical circuits in CHR individuals. PMID:27336033

  8. Decreased White Matter Integrity in Neuropsychologically-Defined Mild Cognitive Impairment is Independent of Cortical Thinning

    PubMed Central

    Stricker, Nikki H.; Salat, David H.; Foley, Jessica M.; Zink, Tyler A.; Kellison, Ida L.; McFarland, Craig P.; Grande, Laura J.; McGlinchey, Regina E.; Milberg, William P.; Leritz, Elizabeth C.

    2014-01-01

    Improved understanding of the pattern of white matter changes in early and prodromal Alzheimer's disease (AD) states such as Mild Cognitive Impairment (MCI) is necessary to support earlier preclinical detection of AD, and debate remains whether white matter changes in MCI are secondary to gray matter changes. We applied neuropsychologically-based MCI criteria to a sample of normally aging older adults; 32 participants met criteria for MCI and 81 participants were classified as normal control (NC) subjects. Whole-head high resolution T1 and DTI scans were completed. Tract-Based Spatial Statistics was applied and a priori selected ROIs were extracted. Hippocampal volume and cortical thickness averaged across regions with known vulnerability to AD were derived. Controlling for cortical thickness, the MCI group showed decreased average FA and decreased FA in parietal white matter and in white matter underlying the entorhinal and posterior cingulate cortices relative to the NC group. Statistically controlling for cortical thickness, medial temporal FA was related to memory and parietal FA was related to executive functioning. These results provide further support for the potential role of white matter integrity as an early biomarker for individuals at risk for AD and highlight that changes in white matter may be independent of gray matter changes. PMID:23809097

  9. 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

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

    PubMed

    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

  11. Reduced Cortical Activity Impairs Development and Plasticity after Neonatal Hypoxia Ischemia

    PubMed Central

    Ranasinghe, Sumudu; Or, Grace; Wang, Eric Y.; Ievins, Aiva; McLean, Merritt A.; Niell, Cristopher M.; Chau, Vann; Wong, Peter K. H.; Glass, Hannah C.; Sullivan, Joseph

    2015-01-01

    Survivors of preterm birth are at high risk of pervasive cognitive and learning impairments, suggesting disrupted early brain development. The limits of viability for preterm birth encompass the third trimester of pregnancy, a “precritical period” of activity-dependent development characterized by the onset of spontaneous and evoked patterned electrical activity that drives neuronal maturation and formation of cortical circuits. Reduced background activity on electroencephalogram (EEG) is a sensitive marker of brain injury in human preterm infants that predicts poor neurodevelopmental outcome. We studied a rodent model of very early hypoxic–ischemic brain injury to investigate effects of injury on both general background and specific patterns of cortical activity measured with EEG. EEG background activity is depressed transiently after moderate hypoxia–ischemia with associated loss of spindle bursts. Depressed activity, in turn, is associated with delayed expression of glutamate receptor subunits and transporters. Cortical pyramidal neurons show reduced dendrite development and spine formation. Complementing previous observations in this model of impaired visual cortical plasticity, we find reduced somatosensory whisker barrel plasticity. Finally, EEG recordings from human premature newborns with brain injury demonstrate similar depressed background activity and loss of bursts in the spindle frequency band. Together, these findings suggest that abnormal development after early brain injury may result in part from disruption of specific forms of brain activity necessary for activity-dependent circuit development. SIGNIFICANCE STATEMENT Preterm birth and term birth asphyxia result in brain injury from inadequate oxygen delivery and constitute a major and growing worldwide health problem. Poor outcomes are noted in a majority of very premature (<25 weeks gestation) newborns, resulting in death or life-long morbidity with motor, sensory, learning, behavioral

  12. 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

  13. 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. PMID:26946128

  14. 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

  15. Topological Properties of Large-Scale Cortical Networks Based on Multiple Morphological Features in Amnestic Mild Cognitive Impairment

    PubMed Central

    Li, Qiongling; Li, Xinwei; Wang, Xuetong; Li, Yuxia; Li, Kuncheng; Yu, Yang; Yin, Changhao; Li, Shuyu; Han, Ying

    2016-01-01

    Previous studies have demonstrated that amnestic mild cognitive impairment (aMCI) has disrupted properties of large-scale cortical networks based on cortical thickness and gray matter volume. However, it is largely unknown whether the topological properties of cortical networks based on geometric measures (i.e., sulcal depth, curvature, and metric distortion) change in aMCI patients compared with normal controls because these geometric features of cerebral cortex may be related to its intrinsic connectivity. Here, we compare properties in cortical networks constructed by six different morphological features in 36 aMCI participants and 36 normal controls. Six cortical features (3 volumetric and 3 geometric features) were extracted for each participant, and brain abnormities in aMCI were identified by cortical network based on graph theory method. All the cortical networks showed small-world properties. Regions showing significant differences mainly located in the medial temporal lobe and supramarginal and right inferior parietal lobe. In addition, we also found that the cortical networks constructed by cortical thickness and sulcal depth showed significant differences between the two groups. Our results indicated that geometric measure (i.e., sulcal depth) can be used to construct network to discriminate individuals with aMCI from controls besides volumetric measures. PMID:27057360

  16. Topological Properties of Large-Scale Cortical Networks Based on Multiple Morphological Features in Amnestic Mild Cognitive Impairment.

    PubMed

    Li, Qiongling; Li, Xinwei; Wang, Xuetong; Li, Yuxia; Li, Kuncheng; Yu, Yang; Yin, Changhao; Li, Shuyu; Han, Ying

    2016-01-01

    Previous studies have demonstrated that amnestic mild cognitive impairment (aMCI) has disrupted properties of large-scale cortical networks based on cortical thickness and gray matter volume. However, it is largely unknown whether the topological properties of cortical networks based on geometric measures (i.e., sulcal depth, curvature, and metric distortion) change in aMCI patients compared with normal controls because these geometric features of cerebral cortex may be related to its intrinsic connectivity. Here, we compare properties in cortical networks constructed by six different morphological features in 36 aMCI participants and 36 normal controls. Six cortical features (3 volumetric and 3 geometric features) were extracted for each participant, and brain abnormities in aMCI were identified by cortical network based on graph theory method. All the cortical networks showed small-world properties. Regions showing significant differences mainly located in the medial temporal lobe and supramarginal and right inferior parietal lobe. In addition, we also found that the cortical networks constructed by cortical thickness and sulcal depth showed significant differences between the two groups. Our results indicated that geometric measure (i.e., sulcal depth) can be used to construct network to discriminate individuals with aMCI from controls besides volumetric measures. PMID:27057360

  17. 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…

  18. 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…

  19. 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…

  20. Summative effects of vascular risk factors on cortical thickness in mild cognitive impairment.

    PubMed

    Tchistiakova, Ekaterina; MacIntosh, Bradley J

    2016-09-01

    Vascular risk factors (VRFs) increase the risk of Alzheimer's disease (AD) and contribute to neurodegenerative processes. The purpose of this study was to investigate whether increasing number of VRFs contributes to within-cohort differences in cortical thickness (CThk) among adults with mild cognitive impairment (MCI) and cognitively intact older controls from the AD Neuroimaging Initiative 1, GO, and 2 data sets. Multivariate partial least squares analysis was used to investigate the effect of VRF index on regional CThk measurements, which produced a significant latent variable and identified patterns of cortical thinning in the MCI group but not controls. Subsequent analyses tested the interaction effects between VRF index and cognitive grouping and examined 1-year follow-up data. There was evidence of a VRF index by cognitive group interaction. Partial least squares results were replicated at 1-year follow-up among MCI cohort in a subset of baseline CThk regions. This study provides evidence that a summative VRF index accounts for some of the variance in brain tissue loss in regions implicated in AD among MCI adults. PMID:27459930

  1. Decisional impairments in cocaine addiction, reward bias, and cortical oscillation "unbalance".

    PubMed

    Balconi, Michela; Finocchiaro, Roberta

    2015-01-01

    A vast amount of research has suggested that subjects with substance use disorder (SUD) might have difficulty making advantageous decisions that opt in favor of a longer-term, larger reward than an immediate, smaller reward. The current research explored the impact of reward bias and cortical frontal asymmetry (left lateralization effect) in SUD in response to a decisional task (Iowa Gambling Task). Fifty SUD participants and 40 controls (CG) were tested using the Iowa Gambling Task. Electrophysiology (electroencephalography) recording was performed during task execution. We measured left and right dorsolateral prefrontal cortex power activity. Behavioral responses (gain/loss options); frequency band modulation (asymmetry index) for delta, theta, alpha, and beta band; and cortical source localization (standardized low-resolution brain electromagnetic tomography) were considered. The SUD group opted in favor of the immediate reward option (loss) more frequently than the long-term option (gain) when compared to the CG. Secondly, SUD showed increased left-hemisphere activation in response to losing (with immediate reward) choices in comparison with the CG. The left hemispheric unbalance effect and the "reward bias" were adduced to explain the decisional impairment in SUD. PMID:25848274

  2. Impaired plasticity of cortical dendritic spines in P301S tau transgenic mice

    PubMed Central

    2013-01-01

    Background Illuminating the role of the microtubule-associated protein tau in neurodegenerative diseases is of increasing importance, supported by recent studies establishing novel functions of tau in synaptic signalling and cytoskeletal organization. In severe dementias like Alzheimer’s disease (AD), synaptic failure and cognitive decline correlate best with the grade of tau-pathology. To address synaptic alterations in tauopathies, we analyzed the effects of mutant tau expression on excitatory postsynapses in vivo. Results Here we followed the fate of single dendritic spines in the neocortex of a tauopathy mouse model, expressing human P301S mutated tau, for a period of two weeks. We observed a continuous decrease in spine density during disease progression, which we could ascribe to a diminished fraction of gained spines. Remaining spines were enlarged and elongated, thus providing evidence for morphological reorganization in compensation for synaptic dysfunction. Remarkably, loss of dendritic spines in cortical pyramidal neurons occurred in the absence of neurofibrillary tangles (NFTs). Therefore, we consider prefibrillar tau species as causative for the observed impairment in spine plasticity. Conclusions Dendritic spine plasticity and morphology are altered in layer V cortical neurons of P301S tau transgenic mice in vivo. This does not coincide with the detection of hyperphosphorylated tau in dendritic spines. PMID:24344647

  3. Decisional impairments in cocaine addiction, reward bias, and cortical oscillation “unbalance”

    PubMed Central

    Balconi, Michela; Finocchiaro, Roberta

    2015-01-01

    A vast amount of research has suggested that subjects with substance use disorder (SUD) might have difficulty making advantageous decisions that opt in favor of a longer-term, larger reward than an immediate, smaller reward. The current research explored the impact of reward bias and cortical frontal asymmetry (left lateralization effect) in SUD in response to a decisional task (Iowa Gambling Task). Fifty SUD participants and 40 controls (CG) were tested using the Iowa Gambling Task. Electrophysiology (electroencephalography) recording was performed during task execution. We measured left and right dorsolateral prefrontal cortex power activity. Behavioral responses (gain/loss options); frequency band modulation (asymmetry index) for delta, theta, alpha, and beta band; and cortical source localization (standardized low-resolution brain electromagnetic tomography) were considered. The SUD group opted in favor of the immediate reward option (loss) more frequently than the long-term option (gain) when compared to the CG. Secondly, SUD showed increased left-hemisphere activation in response to losing (with immediate reward) choices in comparison with the CG. The left hemispheric unbalance effect and the “reward bias” were adduced to explain the decisional impairment in SUD. PMID:25848274

  4. Reduced Cortical Complexity in Children with Prader-Willi Syndrome and Its Association with Cognitive Impairment and Developmental Delay

    PubMed Central

    Lukoshe, Akvile; Hokken-Koelega, Anita C.; van der Lugt, Aad; White, Tonya

    2014-01-01

    Background Prader-Willi Syndrome (PWS) is a complex neurogenetic disorder with symptoms involving not only hypothalamic, but also a global, central nervous system dysfunction. Previously, qualitative studies reported polymicrogyria in adults with PWS. However, there have been no quantitative neuroimaging studies of cortical morphology in PWS and no studies to date in children with PWS. Thus, our aim was to investigate and quantify cortical complexity in children with PWS compared to healthy controls. In addition, we investigated differences between genetic subtypes of PWS and the relationship between cortical complexity and intelligence within the PWS group. Methods High-resolution structural magnetic resonance images were acquired in 24 children with genetically confirmed PWS (12 carrying a deletion (DEL), 12 with maternal uniparental disomy (mUPD)) and 11 age- and sex-matched typically developing siblings as healthy controls. Local gyrification index (lGI) was obtained using the FreeSurfer software suite. Results Four large clusters, two in each hemisphere, comprising frontal, parietal and temporal lobes, had lower lGI in children with PWS, compared to healthy controls. Clusters with lower lGI also had significantly lower cortical surface area in children with PWS. No differences in cortical thickness of the clusters were found between the PWS and healthy controls. lGI correlated significantly with cortical surface area, but not with cortical thickness. Within the PWS group, lGI in both hemispheres correlated with Total IQ and Verbal IQ, but not with Performance IQ. Children with mUPD, compared to children with DEL, had two small clusters with lower lGI in the right hemisphere. lGI of these clusters correlated with cortical surface area, but not with cortical thickness or IQ. Conclusions These results suggest that lower cortical complexity in children with PWS partially underlies cognitive impairment and developmental delay, probably due to alterations in gene

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

    PubMed

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

    2016-02-01

    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

  6. Impaired spare respiratory capacity in cortical synaptosomes from Sod2 null mice

    PubMed Central

    Flynn, James M.; Choi, Sung W.; Day, Nicholas U.; Gerencser, Akos A.; Hubbard, Alan; Melov, Simon

    2011-01-01

    Pre-synaptic nerve terminals require high levels of ATP for the maintenance of synaptic function. Failure of synaptic mitochondria to generate adequate ATP has been implicated as a causative event preceding loss of synaptic networks in neurodegenerative disease. Endogenous oxidative stress has often been postulated as an etiological basis for this pathology, but has been difficult to test in vivo. Inactivation of the superoxide dismutase gene (Sod2) encoding the chief defense enzyme against mitochondrial superoxide radicals results in neonatal lethality. However, intervention with an SOD mimetic extends the lifespan of this model, and uncovers a neurodegenerative phenotype providing a unique model for the examination of in vivo oxidative stress. We present here studies on synaptic termini isolated from the frontal cortex of Sod2 null mice demonstrating impaired bioenergetic function as a result of mitochondrial oxidative stress. Cortical synaptosomes from Sod2 null mice demonstrate a severe decline in mitochondrial spare respiratory capacity to physiological demand induced by mitochondrial respiratory chain uncoupling with FCCP or plasma membrane depolarization induced by 4-aminopyridine treatment. However, Sod2 null animals compensate for impaired oxidative metabolism in part by Pasteur effect allowing for normal neurotransmitter release at the synapse, setting up a potentially detrimental energetic paradigm. The results of this study demonstrate that high throughput respirometry is a facile method for analyzing specific regions of the brain in transgenic models, and can uncover bioenergetic deficits in subcellular regions due to endogenous oxidative stress. PMID:21215798

  7. Shaping the aging brain: role of auditory input patterns in the emergence of auditory cortical impairments

    PubMed Central

    Kamal, Brishna; Holman, Constance; de Villers-Sidani, Etienne

    2013-01-01

    Age-related impairments in the primary auditory cortex (A1) include poor tuning selectivity, neural desynchronization, and degraded responses to low-probability sounds. These changes have been largely attributed to reduced inhibition in the aged brain, and are thought to contribute to substantial hearing impairment in both humans and animals. Since many of these changes can be partially reversed with auditory training, it has been speculated that they might not be purely degenerative, but might rather represent negative plastic adjustments to noisy or distorted auditory signals reaching the brain. To test this hypothesis, we examined the impact of exposing young adult rats to 8 weeks of low-grade broadband noise on several aspects of A1 function and structure. We then characterized the same A1 elements in aging rats for comparison. We found that the impact of noise exposure on A1 tuning selectivity, temporal processing of auditory signal and responses to oddball tones was almost indistinguishable from the effect of natural aging. Moreover, noise exposure resulted in a reduction in the population of parvalbumin inhibitory interneurons and cortical myelin as previously documented in the aged group. Most of these changes reversed after returning the rats to a quiet environment. These results support the hypothesis that age-related changes in A1 have a strong activity-dependent component and indicate that the presence or absence of clear auditory input patterns might be a key factor in sustaining adult A1 function. PMID:24062649

  8. Spousal caregiving in later life: an objective and subjective career.

    PubMed

    Ross, M M

    1991-01-01

    During later life, as a consequence of the deteriorating health of husbands, numerous women experience a period of spousal caregiving that can be considered a new phase in their caregiving career. This phase, which often precedes widowhood, is one that has been relatively neglected by researchers. In this article, the concepts of objective and subjective career (Hughes, 1971) are used as orienting concepts to examine the phenomenon of spousal caregiving in later life. Objectively, the caregiving career is seen as an age-related, gender-specific, and role-contingent phenomenon. The subjective career is seen as the meaning and purposes attributed to complex and extensive responsibilities and activities of caregiving and their potentially serious consequences for health and well-being. PMID:1989956

  9. 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…

  10. Cortical source multivariate EEG synchronization analysis on amnestic mild cognitive impairment in type 2 diabetes.

    PubMed

    Cui, Dong; Liu, Jing; Bian, Zhijie; Li, Qiuli; Wang, Lei; Li, Xiaoli

    2014-01-01

    Is synchronization altered in amnestic mild cognitive impairment (aMCI) and normal cognitive functions subjects in type 2 diabetes mellitus (T2DM)? Resting eye-closed EEG data were recorded in 8 aMCI subjects and 11 age-matched controls in T2DM. Three multivariate synchronization algorithms (S-estimator (S), synchronization index (SI), and global synchronization index (GSI)) were used to measure the synchronization in five ROIs of sLORETA sources for seven bands. Results showed that aMCI group had lower synchronization values than control groups in parietal delta and beta2 bands, temporal delta and beta2 bands, and occipital theta and beta2 bands significantly. Temporal (r = 0.629; P = 0.004) and occipital (r = 0.648; P = 0.003) theta S values were significantly positive correlated with Boston Name Testing. In sum, each of methods reflected that the cortical source synchronization was significantly different between aMCI and control group, and these difference correlated with cognitive functions. PMID:25254248

  11. Sleep deficits in mild cognitive impairment are related to increased levels of plasma amyloid-β and cortical thinning.

    PubMed

    Sanchez-Espinosa, Mayely P; Atienza, Mercedes; Cantero, Jose L

    2014-09-01

    Evidence suggests that amyloid-beta (Aβ) depositions parallel sleep deficits in Alzheimer's disease (AD). However, it remains unknown whether impaired sleep and changes in plasma Aβ levels are related in amnestic mild cognitive impairment (aMCI) subjects, and whether both markers are further associated with cortical thinning in canonical AD regions. To jointly address this issue, we investigated relationships between changes in physiological sleep and plasma Aβ concentrations in 21 healthy old (HO) adults and 21 aMCI subjects, and further assessed whether these two factors were associated with cortical loss in each group. aMCI, but not HO subjects, showed significant relationships between disrupted slow-wave sleep (SWS) and increased plasma levels of Aβ42. We also found that shortened rapid-eye movement (REM) sleep in aMCI correlated with thinning of the posterior cingulate, precuneus, and postcentral gyrus; whereas higher levels of Aβ40 and Aβ42 accounted for grey matter (GM) loss of posterior cingulate and entorhinal cortex, respectively. These results support preliminary relationships between Aβ burden and altered sleep physiology observed in animal models of AD amyloidosis, and provide precise cortical correlates of these changes in older adults with aMCI. Taken together, these findings open new research avenues on the combined role of sleep, peripheral Aβ levels and cortical integrity in tracking the progression from normal aging to early neurodegeneration. PMID:24845621

  12. Differences in cortical thickness in healthy controls, subjects with mild cognitive impairment, and Alzheimer's disease patients: a longitudinal study.

    PubMed

    Julkunen, Valtteri; Niskanen, Eini; Koikkalainen, Juha; Herukka, Sanna-Kaisa; Pihlajamäki, Maija; Hallikainen, Merja; Kivipelto, Miia; Muehlboeck, Sebastian; Evans, Alan C; Vanninen, Ritva; Hilkka Soininen

    2010-01-01

    In this study, we analyzed differences in cortical thickness (CTH) between healthy controls (HC), subjects with stable mild cognitive impairment (S-MCI), progressive MCI (P-MCI), and Alzheimer's disease (AD), and assessed correlations between CHT and clinical disease severity, education, and apolipoprotein E4 (APOE) genotype. Automated CTH analysis was applied to baseline high-resolution structural MR images of 145 subjects with a maximum followup time of 7.4 years pooled from population-based study databases held in the University of Kuopio. Statistical differences in CTH between study groups and significant correlations between CTH and clinical and demographic factors were assessed and displayed on a cortical surface model. Compared to HC group (n = 26), the AD (n = 21) group displayed significantly reduced CTH in several areas of frontal and temporal cortices of the right hemisphere. Higher education and lower MMSE scores were correlated with reduced CTH in the AD group, whereas no significant correlation was found between CDR-SB scores or APOE genotype and CTH. The P-MCI group demonstrated significantly reduced CTH compared to S-MCI in frontal, temporal and parietal cortices even after statistically adjusting for all confounding variables. Ultimately, analysis of CTH can be used to detect cortical thinning in subjects with progressive MCI several years before conversion and clinical diagnosis of AD dementia, irrespective of their cognitive performance, education level, or APOE genotype. PMID:21504134

  13. 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. PMID:26332218

  14. Impairment of Oligodendroglia Maturation Leads to Aberrantly Increased Cortical Glutamate and Anxiety-Like Behaviors in Juvenile Mice

    PubMed Central

    Chen, Xianjun; Zhang, Weiguo; Li, Tao; Guo, Yu; Tian, Yanping; Wang, Fei; Liu, Shubao; Shen, Hai-Ying; Feng, Yue; Xiao, Lan

    2015-01-01

    Adolescence is the critical time for developing proper oligodendrocyte (OL)-neuron interaction and the peak of onset for many cognitive diseases, among which anxiety disorders display the highest prevalence. However, whether impairment of de novo OL development causes neuronal abnormalities and contributes to the early onset of anxiety phenotype in childhood still remains unexplored. In this study, we tested the hypothesis that defects in OL maturation manifests cortical neuron function and leads to anxiety-like behaviors in juvenile mice. We report here that conditional knockout of the Olig2 gene (Olig2 cKO) specifically in differentiating OLs in the mouse brain preferentially impaired OL maturation in the gray matter of cerebral cortex. Interestingly, localized proton magnetic resonance spectroscopy revealed that Olig2 cKO mice displayed abnormally elevated cortical glutamate levels. In addition, transmission electron microscopy demonstrated increased vesicle density in excitatory glutamatergic synapses in the cortex of the Olig2 cKO mice. Moreover, juvenile Olig2 cKO mice exhibited anxiety-like behaviors and impairment in behavioral inhibition. Taken together, our results suggest that impaired OL development affects glutamatergic neuron function in the cortex and causes anxiety-related behaviors in juvenile mice. These discoveries raise an intriguing possibility that OL defects may be a contributing mechanism for the onset of anxiety in childhood. PMID:26696827

  15. Prefrontal cortical thinning in HIV infection is associated with impaired striatal functioning.

    PubMed

    du Plessis, Stéfan; Vink, Matthijs; Joska, John A; Koutsilieri, Eleni; Bagadia, Asif; Stein, Dan J; Emsley, Robin

    2016-06-01

    While cortical thinning has been associated with HIV infection, it is unclear whether this reflects a direct effect of the virus, whether it is related to disruption of subcortical function or whether it is better explained by epiphenomena, such as drug abuse or comorbid medical conditions. The present study investigated the relationship between cortical thickness and subcortical function in HIV+ patients. Specifically, we examined the relationship between prefrontal cortical thickness and striatal function. Twenty-three largely treatment naïve, non-substance abusing HIV+ participants and 19 healthy controls matched for age, gender, and educational status were included. Cortical morphometry was performed using FreeSurfer software analysis. Striatal function was measured during an fMRI stop-signal anticipation task known to engage the striatum. Any cortical regions showing significant thinning were entered as dependent variables into a single linear regression model which included subcortical function, age, CD4 count, and a measure of global cognitive performance as independent predictors. The only cortical region that was significantly reduced after correction for multiple comparisons was the right superior frontal gyrus. Striatal activity was found to independently predict superior frontal gyral cortical thickness. While cortical thinning in HIV infection is likely multifactorial, viral induced subcortical dysfunction appears to play a role. PMID:27173383

  16. 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. PMID:25953057

  17. Later life care planning conversations for older adults and families.

    PubMed

    Stolee, Paul; Zaza, Christine; Sharratt, Michael T

    2014-09-01

    While most older adults have thought about their future care needs, few have discussed their preferences with family members. We interviewed older persons (24), adult children (24), health professionals (23), and representatives of stakeholder associations (3) to understand their views and experiences on later life care (LLC) planning conversations, in terms of (a) their respective roles, and (b) barriers and facilitators that should be taken into account when having these conversations. Roles described included that of information user (older persons), information seeker (family members), and information provider (health care providers). The study identified practical and emotional considerations relevant to LLC planning conversations. This study found strong support for planning for LLC before the need arises, as well as important potential benefits for older adults, family members, and health professionals. There is interest in, and need for, resources to guide families in LLC planning. PMID:24652903

  18. 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. PMID:25456620

  19. Impaired development and competitive refinement of the cortical frequency map in tumor necrosis factor-α-deficient mice.

    PubMed

    Yang, Sungchil; Zhang, Li S; Gibboni, Robert; Weiner, Benjamin; Bao, Shaowen

    2014-07-01

    Early experience shapes sensory representations in a critical period of heightened plasticity. This adaptive process is thought to involve both Hebbian and homeostatic synaptic plasticity. Although Hebbian plasticity has been investigated as a mechanism for cortical map reorganization, less is known about the contribution of homeostatic plasticity. We investigated the role of homeostatic synaptic plasticity in the development and refinement of frequency representations in the primary auditory cortex using the tumor necrosis factor-α (TNF-α) knockout (KO), a mutant mouse with impaired homeostatic but normal Hebbian plasticity. Our results indicate that these mice develop weaker tonal responses and incomplete frequency representations. Rearing in a single-frequency revealed a normal expansion of cortical representations in KO mice. However, TNF-α KOs lacked homeostatic adjustments of cortical responses following exposure to multiple frequencies. Specifically, while this sensory over-stimulation resulted in competitive refinement of frequency tuning in wild-type controls, it broadened frequency tuning in TNF-α KOs. Our results suggest that homeostatic plasticity plays an important role in gain control and competitive interaction in sensory cortical development. PMID:23448874

  20. 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. PMID:25522735

  1. Impairment of learning the voluntary control of posture in patients with cortical lesions of different locations: the cortical mechanisms of pose regulation.

    PubMed

    Ustinova, K I; Chernikova, L A; Ioffe, M E; Sliva, S S

    2001-01-01

    The process of learning to produce voluntary changes in the position of the center of pressures using biological feedback was studied by stabilography in patients with hemipareses due to cerebrovascular lesions in the zone supplied by the middle cerebral artery. There were significant impairments to learning in all groups of patients, who had lesions in different sites, demonstrating that cortical mechanisms are involved in learning to control posture voluntarily. These studies showed that patients with lesions in the right hemisphere had rather greater deficits in performing the task than those with lesions in the left hemisphere. There were significant differences in the initial deficit in performing the task on the first day of training depending on the side of the lesion. All groups of patients differed from healthy subjects in that significant learning occurred only at the initial stages of training (the first five days). Learning at the initial stage in patients with concomitant lesions of the parietal-temporal area and with combined lesions with motor, premotor, and parietal-temporal involvement was significantly worse and the level of task performance at the end of the initial stage was significantly worse than in patient with local lesions of the motor cortex. The level of learning was independent of the severity of the motor deficit (paresis, spasticity), but was associated with the severity of impairment of the proprioceptive sense and the severity of disruption to the upright posture (asymmetry in the distribution of support pressures, amplitude of variation in the position of the center of pressures). The learning process had positive effects on the severity of motor impairment and on the asymmetry of the distribution of support pressures in the standing posture. Reorganization of posture during bodily movements occurred mainly because of impairment to the developed "non-use" stereotype of the paralyzed lower limb. PMID:11430569

  2. Amyloid beta-peptide impairs glucose transport in hippocampal and cortical neurons: involvement of membrane lipid peroxidation.

    PubMed

    Mark, R J; Pang, Z; Geddes, J W; Uchida, K; Mattson, M P

    1997-02-01

    A deficit in glucose uptake and a deposition of amyloid beta-peptide (A beta) each occur in vulnerable brain regions in Alzheimer's disease (AD). It is not known whether mechanistic links exist between A beta deposition and impaired glucose transport. We now report that A beta impairs glucose transport in cultured rat hippocampal and cortical neurons by a mechanism involving membrane lipid peroxidation. A beta impaired 3H-deoxy-glucose transport in a concentration-dependent manner and with a time course preceding neurodegeneration. The decrease in glucose transport was followed by a decrease in cellular ATP levels. Impairment of glucose transport, ATP depletion, and cell death were each prevented in cultures pretreated with antioxidants. Exposure to FeSO4, an established inducer of lipid peroxidation, also impaired glucose transport. Immunoprecipitation and Western blot analyses showed that exposure of cultures to A beta induced conjugation of 4-hydroxynonenal (HNE), an aldehydic product of lipid peroxidation, to the neuronal glucose transport protein GLUT3. HNE induced a concentration-dependent impairment of glucose transport and subsequent ATP depletion. Impaired glucose transport was not caused by a decreased energy demand in the neurons, because ouabain, which inhibits Na+/K(+)-ATPase activity and thereby reduces neuronal ATP hydrolysis rate, had little or no effect on glucose transport. Collectively, the data demonstrate that lipid peroxidation mediates A beta-induced impairment of glucose transport in neurons and suggest that this action of A beta may contribute to decreased glucose uptake and neuronal degeneration in AD. PMID:8994059

  3. Impaired adrenergic-mediated plasticity of prefrontal cortical glutamate synapses in rats with developmental disruption of the ventral hippocampus.

    PubMed

    Bhardwaj, Sanjeev K; Tse, Yiu Chung; Ryan, Richard; Wong, Tak Pan; Srivastava, Lalit K

    2014-12-01

    Neonatal ventral hippocampus (nVH) lesion in rats is a useful model to study developmental origins of adult cognitive deficits and certain features of schizophrenia. nVH lesion-induced reorganization of excitatory and inhibitory neurotransmissions within prefrontal cortical (PFC) circuits is widely believed to be responsible for many of the behavioral abnormalities in these animals. Here we provide evidence that development of an aberrant medial PFC (mPFC) α-1 adrenergic receptor (α-1AR) function following neonatal lesion markedly affects glutamatergic synaptic plasticity within PFC microcircuits and contributes to PFC-related behavior abnormalities. Using whole-cell patch-clamp recording, we report that norepinephrine-induced α-1AR-dependent long-term depression (LTD) in a subset of cortico-cortical glutamatergic inputs is strikingly diminished in mPFC slices from nVH-lesioned rats. The LTD impairment occurs in conjunction with completely blunted α-1AR signaling through extracellular signal-regulated kinase 1/2. These α-1AR abnormalities have functional significance in a mPFC-related function, that is, extinction of conditioned fear memory. Post-pubertal animals with nVH lesion show significant resistance to extinction of fear by repeated presentations of the conditioned tone stimulus. mPFC infusion of an α-1AR antagonist (benoxathian) or LTD blocking peptide (Tat-GluR23Y) impaired fear extinction in sham controls, but had no significant effect in the lesioned animals. The data suggest that impaired α-1 adrenergic regulation of cortical glutamatergic synaptic plasticity may be an important mechanism in cognitive dysfunctions reported in neurodevelopmental psychiatric disorders. PMID:24917197

  4. Childbearing history, later-life health, and mortality in Germany.

    PubMed

    Hank, Karsten

    2010-11-01

    Using data from the German Socio-Economic Panel, we investigated the role of childbearing history in later-life health and mortality, paying particular attention to possible differences by sex and region. Higher parity is associated with better self-rated health in West German mothers and fathers aged 50+, but its relationship with East German women's physical health and survival is negative. Early motherhood is paralleled by poorer physical health in West Germany, whereas late motherhood is associated with lower psychological well-being in Eastern Germany. Moreover, among West German women, having had a non-marital first birth is weakly correlated with poorer physical health. Our findings support the notion of biosocial pathways playing an important role in shaping the fertility-health nexus. Specifically, the West German 'male-breadwinner' model of specialization appears to have buffered the stresses associated with childrearing, whereas fertility off the 'normative' life-course track appears to have had adverse effects on women's health in West Germany. PMID:20845224

  5. Mismatch negativity indexes illness-specific impairments of cortical plasticity in schizophrenia: a comparison with bipolar disorder and Alzheimer's disease.

    PubMed

    Baldeweg, Torsten; Hirsch, Steven R

    2015-02-01

    Cognitive impairment is an important predictor of functional outcome in patients with schizophrenia, yet its neurobiology is still incompletely understood. Neuropathological evidence of impaired synaptic connectivity and NMDA receptor-dependent transmission in superior temporal cortex motivated us to explore the correlation of in vivo mismatch negativity (MMN) with cognitive status in patients with schizophrenia. MMN elicited in a roving stimulus paradigm displayed a response proportional to the number of stimulus repetitions (memory trace effect). Preliminary evidence in patients with chronic schizophrenia suggests that attenuation of this MMN memory trace effect was correlated with the degree of neuropsychological memory dysfunction. Here we present data from a larger confirmatory study in patients with schizophrenia, bipolar disorder, probable Alzheimer's disease and healthy controls. We observed that the diminution of the MMN memory trace effect and its correlation with memory impairment was only found in the schizophrenia group. Recent pharmacological studies using the roving paradigm suggest that attenuation of the MMN trace effect can be understood as abnormal modulation of NMDA receptor-dependent plasticity. We suggest that the convergence of the previously identified synaptic pathology in supragranular cortical layers with the intracortical locus of MMN generation accounts for the remarkable robustness of MMN impairments in schizophrenia. We further speculate that this layer-specific synaptic pathology identified in supragranular neurons plays a pivotal computational role, by weakening the encoding and propagation of prediction errors to higher cortical modules. According to predictive coding theory such breakdown will have grave implications not only for perception, but also for higher-order cognition and may thus account for the MMN-cognition correlations observed here. Finally, MMN is a sensitive and specific biomarker for detecting the early prodromal

  6. 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

  7. Altered Fetal Skeletal Muscle Nutrient Metabolism Following an Adverse In Utero Environment and the Modulation of Later Life Insulin Sensitivity

    PubMed Central

    Dunlop, Kristyn; Cedrone, Megan; Staples, James F.; Regnault, Timothy R.H.

    2015-01-01

    The importance of the in utero environment as a contributor to later life metabolic disease has been demonstrated in both human and animal studies. In this review, we consider how disruption of normal fetal growth may impact skeletal muscle metabolic development, ultimately leading to insulin resistance and decreased insulin sensitivity, a key precursor to later life metabolic disease. In cases of intrauterine growth restriction (IUGR) associated with hypoxia, where the fetus fails to reach its full growth potential, low birth weight (LBW) is often the outcome, and early in postnatal life, LBW individuals display modifications in the insulin-signaling pathway, a critical precursor to insulin resistance. In this review, we will present literature detailing the classical development of insulin resistance in IUGR, but also discuss how this impaired development, when challenged with a postnatal Western diet, may potentially contribute to the development of later life insulin resistance. Considering the important role of the skeletal muscle in insulin resistance pathogenesis, understanding the in utero programmed origins of skeletal muscle deficiencies in insulin sensitivity and how they may interact with an adverse postnatal environment, is an important step in highlighting potential therapeutic options for LBW offspring born of pregnancies characterized by placental insufficiency. PMID:25685986

  8. Altered fetal skeletal muscle nutrient metabolism following an adverse in utero environment and the modulation of later life insulin sensitivity.

    PubMed

    Dunlop, Kristyn; Cedrone, Megan; Staples, James F; Regnault, Timothy R H

    2015-01-01

    The importance of the in utero environment as a contributor to later life metabolic disease has been demonstrated in both human and animal studies. In this review, we consider how disruption of normal fetal growth may impact skeletal muscle metabolic development, ultimately leading to insulin resistance and decreased insulin sensitivity, a key precursor to later life metabolic disease. In cases of intrauterine growth restriction (IUGR) associated with hypoxia, where the fetus fails to reach its full growth potential, low birth weight (LBW) is often the outcome, and early in postnatal life, LBW individuals display modifications in the insulin-signaling pathway, a critical precursor to insulin resistance. In this review, we will present literature detailing the classical development of insulin resistance in IUGR, but also discuss how this impaired development, when challenged with a postnatal Western diet, may potentially contribute to the development of later life insulin resistance. Considering the important role of the skeletal muscle in insulin resistance pathogenesis, understanding the in utero programmed origins of skeletal muscle deficiencies in insulin sensitivity and how they may interact with an adverse postnatal environment, is an important step in highlighting potential therapeutic options for LBW offspring born of pregnancies characterized by placental insufficiency. PMID:25685986

  9. 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

  10. Impaired cortical neurogenesis in plexin-B1 and -B2 double deletion mutant.

    PubMed

    Daviaud, Nicolas; Chen, Karen; Huang, Yong; Friedel, Roland H; Zou, Hongyan

    2016-08-01

    Mammalian cortical expansion is tightly controlled by fine-tuning of proliferation and differentiation of neural progenitors in a region-specific manner. How extrinsic cues interface with cell-intrinsic programs to balance proliferative versus neurogenic decisions remains an unsolved question. We examined the function of Semaphorin receptors Plexin-B1 and -B2 in corticogenesis by generating double mutants, whereby Plexin-B2 was conditionally ablated in the developing brain in a Plexin-B1 null mutant background. Absence of both Plexin-Bs resulted in cortical thinning, particularly in the caudomedial cortex. Plexin-B1/B2 double, but not single, mutants exhibited a reduced neural progenitor pool, attributable to decreased proliferation and an altered division mode favoring cell cycle exit. This resulted in deficient production of neurons throughout the neurogenic period, proportionally affecting all cortical laminae. Consistent with the in vivo data, cultured neural progenitors lacking both Plexin-B1 and -B2 displayed decreased proliferative capacity and increased spontaneous differentiation. Our study therefore defines a novel function of Plexin-B1 and -B2 in transmitting extrinsic signals to maintain proliferative and undifferentiated states of neural progenitors. As single mutants displayed no apparent cortical defects, we conclude that Plexin-B1 and -B2 play redundant or compensatory roles during forebrain development to ensure proper neuronal production and neocortical expansion. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 882-899, 2016. PMID:26579598

  11. 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…

  12. 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

  13. 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

  14. Assessment of Cortical Visual Impairment in Infants with Periventricular Leukomalacia: a Pilot Event-Related fMRI Study

    PubMed Central

    Yu, Bing; Fan, Guoguang; Liu, Na

    2011-01-01

    Objective We wanted to investigate the usefulness of event-related (ER) functional MRI (fMRI) for the assessment of cortical visual impairment in infants with periventricular leukomalacia (PVL). Materials and Methods FMRI data were collected from 24 infants who suffered from PVL and from 12 age-matched normal controls. Slow ER fMRI was performed using a 3.0T MR scanner while visual stimuli were being presented. Data analysis was performed using Statistical Parametric Mapping software (SPM2), the SPM toolbox MarsBar was used to analyze the region of interest data, and the time to peak (TTP) of hemodynamic response functions (HRFs) was estimated for the surviving voxels. The number of activated voxels and the TTP values of HRFs were compared. Pearson correlation analysis was performed to compare visual impairment evaluated by using Teller Acuity Cards (TAC) with the number of activated voxels in the occipital lobes in all patients. Results In all 12 control infants, the blood oxygenation level-dependent (BOLD) signal was negative and the maximum response was located in the anterior and superior part of the calcarine fissure, and this might correspond to the anterior region of the primary visual cortex (PVC). In contrast, for the 24 cases of PVL, there were no activated pixels in the PVC in four subjects, small and weak activations in six subjects, deviated activations in seven subjects and both small and deviated activations in three subjects. The number of active voxels in the occipital lobe was significantly correlated with the TAC-evaluated visual impairment (p < 0.001). The mean TTP of the HRFs was significantly delayed in the cases of PVL as compared with that of the normal controls. Conclusion Determining the characteristics of both the BOLD response and the ER fMRI activation may play an important role in the cortical visual assessment of infants with PVL. PMID:21852907

  15. Cognitive, affective and eudemonic well-being in later life

    PubMed Central

    Vanhoutte, Bram; Nazroo, James

    2016-01-01

    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

  16. Chronic ethanol consumption impairs spatial remote memory in rats but does not affect cortical cholinergic parameters.

    PubMed

    Pereira, S R; Menezes, G A; Franco, G C; Costa, A E; Ribeiro, A M

    1998-06-01

    We have studied learning, memory and cortical cholinergic parameters after oral administration of 20% v/v ethanol solution to male Fisher rats for 6 months. A group of rats were trained to behave efficiently in an eight-arm radial maze and after that split into two subgroups submitted to ethanol or control treatment. Ethanol-treated rats had more difficulty in relearning the same task 1 year later, compared to ethanol-untreated rats (control). Differences in working memory performance were found, but only in the first 10 training sessions. Another group of rats, which had not been pretrained, was also split into two subgroups submitted to ethanol or control treatment. After that, these rats were trained in the radial maze task for the first time. No significant difference was found between the reference memory performance of the untreated subgroup and the treated one. These two subgroups did not significantly differ in their working memory performance either. Moreover, there were no significant differences between treated and control subjects in the following biochemical brain cortical parameters: in vitro acetylcholinesterase (AChE) activity, and stimulated acetylcholine (ACh) release. This work presents an experimental design that allows assessment of remote memory performance after ethanol chronic consumption and shows that the experimental subject is able to retain the behaviors learned 1 year before. It was concluded that chronic ethanol treatment may cause retrograde amnesia, which does not seem to be linked with a cortical cholinergic deficit. PMID:9632211

  17. Prediction of Alzheimer's disease in subjects with mild cognitive impairment from the ADNI cohort using patterns of cortical thinning.

    PubMed

    Eskildsen, Simon F; Coupé, Pierrick; García-Lorenzo, Daniel; Fonov, Vladimir; Pruessner, Jens C; Collins, D Louis

    2013-01-15

    Predicting Alzheimer's disease (AD) in individuals with some symptoms of cognitive decline may have great influence on treatment choice and disease progression. Structural magnetic resonance imaging (MRI) has the potential of revealing early signs of neurodegeneration in the human brain and may thus aid in predicting and diagnosing AD. Surface-based cortical thickness measurements from T1-weighted MRI have demonstrated high sensitivity to cortical gray matter changes. In this study we investigated the possibility for using patterns of cortical thickness measurements for predicting AD in subjects with mild cognitive impairment (MCI). We used a novel technique for identifying cortical regions potentially discriminative for separating individuals with MCI who progress to probable AD, from individuals with MCI who do not progress to probable AD. Specific patterns of atrophy were identified at four time periods before diagnosis of probable AD and features were selected as regions of interest within these patterns. The selected regions were used for cortical thickness measurements and applied in a classifier for testing the ability to predict AD at the four stages. In the validation, the test subjects were excluded from the feature selection to obtain unbiased results. The accuracy of the prediction improved as the time to conversion from MCI to AD decreased, from 70% at 3 years before the clinical criteria for AD was met, to 76% at 6 months before AD. By inclusion of test subjects in the feature selection process, the prediction accuracies were artificially inflated to a range of 73% to 81%. Two important results emerge from this study. First, prediction accuracies of conversion from MCI to AD can be improved by learning the atrophy patterns that are specific to the different stages of disease progression. This has the potential to guide the further development of imaging biomarkers in AD. Second, the results show that one needs to be careful when designing training

  18. Alcohol Problems and Depression in Later Life: Development of Two Knowledge Quizzes.

    ERIC Educational Resources Information Center

    Pratt, Clara C.; And Others

    1992-01-01

    Notes that effective measures of knowledge about mental health in later life are valuable in needs assessments and educational program evaluations. Describes development of two short, true/false quizzes, one on alcohol problems, other on depression and suicide in later life. Discusses usefulness of quizzes in planning and evaluating community…

  19. Silencing TRPM7 in Mouse Cortical Astrocytes Impairs Cell Proliferation and Migration via ERK and JNK Signaling Pathways

    PubMed Central

    Zeng, Zhao; Leng, Tiandong; Feng, Xuechao; Sun, Huawei; Inoue, Koichi; Zhu, Li; Xiong, Zhi-Gang

    2015-01-01

    Transient receptor potential melastatin 7 (TRPM7), a non-selective cation channel, is highly expressed expressed in the brain and plays a critical role in ischemic neuronal death. Astrocyte, the most abundant cell type in central nervous system (CNS), exerts many essential functions in the physiological and pathological conditions. Here we investigated the expression and functions of the TRPM7 channel in mouse cortical astrocytes. Using reverse transcription (RT)-PCR, immunostaining, western blot and patch clamp recording, we showed that functional TRPM7 channel is expressed in cultured mouse cortical astrocytes. Knocking down TRPM7 with specific siRNA impairs the proliferation and migration of astrocytes by 40.2% ± 3.9% and 40.1% ± 11.5%, respectively. Consistently, inhibition of TRPM7 with 2-aminoethoxydiphenyl borate (2-APB) also decreases astrocyte proliferation and migration by 46.1% ± 2.5% and 64.2% ± 2.4%. MAPKs and Akt signaling pathways have been shown to be implicated in TRPM7-mediated responses including cell proliferation and migration. Our data show that suppression of TRPM7 in astrocytes reduces the phosphorylation of extracellular signal-regulated kinases (ERK) and c-Jun N-terminal kinases (JNK), but not p38 mitogen-activated protein kinase and Akt. In addition, TRPM7, as a cation channel, has been involved in the Ca2+ and Mg2+ homeostasis in several types of cells. In our study, we found that silencing TRPM7 decreases the intracellular basal Mg2+ concentration without affecting Ca2+ concentration in astrocytes. However, an addition of Mg2+ to the growth medium could not rescue the impaired proliferation of astrocytes. Together, our data suggest that TRPM7 channel may play a critical role in the proliferation and migration of astrocytes via the ERK and JNK pathways. PMID:25799367

  20. 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. PMID:26708494

  1. 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. PMID:25181316

  2. 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

  3. 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)

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

    PubMed

    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 interventions for

  5. 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

  6. Learning impairment by minimal cortical injury in a mouse model of Alzheimer's disease.

    PubMed

    Zou, Jingyu; Wang, Min; Uchiumi, Osamu; Shui, Yuan; Ishigaki, Yasuhito; Liu, Xiaoyan; Tajima, Nobuyoshi; Akai, Takuya; Iizuka, Hideaki; Kato, Nobuo

    2016-04-15

    Brain injury accelerates amyloid-β (Aβ) deposits and exacerbates Alzheimer's disease (AD). Accumulation of intracellular soluble Aβ impairs cognition prior to emergence of Aβ plaques. However, it is not known whether brain injury affects learning impairment attributable to intracellular soluble Aβ. We made a small injury by injecting glutamate into the parietal cortex in 3xTg AD mice of 4-5 months old, at which age soluble Aβ is accumulated without Aβ deposits. The size of glutamate-induced lesion was significantly larger than that of saline-injected control lesion. We reduced the relative difficulty of Morris water maze (MWM) task by repeating it twice, so that saline-injected 3xTg mice could perform as well as wild-type control mice. Under this condition, glutamate-injected 3xTg mice exhibited learning deficits. DNA microarray analysis revealed that 3 genes are upregulated, with one gene downregulated, more than 2 folds in the hippocampus. These 4 genes do not appear to be involved directly in learning but may be a part of signal cascade triggered by glutamate-induced small injury. Hippocampal content of soluble Aβ1-42 was increased in the glutamate 3xTg group. Facilitation of large-conductance calcium-activated potassium (BK) channel accompanied learning recovery in the saline-control 3xTg group in agreement with our previous reports, in which learning deficits attributable to intracellular Aβ were alleviated by facilitating BK channels. However, BK channel remained suppressed in the glutamate 3xTg group. It is suggested that glutamate-induced injury worsens learning by enhancing the toxicity of soluble Aβ or increasing its content per se. PMID:26876740

  7. Association between mid-life marital status and cognitive function in later life: population based cohort study

    PubMed Central

    Håkansson, Krister; Rovio, Suvi; Helkala, Eeva-Liisa; Vilska, Anna-Riitta; Winblad, Bengt; Soininen, Hilkka; Nissinen, Aulikki; Mohammed, Abdul H

    2009-01-01

    Objectives To evaluate whether mid-life marital status is related to cognitive function in later life. Design Prospective population based study with an average follow-up of 21 years. Setting Kuopio and Joensuu regions in eastern Finland. Participants Participants were derived from random, population based samples previously investigated in 1972, 1977, 1982, or 1987; 1449 individuals (73%), aged 65-79, underwent re-examination in 1998. Main outcome measures Alzheimer’s disease and mild cognitive impairment. Results People cohabiting with a partner in mid-life (mean age 50.4) were less likely than all other categories (single, separated, or widowed) to show cognitive impairment later in life at ages 65-79. Those widowed or divorced in mid-life and still so at follow-up had three times the risk compared with married or cohabiting people. Those widowed both at mid-life and later life had an odds ratio of 7.67 (1.6 to 40.0) for Alzheimer’s disease compared with married or cohabiting people. The highest increased risk for Alzheimer’s disease was in carriers of the apolipoprotein E e4 allele who lost their partner before mid-life and were still widowed or divorced at follow-up. The progressive entering of several adjustment variables from mid-life did not alter these associations. Conclusions Living in a relationship with a partner might imply cognitive and social challenges that have a protective effect against cognitive impairment later in life, consistent with the brain reserve hypothesis. The specific increased risk for widowed and divorced people compared with single people indicates that other factors are needed to explain parts of the results. A sociogenetic disease model might explain the dramatic increase in risk of Alzheimer’s disease for widowed apolipoprotein E e4 carriers. PMID:19574312

  8. Mild cognitive impairment, poor episodic memory, and late-life depression are associated with cerebral cortical thinning and increased white matter hyperintensities

    PubMed Central

    Fujishima, Motonobu; Maikusa, Norihide; Nakamura, Kei; Nakatsuka, Masahiro; Matsuda, Hiroshi; Meguro, Kenichi

    2014-01-01

    In various independent studies to date, cerebral cortical thickness and white matter hyperintensity (WMH) volume have been associated with episodic memory, depression, and mild cognitive impairment (MCI). The aim of this study was to uncover variations in cortical thickness and WMH volume in association with episodic memory, depressive state, and the presence of MCI simultaneously in a single study population. The participants were 186 individuals with MCI (clinical dementia rating [CDR] of 0.5) and 136 healthy elderly controls (HCs; CDR of 0) drawn from two community-based cohort studies in northern Japan. We computed cerebral cortical thickness and WMH volume by using MR scans and statistically analyzed differences in these indices between HCs and MCI participants. We also assessed the associations of these indices with memory performance and depressive state in participants with MCI. Compared with HCs, MCI participants exhibited thinner cortices in the temporal and inferior parietal lobes and greater WMH volumes in the corona radiata and semioval center. In MCI participants, poor episodic memory was associated with thinner cortices in the left entorhinal region and increased WMH volume in the posterior periventricular regions. Compared with non-depressed MCI participants, depressed MCI participants showed reduced cortical thickness in the anterior medial temporal lobe and gyrus adjacent to the amygdala bilaterally, as well as greater WMH volume as a percentage of the total intracranial volume (WMHr). A higher WMHr was associated with cortical thinning in the frontal, temporal, and parietal regions in MCI participants. These results demonstrate that episodic memory and depression are associated with both cortical thickness and WMH volume in MCI participants. Additional longitudinal studies are needed to clarify the dynamic associations and interactions among these indices. PMID:25426066

  9. Cortical Amyloid Burden Differences Across Empirically-Derived Mild Cognitive Impairment Subtypes and Interaction with APOE ε4 Genotype

    PubMed Central

    Bangen, Katherine J.; Clark, Alexandra L.; Werhane, Madeline; Edmonds, Emily C.; Nation, Daniel A.; Evangelista, Nicole; Libon, David J.; Bondi, Mark W.; Delano-Wood, Lisa

    2016-01-01

    We examined cortical amyloid-β (Aβ) levels and interactions with apolipoprotein (APOE) ε4 genotype status across empirically-derived mild cognitive impairment (MCI) subgroups and cognitively normal older adults. Participants were 583 ADNI participants (444 MCI, 139 normal controls [NC]) with baseline florbetapir positron emission tomography (PET) amyloid imaging and neuropsychological testing. Of those with ADNI-defined MCI, a previous cluster analysis [1] classified 51% (n = 227) of the current sample as amnestic MCI, 8% (n = 37) as dysexecutive/mixed MCI, and 41% (n = 180) as cluster-derived normal (cognitively normal). Results demonstrated that the dysexecutive/mixed and amnestic MCI groups showed significantly greater levels of amyloid relative to the cluster-derived normal and NC groups who did not differ from each other. Additionally, 78% of the dysexecutive/mixed, 63% of the amnestic MCI, 42% of the cluster-derived normal, and 34% of the NC group exceeded the amyloid positivity threshold. Finally, a group by APOE genotype interaction demonstrated that APOE ε4 carriers within the amnestic MCI, cluster-derived normal, and NC groups showed significantly greater amyloid accumulation compared to non-carriers of their respective group. Such an interaction was not revealed within the dysexecutive/mixed MCI group which was characterized by both greater cognitive impairment and amyloid accumulation compared to the other participant groups. Our results from the ADNI cohort show considerable heterogeneity in Aβ across all groups studied, even within a group of robust NC participants. Findings suggest that conventional criteria for MCI may be susceptible to false positive diagnostic errors, and that onset of Aβ accumulation may occur earlier in APOE ε4 carriers compared to non-carriers. PMID:27031472

  10. 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

    2016-01-01

    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. PMID:27623622

  11. 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. PMID:24636422

  12. 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

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

    PubMed

    Herd, Pamela; Higgins, Jenny; Sicinski, Kamil; Merkurieva, Irina

    2016-03-01

    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

  14. 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

  15. 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

  16. The magnitude of the somatosensory cortical activity is related to the mobility and strength impairments seen in children with cerebral palsy

    PubMed Central

    Heinrichs-Graham, Elizabeth; Becker, Katherine M.; Wilson, Tony W.

    2015-01-01

    The noted disruption of thalamocortical connections and abnormalities in tactile sensory function has resulted in a new definition of cerebral palsy (CP) that recognizes the sensorimotor integration process as central to the motor impairments seen in these children. Despite this updated definition, the connection between a child's motor impairments and somatosensory processing remains almost entirely unknown. In this investigation, we explored the relationship between the magnitude of neural activity within the somatosensory cortices, the strength of the ankle plantarflexors, and the gait spatiotemporal kinematics of a group of children with CP and a typically developing matched cohort. Our results revealed that the magnitude of somatosensory cortical activity in children with CP had a strong positive relationship with the ankle strength, step length, and walking speed. These results suggest that stronger activity within the somatosensory cortices in response to foot somatosensations was related to enhanced ankle plantarflexor strength and improved mobility in the children with CP. These results provide further support for the notion that children with CP exhibit, not only musculoskeletal deficits, but also somatosensory deficits that potentially contribute to their overall functional mobility and strength limitations. PMID:25717160

  17. Cortical Visual Impairment

    MedlinePlus

    ... Conditions Most Common Searches Adult Strabismus Amblyopia Cataract Conjunctivitis Corneal Abrasions Dilating Eye Drops Lazy eye (defined) ... Loading... Most Common Searches Adult Strabismus Amblyopia Cataract Conjunctivitis Corneal Abrasions Dilating Eye Drops Lazy eye (defined) ...

  18. Cortical Visual Impairment

    MedlinePlus

    ... work? The eyes take a picture of an object. That message is sent to the brain by ... other sensory messages (hearing, proprioceptive (sensing where the object is in relation to the body), etc). The ...

  19. 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…

  20. 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…

  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. 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…

  3. 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…

  4. 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…

  5. Informal Networks and Well-Being in Later Life: A Research Agenda.

    ERIC Educational Resources Information Center

    Ward, Russell A.

    1985-01-01

    Outlines a complex research agenda for understanding the contributions of informal social support to the quality of later life. Suggests a conceptual model for investigating informal support networks and well-being for the elderly and offers suggestions for operationalizing the model. (NRB)

  6. 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. PMID:25661855

  7. 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…

  8. Fetal programming by maternal obesity increases offspring’s susceptibility to obesity in later-life

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To examine whether exposure of the developing fetus to an obese mother during pregnancy increases the risk of obesity in the children in later-life, we have developed an overfeeding-based model of maternal obesity in rats by tube feeding of liquid diets directly into the stomach using total enteral ...

  9. 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

  10. 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. PMID:27103531

  11. 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. PMID:25841731

  12. [Fetal programming: prevention of perinatal acquired predispositions of diseases in later life].

    PubMed

    Kainer, F

    2007-02-01

    Alterations of the metabolic and hormonal environment of the fetus may cause predispositions to the development of disorders and diseases in later life. The timing, duration, severity, and type of insult during development determines the specific physiological outcome. Intrauterine programming of physiological systems occurs at the gene, cell, tissue, organ, and system levels and causes permanent structural and functional changes. Elevated insulin concentrations during critical periods of perinatal life may induce a lasting 'malprogramming' of neuroendocrine systems regulating body weight, food intake, and metabolism. Similar characteristics may occur due to perinatal hyperleptinism, hypercortisolism. Diagnosis and therapy of gestational diabetes in time may prevent metabolic and cardiovascular diseases in later life. This concept has new important implications for chances and challenges of perinatal preventive medicine in the future. PMID:17327986

  13. 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

  14. 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

  15. Alternate models of sibling status effects on health in later life.

    PubMed

    Falbo, Toni; Kim, Sunghun; Chen, Kuan-Yi

    2009-05-01

    Although siblings are thought to be influential in child development, little is known about the influence of sibling status on the health of older adults. Using structural equation modeling, the authors created and tested a series of models with data from a sample (N = 3,968) of 1957 high school graduates from the Wisconsin Longitudinal Study. The results indicated that socioeconomic status of origin, adolescent aptitude, and educational attainment did have significant total effects on health in later life, but sibling status did not. Adults who grew up in families of higher socioeconomic status and who had greater aptitude in high school attained more education, and this advantage, in turn, led to better health in later life. Although the final model was cross-validated, it was not equally plausible for men and women. PMID:19413424

  16. 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

  17. Physical, Cognitive, Social, and Emotional Mediators of Activity Involvement and Health in Later Life.

    PubMed

    Matz-Costa, Christina; Carr, Dawn C; McNamara, Tay K; James, Jacquelyn Boone

    2016-10-01

    The current study tests the indirect effect of activity-related physical activity, cognitive activity, social interaction, and emotional exchange on the relationship between activity involvement and health (physical and emotional) in later life. Longitudinal data from the Health and Retirement Study (N = 5,442) were used to estimate a series of linear regression models. We found significant indirect effects for social interaction and benefit to others (emotional exchange) on emotional health (depressive symptoms) and indirect effects for use of body and benefit to others (physical) on physical health (frailty). The most potent indirect effect associated with emotional and physical health was experienced by those engaged in all four domains (use of body, use of mind, social interaction, and benefit to others). While effect sizes are small and results should be interpreted with caution, findings shed light on ways in which public health interventions aimed toward increasing role engagement in later life could be improved. PMID:26429863

  18. Effect of Intensive Exercise in Early Adult Life on Telomere Length in Later Life in Men

    PubMed Central

    Laine, Merja K.; Eriksson, Johan G.; Kujala, Urho M.; Raj, Rahul; Kaprio, Jaakko; Bäckmand, Heli M.; Peltonen, Markku; Sarna, Seppo

    2015-01-01

    A career as an elite-class male athlete seems to improve metabolic heath in later life and is also associated with longer life expectancy. Telomere length is a biomarker of biological cellular ageing and could thus predict morbidity and mortality. The main aim of this study was to assess the association between vigorous elite-class physical activity during young adulthood on later life leukocyte telomere length (LTL). The study participants consist of former male Finnish elite athletes (n = 392) and their age-matched controls (n = 207). Relative telomere length was determined from peripheral blood leukocytes by quantitative real-time polymerase chain reaction. Volume of leisure-time physical activity (LTPA) was self-reported and expressed in metabolic equivalent hours. No significant difference in mean age-adjusted LTL in late life (p = 0.845) was observed when comparing former male elite athletes and their age-matched controls. Current volume of LTPA had no marked influence on mean age-adjusted LTL (p for trend 0.788). LTL was inversely associated with age (p = 0.004).Our study findings suggest that a former elite athlete career is not associated with LTL later in life. Key points A career as an elite-class athlete is associated with improved metabolic health in late life and is associated with longer life expectancy. A career as an elite-class athlete during young adulthood was not associated with leukocyte telomere length in later life. Current volume of leisure-time physical activity did not influence telomere length in later life. PMID:25983570

  19. Negative density dependence regulates two tree species at later life stage in a temperate forest.

    PubMed

    Piao, Tiefeng; Chun, Jung Hwa; Yang, Hee Moon; Cheon, Kwangil

    2014-01-01

    Numerous studies have demonstrated that tree survival is influenced by negative density dependence (NDD) and differences among species in shade tolerance could enhance coexistence via resource partitioning, but it is still unclear how NDD affects tree species with different shade-tolerance guilds at later life stages. In this study, we analyzed the spatial patterns for trees with dbh (diameter at breast height) ≥2 cm using the pair-correlation g(r) function to test for NDD in a temperate forest in South Korea after removing the effects of habitat heterogeneity. The analyses were implemented for the most abundant shade-tolerant (Chamaecyparis obtusa) and shade-intolerant (Quercus serrata) species. We found NDD existed for both species at later life stages. We also found Quercus serrata experienced greater NDD compared with Chamaecyparis obtusa. This study indicates that NDD regulates the two abundant tree species at later life stages and it is important to consider variation in species' shade tolerance in NDD study. PMID:25058660

  20. Deconstructing positive affect in later life: a differential functionalist analysis of joy and interest.

    PubMed

    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 present study measured trait joy and interest in a population-based sample of 1,118 adults aged 65-86 years. As predicted, trait joy was associated with greater religious participation, while trait interest was associated with greater education. Joy was associated with lower morbidity and stress while interest was not. Interest was, in fact, associated with greater stress. Both emotions were positively associated with social support. We use the pattern of predictors to develop a functionalist conceptualization of these two emotions in later life, concluding that it is worthwhile to treat interest and joy as partially-independent positive affects contributing differentially to human emotionality and later life adaptation. PMID:15248472

  1. 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. PMID:27131278

  2. Vascular cognitive impairment and dementia.

    PubMed

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

    2016-05-01

    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. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock. PMID:26704177

  3. Abnormal Changes of Brain Cortical Anatomy and the Association with Plasma MicroRNA107 Level in Amnestic Mild Cognitive Impairment

    PubMed Central

    Wang, Tao; Shi, Feng; Jin, Yan; Jiang, Weixiong; Shen, Dinggang; Xiao, Shifu

    2016-01-01

    MicroRNA107 (Mir107) has been thought to relate to the brain structure phenotype of Alzheimer’s disease. In this study, we evaluated the cortical anatomy in amnestic mild cognitive impairment (aMCI) and the relation between cortical anatomy and plasma levels of Mir107 and beta-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1). Twenty aMCI (20 aMCI) and 24 cognitively normal control (NC) subjects were recruited, and T1-weighted MR images were acquired. Cortical anatomical measurements, including cortical thickness (CT), surface area (SA), and local gyrification index (LGI), were assessed. Quantitative RT-PCR was used to examine plasma expression of Mir107, BACE1 mRNA. Thinner cortex was found in aMCI in areas associated with episodic memory and language, but with thicker cortex in other areas. SA decreased in aMCI in the areas associated with working memory and emotion. LGI showed a significant reduction in aMCI in the areas involved in language function. Changes in Mir107 and BACE1 messenger RNA plasma expression were correlated with changes in CT and SA. We found alterations in key left brain regions associated with memory, language, and emotion in aMCI that were significantly correlated with plasma expression of Mir107 and BACE1 mRNA. This combination study of brain anatomical alterations and gene information may shed lights on our understanding of the pathology of AD. Clinical Trial Registration: http://www.ClinicalTrials.gov, identifier NCT01819545. PMID:27242521

  4. Impaired consciousness during temporal lobe seizures is related to increased long-distance cortical-subcortical synchronization.

    PubMed

    Arthuis, Marie; Valton, Luc; Régis, Jean; Chauvel, Patrick; Wendling, Fabrice; Naccache, Lionel; Bernard, Christophe; Bartolomei, Fabrice

    2009-08-01

    Loss of consciousness (LOC) is a dramatic clinical manifestation of temporal lobe seizures. Its underlying mechanism could involve altered coordinated neuronal activity between the brain regions that support conscious information processing. The consciousness access hypothesis assumes the existence of a global workspace in which information becomes available via synchronized activity within neuronal modules, often widely distributed throughout the brain. Re-entry loops and, in particular, thalamo-cortical communication would be crucial to functionally bind different modules together. In the present investigation, we used intracranial recordings of cortical and subcortical structures in 12 patients, with intractable temporal lobe epilepsy (TLE), as part of their presurgical evaluation to investigate the relationship between states of consciousness and neuronal activity within the brain. The synchronization of electroencephalography signals between distant regions was estimated as a function of time by using non-linear regression analysis. We report that LOC occurring during temporal lobe seizures is characterized by increased long-distance synchronization between structures that are critical in processing awareness, including thalamus (Th) and parietal cortices. The degree of LOC was found to correlate with the amount of synchronization in thalamo-cortical systems. We suggest that excessive synchronization overloads the structures involved in consciousness processing, preventing them from treating incoming information, thus resulting in LOC. PMID:19416952

  5. The Relationship of Childhood Maltreatment and Household Dysfunction and Drug Use in Later Life in Iran

    NASA Astrophysics Data System (ADS)

    Ziaaddini, Hassan; Dastjerdi, Qasem; Nakhaee, Nouzar

    Few studies have examined the relationship between childhood maltreatment and substance use in later life considering household dysfunction variables especially in Eastern Mediterranean countries. The study was conducted to explore the relationship between adverse childhood experiences and substance misuse during later life in an Iranian sample. A case control study was conducted in Kerman, a city located in southern Iran in 2005. Cases were 200 men and women referred to outpatient clinics of the city seeking treatment for substance use disorder. Controls (n = 200) were selected from the general population. With emphasizing the confidentiality and obtaining oral consent the subjects were asked to fill out a questionnaire including demographic variables and 27 questions concerning all types of child abuse/neglect and household dysfunction. Using multivariate logistic regression the associations between baseline characteristics, childhood maltreatment and household dysfunction variables and substance use disorder were analyzed. The mean age of case group was 32.5±8.3 and in control group was 28±9.3 (p< 0.01). Most of subjects in both groups were male. The prevalence of sexual abuse, household substance use and household criminality were higher in substance dependent patients comparing to control group. The highest odds of substance use disorder was associated with household substance abuse (OR: 2.50, 95% CI: 1.53-4.10) and sexual abuse was the only type of childhood maltreatment which showed significant association with substance use disorder in later life (OR: 1.73, 95% CI: 1.03-2.92). The related factors uncovered by the study conduct us to early interventions among dysfunctional families to decrease the maladaptive lives and stressful household environments.

  6. 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

  7. 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

  8. 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

  9. Rescue of Impaired mGluR5-Driven Endocannabinoid Signaling Restores Prefrontal Cortical Output to Inhibit Pain in Arthritic Rats

    PubMed Central

    Kiritoshi, Takaki; Ji, Guangchen

    2016-01-01

    The medial prefrontal cortex (mPFC) serves executive functions that are impaired in neuropsychiatric disorders and pain. Underlying mechanisms remain to be determined. Here we advance the novel concept that metabotropic glutamate receptor 5 (mGluR5) fails to engage endocannabinoid (2-AG) signaling to overcome abnormal synaptic inhibition in pain, but restoring endocannabinoid signaling allows mGluR5 to increase mPFC output hence inhibit pain behaviors and mitigate cognitive deficits. Whole-cell patch-clamp recordings were made from layer V pyramidal cells in the infralimbic mPFC in rat brain slices. Electrical and optogenetic stimulations were used to analyze amygdala-driven mPFC activity. A selective mGluR5 activator (VU0360172) increased pyramidal output through an endocannabinoid-dependent mechanism because intracellular inhibition of the major 2-AG synthesizing enzyme diacylglycerol lipase or blockade of CB1 receptors abolished the facilitatory effect of VU0360172. In an arthritis pain model mGluR5 activation failed to overcome abnormal synaptic inhibition and increase pyramidal output. mGluR5 function was rescued by restoring 2-AG-CB1 signaling with a CB1 agonist (ACEA) or inhibitors of postsynaptic 2-AG hydrolyzing enzyme ABHD6 (intracellular WWL70) and monoacylglycerol lipase MGL (JZL184) or by blocking GABAergic inhibition with intracellular picrotoxin. CB1-mediated depolarization-induced suppression of synaptic inhibition (DSI) was also impaired in the pain model but could be restored by coapplication of VU0360172 and ACEA. Stereotaxic coadministration of VU0360172 and ACEA into the infralimbic, but not anterior cingulate, cortex mitigated decision-making deficits and pain behaviors of arthritic animals. The results suggest that rescue of impaired endocannabinoid-dependent mGluR5 function in the mPFC can restore mPFC output and cognitive functions and inhibit pain. SIGNIFICANCE STATEMENT Dysfunctions in prefrontal cortical interactions with subcortical

  10. 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

  11. 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…

  12. 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

    2015-10-01

    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. PMID:26188240

  13. 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

  14. 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

  15. 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

  16. Does caregiving increase poverty among women in later life? Evidence from the Health and Retirement survey.

    PubMed

    Wakabayashi, Chizuko; Donato, Katharine M

    2006-09-01

    Given the rapid aging of the U.S. population and reductions in federal funding, elder care has become a major issue for many families. This paper focuses on a long-term consequence of elder care by asking how caring for elderly parents affects women's subsequent risks of living in poverty. Using longitudinal data from the Health and Retirement Study, we examine whether and how caregiving for parents in 1991 increases women's risks of living in households with incomes less than the poverty threshold, receiving public assistance, and receiving Medicaid in 1999. Our findings illustrate that caregiving in earlier life raises women's poverty risks in later life by intensifying the negative effects of stopping work and declining health on women's economic well-being. PMID:17066776

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

    PubMed

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

    2014-10-01

    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

  18. 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. PMID:25651598

  19. Complex Households and the Distribution of Multiple Resources in Later Life: Findings From a National Survey.

    PubMed

    Kim, Juyeon; Waite, Linda J

    2016-02-01

    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

  20. 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

  1. 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

  2. What are the Effects of Severe Visual Impairment on the Cortical Organization and Connectivity of Primary Visual Cortex?

    PubMed Central

    Larsen, DeLaine D.; Luu, Julie D.; Burns, Marie E.; Krubitzer, Leah

    2009-01-01

    The organization and connections of the primary visual area (V1) were examined in mice that lacked functional rods (Gnat−/−), but had normal cone function. Because mice are nocturnal and rely almost exclusively on rod vision for normal behaviors, the Gnat−/− mice used in the present study are considered functionally blind. Our goal was to determine if visual cortex is reorganized in these mice, and to examine the neuroanatomical connections that may subserve reorganization. We found that most neurons in V1 responded to auditory, or some combination of auditory, somatosensory, and/or visual stimulation. We also determined that cortical connections of V1 in Gnat−/− mice were similar to those in normal animals, but even in normal animals, there is sparse input from auditory cortex (AC) to V1. An important observation was that most of the subcortical inputs to V1 were from thalamic nuclei that normally project to V1 such as the lateral geniculate (LG), lateral posterior (LP), and lateral dorsal (LD) nuclei. However, V1 also received some abnormal subcortical inputs from the anterior thalamic nuclei, the ventral posterior, the ventral lateral and the posterior nuclei. While the vision generated from the small number of cones appears to be sufficient to maintain most of the patterns of normal connectivity, the sparse abnormal thalamic inputs to VI, existing inputs from AC, and possibly abnormal inputs to LG and LP may be responsible for generating the alterations in the functional organization of V1. PMID:20057935

  3. Single Dose of a Dopamine Agonist Impairs Reinforcement Learning in Humans: Evidence from Event-related Potentials and Computational Modeling of Striatal-Cortical Function

    PubMed Central

    Santesso, Diane L.; Evins, A. Eden; Frank, Michael J.; Cowman Schetter, Erika M.; Bogdan, Ryan; Pizzagalli, Diego A.

    2011-01-01

    Animal findings have highlighted the modulatory role of phasic dopamine (DA) signaling in incentive learning, particularly in the acquisition of reward-related behavior. In humans, these processes remain largely unknown. In a recent study we demonstrated that a single low dose of a D2/D3 agonist (pramipexole) – assumed to activate DA autoreceptors and thus reduce phasic DA bursts – impaired reward learning in healthy subjects performing a probabilistic reward task. The purpose of the present study was to extend these behavioral findings using event-related potentials and computational modeling. Compared to the placebo group, participants receiving pramipexole showed increased feedback-related negativity to probabilistic rewards and decreased activation in dorsal anterior cingulate regions previously implicated in integrating reinforcement history over time. Additionally, findings of blunted reward learning in participants receiving pramipexole were simulated by reduced presynaptic DA signaling in response to reward in a neural network model of striatal-cortical function. These preliminary findings offer important insights on the role of phasic DA signals on reinforcement learning in humans, and provide initial evidence regarding the spatio-temporal dynamics of brain mechanisms underlying these processes. PMID:18726908

  4. 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. PMID:27161368

  5. Inhibition of Tnf-α R1 signaling can rescue functional cortical plasticity impaired in early post-stroke period.

    PubMed

    Liguz-Lecznar, Monika; Zakrzewska, Renata; Kossut, Malgorzata

    2015-10-01

    Tumor necrosis factor-α (TNF-α) is one of the key players in stroke progression and can interfere with brain functioning. We previously documented an impairment of experience-dependent plasticity in the cortex neighboring the stroke-induced lesion, which was accompanied with an upregulation of Tnf-α level in the brain of ischemic mice 1 week after the stroke. Because TNF receptor 1 (TnfR1) signaling is believed to be a major mediator of the cytotoxicity of Tnf-α through activation of caspases, we used an anti-inflammatory intervention aimed at Tnf-α R1 pathway, in order to try to attenuate the detrimental effect of post-stroke inflammation, and investigated if this will be effective in protecting plasticity in the infarct proximity. Aged mice (12-14 months) were subjected to the photothrombotic stroke localized near somatosensory cortex, and immediately after ischemia sensory deprivation was introduced to induce plasticity. Soluble TNF-α R1 (sTNF-α R1), which competed for TNF-α with receptors localized in the brain, was delivered chronically directly into the brain tissue for the whole period of deprivation using ALZET Micro-Osmotic pumps. We have shown that such approach undertaken simultaneously with the stroke reduced the level of TNF-α in the peri-ischemic tissue and was successful in preserving the post-stroke deprivation-induced brain plasticity. PMID:26189092

  6. 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

  7. Propositional Density and Cognitive Function in Later Life: Findings From the Precursors Study

    PubMed Central

    Agree, Emily M.; Meoni, Lucy A.; Klag, Michael J.

    2010-01-01

    Objectives. We used longitudinal data from the Johns Hopkins Precursors Study to test the hypothesis that written propositional density measured early in life is lower for people who develop dementia categorized as Alzheimer's disease (AD). This association was reported in 1996 for the Nun Study, and the Precursors Study offered an unprecedented chance to reexamine it among respondents with different gender, education, and occupation profiles. Methods. Eighteen individuals classified as AD patients (average age at diagnosis: 74) were assigned 2 sex-and-age matched controls, and propositional density in medical school admission essays (average age at writing: 22) was assessed via Computerized Propositional Idea Density Rater 3 linguistic analysis software. Adjusted odds ratios (ORs) for the matched case-control study were calculated using conditional (fixed-effects) logistic regression. Results. Mean propositional density is lower for cases than for controls (4.70 vs. 4.99 propositions per 10 words, 1-sided p = .01). Higher propositional density substantially lowers the odds of AD (OR = 0.16, 95% confidence interval = 0.03-0.90, 1-sided p = .02). Discussion. Propositional density scores in writing samples from early adulthood appear to predict AD in later life for men as well as women. Studies of cognition across the life course might beneficially incorporate propositional density as a potential marker of cognitive reserve. PMID:20837676

  8. 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

  9. 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. PMID:24984912

  10. 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. PMID:24565146

  11. Leisure Engagement: Medical Conditions, Mobility Difficulties, and Activity Limitations—A Later Life Perspective

    PubMed Central

    Nilsson, Ingeborg; Nyqvist, Fredrica; Gustafson, Yngve; Nygård, Mikael

    2015-01-01

    Objectives. This study aims to investigate the impact of medical conditions, mobility difficulties, and activity limitations on older people's engagement in leisure activities. Methods. The analyses are based on a cross regional survey carried out in 2010 in the Bothnia region (Northern Sweden and Western Finland). A posted questionnaire, which included questions on different aspects of leisure engagement, medical history, and health, was sent out to older persons in the region. The final sample consisted of 5435 persons aged 65, 70, 75, and 80 years. The data was analyzed by using ordinary least squares (OLS) multivariate regression. Results. The most important predictor of leisure engagement abstention among older people is the prevalence of activity limitations, whereas mobility difficulties and medical conditions play less important roles. The strong negative association between activity limitations and leisure engagement remains significant even after we control for individual, sociodemographic characteristics, and country. Discussion. This study provides a window into leisure engagement in later life and factors influencing the magnitude of engagement in leisure activities. PMID:26346706

  12. 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

  13. Early-Life Socioeconomic Status and the Prevalence of Breast Cancer in Later Life

    PubMed Central

    Pudrovska, Tetyana; Anishkin, Andriy; Shen, Yifang

    2012-01-01

    Knowledge of mechanisms linking early-life social environment and breast cancer remains limited. We explore direct and indirect effects of early-life socioeconomic status (SES) on breast cancer prevalence in later life. Using 50-year data from the Wisconsin Longitudinal Study (N = 4,275) and structural equation modeling, we found a negative direct effect of early-life SES, indicating that women from higher-SES family background had lower breast cancer prevalence than women from lower-SES families. Additionally, early-life SES has a positive indirect effect on breast cancer via women's adult SES and age at first birth. Were it not for their higher SES in adulthood and delayed childbearing, women from higher-SES families of origin would have had lower breast cancer prevalence than women from lower-SES families. Yet, early-life SES is associated positively with adult SES and age at first birth, and women's higher adult SES and delayed childbearing are related to higher breast cancer prevalence. PMID:22936839

  14. 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

  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

    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. Improving the rate of Patient Feedback for a Later Life Mental Health Liaison Team

    PubMed Central

    Cooper, Daniel

    2016-01-01

    It is well established that patient feedback is key to service development and improvement in the modern NHS. Certain patient groups can be particularly difficult to get feedback from, including those with dementia. The Later Life Mental Health Liaison Team at the Bristol Royal Infirmary were consistently receiving very low levels of patient feedback, such that it was insufficient to properly contribute to future service development and improvement. This QIP aimed to increase this level of feedback to a target of 15% from an existing average of 3%. The intervention centred around getting feedback from patients face to face and was developed over a number of PDSA cycles. The feedback questions were based upon the NHS Friends and Family Test. Over four PDSA cycles levels of feedback increased to 21% which more than achieved the goal set out at the start. This was however achieved at a time cost and involved an increased success rate of existing systems as well as new ones put into place by the QIP. PMID:27335648

  18. 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

  19. "I'm Sure She Chose Me!" Accuracy of Children's Reports of Mothers' Favoritism in Later Life Families

    ERIC Educational Resources Information Center

    Suitor, J. Jill; Sechrist, Jori; Steinhour, Michael; Pillemer, Karl

    2006-01-01

    We used data from 769 mother-child dyads nested within 300 later life families to explore the accuracy of adult children's perceptions of mothers' patterns of favoritism in terms of closeness and confiding. Adult children were generally accurate regarding whether their mothers preferred a specific child, but often had difficulty identifying whom…

  20. 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

  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. The Relationship Between Borderline Personality Disorder and Major Depression in Later Life: Acute Versus Temperamental Symptoms

    PubMed Central

    Galione, Janine N.; Oltmanns, Thomas F.

    2012-01-01

    Objective A recent issue in the personality disorder field is the prevalence and course of Axis II symptoms in later life. Focusing on the presentation of personality disorder criteria over time may have some utility in exploring the relationship between borderline personality disorder (BPD) and major depression in older adults. Temperamental personality symptoms are relatively resistant to change but tend to be nonspecific to disorders, while acute symptoms remit relatively quickly. We predicted that temperamental BPD symptoms would be positively correlated with a history of depression and did not expect to find a relationship between major depression and acute BPD symptoms. Method One thousand six hundred and thirty participants between the ages of 55 and 64 were recruited to participate in a community-based longitudinal study representative of the St. Louis area. Participants completed a battery of assessments at baseline, including diagnostic interviews for all ten personality disorders and major depressive disorder. Results Temperamental and acute BPD symptoms were significantly correlated with a history of major depression. After adjustments were made for the effects of temperamental symptoms on depression, acute symptoms were no longer correlated with a history of depression. As predicted, temperamental symptoms remained significantly related to depression, even after controlling for the effects of acute symptoms. BPD acute symptoms showed a unique negative correlation with the amount of time following remission from a depressive episode. Conclusions Overall, this study supports associations between major depression and borderline personality in older adults. The findings indicate that a history of major depression is primarily related to stable BPD symptoms related to emotional distress, which are more prevalent in older adults compared to acute features. PMID:23567384

  3. Elevated intracranial dopamine impairs the glutamate‑nitric oxide‑cyclic guanosine monophosphate pathway in cortical astrocytes in rats with minimal hepatic encephalopathy.

    PubMed

    Ding, Saidan; Huang, Weilong; Ye, Yiru; Yang, Jianjing; Hu, Jiangnan; Wang, Xiaobin; Liu, Leping; Lu, Qin; Lin, Yuanshao

    2014-09-01

    In a previous study by our group memory impairment in rats with minimal hepatic encephalopathy (MHE) was associated with the inhibition of the glutamate‑nitric oxide‑cyclic guanosine monophosphate (Glu‑NO‑cGMP) pathway due to elevated dopamine (DA). However, the effects of DA on the Glu‑NO‑cGMP pathway localized in primary cortical astrocytes (PCAs) had not been elucidated in rats with MHE. In the present study, it was identified that when the levels of DA in the cerebral cortex of rats with MHE and high‑dose DA (3 mg/kg)‑treated rats were increased, the co‑localization of N‑methyl‑d‑aspartate receptors subunit 1 (NMDAR1), calmodulin (CaM), nitric oxide synthase (nNOS), soluble guanylyl cyclase (sGC) and cyclic guanine monophosphate (cGMP) with the glial fibrillary acidic protein (GFAP), a marker protein of astrocytes, all significantly decreased, in both the MHE and high‑dose DA‑treated rats (P<0.01). Furthermore, NMDA‑induced augmentation of the expression of NMDAR1, CaM, nNOS, sGC and cGMP localized in PCAs was decreased in MHE and DA‑treated rats, as compared with the controls. Chronic exposure of cultured cerebral cortex PCAs to DA treatment induced a dose‑dependent decrease in the concentration of intracellular calcium, nitrites and nitrates, the formation of cGMP and the expression of NMDAR1, CaM, nNOS and sGC/cGMP. High doses of DA (50 µM) significantly reduced NMDA‑induced augmentation of the formation of cGMP and the contents of NMDAR1, CaM, nNOS, sGC and cGMP (P<0.01). These results suggest that the suppression of DA on the Glu‑NO‑cGMP pathway localized in PCAs contributes to memory impairment in rats with MHE. PMID:25059564

  4. Elevated intracranial dopamine impairs the glutamate-nitric oxide-cyclic guanosine monophosphate pathway in cortical astrocytes in rats with minimal hepatic encephalopathy

    PubMed Central

    DING, SAIDAN; HUANG, WEILONG; YE, YIRU; YANG, JIANJING; HU, JIANGNAN; WANG, XIAOBIN; LIU, LEPING; LU, QIN; LIN, YUANSHAO

    2014-01-01

    In a previous study by our group memory impairment in rats with minimal hepatic encephalopathy (MHE) was associated with the inhibition of the glutamate-nitric oxide-cyclic guanosine monophosphate (Glu-NO-cGMP) pathway due to elevated dopamine (DA). However, the effects of DA on the Glu-NO-cGMP pathway localized in primary cortical astrocytes (PCAs) had not been elucidated in rats with MHE. In the present study, it was identified that when the levels of DA in the cerebral cortex of rats with MHE and high-dose DA (3 mg/kg)-treated rats were increased, the co-localization of N-methyl-d-aspartate receptors subunit 1 (NMDAR1), calmodulin (CaM), nitric oxide synthase (nNOS), soluble guanylyl cyclase (sGC) and cyclic guanine monophosphate (cGMP) with the glial fibrillary acidic protein (GFAP), a marker protein of astrocytes, all significantly decreased, in both the MHE and high-dose DA-treated rats (P<0.01). Furthermore, NMDA-induced augmentation of the expression of NMDAR1, CaM, nNOS, sGC and cGMP localized in PCAs was decreased in MHE and DA-treated rats, as compared with the controls. Chronic exposure of cultured cerebral cortex PCAs to DA treatment induced a dose-dependent decrease in the concentration of intracellular calcium, nitrites and nitrates, the formation of cGMP and the expression of NMDAR1, CaM, nNOS and sGC/cGMP. High doses of DA (50 μM) significantly reduced NMDA-induced augmentation of the formation of cGMP and the contents of NMDAR1, CaM, nNOS, sGC and cGMP (P<0.01). These results suggest that the suppression of DA on the Glu-NO-cGMP pathway localized in PCAs contributes to memory impairment in rats with MHE. PMID:25059564

  5. 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. PMID:26577399

  6. 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. PMID:26908895

  7. Peripheral Hearing and Cognition: Evidence from the Staying Keen in Later Life (SKILL) Study

    PubMed Central

    Bush, Aryn L. Harrison; Lister, Jennifer J.; Lin, Frank R.; Betz, Joshua; Edwards, Jerri D.

    2015-01-01

    Research has increasingly suggested a consistent relationship between peripheral hearing and selected measures of cognition in older adults. However, other studies yield conflicting findings. Objectives The primary purpose of the present study was to further elucidate the relationship between peripheral hearing and three domains of cognition and one measure of global cognitive status. It was hypothesized that peripheral hearing loss would be significantly associated with poorer performance across measures of cognition, even after adjusting for documented risk factors. No study to date has examined the relationship between peripheral hearing and such an extensive array of cognitive measures. Design 894 older adult participants from the Staying Keen in Later Life study cohort were eligible, agreed to participate, and completed the baseline evaluation. Inclusion criteria were minimal to include a sample of older adults with a wide range of sensory and cognitive abilities. Multiple linear regression analyses were conducted to evaluate the extent to which peripheral hearing predicted performance on a global measure of cognitive status, as well as multiple cognitive measures in the domains of speed of processing (Digit Symbol Substitution and Copy, Trail-Making Test Part A, Letter and Pattern Comparison, and Useful Field of View), executive function (Trail-Making Test Part B and Stroop Color-Word Interference Task), and memory (Digit Span, Spatial Span, and Hopkins Verbal Learning Test). Results Peripheral hearing, measured as the three-frequency PTA in the better ear, accounted for a significant, but minimal, amount of the variance in measures of speed of processing, executive function, and memory, as well as global cognitive status. Alternative measures of hearing (i.e., three-frequency PTAs in the right and left ears and a bilateral, six-frequency PTA [three frequencies per ear]) yielded similar findings across measures of cognition and did not alter the study

  8. 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…

  9. Reproductive History and Later-Life Comorbidity Trajectories: A Medicare-Linked Cohort Study From the Utah Population Database.

    PubMed

    Hanson, Heidi A; Smith, Ken R; Zimmer, Zachary

    2015-12-01

    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

  10. The Family Life Course and Health: Partnership, Fertility Histories, and Later-Life Physical Health Trajectories in Australia.

    PubMed

    O'Flaherty, Martin; Baxter, Janeen; Haynes, Michele; Turrell, Gavin

    2016-06-01

    Life course perspectives suggest that later-life health reflects long-term social patterns over an individual's life: in particular, the occurrence and timing of key roles and transitions. Such social patterns have been demonstrated empirically for multiple aspects of fertility and partnership histories, including timing of births and marriage, parity, and the presence and timing of a marital disruption. Most previous studies have, however, addressed particular aspects of fertility or partnership histories singly. We build on this research by examining how a holistic classification of family life course trajectories from ages 18 to 50, incorporating both fertility and partnership histories, is linked to later-life physical health for a sample of Australian residents. Our results indicate that long-term family life course trajectories are strongly linked to later-life health for men but only minimally for women. For men, family trajectories characterized by early family formation, no family formation, an early marital disruption, or high fertility are associated with poorer physical health. Among women, only those who experienced both a disrupted marital history and a high level of fertility were found to be in poorer health. PMID:27189018

  11. 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. PMID:24513634

  12. N-acetylcysteine attenuates lipopolysaccharide-induced impairment in lamination of Ctip2-and Tbr1- expressing cortical neurons in the developing rat fetal brain.

    PubMed

    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

  13. 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

  14. Taking up physical activity in later life and healthy ageing: the English longitudinal study of ageing

    PubMed Central

    Hamer, Mark; Lavoie, Kim L; Bacon, Simon L

    2014-01-01

    Background 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. Methods 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. Results 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. Conclusions 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. PMID:24276781

  15. [Everyday competencies and learning processes in old age. Results and perspectives of the PIAAC extension study "Competencies in later life"].

    PubMed

    Friebe, J; Knauber, C; Weiß, C; Setzer, B

    2014-11-01

    This article deals with the study "Competencies in later life" (CiLL), a parallel study to the German program for the international assessment of adult competencies (PIAAC) survey which assesses the level and distribution of skills of the adult population in a representative study. Assuming the growing importance of learning and education in a society challenged by demographic changes, the first section of the paper outlines the qualitative research of learning activities of focus groups in the daily life of elderly people. The second section of the paper presents the survey design and exemplary findings of the quantitative CiLL study. Initial results show that basic skills of the elderly are highly influenced by personal and sociodemographic variables, particularly by educational background. The data available indicate that the participation of the elderly in adult education and the options available for competence development have to be increased. PMID:25139446

  16. 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. PMID:25651548

  17. The role of family social background and inheritance in later life volunteering: Evidence from SHARE-Israel

    PubMed Central

    Youssim, Iaroslav; Hank, Karsten; Litwin, Howard

    2014-01-01

    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. PMID:25651548

  18. 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

  19. Sexuality in Later Life

    MedlinePlus

    ... find that affection—hugging, kissing, touching, and spending time together—can make a good beginning. For More Information Here are some helpful resources: American Cancer Society 1-800-227-2345 (toll-free/24 hours) ...

  20. 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…

  1. Early-Life Socioeconomic Status and Mortality in Later Life: An Integration of Four Life-Course Mechanisms

    PubMed Central

    2014-01-01

    Objectives. Using data from the Wisconsin Longitudinal Study, we examine (a) how socioeconomic status (SES) at age 18 affects all-cause mortality at ages 54–72, and (b) whether the effect of early-life SES is consistent with the critical period, accumulation of risks, social mobility, and pathway models. We also explore gender differences in the effect of early-life SES and life-course mechanisms. Method. Participants (N = 6,547) were surveyed in 1957, 1975, and 1993, with vital status established until 2011. We combine discrete-time survival analysis with structural equation modeling. SES and health behaviors are modeled as latent factors. Results. Early-life SES affects mortality indirectly via status attainment and health behaviors in adulthood and midlife. This finding is contrary to the critical period and consistent with the pathway model. Persistent disadvantage at three life stages is a strong risk factor for mortality, thus, supporting the accumulation of risks. Moreover, the mortality risk of individuals who experienced downward socioeconomic mobility is comparable to their peers with persistent disadvantage. Discussion. This study highlights the complexity of interrelated life-course processes underlying the effect of early-life SES on mortality in later life. PMID:24496607

  2. 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. PMID:18194031

  3. 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

  4. Long-term effects of childhood sexual abuse: objective and subjective characteristics of the abuse and psychopathology in later life.

    PubMed

    Lange, A; de Beurs, E; Dolan, C; Lachnit, T; Sjollema, S; Hanewald, G

    1999-03-01

    This study investigates the association between objective and subjective characteristics of childhood sexual abuse and psychopathology in later life. The sample consists of 404 Dutch female adults who had been sexually abused in their childhood or adolescence. The participants were recruited by means of articles about childhood sexual abuse in major Dutch newspapers. The characteristics and severity of the sexual abuse were assessed with the Questionnaire Unwanted Sexual Experiences in the Past (QUSEP). General psychopathology was measured with the Symptom Checklist (SCL-90), the degree of dissociation was measured with the Dissociation Questionnaire (DIS-Q). Stepwise multiple regression analyses showed a moderate association between psychopathology and objective characteristics of the abuse, such as number of different types of abusive events and the duration of the abuse. However, more strongly associated with later psychopathology were variables reflecting coping style, such as the degree of self-blame, and circumstantial factors, such as the emotional atmosphere in the family of origin and the reactions after disclosure. Whether or not the abuse was incestuous did not explain additional variance in later psychopathology. PMID:10086471

  5. 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. PMID:26325301

  6. 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

  7. 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

  8. Overexpressed neuroglobin raises threshold for nitric oxide-induced impairment of mitochondrial respiratory activities and stress signaling in primary cortical neurons.

    PubMed

    Singh, Shilpee; Zhuo, Ming; Gorgun, Falih M; Englander, Ella W

    2013-08-01

    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

  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. 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

  11. Early Life Dietary Spray Dried Plasma Influences Immunological and Intestinal Injury Responses to Later Life Salmonella Typhimurium Challenge

    PubMed Central

    Boyer, P.E.; D’Costa, S.; Edwards, L.L.; Milloway, M.; Susick, E.; Borst, L.B.; Thakur, S.; Campbell, J.M.; Crenshaw, J.D.; Polo, J.; Moeser, A.J.

    2015-01-01

    Increasing evidence supports that early life environmental influences, including nutrition and stress, impact long-term health outcomes and disease susceptibility. The objective of the current study was to determine whether dietary spray-dried plasma (SDP) fed during the first 2 weeks post-weaning (PW) influences subsequent immunological and intestinal injury responses to S. Typhimurium challenge. Thirty two piglets (16–17 d of age) were weaned onto nursery diets containing 0% SDP, 2.5% SDP (fed for 7 d PW), or 5% SDP (for 14 d PW) and were then fed control diets (without SDP), for the remainder of the experiment. At 34 d PW (50 d of age), pigs were challenged with 3×109 cfu S. Typhimurium. A control group (non-challenged) that was fed 0% SDP in the nursery was included. At 2 d post-challenge, distal ileum was harvested for measurement of inflammatory, histological, and intestinal physiological parameters. S. Typhimurium challenge induced elevated ileal histological scores, myeloperoxidase (MPO), IL-8, and TNF, and increased intestinal permeability (indicated by reduced transepithelial voltage (PD) and elevated FD4 flux rates). Compared with S. Typhimurium-challenged controls (0% SDP), pigs fed 5% SDP-14 d exhibited reduced ileal histological scores, MPO, IL-8, and FD4 flux rates. Pigs fed 5% SDP-14 d in the nursery exhibited increased levels of plasma and ileal TNFα in response to challenge, compared with other treatments. These results indicate that inclusion of SDP into PW diets can have influence subsequent immunological responses and intestinal injury induced by later life S. Typhimurium challenge. PMID:25671331

  12. Is regular drinking in later life an indicator of good health? Evidence from the English Longitudinal Study of Ageing

    PubMed Central

    Holdsworth, Clare; Mendonça, Marina; Pikhart, Hynek; Frisher, Martin; de Oliveira, Cesar; Shelton, Nicola

    2016-01-01

    Background Older people who drink have been shown to have better health than those who do not. This might suggest that moderate drinking is beneficial for health, or, as considered here, that older people modify their drinking as their health deteriorates. The relationship between how often older adults drink and their health is considered for two heath states: self-rated health (SRH) and depressive symptoms. Methods Data were analysed from the English Longitudinal Study of Ageing (ELSA), a prospective cohort study of older adults, using multilevel ordered logit analysis. The analysis involved 4741 participants present at wave 0, (1998/1999 and 2001), wave 4 (2008/2009) and wave 5 (2010/2011). The outcome measure was frequency of drinking in last year recorded at all three time points. Results Older adults with fair/poor SRH at the onset of the study drank less frequently compared with adults with good SRH (p<0.05). Drinking frequency declined over time for all health statuses, though respondents with both continual fair/poor SRH and declining SRH experienced a sharper reduction in the frequency of their drinking over time compared with older adults who remained in good SRH or whose health improved. The findings were similar for depression, though the association between depressive symptoms and drinking frequency at the baseline was not significant after adjusting for confounding variables. Conclusions The frequency of older adults’ drinking responds to changes in health status and drinking frequency in later life may be an indicator, rather than a cause, of health status. PMID:26797821

  13. Computational modeling of stuttering caused by impairments in a basal ganglia thalamo-cortical circuit involved in syllable selection and initiation.

    PubMed

    Civier, Oren; Bullock, Daniel; Max, Ludo; Guenther, Frank H

    2013-09-01

    Atypical white-matter integrity and elevated dopamine levels have been reported for individuals who stutter. We investigated how such abnormalities may lead to speech dysfluencies due to their effects on a syllable-sequencing circuit that consists of basal ganglia (BG), thalamus, and left ventral premotor cortex (vPMC). "Neurally impaired" versions of the neurocomputational speech production model GODIVA were utilized to test two hypotheses: (1) that white-matter abnormalities disturb the circuit via corticostriatal projections carrying copies of executed motor commands and (2) that dopaminergic abnormalities disturb the circuit via the striatum. Simulation results support both hypotheses: in both scenarios, the neural abnormalities delay readout of the next syllable's motor program, leading to dysfluency. The results also account for brain imaging findings during dysfluent speech. It is concluded that each of the two abnormality types can cause stuttering moments, probably by affecting the same BG-thalamus-vPMC circuit. PMID:23872286

  14. Dopamine D1 receptor activation rescues extinction impairments in low-estrogen female rats and induces cortical layer-specific activation changes in prefrontal-amygdala circuits.

    PubMed

    Rey, Colin D; Lipps, Jennifer; Shansky, Rebecca M

    2014-04-01

    Post-traumatic stress disorder (PTSD) is twice as common in women as in men; it is a major public health problem whose neurobiological basis is unknown. In preclinical studies using fear conditioning and extinction paradigms, women and female animals with low estrogen levels exhibit impaired extinction retrieval, but the mechanisms that underlie these hormone-based discrepancies have not been identified. There is much evidence that estrogen can modulate dopaminergic transmission, and here we tested the hypothesis that dopamine-estrogen interactions drive extinction processes in females. Intact male and female rats were trained on cued fear conditioning, and received an intraperitoneal injection of a D1 agonist or vehicle before extinction learning. As reported previously, females that underwent extinction during low estrogen estrous phases (estrus/metaestrus/diestrus (EMD)) froze more during extinction retrieval than those that had been in the high-estrogen phase (proestrus; PRO). However, D1 stimulation reversed this relationship, impairing extinction retrieval in PRO and enhancing it in EMD. We also combined retrograde tracing and fluorescent immunohistochemistry to measure c-fos expression in infralimbic (IL) projections to the basolateral area of the amygdala (BLA), a neural pathway known to be critical to extinction retrieval. Again we observed diverging, estrous-dependent effects; SKF treatment induced a positive correlation between freezing and IL-BLA circuit activation in EMD animals, and a negative correlation in PRO animals. These results show for the first time that hormone-dependent extinction deficits can be overcome with non-hormone-based interventions, and suggest a circuit-specific mechanism by which these behavioral effects occur. PMID:24343528

  15. Combined alpha2 and D2/3 receptor blockade enhances cortical glutamatergic transmission and reverses cognitive impairment in the rat.

    PubMed

    Marcus, Monica M; Jardemark, Kent E; Wadenberg, Marie-Louise; Langlois, Xavier; Hertel, Peter; Svensson, Torgny H

    2005-09-01

    The alpha(2) adrenoceptor antagonist idazoxan enhances antipsychotic efficacy of classical dopamine D(2) antagonists in treatment-resistant schizophrenia. The mechanisms are not fully understood, but we have previously shown that the combination of idazoxan with the D(2/3) receptor antagonist raclopride, similarly to clozapine but not classical antipsychotic drugs, augments dopamine efflux in the prefrontal cortex, and also generates an enhanced suppression of the conditioned avoidance response. We have now investigated the effects of clozapine, raclopride, idazoxan and the combination of raclopride and idazoxan on (i) electrically evoked excitatory post-synaptic potentials and currents in pyramidal cells of the rat medial prefrontal cortex, using intracellular electrophysiological recording in vitro, (ii) the impaired cognitive function induced by the selective N-methyl-D-aspartate (NMDA) receptor antagonist MK-801, using the 8-arm radial maze test, (iii) the in-vivo D2, alpha(2A) and alpha(2C) receptor occupancies of these pharmacological treatments, using ex-vivo autoradiography. Whereas neither idazoxan nor raclopride alone had any effect, the combination exerted the same facilitation of glutamatergic transmission in rat prefrontal pyramidal neurons as clozapine, and this effect was found to be mediated by dopamine acting at D(1) receptors. Similarly to clozapine, the combination of idazoxan and raclopride also completely reversed the working-memory impairment in rats induced by MK-801. Moreover, these effects of the two treatment regimes were obtained at similar occupancies at D(2), alpha(2A) and alpha(2C) receptors respectively. Our results provide novel neurobiological and behavioural support for a pro-cognitive effect of adjunctive use of idazoxan with antipsychotic drugs that lack appreciable alpha(2) adrenoceptor-blocking properties, and define presynaptic alpha(2) adrenoceptors as major targets in antipsychotic drug development. PMID:15857571

  16. 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

  17. Antibodies directed to Neisseria gonorrhoeae impair nerve growth factor-dependent neurite outgrowth in Rat PC12 cells.

    PubMed

    Reuss, B

    2014-03-01

    In children born from mothers with prenatal infections with the Gram-negative bacterium Neisseria gonorrhoeae, schizophrenia risk is increased in later life. Since cortical neuropil formation is frequently impaired during this disease, actions of a rabbit polyclonal antiserum directed to N. gonorrhoeae on neurite outgrowth in nerve growth factor-stimulated PC12 cells were investigated here. It turned out that 10 μg/ml of the antiserum leads indeed to a significant reduction in neurite outgrowth, whereas an antiserum directed to Neisseria meningitidis had no such effect. Furthermore, reduction in neurite outgrowth could be reversed by the neuroleptic drugs haloperidol, clozapine, risperidone, and olanzapine. On the molecular level, the observed effects seem to include the known neuritogenic transcription factors FoxO3a and Stat3, since reduced neurite outgrowth caused by the antiserum was accompanied by a reduced phosphorylation of both factors. In contrast, restitution of neurite outgrowth by neuroleptic drugs revealed no correlation to the phosphorylation state of these factors. The present report gives a first hint that bacterial infections could indeed lead to impaired neuropil formation in vitro; however, the in vivo relevance of this finding for schizophrenia pathogenesis remains to be clarified in the future. PMID:24203572

  18. Movement-related cortical activation in familial Parkinson disease.

    PubMed

    Delval, A; Defebvre, L; Labyt, E; Douay, X; Bourriez, J-L; Waucquiez, N; Derambure, P; Destée, A

    2006-09-26

    We sought to determine whether or not first-degree relatives of patients with familial Parkinson disease (FDRs) present impaired movement-related cortical activity. We studied 10 familial Parkinson disease subjects, 10 FDRs, and 10 controls and analyzed event-related mu desynchronization (ERD) and beta synchronization. Forty percent FDRs presented reduced premovement mu ERD latency, suggesting that premovement cortical activation is impaired in FDRs. PMID:17000986

  19. 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. PMID:25283080

  20. ‘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

  1. 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. PMID:23326379

  2. 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

  3. Spatiotemporal SERT expression in cortical map development.

    PubMed

    Chen, Xiaoning; Petit, Emilie I; Dobrenis, Kostantin; Sze, Ji Ying

    2016-09-01

    The cerebral cortex is organized into morphologically distinct areas that provide biological frameworks underlying perception, cognition, and behavior. Profiling mouse and human cortical transcriptomes have revealed temporal-specific differential gene expression modules in distinct neocortical areas during cortical map establishment. However, the biological roles of spatiotemporal gene expression in cortical patterning and how cortical topographic gene expression is regulated are largely unknown. Here, we characterize temporal- and spatial-defined expression of serotonin (5-HT) transporter (SERT) in glutamatergic neurons during sensory map development in mice. SERT is transiently expressed in glutamatergic thalamic neurons projecting to sensory cortices and in pyramidal neurons in the prefrontal cortex (PFC) and hippocampus (HPC) during the period that lays down the basic functional neural circuits. We previously identified that knockout of SERT in the thalamic neurons blocks 5-HT uptake by their thalamocortical axons, resulting in excessive 5-HT signaling that impairs sensory map architecture. In contrast, here we show that selective SERT knockout in the PFC and HPC neurons does not perturb sensory map patterning. These data suggest that transient SERT expression in specific glutamatergic neurons provides area-specific instructions for cortical map patterning. Hence, genetic and pharmacological manipulations of this SERT function could illuminate the fundamental genetic programming of cortex-specific maps and biological roles of temporal-specific cortical topographic gene expression in normal development and mental disorders. PMID:27282696

  4. 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

  5. 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

  6. 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

  7. 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

  8. Intelligence and socioeconomic position in childhood in relation to frailty and cumulative allostatic load in later life: the Lothian Birth Cohort 1936

    PubMed Central

    Gale, Catharine R; Booth, Tom; Starr, John M; Deary, Ian J

    2016-01-01

    Background Information on childhood determinants of frailty or allostatic load in later life is sparse. We investigated whether lower intelligence and greater socioeconomic disadvantage in childhood increased the risk of frailty and higher allostatic load, and explored the mediating roles of adult socioeconomic position, educational attainment and health behaviours. Methods Participants were 876 members of the Lothian Birth Cohort 1936 whose intelligence was assessed at age 11. At age 70, frailty was assessed using the Fried criteria. Measurements were made of fibrinogen, triglyceride, total and high-density lipoprotein cholesterol, albumin, glycated haemoglobin, C reactive protein, body mass index and blood pressure, from which an allostatic load score was calculated. Results In sex-adjusted analyses, lower intelligence and lower social class in childhood were associated with an increased risk of frailty: relative risks (95% CIs) were 1.57 (1.21 to 2.03) for a SD decrease in intelligence and 1.48 (1.12 to 1.96) for a category decrease in social class. In the fully adjusted model, both associations ceased to be significant: relative risks were 1.13 (0.83 to 1.54) and 1.19 (0.86 to 1.61), respectively. Educational attainment had a significant mediating effect. Lower childhood intelligence in childhood, but not social class, was associated with higher allostatic load. The sex-adjusted coefficient for allostatic load for a SD decrease in intelligence was 0.10 (0.07 to 0.14). In the fully adjusted model, this association was attenuated but remained significant (0.05 (0.01 to 0.09)). Conclusions Further research will need to investigate the mechanisms whereby lower childhood intelligence is linked to higher allostatic load in later life. PMID:26700299

  9. Developmental exposure to 2,3,7,8 tetrachlorodibenzo-p-dioxin attenuates later-life Notch1-mediated T cell development and leukemogenesis.

    PubMed

    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(ICN-TG)). Following exposure of adult Notch(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 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 Notch(ICN-TG) offspring have a peripheral T cell pool heavily biased toward the CD4 lineage, while TCDD-exposed Notch(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. PMID:25585350

  10. 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. PMID:26286826

  11. Substance abuse in later life.

    PubMed Central

    D'Archangelo, E.

    1993-01-01

    Substance abuse affects an appreciable portion of the elderly population. Elderly people have characteristics that could hinder identification, diagnosis, intervention, and treatment of substance abuse. If physicians use strategies specific to the elderly, management is often successful. PMID:8219846

  12. 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

  13. Can a nudge keep you warm? Using nudges to reduce excess winter deaths: insight from the Keeping Warm in Later Life Project (KWILLT).

    PubMed

    Allmark, Peter; Tod, Angela M

    2014-03-01

    Nudges are interventions that aim to change people's behaviour through changing the environment in which they choose rather than appealing to their reasoning. Nudges have been proposed as of possible use in relation to health-related behaviour. However, nudges have been criticized as ethically dubious because they bypass peoples reasoning and (anyway) are of little help in relation to affecting ill-health that results from social determinants, such as poverty. Reducing the rate of excess winter deaths (EWDs) is a public health priority; however, EWD seems clearly to be socially determined such that nudges arguably have little role. This article defends two claims: (i) nudges could have a place in tackling even the heavily socially determined problem of EWD. We draw on evidence from an empirical study, the Keeping Warm in Later Life Project (KWILLT), to argue that in some cases the risk of cold is within the person's control to some extent such that environmental modifications to influence behaviour such as nudges are possible. (ii) Some uses of behavioural insights in the form of nudges are acceptable, including some in the area of EWD. We suggest a question-based framework by which to judge the ethical acceptability of nudges. PMID:23873728

  14. 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

  15. Can a nudge keep you warm? Using nudges to reduce excess winter deaths: insight from the Keeping Warm in Later Life Project (KWILLT)

    PubMed Central

    Allmark, Peter; Tod, Angela M.

    2014-01-01

    Nudges are interventions that aim to change people's behaviour through changing the environment in which they choose rather than appealing to their reasoning. Nudges have been proposed as of possible use in relation to health-related behaviour. However, nudges have been criticized as ethically dubious because they bypass peoples reasoning and (anyway) are of little help in relation to affecting ill-health that results from social determinants, such as poverty. Reducing the rate of excess winter deaths (EWDs) is a public health priority; however, EWD seems clearly to be socially determined such that nudges arguably have little role. This article defends two claims: (i) nudges could have a place in tackling even the heavily socially determined problem of EWD. We draw on evidence from an empirical study, the Keeping Warm in Later Life Project (KWILLT), to argue that in some cases the risk of cold is within the person’s control to some extent such that environmental modifications to influence behaviour such as nudges are possible. (ii) Some uses of behavioural insights in the form of nudges are acceptable, including some in the area of EWD. We suggest a question-based framework by which to judge the ethical acceptability of nudges. PMID:23873728

  16. Holding on and letting go: the perspectives of pre-seniors and seniors on driving self-regulation in later life.

    PubMed

    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 from the perspective of pre-senior (aged 55-64) drivers, senior (aged 65 years or over) drivers, and senior ex-drivers. Themes resulting from inductive analysis addressed the importance of driving, mechanisms of self-monitoring and self-regulation, people who influenced decision making, and opinions regarding licensing regulations. A preliminary model of the process of self-regulation that highlights intrapersonal, interpersonal, and environmental influences on why, how, and when aging drivers adapt or cease driving is presented. The model identifies areas for future research to enhance understanding of this process, including the effectiveness of self-regulation. Findings suggest that increased public awareness of issues related to driving and aging could assist aging drivers, their families, and their family physicians in optimizing driving safety for this population. Since a near accident or accident was seen as the only factor that would lead many informants to stop driving and few informants planned for driving cessation, there is a need for interventions that help aging drivers make the transition to ex-driver in a timely and personally acceptable way. PMID:16770749

  17. Oral antigen exposure in extreme early life in lambs influences the magnitude of the immune response which can be generated in later life

    PubMed Central

    2013-01-01

    Background 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. Results 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

  18. 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. PMID:16881901

  19. 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

  20. Sleep and olfactory cortical plasticity

    PubMed Central

    Barnes, Dylan C.; Wilson, Donald A.

    2014-01-01

    In many systems, sleep plays a vital role in memory consolidation and synaptic homeostasis. These processes together help store information of biological significance and reset synaptic circuits to facilitate acquisition of information in the future. In this review, we describe recent evidence of sleep-dependent changes in olfactory system structure and function which contribute to odor memory and perception. During slow-wave sleep, the piriform cortex becomes hypo-responsive to odor stimulation and instead displays sharp-wave activity similar to that observed within the hippocampal formation. Furthermore, the functional connectivity between the piriform cortex and other cortical and limbic regions is enhanced during slow-wave sleep compared to waking. This combination of conditions may allow odor memory consolidation to occur during a state of reduced external interference and facilitate association of odor memories with stored hedonic and contextual cues. Evidence consistent with sleep-dependent odor replay within olfactory cortical circuits is presented. These data suggest that both the strength and precision of odor memories is sleep-dependent. The work further emphasizes the critical role of synaptic plasticity and memory in not only odor memory but also basic odor perception. The work also suggests a possible link between sleep disturbances that are frequently co-morbid with a wide range of pathologies including Alzheimer’s disease, schizophrenia and depression and the known olfactory impairments associated with those disorders. PMID:24795585

  1. Prenatal Cerebral Ischemia Disrupts MRI-Defined Cortical Microstructure Through Disturbances in Neuronal Arborization

    PubMed Central

    Hansen, Kelly; Azimi-Zonooz, Aryan; Chen, Kevin; Riddle, Art; Gong, Xi; Sharifnia, Elica; Hagen, Matthew; Ahmad, Tahir; Leigland, Lindsey A.; Back, Stephen A.

    2013-01-01

    Children who survive preterm birth exhibit persistent unexplained disturbances in cerebral cortical growth with associated cognitive and learning disabilities. The mechanisms underlying these deficits remain elusive. We used ex vivo diffusion magnetic resonance imaging to demonstrate in a preterm large-animal model that cerebral ischemia impairs cortical growth and the normal maturational decline in cortical fractional anisotropy (FA). Analysis of pyramidal neurons revealed that cortical deficits were associated with impaired expansion of the dendritic arbor and reduced synaptic density. Together, these findings suggest a link between abnormal cortical FA and disturbances of neuronal morphological development. To experimentally investigate this possibility, we measured the orientation distribution of dendritic branches and observed that it corresponds with the theoretically predicted pattern of increased anisotropy within cases that exhibited elevated cortical FA after ischemia. We conclude that cortical growth impairments are associated with diffuse disturbances in the dendritic arbor and synapse formation of cortical neurons, which may underlie the cognitive and learning disabilities in survivors of preterm birth. Further, measurement of cortical FA may be useful for noninvasively detecting neurological disorders affecting cortical development. PMID:23325800

  2. 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

  3. Pharmacology of cortical inhibition

    PubMed Central

    Krnjević, K.; Randić, Mirjana; Straughan, D. W.

    1966-01-01

    1. We have studied the effects of various pharmacological agents on the cortical inhibitory process described in the previous two papers (Krnjević, Randić & Straughan, 1966a, b); the drugs were mostly administered directly by iontophoresis from micropipettes and by systemic injection (I.V.). 2. Strychnine given by iontophoresis or by the application of a strong solution to the cortical surface potentiated excitatory effects, but very large iontophoretic doses also depressed neuronal firing. Subconvulsive and even convulsive systemic doses had little or no effect at the cortical level. There was no evidence, with any method of application, that strychnine directly interferes with the inhibitory process. 3. Tetanus toxin, obtained from two different sources and injected into the cortex 12-48 hr previously, also failed to block cortical inhibition selectively. As with strychnine, there was some evidence of increased responses to excitatory inputs. 4. Other convulsant drugs which failed to block cortical inhibition included picrotoxin, pentamethylene tetrazole, thiosemicarbazide, longchain ω-amino acids and morphine. 5. The inhibition was not obviously affected by cholinomimetic agents or by antagonists of ACh. 6. α- and β-antagonists of adrenergic transmission were also ineffective. 7. Cortical inhibition was fully developed in the presence of several general anaesthetics, including ether, Dial, pentobarbitone, Mg and chloralose. A temporary reduction in inhibition which is sometimes observed after systemic doses of pentobarbitone, is probably secondary to a fall in blood pressure. 8. Several central excitants such as amphetamine, caffeine and lobeline also failed to show any specific antagonistic action on cortical inhibition. 9. In view of the possibility that GABA is the chemical agent mediating cortical inhibition, an attempt was made to find a selective antagonist of its depressant action on cortical neurones. None of the agents listed above, nor any other

  4. 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. PMID:25895507

  5. 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

  6. Modulation of Cortical Oscillations by Low-Frequency Direct Cortical Stimulation Is State-Dependent

    PubMed Central

    Alagapan, Sankaraleengam; Schmidt, Stephen L.; Lefebvre, Jérémie; Hadar, Eldad; Shin, Hae Won; Frӧhlich, Flavio

    2016-01-01

    Cortical oscillations play a fundamental role in organizing large-scale functional brain networks. Noninvasive brain stimulation with temporally patterned waveforms such as repetitive transcranial magnetic stimulation (rTMS) and transcranial alternating current stimulation (tACS) have been proposed to modulate these oscillations. Thus, these stimulation modalities represent promising new approaches for the treatment of psychiatric illnesses in which these oscillations are impaired. However, the mechanism by which periodic brain stimulation alters endogenous oscillation dynamics is debated and appears to depend on brain state. Here, we demonstrate with a static model and a neural oscillator model that recurrent excitation in the thalamo-cortical circuit, together with recruitment of cortico-cortical connections, can explain the enhancement of oscillations by brain stimulation as a function of brain state. We then performed concurrent invasive recording and stimulation of the human cortical surface to elucidate the response of cortical oscillations to periodic stimulation and support the findings from the computational models. We found that (1) stimulation enhanced the targeted oscillation power, (2) this enhancement outlasted stimulation, and (3) the effect of stimulation depended on behavioral state. Together, our results show successful target engagement of oscillations by periodic brain stimulation and highlight the role of nonlinear interaction between endogenous network oscillations and stimulation. These mechanistic insights will contribute to the design of adaptive, more targeted stimulation paradigms. PMID:27023427

  7. Modulation of Cortical Oscillations by Low-Frequency Direct Cortical Stimulation Is State-Dependent.

    PubMed

    Alagapan, Sankaraleengam; Schmidt, Stephen L; Lefebvre, Jérémie; Hadar, Eldad; Shin, Hae Won; Frӧhlich, Flavio

    2016-03-01

    Cortical oscillations play a fundamental role in organizing large-scale functional brain networks. Noninvasive brain stimulation with temporally patterned waveforms such as repetitive transcranial magnetic stimulation (rTMS) and transcranial alternating current stimulation (tACS) have been proposed to modulate these oscillations. Thus, these stimulation modalities represent promising new approaches for the treatment of psychiatric illnesses in which these oscillations are impaired. However, the mechanism by which periodic brain stimulation alters endogenous oscillation dynamics is debated and appears to depend on brain state. Here, we demonstrate with a static model and a neural oscillator model that recurrent excitation in the thalamo-cortical circuit, together with recruitment of cortico-cortical connections, can explain the enhancement of oscillations by brain stimulation as a function of brain state. We then performed concurrent invasive recording and stimulation of the human cortical surface to elucidate the response of cortical oscillations to periodic stimulation and support the findings from the computational models. We found that (1) stimulation enhanced the targeted oscillation power, (2) this enhancement outlasted stimulation, and (3) the effect of stimulation depended on behavioral state. Together, our results show successful target engagement of oscillations by periodic brain stimulation and highlight the role of nonlinear interaction between endogenous network oscillations and stimulation. These mechanistic insights will contribute to the design of adaptive, more targeted stimulation paradigms. PMID:27023427

  8. Cholinergic systems are essential for late-stage maturation and refinement of motor cortical circuits.

    PubMed

    Ramanathan, Dhakshin S; Conner, James M; Anilkumar, Arjun A; Tuszynski, Mark H

    2015-03-01

    Previous studies reported that early postnatal cholinergic lesions severely perturb early cortical development, impairing neuronal cortical migration and the formation of cortical dendrites and synapses. These severe effects of early postnatal cholinergic lesions preclude our ability to understand the contribution of cholinergic systems to the later-stage maturation of topographic cortical representations. To study cholinergic mechanisms contributing to the later maturation of motor cortical circuits, we first characterized the temporal course of cortical motor map development and maturation in rats. In this study, we focused our attention on the maturation of cortical motor representations after postnatal day 25 (PND 25), a time after neuronal migration has been accomplished and cortical volume has reached adult size. We found significant maturation of cortical motor representations after this time, including both an expansion of forelimb representations in motor cortex and a shift from proximal to distal forelimb representations to an extent unexplainable by simple volume enlargement of the neocortex. Specific cholinergic lesions placed at PND 24 impaired enlargement of distal forelimb representations in particular and markedly reduced the ability to learn skilled motor tasks as adults. These results identify a novel and essential role for cholinergic systems in the late refinement and maturation of cortical circuits. Dysfunctions in this system may constitute a mechanism of late-onset neurodevelopmental disorders such as Rett syndrome and schizophrenia. PMID:25505106

  9. Cholinergic systems are essential for late-stage maturation and refinement of motor cortical circuits

    PubMed Central

    Ramanathan, Dhakshin S.; Conner, James M.; Anilkumar, Arjun A.

    2014-01-01

    Previous studies reported that early postnatal cholinergic lesions severely perturb early cortical development, impairing neuronal cortical migration and the formation of cortical dendrites and synapses. These severe effects of early postnatal cholinergic lesions preclude our ability to understand the contribution of cholinergic systems to the later-stage maturation of topographic cortical representations. To study cholinergic mechanisms contributing to the later maturation of motor cortical circuits, we first characterized the temporal course of cortical motor map development and maturation in rats. In this study, we focused our attention on the maturation of cortical motor representations after postnatal day 25 (PND 25), a time after neuronal migration has been accomplished and cortical volume has reached adult size. We found significant maturation of cortical motor representations after this time, including both an expansion of forelimb representations in motor cortex and a shift from proximal to distal forelimb representations to an extent unexplainable by simple volume enlargement of the neocortex. Specific cholinergic lesions placed at PND 24 impaired enlargement of distal forelimb representations in particular and markedly reduced the ability to learn skilled motor tasks as adults. These results identify a novel and essential role for cholinergic systems in the late refinement and maturation of cortical circuits. Dysfunctions in this system may constitute a mechanism of late-onset neurodevelopmental disorders such as Rett syndrome and schizophrenia. PMID:25505106

  10. Bidirectional plasticity of cortical pattern recognition and behavioral sensory acuity

    PubMed Central

    Chapuis, Julie; Wilson, Donald A.

    2011-01-01

    Learning to adapt to a complex and fluctuating environment requires the ability to adjust neural representations of sensory stimuli. Through pattern completion processes, cortical networks can reconstruct familiar patterns from degraded input patterns, while pattern separation processes allow discrimination of even highly overlapping inputs. Here we show that the balance between pattern separation and completion is experience-dependent. Rats given extensive training with overlapping complex odorant mixtures show improved behavioral discrimination ability and enhanced cortical ensemble pattern separation. In contrast, behavioral training to disregard normally detectable differences between overlapping mixtures results in impaired cortical ensemble pattern separation (enhanced pattern completion) and impaired discrimination. This bidirectional effect was not found in the olfactory bulb, and may be due to plasticity within olfactory cortex itself. Thus pattern recognition, and the balance between pattern separation and completion, is highly malleable based on task demands and occurs in concert with changes in perceptual performance. PMID:22101640