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Sample records for age-related cognitive declines

  1. Consequences of Age-Related Cognitive Declines

    PubMed Central

    Salthouse, Timothy

    2013-01-01

    Adult age differences in a variety of cognitive abilities are well documented, and many of those abilities have been found to be related to success in the workplace and in everyday life. However, increased age is seldom associated with lower levels of real-world functioning, and the reasons for this lab-life discrepancy are not well understood. This article briefly reviews research concerned with relations of age to cognition, relations of cognition to successful functioning outside the laboratory, and relations of age to measures of work performance and achievement. The final section discusses several possible explanations for why there are often little or no consequences of age-related cognitive declines in everyday functioning. PMID:21740223

  2. Veterans have less age-related cognitive decline.

    PubMed

    McLay, R N; Lyketsos, C G

    2000-08-01

    Military service involves exposure to a number of stresses, both psychological and physical. On the other hand, military personnel generally maintain excellent fitness, and veterans have increased access to education and health care. The overall effect on age-related cognitive decline, whether for good or ill, of having served in the armed forces has not been investigated previously. In this study, we examined a diverse population of 208 veterans and 1,216 civilians followed as part of the Epidemiologic Catchment Area Study in 1981, 1982, and 1993 to 1996. We examined change in Mini-Mental State Examination (MMSE) score after a median of 11.5 years. Veterans were found to have significantly less decrease in MMSE scores at follow-up even after sex, race, and education were taken into account. These results suggest an overall positive effect of military service on the rate of age-related cognitive decline. PMID:10957857

  3. Neuroanatomical Substrates of Age-Related Cognitive Decline

    ERIC Educational Resources Information Center

    Salthouse, Timothy A.

    2011-01-01

    There are many reports of relations between age and cognitive variables and of relations between age and variables representing different aspects of brain structure and a few reports of relations between brain structure variables and cognitive variables. These findings have sometimes led to inferences that the age-related brain changes cause the…

  4. The potential effects of meditation on age-related cognitive decline: a systematic review

    PubMed Central

    Gard, Tim; Hölzel, Britta K.; Lazar, Sara W.

    2014-01-01

    With a rapidly aging society it becomes increasingly important to counter normal age-related decline in cognitive functioning. Growing evidence suggests that cognitive training programs may have the potential to counteract this decline. On the basis of a growing body of research that shows that meditation has positive effects on cognition in younger and middle-aged adults, meditation may be able to offset normal age-related cognitive decline or even enhance cognitive function in older adults. In this paper, we review studies investigating the effects of meditation on age-related cognitive decline. We searched the Web of Science (1900 to present), PsycINFO (1597 to present), MEDLINE (1950 to present), and CABI (1910 to present) to identify original studies investigating the effects of meditation on cognition and cognitive decline in the context of aging. Twelve studies were included in the review, six of which were randomized controlled trials. Studies involved a wide variety of meditation techniques and reported preliminary positive effects on attention, memory, executive function, processing speed, and general cognition. However, most studies had a high risk of bias and small sample sizes. Reported dropout rates were low and compliance rates high. We conclude that meditation interventions for older adults are feasible, and preliminary evidence suggests that meditation can offset age-related cognitive decline. PMID:24571182

  5. Hippocampal dysregulation of synaptic plasticity-associated proteins with age-related cognitive decline

    PubMed Central

    VanGuilder, Heather D.; Farley, Julie A.; Yan, Han; Van Kirk, Colleen A.; Mitschelen, Matthew; Sonntag, William E.; Freeman, Willard M.

    2011-01-01

    Age-related cognitive decline occurs without frank neurodegeneration and is the most common cause of memory impairment in aging individuals. With increasing longevity, cognitive deficits, especially in hippocampus-dependent memory processes, are increasing in prevalence. Nevertheless, the neurobiological basis of age-related cognitive decline remains unknown. While concerted efforts have led to the identification of neurobiological changes with aging, few age-related alterations have been definitively correlated to behavioral measures of cognitive decline. In this work, adult (12 Months) and aged (28 months) rats were categorized by Morris water maze performance as Adult cognitively Intact, Aged cognitively Intact or Aged cognitively Impaired, and protein expression was examined in hippocampal synaptosome preparations. Previously described differences in synaptic expression of neurotransmission-associated proteins (Dnm1, Hpca, Stx1, Syn1, Syn2, Syp, SNAP25, VAMP2 and 14-3-3 eta, gamma, and zeta) were confirmed between Adult and Aged rats, with no further dysregulation associated with cognitive impairment. Proteins related to synaptic structural stability (MAP2, drebrin, Nogo-A) and activity-dependent signaling (PSD-95, 14-3-3θ, CaMKIIα) were up- and down-regulated, respectively, with cognitive impairment but were not altered with increasing age. Localization of MAP2, PSD-95, and CaMKIIα demonstrated protein expression alterations throughout the hippocampus. The altered expression of activity- and structural stability-associated proteins suggests that impaired synaptic plasticity is a distinct phenomenon that occurs with age-related cognitive decline, and demonstrates that cognitive decline is not simply an exacerbation of the aging phenotype. PMID:21440628

  6. Recent Advances in Berry Supplementation and Age-Related Cognitive Decline

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To summarize recent findings and current concepts in the beneficial effects of berry consumption on brain function during aging. Berryfruit supplementation has continued to demonstrate efficacy in reversing age-related cognitive decline in animal studies. In terms of the mechanisms behind the effe...

  7. Age-related decline in cognitive control: the role of fluid intelligence and processing speed

    PubMed Central

    2014-01-01

    Background Research on cognitive control suggests an age-related decline in proactive control abilities whereas reactive control seems to remain intact. However, the reason of the differential age effect on cognitive control efficiency is still unclear. This study investigated the potential influence of fluid intelligence and processing speed on the selective age-related decline in proactive control. Eighty young and 80 healthy older adults were included in this study. The participants were submitted to a working memory recognition paradigm, assessing proactive and reactive cognitive control by manipulating the interference level across items. Results Repeated measures ANOVAs and hierarchical linear regressions indicated that the ability to appropriately use cognitive control processes during aging seems to be at least partially affected by the amount of available cognitive resources (assessed by fluid intelligence and processing speed abilities). Conclusions This study highlights the potential role of cognitive resources on the selective age-related decline in proactive control, suggesting the importance of a more exhaustive approach considering the confounding variables during cognitive control assessment. PMID:24401034

  8. Glutamatergic regulation prevents hippocampal-dependent age-related cognitive decline through dendritic spine clustering

    PubMed Central

    Pereira, Ana C.; Lambert, Hilary K.; Grossman, Yael S.; Dumitriu, Dani; Waldman, Rachel; Jannetty, Sophia K.; Calakos, Katina; Janssen, William G.; McEwen, Bruce S.; Morrison, John H.

    2014-01-01

    The dementia of Alzheimer’s disease (AD) results primarily from degeneration of neurons that furnish glutamatergic corticocortical connections that subserve cognition. Although neuron death is minimal in the absence of AD, age-related cognitive decline does occur in animals as well as humans, and it decreases quality of life for elderly people. Age-related cognitive decline has been linked to synapse loss and/or alterations of synaptic proteins that impair function in regions such as the hippocampus and prefrontal cortex. These synaptic alterations are likely reversible, such that maintenance of synaptic health in the face of aging is a critically important therapeutic goal. Here, we show that riluzole can protect against some of the synaptic alterations in hippocampus that are linked to age-related memory loss in rats. Riluzole increases glutamate uptake through glial transporters and is thought to decrease glutamate spillover to extrasynaptic NMDA receptors while increasing synaptic glutamatergic activity. Treated aged rats were protected against age-related cognitive decline displayed in nontreated aged animals. Memory performance correlated with density of thin spines on apical dendrites in CA1, although not with mushroom spines. Furthermore, riluzole-treated rats had an increase in clustering of thin spines that correlated with memory performance and was specific to the apical, but not the basilar, dendrites of CA1. Clustering of synaptic inputs is thought to allow nonlinear summation of synaptic strength. These findings further elucidate neuroplastic changes in glutamatergic circuits with aging and advance therapeutic development to prevent and treat age-related cognitive decline. PMID:25512503

  9. Glutamatergic regulation prevents hippocampal-dependent age-related cognitive decline through dendritic spine clustering.

    PubMed

    Pereira, Ana C; Lambert, Hilary K; Grossman, Yael S; Dumitriu, Dani; Waldman, Rachel; Jannetty, Sophia K; Calakos, Katina; Janssen, William G; McEwen, Bruce S; Morrison, John H

    2014-12-30

    The dementia of Alzheimer's disease (AD) results primarily from degeneration of neurons that furnish glutamatergic corticocortical connections that subserve cognition. Although neuron death is minimal in the absence of AD, age-related cognitive decline does occur in animals as well as humans, and it decreases quality of life for elderly people. Age-related cognitive decline has been linked to synapse loss and/or alterations of synaptic proteins that impair function in regions such as the hippocampus and prefrontal cortex. These synaptic alterations are likely reversible, such that maintenance of synaptic health in the face of aging is a critically important therapeutic goal. Here, we show that riluzole can protect against some of the synaptic alterations in hippocampus that are linked to age-related memory loss in rats. Riluzole increases glutamate uptake through glial transporters and is thought to decrease glutamate spillover to extrasynaptic NMDA receptors while increasing synaptic glutamatergic activity. Treated aged rats were protected against age-related cognitive decline displayed in nontreated aged animals. Memory performance correlated with density of thin spines on apical dendrites in CA1, although not with mushroom spines. Furthermore, riluzole-treated rats had an increase in clustering of thin spines that correlated with memory performance and was specific to the apical, but not the basilar, dendrites of CA1. Clustering of synaptic inputs is thought to allow nonlinear summation of synaptic strength. These findings further elucidate neuroplastic changes in glutamatergic circuits with aging and advance therapeutic development to prevent and treat age-related cognitive decline. PMID:25512503

  10. Prevention of Age-Related Cognitive Decline: Which Strategies, When, and for Whom?

    PubMed

    Shatenstein, Bryna; Barberger-Gateau, Pascale; Mecocci, Patrizia

    2015-01-01

    Brain aging is characterized by the progressive and gradual accumulation of detrimental changes in structure and function, which increase risk of age-related cognitive decline and dementia. This devastating chronic condition generates a huge social and economic burden and accounts for 11.2% of years of disability. The increase in lifespan has contributed to the increase in dementia prevalence; however, there is currently no curative treatment for most causes of dementias. This paper reviews evidence-based strategies to build, enhance, and preserve cognition over the lifespan by examining approaches that work best, proposing when in the life course they should be implemented, and in which population group(s). Recent work shows a tendency to decreased age-specific prevalence and incidence of cognitive problems and dementia among people born later in the first half of the 20th century, citing higher educational levels, improvements in lifestyle, and better handling of vascular risk factors. This implies that we can target modifiable environmental, lifestyle, and health risk factors to modify the trajectory of cognitive decline before the onset of irreversible dementia. Because building cognitive reserve and prevention of cognitive decline are of critical importance, interventions are needed at every stage of the life course to foster cognitive stimulation, and enable healthy eating habits and physical activity throughout the lifespan. Preventive interventions to decrease and delay cognitive decline and its consequences in old age will also require collaboration and action on the part of policy-makers at the political and social level. PMID:26401926

  11. Can psychosocial work conditions protect against age-related cognitive decline? Results from a systematic review

    PubMed Central

    Nexø, Mette Andersen; Meng, Annette; Borg, Vilhelm

    2016-01-01

    According to the use it or lose it hypothesis, intellectually stimulating activities postpone age-related cognitive decline. A previous systematic review concluded that a high level of mental work demands and job control protected against cognitive decline. However, it did not distinguish between outcomes that were measured as cognitive function at one point in time or as cognitive decline. Our study aimed to systematically review which psychosocial working conditions were prospectively associated with high levels of cognitive function and/or changes in cognitive function over time. Articles were identified by a systematic literature search (MEDLINE, Web of Science (WOS), PsycNET, Occupational Safety and Health (OSH)). We included only studies with longitudinal designs examining the impact of psychosocial work conditions on outcomes defined as cognitive function or changes in cognitive function. Two independent reviewers compared title-abstract screenings, full-text screenings and quality assessment ratings. Eleven studies were included in the final synthesis and showed that high levels of mental work demands, occupational complexity or job control at one point in time were prospectively associated with higher levels of cognitive function in midlife or late life. However, the evidence to clarify whether these psychosocial factors also affected cognitive decline was insufficient, conflicting or weak. It remains speculative whether job control, job demands or occupational complexity can protect against cognitive decline. Future studies using methodological advancements can reveal whether workers gain more cognitive reserve in midlife and late life than the available evidence currently suggests. The public health implications of a previous review should thereby be redefined accordingly. PMID:27178844

  12. Can psychosocial work conditions protect against age-related cognitive decline? Results from a systematic review.

    PubMed

    Nexø, Mette Andersen; Meng, Annette; Borg, Vilhelm

    2016-07-01

    According to the use it or lose it hypothesis, intellectually stimulating activities postpone age-related cognitive decline. A previous systematic review concluded that a high level of mental work demands and job control protected against cognitive decline. However, it did not distinguish between outcomes that were measured as cognitive function at one point in time or as cognitive decline. Our study aimed to systematically review which psychosocial working conditions were prospectively associated with high levels of cognitive function and/or changes in cognitive function over time. Articles were identified by a systematic literature search (MEDLINE, Web of Science (WOS), PsycNET, Occupational Safety and Health (OSH)). We included only studies with longitudinal designs examining the impact of psychosocial work conditions on outcomes defined as cognitive function or changes in cognitive function. Two independent reviewers compared title-abstract screenings, full-text screenings and quality assessment ratings. Eleven studies were included in the final synthesis and showed that high levels of mental work demands, occupational complexity or job control at one point in time were prospectively associated with higher levels of cognitive function in midlife or late life. However, the evidence to clarify whether these psychosocial factors also affected cognitive decline was insufficient, conflicting or weak. It remains speculative whether job control, job demands or occupational complexity can protect against cognitive decline. Future studies using methodological advancements can reveal whether workers gain more cognitive reserve in midlife and late life than the available evidence currently suggests. The public health implications of a previous review should thereby be redefined accordingly. PMID:27178844

  13. Contribution of changes in ubiquitin and myelin basic protein to age-related cognitive decline.

    PubMed

    Wang, Deng-Shun; Bennett, David A; Mufson, Elliott J; Mattila, Petri; Cochran, Elizabeth; Dickson, Dennis W

    2004-01-01

    The structural substrates for age-associated cognitive and motor slowing are not known, but age-related white matter changes, such as ubiquitin (UBQ)-immunoreactive granular degeneration of myelin, might contribute to this slowing. To address this hypothesis we measured immunoreactivity for UBQ and myelin basic protein (MBP) in frontal white matter of age-, sex- and postmortem interval-matched cases with no cognitive impairment (NCI; N=12), mild cognitive impairment (MCI; N=14) and Alzheimer disease (AD; N=12). There were no significant correlations between UBQ in white matter and cognitive measures, but MBP was significantly lower in AD compared with NCI and MCI. MBP correlated with overall cognition as assessed by neuropsychological summary scores, as well as with timed cognitive tests and those that reflect frontal functions. An age-related decrease in MBP immunoreactivity was detected in NCI cases (r=0.71). These results support the hypothesis that white matter pathology may contribute to age-associated decline in cognition. PMID:14687885

  14. Foreign language training as cognitive therapy for age-related cognitive decline: A hypothesis for future research

    PubMed Central

    Antoniou, Mark; Gunasekera, Geshri; Wong, Patrick C. M.

    2014-01-01

    Over the next fifty years, the number of older adults is set to reach record levels. Protecting older adults from the age-related effects of cognitive decline is one of the greatest challenges of the next few decades as it places increasing pressure on families, health systems, and economies on a global scale. The disease-state of age-related cognitive decline—Alzheimer's disease and other dementias—hijacks our consciousness and intellectual autonomy. However, there is evidence that cognitively stimulating activities protect against the adverse effects of cognitive decline. Similarly, bilingualism is also considered to be a safeguard. We propose that foreign language learning programs aimed at older populations are an optimal solution for building cognitive reserve because language learning engages an extensive brain network that is known to overlap with the regions negatively affected by the aging process. It is recommended that future research should test this potentially fruitful hypothesis. PMID:24051310

  15. Epigenetic alterations in the suprachiasmatic nucleus and hippocampus contribute to age-related cognitive decline

    PubMed Central

    Deibel, Scott H.; Zelinski, Erin L.; Keeley, Robin J.; Kovalchuk, Olga; McDonald, Robert J.

    2015-01-01

    Circadian rhythm dysfunction and cognitive decline, specifically memory loss, frequently accompany natural aging. Circadian rhythms and memory are intertwined, as circadian rhythms influence memory formation and recall in young and old rodents. Although, the precise relationship between circadian rhythms and memory is still largely unknown, it is hypothesized that circadian rhythm disruption, which occurs during aging, contributes to age-associated cognitive decline, specifically memory loss. While there are a variety of mechanisms that could mediate this effect, changes in the epigenome that occur during aging has been proposed as a potential candidate. Interestingly, epigenetic mechanisms, such as DNA methylation and sirtuin1 (SIRT1) are necessary for both circadian rhythms and memory. During aging, similar alterations of epigenetic mechanisms occur in the suprachiasmatic nucleus (SCN) and hippocampus, which are necessary for circadian rhythm generation and memory, respectively. Recently, circadian rhythms have been linked to epigenetic function in the hippocampus, as some of these epigenetic mechanisms oscillate in the hippocampus and are disrupted by clock gene deletion. The current paper will review how circadian rhythms and memory change with age, and will suggest how epigenetic changes in these processes might contribute to age-related cognitive decline. PMID:26252151

  16. Age-related cognitive decline during normal aging: the complex effect of education.

    PubMed

    Ardila, A; Ostrosky-Solis, F; Rosselli, M; Gómez, C

    2000-08-01

    The purpose of this study was to further analyze the effects of education on cognitive decline during normal aging. An 806-subject sample was taken from five different Mexican regions. Participants ranged in age from 16 to 85 years. Subjects were grouped into four educational levels: illiterate, 1-4, 5-9, and 10 or more years of education, and four age ranges: 16-30, 31-50, 51-65, and 66-85 years. A brief neuropsychological test battery (NEUROPSI), standardized and normalized in Spanish, was administered. The NEUROPSI test battery includes assessment of orientation, attention, memory, language, visuoperceptual abilities, motor skills, and executive functions. In general, test scores were strongly associated with level of educational, and differences among age groups were smaller than differences among education groups. However, there was an interaction between age and education such as that among illiterate individuals scores of participants 31-50 years old were higher than scores of participants 16-30 years old for over 50% of the tests. Different patterns of interaction among educational groups were distinguished. It was concluded that: (a) The course of life-span changes in cognition are affected by education. Among individuals with a low level of education, best neuropsychological test performance is observed at an older age than among higher-educated subjects; and (b) there is not a single relationship between age-related cognitive decline and education, but different patterns may be found, depending upon the specific cognitive domain. PMID:14590204

  17. Microstructural white matter changes mediate age-related cognitive decline on the Montreal Cognitive Assessment (MoCA).

    PubMed

    Jolly, Todd A D; Cooper, Patrick S; Badwi, Syarifah Azizah Wan Ahmadul; Phillips, Natalie A; Rennie, Jaime L; Levi, Christopher R; Drysdale, Karen A; Parsons, Mark W; Michie, Patricia T; Karayanidis, Frini

    2016-02-01

    Although the relationship between aging and cognitive decline is well established, there is substantial individual variability in the degree of cognitive decline in older adults. The present study investigates whether variability in cognitive performance in community-dwelling older adults is related to the presence of whole brain or tract-specific changes in white matter microstructure. Specifically, we examine whether age-related decline in performance on the Montreal Cognitive Assessment (MoCA), a cognitive screening tool, is mediated by the white matter microstructural decline. We also examine if this relationship is driven by the presence of cardiovascular risk factors or variability in cerebral arterial pulsatility, an index of cardiovascular risk. Sixty-nine participants (aged 43-87) completed behavioral and MRI testing including T1 structural, T2-weighted FLAIR, and diffusion-weighted imaging (DWI) sequences. Measures of white matter microstructure were calculated using diffusion tensor imaging analyses on the DWI sequence. Multiple linear regression revealed that MoCA scores were predicted by radial diffusivity (RaD) of white matter beyond age or other cerebral measures. While increasing age and arterial pulsatility were associated with increasing RaD, these factors did not mediate the relationship between total white matter RaD and MoCA. Further, the relationship between MoCA and RaD was specific to participants who reported at least one cardiovascular risk factor. These findings highlight the importance of cardiovascular risk factors in the presentation of cognitive decline in old age. Further work is needed to establish whether medical or lifestyle management of these risk factors can prevent or reverse cognitive decline in old age. PMID:26511789

  18. Molecular aspects of age-related cognitive decline: the role of GABA signaling

    PubMed Central

    McQuail, Joseph A.; Frazier, Charles J.; Bizon, Jennifer L.

    2015-01-01

    Alterations in inhibitory interneurons contribute to cognitive deficits associated with several psychiatric and neurological diseases. Phasic and tonic inhibition imparted by γ-amino-butyric acid (GABA) receptors regulates neural activity and helps to establish the appropriate network dynamics in cortical circuits that support normal cognition. This review highlights basic science demonstrating that inhibitory signaling is altered in aging, and discusses the impact of age-related shifts in inhibition on different forms of memory function, including hippocampus-dependent spatial reference memory and prefrontal cortex (PFU)-dependent working memory. The clinical appropriateness and tractability of select therapeutic candidates for cognitive aging that target receptors mediating inhibition are also discussed. PMID:26070271

  19. Processing Speed, Inhibitory Control, and Working Memory: Three Important Factors to Account for Age-Related Cognitive Decline

    ERIC Educational Resources Information Center

    Pereiro Rozas, Arturo X.; Juncos-Rabadan, Onesimo; Gonzalez, Maria Soledad Rodriguez

    2008-01-01

    Processing speed, inhibitory control and working memory have been identified as the main possible culprits of age-related cognitive decline. This article describes a study of their interrelationships and dependence on age, including exploration of whether any of them mediates between age and the others. We carried out a LISREL analysis of the…

  20. Longitudinal Attentional Engagement Rescues Mice from Age-Related Cognitive Declines and Cognitive Inflexibility

    ERIC Educational Resources Information Center

    Matzel, Louis D.; Light, Kenneth R.; Wass, Christopher; Colas-Zelin, Danielle; Denman-Brice, Alexander; Waddel, Adam C.; Kolata, Stefan

    2011-01-01

    Learning, attentional, and perseverative deficits are characteristic of cognitive aging. In this study, genetically diverse CD-1 mice underwent longitudinal training in a task asserted to tax working memory capacity and its dependence on selective attention. Beginning at 3 mo of age, animals were trained for 12 d to perform in a dual radial-arm…

  1. Effects of a computer-based cognitive exercise program on age-related cognitive decline.

    PubMed

    Bozoki, Andrea; Radovanovic, Mirjana; Winn, Brian; Heeter, Carrie; Anthony, James C

    2013-01-01

    We developed a 'senior friendly' suite of online 'games for learning' with interactive calibration for increasing difficulty, and evaluated the feasibility of a randomized clinical trial to test the hypothesis that seniors aged 60-80 can improve key aspects of cognitive ability with the aid of such games. Sixty community-dwelling senior volunteers were randomized to either an online game suite designed to train multiple cognitive abilities, or to a control arm with online activities that simulated the look and feel of the games but with low level interactivity and no calibration of difficulty. Study assessment included measures of recruitment, retention and play-time. Cognitive change was measured with a computerized assessment battery administered just before and within two weeks after completion of the six-week intervention. Impediments to feasibility included: limited access to in-home high-speed internet, large variations in the amount of time devoted to game play, and a reluctance to pursue more challenging levels. Overall analysis was negative for assessed performance (transference effects) even though subjects improved on the games themselves. Post hoc analyses suggest that some types of games may have more value than others, but these effects would need to be replicated in a study designed for that purpose. We conclude that a six-week, moderate-intensity computer game-based cognitive intervention can be implemented with high-functioning seniors, but the effect size is relatively small. Our findings are consistent with Owen et al. (2010), but there are open questions about whether more structured, longer duration or more intensive 'games for learning' interventions might yield more substantial cognitive improvement in seniors. PMID:23542053

  2. A genome-wide scan for common variants affecting the rate of age-related cognitive decline

    PubMed Central

    De Jager, Philip L.; Shulman, Joshua M.; Chibnik, Lori B.; Keenan, Brendan T.; Raj, Towfique; Wilson, Robert S.; Yu, Lei; Leurgans, Sue E.; Tran, Dong; Aubin, Cristin; Anderson, Christopher D.; Biffi, Alessandro; Corneveaux, Jason J.; Huentelman, Matthew J.; Rosand, Jonathan; Daly, Mark J.; Myers, Amanda J.; Reiman, Eric M.; Bennett, David A.; Evans, Denis A.

    2011-01-01

    Age-related cognitive decline is likely promoted by accumulated brain injury due to chronic conditions of aging, including neurodegenerative and vascular disease. Since common neuronal mechanisms may mediate the adaptation to diverse cerebral insults, we hypothesized that susceptibility for age-related cognitive decline may be due in part to a shared genetic network. We have therefore performed a genome-wide association study using a quantitative measure of global cognitive decline slope, based on repeated measures of 17 cognitive tests in 749 subjects from the Religious Orders Study. Top results were evaluated in three independent replication cohorts, consisting of 2,279 additional subjects with repeated cognitive testing. As expected, we find that the Alzheimer’s disease (AD) susceptibility locus, APOE, is strongly associated with rate of cognitive decline (PDISC=5.6×10−9; PJOINT=3.7×10−27). We additionally discover a variant, rs10808746, which shows consistent effects in the replication cohorts and modestly improved evidence of association in the joint analysis (PDISC=6.7×10−5; PREP=9.4×10−3; PJOINT=2.3×10−5). This variant influences the expression of two adjacent genes, PDE7A and MTFR1, which are potential regulators of inflammation and oxidative injury, respectively. Using aggregate measures of genetic risk, we find that known susceptibility loci for cardiovascular disease, type II diabetes, and inflammatory diseases are not significantly associated with cognitive decline in our cohort. Our results suggest that intermediate phenotypes, when coupled with larger sample sizes, may be a useful tool to dissect susceptibility loci for age-related cognitive decline and uncover shared molecular pathways with a role in neuronal injury. PMID:22054870

  3. Video Games as a Means to Reduce Age-Related Cognitive Decline: Attitudes, Compliance, and Effectiveness

    PubMed Central

    Boot, Walter R.; Champion, Michael; Blakely, Daniel P.; Wright, Timothy; Souders, Dustin J.; Charness, Neil

    2013-01-01

    Recent research has demonstrated broad benefits of video game play to perceptual and cognitive abilities. These broad improvements suggest that video game-based cognitive interventions may be ideal to combat the many perceptual and cognitive declines associated with advancing age. Furthermore, game interventions have the potential to induce higher rates of intervention compliance compared to other cognitive interventions as they are assumed to be inherently enjoyable and motivating. We explored these issues in an intervention that tested the ability of an action game and a “brain fitness” game to improve a variety of abilities. Cognitive abilities did not significantly improve, suggesting caution when recommending video game interventions as a means to reduce the effects of cognitive aging. However, the game expected to produce the largest benefit based on previous literature (an action game) induced the lowest intervention compliance. We explain this low compliance by participants’ ratings of the action game as less enjoyable and by their prediction that training would have few meaningful benefits. Despite null cognitive results, data provide valuable insights into the types of video games older adults are willing to play and why. PMID:23378841

  4. Video games as a means to reduce age-related cognitive decline: attitudes, compliance, and effectiveness.

    PubMed

    Boot, Walter R; Champion, Michael; Blakely, Daniel P; Wright, Timothy; Souders, Dustin J; Charness, Neil

    2013-01-01

    Recent research has demonstrated broad benefits of video game play to perceptual and cognitive abilities. These broad improvements suggest that video game-based cognitive interventions may be ideal to combat the many perceptual and cognitive declines associated with advancing age. Furthermore, game interventions have the potential to induce higher rates of intervention compliance compared to other cognitive interventions as they are assumed to be inherently enjoyable and motivating. We explored these issues in an intervention that tested the ability of an action game and a "brain fitness" game to improve a variety of abilities. Cognitive abilities did not significantly improve, suggesting caution when recommending video game interventions as a means to reduce the effects of cognitive aging. However, the game expected to produce the largest benefit based on previous literature (an action game) induced the lowest intervention compliance. We explain this low compliance by participants' ratings of the action game as less enjoyable and by their prediction that training would have few meaningful benefits. Despite null cognitive results, data provide valuable insights into the types of video games older adults are willing to play and why. PMID:23378841

  5. ROLE OF SOLUBLE EPOXIDE HYDROLASE IN AGE-RELATED VASCULAR COGNITIVE DECLINE

    PubMed Central

    Nelson, Jonathan W.; Young, Jennifer M.; Borkar, Rohan; Woltjer, Randy L.; Quinn, Joseph F.; Silbert, Lisa C.; Grafe, Marjorie R.; Alkayed, Nabil J.

    2014-01-01

    P450 eicosanoids are important regulators of the cerebral microcirculation, but their role in cerebral small vessel disease is unclear. We tested the hypothesis that vascular cognitive impairment (VCI) is linked to reduced cerebral microvascular eicosanoid signaling. We analyzed human brain tissue from individuals formerly enrolled in the Oregon Brain Aging Study, who had a history of cognitive impairment histopathological evidence of microvascular disease. VCI subjects had significantly higher lesion burden both on premortem MRI and postmortem histopathology compared to age- and sex-matched controls. Mass spectrometry-based eicosanoid analysis revealed that 14,15-dihydroxyeicosatrienoic acid (DHET) was elevated in cortical brain tissue from VCI subjects. Immunoreactivity of soluble epoxide hydrolase (sEH), the enzyme responsible for 14,15-DHET formation, was localized to cerebral microvascular endothelium, and was enhanced in microvessels of affected tissue. Finally, we evaluated the genotype frequency of two functional single nucleotide polymorphisms of sEH gene EPHX2 in VCI and control groups. Our findings support a role for sEH and a potential benefit from sEH inhibitors in age-related VCI. PMID:25277097

  6. Are delta-aminolevulinate dehydratase inhibition and metal concentrations additional factors for the age-related cognitive decline?

    PubMed

    Baierle, Marília; Charão, Mariele F; Göethel, Gabriela; Barth, Anelise; Fracasso, Rafael; Bubols, Guilherme; Sauer, Elisa; Campanharo, Sarah C; Rocha, Rafael C C; Saint'Pierre, Tatiana D; Bordignon, Suelen; Zibetti, Murilo; Trentini, Clarissa M; Avila, Daiana S; Gioda, Adriana; Garcia, Solange C

    2014-01-01

    Aging is often accompanied by cognitive impairments and influenced by oxidative status and chemical imbalances. Thus, this study was conducted to examine whether age-related cognitive deficit is associated with oxidative damage, especially with inhibition of the enzyme delta-aminolevulinate dehydratase (ALA-D), as well as to verify the influence of some metals in the enzyme activity and cognitive performance. Blood ALA-D activity, essential (Fe, Zn, Cu, Se) and non-essential metals (Pb, Cd, Hg, As, Cr, Ni, V) were measured in 50 elderly and 20 healthy young subjects. Cognitive function was assessed by tests from Consortium to Establish a Registry for Alzheimer's Disease (CERAD) battery and other. The elderly group presented decreased ALA-D activity compared to the young group. The index of ALA-D reactivation was similar to both study groups, but negatively associated with metals. The mean levels of essential metals were within the reference values, while the most toxic metals were above them in both groups. Cognitive function impairments were observed in elderly group and were associated with decreased ALA-D activity, with lower levels of Se and higher levels of toxic metals (Hg and V). Results suggest that the reduced ALA-D activity in elderly can be an additional factor involved in cognitive decline, since its inhibition throughout life could lead to accumulation of the neurotoxic compound ALA. Toxic metals were found to contribute to cognitive decline and also to influence ALA-D reactivation. PMID:25329536

  7. Computer Simulations of Loss of Organization of Neurons as a Model for Age-related Cognitive Decline

    NASA Astrophysics Data System (ADS)

    Cruz, Luis; Fengometidis, Elene; Jones, Frank; Jampani, Srinivas

    2011-03-01

    In normal aging, brains suffer from progressive cognitive decline not linked with loss of neurons common in neurodegenerative disorders such as Alzheimer's disease. However, in some brain areas neurons have lost positional organization specifically within microcolumns: arrays of interconnected neurons which may constitute fundamental computational units in the brain. This age-related loss of organization, likely a result of micron-sized random displacements in neuronal positions, is hypothesized to be a by-product of the loss of support from the surrounding medium, including dendrites. Using a dynamical model applied to virtual 3D representation of neuronal arrangements, that previously showed loss of organization in brains of cognitively tested rhesus monkeys, the relationship between these displacements and changes to the surrounding dendrite network are presented. The consequences of these displacements on the structure of the dendritic network, with possible disruptions in signal synchrony important to cognitive function, are discussed. NIH R01AG021133.

  8. Age-Related Decline in Cognitive Pain Modulation Induced by Distraction: Evidence From Event-Related Potentials.

    PubMed

    Zhou, Shu; Després, Olivier; Pebayle, Thierry; Dufour, André

    2015-09-01

    Distraction is known to reduce perceived pain but not always efficiently. Overlapping cognitive resources play a role in both pain processing and executive functions. We hypothesized that with aging, the analgesic effects of cognitive modulation induced by distraction would be reduced as a result of functional decline of frontal networks. Twenty-eight elderly and 28 young participants performed a tonic heat pain test with and without distraction (P + D vs P condition), and 2 executive tasks involving the frontal network (1-back [working memory] and go/no-go [response inhibition]), during which event-related potentials were recorded. A significant age-related difference in modulatory effect was observed during the pain-distraction test, with the older group reporting higher pain perception than the younger group during the P + D than during the P condition. Greater brain activity of early processes (P2 component) in both go/no-go and 1-back tasks correlated with less perceived pain during distraction in younger participants. For later processes, more cognitive control and attentional resources (increased N2 and P3 amplitude) needed for working memory processes were associated with greater pain perception in the older group. Inhibition processes were related to conscious distraction estimation in both groups. These findings indicate that cognitive processes subtended by resources in the frontal network, particularly working memory processes, are elicited more in elderly than in younger individuals for pain tolerance when an irrelevant task is performed simultaneously. Perspective: This study suggests that age-related declines in pain modulation are caused by functional degeneration of frontal cerebral networks, which may contribute to a higher prevalence of chronic pain. Analyzing the impact of frontal network function on pain modulation may assist in the development of more effective targeted treatment plans. PMID:26080043

  9. Age-Related Declines in General Cognitive Abilities of Balb/C Mice and General Activity Are Associated with Disparities in Working Memory, Body Weight, and General Activity

    ERIC Educational Resources Information Center

    Matzel, Louis D.; Grossman, Henya; Light, Kenneth; Townsend, David; Kolata, Stefan

    2008-01-01

    A defining characteristic of age-related cognitive decline is a deficit in general cognitive performance. Here we use a testing and analysis regimen that allows us to characterize the general learning abilities of young (3-5 mo old) and aged (19-21 mo old) male and female Balb/C mice. Animals' performance was assessed on a battery of seven diverse…

  10. Over the hill at 24: persistent age-related cognitive-motor decline in reaction times in an ecologically valid video game task begins in early adulthood.

    PubMed

    Thompson, Joseph J; Blair, Mark R; Henrey, Andrew J

    2014-01-01

    Typically studies of the effects of aging on cognitive-motor performance emphasize changes in elderly populations. Although some research is directly concerned with when age-related decline actually begins, studies are often based on relatively simple reaction time tasks, making it impossible to gauge the impact of experience in compensating for this decline in a real world task. The present study investigates age-related changes in cognitive motor performance through adolescence and adulthood in a complex real world task, the real-time strategy video game StarCraft 2. In this paper we analyze the influence of age on performance using a dataset of 3,305 players, aged 16-44, collected by Thompson, Blair, Chen & Henrey [1]. Using a piecewise regression analysis, we find that age-related slowing of within-game, self-initiated response times begins at 24 years of age. We find no evidence for the common belief expertise should attenuate domain-specific cognitive decline. Domain-specific response time declines appear to persist regardless of skill level. A second analysis of dual-task performance finds no evidence of a corresponding age-related decline. Finally, an exploratory analyses of other age-related differences suggests that older participants may have been compensating for a loss in response speed through the use of game mechanics that reduce cognitive load. PMID:24718593

  11. Over the Hill at 24: Persistent Age-Related Cognitive-Motor Decline in Reaction Times in an Ecologically Valid Video Game Task Begins in Early Adulthood

    PubMed Central

    Thompson, Joseph J.; Blair, Mark R.; Henrey, Andrew J.

    2014-01-01

    Typically studies of the effects of aging on cognitive-motor performance emphasize changes in elderly populations. Although some research is directly concerned with when age-related decline actually begins, studies are often based on relatively simple reaction time tasks, making it impossible to gauge the impact of experience in compensating for this decline in a real world task. The present study investigates age-related changes in cognitive motor performance through adolescence and adulthood in a complex real world task, the real-time strategy video game StarCraft 2. In this paper we analyze the influence of age on performance using a dataset of 3,305 players, aged 16-44, collected by Thompson, Blair, Chen & Henrey [1]. Using a piecewise regression analysis, we find that age-related slowing of within-game, self-initiated response times begins at 24 years of age. We find no evidence for the common belief expertise should attenuate domain-specific cognitive decline. Domain-specific response time declines appear to persist regardless of skill level. A second analysis of dual-task performance finds no evidence of a corresponding age-related decline. Finally, an exploratory analyses of other age-related differences suggests that older participants may have been compensating for a loss in response speed through the use of game mechanics that reduce cognitive load. PMID:24718593

  12. Computer-Based Cognitive Programs for Improvement of Memory, Processing Speed and Executive Function during Age-Related Cognitive Decline: A Meta-Analysis

    PubMed Central

    Shao, Yan-kun; Mang, Jing; Li, Pei-lan; Wang, Jie; Deng, Ting; Xu, Zhong-xin

    2015-01-01

    Background Several studies have assessed the effects of computer-based cognitive programs (CCP) in the management of age-related cognitive decline, but the role of CCP remains controversial. Therefore, this systematic review evaluated the evidence on the efficacy of CCP for age-related cognitive decline in healthy older adults. Methods Six electronic databases (through October 2014) were searched. The risk of bias was assessed using the Cochrane Collaboration tool. The standardized mean difference (SMD) and 95% confidence intervals (CI) of a random-effects model were calculated. The heterogeneity was assessed using the Cochran Q statistic and quantified with the I2 index. Results Twelve studies were included in the current review and were considered as moderate to high methodological quality. The aggregated results indicate that CCP improves memory performance (SMD, 0.31; 95% CI 0.16 to 0.45; p < 0.0001) and processing speed (SMD, 0.50; 95% CI 0.14 to 0.87; p = 0.007) but not executive function (SMD, -0.12; 95% CI -0.33 to 0.09; p = 0.27). Furthermore, there were long-term gains in memory performance (SMD, 0.59; 95% CI 0.13 to 1.05; p = 0.01). Conclusion CCP may be a valid complementary and alternative therapy for age-related cognitive decline, especially for memory performance and processing speed. However, more studies with longer follow-ups are warranted to confirm the current findings. PMID:26098943

  13. Hearing, Cognition, and Healthy Aging: Social and Public Health Implications of the Links between Age-Related Declines in Hearing and Cognition.

    PubMed

    Pichora-Fuller, M Kathleen; Mick, Paul; Reed, Marilyn

    2015-08-01

    Sensory input provides the signals used by the brain when listeners understand speech and participate in social activities with other people in a range of everyday situations. When sensory inputs are diminished, there can be short-term consequences to brain functioning, and long-term deprivation can affect brain neuroplasticity. Indeed, the association between hearing loss and cognitive declines in older adults is supported by experimental and epidemiologic evidence, although the causal mechanisms remain unknown. These interactions of auditory and cognitive aging play out in the challenges confronted by people with age-related hearing problems when understanding speech and engaging in social interactions. In the present article, we use the World Health Organization's International Classification of Functioning, Disability and Health and the Selective Optimization with Compensation models to highlight the importance of adopting a healthy aging perspective that focuses on facilitating active social participation by older adults. First, we examine epidemiologic evidence linking ARHL to cognitive declines and other health issues. Next, we examine how social factors influence and are influenced by auditory and cognitive aging and if they may provide a possible explanation for the association between ARHL and cognitive decline. Finally, we outline how audiologists could reposition hearing health care within the broader context of healthy aging. PMID:27516713

  14. Hearing, Cognition, and Healthy Aging: Social and Public Health Implications of the Links between Age-Related Declines in Hearing and Cognition

    PubMed Central

    Pichora-Fuller, M. Kathleen; Mick, Paul; Reed, Marilyn

    2015-01-01

    Sensory input provides the signals used by the brain when listeners understand speech and participate in social activities with other people in a range of everyday situations. When sensory inputs are diminished, there can be short-term consequences to brain functioning, and long-term deprivation can affect brain neuroplasticity. Indeed, the association between hearing loss and cognitive declines in older adults is supported by experimental and epidemiologic evidence, although the causal mechanisms remain unknown. These interactions of auditory and cognitive aging play out in the challenges confronted by people with age-related hearing problems when understanding speech and engaging in social interactions. In the present article, we use the World Health Organization's International Classification of Functioning, Disability and Health and the Selective Optimization with Compensation models to highlight the importance of adopting a healthy aging perspective that focuses on facilitating active social participation by older adults. First, we examine epidemiologic evidence linking ARHL to cognitive declines and other health issues. Next, we examine how social factors influence and are influenced by auditory and cognitive aging and if they may provide a possible explanation for the association between ARHL and cognitive decline. Finally, we outline how audiologists could reposition hearing health care within the broader context of healthy aging. PMID:27516713

  15. Hippocampal expression of myelin-associated inhibitors is induced with age-related cognitive decline and correlates with deficits of spatial learning and memory

    PubMed Central

    VanGuilder, Heather D.; Bixler, Georgina V.; Sonntag, William E.; Freeman, Willard M.

    2012-01-01

    Impairment of cognitive functions including hippocampus-dependent spatial learning and memory affects nearly half of the aged population. Age-related cognitive decline is associated with synaptic dysfunction that occurs in the absence of neuronal cell loss, suggesting that impaired neuronal signaling and plasticity may underlie age-related deficits of cognitive function. Expression of myelin-associated inhibitors (MAIs) of synaptic plasticity, including the ligands MAG, Nogo-A, and OMgp, and their common receptor, NgR1, was examined in hippocampal synaptosomes and CA1, CA3 and DG subregions derived from adult (12–13 months) and aged (26–28 months) Fischer 344 × Brown Norway rats. Rats were behaviorally phenotyped by Morris water maze testing and classified as aged cognitively intact (n=7–8) or aged cognitively impaired (n=7–10) relative to adults (n=5–7). MAI protein expression was induced in cognitively impaired, but not cognitively intact, aged rats and correlated with cognitive performance in individual rats. Immunohistochemical experiments demonstrated that upregulation of MAIs occurs, in part, in hippocampal neuronal axons and somata. While a number of pathways and processes are altered with brain aging, we report a coordinated induction of myelin-associated inhibitors of functional and structural plasticity only in cognitively impaired aged rats. Induction of MAIs may decrease stimulus-induced synaptic strengthening and structural remodeling, ultimately impairing synaptic mechanisms of spatial learning and memory and resulting in cognitive decline. PMID:22269040

  16. Beneficial effects of multisensory and cognitive stimulation on age-related cognitive decline in long-term-care institutions

    PubMed Central

    De Oliveira, Thaís Cristina Galdino; Soares, Fernanda Cabral; De Macedo, Liliane Dias E Dias; Diniz, Domingos Luiz Wanderley Picanço; Bento-Torres, Natáli Valim Oliver; Picanço-Diniz, Cristovam Wanderley

    2014-01-01

    The aim of the present report was to evaluate the effectiveness and impact of multisensory and cognitive stimulation on improving cognition in elderly persons living in long-term-care institutions (institutionalized [I]) or in communities with their families (noninstitutionalized [NI]). We compared neuropsychological performance using language and Mini-Mental State Examination (MMSE) test scores before and after 24 and 48 stimulation sessions. The two groups were matched by age and years of schooling. Small groups of ten or fewer volunteers underwent the stimulation program, twice a week, over 6 months (48 sessions in total). Sessions were based on language and memory exercises, as well as visual, olfactory, auditory, and ludic stimulation, including music, singing, and dance. Both groups were assessed at the beginning (before stimulation), in the middle (after 24 sessions), and at the end (after 48 sessions) of the stimulation program. Although the NI group showed higher performance in all tasks in all time windows compared with I subjects, both groups improved their performance after stimulation. In addition, the improvement was significantly higher in the I group than the NI group. Language tests seem to be more efficient than the MMSE to detect early changes in cognitive status. The results suggest the impoverished environment of long-term-care institutions may contribute to lower cognitive scores before stimulation and the higher improvement rate of this group after stimulation. In conclusion, language tests should be routinely adopted in the neuropsychological assessment of elderly subjects, and long-term-care institutions need to include regular sensorimotor, social, and cognitive stimulation as a public health policy for elderly persons. PMID:24600211

  17. Beneficial effects of multisensory and cognitive stimulation on age-related cognitive decline in long-term-care institutions.

    PubMed

    De Oliveira, Thaís Cristina Galdino; Soares, Fernanda Cabral; De Macedo, Liliane Dias E Dias; Diniz, Domingos Luiz Wanderley Picanço; Bento-Torres, Natáli Valim Oliver; Picanço-Diniz, Cristovam Wanderley

    2014-01-01

    The aim of the present report was to evaluate the effectiveness and impact of multisensory and cognitive stimulation on improving cognition in elderly persons living in long-term-care institutions (institutionalized [I]) or in communities with their families (noninstitutionalized [NI]). We compared neuropsychological performance using language and Mini-Mental State Examination (MMSE) test scores before and after 24 and 48 stimulation sessions. The two groups were matched by age and years of schooling. Small groups of ten or fewer volunteers underwent the stimulation program, twice a week, over 6 months (48 sessions in total). Sessions were based on language and memory exercises, as well as visual, olfactory, auditory, and ludic stimulation, including music, singing, and dance. Both groups were assessed at the beginning (before stimulation), in the middle (after 24 sessions), and at the end (after 48 sessions) of the stimulation program. Although the NI group showed higher performance in all tasks in all time windows compared with I subjects, both groups improved their performance after stimulation. In addition, the improvement was significantly higher in the I group than the NI group. Language tests seem to be more efficient than the MMSE to detect early changes in cognitive status. The results suggest the impoverished environment of long-term-care institutions may contribute to lower cognitive scores before stimulation and the higher improvement rate of this group after stimulation. In conclusion, language tests should be routinely adopted in the neuropsychological assessment of elderly subjects, and long-term-care institutions need to include regular sensorimotor, social, and cognitive stimulation as a public health policy for elderly persons. PMID:24600211

  18. Age-related decline in verbal learning is moderated by demographic factors, working memory capacity, and presence of amnestic mild cognitive impairment.

    PubMed

    Constantinidou, Fofi; Zaganas, Ioannis; Papastefanakis, Emmanouil; Kasselimis, Dimitrios; Nidos, Andreas; Simos, Panagiotis G

    2014-09-01

    Age-related memory changes are highly varied and heterogeneous. The study examined the rate of decline in verbal episodic memory as a function of education level, auditory attention span and verbal working memory capacity, and diagnosis of amnestic mild cognitive impairment (a-MCI). Data were available on a community sample of 653 adults aged 17-86 years and 70 patients with a-MCI recruited from eight broad geographic areas in Greece and Cyprus. Measures of auditory attention span and working memory capacity (digits forward and backward) and verbal episodic memory (Auditory Verbal Learning Test [AVLT]) were used. Moderated mediation regressions on data from the community sample did not reveal significant effects of education level on the rate of age-related decline in AVLT indices. The presence of a-MCI was a significant moderator of the direct effect of Age on both immediate and delayed episodic memory indices. The rate of age-related decline in verbal episodic memory is normally mediated by working memory capacity. Moreover, in persons who display poor episodic memory capacity (a-MCI group), age-related memory decline is expected to advance more rapidly for those who also display relatively poor verbal working memory capacity. PMID:25156204

  19. Age-related cognitive decline and electroencephalogram slowing in Down's syndrome as a model of Alzheimer's disease.

    PubMed

    Soininen, H; Partanen, J; Jousmäki, V; Helkala, E L; Vanhanen, M; Majuri, S; Kaski, M; Hartikainen, P; Riekkinen, P

    1993-03-01

    We studied quantitative electroencephalogram and neuropsychological performance in an aging series of 31 patients with Down's syndrome and compared the findings with those of 36 patients with probable Alzheimer's disease and age-matched controls. We found an age-related decline of cortical functions and slowing of the electroencephalogram in Down's syndrome patients aged from 20 to 60 years. Slowing of the electroencephalogram, i.e. the decrease of the peak frequency, was significantly related to Mini-Mental status scores, and visual, praxic and speech functions, as well as memory in the Down patients, similar to the Alzheimer patients. Similar correlations were not demonstrated for young or elderly controls. This study provides neuropsychological and electrophysiological data to suggest that studying Down's syndrome patients of different ages can serve as a model for progression of Alzheimer's disease. PMID:8469312

  20. Long-term moderate alcohol consumption does not exacerbate age-related cognitive decline in healthy, community-dwelling older adults

    PubMed Central

    Moussa, Malaak N.; Simpson, Sean L.; Mayhugh, Rhiannon E.; Grata, Michelle E.; Burdette, Jonathan H.; Porrino, Linda J.; Laurienti, Paul J.

    2015-01-01

    Recent census data has found that roughly 40% of adults 65 years and older not only consume alcohol but also drink more of it than previous generations. Older drinkers are more vulnerable than younger counterparts to the psychoactive effects of alcohol due to natural biological changes that occur with aging. This study was specifically designed to measure the effect of long-term moderate alcohol consumption on cognitive health in older adult drinkers. An extensive battery of validated tests commonly used in aging and substance use literature was used to measure performance in specific cognitive domains, including working memory and attention. An age (young, old) * alcohol consumption (light, moderate) factorial study design was used to evaluate the main effects of age and alcohol consumption on cognitive performance. The focus of the study was then limited to light and moderate older drinkers, and whether or not long-term moderate alcohol consumption exacerbated age-related cognitive decline. No evidence was found to support the idea that long-term moderate alcohol consumption in older adults exacerbates age-related cognitive decline. Findings were specific to healthy community dwelling social drinkers in older age and they should not be generalized to individuals with other consumption patterns, like heavy drinkers, binge drinkers or ex-drinkers. PMID:25601835

  1. Sex-dependent modulation of age-related cognitive decline by the L-type calcium channel gene Cacna1c (Cav 1.2).

    PubMed

    Zanos, Panos; Bhat, Shambhu; Terrillion, Chantelle E; Smith, Robert J; Tonelli, Leonardo H; Gould, Todd D

    2015-10-01

    Increased calcium influx through L-type voltage-gated calcium channels has been implicated in the neuronal dysfunction underlying age-related memory declines. The present study aimed to test the specific role of Cacna1c (which encodes Cav 1.2) in modulating age-related memory dysfunction. Short-term, spatial and contextual/emotional memory was evaluated in young and aged, wild-type as well as mice with one functional copy of Cacna1c (haploinsufficient), using the novel object recognition, Y-maze and passive avoidance tasks, respectively. Hippocampal expression of Cacna1c mRNA was measured by quantitative polymerase chain reaction. Ageing was associated with object recognition and contextual/emotional memory deficits, and a significant increase in hippocampal Cacna1c mRNA expression. Cacna1c haploinsufficiency was associated with decreased Cacna1c mRNA expression in both young and old animals. However, haploinsufficient mice did not manifest an age-related increase in expression of this gene. Behaviourally, Cacna1c haploinsufficiency prevented object recognition deficits during ageing in both male and female mice. A significant correlation between higher Cacna1c levels and decreased object recognition performance was observed in both sexes. Also, a sex-dependent protective role of decreased Cacna1c levels in contextual/emotional memory loss has been observed, specifically in male mice. These data provide evidence for an association between increased hippocampal Cacna1c expression and age-related cognitive decline. Additionally, they indicate an interaction between the Cacna1c gene and sex in the modulation of age-related contextual memory declines. PMID:25989111

  2. Alzheimer's disease and age-related memory decline (preclinical).

    PubMed

    Terry, Alvin V; Callahan, Patrick M; Hall, Brandon; Webster, Scott J

    2011-08-01

    An unfortunate result of the rapid rise in geriatric populations worldwide is the increasing prevalence of age-related cognitive disorders such as Alzheimer's disease (AD). AD is a devastating neurodegenerative illness that is characterized by a profound impairment of cognitive function, marked physical disability, and an enormous economic burden on the afflicted individual, caregivers, and society in general. The rise in elderly populations is also resulting in an increase in individuals with related (potentially treatable) conditions such as "Mild Cognitive Impairment" (MCI) which is characterized by a less severe (but abnormal) level of cognitive impairment and a high-risk for developing dementia. Even in the absence of a diagnosable disorder of cognition (e.g., AD and MCI), the perception of increased forgetfulness and declining mental function is a clear source of apprehension in the elderly. This is a valid concern given that even a modest impairment of cognitive function is likely to be associated with significant disability in a rapidly evolving, technology-based society. Unfortunately, the currently available therapies designed to improve cognition (i.e., for AD and other forms of dementia) are limited by modest efficacy and adverse side effects, and their effects on cognitive function are not sustained over time. Accordingly, it is incumbent on the scientific community to develop safer and more effective therapies that improve and/or sustain cognitive function in the elderly allowing them to remain mentally active and productive for as long as possible. As diagnostic criteria for memory disorders evolve, the demand for pro-cognitive therapeutic agents is likely to surpass AD and dementia to include MCI and potentially even less severe forms of memory decline. The purpose of this review is to provide an overview of the contemporary therapeutic targets and preclinical pharmacologic approaches (with representative drug examples) designed to enhance memory

  3. Flavonoid Chrysin prevents age-related cognitive decline via attenuation of oxidative stress and modulation of BDNF levels in aged mouse brain.

    PubMed

    Souza, Leandro Cattelan; Antunes, Michelle Silva; Filho, Carlos Borges; Del Fabbro, Lucian; de Gomes, Marcelo Gomes; Goes, André Tiago Rossito; Donato, Franciele; Prigol, Marina; Boeira, Silvana Peterini; Jesse, Cristiano R

    2015-07-01

    In this study, the effect of Chrysin (5,7-dihydroxyflavone), an important member of the flavonoid family, on memory impairment, oxidative stress and BDNF reduction generated by aging in mice were investigated. Young and aged mice were treated daily per 60days with Chrysin (1 and 10mg/kg; per oral, p.o.) or veichle (10ml/kg; p.o.). Mice were trained and tested in Morris Water Maze task. After the behavioural test, the levels of reactive species (RS), the activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), as well as the activity of Na(+), K(+)-ATPase and the levels of brain-derived neurotrophic factor (BDNF) were determined in the prefrontal cortex (PFC) and hippocampus (HC) of mice. Results demonstrated that the age-related memory decline was partially protected by Chrysin at a dose of 1mg/kg, and normalized at the dose of 10mg/kg (p<0.001). Treatment with Chrysin significantly attenuated the increase of RS levels and the inhibition of SOD, CAT and GPx activities of aged mice. Inhibition of Na(+), K(+)-ATPase activity in PFC and HP of aged mice was also attenuated by Chrysin treatment. Moreover, Chrysin marked mitigated the decrease of BDNF levels in the PFC and HC of aged mice. These results demonstrated that flavonoid Chrysin, an antioxidant compound, was able to prevent age-associated memory probably by their free radical scavenger action and modulation of BDNF production. Thus, this study indicates that Chrysin may represent a new pharmacological approach to alleviate the age-related declines during normal age, acting as an anti-aging agent. PMID:25931267

  4. The suprachiasmatic nucleus: age-related decline in biological rhythms.

    PubMed

    Nakamura, Takahiro J; Takasu, Nana N; Nakamura, Wataru

    2016-09-01

    Aging is associated with changes in sleep duration and quality, as well as increased rates of pathologic/disordered sleep. While several factors contribute to these changes, emerging research suggests that age-related changes in the mammalian central circadian clock within the suprachiasmatic nucleus (SCN) may be a key factor. Prior work from our group suggests that circadian output from the SCN declines because of aging. Furthermore, we have previously observed age-related infertility in female mice, caused by a mismatch between environmental light-dark cycles and the intrinsic, internal biological clocks. In this review, we address regulatory mechanisms underlying circadian rhythms in mammals and summarize recent literature describing the effects of aging on the circadian system. PMID:26915078

  5. Fertility preservation for age-related fertility decline.

    PubMed

    Stoop, Dominic; Cobo, Ana; Silber, Sherman

    2014-10-01

    Cryopreservation of eggs or ovarian tissue to preserve fertility for patients with cancer has been studied since 1994 with R G Gosden's paper describing restoration of fertility in oophorectomised sheep, and for decades previously by others in smaller mammals. Clinically this approach has shown great success. Many healthy children have been born from eggs cryopreserved with the Kuwayama egg vitrification technique for non-medical (social) indications, but until now very few patients with cancer have achieved pregnancy with cryopreserved eggs. Often, oncologists do not wish to delay cancer treatment while the patient goes through multiple ovarian stimulation cycles to retrieve eggs, and the patient can only start using the oocytes after full recovery from cancer. Ovarian stimulation and egg retrieval is not a barrier for patients without cancer who wish to delay childbearing, which makes oocyte cryopreservation increasingly popular to overcome an age-related decline in fertility. Cryopreservation of ovarian tissue is an option if egg cryopreservation is ruled out. More than 35 babies have been born so far with cryopreserved ovarian tissue in patients with cancer who have had a complete return of hormonal function, and fertility to baseline. Both egg and ovarian tissue cryopreservation might be ready for application to the preservation of fertility not only in patients with cancer but also in countering the increasing incidence of age-related decline in female fertility. PMID:25283572

  6. Age-related difference in relationships between cognitive processing speed and general cognitive status.

    PubMed

    Tam, Helena M K; Lam, Charlene L M; Huang, Haixia; Wang, Baolan; Lee, Tatia M C

    2015-01-01

    General cognitive status (GCS) is a composite of cognitive abilities reflecting full function. The literature suggests a relationship between cognitive processing speed and GCS, as well as age-related changes of processing speed on cognitive performance. Therefore, this study recruited 34 younger and 39 older adults to verify age-related differences in relationships between cognitive processing speed and GCS. We measured cognitive processing speed with the Processing Speed Index of the Wechsler Adult Intelligence Scale. Findings indicated that cognitive processing speed predicted GCS in older but not younger adults. Future research may be needed to verify the training effect of processing speed on GCS. This study also further examined cognitive factors related to processing speed in aging and the relationships between cognitive processing speed and verbal fluency, cognitive inhibition, and divided attention. A stepwise regression analysis indicated that only verbal fluency contributed significantly to cognitive processing speed in older adults, accounting for 21% of the variance. These observations suggest that age-related changes of prefrontal regions may not fully explain age-related decline in cognitive processing speed. PMID:24927241

  7. Epigenetic modification of PKMζ rescues aging-related cognitive impairment

    PubMed Central

    Chen, Chen; Meng, Shi-Qiu; Xue, Yan-Xue; Han, Ying; Sun, Cheng-Yu; Deng, Jia-Hui; Chen, Na; Bao, Yan-Ping; Zhang, Fei-Long; Cao, Lin-Lin; Zhu, Wei-Guo; Shi, Jie; Song, Wei-Hong; Lu, Lin

    2016-01-01

    Cognition is impacted by aging. However, the mechanisms that underlie aging-associated cognitive impairment are unclear. Here we showed that cognitive decline in aged rats was associated with changes in DNA methylation of protein kinase Mζ (PKMζ) in the prelimbic cortex (PrL). PKMζ is a crucial molecule involved in the maintenance of long-term memory. Using different behavioral models, we confirmed that aged rats exhibited cognitive impairment in memory retention test 24 h after training, and overexpression of PKMζ in the PrL rescued cognitive impairment in aged rats. After fear conditioning, the protein levels of PKMζ and the membrane expression of GluR2 increased in the PrL in young and adult rats but not in aged rats, and the levels of methylated PKMζ DNA in the PrL decreased in all age groups, whereas the levels of unmethylated PKMζ DNA increased only in young and adult rats. We also found that environmentally enriched housing reversed the hypermethylation of PKMζ and restored cognitive performance in aged rats. Inactivation of PKMζ prevented the potentiating effects of environmental enrichment on memory retention in aged rats. These results indicated that PKMζ might be a potential target for the treatment of aging-related cognitive impairment, suggesting a potential therapeutic avenue. PMID:26926225

  8. Shared and Unique Genetic and Environmental Influences on Aging-Related Changes in Multiple Cognitive Abilities

    ERIC Educational Resources Information Center

    Tucker-Drob, Elliot M.; Reynolds, Chandra A.; Finkel, Deborah; Pedersen, Nancy L.

    2014-01-01

    Aging-related declines occur in many different domains of cognitive function during middle and late adulthood. However, whether a global dimension underlies individual differences in changes in different domains of cognition and whether global genetic influences on cognitive changes exist is less clear. We addressed these issues by applying…

  9. The senescence-accelerated prone mouse (SAMP8): a model of age-related cognitive decline with relevance to alterations of the gene expression and protein abnormalities in Alzheimer's disease.

    PubMed

    Butterfield, D Allan; Poon, H Fai

    2005-10-01

    The senescence-accelerated mouse (SAM) is an accelerated aging model that was established through phenotypic selection from a common genetic pool of AKR/J strain of mice. The SAM model was established in 1981, including nine major senescence-accelerated mouse prone (SAMP) substrains and three major senescence-accelerated mouse resistant (SAMR) substrains, each of which exhibits characteristic disorders. Recently, SAMP8 have drawn attention in gerontological research due to its characteristic learning and memory deficits at old age. Many recent reports provide insight into mechanisms of the cognitive impairment and pathological changes in SAMP8. Therefore, this mini review examines the recent findings of SAMP8 mice abnormalities at the gene and protein levels. The genes and proteins described in this review are functionally categorized into neuroprotection, signal transduction, protein folding/degradation, cytoskeleton/transport, immune response and reactive oxygen species (ROS) production. All of these processes are involved in learning and memory. Although these studies provide insight into the mechanisms that contribute to the learning and memory decline in aged SAMP8 mice, higher throughput techniques of proteomics and genomics are necessary to study the alterations of gene expression and protein abnormalities in SAMP8 mice brain in order to more completely understand the central nervous system dysfunction in this mouse model. The SAMP8 is a good animal model to investigate the fundamental mechanisms of age-related learning and memory deficits at the gene and protein levels. PMID:16026957

  10. Age-related decline in global form suppression.

    PubMed

    Wiegand, Iris; Finke, Kathrin; Töllner, Thomas; Starman, Kornelija; Müller, Hermann J; Conci, Markus

    2015-12-01

    Visual selection of illusory 'Kanizsa' figures, an assembly of local elements that induce the percept of a whole object, is facilitated relative to configurations composed of the same local elements that do not induce a global form--an instance of 'global precedence' in visual processing. Selective attention, i.e., the ability to focus on relevant and ignore irrelevant information, declines with increasing age; however, how this deficit affects selection of global vs. local configurations remains unknown. On this background, the present study examined for age-related differences in a global-local task requiring selection of either a 'global' Kanizsa- or a 'local' non-Kanizsa configuration (in the presence of the respectively other configuration) by analyzing event-related lateralizations (ERLs). Behaviorally, older participants showed a more pronounced global-precedence effect. Electrophysiologically, this effect was accompanied by an early (150-225 ms) 'positivity posterior contralateral' (PPC), which was elicited for older, but not younger, participants, when the target was a non-Kanizsa configuration and the Kanizsa figure a distractor (rather than vice versa). In addition, timing differences in the subsequent (250-500 ms) posterior contralateral negativity (PCN) indicated that attentional resources were allocated faster to Kanizsa, as compared to non-Kanizsa, targets in both age groups, while the allocation of spatial attention seemed to be generally delayed in older relative to younger age. Our results suggest that the enhanced global-local asymmetry in the older age group originated from less effective suppression of global distracter forms on early processing stages--indicative of older observers having difficulties with disengaging from a global default selection mode and switching to the required local state of attentional resolution. PMID:26498865

  11. Age-related decline of precision and binding in visual working memory.

    PubMed

    Peich, Muy-Cheng; Husain, Masud; Bays, Paul M

    2013-09-01

    Working memory declines with normal aging, but the nature of this impairment is debated. Studies based on detecting changes to arrays of visual objects have identified two possible components to age-related decline: a reduction in the number of items that can be stored, or a deficit in maintaining the associations (bindings) between individual object features. However, some investigations have reported intact binding with aging, and specific deficits arising only in Alzheimer's disease. Here, using a recently developed continuous measure of recall fidelity, we tested the precision with which adults of different ages could reproduce from memory the orientation and color of a probed array item. The results reveal a further component of cognitive decline: an age-related decrease in the resolution with which visual information can be maintained in working memory. This increase in recall variability with age was strongest under conditions of greater memory load. Moreover, analysis of the distribution of errors revealed that older participants were more likely to incorrectly report one of the unprobed items in memory, consistent with an age-related increase in misbinding. These results indicate a systematic decline with age in working memory resources that can be recruited to store visual information. The paradigm presented here provides a sensitive index of both memory resolution and feature binding, with the potential for assessing their modulation by interventions. The findings have implications for understanding the mechanisms underpinning working memory deficits in both health and disease. PMID:23978008

  12. Young and Older Adults’ Beliefs about Effective Ways to Mitigate Age-Related Memory Decline

    PubMed Central

    Horhota, Michelle; Lineweaver, Tara; Ositelu, Monique; Summers, Kristi; Hertzog, Christopher

    2013-01-01

    This study investigated whether young and older adults vary in their beliefs about the impact of various mitigating factors on age-related memory decline. Eighty young (ages 18–23) and eighty older (ages 60–82) participants reported their beliefs about their own memory abilities and the strategies that they use in their everyday lives to attempt to control their memory. Participants also reported their beliefs about memory change with age for hypothetical target individuals who were described as using (or not using) various means to mitigate memory decline. There were no age differences in personal beliefs about control over current or future memory ability. However, the two age groups differed in the types of strategies they used in their everyday life to control their memory. Young adults were more likely to use internal memory strategies, whereas older adults were more likely to focus on cognitive exercise and maintaining physical health as ways to optimize their memory ability. There were no age differences in rated memory change across the life span in hypothetical individuals. Both young and older adults perceived strategies related to improving physical and cognitive health as effective means of mitigating memory loss with age, whereas internal memory strategies were perceived as less effective means for controlling age-related memory decline. PMID:22082012

  13. Alzheimer’s Disease and Age-Related Memory Decline (Preclinical)

    PubMed Central

    Terry, Alvin V.; Callahan, Patrick M.; Hall, Brandon; Webster, Scott J.

    2011-01-01

    An unfortunate result of the rapid rise in geriatric populations worldwide is the increasing prevalence of age-related cognitive disorders such as Alzheimer’s disease (AD). AD is a devastating neurodegenerative illness that is characterized by a profound impairment of cognitive function, marked physical disability, and an enormous economic burden on the afflicted individual, caregivers, and society in general. The rise in elderly populations is also resulting in an increase in individuals with related (potentially treatable) conditions such as “Mild Cognitive Impairment” (MCI) which is characterized by a less severe (but abnormal) level of cognitive impairment and a high-risk for developing dementia. Even in the absence of a diagnosable disorder of cognition (e.g., AD, MCI), the perception of increased forgetfulness and declining mental function is a clear source of apprehension in the elderly. This is a valid concern given that even a modest impairment of cognitive function is likely to be associated with significant disability in a rapidly evolving, technology-based society. Unfortunately, the currently available therapies designed to improve cognition (i.e., for AD and other forms of dementia) are limited by modest efficacy, adverse side effects, and their effects on cognitive function are not sustained over time. Accordingly, it is incumbent on the scientific community to develop safer and more effective therapies that improve and/or sustain cognitive function in the elderly allowing them to remain mentally active and productive for as long as possible. As diagnostic criteria for memory disorders evolve, the demand for pro-cognitive therapeutic agents is likely to surpass AD and dementia to include MCI and potentially even less severe forms of memory decline. The purpose of this review is to provide an overview of the contemporary therapeutic targets and preclinical pharmacologic approaches (with representative drug examples) designed to enhance memory

  14. Blueberry-enriched diet ameliorates age-related declines in NMDA receptor-dependent LTP

    PubMed Central

    Bickford, Paula C.; Browning, Michael D.

    2008-01-01

    NMDA receptor-dependent long-term potentiation (LTP) in the hippocampus is widely accepted as a cellular substrate for memory formation. Age-related declines in the expression of both NMDAR-dependent LTP and NMDAR subunit proteins in the CA1 region of the hippocampus have been well characterized and likely underlie age-related memory impairment. In the current study, we examined NMDAR-dependent LTP in young Fischer 344 rats (4 months old) and aged rats (24 months old) given either a control diet or a diet supplemented with blueberry extract for 6–8 weeks. NMDAR-dependent LTP was evoked by high-frequency stimulation (HFS) in the presence of nifedipine, to eliminate voltage-gated calcium channel LTP. Field excitatory postsynaptic potentials (fEPSPs) were increased by 57% 1 h after HFS in young animals, but this potentiation was reduced to 31% in aged animals. Supplementation of the diet with blueberry extract elevated LTP (63%) in aged animals to levels seen in young. The normalization of LTP may be due to the blueberry diet preventing a decline in synaptic strength, as measured by the slope of the fEPSP for a given fiber potential. The blueberry diet did not prevent age-related declines in NMDAR protein expression. However, phosphorylation of a key tyrosine residue on the NR2B subunit, important for increasing NMDAR function, was enhanced by the diet, suggesting that an increase in NMDAR function might overcome the loss in protein. This report provides evidence that dietary alterations later in life may prevent or postpone the cognitive declines associated with aging. PMID:19424850

  15. Motor Skills Enhance Procedural Memory Formation and Protect against Age-Related Decline.

    PubMed

    Müller, Nils C J; Genzel, Lisa; Konrad, Boris N; Pawlowski, Marcel; Neville, David; Fernández, Guillén; Steiger, Axel; Dresler, Martin

    2016-01-01

    The ability to consolidate procedural memories declines with increasing age. Prior knowledge enhances learning and memory consolidation of novel but related information in various domains. Here, we present evidence that prior motor experience-in our case piano skills-increases procedural learning and has a protective effect against age-related decline for the consolidation of novel but related manual movements. In our main experiment, we tested 128 participants with a sequential finger-tapping motor task during two sessions 24 hours apart. We observed enhanced online learning speed and offline memory consolidation for piano players. Enhanced memory consolidation was driven by a strong effect in older participants, whereas younger participants did not benefit significantly from prior piano experience. In a follow up independent control experiment, this compensatory effect of piano experience was not visible after a brief offline period of 30 minutes, hence requiring an extended consolidation window potentially involving sleep. Through a further control experiment, we rejected the possibility that the decreased effect in younger participants was caused by training saturation. We discuss our results in the context of the neurobiological schema approach and suggest that prior experience has the potential to rescue memory consolidation from age-related cognitive decline. PMID:27333186

  16. Motor Skills Enhance Procedural Memory Formation and Protect against Age-Related Decline

    PubMed Central

    Müller, Nils C. J.; Genzel, Lisa; Konrad, Boris N.; Pawlowski, Marcel; Neville, David; Fernández, Guillén; Steiger, Axel

    2016-01-01

    The ability to consolidate procedural memories declines with increasing age. Prior knowledge enhances learning and memory consolidation of novel but related information in various domains. Here, we present evidence that prior motor experience–in our case piano skills–increases procedural learning and has a protective effect against age-related decline for the consolidation of novel but related manual movements. In our main experiment, we tested 128 participants with a sequential finger-tapping motor task during two sessions 24 hours apart. We observed enhanced online learning speed and offline memory consolidation for piano players. Enhanced memory consolidation was driven by a strong effect in older participants, whereas younger participants did not benefit significantly from prior piano experience. In a follow up independent control experiment, this compensatory effect of piano experience was not visible after a brief offline period of 30 minutes, hence requiring an extended consolidation window potentially involving sleep. Through a further control experiment, we rejected the possibility that the decreased effect in younger participants was caused by training saturation. We discuss our results in the context of the neurobiological schema approach and suggest that prior experience has the potential to rescue memory consolidation from age-related cognitive decline. PMID:27333186

  17. Age-related decline in differentiated neural responses to rare target versus frequent standard stimuli.

    PubMed

    Mott, Katherine K; Alperin, Brittany R; Holcomb, Phillip J; Daffner, Kirk R

    2014-10-31

    One mechanism hypothesized to contribute to cognitive aging is the failure to recruit specialized neural modules and generate differentiated neural responses to various classes of stimuli. Here, ERPs were used to examine the extent to which target and standard stimulus types were processed differently by well-matched adults ages 19-99. Subjects responded to designated visual target letters under low and high load conditions. Temporospatial PCA was used to parse the P3b component, an index of categorization/memory updating. The P3b amplitude difference between targets and standards decreased substantially as a function of age. Dedifferentiation began in middle age, and continued into old-old age. The reduced differentiation of neural responses was driven by an age-related decline in the size of the P3b to targets and an age-related increase in the P3b to standards. Larger P3b amplitude to standards among older subjects was associated with higher executive capacity and better task performance. In summary, dedifferentiation begins relatively early in adulthood and progresses in a linear fashion throughout the lifespan. The age-related augmentation of the P3b to standards appears to reflect a compensatory mechanism that helps maintain task performance. PMID:25171804

  18. Age-related decline in differentiated neural responses to rare target versus frequent standard stimuli

    PubMed Central

    Mott, Katherine K.; Alperin, Brittany R.; Holcomb, Phillip J.; Daffner, Kirk R.

    2014-01-01

    One mechanism hypothesized to contribute to cognitive aging is the failure to recruit specialized neural modules and generate differentiated neural responses to various classes of stimuli. Here, ERPs were used to examine the extent to which target and standard stimulus types were processed differently by well-matched adults ages 19–99. Subjects responded to designated visual target letters under low and high load conditions. Temporospatial PCA was used to parse the P3b component, an index of categorization/memory updating. The P3b amplitude difference between targets and standards decreased substantially as a function of age. Dedifferentiation began in middle age, and continued into old-old age. The reduced differentiation of neural responses was driven by an age-related decline in the size of the P3b to targets and an age-related increase in the P3b to standards. Larger P3b amplitude to standards among older subjects was associated with higher executive capacity and better task performance. In summary, dedifferentiation begins relatively early in adulthood and progresses in a linear fashion throughout the lifespan. The age-related augmentation of the P3b to standards appears to reflect a compensatory mechanism that helps maintain task performance. PMID:25171804

  19. Aging-related episodic memory decline: are emotions the key?

    PubMed Central

    Kinugawa, Kiyoka; Schumm, Sophie; Pollina, Monica; Depre, Marion; Jungbluth, Carolin; Doulazmi, Mohamed; Sebban, Claude; Zlomuzica, Armin; Pietrowsky, Reinhard; Pause, Bettina; Mariani, Jean; Dere, Ekrem

    2013-01-01

    Episodic memory refers to the recollection of personal experiences that contain information on what has happened and also where and when these events took place. Episodic memory function is extremely sensitive to cerebral aging and neurodegerative diseases. We examined episodic memory performance with a novel test in young (N = 17, age: 21–45), middle-aged (N = 16, age: 48–62) and aged but otherwise healthy participants (N = 8, age: 71–83) along with measurements of trait and state anxiety. As expected we found significantly impaired episodic memory performance in the aged group as compared to the young group. The aged group also showed impaired working memory performance as well as significantly decreased levels of trait anxiety. No significant correlation between the total episodic memory and trait or state anxiety scores was found. The present results show an age-dependent episodic memory decline along with lower trait anxiety in the aged group. Yet, it still remains to be determined whether this difference in anxiety is related to the impaired episodic memory performance in the aged group. PMID:23378831

  20. Aging-associated formaldehyde-induced norepinephrine deficiency contributes to age-related memory decline.

    PubMed

    Mei, Yufei; Jiang, Chun; Wan, You; Lv, Jihui; Jia, Jianping; Wang, Xiaomin; Yang, Xu; Tong, Zhiqian

    2015-08-01

    A norepinephrine (NE) deficiency has been observed in aged rats and in patients with Alzheimer's disease and is thought to cause cognitive disorder. Which endogenous factor induces NE depletion, however, is largely unknown. In this study, we investigated the effects of aging-associated formaldehyde (FA) on the inactivation of NE in vitro and in vivo, and on memory behaviors in rodents. The results showed that age-related DNA demethylation led to hippocampal FA accumulation, and when this occurred, the hippocampal NE content was reduced in healthy male rats of different ages. Furthermore, biochemical analysis revealed that FA rapidly inactivated NE in vitro and that an intrahippocampal injection of FA markedly reduced hippocampal NE levels in healthy adult rats. Unexpectedly, an injection of FA (at a pathological level) or 6-hydroxydopamine (6-OHDA, a NE depletor) can mimic age-related NE deficiency, long-term potentiation (LTP) impairments, and spatial memory deficits in healthy adult rats. Conversely, an injection of NE reversed age-related deficits in both LTP and memory in aged rats. In agreement with the above results, the senescence-accelerated prone 8 (SAMP8) mice also exhibited a severe deficit in LTP and memory associated with a more severe NE deficiency and FA accumulation, when compared with the age-matched, senescence-resistant 1 (SAMR1) mice. Injection of resveratrol (a natural FA scavenger) or NE into SAMP8 mice reversed FA accumulation and NE deficiency and restored the magnitude of LTP and memory. Collectively, these findings suggest that accumulated FA is a critical endogenous factor for aging-associated NE depletion and cognitive decline. PMID:25866202

  1. Aging-associated formaldehyde-induced norepinephrine deficiency contributes to age-related memory decline

    PubMed Central

    Mei, Yufei; Jiang, Chun; Wan, You; Lv, Jihui; Jia, Jianping; Wang, Xiaomin; Yang, Xu; Tong, Zhiqian

    2015-01-01

    A norepinephrine (NE) deficiency has been observed in aged rats and in patients with Alzheimer’s disease and is thought to cause cognitive disorder. Which endogenous factor induces NE depletion, however, is largely unknown. In this study, we investigated the effects of aging-associated formaldehyde (FA) on the inactivation of NE in vitro and in vivo, and on memory behaviors in rodents. The results showed that age-related DNA demethylation led to hippocampal FA accumulation, and when this occurred, the hippocampal NE content was reduced in healthy male rats of different ages. Furthermore, biochemical analysis revealed that FA rapidly inactivated NE in vitro and that an intrahippocampal injection of FA markedly reduced hippocampal NE levels in healthy adult rats. Unexpectedly, an injection of FA (at a pathological level) or 6-hydroxydopamine (6-OHDA, a NE depletor) can mimic age-related NE deficiency, long-term potentiation (LTP) impairments, and spatial memory deficits in healthy adult rats. Conversely, an injection of NE reversed age-related deficits in both LTP and memory in aged rats. In agreement with the above results, the senescence-accelerated prone 8 (SAMP8) mice also exhibited a severe deficit in LTP and memory associated with a more severe NE deficiency and FA accumulation, when compared with the age-matched, senescence-resistant 1 (SAMR1) mice. Injection of resveratrol (a natural FA scavenger) or NE into SAMP8 mice reversed FA accumulation and NE deficiency and restored the magnitude of LTP and memory. Collectively, these findings suggest that accumulated FA is a critical endogenous factor for aging-associated NE depletion and cognitive decline. PMID:25866202

  2. Sleep Duration and Age-Related Changes in Brain Structure and Cognitive Performance

    PubMed Central

    Lo, June C.; Loh, Kep Kee; Zheng, Hui; Sim, Sam K.Y.; Chee, Michael W.L.

    2014-01-01

    Study Objectives: To investigate the contribution of sleep duration and quality to age-related changes in brain structure and cognitive performance in relatively healthy older adults. Design: Community-based longitudinal brain and cognitive aging study using a convenience sample. Setting: Participants were studied in a research laboratory. Participants: Relatively healthy adults aged 55 y and older at study commencement. Interventions: N/A. Measurements and Results: Participants underwent magnetic resonance imaging and neuropsychological assessment every 2 y. Subjective assessments of sleep duration and quality and blood samples were obtained. Each hour of reduced sleep duration at baseline augmented the annual expansion rate of the ventricles by 0.59% (P = 0.007) and the annual decline rate in global cognitive performance by 0.67% (P = 0.050) in the subsequent 2 y after controlling for the effects of age, sex, education, and body mass index. In contrast, global sleep quality at baseline did not modulate either brain or cognitive aging. High-sensitivity C-reactive protein, a marker of systemic inflammation, showed no correlation with baseline sleep duration, brain structure, or cognitive performance. Conclusions: In healthy older adults, short sleep duration is associated with greater age-related brain atrophy and cognitive decline. These associations are not associated with elevated inflammatory responses among short sleepers. Citation: Lo JC, Loh KK, Zheng H, Sim SK, Chee MW. Sleep duration and age-related changes in brain structure and cognitive performance. SLEEP 2014;37(7):1171-1178. PMID:25061245

  3. Do depressive traits and hostility predict age-related decline in general intelligence?

    PubMed

    Mortensen, Erik Lykke; Barefoot, John Calvin; Avlund, Kirsten

    2012-01-01

    Certain personality traits are likely to be associated with stress and distress through the lifespan, and as a consequence these traits may influence the rate of age-related cognitive decline. The present study uses data from the Glostrup 1914 cohort to analyze potential effects of personality on decline in general intelligence over a 30-year period. The Minnesota Multiphasic Personality Inventory was administered at a 50-year baseline exam, and from this inventory the Obvious Depression Scale and an abbreviated version of the Cook-Medley Hostility Scale were derived. At the 50-year baseline and at the 60-, 70-, and 80-year followups the full version of Wechsler's Adult Intelligence Scale (WAIS) was administered to 673, 513, 136, and 184 participants. Mixed effects statistical models were used to evaluate both the effect of the personality scores on level of intelligence and the interaction between the personality scores and the time since followup. Analyses were adjusted for demographic background and a wide range of lifestyle factors. Both obvious depression and hostility were negatively associated with level of intelligence, but personality scores did not influence rate of decline in general intelligence. PMID:22973515

  4. Do Depressive Traits and Hostility Predict Age-Related Decline in General Intelligence?

    PubMed Central

    Mortensen, Erik Lykke; Barefoot, John Calvin; Avlund, Kirsten

    2012-01-01

    Certain personality traits are likely to be associated with stress and distress through the lifespan, and as a consequence these traits may influence the rate of age-related cognitive decline. The present study uses data from the Glostrup 1914 cohort to analyze potential effects of personality on decline in general intelligence over a 30-year period. The Minnesota Multiphasic Personality Inventory was administered at a 50-year baseline exam, and from this inventory the Obvious Depression Scale and an abbreviated version of the Cook-Medley Hostility Scale were derived. At the 50-year baseline and at the 60-, 70-, and 80-year followups the full version of Wechsler's Adult Intelligence Scale (WAIS) was administered to 673, 513, 136, and 184 participants. Mixed effects statistical models were used to evaluate both the effect of the personality scores on level of intelligence and the interaction between the personality scores and the time since followup. Analyses were adjusted for demographic background and a wide range of lifestyle factors. Both obvious depression and hostility were negatively associated with level of intelligence, but personality scores did not influence rate of decline in general intelligence. PMID:22973515

  5. Age-related cochlear synaptopathy: an early-onset contributor to auditory functional decline.

    PubMed

    Sergeyenko, Yevgeniya; Lall, Kumud; Liberman, M Charles; Kujawa, Sharon G

    2013-08-21

    Aging listeners experience greater difficulty understanding speech in adverse listening conditions and exhibit degraded temporal resolution, even when audiometric thresholds are normal. When threshold evidence for peripheral involvement is lacking, central and cognitive factors are often cited as underlying performance declines. However, previous work has uncovered widespread loss of cochlear afferent synapses and progressive cochlear nerve degeneration in noise-exposed ears with recovered thresholds and no hair cell loss (Kujawa and Liberman 2009). Here, we characterize age-related cochlear synaptic and neural degeneration in CBA/CaJ mice never exposed to high-level noise. Cochlear hair cell and neuronal function was assessed via distortion product otoacoustic emissions and auditory brainstem responses, respectively. Immunostained cochlear whole mounts and plastic-embedded sections were studied by confocal and conventional light microscopy to quantify hair cells, cochlear neurons, and synaptic structures, i.e., presynaptic ribbons and postsynaptic glutamate receptors. Cochlear synaptic loss progresses from youth (4 weeks) to old age (144 weeks) and is seen throughout the cochlea long before age-related changes in thresholds or hair cell counts. Cochlear nerve loss parallels the synaptic loss, after a delay of several months. Key functional clues to the synaptopathy are available in the neural response; these can be accessed noninvasively, enhancing the possibilities for translation to human clinical characterization. PMID:23966690

  6. Mechanisms of Age-Related Decline in Memory Search across the Adult Life Span

    ERIC Educational Resources Information Center

    Hills, Thomas T.; Mata, Rui; Wilke, Andreas; Samanez-Larkin, Gregory R.

    2013-01-01

    Three alternative mechanisms for age-related decline in memory search have been proposed, which result from either reduced processing speed (global slowing hypothesis), overpersistence on categories (cluster-switching hypothesis), or the inability to maintain focus on local cues related to a decline in working memory (cue-maintenance hypothesis).…

  7. Disconnected aging: cerebral white matter integrity and age-related differences in cognition.

    PubMed

    Bennett, I J; Madden, D J

    2014-09-12

    Cognition arises as a result of coordinated processing among distributed brain regions and disruptions to communication within these neural networks can result in cognitive dysfunction. Cortical disconnection may thus contribute to the declines in some aspects of cognitive functioning observed in healthy aging. Diffusion tensor imaging (DTI) is ideally suited for the study of cortical disconnection as it provides indices of structural integrity within interconnected neural networks. The current review summarizes results of previous DTI aging research with the aim of identifying consistent patterns of age-related differences in white matter integrity, and of relationships between measures of white matter integrity and behavioral performance as a function of adult age. We outline a number of future directions that will broaden our current understanding of these brain-behavior relationships in aging. Specifically, future research should aim to (1) investigate multiple models of age-brain-behavior relationships; (2) determine the tract-specificity versus global effect of aging on white matter integrity; (3) assess the relative contribution of normal variation in white matter integrity versus white matter lesions to age-related differences in cognition; (4) improve the definition of specific aspects of cognitive functioning related to age-related differences in white matter integrity using information processing tasks; and (5) combine multiple imaging modalities (e.g., resting-state and task-related functional magnetic resonance imaging; fMRI) with DTI to clarify the role of cerebral white matter integrity in cognitive aging. PMID:24280637

  8. ESTROGENS AND AGE-RELATED MEMORY DECLINE IN RODENTS: WHAT HAVE WE LEARNED AND WHERE DO WE GO FROM HERE?

    PubMed Central

    Frick, Karyn M.

    2009-01-01

    The question of whether ovarian hormone therapy can prevent or reduce age-related memory decline in menopausal women has been the subject of much recent debate. Although numerous studies have demonstrated a beneficial effect of estrogen and/or progestin therapy for certain types of memory in menopausal women, recent clinical trials suggest that such therapy actually increases the risk of cognitive decline and dementia. Because rodent models have been frequently used to examine the effects of age and/or ovarian hormone deficiency on mnemonic function, rodent models of age-related hormone and memory decline may be useful in helping to resolve this issue. This review will focus on evidence suggesting that estradiol modulates memory, particularly hippocampal-dependent memory, in young and aging female rats and mice. Various factors affecting the mnemonic response to estradiol in aging females will be highlighted to illustrate the complications inherent to studies of estrogen therapy in aging females. Avenues for future development of estradiol-based therapies will also be discussed, and it is argued that an approach to drug development based on identifying the molecular mechanisms underlying estrogenic modulation of memory may lead to promising future treatments for reducing age-related mnemonic decline. PMID:18835561

  9. Dietary Vitamin D Deficiency in Rats from Middle- to Old-age Leads to Elevated Tyrosine Nitration and Proteomics Changes in Levels of Key Proteins in Brain: Implications for Low Vitamin D-dependent Age-Related Cognitive Decline

    PubMed Central

    Keeney, Jeriel T. R.; Förster, Sarah; Sultana, Rukhsana; Brewer, Lawrence D.; Latimer, Caitlin S.; Cai, Jian; Klein, Jon B.; Porter, Nada M.; Butterfield, D. Allan

    2013-01-01

    status. Together, these results suggest that dietary VitD deficiency contributes to significant nitrosative stress in brain and may promote cognitive decline in middle-aged and elderly adults. PMID:23872023

  10. Dietary vitamin D deficiency in rats from middle to old age leads to elevated tyrosine nitration and proteomics changes in levels of key proteins in brain: implications for low vitamin D-dependent age-related cognitive decline.

    PubMed

    Keeney, Jeriel T R; Förster, Sarah; Sultana, Rukhsana; Brewer, Lawrence D; Latimer, Caitlin S; Cai, Jian; Klein, Jon B; Porter, Nada M; Butterfield, D Allan

    2013-12-01

    results suggest that dietary VitD deficiency contributes to significant nitrosative stress in brain and may promote cognitive decline in middle-aged and elderly adults. PMID:23872023

  11. Age-related hearing decline in individuals with and without occupational noise exposure

    PubMed Central

    Hederstierna, Christina; Rosenhall, Ulf

    2016-01-01

    This study was conducted to compare the pattern of age-related hearing decline in individuals with and without self-reported previous occupational noise exposure. This was a prospective, population-based, longitudinal study of individuals aged 70-75 years, from an epidemiological investigation, comprising three age cohorts. In total there were 1013 subjects (432 men and 581 women). Participants were tested with pure tone audiometry, and they answered a questionnaire to provide information regarding number of years of occupational noise exposure. There were no significant differences in hearing decline, at any frequency, for those aged 70-75 years between the noise-exposed (N= 62 men, 22 women) and the nonexposed groups (N = 96 men, 158 women). This study supports the additive model of noise-induced hearing loss (NIHL) and age-related hearing loss (ARHL). The concept of different patterns of hearing decline between persons exposed and not exposed to noise could not be verified. PMID:26780958

  12. Preventing Age-Related Decline of Gut Compartmentalization Limits Microbiota Dysbiosis and Extends Lifespan.

    PubMed

    Li, Hongjie; Qi, Yanyan; Jasper, Heinrich

    2016-02-10

    Compartmentalization of the gastrointestinal (GI) tract of metazoans is critical for health. GI compartments contain specific microbiota, and microbiota dysbiosis is associated with intestinal dysfunction. Dysbiosis develops in aging intestines, yet how this relates to changes in GI compartmentalization remains unclear. The Drosophila GI tract is an accessible model to address this question. Here we show that the stomach-like copper cell region (CCR) in the middle midgut controls distribution and composition of the microbiota. We find that chronic activation of JAK/Stat signaling in the aging gut induces a metaplasia of the gastric epithelium, CCR decline, and subsequent commensal dysbiosis and epithelial dysplasia along the GI tract. Accordingly, inhibition of JAK/Stat signaling in the CCR specifically prevents age-related metaplasia, commensal dysbiosis and functional decline in old guts, and extends lifespan. Our results establish a mechanism by which age-related chronic inflammation causes the decline of intestinal compartmentalization and microbiota dysbiosis, limiting lifespan. PMID:26867182

  13. Vagal Recovery From Cognitive Challenge Moderates Age-Related Deficits in Executive Functioning.

    PubMed

    Crowley, Olga V; Kimhy, David; McKinley, Paula S; Burg, Matthew M; Schwartz, Joseph E; Lachman, Margie E; Tun, Patricia A; Ryff, Carol D; Seeman, Teresa E; Sloan, Richard P

    2016-05-01

    Decline in executive functioning (EF) is a hallmark of cognitive aging. We have previously reported that faster vagal recovery from cognitive challenge is associated with better EF. This study examined the association between vagal recovery from cognitive challenge and age-related differences in EF among 817 participants in the Midlife in the U.S. study (aged 35-86). Cardiac vagal control was measured as high-frequency heart rate variability. Vagal recovery moderated the association between age and EF (β = .811, p = .004). Secondary analyses revealed that older participants (aged 65-86) with faster vagal recovery had superior EF compared to their peers who had slower vagal recovery. In contrast, among younger (aged 35-54) and middle-aged (aged 55-64) participants, vagal recovery was not associated with EF. We conclude that faster vagal recovery from cognitive challenge is associated with reduced deficits in EF among older, but not younger individuals. PMID:26303063

  14. Vagal Recovery From Cognitive Challenge Moderates Age-Related Deficits in Executive Functioning

    PubMed Central

    Crowley, Olga V.; Kimhy, David; McKinley, Paula S.; Burg, Matthew M.; Schwartz, Joseph E.; Lachman, Margie E.; Tun, Patricia A.; Ryff, Carol D.; Seeman, Teresa E.; Sloan, Richard P.

    2015-01-01

    Decline in executive functioning (EF) is a hallmark of cognitive aging. We have previously reported that faster vagal recovery from cognitive challenge is associated with better EF. This study examined the association between vagal recovery from cognitive challenge and age-related differences in EF among 817 participants in the Midlife in the U.S. study (aged 35–86). Cardiac vagal control was measured as high-frequency heart rate variability. Vagal recovery moderated the association between age and EF (β = .811, p = .004). Secondary analyses revealed that older participants (aged 65–86) with faster vagal recovery had superior EF compared to their peers who had slower vagal recovery. In contrast, among younger (aged 35–54) and middle-aged (aged 55–64) participants, vagal recovery was not associated with EF. We conclude that faster vagal recovery from cognitive challenge is associated with reduced deficits in EF among older, but not younger individuals. PMID:26303063

  15. Brain-derived neurotrophic factor is associated with age-related decline in hippocampal volume.

    PubMed

    Erickson, Kirk I; Prakash, Ruchika Shaurya; Voss, Michelle W; Chaddock, Laura; Heo, Susie; McLaren, Molly; Pence, Brandt D; Martin, Stephen A; Vieira, Victoria J; Woods, Jeffrey A; McAuley, Edward; Kramer, Arthur F

    2010-04-14

    Hippocampal volume shrinks in late adulthood, but the neuromolecular factors that trigger hippocampal decay in aging humans remains a matter of speculation. In rodents, brain-derived neurotrophic factor (BDNF) promotes the growth and proliferation of cells in the hippocampus and is important in long-term potentiation and memory formation. In humans, circulating levels of BDNF decline with advancing age, and a genetic polymorphism for BDNF has been related to gray matter volume loss in old age. In this study, we tested whether age-related reductions in serum levels of BDNF would be related to shrinkage of the hippocampus and memory deficits in older adults. Hippocampal volume was acquired by automated segmentation of magnetic resonance images in 142 older adults without dementia. The caudate nucleus was also segmented and examined in relation to levels of serum BDNF. Spatial memory was tested using a paradigm in which memory load was parametrically increased. We found that increasing age was associated with smaller hippocampal volumes, reduced levels of serum BDNF, and poorer memory performance. Lower levels of BDNF were associated with smaller hippocampi and poorer memory, even when controlling for the variation related to age. In an exploratory mediation analysis, hippocampal volume mediated the age-related decline in spatial memory and BDNF mediated the age-related decline in hippocampal volume. Caudate nucleus volume was unrelated to BDNF levels or spatial memory performance. Our results identify serum BDNF as a significant factor related to hippocampal shrinkage and memory decline in late adulthood. PMID:20392958

  16. Similar Age-Related Decline in Cortical Activity Over Frontotemporal Regions in Schizophrenia: A Multichannel Near-Infrared Spectroscopy Study

    PubMed Central

    Chou, Po-Han; Koike, Shinsuke; Nishimura, Yukika; Satomura, Yoshihiro; Kinoshita, Akihide; Takizawa, Ryu; Kasai, Kiyoto

    2015-01-01

    Objectives: Although recent studies have demonstrated that patients with schizophrenia and healthy controls did not differ in the speed of age-related decline in cortical thickness and performances on cognitive tests, hemodynamic changes assessed by functional neuroimaging remain unclear. This study investigated age effects on regional brain cortical activity to determine whether there is similar age-related decline in cortical activity as those observed in cortical thickness and cognitive test performance. Method: A total of 109 patients with schizophrenia (age range: 16–59 y) and 106 healthy controls (age range: 16–59 y) underwent near-infrared spectroscopy (NIRS) while performing a verbal fluency test (VFT). Group comparison of cortical activity was examined using 2-tailed t tests, adopting the false discovery rate method. The relationship between age and cortical activity was investigated using correlational and multiple regression analyses, adjusting for potential confounding variables. A 2-way ANOVA was conducted to investigate differences in the age effects between diagnostic groups. Results: The patient group exhibited significantly decreased cortical activity in several regions of the frontotemporal cortices. However, slopes of age-dependent decreases in cortical activity were similar between patients and healthy individuals at the bilateral frontotemporal regions. Conclusions: Our study showed no significant between-group differences in the age-related decline in cortical activity, as measured by NIRS, over the frontotemporal regions during a VFT. The results of our study may indicate a decrease in cortical activity in a relatively limited period around illness onset rather than continuously progressing over the course of the illness. PMID:24948388

  17. Dizziness and Imbalance in the Elderly: Age-related Decline in the Vestibular System.

    PubMed

    Iwasaki, Shinichi; Yamasoba, Tatsuya

    2015-02-01

    Dizziness and imbalance are amongst the most common complaints in older people, and are a growing public health concern since they put older people at a significantly higher risk of falling. Although the causes of dizziness in older people are multifactorial, peripheral vestibular dysfunction is one of the most frequent causes. Benign paroxysmal positional vertigo is the most frequent form of vestibular dysfunction in the elderly, followed by Meniere's disease. Every factor associated with the maintenance of postural stability deteriorates during aging. Age-related deterioration of peripheral vestibular function has been demonstrated through quantitative measurements of the vestibulo-ocular reflex with rotational testing and of the vestibulo-collic reflex with testing of vestibular evoked myogenic potentials. Age-related decline of vestibular function has been shown to correlate with the age-related decrease in the number of vestibular hair cells and neurons. The mechanism of age-related cellular loss in the vestibular endorgan is unclear, but it is thought that genetic predisposition and cumulative effect of oxidative stress may both play an important role. Since the causes of dizziness in older people are multi-factorial, management of this disease should be customized according to the etiologies of each individual. Vestibular rehabilitation is found to be effective in treating both unilateral and bilateral vestibular dysfunction. Various prosthetic devices have also been developed to improve postural balance in older people. Although there have been no medical treatments improving age-related vestibular dysfunction, new medical treatments such as mitochondrial antioxidants or caloric restriction, which have been effective in preventing age-related hearing loss, should be ienvestigated in the future. PMID:25657851

  18. Dizziness and Imbalance in the Elderly: Age-related Decline in the Vestibular System

    PubMed Central

    Iwasaki, Shinichi; Yamasoba, Tatsuya

    2015-01-01

    Dizziness and imbalance are amongst the most common complaints in older people, and are a growing public health concern since they put older people at a significantly higher risk of falling. Although the causes of dizziness in older people are multifactorial, peripheral vestibular dysfunction is one of the most frequent causes. Benign paroxysmal positional vertigo is the most frequent form of vestibular dysfunction in the elderly, followed by Meniere’s disease. Every factor associated with the maintenance of postural stability deteriorates during aging. Age-related deterioration of peripheral vestibular function has been demonstrated through quantitative measurements of the vestibulo-ocular reflex with rotational testing and of the vestibulo-collic reflex with testing of vestibular evoked myogenic potentials. Age-related decline of vestibular function has been shown to correlate with the age-related decrease in the number of vestibular hair cells and neurons. The mechanism of age-related cellular loss in the vestibular endorgan is unclear, but it is thought that genetic predisposition and cumulative effect of oxidative stress may both play an important role. Since the causes of dizziness in older people are multi-factorial, management of this disease should be customized according to the etiologies of each individual. Vestibular rehabilitation is found to be effective in treating both unilateral and bilateral vestibular dysfunction. Various prosthetic devices have also been developed to improve postural balance in older people. Although there have been no medical treatments improving age-related vestibular dysfunction, new medical treatments such as mitochondrial antioxidants or caloric restriction, which have been effective in preventing age-related hearing loss, should be ienvestigated in the future. PMID:25657851

  19. Like cognitive function, decision making across the life span shows profound age-related changes

    PubMed Central

    Tymula, Agnieszka; Rosenberg Belmaker, Lior A.; Ruderman, Lital; Glimcher, Paul W.; Levy, Ifat

    2013-01-01

    It has long been known that human cognitive function improves through young adulthood and then declines across the later life span. Here we examined how decision-making function changes across the life span by measuring risk and ambiguity attitudes in the gain and loss domains, as well as choice consistency, in an urban cohort ranging in age from 12 to 90 y. We identified several important age-related patterns in decision making under uncertainty: First, we found that healthy elders between the ages of 65 and 90 were strikingly inconsistent in their choices compared with younger subjects. Just as elders show profound declines in cognitive function, they also show profound declines in choice rationality compared with their younger peers. Second, we found that the widely documented phenomenon of ambiguity aversion is specific to the gain domain and does not occur in the loss domain, except for a slight effect in older adults. Finally, extending an earlier report by our group, we found that risk attitudes across the life span show an inverted U-shaped function; both elders and adolescents are more risk-averse than their midlife counterparts. Taken together, these characterizations of decision-making function across the life span in this urban cohort strengthen the conclusions of previous reports suggesting a profound impact of aging on cognitive function in this domain. PMID:24082105

  20. Shared and unique genetic and environmental influences on aging-related changes in multiple cognitive abilities.

    PubMed

    Tucker-Drob, Elliot M; Reynolds, Chandra A; Finkel, Deborah; Pedersen, Nancy L

    2014-01-01

    Aging-related declines occur in many different domains of cognitive function during middle and late adulthood. However, whether a global dimension underlies individual differences in changes in different domains of cognition and whether global genetic influences on cognitive changes exist is less clear. We addressed these issues by applying multivariate growth curve models to longitudinal data from 857 individuals from the Swedish Adoption/Twin Study of Aging, who had been measured on 11 cognitive variables representative of verbal, spatial, memory, and processing speed abilities up to 5 times over up to 16 years between ages 50 and 96 years. Between ages 50 and 65 years scores on different tests changed relatively independently of one another, and there was little evidence for strong underlying dimensions of change. In contrast, over the period between 65 and 96 years of age, there were strong interrelations among rates of change both within and across domains. During this age period, variability in rates of change were, on average, 52% domain-general, 8% domain-specific, and 39% test-specific. Quantitative genetic decomposition indicated that 29% of individual differences in a global domain-general dimension of cognitive changes during this age period were attributable to genetic influences, but some domain-specific genetic influences were also evident, even after accounting for domain-general contributions. These findings are consistent with a balanced global and domain-specific account of the genetics of cognitive aging. PMID:23586942

  1. Developmental improvement and age-related decline in unfamiliar face matching.

    PubMed

    Megreya, Ahmed M; Bindemann, Markus

    2015-01-01

    Age-related changes have been documented widely in studies of face recognition and eyewitness identification. However, it is not clear whether these changes arise from general developmental differences in memory or occur specifically during the perceptual processing of faces. We report two experiments to track such perceptual changes using a 1-in- 10 (experiment 1) and 1-in-1 (experiment 2) matching task for unfamiliar faces. Both experiments showed improvements in face matching during childhood and adult-like accuracy levels by adolescence. In addition, face-matching performance declined in adults of the age of 65 years. These findings indicate that developmental improvements and aging-related differences in face processing arise from changes in the perceptual encoding of faces. A clear face inversion effect was also present in all age groups. This indicates that those age-related changes in face matching reflect a quantitative effect, whereby typical face processes are engaged but do not operate at the best-possible level. These data suggest that part of the problem of eyewitness identification in children and elderly persons might reflect impairments in the perceptual processing of unfamiliar faces. PMID:26489213

  2. Age-related declines in car following performance under simulated fog conditions

    PubMed Central

    Ni, Rui; Kang, Julie J.; Andersen, George J.

    2010-01-01

    The present study examined age-related differences in car following performance when contrast of the driving scene was reduced by simulated fog. Older (mean age of 72.6) and younger (mean age of 21.1) drivers were presented with a car following scenario in a simulator in which a lead vehicle (LV) varied speed according to a sum of three sine wave functions. Drivers were shown an initial following distance of 18m and were asked to maintain headway distance by controlling speed to match changes in LV speed. Five simulated fog conditions were examined ranging from a no fog condition (contrast of 0.55) to a high fog condition (contrast of 0.03). Average LV speed varied across trials (40, 60, or 80 km/h). The results indicated age-related declines in car following performance for both headway distance and RMS (root mean square) error in matching speed. The greatest decline occurred at moderate speeds under the highest fog density condition, with older drivers maintaining a headway distance that was 21% closer than younger drivers. At higher speeds older drivers maintained a greater headway distance than younger drivers. These results suggest that older drivers may be at greater risk for a collision under high fog density and moderate speeds. PMID:20380908

  3. An age-related decline of CD62L and vaccine response

    PubMed Central

    Shin, Jae Il; Bayry, Jagadeesh

    2014-01-01

    Aging process can affect T cell and antibody response to vaccination and an age-related decline in the expression of CD62L on CD8+ T-lymphocyte is one of the important factors that contribute. A recent report demonstrated that percentage of CD3+CD8+CD62L+ cells and CD8+ T-lymphocyte microRNA-92a levels significantly decline with the age and were positively correlated. These results suggested that the age-related attrition of human naïve T cells could be connected to a reduced microRNA-92a in T-lymphocytes and downregulation of the microRNA-92a level might indicate exhaustion of naïve T-cells due to alteration of the immunologic condition with aging. Further studies are necessary to evaluate whether targeting microRNA-92a as microRNA mimics could be one of the therapeutic strategies in improving vaccine response in elderly. PMID:24401614

  4. The significance of caudate volume for age-related associative memory decline.

    PubMed

    Bauer, E; Toepper, M; Gebhardt, H; Gallhofer, B; Sammer, G

    2015-10-01

    Aging comes along with reduced gray matter (GM) volume in several cerebral areas and with cognitive performance decline in different cognitive domains. Moreover, regional GM volume is linked to specific cognitive sub processes in older adults. However, it remains unclear which regional changes in older individuals are directly associated with decreased cognitive performance. Moreover, most of the studies on this topic focused on hippocampal and prefrontal brain regions and their relation to memory and executive functioning. Interestingly, there are only a few studies that reported an association between striatal brain volume and cognitive performance. This is insofar surprising that striatal structures are (1) highly affected by age and (2) involved in different neural circuits that serve intact cognition. To address these issues, voxel-based morphometry (VBM) was used to analyze GM volume in 18 younger and 18 older adults. Moreover, several neuropsychological tests from different neuropsychological test batteries were applied to assess a broad range of cognitive domains. Older adults showed less GM volume than younger adults within frontal, striatal, and cerebellar brain regions. In the group of older adults, significant correlations were found between striatal GM volume and memory performance and between prefrontal/temporal GM volume and executive functioning. The only direct overlap between brain regions associated with regional atrophy and cognitive performance in older adults was found for the right caudate: older adults showed reduced caudate volume relative to younger adults. Moreover, caudate volume was positively correlated with associative memory accuracy in older adults and older adults showed poorer performances than younger adults in the respective associative memory task. Taken together, the current findings indicate the relevance of the caudate for associative memory decline in the aging brain. PMID:26119913

  5. Dietary Factors and Cognitive Decline

    PubMed Central

    Smith, P.J.; Blumenthal, J.A.

    2015-01-01

    Cognitive decline is an increasingly important public health problem, with more than 100 million adults worldwide projected to develop dementia by 2050. Accordingly, there has been an increased interest in preventive strategies that diminish this risk. It has been recognized that lifestyle factors including dietary patterns, may be important in the prevention of cognitive decline and dementia in later life. Several dietary components have been examined, including antioxidants, fatty acids, and B vitamins. In addition, whole dietary eating plans, including the Mediterranean diet (MeDi), and the Dietary Approaches to Stop Hypertension (DASH) diet, with and without weight loss, have become areas of increasing interest. Although prospective epidemiological studies have observed that antioxidants, fatty acids, and B vitamins are associated with better cognitive functioning, randomized clinical trials have generally failed to confirm the value of any specific dietary component in improving neurocognition. Several randomized trials have examined the impact of changing ‘whole’ diets on cognitive outcomes. The MeDi and DASH diets offer promising preliminary results, but data are limited and more research in this area is needed. PMID:26900574

  6. A neuropsychological instrument measuring age-related cerebral decline in older drivers: development, reliability, and validity of MedDrive

    PubMed Central

    Vaucher, Paul; Cardoso, Isabel; Veldstra, Janet L.; Herzig, Daniela; Herzog, Michael; Mangin, Patrice; Favrat, Bernard

    2014-01-01

    When facing age-related cerebral decline, older adults are unequally affected by cognitive impairment without us knowing why. To explore underlying mechanisms and find possible solutions to maintain life-space mobility, there is a need for a standardized behavioral test that relates to behaviors in natural environments. The aim of the project described in this paper was therefore to provide a free, reliable, transparent, computer-based instrument capable of detecting age-related changes on visual processing and cortical functions for the purposes of research into human behavior in computational transportation science. After obtaining content validity, exploring psychometric properties of the developed tasks, we derived (Study 1) the scoring method for measuring cerebral decline on 106 older drivers aged ≥70 years attending a driving refresher course organized by the Swiss Automobile Association to test the instrument's validity against on-road driving performance (106 older drivers). We then validated the derived method on a new sample of 182 drivers (Study 2). We then measured the instrument's reliability having 17 healthy, young volunteers repeat all tests included in the instrument five times (Study 3) and explored the instrument's psychophysical underlying functions on 47 older drivers (Study 4). Finally, we tested the instrument's responsiveness to alcohol and effects on performance on a driving simulator in a randomized, double-blinded, placebo, crossover, dose-response, validation trial including 20 healthy, young volunteers (Study 5). The developed instrument revealed good psychometric properties related to processing speed. It was reliable (ICC = 0.853) and showed reasonable association to driving performance (R2 = 0.053), and responded to blood alcohol concentrations of 0.5 g/L (p = 0.008). Our results suggest that MedDrive is capable of detecting age-related changes that affect processing speed. These changes nevertheless do not necessarily affect

  7. A neuropsychological instrument measuring age-related cerebral decline in older drivers: development, reliability, and validity of MedDrive.

    PubMed

    Vaucher, Paul; Cardoso, Isabel; Veldstra, Janet L; Herzig, Daniela; Herzog, Michael; Mangin, Patrice; Favrat, Bernard

    2014-01-01

    When facing age-related cerebral decline, older adults are unequally affected by cognitive impairment without us knowing why. To explore underlying mechanisms and find possible solutions to maintain life-space mobility, there is a need for a standardized behavioral test that relates to behaviors in natural environments. The aim of the project described in this paper was therefore to provide a free, reliable, transparent, computer-based instrument capable of detecting age-related changes on visual processing and cortical functions for the purposes of research into human behavior in computational transportation science. After obtaining content validity, exploring psychometric properties of the developed tasks, we derived (Study 1) the scoring method for measuring cerebral decline on 106 older drivers aged ≥70 years attending a driving refresher course organized by the Swiss Automobile Association to test the instrument's validity against on-road driving performance (106 older drivers). We then validated the derived method on a new sample of 182 drivers (Study 2). We then measured the instrument's reliability having 17 healthy, young volunteers repeat all tests included in the instrument five times (Study 3) and explored the instrument's psychophysical underlying functions on 47 older drivers (Study 4). Finally, we tested the instrument's responsiveness to alcohol and effects on performance on a driving simulator in a randomized, double-blinded, placebo, crossover, dose-response, validation trial including 20 healthy, young volunteers (Study 5). The developed instrument revealed good psychometric properties related to processing speed. It was reliable (ICC = 0.853) and showed reasonable association to driving performance (R (2) = 0.053), and responded to blood alcohol concentrations of 0.5 g/L (p = 0.008). Our results suggest that MedDrive is capable of detecting age-related changes that affect processing speed. These changes nevertheless do not necessarily affect

  8. Age-Related Declines in Early Sensory Memory: Identification of Rapid Auditory and Visual Stimulus Sequences

    PubMed Central

    Fogerty, Daniel; Humes, Larry E.; Busey, Thomas A.

    2016-01-01

    Age-related temporal-processing declines of rapidly presented sequences may involve contributions of sensory memory. This study investigated recall for rapidly presented auditory (vowel) and visual (letter) sequences presented at six different stimulus onset asynchronies (SOA) that spanned threshold SOAs for sequence identification. Younger, middle-aged, and older adults participated in all tasks. Results were investigated at both equivalent performance levels (i.e., SOA threshold) and at identical physical stimulus values (i.e., SOAs). For four-item sequences, results demonstrated best performance for the first and last items in the auditory sequences, but only the first item for visual sequences. For two-item sequences, adults identified the second vowel or letter significantly better than the first. Overall, when temporal-order performance was equated for each individual by testing at SOA thresholds, recall accuracy for each position across the age groups was highly similar. These results suggest that modality-specific processing declines of older adults primarily determine temporal-order performance for rapid sequences. However, there is some evidence for a second amodal processing decline in older adults related to early sensory memory for final items in a sequence. This selective deficit was observed particularly for longer sequence lengths and was not accounted for by temporal masking. PMID:27199737

  9. Grip strength is potentially an early indicator of age-related decline in mice.

    PubMed

    Ge, Xuan; Cho, Anthony; Ciol, Marcia A; Pettan-Brewer, Christina; Snyder, Jessica; Rabinovitch, Peter; Ladiges, Warren

    2016-01-01

    The hand grip test has been correlated with mobility and physical performance in older people and has been shown to be a long-term predictor of mortality. Implementation of new strategies for enhancing healthy aging and maintaining independent living are dependent on predictable preclinical studies. The mouse is used extensively as a model in these types of studies, and the paw grip strength test is similar to the hand grip test for people in that it assesses the ability to grip a device with the paw, is non-invasive and easy to perform, and provides reproducible information. However, little has been reported on how grip strength declines with increasing age in mice. This report shows that grip strength was decreased in C57BL/6 (B6) NIA and C57BL/6×BALB/c F1 (CB6F1) NIA male mice at 12 months of age compared to 8-month-old mice, and continued a robust decline to 20 months and then 28 months of age, when the study was terminated. The decline was not related to lean muscle mass, but extensive age-related carpal and digital exostosis could help explain the decreased grip strength times with increasing age. In conclusion, the grip strength test could be useful in mouse preclinical studies to help make translational predictions on treatment strategies to enhance healthy aging. PMID:27613499

  10. Age-related declines in immune response in a wild mammal are unrelated to immune cell telomere length.

    PubMed

    Beirne, Christopher; Waring, Laura; McDonald, Robbie A; Delahay, Richard; Young, Andrew

    2016-02-24

    Senescence has been hypothesized to arise in part from age-related declines in immune performance, but the patterns and drivers of within-individual age-related changes in immunity remain virtually unexplored in natural populations. Here, using a long-term epidemiological study of wild European badgers (Meles meles), we (i) present evidence of a within-individual age-related decline in the response of a key immune-signalling cytokine, interferon-gamma (IFNγ), to ex vivo lymphocyte stimulation, and (ii) investigate three putative drivers of individual variation in the rate of this decline (sex, disease and immune cell telomere length; ICTL). That the within-individual rate of age-related decline markedly exceeded that at the population level suggests that individuals with weaker IFNγ responses are selectively lost from this population. IFNγ responses appeared to decrease with the progression of bovine tuberculosis infection (independent of age) and were weaker among males than females. However, neither sex nor disease influenced the rate of age-related decline in IFNγ response. Similarly, while ICTL also declines with age, variation in ICTL predicted neither among- nor within-individual variation in IFNγ response. Our findings provide evidence of within-individual age-related declines in immune performance in a wild mammal and highlight the likely complexity of the mechanisms that generate them. PMID:26888036

  11. Age-related declines in immune response in a wild mammal are unrelated to immune cell telomere length

    PubMed Central

    Waring, Laura; McDonald, Robbie A.; Delahay, Richard; Young, Andrew

    2016-01-01

    Senescence has been hypothesized to arise in part from age-related declines in immune performance, but the patterns and drivers of within-individual age-related changes in immunity remain virtually unexplored in natural populations. Here, using a long-term epidemiological study of wild European badgers (Meles meles), we (i) present evidence of a within-individual age-related decline in the response of a key immune-signalling cytokine, interferon-gamma (IFNγ), to ex vivo lymphocyte stimulation, and (ii) investigate three putative drivers of individual variation in the rate of this decline (sex, disease and immune cell telomere length; ICTL). That the within-individual rate of age-related decline markedly exceeded that at the population level suggests that individuals with weaker IFNγ responses are selectively lost from this population. IFNγ responses appeared to decrease with the progression of bovine tuberculosis infection (independent of age) and were weaker among males than females. However, neither sex nor disease influenced the rate of age-related decline in IFNγ response. Similarly, while ICTL also declines with age, variation in ICTL predicted neither among- nor within-individual variation in IFNγ response. Our findings provide evidence of within-individual age-related declines in immune performance in a wild mammal and highlight the likely complexity of the mechanisms that generate them. PMID:26888036

  12. The role of cognition in age-related hearing loss.

    PubMed

    Craik, Fergus I M

    2007-01-01

    The article presents a commentary on the accompanying six papers from the perspective of a cognitive psychologist. Treisman's (1964, 1969) levels of analysis model of selective attention is suggested as a framework within which the interactions between 'bottom-up' auditory factors and 'top-down' cognitive factors may be understood. The complementary roles of auditory and cognitive aspects of hearing are explored, and their mutually compensatory properties discussed. The findings and ideas reported in the six accompanying papers fit well into such a 'levels of processing' framework, which may therefore be proposed as a model for understanding the effects of aging on speech processing and comprehension. PMID:18236642

  13. Age-Related Declines in Visuospatial Working Memory Correlate With Deficits in Explicit Motor Sequence Learning

    PubMed Central

    Bo, J.; Borza, V.

    2009-01-01

    Numerous studies have shown that older adults exhibit deficits in motor sequence learning, but the mechanisms underlying this effect remain unclear. Our recent work has shown that visuospatial working-memory capacity predicts the rate of motor sequence learning and the length of motor chunks formed during explicit sequence learning in young adults. In the current study, we evaluate whether age-related deficits in working memory explain the reduced rate of motor sequence learning in older adults. We found that older adults exhibited a correlation between visuospatial working-memory capacity and motor sequence chunk length, as we observed previously in young adults. In addition, older adults exhibited an overall reduction in both working-memory capacity and motor chunk length compared with that of young adults. However, individual variations in visuospatial working-memory capacity did not correlate with the rate of learning in older adults. These results indicate that working memory declines with age at least partially explain age-related differences in explicit motor sequence learning. PMID:19726728

  14. Age-related declines in visuospatial working memory correlate with deficits in explicit motor sequence learning.

    PubMed

    Bo, J; Borza, V; Seidler, R D

    2009-11-01

    Numerous studies have shown that older adults exhibit deficits in motor sequence learning, but the mechanisms underlying this effect remain unclear. Our recent work has shown that visuospatial working-memory capacity predicts the rate of motor sequence learning and the length of motor chunks formed during explicit sequence learning in young adults. In the current study, we evaluate whether age-related deficits in working memory explain the reduced rate of motor sequence learning in older adults. We found that older adults exhibited a correlation between visuospatial working-memory capacity and motor sequence chunk length, as we observed previously in young adults. In addition, older adults exhibited an overall reduction in both working-memory capacity and motor chunk length compared with that of young adults. However, individual variations in visuospatial working-memory capacity did not correlate with the rate of learning in older adults. These results indicate that working memory declines with age at least partially explain age-related differences in explicit motor sequence learning. PMID:19726728

  15. Connecting Age-Related Biological Decline to Frailty and Late-Life Vulnerability.

    PubMed

    Walston, Jeremy D

    2015-01-01

    Frailty is an important construct in aging which allows for the identification of the most vulnerable subset of older adults. At least two conceptual models of frailty have been developed that have in turn facilitated the development of multiple frailty screening tools. This has enabled the study of populations of frail and nonfrail older adults, and facilitated the risk assessment for adverse health outcomes. In addition, using the syndromic approach to frailty, numerous biological hypotheses have been tested, which have identified chronic inflammatory pathway activation, hypothalamic-pituitary-adrenal axis activation, and sympathetic nervous system activity as important in the development of frailty. In addition, age-related molecular changes related to autophagy, mitochondrial decline, apoptosis, senescent cell development, and necroptosis likely contribute to the heterogeneous phenotype of frailty. The recent development of a frail mouse model with chronic inflammatory pathway activation has helped to facilitate further whole organism biological discoveries. The following article attempts to create an understanding of the connections between these age-related biological changes and frailty. PMID:26485518

  16. Age-related decline in bottom-up processing and selective attention in the very old

    PubMed Central

    Zhuravleva, T. Y.; Alperin, B. R.; Haring, A. E.; Rentz, D. M.; Holcomb, P. J.; Daffner, K. R.

    2014-01-01

    Previous research demonstrating age-related deficits in selective attention have not included old-old adults, an increasingly important group to study. The current investigation compared event-related potentials (ERPs) in 15 young-old (65–79) and 23 old-old (80–99) subjects during a color-selective attention task. Subjects responded to target letters in a specified color (Attend) while ignoring letters in a different color (Ignore) under both low and high load. There were no group differences in visual acuity, accuracy, reaction time, or latency of early ERP components. The old-old group showed a disruption in bottom-up processing, indexed by a substantially diminished posterior N1 (smaller amplitude). They also demonstrated markedly decreased modulation of bottom-up processing based on selected visual features, indexed by the posterior selection negativity (SN), with similar attenuation under both loads. In contrast, there were no group differences in frontally-mediated attentional selection, measured by the anterior selection positivity (SP). There was a robust inverse relationship between the size of the SN and SP (the smaller the SN, the larger the SP), which may represent an anteriorly-supported compensatory mechanism. In the absence of a decline in top-down modulation indexed by the SP, the diminished SN may reflect age-related degradation of early bottom-up visual processing in old-old adults. PMID:24887611

  17. Multiple Brain Markers are Linked to Age-Related Variation in Cognition.

    PubMed

    Hedden, Trey; Schultz, Aaron P; Rieckmann, Anna; Mormino, Elizabeth C; Johnson, Keith A; Sperling, Reisa A; Buckner, Randy L

    2016-04-01

    Age-related alterations in brain structure and function have been challenging to link to cognition due to potential overlapping influences of multiple neurobiological cascades. We examined multiple brain markers associated with age-related variation in cognition. Clinically normal older humans aged 65-90 from the Harvard Aging Brain Study (N = 186) were characterized on a priori magnetic resonance imaging markers of gray matter thickness and volume, white matter hyperintensities, fractional anisotropy (FA), resting-state functional connectivity, positron emission tomography markers of glucose metabolism and amyloid burden, and cognitive factors of processing speed, executive function, and episodic memory. Partial correlation and mediation analyses estimated age-related variance in cognition shared with individual brain markers and unique to each marker. The largest relationships linked FA and striatum volume to processing speed and executive function, and hippocampal volume to episodic memory. Of the age-related variance in cognition, 70-80% was accounted for by combining all brain markers (but only ∼20% of total variance). Age had significant indirect effects on cognition via brain markers, with significant markers varying across cognitive domains. These results suggest that most age-related variation in cognition is shared among multiple brain markers, but potential specificity between some brain markers and cognitive domains motivates additional study of age-related markers of neural health. PMID:25316342

  18. From mind wandering to involuntary retrieval: Age-related differences in spontaneous cognitive processes.

    PubMed

    Maillet, David; Schacter, Daniel L

    2016-01-01

    The majority of studies that have investigated the effects of healthy aging on cognition have focused on age-related differences in voluntary and deliberately engaged cognitive processes. Yet many forms of cognition occur spontaneously, without any deliberate attempt at engaging them. In this article we review studies that have assessed age-related differences in four such types of spontaneous thought processes: mind-wandering, involuntary autobiographical memory, intrusive thoughts, and spontaneous prospective memory retrieval. These studies suggest that older adults exhibit a reduction in frequency of both mind-wandering and involuntary autobiographical memory, whereas findings regarding intrusive thoughts have been more mixed. Additionally, there is some preliminary evidence that spontaneous prospective memory retrieval may be relatively preserved in aging. We consider the roles of age-related differences in cognitive resources, motivation, current concerns and emotional regulation in accounting for these findings. We also consider age-related differences in the neural correlates of spontaneous cognitive processes. PMID:26617263

  19. Closed-Loop Rehabilitation of Age-Related Cognitive Disorders

    PubMed Central

    Mishra, Jyoti; Gazzaley, Adam

    2015-01-01

    Cognitive deficits are common in older adults, as a result of both the natural aging process and neurodegenerative disease. Although medical advancements have successfully prolonged the human lifespan, the challenge of remediating cognitive aging remains. The authors discuss the current state of cognitive therapeutic interventions and then present the need for development and validation of more powerful neurocognitive therapeutics. They propose that the next generation of interventions be implemented as closed-loop systems that target specific neural processing deficits, incorporate quantitative feedback to the individual and clinician, and are personalized to the individual’s neurocognitive capacities using real-time performance-adaptive algorithms. This approach should be multimodal and seamlessly integrate other treatment approaches, including neurofeedback and transcranial electrical stimulation. This novel approach will involve the generation of software that engages the individual in an immersive and enjoyable game-based interface, integrated with advanced biosensing hardware, to maximally harness plasticity and assure adherence. Introducing such next-generation closed-loop neurocognitive therapeutics into the mainstream of our mental health care system will require the combined efforts of clinicians, neuroscientists, bioengineers, software game developers, and industry and policy makers working together to meet the challenges and opportunities of translational neuroscience in the 21st century. PMID:25520029

  20. Closed-loop rehabilitation of age-related cognitive disorders.

    PubMed

    Mishra, Jyoti; Gazzaley, Adam

    2014-11-01

    Cognitive deficits are common in older adults, as a result of both the natural aging process and neurodegenerative disease. Although medical advancements have successfully prolonged the human lifespan, the challenge of remediating cognitive aging remains. The authors discuss the current state of cognitive therapeutic interventions and then present the need for development and validation of more powerful neurocognitive therapeutics. They propose that the next generation of interventions be implemented as closed-loop systems that target specific neural processing deficits, incorporate quantitative feedback to the individual and clinician, and are personalized to the individual's neurocognitive capacities using real-time performance-adaptive algorithms. This approach should be multimodal and seamlessly integrate other treatment approaches, including neurofeedback and transcranial electrical stimulation. This novel approach will involve the generation of software that engages the individual in an immersive and enjoyable game-based interface, integrated with advanced biosensing hardware, to maximally harness plasticity and assure adherence. Introducing such next-generation closed-loop neurocognitive therapeutics into the mainstream of our mental health care system will require the combined efforts of clinicians, neuroscientists, bioengineers, software game developers, and industry and policy makers working together to meet the challenges and opportunities of translational neuroscience in the 21st century. PMID:25520029

  1. Age-related changes in dentate gyrus cell numbers, neurogenesis, and associations with cognitive impairments in the rhesus monkey.

    PubMed

    Ngwenya, Laura B; Heyworth, Nadine C; Shwe, Yamin; Moore, Tara L; Rosene, Douglas L

    2015-01-01

    The generation of new neurons in the adult mammalian brain is well-established for the hippocampal dentate gyrus (DG). However, the role of neurogenesis in hippocampal function and cognition, how it changes in aging, and the mechanisms underlying this are yet to be elucidated in the monkey brain. To address this, we investigated adult neurogenesis in the DG of 42 rhesus monkeys (39 cognitively tested) ranging in age from young adult to the elderly. We report here that there is an age-related decline in proliferation and a delayed development of adult neuronal phenotype. Additionally, we show that many of the new neurons survive throughout the lifetime of the animal and may contribute to a modest increase in total neuron number in the granule cell layer of the DG over the adult life span. Lastly, we find that measures of decreased adult neurogenesis are only modestly predictive of age-related cognitive impairment. PMID:26236203

  2. Age-related changes in dentate gyrus cell numbers, neurogenesis, and associations with cognitive impairments in the rhesus monkey

    PubMed Central

    Ngwenya, Laura B.; Heyworth, Nadine C.; Shwe, Yamin; Moore, Tara L.; Rosene, Douglas L.

    2015-01-01

    The generation of new neurons in the adult mammalian brain is well-established for the hippocampal dentate gyrus (DG). However, the role of neurogenesis in hippocampal function and cognition, how it changes in aging, and the mechanisms underlying this are yet to be elucidated in the monkey brain. To address this, we investigated adult neurogenesis in the DG of 42 rhesus monkeys (39 cognitively tested) ranging in age from young adult to the elderly. We report here that there is an age-related decline in proliferation and a delayed development of adult neuronal phenotype. Additionally, we show that many of the new neurons survive throughout the lifetime of the animal and may contribute to a modest increase in total neuron number in the granule cell layer of the DG over the adult life span. Lastly, we find that measures of decreased adult neurogenesis are only modestly predictive of age-related cognitive impairment. PMID:26236203

  3. Musical training orchestrates coordinated neuroplasticity in auditory brainstem and cortex to counteract age-related declines in categorical vowel perception.

    PubMed

    Bidelman, Gavin M; Alain, Claude

    2015-01-21

    Musicianship in early life is associated with pervasive changes in brain function and enhanced speech-language skills. Whether these neuroplastic benefits extend to older individuals more susceptible to cognitive decline, and for whom plasticity is weaker, has yet to be established. Here, we show that musical training offsets declines in auditory brain processing that accompanying normal aging in humans, preserving robust speech recognition late into life. We recorded both brainstem and cortical neuroelectric responses in older adults with and without modest musical training as they classified speech sounds along an acoustic-phonetic continuum. Results reveal higher temporal precision in speech-evoked responses at multiple levels of the auditory system in older musicians who were also better at differentiating phonetic categories. Older musicians also showed a closer correspondence between neural activity and perceptual performance. This suggests that musicianship strengthens brain-behavior coupling in the aging auditory system. Last, "neurometric" functions derived from unsupervised classification of neural activity established that early cortical responses could accurately predict listeners' psychometric speech identification and, more critically, that neurometric profiles were organized more categorically in older musicians. We propose that musicianship offsets age-related declines in speech listening by refining the hierarchical interplay between subcortical/cortical auditory brain representations, allowing more behaviorally relevant information carried within the neural code, and supplying more faithful templates to the brain mechanisms subserving phonetic computations. Our findings imply that robust neuroplasticity conferred by musical training is not restricted by age and may serve as an effective means to bolster speech listening skills that decline across the lifespan. PMID:25609638

  4. Mouse forepaw lumbrical muscles are resistant to age-related declines in force production.

    PubMed

    Russell, Katelyn A; Ng, Rainer; Faulkner, John A; Claflin, Dennis R; Mendias, Christopher L

    2015-05-01

    A progressive loss of skeletal muscle mass and force generating capacity occurs with aging. Mice are commonly used in the study of aging-associated changes in muscle size and strength, with most models of aging demonstrating 15-35% reductions in muscle mass, cross-sectional area (CSA), maximum isometric force production (Po) and specific force (sPo), which is Po/CSA. The lumbrical muscle of the mouse forepaw is exceptionally small, with corresponding short diffusion distances that make it ideal for in vitro pharmacological studies and measurements of contractile properties. However, the aging-associated changes in lumbrical function have not previously been reported. To address this, we tested the hypothesis that compared to adult (12month old) mice, the forepaw lumbrical muscles of old (30month old) mice exhibit aging-related declines in size and force production similar to those observed in larger limb muscles. We found that the forepaw lumbricals were composed exclusively of fibers with type II myosin heavy chain isoforms, and that the muscles accumulated connective tissue with aging. There were no differences in the number of fibers per whole-muscle cross-section or in muscle fiber CSA. The whole muscle CSA in old mice was increased by 17%, but the total CSA of all muscle fibers in a whole-muscle cross-section was not different. No difference in Po was observed, and while sPo normalized to total muscle CSA was decreased in old mice by 22%, normalizing Po by the total muscle fiber CSA resulted in no difference in sPo. Combined, these results indicate that forepaw lumbrical muscles from 30month old mice are largely protected from the aging-associated declines in size and force production that are typically observed in larger limb muscles. PMID:25762422

  5. Age related decline in the proliferative response of human T cells to OKT3 stimulation

    SciTech Connect

    Chrest, F.; Nagel, J.; Adler, W.

    1986-03-05

    The level of the in vitro proliferative response of human peripheral blood mononuclear cells (PBMC) to the OKT3 monoclonal antibody is directly related to the level of monocyte representation in the cell population. The responses to OKT3 stimulation of PBMC obtained from different individual are difficult to interpret due to variable percentage representation of monocytes. To eliminate this problem purified T cells from humans of various ages were incubated with 2 ng/ml OKT3 antibody and 10% purified autologous monocytes. The /sup 3/H-TdR incorporation of 1 x 10/sup 5/ T cells at 72 hrs of culture was 69,939 +/- 6085 (SEM) cpm for young individuals (mean age 35 yrs) and 33,163 +/- 2962 cpm for healthy elderly individuals (mean age 78 yrs). In addition, IL2 receptors were measured using two color fluorescence and flow cytometry with phycoerythrin conjugated anti-IL2 receptor antibody and FITC conjugated OKT11 antibody. The percentage of cells expressing IL2 receptors was 46% for the cells from the young individuals and 23% for cells from old individuals. These results suggest that the age related decline in the proliferative ability of T cells is partially due to a decreased expression of IL2 receptors and that proliferation and IL2 receptor expression is under the control of monocyte accessory cells.

  6. Does chronic exercise attenuate age-related physiological decline in males?

    PubMed

    Hayes, Lawrence D; Grace, Fergal M; Sculthorpe, Nick; Herbert, Peter; Kilduff, Liam P; Baker, Julien S

    2013-01-01

    Alteration in body composition, physical function, and substrate metabolism occur with advancing age. These changes can be attenuated by exercise. This study evaluated whether master athletes (MA [n = 20]) would have improved exercise capabilities, anthropometry, and hormone profiles when compared with age-matched sedentary counterparts (S [n = 28]). The MA group was predominantly aerobically trained with some resistance exercise incorporated in their routine. The VO(2max), peak power output, and salivary testosterone was significantly higher (p < 0.05) in the MA group, while diastolic blood pressure, systolic blood pressure, and body fat percentage were lower (p < 0.05). Cortisol, fat free mass, (FFM) and total body mass were not significantly different between groups. Salivary testosterone correlated positively with VO(2max) (r² = .320), suggesting that increased aerobic capacity is linked with higher concentrations of testosterone. These results suggest that life-long exercise is associated with favorable body composition and attenuation of the age related decline in testosterone. PMID:24067120

  7. Cognitive decline, dietary factors and gut-brain interactions.

    PubMed

    Caracciolo, Barbara; Xu, Weili; Collins, Stephen; Fratiglioni, Laura

    2014-01-01

    Cognitive decline in elderly people often derives from the interaction between aging-related changes and age-related diseases and covers a large spectrum of clinical manifestations, from intact cognition through mild cognitive impairment and dementia. Epidemiological evidence supports the hypothesis that modifiable lifestyle-related factors are associated with cognitive decline, opening new avenues for prevention. Diet in particular has become the object of intense research in relation to cognitive aging and neurodegenerative disease. We reviewed the most recent findings in this rapidly expanding field. Some nutrients, such as vitamins and fatty acids, have been studied longer than others, but strong scientific evidence of an association is lacking even for these compounds. Specific dietary patterns, like the Mediterranean diet, may be more beneficial than a high consumption of single nutrients or specific food items. A strong link between vascular risk factors and dementia has been shown, and the association of diet with several vascular and metabolic diseases is well known. Other plausible mechanisms underlying the relationship between diet and cognitive decline, such as inflammation and oxidative stress, have been established. In addition to the traditional etiological pathways, new hypotheses, such as the role of the intestinal microbiome in cognitive function, have been suggested and warrant further investigation. PMID:24333791

  8. Age-related decline and diagnostic performance of more and less prevalent clinical cases.

    PubMed

    St-Onge, Christina; Landry, Marjolaine; Xhignesse, Marianne; Voyer, Gilles; Tremblay-Lavoie, Stéphanie; Mamede, Sílvia; Schmidt, Henk; Rikers, Remy

    2016-08-01

    Since cognitive abilities have been shown to decrease with age, it is expected that older physicians would not perform as well as their younger counterparts on clinical cases unless their expertise can counteract the cognitive effects of aging. However, studies on the topic have shown contradictory results. This study aimed to further investigate the effect of aging on physicians' diagnostic accuracy when diagnosing prevalent and less prevalent cases based on clinical vignettes. A mixed design was used to assess the influence of case prevalence (high vs. low) as a within-subjects factor, and age group as a between subjects factor (<30; n = 23, 30-39; n = 19, 40-49; n = 27, >50 years old; n = 19) on the diagnostic accuracy of 65 family physicians and 25 residents. Repeated Measure ANOVA revealed a significant effect of case prevalence (p < .001) and age group (p < .001). Post-hoc analyses revealed that younger physicians showed the best performance. This study did not demonstrate the positive effect of experience in older physicians. In line with previous studies on expertise development, findings of the present study suggest that skills should be actively maintained to assure a high performance level throughout one's lifespan. If not, performance level could gradually decline with age. PMID:26584578

  9. Memory’s Aging Echo: Age-related Decline in Neural Reactivation of Perceptual Details During Recollection

    PubMed Central

    McDonough, Ian M.; Cervantes, Sasha N.; Gray, Stephen J.; Gallo, David A.

    2014-01-01

    Episodic memory decline is a hallmark of normal cognitive aging. Here, we report the first event-related fMRI study to directly investigate age differences in the neural reactivation of qualitatively rich perceptual details during recollection. Younger and older adults studied pictures of complex scenes at different presentation durations along with descriptive verbal labels, and these labels subsequently were used during fMRI scanning to cue picture recollections of varying perceptual detail. As expected from prior behavioral work, the two groups subjectively rated their recollections as containing similar amounts of perceptual detail, despite objectively measured recollection impairment in older adults. In both age groups, comparisons of retrieval trials that varied in recollected detail revealed robust activity in brain regions previously linked to recollection, including hippocampus and both medial and lateral regions of the prefrontal and posterior parietal cortex. Critically, this analysis also revealed recollection-related activity in visual processing regions that were active in an independent picture-perception task, and these regions showed age-related reductions in activity during recollection that cannot be attributed to age differences in response criteria. These fMRI findings provide new evidence that aging reduces the absolute quantity of perceptual details that are reactivated from memory, and they help to explain why aging reduces the reliability of subjective memory judgments. PMID:24828546

  10. Age-Related Declines and Disease-Associated Variation in Immune Cell Telomere Length in a Wild Mammal

    PubMed Central

    Beirne, Christopher; Delahay, Richard; Hares, Michelle; Young, Andrew

    2014-01-01

    Immunosenescence, the deterioration of immune system capability with age, may play a key role in mediating age-related declines in whole-organism performance, but the mechanisms that underpin immunosenescence are poorly understood. Biomedical research on humans and laboratory models has documented age and disease related declines in the telomere lengths of leukocytes (‘immune cells’), stimulating interest their having a potentially general role in the emergence of immunosenescent phenotypes. However, it is unknown whether such observations generalise to the immune cell populations of wild vertebrates living under ecologically realistic conditions. Here we examine longitudinal changes in the mean telomere lengths of immune cells in wild European badgers (Meles meles). Our findings provide the first evidence of within-individual age-related declines in immune cell telomere lengths in a wild vertebrate. That the rate of age-related decline in telomere length appears to be steeper within individuals than at the overall population level raises the possibility that individuals with short immune cell telomeres and/or higher rates of immune cell telomere attrition may be selectively lost from this population. We also report evidence suggestive of associations between immune cell telomere length and bovine tuberculosis infection status, with individuals detected at the most advanced stage of infection tending to have shorter immune cell telomeres than disease positive individuals. While male European badgers are larger and show higher rates of annual mortality than females, we found no evidence of a sex difference in either mean telomere length or the average rate of within-individual telomere attrition with age. Our findings lend support to the view that age-related declines in the telomere lengths of immune cells may provide one potentially general mechanism underpinning age-related declines in immunocompetence in natural populations. PMID:25268841

  11. Age-related differences in cognition across the adult lifespan in autism spectrum disorder.

    PubMed

    Lever, Anne G; Geurts, Hilde M

    2016-06-01

    It is largely unknown how age impacts cognition in autism spectrum disorder (ASD). We investigated whether age-related cognitive differences are similar, reduced or increased across the adult lifespan, examined cognitive strengths and weaknesses, and explored whether objective test performance is related to subjective cognitive challenges. Neuropsychological tests assessing visual and verbal memory, generativity, and theory of mind (ToM), and a self-report measure assessing cognitive failures were administered to 236 matched participants with and without ASD, aged 20-79 years (IQ > 80). Group comparisons revealed that individuals with ASD had higher scores on visual memory, lower scores on generativity and ToM, and similar performance on verbal memory. However, ToM impairments were no longer present in older (50+ years) adults with ASD. Across adulthood, individuals with ASD demonstrated similar age-related effects on verbal memory, generativity, and ToM, while age-related differences were reduced on visual memory. Although adults with ASD reported many cognitive failures, those were not associated with neuropsychological test performance. Hence, while some cognitive abilities (visual and verbal memory) and difficulties (generativity and semantic memory) persist across adulthood in ASD, others become less apparent in old age (ToM). Age-related differences characteristic of typical aging are reduced or parallel, but not increased in individuals with ASD, suggesting that ASD may partially protect against an age-related decrease in cognitive functioning. Despite these findings, adults with ASD experience many cognitive daily challenges, which highlights the need for adequate social support and the importance of further research into this topic, including longitudinal studies. Autism Res 2016, 9: 666-676. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. PMID:26333004

  12. Complement C3-Deficient Mice Fail to Display Age-Related Hippocampal Decline.

    PubMed

    Shi, Qiaoqiao; Colodner, Kenneth J; Matousek, Sarah B; Merry, Katherine; Hong, Soyon; Kenison, Jessica E; Frost, Jeffrey L; Le, Kevin X; Li, Shaomin; Dodart, Jean-Cosme; Caldarone, Barbara J; Stevens, Beth; Lemere, Cynthia A

    2015-09-23

    The complement system is part of the innate immune response responsible for removing pathogens and cellular debris, in addition to helping to refine CNS neuronal connections via microglia-mediated pruning of inappropriate synapses during brain development. However, less is known about the role of complement during normal aging. Here, we studied the role of the central complement component, C3, in synaptic health and aging. We examined behavior as well as electrophysiological, synaptic, and neuronal changes in the brains of C3-deficient male mice (C3 KO) compared with age-, strain-, and gender-matched C57BL/6J (wild-type, WT) control mice at postnatal day 30, 4 months, and 16 months of age. We found the following: (1) region-specific and age-dependent synapse loss in aged WT mice that was not observed in C3 KO mice; (2) age-dependent neuron loss in hippocampal CA3 (but not in CA1) that followed synapse loss in aged WT mice, neither of which were observed in aged C3 KO mice; and (3) significantly enhanced LTP and cognition and less anxiety in aged C3 KO mice compared with aged WT mice. Importantly, CA3 synaptic puncta were similar between WT and C3 KO mice at P30. Together, our results suggest a novel and prominent role for complement protein C3 in mediating aged-related and region-specific changes in synaptic function and plasticity in the aging brain. Significance statement: The complement cascade, part of the innate immune response to remove pathogens, also plays a role in synaptic refinement during brain development by the removal of weak synapses. We investigated whether complement C3, a central component, affects synapse loss during aging. Wild-type (WT) and C3 knock-out (C3 KO) mice were examined at different ages. The mice were similar at 1 month of age. However, with aging, WT mice lost synapses in specific brain regions, especially in hippocampus, an area important for memory, whereas C3 KO mice were protected. Aged C3 KO mice also performed better on

  13. Examining age-related shared variance between face cognition, vision, and self-reported physical health: a test of the common cause hypothesis for social cognition

    PubMed Central

    Olderbak, Sally; Hildebrandt, Andrea; Wilhelm, Oliver

    2015-01-01

    The shared decline in cognitive abilities, sensory functions (e.g., vision and hearing), and physical health with increasing age is well documented with some research attributing this shared age-related decline to a single common cause (e.g., aging brain). We evaluate the extent to which the common cause hypothesis predicts associations between vision and physical health with social cognition abilities specifically face perception and face memory. Based on a sample of 443 adults (17–88 years old), we test a series of structural equation models, including Multiple Indicator Multiple Cause (MIMIC) models, and estimate the extent to which vision and self-reported physical health are related to face perception and face memory through a common factor, before and after controlling for their fluid cognitive component and the linear effects of age. Results suggest significant shared variance amongst these constructs, with a common factor explaining some, but not all, of the shared age-related variance. Also, we found that the relations of face perception, but not face memory, with vision and physical health could be completely explained by fluid cognition. Overall, results suggest that a single common cause explains most, but not all age-related shared variance with domain specific aging mechanisms evident. PMID:26321998

  14. Examining age-related shared variance between face cognition, vision, and self-reported physical health: a test of the common cause hypothesis for social cognition.

    PubMed

    Olderbak, Sally; Hildebrandt, Andrea; Wilhelm, Oliver

    2015-01-01

    The shared decline in cognitive abilities, sensory functions (e.g., vision and hearing), and physical health with increasing age is well documented with some research attributing this shared age-related decline to a single common cause (e.g., aging brain). We evaluate the extent to which the common cause hypothesis predicts associations between vision and physical health with social cognition abilities specifically face perception and face memory. Based on a sample of 443 adults (17-88 years old), we test a series of structural equation models, including Multiple Indicator Multiple Cause (MIMIC) models, and estimate the extent to which vision and self-reported physical health are related to face perception and face memory through a common factor, before and after controlling for their fluid cognitive component and the linear effects of age. Results suggest significant shared variance amongst these constructs, with a common factor explaining some, but not all, of the shared age-related variance. Also, we found that the relations of face perception, but not face memory, with vision and physical health could be completely explained by fluid cognition. Overall, results suggest that a single common cause explains most, but not all age-related shared variance with domain specific aging mechanisms evident. PMID:26321998

  15. Atrial Fibrillation, Cognitive Decline And Dementia

    PubMed Central

    Alonso, Alvaro; Arenas de Larriva, Antonio P.

    2016-01-01

    Atrial fibrillation (AF) is a common cardiac arrhythmia. Growing evidence supports a role for AF as a risk factor for cognitive decline and dementia. In this review, we summarize epidemiologic observations linking AF with cognitive outcomes, describe potential mechanisms, and explore the impact of AF treatments on cognitive decline and dementia. Community-based, observational studies show a consistent higher rate of cognitive decline and risk of dementia in persons with AF. These associations are partly due to the increased risk of clinical stroke in AF, but other mechanisms, including incidence of silent cerebral infarcts, microbleeds, and cerebral hypoperfusion, are likely additional contributors. Adequate oral anticoagulation and improved management of the overall cardiovascular risk profile in persons with AF offer the promise of reducing the impact of AF on cognitive decline and dementia. PMID:27547248

  16. Periodontitis and Cognitive Decline in Alzheimer's Disease.

    PubMed

    Ide, Mark; Harris, Marina; Stevens, Annette; Sussams, Rebecca; Hopkins, Viv; Culliford, David; Fuller, James; Ibbett, Paul; Raybould, Rachel; Thomas, Rhodri; Puenter, Ursula; Teeling, Jessica; Perry, V Hugh; Holmes, Clive

    2016-01-01

    Periodontitis is common in the elderly and may become more common in Alzheimer's disease because of a reduced ability to take care of oral hygiene as the disease progresses. Elevated antibodies to periodontal bacteria are associated with an increased systemic pro-inflammatory state. Elsewhere raised serum pro-inflammatory cytokines have been associated with an increased rate of cognitive decline in Alzheimer's disease. We hypothesized that periodontitis would be associated with increased dementia severity and a more rapid cognitive decline in Alzheimer's disease. We aimed to determine if periodontitis in Alzheimer's disease is associated with both increased dementia severity and cognitive decline, and an increased systemic pro inflammatory state. In a six month observational cohort study 60 community dwelling participants with mild to moderate Alzheimer's Disease were cognitively assessed and a blood sample taken for systemic inflammatory markers. Dental health was assessed by a dental hygienist, blind to cognitive outcomes. All assessments were repeated at six months. The presence of periodontitis at baseline was not related to baseline cognitive state but was associated with a six fold increase in the rate of cognitive decline as assessed by the ADAS-cog over a six month follow up period. Periodontitis at baseline was associated with a relative increase in the pro-inflammatory state over the six month follow up period. Our data showed that periodontitis is associated with an increase in cognitive decline in Alzheimer's Disease, independent to baseline cognitive state, which may be mediated through effects on systemic inflammation. PMID:26963387

  17. Myelin Breakdown Mediates Age-Related Slowing in Cognitive Processing Speed in Healthy Elderly Men

    ERIC Educational Resources Information Center

    Lu, Po H.; Lee, Grace J.; Tishler, Todd A.; Meghpara, Michael; Thompson, Paul M.; Bartzokis, George

    2013-01-01

    Background: To assess the hypothesis that in a sample of very healthy elderly men selected to minimize risk for Alzheimer's disease (AD) and cerebrovascular disease, myelin breakdown in late-myelinating regions mediates age-related slowing in cognitive processing speed (CPS). Materials and methods: The prefrontal lobe white matter and the genu of…

  18. Cognitive Abilities Explaining Age-Related Changes in Time Perception of Short and Long Durations

    ERIC Educational Resources Information Center

    Zelanti, Pierre S.; Droit-Volet, Sylvie

    2011-01-01

    The current study investigated how the development of cognitive abilities explains the age-related changes in temporal judgment over short and long duration ranges from 0.5 to 30 s. Children (5- and 9-year-olds) as well as adults were given a temporal bisection task with four different duration ranges: a duration range shorter than 1 s, two…

  19. Age-Related Decline and Diagnostic Performance of More and Less Prevalent Clinical Cases

    ERIC Educational Resources Information Center

    St-Onge, Christina; Landry, Marjolaine; Xhignesse, Marianne; Voyer, Gilles; Tremblay-Lavoie, Stéphanie; Mamede, Sílvia; Schmidt, Henk; Rikers, Remy

    2016-01-01

    Since cognitive abilities have been shown to decrease with age, it is expected that older physicians would not perform as well as their younger counterparts on clinical cases unless their expertise can counteract the cognitive effects of aging. However, studies on the topic have shown contradictory results. This study aimed to further investigate…

  20. Can exercise prevent cognitive decline?

    PubMed

    Behrman, Sophie; Ebmeier, Klaus P

    2014-01-01

    As the tolerability of pharmacological agents decreases with age, exercise may be particularly helpful as a possible treatment or stabiliser of mood and cognitive function in older age. Exercise has been most commonly evaluated for the treatment of depression. Exercise interventions designed primarily for treatment of physical conditions in the elderly do appear to confer psychological benefits as well, with reduction in depressive symptoms over the course of treatment. The effects of exercise on reducing depressive symptoms are not dissimilar to the effects of antidepressant drugs and cognitive behaviour therapy. Exercise may be a useful low-tech intervention for people with mild to moderate depression. In particular, exercise may be helpful in the elderly and in patients who have had insufficient response to, or are intolerant of, pharmacotherapy. Mastery of a new skill and positive feedback from others may increase feelings of self-esteem and improve mood. Exercise may distract participants from persistent negative thoughts. Exercise has been shown to improve executive function acutely in adults of all ages. It is possible that dance routines or other exercise regimens requiring some cognitive input may confer additional benefit to cognitive function. Exercise has a moderate effect on the ability of people with dementia to perform activities of daily living and may improve cognitive function. Midlife exercise may also have an impact on later cognitive function. PMID:24617099

  1. Age-related decline in functional connectivity of the vestibular cortical network.

    PubMed

    Cyran, Carolin Anna Maria; Boegle, Rainer; Stephan, Thomas; Dieterich, Marianne; Glasauer, Stefan

    2016-04-01

    In the elderly, major complaints include dizziness and an increasing number of falls, possibly related to an altered processing of vestibular sensory input. In this study, we therefore investigate age-related changes induced by processing of vestibular sensory stimulation. While previous functional imaging studies of healthy aging have investigated brain function during task performance or at rest, we used galvanic vestibular stimulation during functional MRI in a task-free sensory stimulation paradigm to study the effect of healthy aging on central vestibular processing, which might only become apparent during stimulation processing. Since aging may affect signatures of brain function beyond the BOLD-signal amplitude-such as functional connectivity or temporal signal variability-we employed independent component analysis and partial least squares analysis of temporal signal variability. We tested for age-associated changes unrelated to vestibular processing, using a motor paradigm, voxel-based morphometry and diffusion tensor imaging. This allows us to control for general age-related modifications, possibly originating from vascular, atrophic or structural connectivity changes. Age-correlated decreases of functional connectivity and increases of BOLD-signal variability were associated with multisensory vestibular networks. In contrast, no age-related functional connectivity changes were detected in somatosensory networks or during the motor paradigm. The functional connectivity decrease was not due to structural changes but to a decrease in response amplitude. In synopsis, our data suggest that both the age-dependent functional connectivity decrease and the variability increase may be due to deteriorating reciprocal cortico-cortical inhibition with age and related to multimodal vestibular integration of sensory inputs. PMID:25567421

  2. Caloric restriction impedes age-related decline of mitochondrial function and neuronal activity

    PubMed Central

    Lin, Ai-Ling; Coman, Daniel; Jiang, Lihong; Rothman, Douglas L; Hyder, Fahmeed

    2014-01-01

    Caloric restriction (CR) prolongs lifespan and retards many detrimental effects of aging, but its effect on brain mitochondrial function and neuronal activity—especially in healthy aging—remains unexplored. Here we measured rates of neuronal glucose oxidation and glutamate–glutamine neurotransmitter cycling in young control, old control (i.e., healthy aging), and old CR rats using in vivo nuclear magnetic resonance spectroscopy. We found that, compared with the young control, neuronal energy production and neurotransmission rates were significantly reduced in healthy aging, but were preserved in old CR rats. The results suggest that CR mitigated the age-related deceleration of brain physiology. PMID:24984898

  3. Protective effect of myostatin gene deletion on aging-related muscle metabolic decline.

    PubMed

    Chabi, B; Pauly, M; Carillon, J; Carnac, G; Favier, F B; Fouret, G; Bonafos, B; Vanterpool, F; Vernus, B; Coudray, C; Feillet-Coudray, C; Bonnieu, A; Lacan, D; Koechlin-Ramonatxo, C

    2016-06-01

    While myostatin gene deletion is a promising therapy to fight muscle loss during aging, this approach induces also skeletal muscle metabolic changes such as mitochondrial deficits, redox alteration and increased fatigability. In the present study, we evaluated the effects of aging on these features in aged wild-type (WT) and mstn knockout (KO) mice. Moreover, to determine whether an enriched-antioxidant diet may be useful to prevent age-related disorders, we orally administered to the two genotypes a melon concentrate rich in superoxide dismutase for 12 weeks. We reported that mitochondrial functional abnormalities persisted (decreased state 3 and 4 of respiration; p<0.05) in skeletal muscle from aged KO mice; however, differences with WT mice were attenuated at old age in line with reduced difference on running endurance between the two genotypes. Interestingly, we showed an increase in glutathione levels, associated with lower lipid peroxidation levels in KO muscle. Enriched antioxidant diet reduced the aging-related negative effects on maximal aerobic velocity and running limit time (p<0.05) in both groups, with systemic adaptations on body weight. The redox status and the hypertrophic phenotype appeared to be beneficial to KO mice, mitigating the effect of aging on the skeletal muscle metabolic remodeling. PMID:26944368

  4. Age-Related Declines in the Fidelity of Newly Acquired Category Representations

    ERIC Educational Resources Information Center

    Davis, Tyler; Love, Bradley C.; Maddox, W. Todd

    2012-01-01

    We present a theory suggesting that the ability to build category representations that reflect the nuances of category structures in the environment depends upon clustering mechanisms instantiated in an MTL-PFC-based circuit. Because function in this circuit declines with age, we predict that the ability to build category representations will be…

  5. Lifelong strength training mitigates the age-related decline in efferent drive.

    PubMed

    Unhjem, Runar; Nygård, Mona; van den Hoven, Lene T; Sidhu, Simranjit K; Hoff, Jan; Wang, Eivind

    2016-08-01

    Recently, we documented age-related attenuation of efferent drive to contracting skeletal muscle. It remains elusive if this indication of reduced muscle strength is present with lifelong strength training. For this purpose, we examined evoked potentials in the calf muscles of 11 [71 ± 4 (SD) yr] strength-trained master athletes (MA) contrasted with 10 (71 ± 4 yr) sedentary (SO) and 11 (73 ± 6 yr) recreationally active (AO) old subjects, as well as 9 (22 ± 2 yr) young controls. As expected, MA had higher leg press maximal strength (MA, 185 ± 32 kg; AO, 128 ± 15 kg; SO, 106 ± 11 kg; young, 147 ± 22 kg, P < 0.01) and rate of force development (MA, 5,588 ± 2,488 N/s; AO, 2,156 ± 1,100 N/s; SO, 2,011 ± 825 N/s; young, 3,663 ± 1,140 N/s, P < 0.05) than the other groups. MA also exhibited higher musculus soleus normalized V waves during maximal voluntary contractions (MVC) [maximal V wave amplitude/maximal M wave during MVC (Vsup/Msup); 0.28 ± 0.15] than AO (0.13 ± 0.06, P < 0.01) and SO (0.11 ± 0.05, P < 0.01), yet lower than young (0.45 ± 0.12, P < 0.01). No differences were apparent between the old groups in H reflex recorded at rest or during MVC [maximal H reflex amplitude/maximal M wave during rest (Hmax/Mmax); maximal H reflex amplitude during MVC/maximal M wave during MVC (Hsup/Msup)], and all were lower (P < 0.01) than young. MA (34.4 ± 2.1 ms) had shorter (P < 0.05) H reflex latency compared with AO (36.4 ± 3.7 ms) and SO (37.3 ± 3.2 ms), but longer (P < 0.01) than young (30.7 ± 2.0 ms). Using interpolated twitch analysis, MA (89 ± 7%) had plantar flexion voluntary activation similar to young (90 ± 6%), and this was higher (P < 0.05), or tended to be higher (P = 0.06-0.09), than SO (83 ± 10%) and AO (84 ± 5%). These observations suggest that lifelong strength training has a protective effect against age-related attenuation of efferent drive. In contrast, no beneficial effect seems to derive from habitual recreational activity, indicating

  6. Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice.

    PubMed

    Villeda, Saul A; Plambeck, Kristopher E; Middeldorp, Jinte; Castellano, Joseph M; Mosher, Kira I; Luo, Jian; Smith, Lucas K; Bieri, Gregor; Lin, Karin; Berdnik, Daniela; Wabl, Rafael; Udeochu, Joe; Wheatley, Elizabeth G; Zou, Bende; Simmons, Danielle A; Xie, Xinmin S; Longo, Frank M; Wyss-Coray, Tony

    2014-06-01

    As human lifespan increases, a greater fraction of the population is suffering from age-related cognitive impairments, making it important to elucidate a means to combat the effects of aging. Here we report that exposure of an aged animal to young blood can counteract and reverse pre-existing effects of brain aging at the molecular, structural, functional and cognitive level. Genome-wide microarray analysis of heterochronic parabionts--in which circulatory systems of young and aged animals are connected--identified synaptic plasticity-related transcriptional changes in the hippocampus of aged mice. Dendritic spine density of mature neurons increased and synaptic plasticity improved in the hippocampus of aged heterochronic parabionts. At the cognitive level, systemic administration of young blood plasma into aged mice improved age-related cognitive impairments in both contextual fear conditioning and spatial learning and memory. Structural and cognitive enhancements elicited by exposure to young blood are mediated, in part, by activation of the cyclic AMP response element binding protein (Creb) in the aged hippocampus. Our data indicate that exposure of aged mice to young blood late in life is capable of rejuvenating synaptic plasticity and improving cognitive function. PMID:24793238

  7. Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice

    PubMed Central

    Villeda, Saul A; Plambeck, Kristopher E; Middeldorp, Jinte; Castellano, Joseph M; Mosher, Kira I; Luo, Jian; Smith, Lucas K; Bieri, Gregor; Lin, Karin; Berdnik, Daniela; Wabl, Rafael; Udeochu, Joe; Wheatley, Elizabeth G; Zou, Bende; Simmons, Danielle A; Xie, Xinmin S; Longo, Frank M; Wyss-Coray, Tony

    2014-01-01

    As human lifespan increases, a greater fraction of the population is suffering from age-related cognitive impairments, making it important to elucidate a means to combat the effects of aging1,2. Here we report that exposure of an aged animal to young blood can counteract and reverse pre-existing effects of brain aging at the molecular, structural, functional and cognitive level. Genome-wide microarray analysis of heterochronic parabionts—in which circulatory systems of young and aged animals are connected—identified synaptic plasticity–related transcriptional changes in the hippocampus of aged mice. Dendritic spine density of mature neurons increased and synaptic plasticity improved in the hippocampus of aged heterochronic parabionts. At the cognitive level, systemic administration of young blood plasma into aged mice improved age-related cognitive impairments in both contextual fear conditioning and spatial learning and memory. Structural and cognitive enhancements elicited by exposure to young blood are mediated, in part, by activation of the cyclic AMP response element binding protein (Creb) in the aged hippocampus. Our data indicate that exposure of aged mice to young blood late in life is capable of rejuvenating synaptic plasticity and improving cognitive function. PMID:24793238

  8. Formaldehyde as a trigger for protein aggregation and potential target for mitigation of age-related, progressive cognitive impairment.

    PubMed

    Su, Tao; Monte, Woodrow C; Hu, Xintian; He, Yingge; He, Rongqiao

    2016-01-01

    Recently, formaldehyde (FA), existing in a number of different cells including neural cells, was found to affect age-related cognitive impairment. Oral administration of methanol (the metabolic precursor of FA) triggers formation of senile plaques (SPs) and Tau hyperphosphorylation in the brains of monkeys with memory decline. Intraperitoneal injection of FA leads to hyperphosphorylation of Tau in wild-type mouse brains and N2a cells through activation of glycogen synthase kinase-3β (GSK-3β). Furthermore, formaldehyde at low concentrations can directly induce Tau aggregation and amyloid β (Aβ) peptide deposits in vitro. Formaldehyde-induced Tau aggregation is implicated in cytotoxicity and neural cell apoptosis. Clarifying how FA triggers Aβ deposits and Tau hyperphosphorlyation will not only improve our understanding of the molecular and cellular mechanisms of age-related cognitive impairment but will also contribute to the ongoing investigation of alternate targets for new drugs. Here, we review the role of FA, particularly that of endogenous origin, in protein aggregation and as a potential drug intervention in the development of agerelated cognitive impairment. PMID:26268337

  9. Glutamate cysteine ligase and the age-related decline in cellular glutathione: The therapeutic potential of γ-glutamylcysteine.

    PubMed

    Ferguson, Gavin; Bridge, Wallace

    2016-03-01

    A consistent underlying index of aging is a decline in the cellular levels of the tripeptide glutathione (GSH). GSH is an essential thiol antioxidant produced in the cytosol of all cells and plays a key role in protecting against oxidative stress by neutralising free radicals and reactive oxygen species (ROS). The decline in GSH has been associated with changes in the expression and activity of the rate-limiting enzyme glutamate cysteine ligase (GCL), which produces the intermediate dipeptide γ-glutamylcysteine (γ-GC). The molecular mechanisms that affect these age-related changes remain unclear due to the complexity of GCL regulation. Impairment of the transcriptional activity of Nrf2 has been demonstrated to contribute to GCL dysregulation in aged rats. However, considering the complex nature of GCL regulation, relatively little research has been conducted to investigate the age-associated post-transcriptional controls of the enzyme. Defining these unknown mechanisms may inform our understanding of the aetiology of many age-related diseases and assist in formulating appropriate therapeutic strategies. This review focuses on the suitability of treatment with exogenous γ-GC to raise GSH levels by circumventing the age-related dysregulation of the rate-limiting step of GSH, providing promise for future research for the treatment of chronic oxidative stress-related diseases. PMID:26845022

  10. Age-related annual decline of lung function in patients with COPD

    PubMed Central

    Kim, Soo Jung; Lee, Jinwoo; Park, Young Sik; Lee, Chang-Hoon; Yoon, Ho Il; Lee, Sang-Min; Yim, Jae-Joon; Kim, Young Whan; Han, Sung Koo; Yoo, Chul-Gyu

    2016-01-01

    Background According to the Fletcher–Peto curve, rate of decline in forced expiratory volume in 1-second (FEV1) accelerates as age increases. However, recent studies have not demonstrated that the rate of FEV1 decline accelerates with age among COPD patients. The objective of the study is to evaluate annual rate of FEV1 decline as age increases among COPD patients. Methods In this retrospective cohort study, we enrolled COPD patients who were followed up at two tertiary care university hospitals from January 2000 to August 2013. COPD was defined as post-bronchodilator (BD) FEV1/forced vital capacity (FVC) of <0.7. All participants had more than two spirometries, including BD response. Age groups were categorized as follows: below versus above median age or four quartiles. Results A total of 518 participants (94.2% male; median age, 67 years; range, 42–90 years) were included. Mean absolute and predictive values of post-BD FEV1 were 1.57±0.62 L and 52.53%±18.29%, respectively. Distribution of Global initiative for Chronic Obstructive Lung Disease groups did not show statistical differences between age groups categorized by two different criteria. After grouping the population by age quartiles, the rate of FEV1 decline was faster among older patients than younger ones whether expressed as absolute value (−10.60±5.57 mL/year, −15.84±6.01 mL/year, −18.63±5.53 mL/year, 32.94±6.01 mL/year, respectively; P=0.048) or predicted value (−0.34%±0.19%/year, −0.53%±0.21%/year, −0.62%±0.19%/year, −1.26%±0.21%/year, respectively, P=0.010). Conclusion As suggested conceptually by the Fletcher−Peto curve, annual FEV1 decline among COPD patients is accelerated among older patients than younger ones. PMID:26766907

  11. Translational gene mapping of cognitive decline

    PubMed Central

    Wilmot, Beth; McWeeney, Shannon K.; Nixon, Randal R.; Montine, Thomas J.; Laut, Jamie; Harrington, Christina A.; Kaye, Jeffrey A.; Kramer, Patricia L.

    2009-01-01

    The ability to maintain cognitive function during aging is a complex process subject to genetic and environmental influences. Alzheimer’s disease (AD) is the most common disorder causing cognitive decline among the elderly. Among those with AD, there is broad variation in the relationship between AD neuropathology and clinical manifestations of dementia. Differences in expression of genes involved in neural processing pathways may contribute to individual differences in maintenance of cognitive function. We performed whole genome expression profiling of RNA obtained from frontal cortex of clinically non-demented and AD subjects to identify genes associated with brain aging and cognitive decline. Genetic mapping information and biological function annotation were incorporated to highlight genes of particular interest. The candidate genes identified in this study were compared with those from two other studies in different tissues to identify common underlying transcriptional profiles. In addition to confirming sweeping transcriptomal differences documented in previous studies of cognitive decline, we present new evidence for up-regulation of actin-related processes and down-regulation of translation, RNA processing and localization, and vesicle-mediated transport in individuals with cognitive decline. PMID:17174450

  12. Age-related decline of peripheral visual processing: the role of eye movements.

    PubMed

    Beurskens, Rainer; Bock, Otmar

    2012-03-01

    Earlier work suggests that the area of space from which useful visual information can be extracted (useful field of view, UFoV) shrinks in old age. We investigated whether this shrinkage, documented previously with a visual search task, extends to a bimanual tracking task. Young and elderly subjects executed two concurrent tracking tasks with their right and left arms. The separation between tracking displays varied from 3 to 35 cm. Subjects were asked to fixate straight ahead (condition FIX) or were free to move their eyes (condition FREE). Eye position was registered. In FREE, young subjects tracked equally well at all display separations. Elderly subjects produced higher tracking errors, and the difference between age groups increased with display separation. Eye movements were comparable across age groups. In FIX, elderly and young subjects tracked less well at large display separations. Seniors again produced higher tracking errors in FIX, but the difference between age groups did not increase reliably with display separation. However, older subjects produced a substantial number of illicit saccades, and when the effect of those saccades was factored out, the difference between young and older subjects' tracking did increase significantly with display separation in FIX. We conclude that the age-related shrinkage of UFoV, previously documented with a visual search task, is observable with a manual tracking task as well. Older subjects seem to partly compensate their deficit by illicit saccades. Since the deficit is similar in both conditions, it may be located downstream from the convergence of retinal and oculomotor signals. PMID:22179529

  13. An age-related shift of resting-state functional connectivity of the subthalamic nucleus: a potential mechanism for compensating motor performance decline in older adults

    PubMed Central

    Mathys, Christian; Hoffstaedter, Felix; Caspers, Julian; Caspers, Svenja; Südmeyer, Martin; Grefkes, Christian; Eickhoff, Simon B.; Langner, Robert

    2014-01-01

    Healthy aging is associated with decline in basic motor functioning and higher motor control. Here, we investigated age-related differences in the brain-wide functional connectivity (FC) pattern of the subthalamic nucleus (STN), which plays an important role in motor response control. As earlier studies revealed functional coupling between STN and basal ganglia, which both are known to influence the conservativeness of motor responses on a superordinate level, we tested the hypothesis that STN FC with the striatum becomes dysbalanced with age. To this end, we performed a seed-based resting-state analysis of fMRI data from 361 healthy adults (mean age: 41.8, age range: 18–85) using bilateral STN as the seed region of interest. Age was included as a covariate to identify regions showing age-related changes of FC with the STN seed. The analysis revealed positive FC of the STN with several previously described subcortical and cortical regions like the anterior cingulate and sensorimotor cortex, as well as not-yet reported regions including central and posterior insula. With increasing age, we observed reduced positive FC with caudate nucleus, thalamus, and insula as well as increased positive FC with sensorimotor cortex and putamen. Furthermore, an age-related reduction of negative FC was found with precuneus and posterior cingulate cortex. We suggest that this reduced de-coupling of brain areas involved in self-relevant but motor-unrelated cognitive processing (i.e. precuneus and posterior cingulate cortex) from the STN motor network may represent a potential mechanism behind the age-dependent decline in motor performance. At the same time, older adults appear to compensate for this decline by releasing superordinate motor control areas, in particular caudate nucleus and insula, from STN interference while increasing STN-mediated response control over lower level motor areas like sensorimotor cortex and putamen. PMID:25100995

  14. Selected Micronutrients in Cognitive Decline Prevention and Therapy.

    PubMed

    Visioli, Francesco; Burgos-Ramos, Emma

    2016-08-01

    Population aging is a worldwide demographic trend. Consequently, the prevalence of chronic age-related conditions such as clinically diagnosed neurological diseases, cognitive decline, and dementia will significantly increase in the near future. The important role of diets and healthy lifestyle as preventative of neurodegenerative diseases is widely accepted nowadays, and it may provide preventive strategies in very early, non-symptomatic phases of dementia well, especially because there are still no effective treatments for it. In this article, we review the known effects of selected micronutrients on the aging brain and we propose strategies for dietary improvements. PMID:26198569

  15. Subjective Cognitive Decline: Self and Informant Comparisons

    PubMed Central

    Chen, Kewei; Locke, Dona E.C.; Lee, Wendy; Roontiva, Auttawut; Bandy, Dan; Fleisher, Adam S.; Reiman, Eric M.

    2013-01-01

    Background It is unclear whether self or informant-based subjective cognition better distinguishes emotional factors from early stage Alzheimer’s disease (AD). Methods 447 healthy members of the Arizona Apolipoprotein E (APOE) Cohort and their informants completed both the self and informant paired Multidimensional Assessment of Neurodegenerative Symptoms questionnaire (MANS). Results 30.6% of members and 26.2% of informants endorsed decline on the MANS. Both self and informant-based decliners had higher scores of psychological distress and slightly lower cognitive scores than nondecliners. Over the next 6.7 years, 20 developed mild cognitive impairment (MCI). Converters were older at entry than nonconverters (63.8[7.0] vs 58.8[7.3] years, p=.003), 85% were APOE e4 carriers (p<.0001), and they self-endorsed decline earlier than informants (58.9[39.2] vs 28.0[40.4] months before MCI; p=.002). Conclusions Both self and informant based subjective decline correlated with greater psychological distress, and slightly lower cognitive performance. Those with incident MCI generally self-endorsed decline earlier than informants. PMID:23562429

  16. Neural mechanisms of ageing and cognitive decline

    PubMed Central

    Bishop, Nicholas A.; Lu, Tao; Yankner, Bruce A.

    2010-01-01

    During the past century, treatments for the diseases of youth and middle age have helped raise life expectancy significantly. However, cognitive decline has emerged as one of the greatest health threats of old age, with nearly 50% of adults over the age of 85 afflicted with Alzheimer’s disease. Developing therapeutic interventions for such conditions demands a greater understanding of the processes underlying normal and pathological brain ageing. Recent advances in the biology of ageing in model organisms, together with molecular and systems-level studies of the brain, are beginning to shed light on these mechanisms and their potential roles in cognitive decline. PMID:20336135

  17. Exercise as an Intervention for the Age-Related Decline in Neural Metabolic Support

    PubMed Central

    Anderson, Brenda J.; Greenwood, Shayri J.; McCloskey, Daniel

    2010-01-01

    To identify interventions for brain aging, we must first identify the processes in which we hope to intervene. Brain aging is a period of decreasing functional capacity and increasing vulnerability, which reflect a reduction in morphological organization and perhaps degeneration. Since life is ultimately dependent upon the ability to maintain cellular organization through metabolism, this review explores evidence for a decline in neural metabolic support during aging, which includes a reduction in whole brain cerebral blood flow, and cellular metabolic capacity. Capillary density may also decrease with age, although the results are less clear. Exercise may be a highly effective intervention for brain aging, because it improves the cardiovascular system as a whole, and increases regional capillary density and neuronal metabolic capacity. Although the evidence is strongest for motor regions, more work may yield additional evidence for exercise-related improvement in metabolic support in non-motor regions. The protective effects of exercise may be specific to brain region and the type of insult. For example, exercise protects striatal cells from ischemia, but it produces mixed results after hippocampal seizures. Exercise can improve metabolic support and bioenergetic capacity in adult animals, but it remains to be determined whether it has similar effects in aging animals. What is clear is that exercise can influence the multiple levels of support necessary for maintaining optimal neuronal function, which is unique among proposed interventions for aging. PMID:20802804

  18. Effect of IP3R3 and NPY on age-related declines in olfactory stem cell proliferation

    PubMed Central

    Jia, Cuihong; Hegg, Colleen C.

    2014-01-01

    Losing the sense of smell due to aging compromises health and quality of life. In the mouse olfactory epithelium (OE) aging reduces the capacity for tissue homeostasis and regeneration. The microvillous cell subtype that expresses both inositol trisphosphate receptor type 3 (IP3R3) and the neuroproliferative factor neuropeptide Y (NPY) is critical for regulation of homeostasis, yet its role in aging is undefined. We hypothesized that an age-related decline in IP3R3 expression and NPY signaling underlie age-related homeostatic changes and olfactory dysfunction. We found a decrease in IP3R3+ and NPY+ microvillous cell numbers and NPY protein, and a reduced sensitivity to NPY-mediated proliferation over 24 months. However, in IP3R3-deficient mice, there was no further age-related reduction in cell numbers, proliferation, or olfactory function compared to wild-type. The proliferative response was impaired in aged IP3R3-deficient mice when injury was caused by satratoxin-G, which induces IP3R3-mediated NPY release, but not by bulbectomy, which does not evoke NPY release. These data identify IP3R3 and NPY signaling as targets for improving recovery following olfactotoxicant exposure. PMID:25482245

  19. Effect of IP3R3 and NPY on age-related declines in olfactory stem cell proliferation.

    PubMed

    Jia, Cuihong; Hegg, Colleen C

    2015-02-01

    Losing the sense of smell because of aging compromises health and quality of life. In the mouse olfactory epithelium, aging reduces the capacity for tissue homeostasis and regeneration. The microvillous cell subtype that expresses both inositol trisphosphate receptor type 3 (IP3R3) and the neuroproliferative factor neuropeptide Y (NPY) is critical for regulation of homeostasis, yet its role in aging is undefined. We hypothesized that an age-related decline in IP3R3 expression and NPY signaling underlie age-related homeostatic changes and olfactory dysfunction. We found a decrease in IP3R3(+) and NPY(+) microvillous cell numbers and NPY protein and a reduced sensitivity to NPY-mediated proliferation over 24 months. However, in IP3R3-deficient mice, there was no further age-related reduction in cell numbers, proliferation, or olfactory function compared with wild type. The proliferative response was impaired in aged IP3R3-deficient mice when injury was caused by satratoxin G, which induces IP3R3-mediated NPY release, but not by bulbectomy, which does not evoke NPY release. These data identify IP3R3 and NPY signaling as targets for improving recovery following olfactotoxicant exposure. PMID:25482245

  20. Caloric restriction promotes genomic stability by induction of base excision repair and reversal of its age-related decline.

    PubMed

    Cabelof, Diane C; Yanamadala, Sunitha; Raffoul, Julian J; Guo, ZhongMao; Soofi, Abdulsalam; Heydari, Ahmad R

    2003-03-01

    Caloric restriction is a potent experimental manipulation that extends mean and maximum life span and delays the onset and progression of tumors in laboratory rodents. While caloric restriction (CR) clearly protects the genome from deleterious damage, the mechanism by which genomic stability is achieved remains unclear. We provide evidence that CR promotes genomic stability by increasing DNA repair capacity, specifically base excision repair (BER). CR completely reverses the age-related decline in BER capacity (P<0.01) in all tissues tested (brain, liver, spleen and testes) providing aged, CR animals with the BER phenotype of young, ad libitum-fed animals. This CR-induced reversal of the aged BER phenotype is accompanied by a reversal in the age-related decline in DNA polymerase beta (beta-pol), a rate-limiting enzyme in the BER pathway. CR significantly reversed the age-related loss of beta-pol protein levels (P<0.01), mRNA levels (P<0.01) and enzyme activity (P<0.01) in all tissues tested. Additionally, in young (4-6-month-old) CR animals a significant up-regulation in BER capacity, beta-pol protein and beta-pol mRNA is observed (P<0.01), demonstrating an early effect of CR that may provide insight in distinguishing the anti-tumor from the anti-aging effects of CR. This up-regulation in BER by caloric restriction in young animals corresponds to increased protection from carcinogen exposure, as mutation frequency is significantly reduced in CR animals exposed to either DMS or 2-nitropropane (2-NP) (P<0.01). Overall the data suggest an important biological consequence of moderate BER up-regulation and provides support for the hormesis theory of caloric restriction. PMID:12547392

  1. Migraine and cognitive decline: A topical review

    PubMed Central

    Rist, Pamela M.; Kurth, Tobias

    2013-01-01

    Migraine has been linked with an increased risk of stroke and an increased prevalence of clinically silent brain lesions and white matter hyperintensities. As it is known that stroke and structural brain lesions are associated with an increased risk of cognitive decline, it has been hypothesized that migraine may be a progressive brain disorder and associated with an increased risk of cognitive impairment. Given the prevalence of migraine in the population, especially among women, and the aging of the population, an association between migraine and cognitive impairment would have substantial public health implications. In this review, we will summarize the existing evidence evaluating the association between migraine and cognitive function. Additionally, we will discuss methodological issues in migraine and cognitive function assessment and elaborate on study design strategies to address this important question. PMID:23405909

  2. Age-Related Changes in Creative Thinking

    ERIC Educational Resources Information Center

    Roskos-Ewoldsen, Beverly; Black, Sheila R.; Mccown, Steven M.

    2008-01-01

    Age-related differences in cognitive processes were used to understand age-related declines in creativity. According to the Geneplore model (Finke, Ward, & Smith, 1992), there are two phases of creativity--generating an idea and exploring the implications of the idea--each with different underlying cognitive processes. These two phases are…

  3. Reversal of cognitive decline in Alzheimer's disease

    PubMed Central

    Bredesen, Dale E.; Amos, Edwin C.; Canick, Jonathan; Ackerley, Mary; Raji, Cyrus; Fiala, Milan; Ahdidan, Jamila

    2016-01-01

    Alzheimer's disease is one of the most significant healthcare problems nationally and globally. Recently, the first description of the reversal of cognitive decline in patients with early Alzheimer's disease or its precursors, MCI (mild cognitive impairment) and SCI (subjective cognitive impairment), was published [1]. The therapeutic approach used was programmatic and personalized rather than monotherapeutic and invariant, and was dubbed metabolic enhancement for neurodegeneration (MEND). Patients who had had to discontinue work were able to return to work, and those struggling at work were able to improve their performance. The patients, their spouses, and their co-workers all reported clear improvements. Here we report the results from quantitative MRI and neuropsychological testing in ten patients with cognitive decline, nine ApoE4+ (five homozygous and four heterozygous) and one ApoE4−, who were treated with the MEND protocol for 5-24 months. The magnitude of the improvement is unprecedented, providing additional objective evidence that this programmatic approach to cognitive decline is highly effective. These results have far-reaching implications for the treatment of Alzheimer's disease, MCI, and SCI; for personalized programs that may enhance pharmaceutical efficacy; and for personal identification of ApoE genotype. PMID:27294343

  4. Dietary anthocyanin intake and age-related decline in lung function: longitudinal findings from the VA Normative Aging Study123

    PubMed Central

    Mehta, Amar J; Cassidy, Aedín; Litonjua, Augusto A; Sparrow, David; Vokonas, Pantel; Schwartz, Joel

    2016-01-01

    Background: It is unknown whether habitual intake of dietary flavonoids, known for their antioxidative and anti-inflammatory properties, affects longitudinal change in lung function. Objective: We investigated whether different flavonoid subclasses present in the habitual diet were associated with beneficial changes in lung function over time in the elderly. Design: This longitudinal analysis included 839 participants from the VA (Veterans Affairs) Normative Aging Study whose lung function [forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC)] was measured at 2 and up to 5 visits between 1992 and 2008 (n = 2623 measurements). Yearly average intake of major flavonoid subclasses (anthocyanins, flavanones, flavan-3-ols, flavonols, flavones, and polymers) was calculated from food-frequency questionnaires at each visit. We estimated adjusted differences in annual change in lung function associated with each flavonoid subclass, categorized into quartiles, in linear mixed-effects regression models after adjustment for lifestyle and dietary confounders. Results: Strong inverse associations were found between anthocyanin intake and age-related decline in lung function. Independent of dietary and nondietary risk factors, slower rates of FEV1 and FVC decline by 23.6 (95% CI: 16.6, 30.7) and 37.3 (95% CI: 27.8, 46.8) mL/y, respectively, were observed in participants in the fourth quartile of intake compared with participants in the first quartile (P-trend < 0.0001). The protective associations observed for anthocyanin intake were present in both current/former and never smokers. Compared with no or very low intakes, an intake of ≥2 servings of anthocyanin-rich blueberries/wk was associated with slower decline in FEV1 and FVC by 22.5 (95% CI: 10.8, 34.2) and 37.9 (95% CI: 22.1, 53.7) mL/y, respectively. To a lesser extent, higher flavan-3-ol intake was also associated with slower lung function decline. Conclusions: An attenuation of age-related lung function

  5. High cognitive reserve is associated with a reduced age-related deficit in spatial conflict resolution

    PubMed Central

    Puccioni, Olga; Vallesi, Antonino

    2012-01-01

    Several studies support the existence of a specific age-related difficulty in suppressing potentially distracting information. The aim of the present study is to investigate whether spatial conflict resolution is selectively affected by aging. The way aging affects individuals could be modulated by many factors determined by the socieconomic status: we investigated whether factors such as cognitive reserve (CR) and years of education may play a compensatory role against age-related deficits in the spatial domain. A spatial Stroop task with no feature repetitions was administered to a sample of 17 non-demented older adults (69–79 years-old) and 18 younger controls (18–34 years-old) matched for gender and years of education. The two age groups were also administered with measures of intelligence and CR. The overall spatial Stroop effect did not differ according to age, neither for speed nor for accuracy. The two age groups equally showed sequential effects for congruent trials: reduced response times (RTs) if another congruent trial preceded them, and accuracy at ceiling. For incongruent trials, older adults, but not younger controls, were influenced by congruency of trialn−1, since RTs increased with preceding congruent trials. Interestingly, such an age-related modulation negatively correlated with CR. These findings suggest that spatial conflict resolution in aging is predominantly affected by general slowing, rather than by a more specific deficit. However, a high level of CR seems to play a compensatory role for both factors. PMID:23248595

  6. Age-related differences in gap detection: Effects of task difficulty and cognitive ability

    PubMed Central

    Harris, Kelly C.; Eckert, Mark A.; Ahlstrom, Jayne B.; Dubno, Judy R.

    2009-01-01

    Differences in gap detection for younger and older adults have been shown to vary with the complexity of the task or stimuli, but the factors that contribute to these differences remain unknown. To address this question, we examined the extent to which age-related differences in processing speed and workload predicted age-related differences in gap detection. Gap detection thresholds were measured for 10 younger and 11 older adults in two conditions that varied in task complexity but used identical stimuli: (1) gap location fixed at the beginning, middle, or end of a noise burst and (2) gap location varied randomly from trial to trial from the beginning, middle, or end of the noise. We hypothesized that gap location uncertainty would place increased demands on cognitive and attentional resources and result in significantly higher gap detection thresholds for older but not younger adults. Overall, gap detection thresholds were lower for the middle location as compared to beginning and end locations and were lower for the fixed than the random condition. In general, larger age-related differences in gap detection were observed for more challenging conditions. That is, gap detection thresholds for older adults were significantly larger for the random condition than for the fixed condition when the gap was at the beginning and end locations but not the middle. In contrast, gap detection thresholds for younger adults were not significantly different for the random and fixed condition at any location. Subjective ratings of workload indicated that older adults found the gap-detection task more mentally demanding than younger adults. Consistent with these findings, results of the Purdue Pegboard and Connections tests revealed age-related slowing of processing speed. Moreover, age group differences in workload and processing speed predicted gap detection in younger and older adults when gap location varied from trial to trial; these associations were not observed when gap

  7. Is vitrification of oocytes useful for fertility preservation for age-related fertility decline and in cancer patients?

    PubMed

    Cobo, Ana; Garcia-Velasco, Juan A; Domingo, Javier; Remohí, José; Pellicer, Antonio

    2013-05-01

    The aim of this review is to provide current knowledge on oocyte cryopreservation, with special emphasis on vitrification as a means to preserve fertility in different indications. Major advancements achieved in the past few years in the cryolaboratory have facilitated major changes in our practice. Areas such as fertility preservation for social or oncologic reasons, the possibility to create oocyte banks for egg donation programs, the opportunity to avoid ovarian hyperstimulation syndrome, or to accumulate oocytes in low-yield patients, or even to offer treatment segmentation by stimulating the ovaries, vitrifying, and then transferring in a natural cycle are some of the options that are now available with the development of cryopreservation. We present general experience from our group and others on fertility preservation for age-related fertility decline as well as in oncologic patients, confirming that oocyte vitrification is a standardized, simple, reproducible, and efficient option. PMID:23541405

  8. A Review of Age-Related Dehydroepiandrosterone Decline and Its Association with Well-Known Geriatric Syndromes: Is Treatment Beneficial?

    PubMed Central

    Samaras, Dimitrios; Frangos, Emilia; Forster, Alexandre; Philippe, Jacques

    2013-01-01

    Abstract Dehydroepiandrosterone (DHEA) and its sulfate ester are the most abundant steroids in humans. DHEA levels fall with age in men and women, reaching values sometimes as low as 10%–20% of those encountered in young individuals. This age-related decrease suggests an “adrenopause” phenomenon. Studies point toward several potential roles of DHEA, mainly through its hormonal end products, making this decline clinically relevant. Unfortunately, even if positive effects of DHEA on muscle, bone, cardiovascular disease, and sexual function seem rather robust, extremely few studies are large enough and/or long enough for conclusions regarding its effects on aging. Moreover, because it has been publically presented as a “fountain of youth” equivalent, over-the-counter preparations lacking pharmacokinetic and pharmacodynamic data are widely used worldwide. Conceptually, supplementing a pre-hormone is extremely interesting, because it would permit the human organism to adequately use it throughout long periods, increasing or decreasing end products according to his needs. Nevertheless, data on the safety profile of long-term DHEA supplementation are still lacking. In this article, we examine the potential relation between low DHEA levels and well-known age-related diseases, such as sarcopenia, osteoporosis, dementia, sexual disorders, and cardiovascular disease. We also review risks and benefits of existing protocols of DHEA supplementation. PMID:23647054

  9. Age-related differences in white matter integrity and cognitive function are related to APOE status

    PubMed Central

    Ryan, Lee; Walther, Katrin; Bendlin, Barbara B.; Lue, Lih-Fen; Walker, Douglas G.; Glisky, Elizabeth L.

    2010-01-01

    While an extensive literature is now available on age-related differences in white matter integrity measured by diffusion MRI, relatively little is known about the relationships between diffusion and cognitive functions in older adults. Even less is known about whether these relationships are influenced by the apolipoprotein (APOE) ε4 allele, despite growing evidence that ε4 increases cognitive impairment in older adults. The purpose of the present study was to examine these relationships in a group of community-dwelling cognitively normal older adults. Data were obtained from a sample of 126 individuals (ages 52–92) that included 32 ε4 heterozygotes, 6 ε4 homozygotes, and 88 non-carriers. Two measures of diffusion, the apparent diffusion coefficient (ADC) and fractional anisotropy (FA), were obtained from six brain regions – frontal white matter, lateral parietal white matter, the centrum semiovale, the genu and splenium of the corpus callosum, and the temporal stem white matter – and were used to predict composite scores of cognitive function in two domains, executive function and memory function. Results indicated that ADC and FA differed with increasing age in all six brain regions, and these differences were significantly greater for ε4 carriers compared to noncarriers. Importantly, after controlling for age, diffusion measures predicted cognitive function in a region-specific way that was also influenced by ε4 status. Regardless of APOE status, frontal ADC and FA independently predicted executive function scores for all participants, while temporal lobe ADC additionally predicted executive function for ε4 carriers, but not noncarriers. Memory scores were predicted by temporal lobe ADC but not frontal diffusion for all participants, and this relationship was significantly stronger in ε4 carriers compared to noncarriers. Taken together, age and temporal lobe ADC accounted for a striking 53% of the variance in memory scores within the ε4 carrier

  10. Inspection Time and Cognitive Abilities in Twins Aged 7 to 17 Years: Age-Related Changes, Heritability and Genetic Covariance

    ERIC Educational Resources Information Center

    Edmonds, Caroline J.; Isaacs, Elizabeth B.; Visscher, Peter M.; Rogers, Mary; Lanigan, Julie; Singhal, Atul; Lucas, Alan; Gringras, Paul; Denton, Jane; Deary, Ian J.

    2008-01-01

    We studied the age-related differences in inspection time and multiple cognitive domains in a group of monozygotic (MZ) and dizygotic (DZ) twins aged 7 to 17 years. Data from 111 twin pairs and 19 singleton siblings were included. We found clear age-related trends towards more efficient visual information processing in older participants. There…

  11. Common SIRT1 variants modify the effect of abdominal adipose tissue on aging-related lung function decline.

    PubMed

    Curjuric, Ivan; Imboden, Medea; Bridevaux, Pierre-Olivier; Gerbase, Margaret W; Haun, Margot; Keidel, Dirk; Kumar, Ashish; Pons, Marco; Rochat, Thierry; Schikowski, Tamara; Schindler, Christian; von Eckardstein, Arnold; Kronenberg, Florian; Probst-Hensch, Nicole M

    2016-06-01

    Lung function is an independent predictor of mortality and serves as an aging marker in never smokers. The protein sirtuin-1 of gene SIRT1 has profound anti-inflammatory effects and regulates metabolic pathways. Its suggested longevity effects on lower organisms remain poorly studied in humans. In 1132 never smokers of the population-based SAPALDIA cohort, we investigated associations between single nucleotide polymorphisms (SNPs; rs730821, rs10997868, rs10823116) of SIRT1 and aging-related lung function decline over 11 years in terms of change in forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, and forced expiratory flow between 25 and 75 % of FVC (FEF25-75) using multiple linear regression models. Interactions between the SIRT1 SNPs and adiposity parameters (body mass index (BMI), its change and weight gain) were tested by including multiplicative interaction terms into the models. SIRT1 polymorphisms exhibited no main effects, but modified the association between obesity measures and FEV1/FVC and FEF25-75 decline (p = 0.009-0.046). Per risk allele, FEV1/FVC decline was accelerated up to -0.5 % (95 % CI -1.0 to 0 %) and -0.7 % (-1.3 to -0.2 %) over interquartile range increases in BMI (2.4 kg/m(2)) or weight (6.5 kg), respectively. For FEF25-75 decline, corresponding estimates were -57 mL/s (-117 to 4 mL/s) and -76 mL/s (-1429 to -9 mL/s). Interactions were not present in participants with genetically lowered C-reactive protein concentrations. Genetic variation in SIRT1 might therefore affect lung function and human longevity by modifying subclinical inflammation arising from abdominal adipose tissue. PMID:27125385

  12. Perspective: A Critical Look at the Ancillary Age-Related Eye Disease Study 2: Nutrition and Cognitive Function Results in Older Individuals with Age-Related Macular Degeneration.

    PubMed

    Hammond, Billy R; Renzi-Hammond, Lisa M

    2016-05-01

    A large body of literature suggests that the dietary carotenoids lutein and zeaxanthin and long-chain polyunsaturated fatty acids such as docosahexaenoic acid are related to improved cognitive function across the life span. A recent report by the Age-Related Eye Disease Study (AREDS) group appears to contradict the general findings of others in the field. In this review, we look critically at the methods, study designs, and analysis techniques used in the larger body of literature and compare them with the recent AREDS reports. PMID:27184270

  13. Effect of S-adenosylmethionine tablets on the reduction of age-related mental decline in dogs: a double-blinded, placebo-controlled trial.

    PubMed

    Rème, C A; Dramard, V; Kern, L; Hofmans, J; Halsberghe, C; Mombiela, D Vida

    2008-01-01

    Oral S-adenosylmethionine (SAMe) tosylate supplementation (Novifit tablets, Virbac) was evaluated as a dietary aid for the management of age-related mental impairment in dogs. Thirty-six dogs older than 8 years that had displayed signs of cognitive dysfunction for at least 1 month were selected for the study. The dogs were administered 18 mg/kg SAMe tosylate (n=17) or identical placebo tablets (n=19) for 2 months. Concurrent behavioral treatment was forbidden. A 14-item standardized questionnaire evaluated behavior and locomotion difficulties. Compared with the placebo group, SAMe-treated dogs showed greater improvement in activity (41.7% versus 2.6% after 4 weeks, P<.0003; 57.1% versus 9.0% after 8 weeks, P<.003) and awareness (33.3% versus 17.9% after 4 weeks, P<.05; 59.5% versus 21.4% after 8 weeks, P<.01). The aggregate mental impairment score was reduced by more than 50% in 41.2% and 15.8% of dogs treated with SAMe and placebo, respectively, at week 8. SAMe tosylate tablets proved safe and effective in improving signs of age-related mental decline in dogs. PMID:18597245

  14. Age-related changes in brain activity are specific for high order cognitive processes during successful encoding of information in working memory

    PubMed Central

    Pinal, Diego; Zurrón, Montserrat; Díaz, Fernando

    2015-01-01

    Memory capacity suffers an age-related decline, which is supposed to be due to a generalized slowing of processing speed and to a reduced availability of processing resources. Information encoding in memory has been demonstrated to be very sensitive to age-related changes, especially when carried out through self-initiated strategies or under high cognitive demands. However, most event-related potentials (ERP) research on age-related changes in working memory (WM) has used tasks that preclude distinction between age-related changes in encoding and retrieval processes. Here, we used ERP recording and a delayed match to sample (DMS) task with two levels of memory load to assess age-related changes in electrical brain activity in young and old adults during successful information encoding in WM. Age-related decline was reflected in lower accuracy rates and longer reaction times in the DMS task. Beside, only old adults presented lower accuracy rates under high than low memory load conditions. However, effects of memory load on brain activity were independent of age and may indicate an increased need of processing after stimulus classification as reflected in larger mean voltages in high than low load conditions between 550 and 1000 ms post-stimulus for young and old adults. Regarding age-related effects on brain activity, results also revealed smaller P2 and P300 amplitudes that may signal the existence of an age dependent reduction in the processing resources available for stimulus evaluation and categorization. Additionally, P2 and N2 latencies were longer in old than in young participants. Furthermore, longer N2 latencies were related to greater accuracy rates on the DMS task, especially in old adults. These results suggest that age-related slowing of processing speed may be specific for target stimulus analysis and evaluation processes. Thus, old adults seem to improve their performance the longer they take to evaluate the stimulus they encode in visual WM. PMID

  15. Age-related changes in brain activity are specific for high order cognitive processes during successful encoding of information in working memory.

    PubMed

    Pinal, Diego; Zurrón, Montserrat; Díaz, Fernando

    2015-01-01

    Memory capacity suffers an age-related decline, which is supposed to be due to a generalized slowing of processing speed and to a reduced availability of processing resources. Information encoding in memory has been demonstrated to be very sensitive to age-related changes, especially when carried out through self-initiated strategies or under high cognitive demands. However, most event-related potentials (ERP) research on age-related changes in working memory (WM) has used tasks that preclude distinction between age-related changes in encoding and retrieval processes. Here, we used ERP recording and a delayed match to sample (DMS) task with two levels of memory load to assess age-related changes in electrical brain activity in young and old adults during successful information encoding in WM. Age-related decline was reflected in lower accuracy rates and longer reaction times in the DMS task. Beside, only old adults presented lower accuracy rates under high than low memory load conditions. However, effects of memory load on brain activity were independent of age and may indicate an increased need of processing after stimulus classification as reflected in larger mean voltages in high than low load conditions between 550 and 1000 ms post-stimulus for young and old adults. Regarding age-related effects on brain activity, results also revealed smaller P2 and P300 amplitudes that may signal the existence of an age dependent reduction in the processing resources available for stimulus evaluation and categorization. Additionally, P2 and N2 latencies were longer in old than in young participants. Furthermore, longer N2 latencies were related to greater accuracy rates on the DMS task, especially in old adults. These results suggest that age-related slowing of processing speed may be specific for target stimulus analysis and evaluation processes. Thus, old adults seem to improve their performance the longer they take to evaluate the stimulus they encode in visual WM. PMID

  16. Multimodal white matter imaging to investigate reduced fractional anisotropy and its age-related decline in schizophrenia

    PubMed Central

    Kochunov, Peter; Chiappelli, Joshua; Wright, Susan N.; Rowland, Laura M.; Patel, Benish; Wijtenburg, S. Andrea; Nugent, Katie; McMahon, Robert P.; Carpenter, William T.; Muellerklein, Florian; Sampath, Hemalatha; Hong, L. Elliot

    2014-01-01

    We hypothesized that reduced fractional anisotropy (FA) of water diffusion and its elevated aging-related decline in schizophrenia patients may be caused by elevated hyperintensive white matter (HWM) lesions, by reduced permeability-diffusivity index (PDI), or both. We tested this hypothesis in 40/30 control/patient participants. FA values for the corpus callosum were calculated from high angular resolution diffusion tensor imaging (DTI). Whole-brain volume of HWM lesions was quantified by 3D-T2w-fluid-attenuated inversion recovery (FLAIR) imaging. PDI for corpus callosum was ascertained using multi b-value diffusion imaging (15 b-shells with 30 directions per shell). Patients had significantly lower corpus callosum FA values, and there was a significant age-by-diagnosis interaction. Patients also had significantly reduced PDI but no difference in HWM volume. PDI and HWM volume were significant predictors of FA and captured the diagnosis-related variance. Separately, PDI robustly explained FA variance in schizophrenia patients, but not in controls. Conversely, HWM volume made equally significant contributions to variability in FA in both groups. The diagnosis-by-age effect of FA was explained by a PDI-by-diagnosis interaction. Post hoc testing showed a similar trend for PDI of gray mater. Our study demonstrated that reduced FA and its accelerated decline with age in schizophrenia were explained by pathophysiology indexed by PDI, rather than HWM volume. PMID:24909602

  17. Genetic background influences age-related decline in visual and nonvisual retinal responses, circadian rhythms, and sleep☆

    PubMed Central

    Banks, Gareth; Heise, Ines; Starbuck, Becky; Osborne, Tamzin; Wisby, Laura; Potter, Paul; Jackson, Ian J.; Foster, Russell G.; Peirson, Stuart N.; Nolan, Patrick M.

    2015-01-01

    The circadian system is entrained to the environmental light/dark cycle via retinal photoreceptors and regulates numerous aspects of physiology and behavior, including sleep. These processes are all key factors in healthy aging showing a gradual decline with age. Despite their importance, the exact mechanisms underlying this decline are yet to be fully understood. One of the most effective tools we have to understand the genetic factors underlying these processes are genetically inbred mouse strains. The most commonly used reference mouse strain is C57BL/6J, but recently, resources such as the International Knockout Mouse Consortium have started producing large numbers of mouse mutant lines on a pure genetic background, C57BL/6N. Considering the substantial genetic diversity between mouse strains we expect there to be phenotypic differences, including differential effects of aging, in these and other strains. Such differences need to be characterized not only to establish how different mouse strains may model the aging process but also to understand how genetic background might modify age-related phenotypes. To ascertain the effects of aging on sleep/wake behavior, circadian rhythms, and light input and whether these effects are mouse strain-dependent, we have screened C57BL/6J, C57BL/6N, C3H-HeH, and C3H-Pde6b+ mouse strains at 5 ages throughout their life span. Our data show that sleep, circadian, and light input parameters are all disrupted by the aging process. Moreover, we have cataloged a number of strain-specific aging effects, including the rate of cataract development, decline in the pupillary light response, and changes in sleep fragmentation and the proportion of time spent asleep. PMID:25179226

  18. Is age-related decline in lean mass and physical function accelerated by Obstructive Lung Disease or smoking?

    PubMed Central

    van den Borst, Bram; Koster, Annemarie; Yu, Binbing; Gosker, Harry R.; Meibohm, Bernd; Bauer, Douglas C.; Kritchevsky, Stephen B.; Liu, Yongmei; Newman, Anne B.; Harris, Tamara B.; Schols, Annemie M.W.J.

    2012-01-01

    Background and aims Cross-sectional studies suggest that Obstructive Lung Disease (OLD) and smoking affect lean mass and mobility. We aimed to investigate whether OLD and smoking accelerate aging-related decline in lean mass and physical functioning. Methods 260 persons with OLD (FEV1 63±18 %predicted), 157 smoking controls (FEV1 95±16 %predicted), 866 formerly smoking controls (FEV1 100±16 %predicted) and 891 never-smoking controls (FEV1 104±17 %predicted) participating in the Health, Aging and Body Composition (ABC) Study were studied. At baseline, the mean age was 74±3 y and participants reported no functional limitations. Baseline and seven-year longitudinal data were investigated of body composition (by Dual-energy X-ray absorptiometry), muscle strength (by hand and leg dynamometry) and Short Physical Performance Battery (SPPB). Results Compared to never-smoking controls, OLD persons and smoking controls had a significantly lower weight, fat mass, lean mass and bone mineral content (BMC) at baseline (p<0.05). While the loss of weight, fat mass, lean mass and strength was comparable between OLD persons and never-smoking controls, the SPPB declined 0.12 points/yr faster in OLD men (p=0.01) and BMC 4 g/yr faster in OLD women (p=0.02). In smoking controls, only lean mass declined 0.1 kg/yr faster in women (p=0.03) and BMC 8 g/yr faster in men (p=0.02) compared to never-smoking controls. Conclusions Initially well-functioning older adults with mild-to-moderate OLD and smokers without OLD have a comparable compromised baseline profile of body composition and physical functioning, while seven-year longitudinal trajectories are to a large extent comparable to those observed in never-smokers without OLD. This suggests a common insult earlier in life related to smoking. 3 PMID:21724748

  19. Jumping Stand Apparatus Reveals Rapidly Specific Age-Related Cognitive Impairments in Mouse Lemur Primates

    PubMed Central

    Picq, Jean-Luc; Villain, Nicolas; Gary, Charlotte; Pifferi, Fabien; Dhenain, Marc

    2015-01-01

    The mouse lemur (Microcebus murinus) is a promising primate model for investigating normal and pathological cerebral aging. The locomotor behavior of this arboreal primate is characterized by jumps to and from trunks and branches. Many reports indicate insufficient adaptation of the mouse lemur to experimental devices used to evaluate its cognition, which is an impediment to the efficient use of this animal in research. In order to develop cognitive testing methods appropriate to the behavioral and biological traits of this species, we adapted the Lashley jumping stand apparatus, initially designed for rats, to the mouse lemur. We used this jumping stand apparatus to compare performances of young (n = 12) and aged (n = 8) adults in acquisition and long-term retention of visual discriminations. All mouse lemurs completed the tasks and only 25 trials, on average, were needed to master the first discrimination problem with no age-related differences. A month later, all mouse lemurs made progress for acquiring the second discrimination problem but only the young group reached immediately the criterion in the retention test of the first discrimination problem. This study shows that the jumping stand apparatus allows rapid and efficient evaluation of cognition in mouse lemurs and demonstrates that about half of the old mouse lemurs display a specific deficit in long-term retention but not in acquisition of visual discrimination. PMID:26716699

  20. Jumping Stand Apparatus Reveals Rapidly Specific Age-Related Cognitive Impairments in Mouse Lemur Primates.

    PubMed

    Picq, Jean-Luc; Villain, Nicolas; Gary, Charlotte; Pifferi, Fabien; Dhenain, Marc

    2015-01-01

    The mouse lemur (Microcebus murinus) is a promising primate model for investigating normal and pathological cerebral aging. The locomotor behavior of this arboreal primate is characterized by jumps to and from trunks and branches. Many reports indicate insufficient adaptation of the mouse lemur to experimental devices used to evaluate its cognition, which is an impediment to the efficient use of this animal in research. In order to develop cognitive testing methods appropriate to the behavioral and biological traits of this species, we adapted the Lashley jumping stand apparatus, initially designed for rats, to the mouse lemur. We used this jumping stand apparatus to compare performances of young (n = 12) and aged (n = 8) adults in acquisition and long-term retention of visual discriminations. All mouse lemurs completed the tasks and only 25 trials, on average, were needed to master the first discrimination problem with no age-related differences. A month later, all mouse lemurs made progress for acquiring the second discrimination problem but only the young group reached immediately the criterion in the retention test of the first discrimination problem. This study shows that the jumping stand apparatus allows rapid and efficient evaluation of cognition in mouse lemurs and demonstrates that about half of the old mouse lemurs display a specific deficit in long-term retention but not in acquisition of visual discrimination. PMID:26716699

  1. The Hippocampal Neuroproteome with Aging and Cognitive Decline: Past Progress and Future Directions

    PubMed Central

    VanGuilder, Heather D.; Freeman, Willard M.

    2011-01-01

    Although steady progress on understanding brain aging has been made over recent decades through standard anatomical, immunohistochemical, and biochemical techniques, the biological basis of non-neurodegenerative cognitive decline with aging remains to be determined. This is due in part to technical limitations of traditional approaches, in which only a small fraction of neurobiologically relevant proteins, mRNAs or metabolites can be assessed at a time. With the development and refinement of proteomic technologies that enable simultaneous quantitative assessment of hundreds to thousands of proteins, neuroproteomic studies of brain aging and cognitive decline are becoming more widespread. This review focuses on the contributions of neuroproteomic investigations to advances in our understanding of age-related deficits of hippocampus-dependent spatial learning and memory. Accumulating neuroproteomic data demonstrate that hippocampal aging involves common themes of dysregulated metabolism, increased oxidative stress, altered protein processing, and decreased synaptic function. Additionally, growing evidence suggests that cognitive decline does not represent a “more aged” phenotype, but rather is associated with specific neuroproteomic changes that occur in addition to age-related alterations. Understanding if and how age-related changes in the hippocampal neuroproteome contribute to cognitive decline and elucidating the pathways and processes that lead to cognitive decline are critical objectives that remain to be achieved. Progress in the field and challenges that remain to be addressed with regard to animal models, behavioral testing, and proteomic reporting are also discussed. PMID:21647399

  2. The emerging role of dietary fructose in obesity and cognitive decline

    PubMed Central

    2013-01-01

    The incidence of obesity has increased dramatically over the past several years, and in parallel, so has the prevalence of type 2 diabetes (T2D). Numerous studies have demonstrated that both obesity and T2D are associated with lower cognitive performance, cognitive decline, and dementia. Intake of dietary fructose has also increased. In fact, high-fructose corn syrup (HFCS) accounts for as much as 40% of caloric sweeteners used in the United States. Given the increase in the incidence of Alzheimer’s disease (AD), characterized by an age-related decline in memory and cognitive functioning, in this report we review the effects of obesity on cognitive performance and the impact of high fructose intake in promoting cognitive decline. The paper then considers the effects of omega-3 fatty acids (FAs), which have been linked to promising results in cognitive function including ameliorating the impact of a high-fructose diet. PMID:23924506

  3. White matter microstructure contributes to age-related declines in task-induced deactivation of the default mode network.

    PubMed

    Brown, Christopher A; Hakun, Jonathan G; Zhu, Zude; Johnson, Nathan F; Gold, Brian T

    2015-01-01

    Task-induced deactivations within the brain's default mode network (DMN) are thought to reflect suppression of endogenous thought processes to support exogenous goal-directed task processes. Older adults are known to show reductions in deactivation of the DMN compared to younger adults. However, little is understood about the mechanisms contributing to functional dysregulation of the DMN in aging. Here, we explored the relationships between functional modulation of the DMN and age, task performance and white matter (WM) microstructure. Participants were 117 adults ranging from 25 to 83 years old who completed an fMRI task switching paradigm, including easy (single) and difficult (mixed) conditions, and underwent diffusion tensor imaging (DTI). The fMRI results revealed an age by condition interaction (β = -0.13, t = -3.16, p = 0.002) such that increasing age affected deactivation magnitude during the mixed condition (β = -0.29, t = -3.24 p = 0.002) but not the single condition (p = 0.58). Additionally, there was a WM by condition interaction (β = 0.10, t = 2.33, p = 0.02) such that decreasing WM microstructure affected deactivation magnitude during the mixed condition (β = 0.30, t = 3.42 p = 0.001) but not the single condition (p = 0.17). Critically, mediation analyses indicated that age-related reductions in WM microstructure accounted for the relationship between age and DMN deactivation in the more difficult mixed condition. These findings suggest that age-related declines in anatomical connectivity between DMN regions contribute to functional dysregulation within the DMN in older adults. PMID:26500549

  4. White matter microstructure contributes to age-related declines in task-induced deactivation of the default mode network

    PubMed Central

    Brown, Christopher A.; Hakun, Jonathan G.; Zhu, Zude; Johnson, Nathan F.; Gold, Brian T.

    2015-01-01

    Task-induced deactivations within the brain’s default mode network (DMN) are thought to reflect suppression of endogenous thought processes to support exogenous goal-directed task processes. Older adults are known to show reductions in deactivation of the DMN compared to younger adults. However, little is understood about the mechanisms contributing to functional dysregulation of the DMN in aging. Here, we explored the relationships between functional modulation of the DMN and age, task performance and white matter (WM) microstructure. Participants were 117 adults ranging from 25 to 83 years old who completed an fMRI task switching paradigm, including easy (single) and difficult (mixed) conditions, and underwent diffusion tensor imaging (DTI). The fMRI results revealed an age by condition interaction (β = −0.13, t = −3.16, p = 0.002) such that increasing age affected deactivation magnitude during the mixed condition (β = −0.29, t = −3.24 p = 0.002) but not the single condition (p = 0.58). Additionally, there was a WM by condition interaction (β = 0.10, t = 2.33, p = 0.02) such that decreasing WM microstructure affected deactivation magnitude during the mixed condition (β = 0.30, t = 3.42 p = 0.001) but not the single condition (p = 0.17). Critically, mediation analyses indicated that age-related reductions in WM microstructure accounted for the relationship between age and DMN deactivation in the more difficult mixed condition. These findings suggest that age-related declines in anatomical connectivity between DMN regions contribute to functional dysregulation within the DMN in older adults. PMID:26500549

  5. The effectiveness of unitization in mitigating age-related relational learning impairments depends on existing cognitive status.

    PubMed

    D'Angelo, Maria C; Smith, Victoria M; Kacollja, Arber; Zhang, Felicia; Binns, Malcolm A; Barense, Morgan D; Ryan, Jennifer D

    2016-11-01

    Binding relations among items in the transverse patterning (TP) task is dependent on the integrity of the hippocampus and its extended network. Older adults have impaired TP learning, corresponding to age-related reductions in hippocampal volumes. Unitization is a training strategy that can mitigate TP impairments in amnesia by reducing reliance on hippocampal-dependent relational binding and increasing reliance on fused representations. Here we examined whether healthy older adults and those showing early signs of cognitive decline would also benefit from unitization. Although both groups of older adults had neuropsychological performance within the healthy range, their TP learning differed both under standard and unitized training conditions. Healthy older adults with impaired TP learning under standard training benefited from unitized training. Older adults who failed the Montreal Cognitive Assessment (MoCA) showed greater impairments under standard conditions, and showed no evidence of improvement with unitization. These individuals' failures to benefit from unitization may be a consequence of early deficits not seen in older adults who pass the MoCA. PMID:27049878

  6. The effectiveness of unitization in mitigating age-related relational learning impairments depends on existing cognitive status

    PubMed Central

    D’Angelo, Maria C.; Smith, Victoria M.; Kacollja, Arber; Zhang, Felicia; Binns, Malcolm A.; Barense, Morgan D.; Ryan, Jennifer D.

    2016-01-01

    ABSTRACT Binding relations among items in the transverse patterning (TP) task is dependent on the integrity of the hippocampus and its extended network. Older adults have impaired TP learning, corresponding to age-related reductions in hippocampal volumes. Unitization is a training strategy that can mitigate TP impairments in amnesia by reducing reliance on hippocampal-dependent relational binding and increasing reliance on fused representations. Here we examined whether healthy older adults and those showing early signs of cognitive decline would also benefit from unitization. Although both groups of older adults had neuropsychological performance within the healthy range, their TP learning differed both under standard and unitized training conditions. Healthy older adults with impaired TP learning under standard training benefited from unitized training. Older adults who failed the Montreal Cognitive Assessment (MoCA) showed greater impairments under standard conditions, and showed no evidence of improvement with unitization. These individuals’ failures to benefit from unitization may be a consequence of early deficits not seen in older adults who pass the MoCA. PMID:27049878

  7. Ascorbic Acid and the Brain: Rationale for the Use against Cognitive Decline

    PubMed Central

    Harrison, Fiona E.; Bowman, Gene L.; Polidori, Maria Cristina

    2014-01-01

    This review is focused upon the role of ascorbic acid (AA, vitamin C) in the promotion of healthy brain aging. Particular attention is attributed to the biochemistry and neuronal metabolism interface, transport across tissues, animal models that are useful for this area of research, and the human studies that implicate AA in the continuum between normal cognitive aging and age-related cognitive decline up to Alzheimer’s disease. Vascular risk factors and comorbidity relationships with cognitive decline and AA are discussed to facilitate strategies for advancing AA research in the area of brain health and neurodegeneration. PMID:24763117

  8. An olive oil-derived antioxidant mixture ameliorates the age-related decline of skeletal muscle function.

    PubMed

    Pierno, Sabata; Tricarico, Domenico; Liantonio, Antonella; Mele, Antonietta; Digennaro, Claudio; Rolland, Jean-François; Bianco, Gianpatrizio; Villanova, Luciano; Merendino, Alessandro; Camerino, Giulia Maria; De Luca, Annamaria; Desaphy, Jean-François; Camerino, Diana Conte

    2014-02-01

    Age-related skeletal muscle decline is characterized by the modification of sarcolemma ion channels important to sustain fiber excitability and to prevent metabolic dysfunction. Also, calcium homeostasis and contractile function are impaired. In the aim to understand whether these modifications are related to oxidative damage and can be reverted by antioxidant treatment, we examined the effects of in vivo treatment with an waste water polyphenolic mixture (LACHI MIX HT) supplied by LACHIFARMA S.r.l. Italy containing hydroxytirosol (HT), gallic acid, and homovanillic acid on the skeletal muscles of 27-month-old rats. After 6-week treatment, we found an improvement of chloride ClC-1 channel conductance, pivotal for membrane electrical stability, and of ATP-dependent potassium channel activity, important in coupling excitability with fiber metabolism. Both of them were analyzed using electrophysiological techniques. The treatment also restored the resting cytosolic calcium concentration, the sarcoplasmic reticulum calcium release, and the mechanical threshold for contraction, an index of excitation-contraction coupling mechanism. Muscle weight and blood creatine kinase levels were preserved in LACHI MIX HT-treated aged rats. The antioxidant activity of LACHI MIX HT was confirmed by the reduction of malondialdehyde levels in the brain of the LACHI MIX HT-treated aged rats. In comparison, the administration of purified HT was less effective on all the parameters studied. Although muscle function was not completely recovered, the present study provides evidence of the beneficial effects of LACHI MIX HT, a natural compound, to ameliorate skeletal muscle functional decline due to aging-associated oxidative stress. PMID:23716142

  9. Lower cognitive function in patients with age-related macular degeneration: a meta-analysis

    PubMed Central

    Zhou, Li-Xiao; Sun, Cheng-Lin; Wei, Li-Juan; Gu, Zhi-Min; Lv, Liang; Dang, Yalong

    2016-01-01

    Objective To investigate the cognitive impairment in patients with age-related macular degeneration (AMD). Methods Relevant articles were identified through a search of the following electronic databases through October 2015, without language restriction: 1) PubMed; 2) the Cochrane Library; 3) EMBASE; 4) ScienceDirect. Meta-analysis was conducted using STATA 12.0 software. Standardized mean differences with corresponding 95% confidence intervals were calculated. All of the included studies met the following four criteria: 1) the study design was a case–control or randomized controlled trial (RCT) study; 2) the study investigated cognitive function in the patient with AMD; 3) the diagnoses of AMD must be provided; 4) there were sufficient scores data to extract for evaluating cognitive function between cases and controls. The Newcastle–Ottawa Scale criteria were used to assess the methodological quality of the studies. Results Of the initial 278 literatures, only six case–control and one RCT studies met all of the inclusion criteria. A total of 794 AMD patients and 1,227 controls were included in this study. Five studies were performed with mini-mental state examination (MMSE), two studies with animal fluency, two studies with trail making test (TMT)-A and -B, one study with Mini-Cog. Results of the meta-analysis revealed lower cognitive function test scores in patients with AMD, especially with MMSE and Mini-Cog test (P≤0.001 for all). The results also showed that differences in the TMT-A (except AMD [total] vs controls) and TMT-B test had no statistical significance (P>0.01). The Newcastle–Ottawa Scale score was ≥5 for all of the included studies. Based on the sensitivity analysis, no single study influenced the overall pooled estimates. Conclusion This meta-analysis suggests lower cognitive function test scores in patients with AMD, especially with MMSE and Mini-Cog test. The other cognitive impairment screening tests, such as animal fluency test and

  10. Cognitive Load and Listening Effort: Concepts and Age-Related Considerations.

    PubMed

    Lemke, Ulrike; Besser, Jana

    2016-01-01

    Listening effort has been recognized as an important dimension of everyday listening, especially with regard to the comprehension of spoken language. At constant levels of comprehension performance, the level of effort exerted and perceived during listening can differ considerably across listeners and situations. In this article, listening effort is used as an umbrella term for two different types of effort that can arise during listening. One of these types is processing effort, which is used to denote the utilization of "extra" mental processing resources in listening conditions that are adverse for an individual. A conceptual description is introduced how processing effort could be defined in terms of situational influences, the listener's auditory and cognitive resources, and the listener's personal state. Also, the proposed relationship between processing effort and subjectively perceived listening effort is discussed. Notably, previous research has shown that the availability of mental resources, as well as the ability to use them efficiently, changes over the course of adult aging. These common age-related changes in cognitive abilities and their neurocognitive organization are discussed in the context of the presented concept, especially regarding situations in which listening effort may be increased for older people. PMID:27355774

  11. Age-related differences in the course of cognitive skill acquisition: the role of regional cortical shrinkage and cognitive resources.

    PubMed

    Head, Denise; Raz, Naftali; Gunning-Dixon, Faith; Williamson, Adrienne; Acker, James D

    2002-03-01

    This study examined the impact of age-related differences in regional cerebral volumes and cognitive resources on acquisition of a cognitive skill. Volumes of brain regions were measured on magnetic resonance images of healthy adults (aged 22-80). At the early stage of learning to solve the Tower of Hanoi puzzle, speed and efficiency were associated with age, prefrontal cortex volume, and working memory. A similar pattern of brain-behavior associations was observed with perseveration measured on the Wisconsin Card Sorting Test. None of the examined structural brain variables were important at the later stages of skill acquisition. When hypertensive participants were excluded, the effect of prefrontal shrinkage on executive aspects of performance was no longer significant, but the effect of working memory remained. PMID:11931289

  12. High Blood Pressure and Cognitive Decline in Mild Cognitive Impairment

    PubMed Central

    Goldstein, Felicia C.; Levey, Allan I.; Steenland, N. Kyle

    2013-01-01

    Objectives To determine whether high blood pressure (BP) levels are associated with faster decline in specific cognitive domains. Design Prospective longitudinal cohort. Setting Uniform Data Set of the National Institutes of Health, National Institute on Aging Alzheimer's Disease Centers. Participants One thousand three hundred eighty-five participants with a diagnosis of mild cognitive impairment (MCI) and measured BP values at baseline and two annual follow-up visits. Measurements Neuropsychological test scores and Clinical Dementia Rating Sum of Boxes (CDR Sum) score. Results Participants with MCI with two or three annual occasions of high BP values (systolic BP ≥ 140 mmHg or diastolic BP ≥ 90 mmHg) had significantly faster decline on neuropsychological measures of visuomotor sequencing, set shifting, and naming than those who were normotensive on all three occasions. High systolic BP values were associated as well with faster decline on the CDR Sum score. Conclusion Hypertension is associated with faster cognitive decline in persons at risk for dementia. PMID:23301925

  13. Use it or lose it? SES mitigates age-related decline in a recency/recognition task

    PubMed Central

    Czernochowski, Daniela; Fabiani, Monica; Friedman, David

    2008-01-01

    An important goal of aging research is to determine factors leading to individual differences that might compensate for some of the deleterious effects of aging on cognition. To determine whether socio-economic status (SES) plays a role in mitigating age-related decrements in the recollection of contextual details, we categorized older participants into low- and high-SES groups. Event-related potentials (ERPs) and behavioral data were recorded in a picture memory task involving recency and recognition judgments. Young, old-low and old-high SES groups did not differ in recognition performance. However, on recency judgments, old-low subjects performed at chance, whereas old-high subjects did not differ significantly from young adults. Consistent with their preserved recency performance, a long-duration frontal negativity was significantly larger for recency compared to recognition trials in the ERPs of the old-high SES group only. These data suggest that older adults with higher SES levels can use strategies to compensate for the adverse effects of aging in complex source memory tasks by recruiting additional neural resources apparently not required by the young. PMID:17280741

  14. The Relation between canine cognitive dysfunction and age-related brain lesions

    PubMed Central

    OZAWA, Makiko; CHAMBERS, James K.; UCHIDA, Kazuyuki; NAKAYAMA, Hiroyuki

    2016-01-01

    Canine cognitive dysfunction (CCD) is a syndrome that manifests itself in abnormal behaviors, such as disorientation and wandering. β-amyloid deposition in the brain, including the senile plaque (SP) and cerebral amyloid angiopathy (CAA), has been suggested as a major cause of the syndrome. However, the pathological significance of β-amyloid deposition in CCD dogs remains unclear. The present study was conducted using 16 dogs aged 10 years or older to clarify the relationship between the age-related histopathological lesions, such as β-amyloid deposition, in the brain and the clinical symptoms of CCD as evaluated in a questionnaire previously established in a large survey. In addition, age-related brain lesions were assessed in 37 dogs. The pathological lesions were evaluated by the severity of β-amyloid deposition (SP and CAA), the amount of ubiquitin-positive granules (UBQ), GFAP-positive astrocytes, Iba-1-positive microglia and Nissle stain-positive nerve cells. The results revealed that there was no significant correlation between the severities of canine SP and CCD. The SP increased until 14 years old, but decreased thereafter, although the incidence of CCD is high at these ages. The CAA consistently increased with age, but did not correlate greatly with the CCD score. In contrast, the increases of UBQ, astrocytes and microglia were significantly correlated with CCD. Thus, the impairment in the synapse and/or myelin suggested by increased UBQ and glial activation might be involved in CCD pathogenesis, but β-amyloid deposition, especially SP, is not a direct pathogenic factor of CCD. PMID:26922972

  15. Age-related decline in muscle mass and muscle function in Flemish Caucasians: a 10-year follow-up.

    PubMed

    Charlier, Ruben; Knaeps, Sara; Mertens, Evelien; Van Roie, Evelien; Delecluse, Christophe; Lefevre, Johan; Thomis, Martine

    2016-04-01

    Aging is a complex process that is accompanied with changes in both muscle mass and muscle function (strength and performance). Therefore, the current longitudinal study aimed to provide a better insight in 10-year aging-related changes in whole-body muscle mass and strength performance of the leg extensors during the adult life span. Data were gathered within the framework of the first- (2002-2004: baseline) and third-generation Flemish Policy Research Center Sport (2012-2014: follow-up). Results are based on muscle characteristics data of 591 Flemish Caucasian adults (19-73 years, 381 men). Skeletal muscle mass (SMM) was determined with bioelectrical impedance analysis. Biodex Medical System 3® dynamometer was used to measure isometric (PTstatic120°) and isokinetic (PTdynamic60° and PTdynamic240°) strength, ballistic movement speed (S 20 %), and muscular endurance (work) of the knee extensors. Overall strength performance was higher at both evaluation moments in men compared to women (p < 0.01). But only S 20 % declined significantly faster in men compared to women (p < 0.01). Age and baseline strength performance were negatively related with the change in strength performance, even when corrected for SMM, protein intake, and energy expenditure during sports (E sport). In conclusion, strength performance was not associated with E sport in this study, but protein intake was associated with isometric strength in men, and with ballistic and isokinetic strength in women. Changes in S 20 % were significantly greater in men compared to women. Baseline values of strength performance and age were associated with changes in strength performance parameters, even after correction for SMM, protein intake, and E sport. PMID:26961694

  16. Greater Cognitive Decline with Aging among Elders with High Serum Concentrations of Organochlorine Pesticides

    PubMed Central

    Kim, Se-A; Lee, Yu-Mi; Lee, Ho-Won; Jacobs, David R; Lee, Duk-Hee

    2015-01-01

    Although cognitive decline is very common in elders, age-related cognitive decline substantially differs among elders and the determinants of the differences in age-related cognitive decline are unclear. We investigated our hypothesis that the association between age and cognition was stronger in those with higher serum concentrations of organochlorine (OC) pesticides, common persistent and strongly lipophilic neurotoxic chemicals. Participants were 644 elders aged 60-85, participating in the National Health and Nutrition Examination Survey 1999-2002. Six OC pesticides (p,p'-dichlorodiphenyltrichloroethane (DDT), p,p'-dichlorodipenyldichloroethylene (DDE), β-hexachlorocyclohexane, trans-nonachlor, oxychlordane, and heptachlor epoxide) were evaluated. “Lower cognitive function” was defined as having a low Digit-Symbol Substitution Test (DSST) score (<25th percentile of DSST score, cutpoint 28 symbols substituted). Higher levels of β-hexachlorocyclohexane, trans-nonachlor, oxychlordane, and heptachlor epoxide modified the associations between age and lower cognitive function (Pinteraction<0.01, 0.03, <0.01, and 0.02, respectively). Elders in the 3rd tertile of these chemicals demonstrated a greater risk of lower cognitive function with aging, compared to those in the combined 1st and 2nd tertiles. Among those with highest OC pesticides (3rd tertile), the odds ratio for the risk of lower cognitive function was about 6 to 11 for the highest quintile of age (80-85 years) vs. the first quintile of age (60-63 years), while the association between age and lower cognitive function became flatter in those with lower OC pesticides (combined 1st and 2nd tertiles). Both DDT and DDE showed no interaction, with lower DSST scores for higher age irrespective of serum concentrations of DDT or DDE. Even though DSST score measures only one aspect of cognition, several OC pesticides modified aging-related prevalence of low cognitive score, a finding which should be evaluated in

  17. Depressed Mood Mediates Decline in Cognitive Processing Speed in Caregivers

    ERIC Educational Resources Information Center

    Vitaliano, Peter P.; Zhang, Jianping; Young, Heather M.; Caswell, Lisa W.; Scanlan, James M.; Echeverria, Diana

    2009-01-01

    Purpose: Very few studies have examined cognitive decline in caregivers versus noncaregivers, and only 1 study has examined mediators of such decline. We evaluated the relationship between caregiver status and decline on the digit symbol test (DST; a measure of processing speed, attention, cognitive-motor translation, and visual scanning) and…

  18. Evaluating the Association between Diabetes, Cognitive Decline and Dementia

    PubMed Central

    Ojo, Omorogieva; Brooke, Joanne

    2015-01-01

    The aim of this article is to review the association between diabetes mellitus, cognitive decline and dementia, including the effects of cognitive decline and dementia on self management of diabetes. This is a literature review of primary research articles. A number of contemporary research articles that met the inclusion criteria were selected for this review paper. These articles were selected using a number of search strategies and electronic databases, such as EBSCOhost Research and SwetsWise databases. The duration of diabetes, glycated haemoglobin levels and glycaemic fluctuations were associated with cognitive decline and dementia. Similarly, hypoglycaemia was significantly related to increased risk of developing cognitive decline and dementia. Furthermore, cognitive decline and dementia were associated with poorer diabetes management. There is evidence of the association between diabetes, cognitive decline and dementia including the shared pathogenesis between diabetes and Alzheimer’s disease. In addition, the self management of diabetes is affected by dementia and cognitive decline. It could be suggested that the association between diabetes and dementia is bidirectional with the potential to proceed to a vicious cycle. Further studies are needed in order to fully establish the relationship between diabetes, cognitive decline and dementia. Patients who have diabetes and dementia could benefit from structured education strategies, which should involve empowerment programmes and lifestyle changes. The detection of cognitive decline should highlight the need for education strategies. PMID:26193295

  19. Falls May Be Sign of Future Alzheimer's Disease, Cognitive Decline

    MedlinePlus

    ... About ADEAR Falls may be sign of future Alzheimer’s disease, cognitive decline June 28, 2013 Cognitively normal older ... with evidence of early brain changes typical of Alzheimer’s disease fell more often than did their peers without ...

  20. Age-associated Cognitive Decline: Insights into Molecular Switches and Recovery Avenues

    PubMed Central

    Konar, Arpita; Singh, Padmanabh; Thakur, Mahendra K.

    2016-01-01

    Age-associated cognitive decline is an inevitable phenomenon that predisposes individuals for neurological and psychiatric disorders eventually affecting the quality of life. Scientists have endeavored to identify the key molecular switches that drive cognitive decline with advancing age. These newly identified molecules are then targeted as recovery of cognitive aging and related disorders. Cognitive decline during aging is multi-factorial and amongst several factors influencing this trajectory, gene expression changes are pivotal. Identifying these genes would elucidate the neurobiological underpinnings as well as offer clues that make certain individuals resilient to withstand the inevitable age-related deteriorations. Our laboratory has focused on this aspect and investigated a wide spectrum of genes involved in crucial brain functions that attribute to senescence induced cognitive deficits. We have recently identified master switches in the epigenome regulating gene expression alteration during brain aging. Interestingly, these factors when manipulated by chemical or genetic strategies successfully reverse the age-related cognitive impairments. In the present article, we review findings from our laboratory and others combined with supporting literary evidences on molecular switches of brain aging and their potential as recovery targets. PMID:27114845

  1. Cognitive Decline Is Associated with Risk Aversion and Temporal Discounting in Older Adults without Dementia

    PubMed Central

    James, Bryan D.; Boyle, Patricia A.; Yu, Lei; Han, S. Duke; Bennett, David A.

    2015-01-01

    Risk aversion and temporal discounting are preferences that are strongly linked to sub-optimal financial and health decision making ability. Prior studies have shown they differ by age and cognitive ability, but it remains unclear whether differences are due to age-related cognitive decline or lower cognitive abilities over the life span. We tested the hypothesis that cognitive decline is associated with higher risk aversion and temporal discounting in 455 older persons without dementia from the Memory and Aging Project, a longitudinal cohort study of aging in Chicago. All underwent repeated annual cognitive evaluations using a detailed battery including 19 tests. Risk aversion was measured using standard behavioral economics questions: participants were asked to choose between a certain monetary payment versus a gamble in which they could gain more or nothing; potential gamble gains varied across questions. Temporal discounting: participants were asked to choose between an immediate, smaller payment and a delayed, larger one; two sets of questions addressed small and large stakes based on payment amount. Regression analyses were used to examine whether prior rate of cognitive decline predicted level of risk aversion and temporal discounting, controlling for age, sex, and education. Over an average of 5.5 (SD=2.9) years, cognition declined at an average of 0.016 units per year (SD=0.03). More rapid cognitive decline predicted higher levels of risk aversion (p=0.002) and temporal discounting (small stakes: p=0.01, high stakes: p=0.006). Further, associations between cognitive decline and risk aversion (p=0.015) and large stakes temporal discounting (p=0.026) persisted in analyses restricted to persons without any cognitive impairment (i.e., no dementia or mild cognitive impairment); the association of cognitive decline and small stakes temporal discounting was no longer statistically significant (p=0.078). These findings are consistent with the hypothesis that

  2. Cognitive decline is associated with risk aversion and temporal discounting in older adults without dementia.

    PubMed

    James, Bryan D; Boyle, Patricia A; Yu, Lei; Han, S Duke; Bennett, David A

    2015-01-01

    Risk aversion and temporal discounting are preferences that are strongly linked to sub-optimal financial and health decision making ability. Prior studies have shown they differ by age and cognitive ability, but it remains unclear whether differences are due to age-related cognitive decline or lower cognitive abilities over the life span. We tested the hypothesis that cognitive decline is associated with higher risk aversion and temporal discounting in 455 older persons without dementia from the Memory and Aging Project, a longitudinal cohort study of aging in Chicago. All underwent repeated annual cognitive evaluations using a detailed battery including 19 tests. Risk aversion was measured using standard behavioral economics questions: participants were asked to choose between a certain monetary payment versus a gamble in which they could gain more or nothing; potential gamble gains varied across questions. Temporal discounting: participants were asked to choose between an immediate, smaller payment and a delayed, larger one; two sets of questions addressed small and large stakes based on payment amount. Regression analyses were used to examine whether prior rate of cognitive decline predicted level of risk aversion and temporal discounting, controlling for age, sex, and education. Over an average of 5.5 (SD=2.9) years, cognition declined at an average of 0.016 units per year (SD=0.03). More rapid cognitive decline predicted higher levels of risk aversion (p=0.002) and temporal discounting (small stakes: p=0.01, high stakes: p=0.006). Further, associations between cognitive decline and risk aversion (p=0.015) and large stakes temporal discounting (p=0.026) persisted in analyses restricted to persons without any cognitive impairment (i.e., no dementia or mild cognitive impairment); the association of cognitive decline and small stakes temporal discounting was no longer statistically significant (p=0.078). These findings are consistent with the hypothesis that

  3. Electrophysiological markers of rapid cognitive decline in mild cognitive impairment.

    PubMed

    Giannakopoulos, Panteleimon; Missonnier, Pascal; Kövari, Enikö; Gold, Gabriel; Michon, Agnès

    2009-01-01

    Electroencephalography (EEG) is an easily accessible and low-cost modality that might prove to be a particularly powerful tool for the identification of subtle functional changes preceding structural or metabolic deficits in progressive mild cognitive impairment (PMCI). Most previous contributions in this field assessed quantitative EEG differences between healthy controls, MCI and Alzheimer's disease(AD) cases leading to contradictory data. In terms of MCI conversion to AD, certain longitudinal studies proposed various quantitative EEG parameters for an a priori distinction between PMCI and stable MCI. However, cross-sectional comparisons revealed a substantial overlap in these parameters between MCI patients and elderly controls. Methodological differences including variable clinical definition of MCI cases and substantial interindividual differences within the MCI group could partly explain these discrepancies. Most importantly, EEG measurements without cognitive demand in both cross-sectional and longitudinal designs have demonstrated limited sensitivity and generally do not produce significant group differences in spectral EEG parameters. Since the evolution of AD is characterized by the progressive loss of functional connectivity within neocortical association areas, event-modulated EEG dynamic analysis which makes it possible to investigate the functional activation of neocortical circuits may represent a more sensitive method to identify early alterations of neuronal networks predictive of AD development among MCI cases. The present review summarizes clinically significant results of EEG activation studies in this field and discusses future perspectives of research aiming to reach an early and individual prediction of cognitive decline in healthy elderly controls. PMID:19182461

  4. Corpus callosum atrophy as a predictor of age-related cognitive and motor impairment: a 3-year follow-up of the LADIS study cohort.

    PubMed

    Ryberg, C; Rostrup, E; Paulson, O B; Barkhof, F; Scheltens, P; van Straaten, E C W; van der Flier, W M; Fazekas, F; Schmidt, R; Ferro, J M; Baezner, H; Erkinjuntti, T; Jokinen, H; Wahlund, L-O; Poggesi, A; Pantoni, L; Inzitari, D; Waldemar, G

    2011-08-15

    The aim of this 3-year follow-up study was to investigate whether corpus callosum (CC) atrophy may predict future motor and cognitive impairment in an elderly population. On baseline MRI from 563 subjects with age-related white matter changes (ARWMC) from the Leukoaraiosis And DISability (LADIS) study, the CC was segmented and subdivided into five anterior-posterior regions (CC1-CC5). Associations between the CC areas and decline in motor performance and cognitive functions over a 3-year period were analyzed. CC atrophy at baseline was significantly associated with impaired cognitive performance (p<0.01 for CC1, p<0.05 for CC5), motor function (p<0.05 for CC2 and CC5), and walking speed (p<0.01 for CC2 and CC5, p<0.05 for CC3 and total CC), and with development of dementia at 3 years (p<0.05 for CC1) after correction for appropriate confounders (ARWMC volume, atrophy, age, gender and handedness). In conclusion, CC atrophy, an indicator of reduced functional connectivity between cortical areas, seems to contribute, independently of ARWMC load, to future cognitive and motor decline in the elderly. PMID:21621224

  5. Hot Topics in Research: Preventive Neuroradiology in Brain Aging and Cognitive Decline

    PubMed Central

    Raji, Cyrus A.; Eyre, Harris; Wei, Sindy H.; Bredesen, Dale; Moylan, Steven; Law, Meng; Small, Gary; Thompson, Paul; Friedlander, Robert; Silverman, Dan H.; Baune, Bernhard T; Hoang, Thu-Anh; Salamon, Noriko; Toga, Arthur; Vernooij, Meike W.

    2015-01-01

    Preventive neuroradiology is a new concept supported by a growing literature. The main rationale of preventive neuroradiology is the application of multi-modal brain imaging towards early and subclinical detection of brain disease and subsequent preventive actions through identification of modifiable risk factors. An insightful example of this is in the area of age-related cognitive decline, mild cognitive impairment and dementia with potentially modifiable risk factors such as obesity, diet, sleep, hypertension, diabetes, depression, supplementation, smoking and physical activity. In studying this link between lifestyle and cognitive decline, brain imaging markers may be instrumental as quantitative measures or even indicators of early disease. The purpose of this article is to provide an overview of the major studies reflecting how lifestyle factors affect the brain and cognition ageing. In this hot topics review we will specifically focus on obesity and physical activity. PMID:26045577

  6. Hot Topics in Research: Preventive Neuroradiology in Brain Aging and Cognitive Decline.

    PubMed

    Raji, C A; Eyre, H; Wei, S H; Bredesen, D E; Moylan, S; Law, M; Small, G; Thompson, P M; Friedlander, R M; Silverman, D H; Baune, B T; Hoang, T A; Salamon, N; Toga, A W; Vernooij, M W

    2015-10-01

    Preventive neuroradiology is a new concept supported by growing literature. The main rationale of preventive neuroradiology is the application of multimodal brain imaging toward early and subclinical detection of brain disease and subsequent preventive actions through identification of modifiable risk factors. An insightful example of this is in the area of age-related cognitive decline, mild cognitive impairment, and dementia with potentially modifiable risk factors such as obesity, diet, sleep, hypertension, diabetes, depression, supplementation, smoking, and physical activity. In studying this link between lifestyle and cognitive decline, brain imaging markers may be instrumental as quantitative measures or even indicators of early disease. The purpose of this article is to provide an overview of the major studies reflecting how lifestyle factors affect the brain and cognition aging. In this hot topics review, we will specifically focus on obesity and physical activity. PMID:26045577

  7. Guidelines for the Evaluation of Dementia and Age-Related Cognitive Change

    ERIC Educational Resources Information Center

    American Psychologist, 2012

    2012-01-01

    Dementia in its many forms is a leading cause of functional limitation among older adults worldwide and will continue to ascend in global health importance as populations continue to age and effective cures remain elusive. The following guidelines were developed for psychologists who perform evaluations of dementia and age-related cognitive…

  8. Longitudinal cognitive decline in the AIBL cohort: The role of APOE ε4 status.

    PubMed

    Albrecht, Matthew A; Szoeke, Cassandra; Maruff, Paul; Savage, Greg; Lautenschlager, Nicola T; Ellis, Kathryn A; Taddei, Kevin; Martins, Ralph; Masters, Colin L; Ames, David; Foster, Jonathan K

    2015-08-01

    The ε4 polymorphism of the APOE gene confers a substantially increased risk of developing Alzheimer's disease. However, the influence of the ε4 allele on age-related cognitive functioning is more contentious. Previously, we demonstrated relatively little evidence for a role of the ε4 allele on baseline cognitive performance in older adults in the Australian Imaging, Biomarkers and Lifestyle (AIBL) Study of Ageing (Foster et al., 2013). We here investigated whether the APOE ε4 allele influenced cognitive status over time when the AIBL cohort was studied longitudinally over a 3-year period. The AIBL neuropsychological test battery was administered at baseline, after 18 months and again after 36 months. Participants comprised 764 Healthy Controls and 131 Mild Cognitively Impaired individuals enrolled in the AIBL Study of Ageing. We compared individuals within each group with and without an ε4 allele. Healthy Controls with an ε4 allele manifested a modest acceleration in cognitive decline over 36 months on measures of verbal episodic memory. By contrast, Mild Cognitively Impaired individuals with an ε4 allele showed increased cognitive decline across a range of cognitive tasks, putatively reflecting early cognitive signs of Alzheimer's disease. Given the long prodromal period that has been noted in late onset Alzheimer's disease, we suggest that these findings are consistent with a prodromal account rather than a phenotypic account of ε4-related cognitive ageing. PMID:26102189

  9. Age-Related Changes in Sleep and Circadian Rhythms: Impact on Cognitive Performance and Underlying Neuroanatomical Networks

    PubMed Central

    Schmidt, Christina; Peigneux, Philippe; Cajochen, Christian

    2012-01-01

    Circadian and homeostatic sleep-wake regulatory processes interact in a fine tuned manner to modulate human cognitive performance. Dampening of the circadian alertness signal and attenuated deterioration of psychomotor vigilance in response to elevated sleep pressure with aging change this interaction pattern. As evidenced by neuroimaging studies, both homeostatic sleep pressure and circadian sleep-wake promotion impact on cognition-related cortical and arousal-promoting subcortical brain regions including the thalamus, the anterior hypothalamus, and the brainstem locus coeruleus (LC). However, how age-related changes in circadian and homeostatic processes impact on the cerebral activity subtending waking performance remains largely unexplored. Post-mortem studies point to neuronal degeneration in the SCN and age-related modifications in the arousal-promoting LC. Alongside, cortical frontal brain areas are particularly susceptible both to aging and misalignment between circadian and homeostatic processes. In this perspective, we summarize and discuss here the potential neuroanatomical networks underlying age-related changes in circadian and homeostatic modulation of waking performance, ranging from basic arousal to higher order cognitive behaviors. PMID:22855682

  10. Age-Related Testosterone Decline is due to Waning of Both Testicular and Hypothalamic-Pituitary Function

    PubMed Central

    Golan, Ron; Scovell, Jason M.; Ramasamy, Ranjith

    2016-01-01

    Hypogonadism is a condition in which the endogenous secretion of testosterone is either insufficient or inadequate to maintain serum testosterone levels within normal range, and may manifest as a variety of signs and symptoms. Age-related hypogonadism is due to a combination of primary hypogonadism (testicular failure) and secondary hypogonadism (hypothalamic-pituitary axis failure). This review provides insight into the mechanisms resulting in the multifactorial nature of acquired androgen-deficiency, and outlines the current controversy regarding testosterone-replacement therapy in aging males. PMID:26075536

  11. Dietary Approaches and Supplements in the Prevention of Cognitive Decline and Alzheimer's Disease.

    PubMed

    Dominguez, Ligia J; Barbagallo, Mario

    2016-01-01

    Age-associated cognitive decline and dementia are conditions in which there is deterioration in memory, thinking, and behavior, with profound effects on the ability to perform everyday activities and well-being. Even if dementia mainly affects older persons, it is not a normal part of aging. Alzheimer's disease accounts for 60-75% of dementia cases. The number of persons affected will increase in the next decades in parallel with aging of the world population. Hence, unless some approach is found to reduce age-related deterioration of cognitive functions, health care costs will continue to rise exponentially. There is a wealth of epidemiological evidence supporting a relationship between diet and Alzheimer's disease, and suggesting that the risk of cognitive decline may be reduced by dietary interventions. It has been proposed that adopting a healthy diet and lifestyle that improves cardiovascular function may help delaying the onset of Alzheimer's disease due to its potential association with vascular disease. Several nutrients, dietary components, supplements and dietary patterns have been reported in relation to their association with cognition and with the development of cognitive decline and Alzheimer's disease. The possible effect of diet on the prevention of dementia is of tremendous scientific and general interest, because hitherto there is no definitive evidence of any effective pharmacological treatment for dementia. The aim of this review is to evaluate the evidence for the effects of some dietary components, supplements, and dietary patterns as neuroprotective, with potential to delay cognitive decline and the onset of dementia. PMID:26635270

  12. Age-related decline in multiple unit action potentials of CA3 region of rat hippocampus: correlation with lipid peroxidation and lipofuscin concentration and the effect of centrophenoxine.

    PubMed

    Sharma, D; Maurya, A K; Singh, R

    1993-01-01

    Changes in lipid peroxidation, lipofuscin concentration, and multiple unit activity (MUA recorded in conscious animals) in the CA3 region were studied in the hippocampus of male Wistar rats aged 4, 8, 16, and 24 months. The lipid peroxidation and lipofuscin concentration were increased with age. The MUA, however, declined with age. Correlational analyses were performed for the four age groups to determine the relationship between the age-associated decline in MUA with the age-related alterations in lipid peroxidation and lipofuscin concentrations. The age-related increase in lipid peroxidation correlated positively with the age-associated increase in lipofuscin concentration. The age-related increases in lipid peroxidation and lipofuscin concentration correlated negatively with the changes in MUA. Since lipid peroxidation may affect neuronal electrophysiology, our data suggested that age-related increase in lipid peroxidation may contribute to an age-associated decline in neuronal electrical activity. Centrophenoxine effects were studied on the three above-mentioned age-associated changes in the hippocampus. The drug had no effect on all three parameters in 4- and 8-month-old rats. In 16- and 24-month-old rats, however, the drug significantly increased the MUA but concomitantly decreased lipofuscin concentration and lipid peroxidation. Correlational analyses of the data on MUA, lipid peroxidation and lipofuscin concentration from the centrophenoxine-treated animals showed that the drug-induced diminution in both lipofuscin and lipid peroxidation was significantly correlated with the drug-induced increase in MUA. The differential effect of the drug in younger (4-8 months) and older (16-24 months) animals indicated that the stimulation of MUA was clearly associated with concomitant decrease in lipid peroxidation and lipofuscin concentration. PMID:8367013

  13. Age-related changes in the cerebral substrates of cognitive procedural learning.

    PubMed

    Hubert, Valérie; Beaunieux, Hélène; Chételat, Gaël; Platel, Hervé; Landeau, Brigitte; Viader, Fausto; Desgranges, Béatrice; Eustache, Francis

    2009-04-01

    Cognitive procedural learning occurs in three qualitatively different phases (cognitive, associative, and autonomous). At the beginning of this process, numerous cognitive functions are involved, subtended by distinct brain structures such as the prefrontal and parietal cortex and the cerebellum. As the learning progresses, these cognitive components are gradually replaced by psychomotor abilities, reflected by the increasing involvement of the cerebellum, thalamus, and occipital regions. In elderly subjects, although cognitive studies have revealed a learning effect, performance levels differ during the acquisition of a procedure. The effects of age on the learning of a cognitive procedure have not yet been examined using functional imaging. The aim of this study was therefore to characterize the cerebral substrates involved in the learning of a cognitive procedure, comparing a group of older subjects with young controls. For this purpose, we performed a positron emission tomography activation study using the Tower of Toronto task. A direct comparison of the two groups revealed the involvement of a similar network of brain regions at the beginning of learning (cognitive phase). However, the engagement of frontal and cingulate regions persisted in the older group as learning continued, whereas it ceased in the younger controls. We assume that this additional activation in the older group during the associative and autonomous phases reflected compensatory processes and the fact that some older subjects failed to fully automate the procedure. PMID:18537110

  14. Age-related changes in the cerebral substrates of cognitive procedural learning

    PubMed Central

    Hubert, Valérie; Beaunieux, Hélène; Chételat, Gaël; Platel, Hervé; Landeau, Brigitte; Viader, Fausto; Desgranges, Béatrice; Eustache, Francis

    2009-01-01

    Cognitive procedural learning occurs in three qualitatively different phases (cognitive, associative and autonomous). At the beginning of this process, numerous cognitive functions are involved, subtended by distinct brain structures such as the prefrontal and parietal cortex and the cerebellum. As the learning progresses, these cognitive components are gradually replaced by psychomotor abilities, reflected by the increasing involvement of the cerebellum, thalamus and occipital regions. In elderly subjects, although cognitive studies have revealed a learning effect, performance levels differ during the acquisition of a procedure. The effects of age on the learning of a cognitive procedure have not yet been examined using functional imaging. The aim of this study was therefore to characterize the cerebral substrates involved in the learning of a cognitive procedure, comparing a group of older subjects with young controls. For this purpose, we performed a positron emission tomography activation study using the Tower of Toronto task. A direct comparison of the two groups revealed the involvement of a similar network of brain regions at the beginning of learning (cognitive phase). However, whereas the engagement of frontal and cingulate regions persisted in the older group as learning continued, it ceased in the younger controls. We assume that this additional activation in the older group during the associative and autonomous phases reflected compensatory processes and the fact that some older subjects failed to fully automate the procedure. PMID:18537110

  15. Causes of Age-Related Decline in Adaptive Behavior of Adults with Down Syndrome: Differential Diagnoses of Dementia.

    ERIC Educational Resources Information Center

    Prasher, V. P.; Chung, Man Cheung

    1996-01-01

    A study was conducted of 201 adults with Down's syndrome to investigate the differential causes of decline in adaptive behavior. Results indicated that aging, dementia, and severity of mental retardation were significant factors, while absence of a medical illness predicted a higher level of adaptive behavior. (CR)

  16. Can Exercise Ameliorate Aromatase Inhibitor-Induced Cognitive Decline in Breast Cancer Patients?

    PubMed

    Li, Cuicui; Zhou, Chenglin; Li, Rena

    2016-08-01

    Aromatase inhibitors (AIs) have been commonly used as an effective adjuvant therapy in treatment of breast cancer, especially for menopausal women with estrogen receptor-positive breast cancer. Due to the nature of aromatase, the key enzyme for endogenous estrogen synthesis, inhibitory of aromatase-induced side effects, such as cognitive impairment has been reported in both human and animal studies. While extensive evidence suggested that physical exercises can improve learning and memory activity and even prevent age-related cognitive decline, basic research revealed some common pathways between exercise and estrogen signaling that affected cognitive function. This review draws on clinical and basic studies to assess the potential impact of exercise in cognitive function from women treated with AIs for breast cancer and explore the potential mechanism and effects of exercise on estrogen-related cognition. PMID:26223800

  17. Polyphenols and Polyunsaturate Fatty Acids: The Pollyanna's of Age-Related Cognitive Decline, Neurodegenerative Disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    As children, there are very few of us who have not heard Mom's familiar refrain: "Eat your fruits and vegetables. They're good for you"! Little did we realize until later in life how much Mom knew about what we should eat to stay healthy. Now, it seems as though Mom's prophetic statement appears da...

  18. Cerebrospinal fluid biomarkers mirror rate of cognitive decline.

    PubMed

    Rolstad, Sindre; Berg, Anne Ingeborg; Bjerke, Maria; Johansson, Boo; Zetterberg, Henrik; Wallin, Anders

    2013-01-01

    The ability to predict future decline in cognitive systems using the cerebrospinal fluid (CSF) biomarkers 42 amino acid form of amyloid-β (Aβ42) and total tau (T-tau) is not fully understood. In a clinical sample ranging from cognitively healthy to dementia (n = 326), linear regression models were performed in order to investigate the ability of CSF biomarkers to predict cognitive decline in all cognitive domains from baseline to 2-year follow-up. Gender, age, and years of education were included as covariates. In patients with subjective cognitive impairment, T-tau had a small impact on executive functions (r2 = 0.07). T-tau had a small to moderate influence (r2 = 0.06-0.11) on all cognitive functions with the exception of visuospatial functions in patients with mild cognitive impairment (MCI). In patients with dementia, the impact of T-tau was large (r2 = 0.29) on semantic memory. Aβ42 had a small effect (r2 = 0.07) on speed and executive functions in MCI. In patients with dementia, Aβ42 had a moderate influence (r2 = 0.13-0.24) on semantic and verbal working memory/fluency. Our results speak in favor of the notion that CSF biomarkers reflect the rate of cognitive decline across the continuum of cognitive impairment from healthy to dementia. CSF predicted subsequent decline in more cognitive domains among MCI cases, but the impact was most pronounced in patients with dementia. PMID:23313924

  19. Inspection Time: A Biomarker for Cognitive Decline

    ERIC Educational Resources Information Center

    Gregory, Tess; Nettelbeck, Ted; Howard, Sara; Wilson, Carlene

    2008-01-01

    Inspection Time (IT) is a psychophysical speed measure that has been linked to a range of cognitive abilities with results finding that shorter IT is associated with superior performance in cognitive abilities. Following a recent suggestion by Nettelbeck and Wilson [Nettelbeck, T., & Wilson, C. (2004). The Flynn effect: Smarter not faster.…

  20. Looking for age-related growth decline in natural forests: unexpected biomass patterns from tree rings and simulated mortality

    USGS Publications Warehouse

    Foster, Jane R.; D'Amato, Anthony W.; Bradford, John B.

    2014-01-01

    Forest biomass growth is almost universally assumed to peak early in stand development, near canopy closure, after which it will plateau or decline. The chronosequence and plot remeasurement approaches used to establish the decline pattern suffer from limitations and coarse temporal detail. We combined annual tree ring measurements and mortality models to address two questions: first, how do assumptions about tree growth and mortality influence reconstructions of biomass growth? Second, under what circumstances does biomass production follow the model that peaks early, then declines? We integrated three stochastic mortality models with a census tree-ring data set from eight temperate forest types to reconstruct stand-level biomass increments (in Minnesota, USA). We compared growth patterns among mortality models, forest types and stands. Timing of peak biomass growth varied significantly among mortality models, peaking 20–30 years earlier when mortality was random with respect to tree growth and size, than when mortality favored slow-growing individuals. Random or u-shaped mortality (highest in small or large trees) produced peak growth 25–30 % higher than the surviving tree sample alone. Growth trends for even-aged, monospecific Pinus banksiana or Acer saccharum forests were similar to the early peak and decline expectation. However, we observed continually increasing biomass growth in older, low-productivity forests of Quercus rubra, Fraxinus nigra, and Thuja occidentalis. Tree-ring reconstructions estimated annual changes in live biomass growth and identified more diverse development patterns than previous methods. These detailed, long-term patterns of biomass development are crucial for detecting recent growth responses to global change and modeling future forest dynamics.

  1. SIRT6 rescues the age related decline in base excision repair in a PARP1-dependent manner

    PubMed Central

    Xu, Zhu; Zhang, Lei; Zhang, Wenjun; Meng, Du; Zhang, Hongxia; Jiang, Ying; Xu, Xiaojun; Van Meter, Michael; Seluanov, Andrei; Gorbunova, Vera; Mao, Zhiyong

    2015-01-01

    In principle, a decline in base excision repair (BER) efficiency with age should lead to genomic instability and ultimately contribute to the onset of the aging phenotype. Although multiple studies have indicated a negative link between aging and BER, the change of BER efficiency with age in humans has not been systematically analyzed. Here, with foreskin fibroblasts isolated from 19 donors between 20 and 64 y of age, we report a significant decline of BER efficiency with age using a newly developed GFP reactivation assay. We further observed a very strong negative correlation between age and the expression levels of SIRT6, a factor which is known to maintain genomic integrity by improving DNA double strand break (DSB) repair. Our mechanistic study suggests that, similar to the regulatory role that SIRT6 plays in DNA DSB repair, SIRT6 regulates BER in a PARP1-depdendent manner. Moreover, overexpression of SIRT6 rescues the decline of BER in aged fibroblasts. In summary, our results uncovered the regulatory mechanisms of BER by SIRT6, suggesting that SIRT6 reactivation in aging tissues may help delay the process of aging through improving BER. PMID:25607651

  2. Neuropsychological tests for predicting cognitive decline in older adults

    PubMed Central

    Baerresen, Kimberly M; Miller, Karen J; Hanson, Eric R; Miller, Justin S; Dye, Richelin V; Hartman, Richard E; Vermeersch, David; Small, Gary W

    2015-01-01

    Summary Aim To determine neuropsychological tests likely to predict cognitive decline. Methods A sample of nonconverters (n = 106) was compared with those who declined in cognitive status (n = 24). Significant univariate logistic regression prediction models were used to create multivariate logistic regression models to predict decline based on initial neuropsychological testing. Results Rey–Osterrieth Complex Figure Test (RCFT) Retention predicted conversion to mild cognitive impairment (MCI) while baseline Buschke Delay predicted conversion to Alzheimer’s disease (AD). Due to group sample size differences, additional analyses were conducted using a subsample of demographically matched nonconverters. Analyses indicated RCFT Retention predicted conversion to MCI and AD, and Buschke Delay predicted conversion to AD. Conclusion Results suggest RCFT Retention and Buschke Delay may be useful in predicting cognitive decline. PMID:26107318

  3. APOE and aging-related cognitive change in a longitudinal cohort of men.

    PubMed

    Rantalainen, Ville; Lahti, Jari; Henriksson, Markus; Kajantie, Eero; Tienari, Pentti; Eriksson, Johan G; Raikkonen, Katri

    2016-08-01

    We examined associations between APOE major isoforms, rs405509 promoter and rs440446 intron-1 polymorphisms, and nonpathologic cognitive aging. Men from the Helsinki Birth Cohort Study took the Finnish Defence Forces Basic Intellectual Ability Test twice, at age 20.1 (n = 404) and 67.6 years (n = 247). APOE major isoforms did not associate with cognitive ability. In the APOE major isoform-adjusted analyses, the number of rs405509 minor alleles was associated with a higher cognitive ability total and verbal, arithmetic, and visuospatial subtest scores at 67.6 years (p-values < 0.004). In the analyses of cognitive change, the visuospatial subtest score increased across time in rs440446 minor allele carriers but decreased in noncarriers (p = 0.007). Associations in the APOE major isoform-stratified analyses were significant in the APOE ε3/3 homozygotes only. The APOE locus harbors additional modifying alleles, independent of APOE major isoforms that are associated with better preserved general cognitive ability in nondemented elderly men and change in visuospatial ability across 5 decades. These results suggest that at least 2 distinct mechanisms link the APOE locus with cognitive ability. PMID:27318143

  4. Age-Related Wayfinding Differences in Real Large-Scale Environments: Detrimental Motor Control Effects during Spatial Learning Are Mediated by Executive Decline?

    PubMed Central

    Taillade, Mathieu; Sauzéon, Hélène; Arvind Pala, Prashant; Déjos, Marie; Larrue, Florian; Gross, Christian; N’Kaoua, Bernard

    2013-01-01

    The aim of this study was to evaluate motor control activity (active vs. passive condition) with regards to wayfinding and spatial learning difficulties in large-scale spaces for older adults. We compared virtual reality (VR)-based wayfinding and spatial memory (survey and route knowledge) performances between 30 younger and 30 older adults. A significant effect of age was obtained on the wayfinding performances but not on the spatial memory performances. Specifically, the active condition deteriorated the survey measure in all of the participants and increased the age-related differences in the wayfinding performances. Importantly, the age-related differences in the wayfinding performances, after an active condition, were further mediated by the executive measures. All of the results relative to a detrimental effect of motor activity are discussed in terms of a dual task effect as well as executive decline associated with aging. PMID:23843992

  5. Age-related Decline in Kv3.1b Expression in the Mouse Auditory Brainstem Correlates with Functional Deficits in the Medial Olivocochlear Efferent System

    PubMed Central

    Zhu, Xiaoxia; O’Neill, William E.; Frisina, Robert D.

    2007-01-01

    Kv3.1b channel protein is widely distributed in the mammalian auditory brainstem, but studies have focused mainly on regions critical for temporal processing, including the medial nucleus of the trapezoid body (MNTB) and anteroventral cochlear nucleus (AVCN). Because temporal processing declines with age, this study was undertaken to determine if the expression of Kv3.1b likewise declines, and if changes are specific to these nuclei. Immunocytochemistry using an anti-Kv3.1b antibody was performed, and the relative optical density of cells and neuropil was determined from CBA/CaJ mice of four age groups. Declines in expression in AVCN, MNTB, and lateral superior olive (35, 26, and 23%) were found, but changes were limited to neuropil. Interestingly, cellular optical density declines were found in superior paraolivary nucleus, ventral nucleus of the trapezoid body, and lateral nucleus of the trapezoid body (24, 29, and 26%), which comprise the medial olivocochlear (MOC) feedback system. All declines occurred by middle age (15 months old). No age-related changes were found in the remaining regions of cochlear nucleus or in the inferior colliculus. Contralateral suppression of distortion-product otoacoustic emission amplitudes of age-matched littermates also declined by middle age, suggesting a correlation between Kv3.1 expression and MOC function. In search of more direct evidence for such a correlation, Kv3.1b knockout mice were examined. Knockouts show poor MOC function as compared to +/+ and +/− genotypes. Thus, Kv3.1b expression declines in MOC neurons by middle age, and these changes appear to correlate with functional declines in efferent activity in both middle-aged CBA mice and Kv3.1b knockout mice. PMID:17453307

  6. Age-Related Changes in Cognitive Processing of Moral and Social Conventional Violations

    ERIC Educational Resources Information Center

    Lahat, Ayelet; Helwig, Charles C.; Zelazo, Philip David

    2012-01-01

    Moral and conventional violations are usually judged differently: Only moral violations are treated as independent of social rules. To investigate the cognitive processing involved in the development of this distinction, undergraduates (N = 34), adolescents (N = 34), and children (N = 14) read scenarios presented on a computer that had 1 of 3…

  7. Obesity and cognitive decline: role of inflammation and vascular changes

    PubMed Central

    Nguyen, Jason C. D.; Killcross, A. Simon; Jenkins, Trisha A.

    2014-01-01

    The incidence of obesity in middle age is increasing markedly, and in parallel the prevalence of metabolic disorders including cardiovascular disease and type II diabetes is also rising. Numerous studies have demonstrated that both obesity and metabolic disorders are associated with poorer cognitive performance, cognitive decline, and dementia. In this review we discuss the effects of obesity on cognitive performance, including both clinical and preclinical observations, and discuss some of the potential mechanisms involved, namely inflammation and vascular and metabolic alterations. PMID:25477778

  8. The Role of RFamide-Related Peptide-3 in Age-Related Reproductive Decline in Female Rats.

    PubMed

    Geraghty, Anna C; Muroy, Sandra E; Kriegsfeld, Lance J; Bentley, George E; Kaufer, Daniela

    2016-01-01

    Reproductive senescence, the point in time when females cease to show estrous cyclicity, is associated with endocrine changes in the hypothalamus, pituitary, and gonads. However, the mechanisms triggering this transition are not well understood. To gain a better understanding of the top-down control of the transition from reproductive competence to a state of reproductive senescence, we investigated middle-aged female rats exhibiting varying degrees of reproductive decline, including individuals with normal cycles, irregular cycles, and complete cessation of cycles. We identified hormonal changes in the brain that manifest before ovarian cycles exhibit any deterioration. We found that females exhibit an increase in RFamide-related peptide-3 (RFRP3) mRNA expression in the hypothalamus in middle age prior to changes in estrous cycle length. This increase is transient and followed by subsequent decreases in kisspeptin (KiSS1) and gonadotropin-releasing hormone (GnRH) mRNA expression. Expression of RFRP3 and its receptor also increased locally in the ovaries with advancing age. While it is well known that aging is associated with decreased GnRH release and downstream disruption of the hypothalamic-pituitary-gonadal (HPG) axis, herein, we provide evidence that reproductive senescence is likely triggered by alterations in a network of regulatory neuropeptides upstream of the GnRH system. PMID:27445974

  9. Rapamycin increases grip strength and attenuates age-related decline in maximal running distance in old low capacity runner rats

    PubMed Central

    Xue, Qian-Li; Yang, Huanle; Li, Hui-Fen; Abadir, Peter M.; Burks, Tyesha N.; Koch, Lauren G.; Britton, Steven L.; Carlson, Joshua; Chen, Laura; Walston, Jeremy D.; Leng, Sean X.

    2016-01-01

    Rapamycin is known to extend lifespan. We conducted a randomized placebo-controlled study of enteric rapamycin-treatment to evaluate its effect on physical function in old low capacity runner (LCR) rats, a rat model selected from diverse genetic background for low intrinsic aerobic exercise capacity without genomic manipulation and characterized by increased complex disease risks and aging phenotypes. The study was performed in 12 male and 16 female LCR rats aged 16-22 months at baseline. The treatment group was fed with rapamycin-containing diet pellets at approximately 2.24mg/kg body weight per day and the placebo group with the same diet without rapamycin for six months. Observation was extended for additional 2 months. Physical function measurements include grip strength measured as maximum tensile force using a rat grip strength meter and maximum running distance (MRD) using rat physical treadmill test. The results showed that rapamycin improved grip strength by 13% (p=.036) and 60% (p<.001) from its baseline in female and male rats, respectively. Rapamycin attenuated MRD decline by 66% (p<.001) and 46% (p=.319) in females and males, respectively. These findings provide initial evidence for beneficial effect of rapamycin on physical functioning in an aging rat model of high disease risks with significant implication in humans. PMID:26997106

  10. The Role of RFamide-Related Peptide-3 in Age-Related Reproductive Decline in Female Rats

    PubMed Central

    Geraghty, Anna C.; Muroy, Sandra E.; Kriegsfeld, Lance J.; Bentley, George E.; Kaufer, Daniela

    2016-01-01

    Reproductive senescence, the point in time when females cease to show estrous cyclicity, is associated with endocrine changes in the hypothalamus, pituitary, and gonads. However, the mechanisms triggering this transition are not well understood. To gain a better understanding of the top-down control of the transition from reproductive competence to a state of reproductive senescence, we investigated middle-aged female rats exhibiting varying degrees of reproductive decline, including individuals with normal cycles, irregular cycles, and complete cessation of cycles. We identified hormonal changes in the brain that manifest before ovarian cycles exhibit any deterioration. We found that females exhibit an increase in RFamide-related peptide-3 (RFRP3) mRNA expression in the hypothalamus in middle age prior to changes in estrous cycle length. This increase is transient and followed by subsequent decreases in kisspeptin (KiSS1) and gonadotropin-releasing hormone (GnRH) mRNA expression. Expression of RFRP3 and its receptor also increased locally in the ovaries with advancing age. While it is well known that aging is associated with decreased GnRH release and downstream disruption of the hypothalamic–pituitary–gonadal (HPG) axis, herein, we provide evidence that reproductive senescence is likely triggered by alterations in a network of regulatory neuropeptides upstream of the GnRH system. PMID:27445974

  11. Intranasal Insulin Improves Age-Related Cognitive Deficits and Reverses Electrophysiological Correlates of Brain Aging.

    PubMed

    Maimaiti, Shaniya; Anderson, Katie L; DeMoll, Chris; Brewer, Lawrence D; Rauh, Benjamin A; Gant, John C; Blalock, Eric M; Porter, Nada M; Thibault, Olivier

    2016-01-01

    Peripheral insulin resistance is a key component of metabolic syndrome associated with obesity, dyslipidemia, hypertension, and type 2 diabetes. While the impact of insulin resistance is well recognized in the periphery, it is also becoming apparent in the brain. Recent studies suggest that insulin resistance may be a factor in brain aging and Alzheimer's disease (AD) whereby intranasal insulin therapy, which delivers insulin to the brain, improves cognition and memory in AD patients. Here, we tested a clinically relevant delivery method to determine the impact of two forms of insulin, short-acting insulin lispro (Humalog) or long-acting insulin detemir (Levemir), on cognitive functions in aged F344 rats. We also explored insulin effects on the Ca(2+)-dependent hippocampal afterhyperpolarization (AHP), a well-characterized neurophysiological marker of aging which is increased in the aged, memory impaired animal. Low-dose intranasal insulin improved memory recall in aged animals such that their performance was similar to that seen in younger animals. Further, because ex vivo insulin also reduced the AHP, our results suggest that the AHP may be a novel cellular target of insulin in the brain, and improved cognitive performance following intranasal insulin therapy may be the result of insulin actions on the AHP. PMID:25659889

  12. [Presbycusis - Age Related Hearing Loss].

    PubMed

    Fischer, N; Weber, B; Riechelmann, H

    2016-07-01

    Presbycusis or age related hearing loss can be defined as a progressive, bilateral and symmetrical sensorineural hearing loss due to age related degeneration of inner ear structures. It can be considered a multifactorial complex disorder with environmental and genetic factors. The molecular, electrophysiological and histological damage at different levels of the inner ear cause a progressive hearing loss, which usually affects the high frequencies of hearing. The resulting poor speech recognition has a negative impact on cognitive, emotional and social function in older adults. Recent investigations revealed an association between hearing impairment and social isolation, anxiety, depression and cognitive decline in elderly. These findings emphasize the importance of diagnosis and treating hearing loss in the elderly population. Hearing aids are the most commonly used devices for treating presbycusis. The technical progress of implantable hearing devices allows an effective hearing rehabilitation even in elderly with severe hearing loss. However, most people with hearing impairments are not treated adequately. PMID:27392191

  13. Mitochondrial haplogroups modify the effect of black carbon on age-related cognitive impairment

    PubMed Central

    2014-01-01

    Background Traffic-related air pollution has been linked with impaired cognition in older adults, possibly due to effects of oxidative stress on the brain. Mitochondria are the main source of cellular oxidation. Haplogroups in mitochondrial DNA (mtDNA) mark individual differences in oxidative potential and are possible determinants of neurodegeneration. The aim of this study was to investigate whether mtDNA haplogroups determined differential susceptibility to cognitive effects of long-term exposure to black carbon (BC), a marker of traffic-related air pollution. Methods We investigated 582 older men (72 ± 7 years) in the VA Normative Aging Study cohort with ≤4 visits per participant (1.8 in average) between 1995–2007. Low (≤25) Mini Mental State Examination (MMSE) was used to assess impaired cognition in multiple domains. We fitted repeated-measure logistic regression using validated-LUR BC estimated in the year before their first visit at the participant’s address. Results Mitochondrial haplotyping identified nine haplogroups phylogenetically categorized in four clusters. BC showed larger effect on MMSE in Cluster 4 carriers, including I, W and X haplogroups, [OR = 2.7; 95% CI (1.3-5.6)], moderate effect in Cluster 1, including J and T haplogroups [OR = 1.6; 95% CI: (0.9-2.9)], and no effect in Cluster 2 (H and V haplogroups) [OR = 1.1; 95% CI: (0.8-1.5)] or Cluster 3 (K and U haplogroups) [OR = 1.0; 95% CI: (0.6-1.6)]. BC effect varied only moderately across the I, X, and W haplogroups or across the J and T haplogroups. Conclusions The association of BC with impaired cognition was worsened in carriers of phylogenetically-related mtDNA haplogroups in Cluster 4. No BC effects were detected in Cluster 2 and 3 carriers. MtDNA haplotypes may modify individual susceptibility to the particle cognitive effects. PMID:24884505

  14. Age-related Declines in Thirst and Salt Appetite Responses in Male Fischer 344 x Brown Norway Rats

    PubMed Central

    Thunhorst, Robert L.; Beltz, Terry; Johnson, Alan Kim

    2014-01-01

    The F344xBN strain is the first generational cross between Fischer 344 (F344) and Brown Norway (BN) rats. The F344xBN strain is widely used in aging studies as it is regarded as a model of “healthy” aging (Sprott, 1991). In the present work, male F344xBN rats aged 4 mo (young, n = 6) and 20 mo (old, n = 9) received a series of experimental challenges to body fluid homeostasis to determine their thirst and salt appetite responses. Corresponding urinary responses were measured in some of the studies. Following sodium depletion, old rats ingested less saline solution (0.3 M NaCl) than young rats on a body weight basis, but both ages drank enough saline solution to completely repair the accrued sodium deficits. Following intracellular dehydration, old rats drank less water than young rats, again on a body weight basis, and were less able than young rats to drink amounts of water proportionate to the osmotic challenge. Compared with young rats, old rats drank less of both water and saline solution after combined food and fluid restriction, and also were refractory to the stimulatory effects of low doses of captopril on water drinking and sodium ingestion. Age differences in urinary water and sodium excretion could not account for the age differences in accumulated water and sodium balances. These results extend observations of diminished behavioral responses of aging animals to the F344xBN rat strain and support the idea that impairments in behavior contribute more to the waning ability of aging animals to respond to body fluid challenges than do declines in kidney function. In addition, the results suggest that behavioral defense of sodium homeostasis is less diminished with age in the F344xBN strain compared to other strains so far studied. PMID:24952266

  15. Periodontitis and Cognitive Decline in Alzheimer’s Disease

    PubMed Central

    Ide, Mark; Harris, Marina; Stevens, Annette; Sussams, Rebecca; Hopkins, Viv; Culliford, David; Fuller, James; Ibbett, Paul; Raybould, Rachel; Thomas, Rhodri; Puenter, Ursula; Teeling, Jessica; Perry, V. Hugh; Holmes, Clive

    2016-01-01

    Periodontitis is common in the elderly and may become more common in Alzheimer’s disease because of a reduced ability to take care of oral hygiene as the disease progresses. Elevated antibodies to periodontal bacteria are associated with an increased systemic pro-inflammatory state. Elsewhere raised serum pro-inflammatory cytokines have been associated with an increased rate of cognitive decline in Alzheimer’s disease. We hypothesized that periodontitis would be associated with increased dementia severity and a more rapid cognitive decline in Alzheimer’s disease. We aimed to determine if periodontitis in Alzheimer’s disease is associated with both increased dementia severity and cognitive decline, and an increased systemic pro inflammatory state. In a six month observational cohort study 60 community dwelling participants with mild to moderate Alzheimer’s Disease were cognitively assessed and a blood sample taken for systemic inflammatory markers. Dental health was assessed by a dental hygienist, blind to cognitive outcomes. All assessments were repeated at six months. The presence of periodontitis at baseline was not related to baseline cognitive state but was associated with a six fold increase in the rate of cognitive decline as assessed by the ADAS-cog over a six month follow up period. Periodontitis at baseline was associated with a relative increase in the pro-inflammatory state over the six month follow up period. Our data showed that periodontitis is associated with an increase in cognitive decline in Alzheimer’s Disease, independent to baseline cognitive state, which may be mediated through effects on systemic inflammation. PMID:26963387

  16. Clinical Report: Cognitive decline in a patient with Cardiofaciocutaneous syndrome.

    PubMed

    Cabrera, Sergio; Morel, Chantal; Tartaglia, Maria Carmela

    2016-05-01

    Cardiofaciocutaneous Syndrome (CFCS) is a rare genetic syndrome caused by mutations in one of four genes: BRAF, MAP2K1, MAP2K2, and KRAS. There is tremendous phenotypic heterogeneity in patients with CFCS and so confirmation of diagnosis requires genetic testing. Neurologic and/or cognitive symptoms are present in almost all CFCS individuals. Little is known about cognitive function in older patients with CFCS. In this report, we present the cognitive, neuropsychiatric, and imaging findings of a patient diagnosed with CFCS who after having remained stable developed progressive cognitive/behavioral and motor decline. © 2016 Wiley Periodicals, Inc. PMID:26842671

  17. Sex Differences in Age-Related Decline of Urinary Insulin-Like Growth Factor-Binding Protein-3 Levels in Adult Bonobos and Chimpanzees.

    PubMed

    Behringer, Verena; Wudy, Stefan A; Blum, Werner F; Stevens, Jeroen M G; Remer, Thomas; Boesch, Christophe; Hohmann, Gottfried

    2016-01-01

    There is increasing interest in the characterization of normative senescence in humans. To assess to what extent aging patterns in humans are unique, comparative data from closely related species, such as non-human primates, can be very useful. Here, we use data from bonobos and chimpanzees, two closely related species that share a common ancestor with humans, to explore physiological markers that are indicative of aging processes. Many studies on aging in humans focus on the somatotropic axis, consisting of growth hormone (GH), insulin-like growth factors (IGFs), and IGF binding proteins (IGFBPs). In humans, IGFBP-3 levels decline steadily with increasing age. We used urinary IGFBP-3 levels as an alternative endocrine marker for IGF-I to identify the temporal pattern known to be related with age-related changes in cell proliferation, growth, and apoptosis. We measured urinary IGFBP-3 levels in samples from 71 bonobos and 102 chimpanzees. Focusing on samples from individuals aged 10 years or older, we found that urinary IGFBP-3 levels decline in both ape species with increasing age. However, in both species, females start with higher urinary IGFBP-3 levels than males, experience a steeper decline with increasing age, and converge with male levels around the age of 30-35 years. Our measurements of urinary IGFBP-3 levels indicate that bonobos and chimpanzees mirror human patterns of age-related decline in IGFBP-3 in older individuals (<10 years) of both sexes. Moreover, such as humans, both ape species show sex-specific differences in IGFBP-3 levels with females having higher levels than males, a result that correlates with sex differences in life expectancy. Using changes in urinary IGFBP-3 levels as a proxy for changes in GH and IGF-I levels that mark age-related changes in cell proliferation, this approach provides an opportunity to investigate trade-offs in life-history strategies in cross-sectional and in longitudinal studies, both in captivity and in the

  18. Sex Differences in Age-Related Decline of Urinary Insulin-Like Growth Factor-Binding Protein-3 Levels in Adult Bonobos and Chimpanzees

    PubMed Central

    Behringer, Verena; Wudy, Stefan A.; Blum, Werner F.; Stevens, Jeroen M. G.; Remer, Thomas; Boesch, Christophe; Hohmann, Gottfried

    2016-01-01

    There is increasing interest in the characterization of normative senescence in humans. To assess to what extent aging patterns in humans are unique, comparative data from closely related species, such as non-human primates, can be very useful. Here, we use data from bonobos and chimpanzees, two closely related species that share a common ancestor with humans, to explore physiological markers that are indicative of aging processes. Many studies on aging in humans focus on the somatotropic axis, consisting of growth hormone (GH), insulin-like growth factors (IGFs), and IGF binding proteins (IGFBPs). In humans, IGFBP-3 levels decline steadily with increasing age. We used urinary IGFBP-3 levels as an alternative endocrine marker for IGF-I to identify the temporal pattern known to be related with age-related changes in cell proliferation, growth, and apoptosis. We measured urinary IGFBP-3 levels in samples from 71 bonobos and 102 chimpanzees. Focusing on samples from individuals aged 10 years or older, we found that urinary IGFBP-3 levels decline in both ape species with increasing age. However, in both species, females start with higher urinary IGFBP-3 levels than males, experience a steeper decline with increasing age, and converge with male levels around the age of 30–35 years. Our measurements of urinary IGFBP-3 levels indicate that bonobos and chimpanzees mirror human patterns of age-related decline in IGFBP-3 in older individuals (<10 years) of both sexes. Moreover, such as humans, both ape species show sex-specific differences in IGFBP-3 levels with females having higher levels than males, a result that correlates with sex differences in life expectancy. Using changes in urinary IGFBP-3 levels as a proxy for changes in GH and IGF-I levels that mark age-related changes in cell proliferation, this approach provides an opportunity to investigate trade-offs in life-history strategies in cross-sectional and in longitudinal studies, both in captivity and in

  19. Quantitative EEG and Cognitive Decline in Parkinson's Disease

    PubMed Central

    Cozac, Vitalii V.; Gschwandtner, Ute; Hatz, Florian; Hardmeier, Martin; Rüegg, Stephan

    2016-01-01

    Cognitive decline is common with the progression of Parkinson's disease (PD). Different candidate biomarkers are currently studied for the risk of dementia in PD. Several studies have shown that quantitative EEG (QEEG) is a promising predictor of PD-related cognitive decline. In this paper we briefly outline the basics of QEEG analysis and analyze the recent publications addressing the predictive value of QEEG in the context of cognitive decline in PD. The MEDLINE database was searched for relevant publications from January 01, 2005, to March 02, 2015. Twenty-four studies reported QEEG findings in various cognitive states in PD. Spectral and connectivity markers of QEEG could help to discriminate between PD patients with different level of cognitive decline. QEEG variables correlate with tools for cognitive assessment over time and are associated with significant hazard ratios to predict PD-related dementia. QEEG analysis shows high test-retest reliability and avoids learning effects associated with some neuropsychological testing; it is noninvasive and relatively easy to repeat. PMID:27148466

  20. MORPHOMETRIC ANALYSIS OF HIPPOCAMPUS AND LATERAL VENTRICLE REVEALS REGIONAL DIFFERENCE BETWEEN COGNITIVELY STABLE AND DECLINING PERSONS

    PubMed Central

    Zhang, Wen; Shi, Jie; Stonnington, Cynthia; Bauer, Robert J.; Gutman, Boris A.; Chen, Kewei; Thompson, Paul M.; Reiman, Eric M.; Caselli, Richard J.; Wang, Yalin

    2016-01-01

    Alzheimers disease (AD) is a progressive neurodegenerative disease most prevalent in the elderly. Distinguishing disease-related memory decline from normal age-related memory decline has been clinically difficult due to the subtlety of cognitive change during the preclinical stage of AD. In contrast, sensitive biomarkers derived from in vivo neuroimaging data could improve the early identification of AD. In this study, we employed a morphometric analysis in the hippocampus and lateral ventricle. A novel group-wise template-based segmentation algorithm was developed for ventricular segmentation. Further, surface multivariate tensor-based morphometry and radial distance on each surface point were computed. Using Hotellings T2 test, we found significant morphometric differences in both hippocampus and lateral ventricle between stable and clinically declining subjects. The left hemisphere was more severely affected than the right during this early disease stage. Hippocampal and ventricular morphometry has significant potential as an imaging biomarker for onset prediction and early diagnosis of AD. PMID:27499828

  1. Factors Associated with Cognitive Decline in Elderly Diabetics

    PubMed Central

    Umegaki, Hiroyuki; Kawamura, Takahiko; Kawano, Naoko; Umemura, Toshitaka; Kanai, Akio; Sano, Takahisa

    2011-01-01

    Background/Aims Although recent evidence has indicated that type 2 diabetes mellitus (T2DM) in the elderly is a risk factor for cognitive dysfunction or dementia, few studies have prospectively observed this potential cognitive decline. In the current study, we performed cognitive assessments at baseline and after 3 years in the same patient group in an attempt to reveal the contributions of diabetes-related factors to the increased decline in cognitive function in elderly patients with T2DM. Methods We recruited 55 consecutive T2DM patients with a Mini-Mental State Examination (MMSE) score ≥24 from the Diabetic Center at the Chubu Rosai Hospital. These patients ranged in age from 65 to 85 years. Cognitive and clinical assessments, including brain MRI, were performed at baseline and at the 3-year follow-up. Results The higher plasma insulin and HbA1c levels observed at baseline were significantly associated with a worse cognitive performance at baseline and a more neurocognitive decline at the follow-up visit. Conclusion The current prospective study suggests that higher insulin and glycohemoglobin levels may be associated with diabetes-related cognitive dysfunction. PMID:22163228

  2. Entorhinal cortex thickness predicts cognitive decline in Alzheimer's disease.

    PubMed

    Velayudhan, Latha; Proitsi, Petroula; Westman, Eric; Muehlboeck, J-Sebastian; Mecocci, Patrizia; Vellas, Bruno; Tsolaki, Magda; Kłoszewska, Iwona; Soininen, Hilkka; Spenger, Christian; Hodges, Angela; Powell, John; Lovestone, Simon; Simmons, Andrew

    2013-01-01

    Biomarkers for Alzheimer's disease (AD) based on non-invasive methods are highly desirable for diagnosis, disease progression, and monitoring therapeutics. We aimed to study the use of hippocampal volume, entorhinal cortex (ERC) thickness, and whole brain volume (WBV) as predictors of cognitive change in patients with AD. 120 AD subjects, 106 mild cognitive impairment (MCI), and 99 non demented controls (NDC) from the multi-center pan-European AddNeuroMed study underwent MRI scanning at baseline and clinical evaluations at quarterly follow-up up to 1 year. The rate of cognitive decline was estimated using cognitive outcomes, Mini-Mental State Examination (MMSE) and Alzheimer disease assessment scale-cognitive (ADAS-cog) by fitting a random intercept and slope model. AD subjects had smaller ERC thickness and hippocampal and WBV volumes compared to MCI and NDC subjects. Within the AD group, ERC > WBV was significantly associated with baseline cognition (MMSE, ADAS-cog) and disease severity (Clinical Dementia Rating). Baseline ERC thickness was associated with both longitudinal MMSE and ADAS-cog score changes and WBV with ADAS-cog decline. These data indicate that AD subjects with thinner ERC had lower baseline cognitive scores, higher disease severity, and predicted greater subsequent cognitive decline at one year follow up. ERC is a region known to be affected early in the disease. Therefore, the rate of atrophy in this structure is expected to be higher since neurodegeneration begins earlier. Focusing on structural analyses that predict decline can identify those individuals at greatest risk for future cognitive loss. This may have potential for increasing the efficacy of early intervention. PMID:23047370

  3. Quantitative T2 mapping of white matter: applications for ageing and cognitive decline.

    PubMed

    Knight, Michael J; McCann, Bryony; Tsivos, Demitra; Dillon, Serena; Coulthard, Elizabeth; Kauppinen, Risto A

    2016-08-01

    In MRI, the coherence lifetime T2 is sensitive to the magnetic environment imposed by tissue microstructure and biochemistry in vivo. Here we explore the possibility that the use of T2 relaxometry may provide information complementary to that provided by diffusion tensor imaging (DTI) in ageing of healthy controls (HC), Alzheimer's disease (AD) and mild cognitive impairment (MCI). T2 and diffusion MRI metrics were quantified in HC and patients with MCI and mild AD using multi-echo MRI and DTI. We used tract-based spatial statistics (TBSS) to evaluate quantitative MRI parameters in white matter (WM). A prolonged T2 in WM was associated with AD, and able to distinguish AD from MCI, and AD from HC. Shorter WM T2 was associated with better cognition and younger age in general. In no case was a reduction in T2 associated with poorer cognition. We also applied principal component analysis, showing that WM volume changes independently of  T2, MRI diffusion indices and cognitive performance indices. Our data add to the evidence that age-related and AD-related decline in cognition is in part attributable to WM tissue state, and much less to WM quantity. These observations suggest that WM is involved in AD pathology, and that T2 relaxometry is a potential imaging modality for detecting and characterising WM in cognitive decline and dementia. PMID:27384985

  4. Quantitative T2 mapping of white matter: applications for ageing and cognitive decline

    NASA Astrophysics Data System (ADS)

    Knight, Michael J.; McCann, Bryony; Tsivos, Demitra; Dillon, Serena; Coulthard, Elizabeth; Kauppinen, Risto A.

    2016-08-01

    In MRI, the coherence lifetime T2 is sensitive to the magnetic environment imposed by tissue microstructure and biochemistry in vivo. Here we explore the possibility that the use of T2 relaxometry may provide information complementary to that provided by diffusion tensor imaging (DTI) in ageing of healthy controls (HC), Alzheimer’s disease (AD) and mild cognitive impairment (MCI). T2 and diffusion MRI metrics were quantified in HC and patients with MCI and mild AD using multi-echo MRI and DTI. We used tract-based spatial statistics (TBSS) to evaluate quantitative MRI parameters in white matter (WM). A prolonged T2 in WM was associated with AD, and able to distinguish AD from MCI, and AD from HC. Shorter WM T2 was associated with better cognition and younger age in general. In no case was a reduction in T2 associated with poorer cognition. We also applied principal component analysis, showing that WM volume changes independently of  T2, MRI diffusion indices and cognitive performance indices. Our data add to the evidence that age-related and AD-related decline in cognition is in part attributable to WM tissue state, and much less to WM quantity. These observations suggest that WM is involved in AD pathology, and that T2 relaxometry is a potential imaging modality for detecting and characterising WM in cognitive decline and dementia.

  5. Moving forward: age effects on the cerebellum underlie cognitive and motor declines.

    PubMed

    Bernard, Jessica A; Seidler, Rachael D

    2014-05-01

    Though the cortical contributions to age-related declines in motor and cognitive performance are well-known, the potential contributions of the cerebellum are less clear. The diverse functions of the cerebellum make it an important structure to investigate in aging. Here, we review the extant literature on this topic. To date, there is evidence to indicate that there are morphological age differences in the cerebellum that are linked to motor and cognitive behavior. Cerebellar morphology is often as good as - or even better - at predicting performance than the prefrontal cortex. We also touch on the few studies using functional neuroimaging and connectivity analyses that further implicate the cerebellum in age-related performance declines. Importantly, we provide a conceptual framework for the cerebellum influencing age differences in performance, centered on the notion of degraded internal models. The evidence indicating that cerebellar age differences associate with performance highlights the need for additional work in this domain to further elucidate the role of the cerebellum in age differences in movement control and cognitive function. PMID:24594194

  6. A review of new insights on the association between hearing loss and cognitive decline in ageing.

    PubMed

    Fortunato, S; Forli, F; Guglielmi, V; De Corso, E; Paludetti, G; Berrettini, S; Fetoni, A R

    2016-06-01

    Age-related hearing loss (ARHL) has a multifactorial pathogenesis and it is an inevitable hearing impairment associated with reduction of communicative skills related to ageing. Increasing evidence has linked ARHL to more rapid progression of cognitive decline and incidental dementia. Many aspects of daily living of elderly people have been associated to hearing abilities, showing that hearing loss (HL) affects the quality of life, social relationships, motor skills, psychological aspects and function and morphology in specific brain areas. Epidemiological and clinical studies confirm the assumption of a relationship between these conditions. However, the mechanisms are still unclear and are reviewed herein. Long-term hearing deprivation of auditory inputs can impact cognitive performance by decreasing the quality of communication leading to social isolation and depression and facilitate dementia. On the contrary, the limited cognitive skills may reduce the cognitive resources available for auditory perception, increasing the effects of HL. In addition, hearing loss and cognitive decline may reflect a 'common cause' on the auditory pathway and brain. In fact, some pathogenetic factors are recongised in common microvascular disease factors such as diabetes, atherosclerosis and hypertension. Interdisciplinary efforts to investigate and address HL in the context of brain and cognitive ageing are needed. Surprisingly, few studies have been adressed on the effectiveness of hearing aids in changing the natural history of cognitive decline. Effective interventions with hearing aids or cochlear implant may improve social and emotional function, communication, cognitive function and positively impact quality of life. The aim of this review is to overview new insights on this challenging topic and provide new ideas for future research. PMID:27214827

  7. Homocysteine and inflammation: predictors of cognitive decline in older persons?

    PubMed

    van den Kommer, T N; Dik, M G; Comijs, H C; Jonker, C; Deeg, D J H

    2010-10-01

    The aim of the current study was to examine the association between homocysteine and 6-year cognitive decline, and the modifying role of the inflammatory markers Interleukin-6 (IL-6), C-reactive protein (CRP) and alpha-1-antichymotrypsin (ACT). Data were collected within the Longitudinal Aging Study Amsterdam (ages >or=65 years) and analyzed using multiple longitudinal regression models (N=1257 of whom N=1076 had longitudinal data). Cognition was measured with the Mini-Mental State Examination (general cognition), Auditory Verbal Learning Test (memory), Coding Task (information processing speed) and Raven Coloured Progressive Matrices (fluid intelligence). Higher homocysteine at baseline was negatively associated with prolonged lower cognitive functioning and a faster rate of decline in information processing speed and fluid intelligence. The negative association between higher homocysteine and immediate recall was strongest in persons with a high level of IL-6. Only in the highest tertile of CRP, higher homocysteine was negatively associated with retention. In the middle tertile of ACT, higher homocysteine was associated with lower information processing speed and faster decline. Both in the lower and middle tertile of CRP, higher homocysteine was associated with a faster rate of decline in information processing speed. The results implicate that a combination of both risk factors may be used as a marker for cognitive impairment. PMID:19004529

  8. Cognitive Decline in Older Persons Initiating Anticholinergic Medications

    PubMed Central

    Shah, Raj C.; Janos, Alicia L.; Kline, Julia E.; Yu, Lei; Leurgans, Sue E.; Wilson, Robert S.; Wei, Peter; Bennett, David A.; Heilman, Kenneth M.; Tsao, Jack W.

    2013-01-01

    Background This study examines the effect of initiating medications with anticholinergic activity on the cognitive functions of older persons. Methods Participants were 896 older community-dwelling, Catholic clergy without baseline dementia. Medication data was collected annually. The Anticholinergic Cognitive Burden Scale was utilized to identify use of a medication with probable or definite anticholinergic activity. Participants had at least two annual cognitive evaluations. Results Over a mean follow-up of 10 years, the annual rate of global cognitive function decline for never users, prevalent users, and incident users was −0.062 (SE = 0.005), −0.081(SE = 0.011), and −0.096 (SE = 0.007) z-score units/year, respectively. Compared to never users, incident users had a more rapid decline (difference = −0.034 z-score units/year, SE = 0.008, p<0.001) while prevalent users did not have a significantly more rapid decline (p = 0.1). Conclusions Older persons initiating a medication with anticholinergic activity have a steeper annual decline in cognitive functioning than those who are not taking these medications. PMID:23741303

  9. Performances on a cognitive theory of mind task: specific decline or general cognitive deficits? Evidence from normal aging.

    PubMed

    Fliss, Rafika; Lemerre, Marion; Mollard, Audrey

    2016-06-01

    Compromised theory of mind (ToM) can be explained either by a failure to implement specific representational capacities (mental state representations) or by more general executive selection demands. In older adult populations, evidence supporting affected executive functioning and cognitive ToM in normal aging are reported. However, links between these two functions remain unclear. In the present paper, we address these shortcomings by using a specific task of ToM and classical executive tasks. We studied, using an original cognitive ToM task, the effect of age on ToM performances, in link with the progressive executive decline. 96 elderly participants were recruited. They were asked to perform a cognitive ToM task, and 5 executive tests (Stroop test and Hayling Sentence Completion Test to appreciate inhibitory process, Trail Making Test and Verbal Fluency for shifting assessment and backward span dedicated to estimate working memory capacity). The results show changes in cognitive ToM performance according to executive demands. Correlational studies indicate a significant relationship between ToM performance and the selected executive measures. Regression analyzes demonstrates that level of vocabulary and age as the best predictors of ToM performance. The results are consistent with the hypothesis that ToM deficits are related to age-related domain-general decline rather than as to a breakdown in specialized representational system. The implications of these findings for the nature of social cognition tests in normal aging are also discussed. PMID:27277154

  10. Neighborhood Integration and Connectivity Predict Cognitive Performance and Decline

    PubMed Central

    Watts, Amber; Ferdous, Farhana; Moore, Keith Diaz; Burns, Jeffrey M.

    2015-01-01

    Objective Neighborhood characteristics may be important for promoting walking, but little research has focused on older adults, especially those with cognitive impairment. We evaluated the role of neighborhood characteristics on cognitive function and decline over a 2-year period adjusting for measures of walking. Method In a study of 64 older adults with and without mild Alzheimer's disease (AD), we evaluated neighborhood integration and connectivity using geographical information systems data and space syntax analysis. In multiple regression analyses, we used these characteristics to predict 2-year declines in factor analytically derived cognitive scores (attention, verbal memory, mental status) adjusting for age, sex, education, and self-reported walking. Results Neighborhood integration and connectivity predicted cognitive performance at baseline, and changes in cognitive performance over 2 years. The relationships between neighborhood characteristics and cognitive performance were not fully explained by self-reported walking. Discussion Clearer definitions of specific neighborhood characteristics associated with walkability are needed to better understand the mechanisms by which neighborhoods may impact cognitive outcomes. These results have implications for measuring neighborhood characteristics, design and maintenance of living spaces, and interventions to increase walking among older adults. We offer suggestions for future research measuring neighborhood characteristics and cognitive function. PMID:26504889

  11. Non-pharmacological strategies to delay cognitive decline.

    PubMed

    Lautenschlager, Nicola T; Anstey, Kaarin J; Kurz, Alexander F

    2014-10-01

    Non-pharmacological preventive strategies to delay cognitive decline have become the focus of recent research. This review aims to discuss evidence supporting the use of physical and cognitive activity to reduce the risk of cognitive decline and dementia in later life. Both strategies are associated with better cognitive health in older adults. This positive effect seems stronger for middle-aged and older adults with normal cognition and less clear when cognitive impairment is present. Physical and cognitive activities have been linked to indirect and direct biological factors affecting brain health. Future research will need to explore details about type, intensity, duration and combination of interventions. An important aim is standardization between studies, as well as evidence of improved clinical outcomes and cost-effectiveness. Identifying strategies that succeed at sustaining improved lifestyle is necessary, and the use of modern technology could play a crucial role in this regard. In the meantime advice on physical and cognitive activities should be included when health advice is given to middle-aged and older adults. PMID:25231337

  12. Postmortem MRI: a novel window into the neurobiology of late life cognitive decline.

    PubMed

    Dawe, Robert J; Yu, Lei; Leurgans, Sue E; Schneider, Julie A; Buchman, Aron S; Arfanakis, Konstantinos; Bennett, David A; Boyle, Patricia A

    2016-09-01

    This study tested the hypothesis that indices of brain tissue integrity derived from postmortem magnetic resonance imaging (MRI) are associated with late life decline in cognitive function and dementia, over and above contributions from common age-related neuropathologies. Cerebral hemispheres were obtained from 425 deceased older adults who had undergone 2 or more annual cognitive assessments, which included clinical diagnosis of dementia. Specimens underwent MRI to produce maps of transverse relaxation rate, R2. Voxelwise regression revealed brain regions where R2 was associated with cognitive decline. We then used random effects models to quantify the extent to which R2 accounted for variation in decline, after adjustment for demographics and neuropathologic indices of the 3 most common causes of dementia: Alzheimer's disease, cerebrovascular disease, and Lewy body disease. We additionally tested whether R2 was tied to greater likelihood of clinical diagnosis of Alzheimer's dementia using logistic regression models. During an average of 8.1 years, the mean rate of decline in global cognitive function was 0.13 unit per year (p < 0.0001). The tissue alteration most commonly related to decline was R2 slowing in white matter. Each unit decrease in R2 was associated with an additional 0.053-unit per year steepening of the rate of global cognitive decline (p < 0.001). Furthermore, R2 accounted for 8.4% of the variance in rate of global cognitive decline, above and beyond the 26.5% accounted for by demographics and neuropathologic indices, and 7.1%-11.2% of the variance of the decline rates in episodic, semantic, and working memory and perceptual speed. Alterations in R2 were also related to an increased odds of clinical diagnosis of Alzheimer's dementia (odds ratio = 2.000, 95% confidence interval 1.600, 2.604). Therefore, postmortem MRI indices of brain tissue integrity, particularly in white matter, are useful for elucidating the basis of late life cognitive

  13. Combined effects of physical exercise and education on age-related cortical thinning in cognitively normal individuals

    PubMed Central

    Lee, Jin San; Shin, Hee Young; Kim, Hee Jin; Jang, Young Kyoung; Jung, Na-Yeon; Lee, Juyoun; Kim, Yeo Jin; Chun, Phillip; Yang, Jin-Ju; Lee, Jong-Min; Kang, Mira; Park, Key-Chung; Na, Duk L.; Seo, Sang Won

    2016-01-01

    We investigated the association between self-reported physical exercise and cortical thickness in a large sample of cognitively normal individuals. We also determined whether a combination of physical exercise and education had more protective effects on age-related cortical thinning than either parameter alone. A total of 1,842 participants were included in this analysis. Physical exercise was assessed using a questionnaire regarding intensity, frequency, and duration. Cortical thickness was measured using a surface-based method. Longer duration of exercise (≥1 hr/day), but not intensity or frequency, was associated with increased mean cortical thickness globally (P-value = 0.013) and in the frontal regions (P-value = 0.007). In particular, the association of exercise with cortical thinning had regional specificity in the bilateral dorsolateral prefrontal, precuneus, left postcentral, and inferior parietal regions. The combination of higher exercise level and higher education level showed greater global and frontal mean thickness than either parameter alone. Testing for a trend with the combination of high exercise level and high education level confirmed this finding (P-value = 0.001–0.003). Our findings suggest that combined exercise and education have important implications for brain health, especially considering the paucity of known protective factors for age-related cortical thinning. PMID:27063336

  14. Crowdsourced estimation of cognitive decline and resilience in Alzheimer's disease.

    PubMed

    Allen, Genevera I; Amoroso, Nicola; Anghel, Catalina; Balagurusamy, Venkat; Bare, Christopher J; Beaton, Derek; Bellotti, Roberto; Bennett, David A; Boehme, Kevin L; Boutros, Paul C; Caberlotto, Laura; Caloian, Cristian; Campbell, Frederick; Chaibub Neto, Elias; Chang, Yu-Chuan; Chen, Beibei; Chen, Chien-Yu; Chien, Ting-Ying; Clark, Tim; Das, Sudeshna; Davatzikos, Christos; Deng, Jieyao; Dillenberger, Donna; Dobson, Richard J B; Dong, Qilin; Doshi, Jimit; Duma, Denise; Errico, Rosangela; Erus, Guray; Everett, Evan; Fardo, David W; Friend, Stephen H; Fröhlich, Holger; Gan, Jessica; St George-Hyslop, Peter; Ghosh, Satrajit S; Glaab, Enrico; Green, Robert C; Guan, Yuanfang; Hong, Ming-Yi; Huang, Chao; Hwang, Jinseub; Ibrahim, Joseph; Inglese, Paolo; Iyappan, Anandhi; Jiang, Qijia; Katsumata, Yuriko; Kauwe, John S K; Klein, Arno; Kong, Dehan; Krause, Roland; Lalonde, Emilie; Lauria, Mario; Lee, Eunjee; Lin, Xihui; Liu, Zhandong; Livingstone, Julie; Logsdon, Benjamin A; Lovestone, Simon; Ma, Tsung-Wei; Malhotra, Ashutosh; Mangravite, Lara M; Maxwell, Taylor J; Merrill, Emily; Nagorski, John; Namasivayam, Aishwarya; Narayan, Manjari; Naz, Mufassra; Newhouse, Stephen J; Norman, Thea C; Nurtdinov, Ramil N; Oyang, Yen-Jen; Pawitan, Yudi; Peng, Shengwen; Peters, Mette A; Piccolo, Stephen R; Praveen, Paurush; Priami, Corrado; Sabelnykova, Veronica Y; Senger, Philipp; Shen, Xia; Simmons, Andrew; Sotiras, Aristeidis; Stolovitzky, Gustavo; Tangaro, Sabina; Tateo, Andrea; Tung, Yi-An; Tustison, Nicholas J; Varol, Erdem; Vradenburg, George; Weiner, Michael W; Xiao, Guanghua; Xie, Lei; Xie, Yang; Xu, Jia; Yang, Hojin; Zhan, Xiaowei; Zhou, Yunyun; Zhu, Fan; Zhu, Hongtu; Zhu, Shanfeng

    2016-06-01

    Identifying accurate biomarkers of cognitive decline is essential for advancing early diagnosis and prevention therapies in Alzheimer's disease. The Alzheimer's disease DREAM Challenge was designed as a computational crowdsourced project to benchmark the current state-of-the-art in predicting cognitive outcomes in Alzheimer's disease based on high dimensional, publicly available genetic and structural imaging data. This meta-analysis failed to identify a meaningful predictor developed from either data modality, suggesting that alternate approaches should be considered for prediction of cognitive performance. PMID:27079753

  15. Age-Related Cognitive Impairment as a Sign of Geriatric Neurocardiovascular Interactions: May Polyphenols Play a Protective Role?

    PubMed Central

    Jagla, Fedor; Pechanova, Olga

    2015-01-01

    It is known that endothelial dysfunction plays an important role in the development and progression of cardiovascular diseases implicated also in cognitive decline. Experimental studies pointed to the fact that the modification of NO levels via NOS activity may affect the blood pressure level as well as several higher nervous functions—for example, learning and memory. There are emerging evidences from in vitro and animal studies suggesting that polyphenols may potentially have a protective effect on the development of neurodegenerative diseases and may improve cognitive function as well as positively affecting the blood pressure regulatory mechanisms. This review accentuates the need for precisely defined clinically controlled studies as well as for use of adequate experimental procedures discriminating between the human higher brain functions and the only overall activation of the brain cortex. The physiological neurocardiovascular interactions are implicated in the increased healthy life span as well. PMID:26180593

  16. Monounsaturated, trans & saturated fatty acids and cognitive decline in women

    PubMed Central

    Naqvi, Asghar Z.; Harty, Brian; Mukamal, Kenneth J.; Stoddard, Anne M.; Vitolins, Mara; Dunn, Julie E.

    2011-01-01

    Objectives Prospectively assess effects of select dietary fats on cognitive decline Design Prospective observational; 3-year follow-up Setting Subjects recruited at Northwestern University who participated in Women's Health Initiative Observational Study or control group of Diet Modification arm. Participants 482 women ≥ 60 years Measurements We averaged dietary intake from a validated food frequency questionnaire (FFQ) administered twice (mean=2.7 years apart) before baseline cognitive assessment (mean=2.9 years after 2nd FFQ). Testing of memory, vision, executive function, language, and attention was performed at 2 time points, 3 years apart. We created a global Z-score for both time points by averaging all Z-scores for each participant and defined global cognitive change as the difference between follow-up and baseline Z-scores. Results Median intakes of saturated fats (SFA), trans-fats, (TFA), dietary cholesterol (DC) and monounsaturated fats (MUFA) were 18.53 g/d, 3.45 g/d, 0.201 g/d and 19.39 g/d, respectively. There were no associations between degree of cognitive decline and intakes of SFA (p=0.69), TFA (p=0.54) or DC (p=0.64) after adjusting for baseline cognition, total energy, age, education, reading ability, Apolipoprotein E (ε4) allele, BMI, estrogen and beta-blocker use, and intake of caffeine and other fatty acids. In contrast, compared with participants in the lowest quartile, MUFA intake was associated with lower cognitive decline in fully adjusted linear regression models, with decline of 0.21 + 0.05 SE in the lowest versus 0.05 + 0.05 SE in the highest quartiles (p=0.02). This effect of MUFA intake was primarily in the visual and memory domains (p=0.03 for both). Conclusion Higher intakes of SFA, TFA and DC in these women were not associated with cognitive decline, while MUFA intake was associated with less cognitive decline. PMID:21568955

  17. Dietary Patterns, Cognitive Decline, and Dementia: A Systematic Review12

    PubMed Central

    van de Rest, Ondine; Berendsen, Agnes AM; Haveman-Nies, Annemien; de Groot, Lisette CPGM

    2015-01-01

    Nutrition is an important modifiable risk factor that plays a role in the strategy to prevent or delay the onset of dementia. Research on nutritional effects has until now mainly focused on the role of individual nutrients and bioactive components. However, the evidence for combined effects, such as multinutrient approaches, or a healthy dietary pattern, such as the Mediterranean diet, is growing. These approaches incorporate the complexity of the diet and possible interaction and synergy between nutrients. Over the past few years, dietary patterns have increasingly been investigated to better understand the link between diet, cognitive decline, and dementia. In this systematic review we provide an overview of the literature on human studies up to May 2014 that examined the role of dietary patterns (derived both a priori as well as a posteriori) in relation to cognitive decline or dementia. The results suggest that better adherence to a Mediterranean diet is associated with less cognitive decline, dementia, or Alzheimer disease, as shown by 4 of 6 cross-sectional studies, 6 of 12 longitudinal studies, 1 trial, and 3 meta-analyses. Other healthy dietary patterns, derived both a priori (e.g., Healthy Diet Indicator, Healthy Eating Index, and Program National Nutrition Santé guideline score) and a posteriori (e.g., factor analysis, cluster analysis, and reduced rank regression), were shown to be associated with reduced cognitive decline and/or a reduced risk of dementia as shown by all 6 cross-sectional studies and 6 of 8 longitudinal studies. More conclusive evidence is needed to reach more targeted and detailed guidelines to prevent or postpone cognitive decline. PMID:25770254

  18. Dietary patterns, cognitive decline, and dementia: a systematic review.

    PubMed

    van de Rest, Ondine; Berendsen, Agnes Am; Haveman-Nies, Annemien; de Groot, Lisette Cpgm

    2015-03-01

    Nutrition is an important modifiable risk factor that plays a role in the strategy to prevent or delay the onset of dementia. Research on nutritional effects has until now mainly focused on the role of individual nutrients and bioactive components. However, the evidence for combined effects, such as multinutrient approaches, or a healthy dietary pattern, such as the Mediterranean diet, is growing. These approaches incorporate the complexity of the diet and possible interaction and synergy between nutrients. Over the past few years, dietary patterns have increasingly been investigated to better understand the link between diet, cognitive decline, and dementia. In this systematic review we provide an overview of the literature on human studies up to May 2014 that examined the role of dietary patterns (derived both a priori as well as a posteriori) in relation to cognitive decline or dementia. The results suggest that better adherence to a Mediterranean diet is associated with less cognitive decline, dementia, or Alzheimer disease, as shown by 4 of 6 cross-sectional studies, 6 of 12 longitudinal studies, 1 trial, and 3 meta-analyses. Other healthy dietary patterns, derived both a priori (e.g., Healthy Diet Indicator, Healthy Eating Index, and Program National Nutrition Santé guideline score) and a posteriori (e.g., factor analysis, cluster analysis, and reduced rank regression), were shown to be associated with reduced cognitive decline and/or a reduced risk of dementia as shown by all 6 cross-sectional studies and 6 of 8 longitudinal studies. More conclusive evidence is needed to reach more targeted and detailed guidelines to prevent or postpone cognitive decline. PMID:25770254

  19. Body Mass Index and Decline of Cognitive Function

    PubMed Central

    Kim, Sujin; Kim, Yongjoo; Park, Sang Min

    2016-01-01

    Background The association between body mass index (BMI) and cognitive function is a public health issue. This study investigated the relationship between obesity and cognitive impairment which was assessed by the Korean version of the Mini-mental state examination (K-MMSE) among mid- and old-aged people in South Korea. Methods A cohort of 5,125 adults, age 45 or older with normal cognitive function (K-MMSE≥24) at baseline (2006), was derived from the Korean Longitudinal Study of Aging (KLoSA) 2006~2012. The association between baseline BMI and risk of cognitive impairment was assessed using multiple logistic regression models. We also assessed baseline BMI and change of cognitive function over the 6-year follow-up using multiple linear regressions. Results During the follow-up, 358 cases of severe cognitive impairment were identified. Those with baseline BMI≥25 kg/m2 than normal-weight (18.5≤BMI<23 kg/m2) were marginally less likely to experience the development of severe cognitive impairment (adjusted odds ratio [aOR] = 0.73, 95% CI = 0.52 to 1.03; Ptrend = 0.03). This relationship was stronger among female (aOR = 0.63, 95% CI = 0.40 to 1.00; Ptrend = 0.01) and participants with low-normal K-MMSE score (MMSE: 24–26) at baseline (aOR = 0.59, 95% CI = 0.35 to 0.98; Ptrend<0.01). In addition, a slower decline of cognitive function was observed in obese individuals than those with normal weight, especially among women and those with low-normal K-MMSE score at baseline. Conclusion In this nationally representative study, we found that obesity was associated with lower risk of cognitive decline among mid- and old-age population. PMID:26867138

  20. Decreased PM10 Exposure Attenuates Age-Related Lung Function Decline: Genetic Variants in p53, p21, and CCND1 Modify This Effect

    PubMed Central

    Imboden, Medea; Schwartz, Joel; Schindler, Christian; Curjuric, Ivan; Berger, Wolfgang; Liu, Sally L.J.; Russi, Erich W.; Ackermann-Liebrich, Ursula; Rochat, Thierry; Probst-Hensch, Nicole M.

    2009-01-01

    Background Decreasing exposure to airborne particulates was previously associated with reduced age-related decline in lung function. However, whether the benefit from improved air quality depends on genetic background is not known. Recent evidence points to the involvement of the genes p53 and p21 and of the cell cycle control gene cyclin D1 (CCND1) in the response of bronchial cells to air pollution. Objective We determined in 4,326 participants of the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA) whether four single-nucleotide polymorphisms in three genes [CCND1 (rs9344 [P242P], rs667515), p53 (rs1042522 [R72P]), and p21 (rs1801270 [S31R])] modified the previously observed attenuation of the decline in the forced expiratory flow between 25% and 75% of the forced vital capacity (FEF25–75) associated with improved air quality. Methods Subjects of the prospective population-based SAPALDIA cohort were assessed in 1991 and 2002 by spirometry, questionnaires, and biological sample collection for genotyping. We assigned spatially resolved concentrations of particulate matter with aerodynamic diameter ≤ 10 μm (PM10) to each participant’s residential history 12 months before the baseline and follow-up assessments. Results The effect of diminishing PM10 exposure on FEF25–75 decline appeared to be modified by p53 R72P, CCND1 P242P, and CCND1 rs667515. For example, a 10-μg/m3 decline in aver-age PM10 exposure over an 11-year period attenuated the average annual decline in FEF25–75 by 21.33 mL/year (95% confidence interval, 10.57–32.08) among participants homozygous for the CCND1 (P242P) GG genotype, by 13.72 mL/year (5.38–22.06) among GA genotypes, and by 6.00 mL/year (−4.54 to 16.54) among AA genotypes. Conclusions Our results suggest that cell cycle control genes may modify the degree to which improved air quality may benefit respiratory function in adults. PMID:19750108

  1. Human-specific derived alleles of CD33 and other genes protect against postreproductive cognitive decline

    PubMed Central

    Schwarz, Flavio; Springer, Stevan A.; Altheide, Tasha K.; Varki, Nissi M.; Gagneux, Pascal; Varki, Ajit

    2016-01-01

    The individuals of most vertebrate species die when they can no longer reproduce. Humans are a rare exception, having evolved a prolonged postreproductive lifespan. Elders contribute to cooperative offspring care, assist in foraging, and communicate important ecological and cultural knowledge, increasing the survival of younger individuals. Age-related deterioration of cognitive capacity in humans compromises these benefits and also burdens the group with socially costly members. We investigated the contribution of the immunoregulatory receptor CD33 to a uniquely human postreproductive disease, Alzheimer’s dementia. Surprisingly, even though selection at advanced age is expected to be weak, a CD33 allele protective against Alzheimer’s disease is derived and unique to humans and favors a functional molecular state of CD33 resembling that of the chimpanzee. Thus, derived alleles may be compensatory and restore interactions altered as a consequence of human-specific brain evolution. We found several other examples of derived alleles at other human loci that protect against age-related cognitive deterioration arising from neurodegenerative disease or cerebrovascular insufficiency. Selection by inclusive fitness may be strong enough to favor alleles protecting specifically against cognitive decline in postreproductive humans. Such selection would operate by maximizing the contributions of postreproductive individuals to the fitness of younger kin. PMID:26621708

  2. Human-specific derived alleles of CD33 and other genes protect against postreproductive cognitive decline.

    PubMed

    Schwarz, Flavio; Springer, Stevan A; Altheide, Tasha K; Varki, Nissi M; Gagneux, Pascal; Varki, Ajit

    2016-01-01

    The individuals of most vertebrate species die when they can no longer reproduce. Humans are a rare exception, having evolved a prolonged postreproductive lifespan. Elders contribute to cooperative offspring care, assist in foraging, and communicate important ecological and cultural knowledge, increasing the survival of younger individuals. Age-related deterioration of cognitive capacity in humans compromises these benefits and also burdens the group with socially costly members. We investigated the contribution of the immunoregulatory receptor CD33 to a uniquely human postreproductive disease, Alzheimer's dementia. Surprisingly, even though selection at advanced age is expected to be weak, a CD33 allele protective against Alzheimer's disease is derived and unique to humans and favors a functional molecular state of CD33 resembling that of the chimpanzee. Thus, derived alleles may be compensatory and restore interactions altered as a consequence of human-specific brain evolution. We found several other examples of derived alleles at other human loci that protect against age-related cognitive deterioration arising from neurodegenerative disease or cerebrovascular insufficiency. Selection by inclusive fitness may be strong enough to favor alleles protecting specifically against cognitive decline in postreproductive humans. Such selection would operate by maximizing the contributions of postreproductive individuals to the fitness of younger kin. PMID:26621708

  3. ω-3 Fatty Acids in the Prevention of Cognitive Decline in Humans123

    PubMed Central

    Cederholm, Tommy; Salem, Norman; Palmblad, Jan

    2013-01-01

    The brain is a lipid-rich organ where docosahexaenoic acid (DHA) is enriched and where eicosapentaenoic acid (EPA) may have anti-inflammatory effects. The potential role for n–3 (ω-3) fatty acids such as DHA and EPA in the prevention of cognitive decline, including Alzheimer’s disease (AD) has attracted major interest for the past 20 y. This review presents our understanding of recent observational, interventional, and experimental studies, with the aim of providing some answers to the following question: Can n–3 FA intake modulate cognitive function during aging? In longitudinal observation studies we mainly observe inverse relations between fish intake or serum concentrations of DHA and cognitive impairment. Intervention studies of EPA and DHA supplementation in healthy old individuals have been negative so far (i.e., after up to 2 years of treatment, no differences in cognitive decline between treated and nontreated participants have been observed). In studies that provided EPA and DHA to adults with mild cognitive impairment or age-related cognitive impairment the data seem to be positive. However, when patients with established AD were supplemented with EPA and DHA it appears no benefit was gained. For studies on healthy individuals, a major concern is that the treatment periods may have been too short. There might also be subgroup effects because of the carriage of apolipoprotein Eε4 alleles or risk factor burden. Experimental studies appear to be consistently positive (i.e., n–3 FA supplementation in rodents over a substantial portion of their lives reduces amyloid-β deposition and hippocampal neuron loss and improves cognitive functioning). We are getting closer to providing evidence-based recommendations on fish and fish oil intake to facilitate memory function during old age. In the meantime it is advised to follow the general CDC dietary recommendations of 2–3 fish meals per week or the equivalent intake of long chain n–3 fatty acids

  4. Bilingualism Does Not Alter Cognitive Decline or Dementia Risk among Spanish-Speaking Immigrants

    PubMed Central

    Zahodne, Laura B.; Schofield, Peter W.; Farrell, Meagan T.; Stern, Yaakov; Manly, Jennifer J.

    2013-01-01

    Objective Clinic-based studies suggest that dementia is diagnosed at older ages in bilinguals compared to monolinguals. The current study sought to test this hypothesis in a large, prospective, community-based study of initially non-demented Hispanic immigrants living in a Spanish-speaking enclave of Northern Manhattan. Method Participants included 1,067 participants in the Washington/Hamilton Heights Inwood Columbia Aging Project (WHICAP) who were tested in Spanish and followed at 18–24 month intervals for up to 23 years. Spanish-English bilingualism was estimated via both self-report and an objective measure of English reading level. Multilevel models for change estimated the independent effects of bilingualism on cognitive decline in four domains: episodic memory, language, executive function, and speed. Over the course of the study, 282 participants developed dementia. Cox regression was used to estimate the independent effect of bilingualism on dementia conversion. Covariates included country of origin, gender, education, time spent in the United States, recruitment cohort, and age at enrollment. Results Independent of the covariates, bilingualism was associated with better memory and executive function at baseline. However bilingualism was not independently associated with rates of cognitive decline or dementia conversion. Results were similar whether bilingualism was measured via self-report or an objective test of reading level. Conclusions This study does not support a protective effect of bilingualism on age-related cognitive decline or the development of dementia. In this sample of Hispanic immigrants, bilingualism is related to higher initial scores on cognitive tests and higher educational attainment and may not represent a unique source of cognitive reserve. PMID:24188113

  5. Imaging Biomarkers Associated with Cognitive Decline: A Review

    PubMed Central

    McConathy, Jonathan; Sheline, Yvette I.

    2014-01-01

    In evaluating disease changes it is critical to have measurements that are sensitive, specific and reliable. Cognitive decline, particularly in the context of Alzheimer’s disease (AD), is an area that has attracted a large number of recent studies, and as such the proposed biomarkers used in these investigations need to be validated. In this review we highlight studies with important implications about the role of imaging biomarkers in cognitive decline and dementia as well as in distinguishing preclinical dementia, prior to evidence of cognitive decline. Structural changes determined on magnetic resonance imaging (MRI), both cross-sectional and longitudinal provide early prediction of dementia, particularly when combined with other measures. Molecular imaging using PET and SPECT tracers quantify the presence or activity of receptors, transporters, enzymes, metabolic pathways and proteins. The newest developments in molecular imaging will be described and methods compared. Distinguishing features of imaging biomarkers among dementias and the spectrum of preclinical AD, MCI and AD will be described. Appropriate use criteria for amyloid PET will be delineated. While these efforts are still in the early phase of development, there is great promise for further development in structural MRI and PET technologies. PMID:25442005

  6. Ascorbic acid and rates of cognitive decline in Alzheimer's disease.

    PubMed

    Bowman, Gene L; Dodge, Hiroko; Frei, Balz; Calabrese, Carlo; Oken, Barry S; Kaye, Jeffrey A; Quinn, Joseph F

    2009-01-01

    The brain maintains high levels of ascorbic acid (AA) despite a concentration gradient favoring diffusion from brain to peripheral tissues. Dietary antioxidants, including AA, appear to modify the risk of Alzheimer's disease (AD). The objective of this study was to test the hypothesis that neurodegeneration in AD is modified by brain levels of AA. Thirty-two patients with mild to moderate AD participated in a biomarker study involving standardized clinical assessments over one year. Cerebrospinal fluid (CSF) and serum were collected at baseline for AA and albumin content. Cognitive measures were collected at baseline and one year. CSF and plasma AA failed to predict cognitive decline independently, however, CSF: plasma AA ratio did. After adding CSF Albumin Index (an established marker of blood-brain barrier integrity) to the regression models the effect of CSF: plasma AA ratio as a predictor of cognitive decline was weakened. CSF: plasma AA ratio predicts rate of decline in AD. This relationship may indicate that the CSF: plasma AA ratio is an index of AA availability to the brain or may be an artifact of a relationship between blood-brain barrier impairment and neurodegeneration. PMID:19158425

  7. Age-related neurogenesis decline in the subventricular zone is associated with specific cell cycle regulation changes in activated neural stem cells

    PubMed Central

    Daynac, Mathieu; Morizur, Lise; Chicheportiche, Alexandra; Mouthon, Marc-André; Boussin, François D.

    2016-01-01

    Although neural stem cells (NSCs) sustain continuous neurogenesis throughout the adult lifespan of mammals, they progressively exhibit proliferation defects that contribute to a sharp reduction in subventricular neurogenesis during aging. However, little is known regarding the early age-related events in neurogenic niches. Using a fluorescence-activated cell sorting technique that allows for the prospective purification of the main neurogenic populations from the subventricular zone (SVZ), we demonstrated an early decline in adult neurogenesis with a dramatic loss of progenitor cells in 4 month-old young adult mice. Whereas the activated and quiescent NSC pools remained stable up to 12 months, the proliferative status of activated NSCs was already altered by 6 months, with an overall extension of the cell cycle resulting from a specific lengthening of G1. Whole genome analysis of activated NSCs from 2- and 6-month-old mice further revealed distinct transcriptomic and molecular signatures, as well as a modulation of the TGFβ signalling pathway. Our microarray study constitutes a cogent identification of new molecular players and signalling pathways regulating adult neurogenesis and its early modifications. PMID:26893147

  8. Age-related neurogenesis decline in the subventricular zone is associated with specific cell cycle regulation changes in activated neural stem cells.

    PubMed

    Daynac, Mathieu; Morizur, Lise; Chicheportiche, Alexandra; Mouthon, Marc-André; Boussin, François D

    2016-01-01

    Although neural stem cells (NSCs) sustain continuous neurogenesis throughout the adult lifespan of mammals, they progressively exhibit proliferation defects that contribute to a sharp reduction in subventricular neurogenesis during aging. However, little is known regarding the early age-related events in neurogenic niches. Using a fluorescence-activated cell sorting technique that allows for the prospective purification of the main neurogenic populations from the subventricular zone (SVZ), we demonstrated an early decline in adult neurogenesis with a dramatic loss of progenitor cells in 4 month-old young adult mice. Whereas the activated and quiescent NSC pools remained stable up to 12 months, the proliferative status of activated NSCs was already altered by 6 months, with an overall extension of the cell cycle resulting from a specific lengthening of G1. Whole genome analysis of activated NSCs from 2- and 6-month-old mice further revealed distinct transcriptomic and molecular signatures, as well as a modulation of the TGFβ signalling pathway. Our microarray study constitutes a cogent identification of new molecular players and signalling pathways regulating adult neurogenesis and its early modifications. PMID:26893147

  9. Faith-based cognitive behavioral therapy: easing depression in the elderly with cognitive decline.

    PubMed

    Ceramidas, Dagmar M

    2012-01-01

    Minimizing depression in residential aged care facilities is a formidable challenge but doing so may improve quality of life and protect against dementia. A pilot project with residents with cognitive decline and concurrent depression tested the suitability of a faith-based cognitive behavioral therapy (CBT) intervention in reducing participant levels of depression, offering promising results. PMID:22359836

  10. Flavonol Intake and Cognitive Decline in Middle-Aged Adults.

    PubMed

    Root, Martin; Ravine, Erin; Harper, Anne

    2015-12-01

    Cognitive decline occurs with age and may be slowed by dietary measures, including increased intake of dietary phytochemicals. However, evidence from large and long-term studies of flavonol intake is limited. Dietary intakes of flavonols were assessed from a large biracial study of 10,041 subjects, aged 45-64, by analysis of a food frequency questionnaire administered at visit 1 of triennial visits. Cognitive function was assessed at visits 2 and 4 with the following three cognitive performance tests: the delayed word recall test, the revised Wechsler Adult Intelligence Scale digit symbol subtest, and the word fluency test of the Multilingual Aphasia Examination. The change in each score over 6 years was calculated, and a combined standardized change score was calculated. Generalized linear models controlled for age, ethnicity, gender, education level, energy intake, current smoking, physical activity, body mass index, diabetes, and vitamin C intake. Total flavonols across quintiles of intake were positively associated with preserved combined cognitive function (P<.001). This pattern with preserved combined cognitive function was consistent for the three major individual flavonols in the diet, myricetin, kaempferol, and quercetin (each P<.001). The positive association with total flavonols was strongest for the digit symbol subtest (P<.001). In this cohort, flavonol intake was correlated with protected cognitive function over time. PMID:26325006

  11. Cognitive decline due to aging among persons with Down syndrome.

    PubMed

    Das, J P; Divis, B; Alexander, J; Parrila, R K; Naglieri, J A

    1995-01-01

    This study examined decline in cognitive functions in individuals with Down syndrome (DS) over the age of 40 in comparison to participants of the same age and comparable mental handicap without Down syndrome (NonDS). Both DS (n = 32) and NonDS (n = 31) samples were divided into "younger" (40-49 years) and "older" (50-62) groups. Cognitive processes were examined by tests of general intellectual functioning (Dementia Rating Scale, Peabody Picture Vocabulary Test-Revised, and the Matrix Analogies Test-Expanded form), as well as planning, attention, simultaneous, and successive processing tests taken from Das-Naglieri Cognitive Assessment System. The older individuals with Down syndrome performed more poorly than those in the other three groups. The differences were particularly evident in tasks requiring planning and attention. The possibility of using these tests as indicators of the early signs of Alzheimer's disease is discussed. PMID:8584766

  12. Intrinsic Hippocampal Excitability Changes of Opposite Signs and Different Origins in CA1 and CA3 Pyramidal Neurons Underlie Aging-Related Cognitive Deficits

    PubMed Central

    Oh, M. Matthew; Simkin, Dina; Disterhoft, John F.

    2016-01-01

    Aging-related cognitive deficits have been attributed to dysfunction of neurons due to failures at synaptic or intrinsic loci, or both. Given the importance of the hippocampus for successful encoding of memory and that the main output of the hippocampus is via the CA1 pyramidal neurons, much of the research has been focused on identifying the aging-related changes of these CA1 pyramidal neurons. We and others have discovered that the postburst afterhyperpolarization (AHP) following a train of action potentials is greatly enlarged in CA1 pyramidal neurons of aged animals. This enlarged postburst AHP is a significant factor in reducing the intrinsic excitability of these neurons, and thus limiting their activity in the neural network during learning. Based on these data, it has largely been thought that aging-related cognitive deficits are attributable to reduced activity of pyramidal neurons. However, recent in vivo and ex vivo studies provide compelling evidence that aging-related deficits could also be due to a converse change in CA3 pyramidal neurons, which show increased activity with aging. In this review, we will incorporate these recent findings and posit that an interdependent dynamic dysfunctional change occurs within the hippocampal network, largely due to altered intrinsic excitability in CA1 and CA3 hippocampal pyramidal neurons, which ultimately leads to the aging-related cognitive deficits. PMID:27375440

  13. Preclinical Magnetic Resonance Imaging and Spectroscopy Studies of Memory, Aging, and Cognitive Decline

    PubMed Central

    Febo, Marcelo; Foster, Thomas C.

    2016-01-01

    Neuroimaging provides for non-invasive evaluation of brain structure and activity and has been employed to suggest possible mechanisms for cognitive aging in humans. However, these imaging procedures have limits in terms of defining cellular and molecular mechanisms. In contrast, investigations of cognitive aging in animal models have mostly utilized techniques that have offered insight on synaptic, cellular, genetic, and epigenetic mechanisms affecting memory. Studies employing magnetic resonance imaging and spectroscopy (MRI and MRS, respectively) in animal models have emerged as an integrative set of techniques bridging localized cellular/molecular phenomenon and broader in vivo neural network alterations. MRI methods are remarkably suited to longitudinal tracking of cognitive function over extended periods permitting examination of the trajectory of structural or activity related changes. Combined with molecular and electrophysiological tools to selectively drive activity within specific brain regions, recent studies have begun to unlock the meaning of fMRI signals in terms of the role of neural plasticity and types of neural activity that generate the signals. The techniques provide a unique opportunity to causally determine how memory-relevant synaptic activity is processed and how memories may be distributed or reconsolidated over time. The present review summarizes research employing animal MRI and MRS in the study of brain function, structure, and biochemistry, with a particular focus on age-related cognitive decline. PMID:27468264

  14. Reversal of cognitive decline: A novel therapeutic program

    PubMed Central

    Bredesen, Dale E.

    2014-01-01

    This report describes a novel, comprehensive, and personalized therapeutic program that is based on the underlying pathogenesis of Alzheimer's disease, and which involves multiple modalities designed to achieve metabolic enhancement for neurodegeneration (MEND). The first 10 patients who have utilized this program include patients with memory loss associated with Alzheimer's disease (AD), amnestic mild cognitive impairment (aMCI), or subjective cognitive impairment (SCI). Nine of the 10 displayed subjective or objective improvement in cognition beginning within 3-6 months, with the one failure being a patient with very late stage AD. Six of the patients had had to discontinue working or were struggling with their jobs at the time of presentation, and all were able to return to work or continue working with improved performance. Improvements have been sustained, and at this time the longest patient follow-up is two and one-half years from initial treatment, with sustained and marked improvement. These results suggest that a larger, more extensive trial of this therapeutic program is warranted. The results also suggest that, at least early in the course, cognitive decline may be driven in large part by metabolic processes. Furthermore, given the failure of monotherapeutics in AD to date, the results raise the possibility that such a therapeutic system may be useful as a platform on which drugs that would fail as monotherapeutics may succeed as key components of a therapeutic system. PMID:25324467

  15. Reversal of cognitive decline: a novel therapeutic program.

    PubMed

    Bredesen, Dale E

    2014-09-01

    This report describes a novel, comprehensive, and personalized therapeutic program that is based on the underlying pathogenesis of Alzheimer's disease, and which involves multiple modalities designed to achieve metabolic enhancement for neurodegeneration (MEND). The first 10 patients who have utilized this program include patients with memory loss associated with Alzheimer's disease (AD), amnestic mild cognitive impairment (aMCI), or subjective cognitive impairment (SCI). Nine of the 10 displayed subjective or objective improvement in cognition beginning within 3-6 months, with the one failure being a patient with very late stage AD. Six of the patients had had to discontinue working or were struggling with their jobs at the time of presentation, and all were able to return to work or continue working with improved performance. Improvements have been sustained, and at this time the longest patient follow-up is two and one-half years from initial treatment, with sustained and marked improvement. These results suggest that a larger, more extensive trial of this therapeutic program is warranted. The results also suggest that, at least early in the course, cognitive decline may be driven in large part by metabolic processes. Furthermore, given the failure of monotherapeutics in AD to date, the results raise the possibility that such a therapeutic system may be useful as a platform on which drugs that would fail as monotherapeutics may succeed as key components of a therapeutic system. PMID:25324467

  16. Patterns of cognitive decline in aged rhesus monkeys.

    PubMed

    Herndon, J G; Moss, M B; Rosene, D L; Killiany, R J

    1997-08-01

    Although cognitive decline has been well established as a consequence of aging in non-human primate models, the prevalence or frequency of impairment for specific age ranges has not been described. The first aim of this study was to estimate prevalence of cognitive impairment on each of the six tests of cognitive performance by comparing the performance of early-aged (19-23 years old), advanced-aged (24-28 years old), and oldest-aged (29+ years old) monkeys to that of young adults (< 15 years old). The second aim was to derive a single overall measure of cognitive performance to help classify behavioral function in our aged monkeys. Accordingly, we obtained performance measures for these age groups on six behavioral measures: (1) acquisition of the delayed non-matching-to-sample task (DNMS); (2) performance of the DNMS with a delay of 120 sec; (3) the spatial condition of the delayed recognition span test (DRST); (4) the color condition of the DRST; (5) spatial reversal learning; and (6) object reversal learning. Early-aged monkeys displayed prevalence rates of impairment significantly greater than zero on all tasks except the DRST-color. The highest prevalence of impairment was observed in this age group in a task measuring spatial memory (DRST). Significant trends toward progressively higher impairment rates in advanced-aged and oldest-aged monkeys were observed for DNMS-acquisition, DRST-color and spatial reversal learning tasks. A linear transformation of standardized scores on the six cognitive tests was derived by means of principal components analysis (PCA). The first PCA (PCA1) included data from 30 monkeys with available data on all six measures, and yielded a composite measure which declined linearly with increasing age (r = -0.74). A second PCA (PCA2) was performed on data from 53 monkeys for which three test scores (DNMS-acquisition, DNMS-120s delay, and DRST-spatial condition) were available. The composite score derived from this analysis was highly

  17. Dissecting the age-related decline on spatial learning and memory tasks in rodent models: N-methyl-D-aspartate receptors and voltage-dependent Ca2+ channels in senescent synaptic plasticity

    PubMed Central

    Foster, Thomas C.

    2012-01-01

    In humans, heterogeneity in the decline of hippocampal-dependent episodic memory is observed during aging. Rodents have been employed as models of age-related cognitive decline and the spatial water maze has been used to show variability in the emergence and extent of impaired hippocampal-dependent memory. Impairment in the consolidation of intermediate-term memory for rapidly acquired and flexible spatial information emerges early, in middle-age. As aging proceeds, deficits may broaden to include impaired incremental learning of a spatial reference memory. The extent and time course of impairment has been be linked to senescence of calcium (Ca2+) regulation and Ca2+-dependent synaptic plasticity mechanisms in region CA1. Specifically, aging is associated with altered function of N-methyl-D-aspartate receptors (NMDARs), voltage-dependent Ca2+ channels (VDCCs), and ryanodine receptors (RyRs) linked to intracellular Ca2+ stores (ICS). In young animals, NMDAR activation induces long-term potentiation of synaptic transmission (NMDAR-LTP), which is thought to mediate the rapid consolidation of intermediate-term memory. Oxidative stress, starting in middle-age, reduces NMDAR function. In addition, VDCCs and ICS can actively inhibit NMDAR-dependent LTP and oxidative stress enhances the role of VDCC and RyR-ICS in regulating synaptic plasticity. Blockade of L-type VDCCs promotes NMDAR-LTP and memory in older animals. Interestingly, pharmacological or genetic manipulations to reduce hippocampal NMDAR function readily impair memory consolidation or rapid learning, generally leaving incremental learning intact. Finally, evidence is mounting to indicate a role for VDCC-dependent synaptic plasticity in associative learning and the consolidation of remote memories. Thus, VDCC-dependent synaptic plasticity and extrahippocampal systems may contribute to incremental learning deficits observed with advanced aging. PMID:22307057

  18. Cognitive Stimulation and Cognitive and Functional Decline in Alzheimer's Disease: The Cache County Dementia Progression Study

    PubMed Central

    Treiber, Katherine A.; Carlson, Michelle C.; Corcoran, Chris; Norton, Maria C.; Breitner, John C. S.; Piercy, Kathleen W.; DeBerard, Michael Scott; Stein, David; Foley, Beth; Welsh-Bohmer, Kathleen A.; Frye, Amber; Lyketsos, Constantine G.

    2011-01-01

    Objectives. To examine the association of engagement in cognitively stimulating activities with cognitive and functional decline in a population-based sample of incident Alzheimer's disease (AD). Method. After diagnosis, 187 participants (65% females) were followed semiannually for a mean 2.7 (SD = 0.4) years. Mean age and education were 84.6 (SD = 5.8) and 13.2 (SD = 2.9) years. Caregivers enumerated cognitively stimulating leisure activities via the Lifestyle Activities Questionnaire. Cognition was assessed using the Mini-Mental State Examination and functional ability via the Clinical Dementia Rating sum of boxes. Linear mixed models tested the association between stimulating activities and change over time in each outcome. Covariates were demographic factors, estimated premorbid IQ, presence/absence of the APOE ϵ4 allele, duration of dementia, level of physical activity, and general health. Results. At initial assessment, 87% of participants were engaged in one or more stimulating activities, with mean (SD) activities = 4.0 (3.0). This number declined to 2.4 (2.0) at the final visit. There was a statistical interaction between dementia duration and number of activities in predicting rate of cognitive decline (p = .02) and overall functional ability (p = .006). Discussion. Active involvement in cognitively stimulating pursuits may be beneficial for persons with AD. PMID:21441386

  19. Apolipoprotein E: non-cognitive symptoms and cognitive decline in late onset Alzheimer's disease.

    PubMed Central

    Holmes, C; Levy, R; McLoughlin, D M; Powell, J F; Lovestone, S

    1996-01-01

    OBJECTIVES: To determine the association between the epsilon2 and epsilon4 alleles of apolipoprotein E (ApoE) and independent measures of cognitive decline and non-cognitive symptomatology in late onset Alzheimer's disease. METHODS: The frequency of the epsilon2 and epsilon4 alleles of ApoE and their association with measures of cognitive decline and non-cognitive symptomatology were assessed in a population based case register study of 164 patients with late onset Alzheimer's disease from the east Lambeth and south Southwark districts of south London. RESULTS: Analysis of a wide range of non-cognitive symptoms against ApoE epsilon4 genotype showed no significant association but a positive relation was found between ApoE epsilon2 genotype and depressive symptomatology (P = 0.004). No relation was found between measurements of cognitive decline and the presence of the ApoE epsilon4 allele. A trend for decreasing age at onset of 3 to 4 years in carriers of the ApoE epsilon4 allele was found, confirming earlier studies. CONCLUSION: Presence of the epsilon4 allele of ApoE is associated with an earlier age at onset but does not seem to be related to either a more severe psychopathology or a more rapid progression of the illness. The epsilon2 allele of ApoE is associated with depressive symptomatology in late onset Alzheimer's disease. PMID:8971103

  20. Cognitive declines in healthy aging: evidence from multiple aspects of interference resolution.

    PubMed

    Pettigrew, Corinne; Martin, Randi C

    2014-06-01

    The present study tested the hypothesis that older adults show age-related deficits in interference resolution, also referred to as inhibitory control. Although oftentimes considered as a unitary aspect of executive function, various lines of work support the notion that interference resolution may be better understood as multiple constructs, including resistance to proactive interference (PI) and response-distractor inhibition (e.g., Friedman & Miyake, 2004). Using this dichotomy, the present study assessed whether older adults (relative to younger adults) show impaired performance across both, 1, or neither of these interference resolution constructs. To do so, we used multiple tasks to tap each construct and examined age effects at both the single task and latent variable levels. Older adults consistently demonstrated exaggerated interference effects across resistance to PI tasks. Although the results for the response-distractor inhibition tasks were less consistent at the individual task level analyses, age effects were evident on multiple tasks, as well as at the latent variable level. However, results of the latent variable modeling suggested declines in interference resolution are best explained by variance that is common to the 2 interference resolution constructs measured herein. Furthermore, the effect of age on interference resolution was found to be both distinct from declines in working memory, and independent of processing speed. These findings suggest multiple cognitive domains are independently sensitive to age, but that declines in the interference resolution constructs measured herein may originate from a common cause. PMID:24955989

  1. Cognitive decline is associated with reduced surface GluR1 expression in the hippocampus of aged rats.

    PubMed

    Yang, Yuan-Jian; Chen, Hai-Bo; Wei, Bo; Wang, Wei; Zhou, Ping-Liang; Zhan, Jin-Qiong; Hu, Mao-Rong; Yan, Kun; Hu, Bin; Yu, Bin

    2015-03-30

    Individual differences in cognitive aging exist in humans and in rodent populations, yet the underlying mechanisms remain largely unclear. Activity-dependent delivery of GluR1-containing AMPA receptor (AMPARs) plays an essential role in hippocampal synaptic plasticity, learning and memory. We hypothesize that alterations of surface GluR1 expression in the hippocampus might correlate with age-related cognitive decline. To test this hypothesis, the present study evaluated the cognitive function of young adult and aged rats using Morris water maze. After the behavioral test, the surface expression of GluR1 protein in hippocampal CA1 region of rats was determined using Western blotting. The results showed that the surface expression of GluR1 in the hippocampus of aged rats that are cognitively impaired was much lower than that of young adults and aged rats with preserved cognitive abilities. The phosphorylation levels of GluR1 at Ser845 and Ser831 sites, which promote the synaptic delivery of GluR1, were also selectively decreased in the hippocampus of aged-impaired rats. Correlation analysis reveals that greater decrease in surface GluR1 expression was associated with worse behavioral performance. These results suggest that reduced surface GluR1 expression may contribute to cognitive decline that occurs in normal aging, and different pattern of surface GluR1 expression might be responsible for the individual differences in cognitive aging. PMID:25697598

  2. Temperature affects longevity and age-related locomotor and cognitive decay in the short-lived fish Nothobranchius furzeri.

    PubMed

    Valenzano, Dario R; Terzibasi, Eva; Cattaneo, Antonino; Domenici, Luciano; Cellerino, Alessandro

    2006-06-01

    Temperature variations are known to modulate aging and life-history traits in poikilotherms as different as worms, flies and fish. In invertebrates, temperature affects lifespan by modulating the slope of age-dependent acceleration in death rate, which is thought to reflect the rate of age-related damage accumulation. Here, we studied the effects of temperature on aging kinetics, aging-related behavioural deficits, and age-associated histological markers of senescence in the short-lived fish Nothobranchius furzeri. This species shows a maximum captive lifespan of only 3 months, which is tied with acceleration in growth and expression of aging biomarkers. These biological peculiarities make it a very convenient animal model for testing the effects of experimental manipulations on life-history traits in vertebrates. Here, we show that (i) lowering temperature from 25 degrees C to 22 degrees C increases both median and maximum lifespan; (ii) life extension is due to reduction in the slope of the age-dependent acceleration in death rate; (iii) lowering temperature from 25 degrees C to 22 degrees C retards the onset of age-related locomotor and learning deficits; and (iv) lowering temperature from 25 degrees C to 22 degrees C reduces the accumulation of the age-related marker lipofuscin. We conclude that lowering water temperature is a simple experimental manipulation which retards the rate of age-related damage accumulation in this short-lived species. PMID:16842500

  3. Lifelong Bilingualism Contributes to Cognitive Reserve against White Matter Integrity Declines in Aging

    PubMed Central

    Gold, Brian T.; Johnson, Nathan F.; Powell, David K.

    2013-01-01

    Recent evidence suggests that lifelong bilingualism may contribute to cognitive reserve (CR) in normal aging. However, there is currently no neuroimaging evidence to suggest that lifelong bilinguals can retain normal cognitive functioning in the face of age-related neurodegeneration. Here we explored this issue by comparing white matter (WM) integrity and gray matter (GM) volumetric patterns of older adult lifelong bilinguals (N = 20) and monolinguals (N = 20). The groups were matched on a range of relevant cognitive test scores and on the established CR variables of education, socioeconomic status and intelligence. Participants underwent high-resolution structural imaging for assessment of GM volume and diffusion tensor imaging (DTI) for assessment of WM integrity. Results indicated significantly lower microstructural integrity in the bilingual group in several WM tracts. In particular, compared to their monolingual peers, the bilingual group showed lower fractional anisotropy and/or higher radial diffusivity in the inferior longitudinal fasciculus/inferior fronto-occipital fasciculus bilaterally, the fornix, and multiple portions of the corpus callosum. There were no group differences in GM volume. Our results suggest that lifelong bilingualism contributes to CR against WM integrity declines in aging. PMID:24103400

  4. The Cognitive Decline of Marshal Philippe Pétain.

    PubMed

    Jennekens, Frans G I

    2015-01-01

    In 1940, at the age of 84, Marshal Pétain was appointed the head of state and government of France. His health was excellent but he tired easily. He felt unable to learn and his memory was weak. During a crisis situation in 1942, he did not lead, plan and decide and he was replaced as head of government. From 1943 on, he was increasingly apathetic. In 1945/1946 he had difficulty finding words after a short conversation. A parliamentary committee concluded in 1947 that he was senile. His mental condition worsened in the years thereafter. In retrospect, it is clear that the final responsibility for the policies of the French government in the Second World War had rested on a man who was going through a predementia process of cognitive decline. PMID:26107612

  5. Age-Related Cognitive Impairments in Mice with a Conditional Ablation of the Neural Cell Adhesion Molecule

    ERIC Educational Resources Information Center

    Bisaz, Reto; Boadas-Vaello, Pere; Genoux, David; Sandi, Carmen

    2013-01-01

    Most of the mechanisms involved in neural plasticity support cognition, and aging has a considerable effect on some of these processes. The neural cell adhesion molecule (NCAM) of the immunoglobulin superfamily plays a pivotal role in structural and functional plasticity and is required to modulate cognitive and emotional behaviors. However,…

  6. Touchscreen-Based Cognitive Tasks Reveal Age-Related Impairment in a Primate Aging Model, the Grey Mouse Lemur (Microcebus murinus)

    PubMed Central

    2014-01-01

    Mouse lemurs are suggested to represent promising novel non-human primate models for aging research. However, standardized and cross-taxa cognitive testing methods are still lacking. Touchscreen-based testing procedures have proven high stimulus control and reliability in humans and rodents. The aim of this study was to adapt these procedures to mouse lemurs, thereby exploring the effect of age. We measured appetitive learning and cognitive flexibility of two age groups by applying pairwise visual discrimination (PD) and reversal learning (PDR) tasks. On average, mouse lemurs needed 24 days of training before starting with the PD task. Individual performances in PD and PDR tasks correlate significantly, suggesting that individual learning performance is unrelated to the respective task. Compared to the young, aged mouse lemurs showed impairments in both PD and PDR tasks. They needed significantly more trials to reach the task criteria. A much higher inter-individual variation in old than in young adults was revealed. Furthermore, in the PDR task, we found a significantly higher perseverance in aged compared to young adults, indicating an age-related deficit in cognitive flexibility. This study presents the first touchscreen-based data on the cognitive skills and age-related dysfunction in mouse lemurs and provides a unique basis to study mechanisms of inter-individual variation. It furthermore opens exciting perspectives for comparative approaches in aging, personality, and evolutionary research. PMID:25299046

  7. Comparing three methods of computerised cognitive training for older adults with subclinical cognitive decline.

    PubMed

    Gooding, Amanda L; Choi, Jimmy; Fiszdon, Joanna M; Wilkins, Kirsten; Kirwin, Paul D; van Dyck, Christopher H; Devanand, Davangere; Bell, Morris D; Rivera Mindt, Monica

    2016-10-01

    Cognitive rehabilitation for mild cognitive impairment (MCI) and early Alzheimer's disease is readily available to the geriatric population. Initial evidence suggests that techniques incorporating motivational strategies to enhance treatment engagement may provide more benefit than computerised training alone. Seventy four adults with subclinical cognitive decline were randomly assigned to computerised cognitive training (CCT), Cognitive Vitality Training (CVT), or an Active Control Group (ACG), and underwent neuropsychological evaluations at baseline and four-month follow-up. Significant differences were found in changes in performance on the Modified Mini Mental State Examination (mMMSE) and measures of verbal learning and memory across treatment groups. Experimental groups showed greater preservation of functioning on the mMMSE than the ACG group, the CVT group performed better than the ACG group on one measure of verbal learning and both measures of verbal memory, and the CCT group performed better than the ACG group on one measure of verbal learning and one measure of verbal memory. There were no significant group differences between the CVT and CCT groups on measures of verbal learning or memory. It was concluded that computerised cognitive training may offer the most benefit when incorporated into a therapeutic milieu rather than administered alone, although both appear superior to more generic forms of cognitive stimulation. PMID:26674122

  8. Glutamatergic treatment strategies for age-related memory disorders.

    PubMed

    Müller, W E; Scheuer, K; Stoll, S

    1994-01-01

    Age-related changes of N-methyl-D-aspartate (NMDA) receptors have been found in cortical areas and in the hippocampus of many species. On the basis of a variety of experimental observations it has been suggested that the decrease of NMDA receptor density might be one of the causative factors of the cognitive decline with aging. Based on these findings several strategies have been developed to improve cognition by compensating the NMDA receptor deficits in aging. The most promising approaches are the indirect activation of glutamatergic neurotransmission by agonists of the glycine site or the restoration of the age-related deficit of receptor density by several nootropics. PMID:7997073

  9. Age-related cortical thinning in cognitively healthy individuals in their 60s: the PATH Through Life study.

    PubMed

    Shaw, Marnie E; Sachdev, Perminder S; Anstey, Kaarin J; Cherbuin, Nicolas

    2016-03-01

    Although it is recognized that the human cortex thins with age, longitudinal estimates of thinning patterns specific to healthy young-old age (<75 years) individuals are lacking. Importantly, many neurodegenerative disorders first manifest between midlife and old age, and normative estimates may provide a reference for differential change associated with such disorders. Here, we provide longitudinal estimates of cortical thinning observed over 12 years in a large group (n = 396) of healthy individuals, aged 60-66 years at baseline scan, who were scanned with magnetic resonance imaging (1.5T) on 4 occasions. Longitudinal age-related thinning was observed across most of the cortices, with a mean change of -0.3% per year. We measured significant thinning in heteromodal association cortex, with less thinning in regions expected to atrophy later in life (e.g., primary sensory cortex). Men showed more extensive thinning than women. Our comparison of cross-sectional and longitudinal estimates adds to growing evidence that cross-sectional designs may underestimate age-related changes in cortical thickness. PMID:26923417

  10. Age-related Changes in Respiratory Function and Daily Living. A Tentative Model Including Psychosocial Variables, Respiratory Diseases and Cognition.

    PubMed

    Facal, David; González-Barcala, Francisco-Javier

    2016-01-01

    Changes in respiratory function are common in older populations and affect quality of life, social relationships, cognitive function and functional capacity. This paper reviews evidence reported in medical and psychological journals between 2000 and 2014 concerning the impact of changes in respiratory function on daily living in older adults. A tentative model establishes relationships involving respiratory function, cognitive function and functional capacities. The conclusion stresses the need for both longitudinal studies, to establish causal pathways between respiratory function and psychosocial aspects in aging, and intervention studies. PMID:26593253

  11. Age-Related Changes in Electrophysiological and Neuropsychological Indices of Working Memory, Attention Control, and Cognitive Flexibility

    PubMed Central

    Peltz, Carrie Brumback; Gratton, Gabriele; Fabiani, Monica

    2011-01-01

    Older adults exhibit great variability in their cognitive abilities, with some maintaining high levels of performance on executive control tasks and others showing significant deficits. Previous event-related potential (ERP) work has shown that some of these performance differences are correlated with persistence of the novelty/frontal P3 in older adults elicited by task-relevant events, presumably reflecting variability in the capacity to suppress orienting to unexpected but no longer novel events. In recent ERP work in young adults, we showed that the operation-span (OSPAN) task (a measure of attention control) is predictive of the ability of individuals to keep track of stimulus sequencing and to maintain running mental representations of task stimuli, as indexed by the parietally distributed P300 (or P3b). Both of these phenomena reflect aspects of frontal function (cognitive flexibility and attention control, respectively). To investigate these phenomena we sorted both younger and older adults into low- and high-working memory spans and low- and high-cognitive flexibility subgroups, and examined ERPs during an equal-probability choice reaction time task. For both age groups (a) participants with high OSPAN scores were better able to keep track of stimulus sequencing, as indicated by their smaller P3b to sequential changes; and (b) participants with lower cognitive flexibility had larger P3a than their high-scoring counterparts. However, these two phenomena did not interact suggesting that they manifest dissociable control mechanisms. Further, the fact that both effects are already visible in younger adults suggests that at least some of the brain mechanisms underlying individual differences in cognitive aging may already operate early in life. PMID:21887150

  12. Age-Related Differences and Cognitive Correlates of Self-Reported and Direct Navigation Performance: The Effect of Real and Virtual Test Conditions Manipulation

    PubMed Central

    Taillade, Mathieu; N'Kaoua, Bernard; Sauzéon, Hélène

    2016-01-01

    The present study investigated the effect of aging on direct navigation measures and self-reported ones according to the real-virtual test manipulation. Navigation (wayfinding tasks) and spatial memory (paper-pencil tasks) performances, obtained either in real-world or in virtual-laboratory test conditions, were compared between young (n = 32) and older (n = 32) adults who had self-rated their everyday navigation behavior (SBSOD scale). Real age-related differences were observed in navigation tasks as well as in paper-pencil tasks, which investigated spatial learning relative to the distinction between survey-route knowledge. The manipulation of test conditions (real vs. virtual) did not change these age-related differences, which are mostly explained by age-related decline in both spatial abilities and executive functioning (measured with neuropsychological tests). In contrast, elderly adults did not differ from young adults in their self-reporting relative to everyday navigation, suggesting some underestimation of navigation difficulties by elderly adults. Also, spatial abilities in young participants had a mediating effect on the relations between actual and self-reported navigation performance, but not for older participants. So, it is assumed that the older adults carried out the navigation task with fewer available spatial abilities compared to young adults, resulting in inaccurate self-estimates. PMID:26834666

  13. Impaired Sleep Predicts Cognitive Decline in Old People: Findings from the Prospective KORA Age Study

    PubMed Central

    Johar, Hamimatunnisa; Kawan, Rasmila; Emeny, Rebecca Thwing; Ladwig, Karl-Heinz

    2016-01-01

    Study Objectives: To investigate the association between sleep-related characteristics and cognitive change over 3 years of follow up in an aged population. Methods: Sleep characteristics and covariates were assessed at baseline in a standardized interview and clinical examination of the population-based KORA Age Study (n = 740, mean age = 75 years). Cognitive score (determined by telephone interview for cognitive status, TICS-m) was recorded at baseline and 3 years later. Results: At baseline, 82.83% (n = 613) of participants had normal cognitive status, 13.51% (n = 100) were classified with mild cognitive impairment (MCI), and 3.64% (n = 27) with probable dementia. The effect of three distinct patterns of poor sleep (difficulties initiating [DIS] or maintaining sleep [DMS], daytime sleepiness [DS] or sleep duration) were considered on a change in cognitive score with adjustments for potential confounders in generalized linear regression models. Cognitive decline was more pronounced in individuals with DMS compared to those with no DMS (β = 1.33, 95% CI = 0.41–2.24, P < 0.001). However, the predictive power of DMS was only significant in individuals with normal cognition and not impaired subjects at baseline. Prolonged sleep duration increased the risk for cognitive decline in cognitively impaired elderly (β = 1.86, 95% CI = 0.15–3.57, P = 0.03). Other sleep characteristics (DIS and DS) were not significantly associated with cognitive decline. Conclusions: DMS and long sleep duration were associated with cognitive decline in normal and cognitively impaired elderly, respectively. The identification of impaired sleep quality may offer intervention strategies to deter cognitive decline in the elderly with normal cognitive function. Citation: Johar H, Kawan R, Emeny RT, Ladwig KH. Impaired sleep predicts cognitive decline in old people: findings from the prospective KORA age study. SLEEP 2016;39(1):217–226. PMID:26414903

  14. Operationalizing diagnostic criteria for Alzheimer’s disease and other age-related cognitive impairment—Part 2*

    PubMed Central

    Seshadri, Sudha; Beiser, Alexa; Au, Rhoda; Wolf, Philip A.; Evans, Denis A.; Wilson, Robert S.; Petersen, Ronald C.; Knopman, David S.; Rocca, Walter A.; Kawas, Claudia H.; Corrada, Maria M.; Plassman, Brenda L.; Langa, Kenneth M.; Chui, Helena C.

    2011-01-01

    This article focuses on the effects of operational differences in case ascertainment on estimates of prevalence and incidence of cognitive impairment/dementia of the Alzheimer type. Experience and insights are discussed by investigators from the Framingham Heart Study, the East Boston Senior Health Project, the Chicago Health and Aging Project, the Mayo Clinic Study of Aging, the Baltimore Longitudinal Study of Aging, and the Aging, Demographics, and Memory Study. There is a general consensus that the single most important factor regulating prevalence estimates of Alzheimer’s disease (AD) is the severity of cognitive impairment used for case ascertainment. Studies that require a level of cognitive impairment in which persons are unable to provide self-care will have much lower estimates than studies aimed at identifying persons in the earliest stages of AD. There is limited autopsy data from the above-mentioned epidemiologic studies to address accuracy in the diagnosis of etiologic subtype, namely the specification of AD alone or in combination with other types of pathology. However, other community-based cohort studies show that many persons with mild cognitive impairment (MCI) meet pathologic criteria for AD, and a large minority of persons without dementia or MCI also meets pathologic criteria for AD, thereby suggesting that the number of persons who would benefit from an effective secondary prevention intervention is probably higher than the highest published prevalence estimates. Improved accuracy in the clinical diagnosis of AD is anticipated with the addition of molecular and structural biomarkers in the next generation of epidemiologic studies. PMID:21255742

  15. Trajectories of cognitive decline and functional status in the frail older adults.

    PubMed

    Nikolova, Rossitza; Demers, Louise; Béland, François

    2009-01-01

    This study investigates the implications of different levels of cognitive decline on functional status in frail older adults. Four cognitive trajectories, including two with catastrophic cognitive decline, were defined in a 3-year study. Participants with complete cognitive and functional status data at baseline, 12 and 36 months of follow-up were included in the study (n=456). Data were analysed with repeated measures statistics. Substantial functional deterioration over time was observed for the participants with catastrophic cognitive decline. Catastrophic cognitive decline influenced performance in instrumental activities of daily living (IADL) and activities of daily living (ADL) at 12 months, whereas basic physical and mental actions were affected at 36 months. IADL were found to deteriorate more than ADL. The results have implications on planning appropriate geriatric rehabilitation and long-term care program. PMID:17976840

  16. Trade off situation between thymus and growth hormone: age-related decline of growth hormone is a cause of thymic involution but favorable for elongation of lifespan.

    PubMed

    Hirokawa, Katsuiku; Utsuyama, Masanori; Kikuchi, Yuko

    2016-02-01

    High level of growth hormone (GH) is necessary for the activation of thymic function to promote T cell differentiation in the early stage of animal life. In the later stage of the life, administration of GH promotes the development of immune system and rejuvenates declined immune function of elderly people. By contraries, GH deficiency is favorable for the longer lifespan, as hypo-pituitary dwarf mice such as Ames and Snell dwarf mice exhibit longer lifespan than control. Furthermore over-expression of heterologous or homologous GH in transgenic mice shortens the lifespan. Ecuadorians carrying mutations of GH receptor gene are short in height, but exhibited low frequency of malignancy and no cases of diabetes. These data indicate that GH is necessary for the development of thymus dependent immune system but GH deficiency is favorable for long life span and decreases occurrence of cancer and DM. This situation is a kind of trade off situation between the immune system and GH. Thus the early decline of high level of GH occurring shortly after the birth is a cause of early decline of thymic functions, but favorable for longer lifespan. This situation could be a kind of trade off situation between thymus and GH. PMID:26169108

  17. No association of the variant rs11887120 in DNMT3A with cognitive decline in individuals with mild cognitive impairment.

    PubMed

    Bey, Katharina; Wolfsgruber, Steffen; Karaca, Ilker; Wagner, Holger; Lardenoije, Roy; Becker, Julian; Milz, Esther; Kornhuber, Johannes; Peters, Oliver; Frölich, Lutz; Hüll, Michael; Rüther, Eckart; Wiltfang, Jens; Riedel-Heller, Steffi; Scherer, Martin; Jessen, Frank; Maier, Wolfgang; van den Hove, Daniel L; Rutten, Bart Pf; Wagner, Michael; Ramirez, Alfredo

    2016-05-01

    Alterations in DNA methylation have been associated with cognitive decline and Alzheimer's disease. A recent study of mild cognitive impairment (MCI) reported a significant association between annual decline in cognitive function and the rs11887120 SNP located in DNMT3A, a gene implicated in DNA methylation. Here, we aimed to replicate this finding in two independent MCI cohorts (n = 1024); however, no significant association was observed in either cohort or the pooled dataset. In stratified analyses for conversion to Alzheimer's disease status, no association between rs11887120 and cognitive decline was observed in either converters or nonconverters. In conclusion, our analyses provide no support for the hypothesis that genetic variants in DNMT3A are implicated in cognitive performance decline in individuals with MCI. PMID:27092400

  18. Walking ability to predict future cognitive decline in old adults: A scoping review.

    PubMed

    Kikkert, Lisette H J; Vuillerme, Nicolas; van Campen, Jos P; Hortobágyi, Tibor; Lamoth, Claudine J

    2016-05-01

    Early identification of individuals at risk for cognitive decline may facilitate the selection of those who benefit most from interventions. Current models predicting cognitive decline include neuropsychological and/or biological markers. Additional markers based on walking ability might improve accuracy and specificity of these models because motor and cognitive functions share neuroanatomical structures and psychological processes. We reviewed the relationship between walking ability at one point of (mid) life and cognitive decline at follow-up. A systematic literature search identified 20 longitudinal studies. The average follow-up time was 4.5 years. Gait speed quantified walking ability in most studies (n=18). Additional gait measures (n=4) were step frequency, variability and step-length. Despite methodological weaknesses, results revealed that gait slowing (0.68-1.1 m/sec) preceded cognitive decline and the presence of dementia syndromes (maximal odds and hazard ratios of 10.4 and 11.1, respectively). The results indicate that measures of walking ability could serve as additional markers to predict cognitive decline. However, gait speed alone might lack specificity. We recommend gait analysis, including dynamic gait parameters, in clinical evaluations of patients with suspected cognitive decline. Future studies should focus on examining the specificity and accuracy of various gait characteristics to predict future cognitive decline. PMID:26861693

  19. A Simulation Platform for Quantifying Survival Bias: An Application to Research on Determinants of Cognitive Decline.

    PubMed

    Mayeda, Elizabeth Rose; Tchetgen Tchetgen, Eric J; Power, Melinda C; Weuve, Jennifer; Jacqmin-Gadda, Hélène; Marden, Jessica R; Vittinghoff, Eric; Keiding, Niels; Glymour, M Maria

    2016-09-01

    Bias due to selective mortality is a potential concern in many studies and is especially relevant in cognitive aging research because cognitive impairment strongly predicts subsequent mortality. Biased estimation of the effect of an exposure on rate of cognitive decline can occur when mortality is a common effect of exposure and an unmeasured determinant of cognitive decline and in similar settings. This potential is often represented as collider-stratification bias in directed acyclic graphs, but it is difficult to anticipate the magnitude of bias. In this paper, we present a flexible simulation platform with which to quantify the expected bias in longitudinal studies of determinants of cognitive decline. We evaluated potential survival bias in naive analyses under several selective survival scenarios, assuming that exposure had no effect on cognitive decline for anyone in the population. Compared with the situation with no collider bias, the magnitude of bias was higher when exposure and an unmeasured determinant of cognitive decline interacted on the hazard ratio scale to influence mortality or when both exposure and rate of cognitive decline influenced mortality. Bias was, as expected, larger in high-mortality situations. This simulation platform provides a flexible tool for evaluating biases in studies with high mortality, as is common in cognitive aging research. PMID:27578690

  20. Age-related changes in brain metabolites and cognitive function in APP/PS1 transgenic mice.

    PubMed

    Chen, Shuang-qing; Cai, Qing; Shen, Yu-ying; Wang, Pei-jun; Teng, Gao-jun; Zhang, Wei; Zang, Feng-chao

    2012-11-01

    Proton magnetic resonance spectroscopy ((1)H-MRS) and the Morris water maze (MWM) have played an important role in Alzheimer's disease (AD) research. The aim of this study was to determine whether (1)H-MRS and the MWM can detect for early AD in APP/PS1 transgenic (tg) mice. (1)H-MRS was performed in 20 tg mice and 15 wild-type mice at 3, 5 and 8 months of age. The concentration of N-acetylaspartate (NAA), glutamate (Glu), myo-inositol (mI), choline (Cho) and creatine (Cr) in the hippocampus were measured, and the NAA/Cr, Glu/Cr, mI/Cr and Cho/Cr ratios were quantified. Additionally, the spatial learning and memory of the mice were evaluated by MWM. The (1)H-MRS revealed that mI levels in tg mice were significantly higher at 3 months of age compared to wt mice, while the NAA and Glu levels in 5- and 8-month-old tg mice were significantly decreased (p<0.05). Additionally, significant cognitive changes only occurred at 8 months of age in APP/PS1 tg mice. These results indicated that metabolic changes preceded overt cognitive dysfunctions in early-stage AD, suggesting that (1)H-MRS is a more sensitive biomarker for assessing early AD. PMID:22828014

  1. Age-related differences in neural recruitment during the use of cognitive reappraisal and selective attention as emotion regulation strategies

    PubMed Central

    Allard, Eric S.; Kensinger, Elizabeth A.

    2014-01-01

    The present study examined age differences in the timing and neural recruitment within lateral and medial PFC while younger and older adults hedonically regulated their responses to unpleasant film clips. When analyses focused on activity during the emotional peak of the film clip (the most emotionally salient portion of the film), several age differences emerged. When comparing regulation to passive viewing (combined effects of selective attention and reappraisal) younger adults showed greater regulation related activity in lateral PFC (DLPFC, VLPFC, OFC) and medial PFC (ACC) while older adults showed greater activation within a region DLPFC. When assessing distinct effects of the regulation conditions, an ANOVA revealed a significant Age × Regulation Condition interaction within bilateral DLPFC and ACC; older adults but not young adults showed greater recruitment within these regions for reappraisal than selective attention. When examining activity at the onset of the film clip and at its emotional peak, the timing of reappraisal-related activity within VLPFC differed between age groups: younger adults showed greater activity at film onset while older adults showed heightened activity during the peak. Our results suggest that older adults rely more heavily on PFC recruitment when engaging cognitively demanding reappraisal strategies while PFC-mediated regulation might not be as task-specific for younger adults. Older adults' greater reliance on cognitive control processing during emotion regulation may also be reflected in the time needed to implement these strategies. PMID:24782800

  2. Bereavement and behavioral changes as risk factors for cognitive decline in adults with Down syndrome

    PubMed Central

    Fonseca, Luciana Mascarenhas; de Oliveira, Melaine Cristina; de Figueiredo Ferreira Guilhoto, Laura Maria; Cavalheiro, Esper Abrao; Bottino, Cássio MC

    2014-01-01

    Background Cognitive decline and Alzheimer’s disease often affect older adults with Down syndrome (DS) much earlier than those in the general population. There is also growing evidence of the effects of negative life events on the mental health and behavior of individuals with intellectual disability. However, to our knowledge, this is the first study investigating objective cognitive decline following bereavement in aging individuals with DS. Objective The objective of this study was to determine whether cognitive decline correlates with bereavement following the recent loss of a caregiver or with behavioral changes in a sample of adult individuals with DS who do not meet the criteria for dementia or depression, using the longitudinal assessment of the Cambridge Cognitive Examination (CAMCOG), together with the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Methods We evaluated 18 subjects at baseline and over a follow-up period of 14–22 months, attempting to determine whether cognitive decline correlates with bereavement following the recent loss of the main caregiver or with behavioral changes (as assessed with the Neuropsychiatric Inventory). Results The mean rate of change in CAMCOG was −1.83 (standard deviation 4.51). Behavioral changes had a significant direct influence on cognitive decline. When bereavement was accompanied by behavioral changes, the probability of cognitive decline was 87% (odds ratio 3.82). Conclusion The occurrence of behavioral changes attributed to bereavement following the loss of the primary caregiver significantly increases the probability of cognitive decline in individuals with DS. Longitudinal comparison of the CAMCOG and use of the IQCODE appear to enrich the analysis of cognitive decline in individuals with DS. Further studies involving larger samples are needed in order to corroborate and expand upon our findings, which can have implications for the clinical management of older adults with DS. PMID

  3. Age-related decline in the microstructural integrity of white matter in children with early- and continuously-treated PKU: A DTI study of the corpus callosum☆

    PubMed Central

    White, Desiree A.; Connor, Lisa Tabor; Nardos, Binyam; Shimony, Joshua S.; Archer, Rebecca; Snyder, Abraham Z.; Moinuddin, Asif; Grange, Dorothy K.; Steiner, Robert D.; McKinstry, Robert C.

    2013-01-01

    Structural, volumetric, and microstructural abnormalities have been reported in the white matter of the brain in individuals with phenylketonuria (PKU). Very little research, however, has been conducted to investigate the development of white matter in children with PKU, and the developmental trajectory of their white matter microstructure is unknown. In the current study, diffusion tensor imaging (DTI) was used to examine the development of the microstructural integrity of white matter across six regions of the corpus callosum in 34 children (7–18 years of age) with early- and continuously-treated PKU. Comparison was made with 61 demographically-matched healthy control children. Two DTI variables were examined: mean diffusivity (MD) and relative anisotropy (RA). RA was comparable to that of controls across all six regions of the corpus callosum. In contrast, MD was restricted for children with PKU in anterior (i.e., genu, rostral body, anterior midbody) but not posterior (posterior midbody, isthmus, splenium) regions of the corpus callosum. In addition, MD restriction became more pronounced with increasing age in children with PKU in the two most anterior regions of the corpus callosum (i.e., genu, rostral body). These findings point to an age-related decrement in the microstructural integrity of the anterior white matter of the corpus callosum in children with PKU. PMID:20123469

  4. Age-related decline in multiple unit action potentials of cerebral cortex correlates with the number of lipofuscin-containing neurons.

    PubMed

    Sharma, D; Singh, R

    1996-08-01

    The present study examined whether there is any obvious correlation between the density of lipofuscin-containing neurons and the spontaneous neuronal action potentials (Multiple Unit Activity, MUA) in the parietal cortex of the aging rat brain. The results showed that MUA counts were decreased with age while the number of lipofuscin-containing neurons was increased. The cortex with the highest percentage of lipofuscin-containing neurons had the lowest MUA counts while the cortex with the lowest percentage of lipofuscin-containing neurons had the highest MUA counts. The inverse correlation between MUA and lipofuscin-containing neuron number was also evident when the population of the lipofuscin-containing neurons was pharmacologically altered in vivo by the administration of anti-lipofuscin drug centrophenoxine. The inverse relationship between MUA and the lipofuscin-containing neuron numbers is consistent with: (i) the correlations of MUA with age-related changes in lipid peroxidation and biochemically measured lipofuscin concentration, and (ii) the oxidative stress-induced impairments of neuronal electrophysiology. PMID:8979484

  5. A validated age-related normative model for male total testosterone shows increasing variance but no decline after age 40 years.

    PubMed

    Kelsey, Thomas W; Li, Lucy Q; Mitchell, Rod T; Whelan, Ashley; Anderson, Richard A; Wallace, W Hamish B

    2014-01-01

    The diagnosis of hypogonadism in human males includes identification of low serum testosterone levels, and hence there is an underlying assumption that normal ranges of testosterone for the healthy population are known for all ages. However, to our knowledge, no such reference model exists in the literature, and hence the availability of an applicable biochemical reference range would be helpful for the clinical assessment of hypogonadal men. In this study, using model selection and validation analysis of data identified and extracted from thirteen studies, we derive and validate a normative model of total testosterone across the lifespan in healthy men. We show that total testosterone peaks [mean (2.5-97.5 percentile)] at 15.4 (7.2-31.1) nmol/L at an average age of 19 years, and falls in the average case [mean (2.5-97.5 percentile)] to 13.0 (6.6-25.3) nmol/L by age 40 years, but we find no evidence for a further fall in mean total testosterone with increasing age through to old age. However we do show that there is an increased variation in total testosterone levels with advancing age after age 40 years. This model provides the age related reference ranges needed to support research and clinical decision making in males who have symptoms that may be due to hypogonadism. PMID:25295520

  6. Age-Related Changes in 1/f Neural Electrophysiological Noise

    PubMed Central

    Kramer, Mark A.; Case, John; Lepage, Kyle Q.; Tempesta, Zechari R.; Knight, Robert T.; Gazzaley, Adam

    2015-01-01

    Aging is associated with performance decrements across multiple cognitive domains. The neural noise hypothesis, a dominant view of the basis of this decline, posits that aging is accompanied by an increase in spontaneous, noisy baseline neural activity. Here we analyze data from two different groups of human subjects: intracranial electrocorticography from 15 participants over a 38 year age range (15–53 years) and scalp EEG data from healthy younger (20–30 years) and older (60–70 years) adults to test the neural noise hypothesis from a 1/f noise perspective. Many natural phenomena, including electrophysiology, are characterized by 1/f noise. The defining characteristic of 1/f is that the power of the signal frequency content decreases rapidly as a function of the frequency (f) itself. The slope of this decay, the noise exponent (χ), is often <−1 for electrophysiological data and has been shown to approach white noise (defined as χ = 0) with increasing task difficulty. We observed, in both electrophysiological datasets, that aging is associated with a flatter (more noisy) 1/f power spectral density, even at rest, and that visual cortical 1/f noise statistically mediates age-related impairments in visual working memory. These results provide electrophysiological support for the neural noise hypothesis of aging. SIGNIFICANCE STATEMENT Understanding the neurobiological origins of age-related cognitive decline is of critical scientific, medical, and public health importance, especially considering the rapid aging of the world's population. We find, in two separate human studies, that 1/f electrophysiological noise increases with aging. In addition, we observe that this age-related 1/f noise statistically mediates age-related working memory decline. These results significantly add to this understanding and contextualize a long-standing problem in cognition by encapsulating age-related cognitive decline within a neurocomputational model of 1/f noise

  7. Diet and cognitive decline at middle age: the role of antioxidants.

    PubMed

    Nooyens, Astrid C J; Milder, Ivon E J; van Gelder, Boukje M; Bueno-de-Mesquita, H Bas; van Boxtel, Martin P J; Verschuren, W M Monique

    2015-05-14

    To assess the relationship between dietary intake of antioxidants (vitamin C, vitamin E, β-carotene, lutein, flavonoids and lignans) and cognitive decline at middle age, analyses were performed on data from the population based Doetinchem Cohort Study. Habitual diet and cognitive function were assessed twice with a 5-year interval in 2613 persons aged 43-70 year at baseline (1995-2002). Diet was assessed with a validated 178-item semi-quantitative FFQ. Cognitive function was assessed with a neuropsychological test battery, consisting of the 15 Words Learning Test, the Stroop Test, the Word Fluency test, and the Letter Digit Substitution Test. Scores on global cognitive function, memory, processing speed, and cognitive flexibility were calculated. In regression analyses, quintiles of antioxidant intake were associated with change in cognitive domain scores. Results showed that higher lignan intake was linearly associated with less decline in global cognitive function (P= 0.01), memory (P< 0.01) and processing speed (P= 0.04), with about two times less declines in the highest v. the lowest quintile. In the lowest quintile of vitamin E intake, decline in memory was twice as fast as in all higher quintiles (P< 0.01). Global cognitive decline in the highest lutein intake group was greater than in the lowest intake group (P< 0.05). Higher flavonoid intake was associated with greater decline in cognitive flexibility (P for trend = 0.04). Intakes of other antioxidants were not associated with cognitive decline. We conclude that within the range of a habitual dietary intake, higher intake of lignans is associated with less cognitive decline at middle age. PMID:25851267

  8. Long-term association of food and nutrient intakes with cognitive and functional decline: a 13-year follow-up study of elderly French women.

    PubMed

    Vercambre, Marie-Noël; Boutron-Ruault, Marie-Christine; Ritchie, Karen; Clavel-Chapelon, Françoise; Berr, Claudine

    2009-08-01

    The objective of the present study was to determine the potential long-term impact of dietary habits on age-related decline among 4809 elderly women (born between 1925 and 1930) in the 'Etude Epidémiologique de Femmes de la Mutuelle Générale de l'Education Nationale' (E3N) study, a French epidemiological cohort. In 1993, an extensive diet history self-administered questionnaire was sent to all participants, and in 2006 another questionnaire on instrumental activities of daily living (IADL) and recent cognitive change was sent to a close relative or friend of each woman. Logistic models adjusted for socio-demographic, lifestyle and health factors were performed to evaluate associations between habitual dietary intakes and two outcomes of interest based on the informant response: recent cognitive decline and IADL impairment. Recent cognitive decline was associated with lower intakes of poultry, fish, and animal fats, as well as higher intakes of dairy desserts and ice-cream. IADL impairment was associated with a lower intake of vegetables. The odds of recent cognitive decline increased significantly with decreasing intake of soluble dietary fibre and n-3 fatty acids but with increasing intake of retinol. The odds of IADL impairment increased significantly with decreasing intakes of vitamins B2, B6 and B12. These results are consistent with a possible long-term neuroprotective effect of dietary fibre, n-3 polyunsaturated fats and B-group vitamins, and support dietary intervention to prevent cognitive decline. PMID:19203415

  9. Age-Related Decline in Natural IgM Function: Diversification and Selection of the B-1a Cell Pool with Age.

    PubMed

    Holodick, Nichol E; Vizconde, Teresa; Hopkins, Thomas J; Rothstein, Thomas L

    2016-05-15

    Streptococcus pneumoniae is the most common cause of pneumonia, which claims the lives of people over the age of 65 y seven times more frequently than those aged 5-49 y. B-1a cells provide immediate and essential protection from S. pneumoniae through production of natural Ig, which has minimal insertion of N-region additions added by the enzyme TdT. In experiments with SCID mice infected with S. pneumoniae, we found passive transfer of IgG-depleted serum from aged (18-24 mo old) mice had no effect whereas IgG-depleted serum from young (3 mo old) mice was protective. This suggests protective natural IgM changes with age. Using single cell PCR we found N-region addition, which is initially low in fetal-derived B-1a cell IgM developing in the absence of TdT, increased in 7- to 24-mo-old mice as compared with 3-mo-old mice. To determine the mechanism responsible for the age related change in B-1a cell IgM, we established a mixed chimera system in which mice were reconstituted with allotype-marked mature peritoneal B-1a cells and adult bone marrow cells. We demonstrated even in the presence of mature peritoneal B-1a cells, adult bone marrow contributed to the mature B-1a cell pool. More importantly, using this system we found over a 10-mo-period peritoneal B-1a cell IgM changed, showing the number of cells lacking N-region additions at both junctions fell from 49 to 29% of sequences. These results strongly suggest selection-induced skewing alters B-1a cell-derived natural Ab, which may in turn be responsible for the loss of natural IgM-mediated protection against pneumococcal infection. PMID:27183643

  10. Diabetes and Cognitive Decline: Investigating the Potential Influence of Factors Related to Health Disparities

    PubMed Central

    Crowe, Michael; Sartori, Andrea; Clay, Olivio J.; Wadley, Virginia G.; Andel, Ross; Wang, Hui-Xin; Sawyer, Patricia; Allman, Richard M.

    2010-01-01

    Objectives We investigated whether factors related to health disparities – race, rural residence, education, perceived racial discrimination, vascular disease, and health care access and utilization – may moderate the association between diabetes and cognitive decline. Methods Participants were 624 community-dwelling older adults (49% African American, 49% rural) who completed in-home Mini-Mental State Examination at baseline and four-year follow-up. Results Diabetes at baseline predicted cognitive decline over four years in regression models adjusted for a number of possible confounds. Only perceived discrimination and health utilization showed significant interaction effects with diabetes. Among African Americans who reported experiencing racial discrimination, there was a stronger relationship between diabetes and cognitive decline. Among participants who reported absence of visiting a physician within the past six months, the association between diabetes and cognitive decline was substantially larger. Discussion Findings suggest that factors related to health disparities may influence cognitive outcomes among older adults with diabetes. PMID:20103688

  11. Interactive effect of APOE genotype and blood pressure on cognitive decline: the PATH through life study.

    PubMed

    Andrews, Shea; Das, Debjani; Anstey, Kaarin J; Easteal, Simon

    2015-01-01

    The apolipoprotein E (APOE) *ε4 allele and hypertension are two of the most prevalent risk factors for cognitive decline in later life. Here we investigate whether cognitive decline is affected by interaction between these two risk factors. Specifically, we examine whether APOE*ε4 moderates the association between high blood pressure and cognition in later life. Cognitive function was assessed at three time points over a period of 8 years in 1,474 cognitively normal, community-dwelling adults aged 60-64 years at baseline. Blood pressure and APOE genotype were assessed at baseline. Blood pressure was measured categorically as 'Hypertension' and continuously as 'Mean Arterial Pressure' (MAP). Multilevel models were used to investigate main and interactive effects of APOE genotype and both hypertension and MAP on the rate of change of episodic memory, working memory, verbal ability, perceptual speed, and global cognition. The APOE-hypertension interaction was associated with a small but statistically significant increase in the rate of decline of episodic memory, verbal ability, and global cognition. However, its inclusion in the model did not increase the amount of outcome variation explained beyond that already explained by the effect of time. In contrast, the APOE-MAP interaction had no effect on the rate of decline in any of these domains of cognitive performance. These results provide tentative evidence that APOE genotype moderates the association between high blood pressure and cognitive decline in later life. PMID:25672766

  12. Diffusion tensor imaging correlates of cognitive-motor decline in normal aging and increased Alzheimer's disease risk.

    PubMed

    Hawkins, Kara M; Goyal, Aman I; Sergio, Lauren E

    2015-01-01

    Alzheimer's disease (AD) is typically associated with impairments in memory and other aspects of cognition, while deficits in complex movements are commonly observed later in the course of the disease. Recent studies, however, have indicated that subtle deteriorations in visuomotor control under cognitively demanding conditions may in fact be an early identifying feature of AD. Our previous work has shown that the ability to perform visuomotor tasks that rely on visual-spatial and rule-based transformations is disrupted in prodromal and preclinical AD. Here, in a sample of 30 female participants (10 young: mean age = 26.6 ± 2.7, 10 low AD risk: mean age = 58.7 ± 5.6, and 10 high AD risk: mean age = 58.5 ± 6.9), we test the hypothesis that these cognitive-motor impairments are associated with early AD-related brain alterations. Using diffusion-weighted magnetic resonance imaging, we examined changes in white matter (WM) integrity associated with normal aging and increased AD risk, and assessed the relationship between these underlying WM alterations and cognitive-motor performance. Our whole-brain analysis revealed significant age-related declines in WM integrity, which were more widespread in high relative to low AD risk participants. Furthermore, analysis of mean diffusivity measures within isolated WM clusters revealed a stepwise decline in WM integrity across young, low AD risk, and high AD risk groups. In support of our hypothesis, we also observed that lower WM integrity was associated with poorer cognitive-motor performance. These results are the first to demonstrate a relationship between AD-related WM alterations and impaired cognitive-motor control. The application of these findings may provide a novel clinical strategy for the early detection of individuals at increased AD risk. PMID:25374102

  13. Prospective study of Dietary Approaches to Stop Hypertension– and Mediterranean-style dietary patterns and age-related cognitive change: the Cache County Study on Memory, Health and Aging123

    PubMed Central

    Munger, Ronald G; Cutler, Adele; Quach, Anna; Bowles, Austin; Corcoran, Christopher; Tschanz, JoAnn T; Norton, Maria C; Welsh-Bohmer, Kathleen A

    2013-01-01

    Background: Healthy dietary patterns may protect against age-related cognitive decline, but results of studies have been inconsistent. Objective: We examined associations between Dietary Approaches to Stop Hypertension (DASH)– and Mediterranean-style dietary patterns and age-related cognitive change in a prospective, population-based study. Design: Participants included 3831 men and women ≥65 y of age who were residents of Cache County, UT, in 1995. Cognitive function was assessed by using the Modified Mini-Mental State Examination (3MS) ≤4 times over 11 y. Diet-adherence scores were computed by summing across the energy-adjusted rank-order of individual food and nutrient components and categorizing participants into quintiles of the distribution of the diet accordance score. Mixed-effects repeated-measures models were used to examine 3MS scores over time across increasing quintiles of dietary accordance scores and individual food components that comprised each score. Results: The range of rank-order DASH and Mediterranean diet scores was 1661–25,596 and 2407–26,947, respectively. Higher DASH and Mediterranean diet scores were associated with higher average 3MS scores. People in quintile 5 of DASH averaged 0.97 points higher than those in quintile 1 (P = 0.001). The corresponding difference for Mediterranean quintiles was 0.94 (P = 0.001). These differences were consistent over 11 y. Higher intakes of whole grains and nuts and legumes were also associated with higher average 3MS scores [mean quintile 5 compared with 1 differences: 1.19 (P < 0.001), 1.22 (P < 0.001), respectively]. Conclusions: Higher levels of accordance with both the DASH and Mediterranean dietary patterns were associated with consistently higher levels of cognitive function in elderly men and women over an 11-y period. Whole grains and nuts and legumes were positively associated with higher cognitive functions and may be core neuroprotective foods common to various healthy plant

  14. Neuropsychological Practice Effects in the Context of Cognitive Decline: Contributions from Learning and Task Novelty.

    PubMed

    Thorgusen, Sommer R; Suchy, Yana; Chelune, Gordon J; Baucom, Brian R

    2016-04-01

    Although cognitive decline is typically associated with decreasing practice effects (PEs) (presumably due to declining memory), some studies show increased PEs with declines in cognition. One explanation for these inconsistencies is that PEs reflect not only memory, but also rebounds from adapting to task novelty (i.e., novelty effect), leading to increased PEs. We examined a theoretical model of relationships among novelty effects, memory, cognitive decline, and within-session PEs. Sixty-six older adults ranging from normal to severely impaired completed measures of memory, novelty effects, and two trials each of Wechsler Adult Intelligence Scale, 4 th Edition Symbol Search and Coding. Interrelationships among variables were examined using regression analyses. PEs for Symbol Search and Coding (a) were related to different proposed PE components (i.e., memory and novelty effects), such that novelty effect predicted Symbol Search PE (R 2 =.239, p<.001) and memory predicted Coding PE (R 2 =.089, p=.015), and (b) showed different patterns across stages of cognitive decline, such that the greatest cognitive decline was associated with smallest Coding PE (R 2 =.125, p=.004), whereas intermediate cognitive decline was associated with the greatest Symbol Search PE (R 2 =.097, p=.040). The relationship between cognitive decline and PE for Symbol Search was partially mediated by novelty effect among older adults with abnormal cognitive decline (model R 2 =.286, p<.001). These findings (a) suggest that PE is not a unitary construct, (b) offer an explanation for contradictory findings in the literature, and (c) highlight the need for a better understanding of component processes of PE across different neuropsychological measures. (JINS, 2016, 22, 453-466). PMID:26790693

  15. Cognitive decline and oral health in middle-aged adults in the ARIC study.

    PubMed

    Naorungroj, S; Slade, G D; Beck, J D; Mosley, T H; Gottesman, R F; Alonso, A; Heiss, G

    2013-09-01

    Even before dementia becomes apparent, cognitive decline may contribute to deterioration in oral health. This cohort study of middle-aged adults evaluated associations of six-year change in cognitive function with oral health behaviors and conditions in the Atherosclerosis Risk in Communities (ARIC) study. Cognitive function was measured at study visits in 1990-1992 and 1996-1998 with three tests: (a) Delayed Word Recall (DWR), (b) Digit Symbol Substitution (DSS), and (c) Word Fluency (WF). Cognitive decline scores were computed as 'studentized' residuals of 1996-1998 scores regressed against 1990-1992 scores. In 1996-1998, 10,050 participants answered dental screening questions, and 5,878 of 8,782 dentate participants received a comprehensive oral examination. Multiple regression models used cognitive change to predict oral health behaviors and conditions with adjustment for covariates. In the fully adjusted models, greater decline in all three measures of cognitive function was associated with increased odds of complete tooth loss. Greater decline in DSS and WF scores was associated with infrequent toothbrushing. Decline in WF scores was also associated with higher plaque levels. In these middle-aged adults, six-year cognitive decline was modestly associated with less frequent toothbrushing, plaque deposit, and greater odds of edentulism, but not with other oral behaviors or diseases. PMID:23872988

  16. Cognitive Decline and Oral Health in Middle-aged Adults in the ARIC Study

    PubMed Central

    Naorungroj, S.; Slade, G.D.; Beck, J.D.; Mosley, T.H.; Gottesman, R.F.; Alonso, A.; Heiss, G.

    2013-01-01

    Even before dementia becomes apparent, cognitive decline may contribute to deterioration in oral health. This cohort study of middle-aged adults evaluated associations of six-year change in cognitive function with oral health behaviors and conditions in the Atherosclerosis Risk in Communities (ARIC) study. Cognitive function was measured at study visits in 1990-1992 and 1996-1998 with three tests: (a) Delayed Word Recall (DWR), (b) Digit Symbol Substitution (DSS), and (c) Word Fluency (WF). Cognitive decline scores were computed as ‘studentized’ residuals of 1996-1998 scores regressed against 1990-1992 scores. In 1996-1998, 10,050 participants answered dental screening questions, and 5,878 of 8,782 dentate participants received a comprehensive oral examination. Multiple regression models used cognitive change to predict oral health behaviors and conditions with adjustment for covariates. In the fully adjusted models, greater decline in all three measures of cognitive function was associated with increased odds of complete tooth loss. Greater decline in DSS and WF scores was associated with infrequent toothbrushing. Decline in WF scores was also associated with higher plaque levels. In these middle-aged adults, six-year cognitive decline was modestly associated with less frequent toothbrushing, plaque deposit, and greater odds of edentulism, but not with other oral behaviors or diseases. PMID:23872988

  17. Acetyl-L-carnitine supplementation reverses the age-related decline in carnitine palmitoyltransferase 1 (CPT1) activity in interfibrillar mitochondria without changing the L-carnitine content in the rat heart.

    PubMed

    Gómez, Luis A; Heath, Shi-Hua D; Hagen, Tory M

    2012-01-01

    The aging heart displays a loss of bioenergetic reserve capacity partially mediated through lower fatty acid utilization. We investigated whether the age-related impairment of cardiac fatty acid catabolism occurs, at least partially, through diminished levels of L-carnitine, which would adversely affect carnitine palmitoyltransferase 1 (CPT1), the rate-limiting enzyme for fatty acyl-CoA uptake into mitochondria for β-oxidation. Old (24-28 mos) Fischer 344 rats were fed±acetyl-L-carnitine (ALCAR; 1.5% [w/v]) for up to four weeks prior to sacrifice and isolation of cardiac interfibrillar (IFM) and subsarcolemmal (SSM) mitochondria. IFM displayed a 28% (p<0.05) age-related loss of CPT1 activity, which correlated with a decline (41%, p<0.05) in palmitoyl-CoA-driven state 3 respiration. Interestingly, SSM had preserved enzyme function and efficiently utilized palmitate. Analysis of IFM CPT1 kinetics showed both diminished V(max) and K(m) (60% and 49% respectively, p<0.05) when palmitoyl-CoA was the substrate. However, no age-related changes in enzyme kinetics were evident with respect to L-carnitine. ALCAR supplementation restored CPT1 activity in heart IFM, but not apparently through remediation of L-carnitine levels. Rather, ALCAR influenced enzyme activity over time, potentially by modulating conditions in the aging heart that ultimately affect palmitoyl-CoA binding and CPT1 kinetics. PMID:22322067

  18. Acetyl-L-carnitine supplementation reverses the age-related decline in carnitine palmitoyltransferase 1 (CPT1) activity in interfibrillar mitochondria without changing the L-carnitine content in the rat heart

    PubMed Central

    Gómez, Luis A.; Heath, Shi-Hua D.; Hagen, Tory M.

    2014-01-01

    The aging heart displays a loss of bioenergetic reserve capacity partially mediated through lower fatty acid utilization. We investigated whether the age-related impairment of cardiac fatty acid catabolism occurs, at least partially, through diminished levels of L-carnitine, which would adversely affect carnitine palmitoyltransferase 1 (CPT1), the rate-limiting enzyme for fatty acyl-CoA uptake into mitochondria for β-oxidation. Old (24–28 mos) Fischer 344 rats were fed ± acetyl-L-carnitine (ALCAR; 1.5% [w/v]) for up to four weeks prior to sacrifice and isolation of cardiac interfibrillar (IFM) and subsarcolemmal (SSM) mitochondria. IFM displayed a 28% (p < 0.05) age-related loss of CPT1 activity, which correlated with a decline (41%, p < 0.05) in palmitoyl-CoA-driven state 3 respiration. Interestingly, SSM had preserved enzyme function and efficiently utilized palmitate. Analysis of IFM CPT1 kinetics showed both diminished Vmax and Km (60% and 49% respectively, p < 0.05) when palmitoyl-CoA was the substrate. However, no age-related changes in enzyme kinetics were evident with respect to L-carnitine. ALCAR supplementation restored CPT1 activity in heart IFM, but not apparently through remediation of L-carnitine levels. Rather, ALCAR influenced enzyme activity over time, potentially by modulating conditions in the aging heart that ultimately affect palmitoyl-CoA binding and CPT1 kinetics. PMID:22322067

  19. Pattern and Rate of Cognitive Decline in Cerebral Small Vessel Disease: A Prospective Study

    PubMed Central

    Lawrence, Andrew J.; Brookes, Rebecca L.; Zeestraten, Eva A.; Barrick, Thomas R.; Morris, Robin G.; Markus, Hugh S.

    2015-01-01

    Objectives Cognitive impairment, predominantly affecting processing speed and executive function, is an important consequence of cerebral small vessel disease (SVD). To date, few longitudinal studies of cognition in SVD have been conducted. We determined the pattern and rate of cognitive decline in SVD and used the results to determine sample size calculations for clinical trials of interventions reducing cognitive decline. Methods 121 patients with MRI confirmed lacunar stroke and leukoaraiosis were enrolled into the prospective St George’s Cognition And Neuroimaging in Stroke (SCANS) study. Patients attended one baseline and three annual cognitive assessments providing 36 month follow-up data. Neuropsychological assessment comprised a battery of tests assessing working memory, long-term (episodic) memory, processing speed and executive function. We calculated annualized change in cognition for the 98 patients who completed at least two time-points. Results Task performance was heterogeneous, but significant cognitive decline was found for the executive function index (p<0.007). Working memory and processing speed decreased numerically, but not significantly. The executive function composite score would require the smallest samples sizes for a treatment trial with an aim of halting decline, but this would still require over 2,000 patients per arm to detect a 30% difference with power of 0.8 over a three year follow-up. Conclusions The pattern of cognitive decline seen in SVD over three years is consistent with the pattern of impairments at baseline. Rates of decline were slow and sample sizes would need to be large for clinical trials aimed at halting decline beyond initial diagnosis using cognitive scores as an outcome measure. This emphasizes the importance of more sensitive surrogate markers in this disease. PMID:26273828

  20. A phytochemical-rich diet may explain the absence of age-related decline in visual acuity of Amazonian hunter-gatherers in Ecuador.

    PubMed

    London, Douglas S; Beezhold, Bonnie

    2015-02-01

    Myopia is absent in undisturbed hunter-gatherers but ubiquitous in modern populations. The link between dietary phytochemicals and eye health is well established, although transition away from a wild diet has reduced phytochemical variety. We hypothesized that when larger quantities and greater variety of wild, seasonal phytochemicals are consumed in a food system, there will be a reduced prevalence of degenerative-based eye disease as measured by visual acuity. We compared food systems and visual acuity across isolated Amazonian Kawymeno Waorani hunter-gatherers and neighboring Kichwa subsistence agrarians, using dietary surveys, dietary pattern observation, and Snellen Illiterate E visual acuity examinations. Hunter-gatherers consumed more food species (130 vs. 63) and more wild plants (80 vs. 4) including 76 wild fruits, thereby obtaining larger variety and quantity of phytochemicals than agrarians. Visual acuity was inversely related to age only in agrarians (r = -.846, P < .001). As hypothesized, when stratified by age (<40 and ≥ 40 years), Mann-Whitney U tests revealed that hunter-gatherers maintained high visual acuity throughout life, whereas agrarian visual acuity declined (P values < .001); visual acuity of younger participants was high across the board, however, did not differ between groups (P > .05). This unusual absence of juvenile-onset vision problems may be related to local, organic, whole food diets of subsistence food systems isolated from modern food production. Our results suggest that intake of a wider variety of plant foods supplying necessary phytochemicals for eye health may help maintain visual acuity and prevent degenerative eye conditions as humans age. PMID:25636674

  1. Hippocampal Subregions Exhibit Both Distinct and Shared Transcriptomic Responses to Aging and Nonneurodegenerative Cognitive Decline

    PubMed Central

    Masser, Dustin R.; Bixler, Georgina V.; Brucklacher, Robert M.; Yan, Han; Giles, Cory B.; Wren, Jonathan D.; Sonntag, William E.

    2014-01-01

    Impairment of hippocampal-dependent spatial learning and memory with aging affects a large segment of the aged population. Hippocampal subregions (CA1, CA3, and DG) have been previously reported to express both common and specific morphological, functional, and gene/protein alterations with aging and cognitive decline. To comprehensively assess gene expression with aging and cognitive decline, transcriptomic analysis of CA1, CA3, and DG was conducted using Adult (12M) and Aged (26M) F344xBN rats behaviorally characterized by Morris water maze performance. Each subregion demonstrated a specific pattern of responses with aging and with cognitive performance. The CA1 and CA3 demonstrating the greatest degree of shared gene expression changes. Analysis of the pathways, processes, and regulators of these transcriptomic changes also exhibit a similar pattern of commonalities and differences across subregions. Gene expression changes between Aged cognitively Intact and Aged cognitively Impaired rats often showed an inversion of the changes between Adult and Aged rats. This failure to adapt rather than an exacerbation of the aging phenotype questions a conventional view that cognitive decline is exaggerated aging. These results are a resource for investigators studying cognitive decline and also demonstrate the need to individually examine hippocampal subregions in molecular analyses of aging and cognitive decline. PMID:24994846

  2. Hippocampal subregions exhibit both distinct and shared transcriptomic responses to aging and nonneurodegenerative cognitive decline.

    PubMed

    Masser, Dustin R; Bixler, Georgina V; Brucklacher, Robert M; Yan, Han; Giles, Cory B; Wren, Jonathan D; Sonntag, William E; Freeman, Willard M

    2014-11-01

    Impairment of hippocampal-dependent spatial learning and memory with aging affects a large segment of the aged population. Hippocampal subregions (CA1, CA3, and DG) have been previously reported to express both common and specific morphological, functional, and gene/protein alterations with aging and cognitive decline. To comprehensively assess gene expression with aging and cognitive decline, transcriptomic analysis of CA1, CA3, and DG was conducted using Adult (12M) and Aged (26M) F344xBN rats behaviorally characterized by Morris water maze performance. Each subregion demonstrated a specific pattern of responses with aging and with cognitive performance. The CA1 and CA3 demonstrating the greatest degree of shared gene expression changes. Analysis of the pathways, processes, and regulators of these transcriptomic changes also exhibit a similar pattern of commonalities and differences across subregions. Gene expression changes between Aged cognitively Intact and Aged cognitively Impaired rats often showed an inversion of the changes between Adult and Aged rats. This failure to adapt rather than an exacerbation of the aging phenotype questions a conventional view that cognitive decline is exaggerated aging. These results are a resource for investigators studying cognitive decline and also demonstrate the need to individually examine hippocampal subregions in molecular analyses of aging and cognitive decline. PMID:24994846

  3. Structural Neuroimaging Markers of Cognitive Decline in Parkinson's Disease

    PubMed Central

    Hanganu, Alexandru; Monchi, Oury

    2016-01-01

    Cognitive impairment in patients with Parkinson's disease is a major challenge since it has been established that 25 to 40% of patients will develop cognitive impairment early in the disease. Furthermore, it has been reported that up to 80% of Parkinsonian patients will eventually develop dementia. Thus, it is important to improve the diagnosing procedures in order to detect cognitive impairment at early stages of development and to delay as much as possible the developing of dementia. One major challenge is that patients with mild cognitive impairment exhibit measurable cognitive deficits according to recently established criteria, yet those deficits are not severe enough to interfere with daily living, hence being avoided by patients, and might be overseen by clinicians. Recent advances in neuroimaging brain analysis allowed the establishment of several anatomical markers that have the potential to be considered for early detection of cognitive impairment in Parkinsonian patients. This review aims to outline the neuroimaging possibilities in diagnosing cognitive impairment in patients with Parkinson's disease and to take into consideration the near-future possibilities of their implementation into clinical practice. PMID:27190672

  4. Antibodies to myelin basic protein are associated with cognitive decline after stroke.

    PubMed

    Becker, Kyra J; Tanzi, Patricia; Zierath, Dannielle; Buckwalter, Marion S

    2016-06-15

    B lymphocytes cause post-stroke cognitive decline in mice. We therefore evaluated the association between autoantibodies and post-stroke cognitive decline in a prospectively collected human cohort. The mini-mental state exam (MMSE) was administered 30, 90, 180, and 365days after stroke. Antibody titers to myelin basic protein (MBP), proteolipid protein, and several non-specific proteins were determined. Among 58 subjects with initial MMSE≥20 and at least 2 MMSE examinations in the year after stroke, cognitive decline (MMSE decrease ≥2) occurred in 10 (17%) subjects. In multivariate analysis, MBP antibody titers were the only independent predictor of cognitive decline (OR=9.02 [1.18, 68.90]; P=0.03). PMID:27235342

  5. Aberrant hippocampal neurogenesis contributes to epilepsy and associated cognitive decline.

    PubMed

    Cho, Kyung-Ok; Lybrand, Zane R; Ito, Naoki; Brulet, Rebecca; Tafacory, Farrah; Zhang, Ling; Good, Levi; Ure, Kerstin; Kernie, Steven G; Birnbaum, Shari G; Scharfman, Helen E; Eisch, Amelia J; Hsieh, Jenny

    2015-01-01

    Acute seizures after a severe brain insult can often lead to epilepsy and cognitive impairment. Aberrant hippocampal neurogenesis follows the insult but the role of adult-generated neurons in the development of chronic seizures or associated cognitive deficits remains to be determined. Here we show that the ablation of adult neurogenesis before pilocarpine-induced acute seizures in mice leads to a reduction in chronic seizure frequency. We also show that ablation of neurogenesis normalizes epilepsy-associated cognitive deficits. Remarkably, the effect of ablating adult neurogenesis before acute seizures is long lasting as it suppresses chronic seizure frequency for nearly 1 year. These findings establish a key role of neurogenesis in chronic seizure development and associated memory impairment and suggest that targeting aberrant hippocampal neurogenesis may reduce recurrent seizures and restore cognitive function following a pro-epileptic brain insult. PMID:25808087

  6. Aberrant hippocampal neurogenesis contributes to epilepsy and associated cognitive decline

    PubMed Central

    Cho, Kyung-Ok; Lybrand, Zane R.; Ito, Naoki; Brulet, Rebecca; Tafacory, Farrah; Zhang, Ling; Good, Levi; Ure, Kerstin; Kernie, Steven G.; Birnbaum, Shari G.; Scharfman, Helen E.; Eisch, Amelia J.; Hsieh, Jenny

    2015-01-01

    Acute seizures after a severe brain insult can often lead to epilepsy and cognitive impairment. Aberrant hippocampal neurogenesis follows the insult but the role of adult-generated neurons in the development of chronic seizures or associated cognitive deficits remains to be determined. Here we show that the ablation of adult neurogenesis before pilocarpine-induced acute seizures in mice leads to a reduction in chronic seizure frequency. We also show that ablation of neurogenesis normalizes epilepsy-associated cognitive deficits. Remarkably, the effect of ablating adult neurogenesis before acute seizures is long lasting as it suppresses chronic seizure frequency for nearly 1 year. These findings establish a key role of neurogenesis in chronic seizure development and associated memory impairment and suggest that targeting aberrant hippocampal neurogenesis may reduce recurrent seizures and restore cognitive function following a pro-epileptic brain insult. PMID:25808087

  7. A 29-year-old female with progressive myoclonus and cognitive decline.

    PubMed

    Taylor, D; Haynes, H R; Graham, A; Gerhand, S; Kurian, K M

    2013-01-01

    Myoclonic epilepsy with red ragged fibres (MERRF) is a rare mitochondrial disorder presenting with progressive myoclonus, epilepsy, and cognitive decline. Here, the authors present a case of a 29-year-old lady presenting with myoclonus and describe the subsequent investigations that led to a diagnosis of MERRF. In addition, we examine her cognitive decline over a 9-year period, demonstrating a feature commonly seen in mitochondrial cytopathies. PMID:23662223

  8. Treatment of cardiovascular risk factors to prevent cognitive decline and dementia: a systematic review

    PubMed Central

    Ligthart, Suzanne A; Moll van Charante, Eric P; Van Gool, Willem A; Richard, Edo

    2010-01-01

    Background: Over the last decade, evidence has accumulated that vascular risk factors increase the risk of Alzheimer disease (AD). So far, few randomized controlled trials have focused on lowering the vascular risk profile to prevent or postpone cognitive decline or dementia. Objective: To systematically perform a review of randomized controlled trials (RCTs) evaluating drug treatment effects for cardiovascular risk factors on the incidence of dementia or cognitive decline. Selection criteria: RCTs studying the effect of treating hypertension, dyslipidemia, hyperhomocysteinemia, obesity, or diabetes mellitus (DM) on cognitive decline or dementia, with a minimum follow-up of 1 year in elderly populations. Outcome measure: Cognitive decline or incident dementia. Main results: In the identified studies, dementia was never the primary outcome. Statins (2 studies) and intensified control of type II DM (1 study) appear to have no effect on prevention of cognitive decline. Studies on treatment of obesity are lacking, and the results of lowering homocysteine (6 studies) are inconclusive. There is some evidence of a preventive effect of antihypertensive medication (6 studies), but results are inconsistent. Conclusion: The evidence of a preventive treatment effect aimed at vascular risk factors on cognitive decline and dementia in later life is scarce and mostly based on secondary outcome parameters. Several important sources of bias such as differential dropout may importantly affect interpretation of trial results. PMID:20859546

  9. C-reactive protein and genetic variants and cognitive decline in old age: The PROSPER Study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plasma concentrations of C-reactive protein (CRP), a marker of chronic inflammation, have been associated with cognitive impairment in old age. However, it is unknown whether CRP is causally linked to cognitive decline. Within the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) tri...

  10. The role of B-vitamins in preventing and treating cognitive impairment and decline

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Many epidemiologic studies have considered the question of whether markers of B-vitamin status are associated with cognitive function and cognitive decline. This avenue of research was sparked by the homocysteine (Hcy) theory of cardiovascular disease (CVD), which was extended to Alzheimer’s disease...

  11. HOMOCYSTEINE AND COGNITIVE DECLINE: EVIDENCE FROM POPULATION STUDIES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Elevated homocysteine has been associated with cognitive impairment and Alzheimer's disease. However, it remains unclear if observed associations are causal and, if so, what the mechanisms are. Because the effects of homocysteine on the vasculature that contribute to heart disease and stroke are a...

  12. Correcting Bias Caused by Missing Data in the Estimate of the Effect of Apolipoprotein ε4 on Cognitive Decline.

    PubMed

    Hall, Charles B; Lipton, Richard B; Katz, Mindy J; Wang, Cuiling

    2015-01-01

    Longitudinal administration of neuropsychological instruments are often used to assess age-related changes in cognition. Informative loss to follow-up may bias the results of these studies. Herein, we use auxiliary data to adjust for informative loss to follow-up. In the Einstein Aging Study, memory was assessed annually in a community sample of adults age 70+, free of dementia at baseline, using the free recall from the Free and Cued Selective Reminding Test, and via telephone using the Memory Impairment Screen for Telephone (the auxiliary data). Joint linear mixed models were used to assess how the effect of the APOE ε4 genotype may be affected by informative missingness in the in-person data. A total of 620 EAS participants contributed 2085 person years of follow-up to the analyses. Memory decline rates estimated in joint models were 19% greater in ε4 negative participants and 27% greater in ε4 positive participants compared to traditional approaches; the effect of APOE ε4 on memory decline was 37% greater. Joint modeling methods can help address bias caused by informative missing data in the estimation of the effect of risk factors on cognitive change, and may be applicable to a broader range of outcomes in longitudinal aging studies. PMID:25389642

  13. A systematic review of cognitive decline in dementia with Lewy bodies versus Alzheimer’s disease

    PubMed Central

    2014-01-01

    Introduction The aim of this review was to investigate whether there is a faster cognitive decline in dementia with Lewy bodies (DLB) than in Alzheimer’s disease (AD) over time. Methods PsycINFO and Medline were searched from 1946 to February 2013. A quality rating from 1 to 15 (best) was applied to the included studies. A quantitative meta-analysis was done on studies with mini mental state examination (MMSE) as the outcome measure. Results A total of 18 studies were included. Of these, six (36%) reported significant differences in the rate of cognitive decline. Three studies reported a faster cognitive decline on MMSE in patients with mixed DLB and AD compared to pure forms, whereas two studies reported a faster decline on delayed recall and recognition in AD and one in DLB on verbal fluency. Mean quality scores for studies that did or did not differ were not significantly different. Six studies reported MMSE scores and were included in the meta-analysis, which showed no significant difference in annual decline on MMSE between DLB (mean 3.4) and AD (mean 3.3). Conclusions Our findings do not support the hypothesis of a faster rate of cognitive decline in DLB compared to AD. Future studies should apply recent diagnostic criteria, as well as extensive diagnostic evaluation and ideally autopsy diagnosis. Studies with large enough samples, detailed cognitive tests, at least two years follow up and multivariate statistical analysis are also needed. PMID:25478024

  14. Education does not slow cognitive decline with aging: 12-year evidence from the victoria longitudinal study.

    PubMed

    Zahodne, Laura B; Glymour, M Maria; Sparks, Catharine; Bontempo, Daniel; Dixon, Roger A; MacDonald, Stuart W S; Manly, Jennifer J

    2011-11-01

    Although the relationship between education and cognitive status is well-known, evidence regarding whether education moderates the trajectory of cognitive change in late life is conflicting. Early studies suggested that higher levels of education attenuate cognitive decline. More recent studies using improved longitudinal methods have not found that education moderates decline. Fewer studies have explored whether education exerts different effects on longitudinal changes within different cognitive domains. In the present study, we analyzed data from 1014 participants in the Victoria Longitudinal Study to examine the effects of education on composite scores reflecting verbal processing speed, working memory, verbal fluency, and verbal episodic memory. Using linear growth models adjusted for age at enrollment (range, 54-95 years) and gender, we found that years of education (range, 6-20 years) was strongly related to cognitive level in all domains, particularly verbal fluency. However, education was not related to rates of change over time for any cognitive domain. Results were similar in individuals older or younger than 70 at baseline, and when education was dichotomized to reflect high or low attainment. In this large longitudinal cohort, education was related to cognitive performance but unrelated to cognitive decline, supporting the hypothesis of passive cognitive reserve with aging. PMID:21923980

  15. Education Does Not Slow Cognitive Decline with Aging: 12-Year Evidence from the Victoria Longitudinal Study

    PubMed Central

    Zahodne, L.B.; Glymour, M.M.; Sparks, C.; Bontempo, D.; Dixon, R.A.; MacDonald, S.W.S.; Manly, J.J.

    2012-01-01

    Although the relationship between education and cognitive status is well-known, evidence regarding whether education moderates the trajectory of cognitive change in late life is conflicting. Early studies suggested that higher levels of education attenuate cognitive decline. More recent studies using improved longitudinal methods have not found that education moderates decline. Few studies have explored whether education exerts different effects on longitudinal changes within different cognitive domains. In the present study, we analyzed data from 1,023 participants in the Victoria Longitudinal Study to examine the effects of education on composite scores reflecting verbal processing speed, working memory, verbal fluency, and verbal episodic memory. Using linear growth models adjusted for age at enrollment (range: 55–94) and gender, we found that years of education (range: 6–20) was strongly related to cognitive level in all domains, particularly verbal fluency. However, education was not related to rates of change over time for any cognitive domain. Results were similar in individuals older or younger than 70 at baseline, and when education was dichotomized to reflect high or low attainment. In this large longitudinal cohort, education was related to cognitive performance but unrelated to cognitive decline, supporting the hypothesis of passive cognitive reserve with aging. PMID:21923980

  16. Pulse Pressure and Cognitive Decline in Stroke Patients With White Matter Changes.

    PubMed

    Wang, Zhaolu; Wong, Adrian; Liu, Wenyan; Yang, Jie; Chu, Winnie C W; Au, Lisa; Lau, Alexander; Xiong, Yunyun; Mok, Vincent C T

    2015-09-01

    The authors hypothesized that both high and low pulse pressure (PP) may predict cognitive decline in stroke/transient ischemic attack (TIA) patients with white matter changes (WMCs). The authors prospectively followed up 406 ischemic stroke/TIA patients with confluent WMCs over 18 months. PP was measured at 3 to 6 months after stroke/TIA and categorized into four groups by quartile. Cognition was assessed 3 to 6 months and 15 to 18 months after stroke/TIA using the Clinical Dementia Rating and Mini-Mental State Examination (MMSE). Logistic regression showed that patients in the first quartile of PP had a 5.9-fold higher risk for developing cognitive decline than patients in the third quartile (odds ratio, 5.9; 95% confidence interval, 1.7-20.6), while patients in the fourth quartile had a 3.5-fold higher risk for cognitive decline than those in the third quartile (odds ratio, 3.5; 95% confidence interval, 1.0-12.4). This U-shaped relationship was also evident between PP and cognitive decline in MMSE, underlining the role of arterial stiffness and hypoperfusion in cognitive decline related to small vessel disease. PMID:26033405

  17. Hippocampal Extracellular Matrix Levels and Stochasticity in Synaptic Protein Expression Increase with Age and Are Associated with Age-dependent Cognitive Decline*

    PubMed Central

    Végh, Marlene J.; Rausell, Antonio; Loos, Maarten; Heldring, Céline M.; Jurkowski, Wiktor; van Nierop, Pim; Paliukhovich, Iryna; Li, Ka Wan; del Sol, Antonio; Smit, August B.; Spijker, Sabine; van Kesteren, Ronald E.

    2014-01-01

    Age-related cognitive decline is a serious health concern in our aging society. Decreased cognitive function observed during healthy brain aging is most likely caused by changes in brain connectivity and synaptic dysfunction in particular brain regions. Here we show that aged C57BL/6J wild-type mice have hippocampus-dependent spatial memory impairments. To identify the molecular mechanisms that are relevant to these memory deficits, we investigated the temporal profile of mouse hippocampal synaptic proteome changes at 20, 40, 50, 60, 70, 80, 90, and 100 weeks of age. Extracellular matrix proteins were the only group of proteins that showed robust and progressive up-regulation over time. This was confirmed by immunoblotting and histochemical analysis, which indicated that the increased levels of hippocampal extracellular matrix might limit synaptic plasticity as a potential cause of age-related cognitive decline. In addition, we observed that stochasticity in synaptic protein expression increased with age, in particular for proteins that were previously linked with various neurodegenerative diseases, whereas low variance in expression was observed for proteins that play a basal role in neuronal function and synaptic neurotransmission. Together, our findings show that both specific changes and increased variance in synaptic protein expression are associated with aging and may underlie reduced synaptic plasticity and impaired cognitive performance in old age. PMID:25044018

  18. Age Related Decline in Postural Control Mechanisms.

    ERIC Educational Resources Information Center

    Stelmach, George E.; And Others

    1989-01-01

    Studied voluntary and reflexive mechanisms of postural control of young (N=8) and elderly (N=8) adults through measurement of reflexive reactions to large-fast and small-slow ankle rotation postural disturbances. Found reflexive mechanisms relatively intact for both groups although elderly appeared more disadvantaged when posture was under the…

  19. Age-Related Declines Evident Before 60

    MedlinePlus

    ... Services, or federal policy. More Health News on: Exercise for Seniors Healthy Aging Recent Health News Related MedlinePlus Health Topics Exercise for Seniors Healthy Aging About MedlinePlus Site Map FAQs Contact Us Get ...

  20. Global cognitive decline in schizophrenia with remission of symptoms?

    PubMed

    Barbarotto, R; Castignoli, G; Pasetti, C; Laiacona, M

    2001-01-01

    The relation of symptoms to cognitive dysfunction in schizophrenia is still controversial. This study was aimed (i) at verifying if a homogeneous sample of 10 young treated outpatients in remission from psychotic symptoms displays a characteristic pattern of cognitive dysfunction and (ii) at testing the issue of a general cognitive impairment. The neuropsychological performance of the patients was confronted with a large control group by means of Equivalent Scores, a normative method widely used in Italy, which allows direct, reliable comparison between tests and between patients. We found that our patients, as a group, were affected by a basic activation deficit in attention and by a semantic impairment. These deficits in symptom-free patients could indicate that their brains are in some ways working differently from those of normal controls and that this pattern is not necessarily linked to psychotic symptoms: their neuropsychological impairment might reflect a basic difference in the way of processing information that is always present and is independent of general intellectual decay. PMID:11527351

  1. Physical Exercise-Induced Adult Neurogenesis: A Good Strategy to Prevent Cognitive Decline in Neurodegenerative Diseases?

    PubMed Central

    Yau, Suk-yu; Christie, Brian R.; So, Kwok-fai

    2014-01-01

    Cumulative evidence has indicated that there is an important role for adult hippocampal neurogenesis in cognitive function. With the increasing prevalence of cognitive decline associated with neurodegenerative diseases among the ageing population, physical exercise, a potent enhancer of adult hippocampal neurogenesis, has emerged as a potential preventative strategy/treatment to reduce cognitive decline. Here we review the functional role of adult hippocampal neurogenesis in learning and memory, and how this form of structural plasticity is altered in neurodegenerative diseases known to involve cognitive impairment. We further discuss how physical exercise may contribute to cognitive improvement in the ageing brain by preserving adult neurogenesis, and review the recent approaches for measuring changes in neurogenesis in the live human brain. PMID:24818140

  2. Cognitive decline and brain volume loss are signatures of cerebral Aβ deposition identified with PIB

    PubMed Central

    Storandt, Martha; Mintun, Mark A.; Head, Denise; Morris, John C.

    2009-01-01

    Objective To examine the relation of amyloid-beta (Aβ) levels in cerebral cortex with structural brain integrity and cognitive performance in older people with a Clinical Dementia Rating (CDR) of 0 (cognitively normal). Methods The relations between mean cortical [11C] PIB binding potential values, proportional to the density of fibrillar Aβ binding sites in the brain, concurrent regional brain volumes as assessed by magnetic resonance imaging, and both concurrent and longitudinal (up to 19 years) cognitive performance in multiple domains were examined in 135 CDR 0 individuals aged 65 to 88 years. Results Elevated cerebral Aβ levels, in some cases comparable to that seen in individuals with Alzheimer's disease, were observed in 29 CDR 0 individuals. Significantly smaller regional volumes in the hippocampus, temporal neocortex, anterior cingulate, and posterior cingulate were observed in these CDR 0 individuals with elevated Aβ levels. Concurrent cognitive performance was unrelated to Aβ levels but was related to regional brain volumes with the exception of caudate. Longitudinal cognitive decline was associated with elevated Aβ levels and decreased hippocampal volume. Decline was not limited to episodic memory but included working memory and visuospatial abilities as well. Interpretation [11C] PIB, an in vivo measure of cerebral amyloidosis, is associated with regionally specific brain atrophy cross-sectionally and a pattern of longitudinal cognitive decline in multiple cognitive domains that occurs prior to the clinical diagnosis of Alzheimer' disease. These findings contribute to the understanding of the cognitive and structural consequences of Aβ levels in CDR 0 older adults. PMID:20008651

  3. Association of Lifetime Intellectual Enrichment with Cognitive Decline in the Older Population

    PubMed Central

    Vemuri, Prashanthi; Lesnick, Timothy G.; Przybelski, Scott A.; Machulda, Mary; Knopman, David S.; Mielke, Michelle M.; Roberts, Rosebud O.; Geda, Yonas E.; Rocca, Walter A.; Petersen, Ronald C.; Jack, Clifford R.

    2014-01-01

    IMPORTANCE Intellectual lifestyle enrichment throughout life is increasingly viewed as a protective strategy against commonly observed cognitive decline in the elderly. OBJECTIVE To investigate the association of lifetime intellectual enrichment with baseline cognitive performance and rate of cognitive decline in a non-demented elderly population and to estimate difference (in years) associated with lifetime intellectual enrichment to the onset of cognitive impairment. DESIGN, SETTING, PARTICIPANTS Prospective analysis of subjects enrolled in the Mayo Clinic Study of Aging (MCSA), a longitudinal population-based study of cognitive aging in Olmsted County, Minnesota. We studied 1995 non-demented (1718 cognitively normal, 277 MCI) participants in MCSA who completed intellectual lifestyle measures at baseline and underwent at least one follow-up visit. MAIN OUTCOMES AND MEASURES We studied the effect of lifetime intellectual enrichment by separating the variables into two non-overlapping principal components: education/occupation-score and mid/late-life cognitive activity measure based on self-report questionnaires. A global cognitive Z-score served as our summary cognition measure. We used linear mixed-effects models to investigate the associations of demographic and intellectual enrichment measures with global cognitive Z-score trajectories. RESULTS Baseline cognitive performance was lower in older subjects and in those with lower education/occupation, lower mid/late-life cognitive activity, apolipoprotein E4 (APOE) genotype, and in men. The interaction between the two intellectual enrichment measures was significant such that the beneficial effect of mid/late-life cognitive activity on baseline cognitive performance was reduced with increasing education/occupation. Only baseline age, mid/late-life cognitive activity, and APOE4 genotype were significantly associated with longitudinal change in cognitive performance from baseline. For APOE4 carriers with high

  4. Controlled processes account for age-related decrease in episodic memory.

    PubMed

    Vanderaspoilden, Valérie; Adam, Stéphane; der Linden, Martial Van; Morais, José

    2007-05-01

    A decrease in controlled processes has been proposed to be responsible for age-related episodic memory decline. We used the Process Dissociation Procedure, a method that attempts to estimate the contribution of controlled and automatic processes to cognitive performance, and entered both estimates in regression analyses. Results indicate that only controlled processes explained a great part of the age-related variance in a word recall task, especially when little environmental support was offered. PMID:16860766

  5. Recognition of Famous Names Predicts Episodic Memory Decline in Cognitively Intact Elders

    PubMed Central

    Seidenberg, Michael; Kay, Christina; Woodard, John L.; Nielson, Kristy A.; Smith, J. Carson; Kandah, Cassandra; Guidotti Breting, Leslie M.; Novitski, Julia; Lancaster, Melissa; Matthews, Monica; Hantke, Nathan; Butts, Alissa; Rao, Stephen M.

    2013-01-01

    Objective: Semantic memory impairment is common in both Mild Cognitive Impairment (MCI) and early Alzheimer’s disease (AD), and the ability to recognize familiar people is particularly vulnerable. A time-limited temporal gradient (TG) in which well known people from decades earlier are better recalled than those learned recently is also reported in both AD and MCI. In this study, we hypothesized that the TG pattern on a famous name recognition task (FNRT) administered to cognitively intact elders would predict future episodic memory decline, and would also show a significant correlation with hippocampal volume. Methods: 78 healthy elders (ages 65-90) with normal cognition and episodic memory at baseline were administered a FNRT. Follow-up episodic memory testing 18 months later produced two groups: Declining (≥ 1 SD reduction in episodic memory) and Stable (< 1 SD). Results: The Declining group (N=27) recognized fewer recent famous names than the Stable group (N=51), while recognition for remote names was comparable. Baseline MRI volumes for both the left and right hippocampus was significantly smaller in the Declining group than the Stable group. Smaller baseline hippocampal volume was also significantly correlated with poorer performance for recent, but not remote famous names. Logistic regression analyses indicated that baseline TG performance was a significant predictor of group status (Declining versus Stable) independent of chronological age and APOE ε4 inheritance. Conclusions: Famous name recognition may serve as an early pre-clinical cognitive marker of episodic memory decline in older individuals. PMID:23688215

  6. Demographic and clinical characteristics related to cognitive decline in Alzheimer disease in China

    PubMed Central

    Peng, Dantao; Shi, Zhihong; Xu, Jun; Shen, Lu; Xiao, Shifu; Zhang, Nan; Li, Yi; Jiao, Jinsong; Wang, Yan-Jiang; Liu, Shuai; Zhang, Meilin; Wang, Meng; Liu, Shuling; Zhou, Yuying; Zhang, Xiao; Gu, Xiao-hua; Yang, Ce-ce; Wang, Yu; Jiao, Bin; Tang, Beisha; Wang, Jinhuan; Yu, Tao; Ji, Yong

    2016-01-01

    Abstract Alzheimer disease (AD) is the most frequent cause of dementia. AD diagnosis, progression, and treatment have not been analyzed nationwide in China. The primary aim of this study was to analyze demographic and clinical characteristics related to cognitive decline in AD patients treated at outpatient clinics in China. We performed a retrospective study of 1993 AD patients at 10 cognitive centers across 8 cities in China from March 2011 to October 2014. Of these, 891 patients were followed for more than 1 year. The mean age at diagnosis was 72.0 ± 10.0 years (range 38–96 years), and the mean age at onset of AD was 69.8 ± 9.5 years. Most patients (65.1%) had moderate to severe symptoms at the time of diagnosis, and mean Mini-Mental State Examination at diagnosis was 15.7 ± 7.7. AD patients showed significant cognitive decline at 12 months after diagnosis. Having more than 9 years of formal education was an independent risk factor related to rapid cognitive decline [odds ratio (OR) = 1.80; 95% confidence interval (95% CI): 1.11–2.91]. Early-onset AD patients experienced more rapid cognitive decline than late-onset patients (OR = 1.83; 95% CI: 1.09–3.06). Most AD patients in China had moderate to severe symptoms at the time of diagnosis and experienced significant cognitive decline within 1 year. Rapid cognitive decline in AD was related to having a higher educational level and younger age of onset. PMID:27367978

  7. Gene-based aggregate SNP associations between candidate AD genes and cognitive decline.

    PubMed

    Nettiksimmons, Jasmine; Tranah, Gregory; Evans, Daniel S; Yokoyama, Jennifer S; Yaffe, Kristine

    2016-04-01

    Single nucleotide polymorphisms (SNPs) in and near ABCA7, BIN1, CASS4, CD2AP, CD33, CELF1, CLU, complement receptor 1 (CR1), EPHA1, EXOC3L2, FERMT2, HLA cluster (DRB5-DQA), INPP5D, MEF2C, MS4A cluster (MS4A3-MS4A6E), NME8, PICALM, PTK2B, SLC24A4, SORL1, and ZCWPW1 have been associated with Alzheimer's disease (AD) in large meta-analyses. We aimed to determine whether established AD-associated genes are associated with longitudinal cognitive decline by examining aggregate variation across these gene regions. In two single-sex cohorts of older, community-dwelling adults, we examined the association between SNPs in previously implicated gene regions and cognitive decline (age-adjusted person-specific cognitive slopes) using a Sequence Kernel Association Test (SKAT). In regions which showed aggregate significance, we examined the univariate association between individual SNPs in the region and cognitive decline. Only two of the original AD-associated SNPs were significantly associated with cognitive decline in our cohorts. We identified significant aggregate-level associations between cognitive decline and the gene regions BIN1, CD33, CELF1, CR1, HLA cluster, and MEF2C in the all-female cohort and significant associations with ABCA7, HLA cluster, MS4A6E, PICALM, PTK2B, SLC24A4, and SORL1 in the all-male cohort. We also identified a block of eight correlated SNPs in CD33 and several blocks of correlated SNPs in CELF1 that were significantly associated with cognitive decline in univariate analysis in the all-female cohort. PMID:27005436

  8. Telmisartan prevented cognitive decline partly due to PPAR-{gamma} activation

    SciTech Connect

    Mogi, Masaki; Li Jianmei; Tsukuda, Kana; Iwanami, Jun; Min, Li-Juan; Sakata, Akiko; Fujita, Teppei; Iwai, Masaru; Horiuchi, Masatsugu

    2008-10-24

    Telmisartan is a unique angiotensin receptor blocker (ARB) and partial agonist of peroxisome proliferator-activated receptor (PPAR)-{gamma}. Here, we investigated the preventive effect of telmisartan on cognitive decline in Alzheimer disease. In ddY mice, intracerebroventricular injection of A{beta} 1-40 significantly attenuated their cognitive function evaluated by shuttle avoidance test. Pretreatment with a non-hypotensive dose of telmisartan significantly inhibited such cognitive decline. Interestingly, co-treatment with GW9662, a PPAR-{gamma} antagonist, partially inhibited this improvement of cognitive decline. Another ARB, losartan, which has less PPAR-{gamma} agonistic effect, also inhibited A{beta}-injection-induced cognitive decline; however the effect was smaller than that of telmisartan and was not affected by GW9662. Immunohistochemical staining for A{beta} showed the reduced A{beta} deposition in telmisartan-treated mice. However, this reduction was not observed in mice co-administered GW9662. These findings suggest that ARB has a preventive effect on cognitive impairment in Alzheimer disease, and telmisartan, with PPAR-{gamma} activation, could exert a stronger effect.

  9. Chocolate Consumption is Associated with a Lower Risk of Cognitive Decline.

    PubMed

    Moreira, Afonso; Diógenes, Maria José; de Mendonça, Alexandre; Lunet, Nuno; Barros, Henrique

    2016-05-01

    Cocoa-related products like chocolate have taken an important place in our food habits and culture. In this work, we aim to examine the relationship between chocolate consumption and cognitive decline in an elderly cognitively healthy population. In the present longitudinal prospective study, a cohort of 531 participants aged 65 and over with normal Mini-Mental State Examination (MMSE; median 28) was selected. The median follow-up was 48 months. Dietary habits were evaluated at baseline. The MMSE was used to assess global cognitive function at baseline and at follow-up. Cognitive decline was defined by a decrease ≥ 2 points in the MMSE score between evaluations. Relative risk (RR) and 95% confidence interval (95% CI) estimates were adjusted for age, education, smoking, alcohol drinking, body mass index, hypertension, and diabetes. Chocolate intake was associated with a lower risk of cognitive decline (RR = 0.59, 95% CI 0.38-0.92). This protective effect was observed only among subjects with an average daily consumption of caffeine lower than 75 mg (69% of the participants; RR = 0.50, 95% CI 0.31-0.82). To our knowledge, this is the first prospective cohort study to show an inverse association between regular long-term chocolate consumption and cognitive decline in humans. PMID:27163823

  10. Visit-to-Visit Variability in Blood Pressure Is Related to Late-Life Cognitive Decline.

    PubMed

    Qin, Bo; Viera, Anthony J; Muntner, Paul; Plassman, Brenda L; Edwards, Lloyd J; Adair, Linda S; Popkin, Barry M; Mendez, Michelle A

    2016-07-01

    The association between visit-to-visit variability of blood pressure (BP) and cognitive decline over time remains incompletely understood in a general population of older adults. We assessed the hypothesis that higher visit-to-visit variability in BP, but not mean BP, would be associated with faster decline in cognitive function among community-dwelling older adults. This prospective cohort study comprised 976 adults who had 3 or 4 visits with BP measurements as part of the China Health and Nutrition Survey from 1991, up to their first cognitive tests, and completed cognitive screening tests at ≥2 visits in 1997, 2000, or 2004. Visit-to-visit BP variability was expressed as the SD, coefficient of variation, or as the variation independent of mean BP across visits conducted at a mean interval of 3.2 years. Mean (SD) age at the first cognitive test was 64 (6) years. Using multivariable-adjusted linear mixed-effects models, we found higher visit-to-visit variability in systolic BP, but not mean systolic BP, was associated with a faster decline of cognitive function (adjusted mean difference [95% confidence interval] for high versus low tertile of SD variability: standardized composite scores -0.038 standard units (SU)/y [-0.066 to -0.009] and verbal memory -0.041 SU/y [-0.075 to -0.008]). Higher visit-to-visit variability in diastolic BP was associated with a faster decline of cognitive function, independent of mean diastolic BP, among adults aged 55 to 64 years but not those ≥65 years. Our results suggest that higher long-term BP visit-to-visit variability is associated with a faster rate of cognitive decline among older adults. PMID:27217401

  11. Association Between Long-Term Cognitive Decline in Vietnam Veterans With TBI and Caregiver Attachment Style

    PubMed Central

    Guevara, Andrea Brioschi; Demonet, Jean-François; Polejaeva, Elena; Knutson, Kristine M.; Wassermann, Eric M.; Krueger, Frank; Grafman, Jordan

    2015-01-01

    Objective To examine whether a caregiver's attachment style is associated with patient cognitive trajectory after traumatic brain injury (TBI). Setting National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland. Participants Forty Vietnam War veterans with TBI and their caregivers. Main Outcome Measure Cognitive performance, measured by the Armed Forces Qualification Test percentile score, completed at 2 time points: preinjury and 40 years postinjury. Design On the basis of caregivers’ attachment style (secure, fearful, preoccupied, dismissing), participants with TBI were grouped into a high or low group. To examine the association between cognitive trajectory of participants with TBI and caregivers’ attachment style, we ran four 2 × 2 analysis of covariance on cognitive performances. Results After controlling for other factors, cognitive decline was more pronounced in participants with TBI with a high fearful caregiver than among those with a low fearful caregiver. Other attachment styles were not associated with decline. Conclusion and Implication Caregiver fearful attachment style is associated with a significant decline in cognitive status after TBI. We interpret this result in the context of the neural plasticity and cognitive reserve literatures. Finally, we discuss its impact on patient demand for healthcare services and potential interventions. PMID:24695269

  12. Relation of DASH- and Mediterranean-like dietary patterns to cognitive decline in older persons

    PubMed Central

    Li, Hong; Wang, Yamin; Barnes, Lisa; Schneider, Julie A.; Bennett, David A.; Morris, Martha C.

    2014-01-01

    Objectives: We examined whether accordance to the DASH (Dietary Approach to Stop Hypertension) and Mediterranean diets is associated with slower cognitive decline in a prospective Chicago cohort study of older persons, the Memory and Aging Project. Methods: The sample comprised 826 Memory and Aging Project participants (aged 81.5 ± 7.1 years) who completed a 144-item food frequency questionnaire at baseline and 2 or more cognitive assessments over 4.1 years. Dietary scores were computed for accordance to the DASH diet (0–10) and the Mediterranean diet (MedDietScore) (0–55). For both, higher scores reflect greater accordance. Both patterns share at least 3 common food components. Cognitive function was assessed annually with 19 cognitive tests from which global cognitive scores and summary measures are computed. Results: The mean global cognitive score at baseline was 0.12 (range, −3.23 to 1.60) with an overall mean annual change in score of −0.08 standardized units. Only 13 participants had possible dementia. The mean DASH score was 4.1 (range, 1.0–8.5) and the MedDietScore was 31.3 (range, 18–46). In mixed models adjusted for covariates, a 1-unit difference in DASH score was associated with a slower rate of global cognitive decline by 0.007 standardized units (standard error of estimate = 0.003, p = 0.03). Similarly, a 1-unit-higher MedDietScore was associated with a slower rate of global cognitive decline by 0.002 standardized units (standard error of estimate = 0.001, p = 0.01). Conclusions: These findings support the hypothesis that both the DASH and Mediterranean diet patterns are associated with slower rates of cognitive decline in the same cohort of older persons. PMID:25230996

  13. Vascular and amyloid pathologies are independent predictors of cognitive decline in normal elderly

    PubMed Central

    Lesnick, Timothy G.; Przybelski, Scott A.; Knopman, David S.; Preboske, Greg M.; Kantarci, Kejal; Raman, Mekala R.; Machulda, Mary M.; Mielke, Michelle M.; Lowe, Val J.; Senjem, Matthew L.; Gunter, Jeffrey L.; Rocca, Walter A.; Roberts, Rosebud O.; Petersen, Ronald C.; Jack, Clifford R.

    2015-01-01

    Our primary objective was to investigate a biomarker driven model for the interrelationships between vascular disease pathology, amyloid pathology, and longitudinal cognitive decline in cognitively normal elderly subjects between 70 and 90 years of age. Our secondary objective was to investigate the beneficial effect of cognitive reserve on these interrelationships. We used brain amyloid-β load measured using Pittsburgh compound B positron emission tomography as a marker for amyloid pathology. White matter hyperintensities and brain infarcts were measured using fluid-attenuated inversion recovery magnetic resonance imaging as a marker for vascular pathology. We studied 393 cognitively normal elderly participants in the population-based Mayo Clinic Study of Aging who had a baseline 3 T fluid-attenuated inversion recovery magnetic resonance imaging assessment, Pittsburgh compound B positron emission tomography scan, baseline cognitive assessment, lifestyle measures, and at least one additional clinical follow-up. We classified subjects as being on the amyloid pathway if they had a global cortical amyloid-β load of ≥1.5 standard uptake value ratio and those on the vascular pathway if they had a brain infarct and/or white matter hyperintensities load ≥1.11% of total intracranial volume (which corresponds to the top 25% of white matter hyperintensities in an independent non-demented sample). We used a global cognitive z-score as a measure of cognition. We found no evidence that the presence or absence of vascular pathology influenced the presence or absence of amyloid pathology and vice versa, suggesting that the two processes seem to be independent. Baseline cognitive performance was lower in older individuals, in males, those with lower education/occupation, and those on the amyloid pathway. The rate of cognitive decline was higher in older individuals (P < 0.001) and those with amyloid (P = 0.0003) or vascular (P = 0.0037) pathologies. In those subjects with

  14. Ten-year change in plasma amyloid β levels and late-life cognitive decline

    PubMed Central

    Okereke, Olivia I.; Xia, Weiming; Selkoe, Dennis J.; Grodstein, Francine

    2009-01-01

    Background Plasma levels of the amyloid β-peptides (Aβ) are potential biomarkers of early cognitive impairment and decline, and of Alzheimer disease (AD) risk. Objective To relate mid-life plasma Aβ measures, and ten-year change in plasma Aβ since mid-life, to later-life cognitive decline. Design, setting, participants Plasma Aβ-40 and Aβ-42 levels were measured in 481 Nurses’ Health Study participants in late mid-life (mean age=63.6 years) and again 10 years later (mean age=74.6 years). Cognitive testing also began 10 years after the initial blood draw. Participants completed three repeated telephone-based assessments (average span=4.1 years). Multivariable linear mixed effects models were used to estimate relations of mid-life plasma Aβ-40:Aβ-42 ratios and Aβ-42 levels to later-life cognitive decline, and to relate ten-year change in Aβ-40:Aβ-42 and Aβ-42 to cognitive decline. Main Outcome Measures The primary outcomes were: the Telephone Interview for Cognitive Status (TICS); a global score averaging all tests (TICS, immediate and delayed verbal recall, category fluency, and attention); and a verbal memory score averaging four tests of verbal recall. Results Higher mid-life plasma Aβ-40:Aβ-42 ratio was associated with worse later-life decline on the global score (p-trend=0.04). Furthermore, an increase in Aβ-40:Aβ-42 since mid-life predicted greater decline on the global score (p-trend=0.03) and the TICS (p-trend=0.02). There was no association between mid-life plasma Aβ-42 levels alone – or change in Aβ-42 since mid-life – and cognitive decline. Conclusions In this large community-dwelling sample, higher plasma Aβ-40:Aβ-42 ratios in late mid-life, and increases in Aβ-40:Aβ-42 ten years later, were significantly associated with greater decline in global cognition at late-life. PMID:19822780

  15. Critical levels of brain atrophy associated with homocysteine and cognitive decline.

    PubMed

    de Jager, Celeste A

    2014-09-01

    Few B-vitamin trials to lower homocysteine (Hcy) have reported evidence of beneficial effects on cognition in older adults with cognitive impairment or Alzheimer's disease. This article reviews the role of Hcy in cognitive decline. It also considers some reasons why meta-analyses have failed to find effects of B-vitamin treatment. Findings from the successful VITACOG trial are examined from a new perspective of critical levels of Hcy and brain atrophy that may impact on the efficacy of B-vitamin treatment. It appears that there is a critical level of brain shrinkage, possibly mediated by elevated Hcy, which when reached, results in cognitive decline, especially in episodic memory performance. Supplements, food sources, and effects of folic acid fortification are discussed in relation to B12 deficiency. PMID:24927906

  16. A conceptual framework for research on subjective cognitive decline in preclinical Alzheimer’s disease

    PubMed Central

    Jessen, Frank; Amariglio, Rebecca E.; van Boxtel, Martin; Breteler, Monique; Ceccaldi, Mathieu; Chételat, Gaël; Dubois, Bruno; Dufouil, Carole; Ellis, Kathryn A.; van der Flier, Wiesje M.; Glodzik, Lidia; van Harten, Argonde C.; de Leon, Mony J.; McHugh, Pauline; Mielke, Michelle M.; Molinuevo, Jose Luis; Mosconi, Lisa; Osorio, Ricardo S.; Perrotin, Audrey; Petersen, Ronald C.; Rabin, Laura A.; Rami, Lorena; Reisberg, Barry; Rentz, Dorene M.; Sachdev, Perminder S.; de la Sayette, Vincent; Saykin, Andrew J.; Scheltens, Philip; Shulman, Melanie B.; Slavin, Melissa J.; Sperling, Reisa A.; Stewart, Robert; Uspenskaya, Olga; Vellas, Bruno; Visser, Pieter Jelle; Wagner, Michael

    2014-01-01

    There is increasing evidence that subjective cognitive decline (SCD) in individuals with unimpaired performance on cognitive tests may represent the first symptomatic manifestation of Alzheimer’s disease (AD). The research on SCD in early AD, however, is limited by the absence of common standards. The working group of the Subjective Cognitive Decline Initiative (SCD-I) addressed this deficiency by reaching consensus on terminology and on a conceptual framework for research on SCD in AD. In this publication, research criteria for SCD in pre-mild cognitive impairment (MCI) are presented. In addition, a list of core features proposed for reporting in SCD studies is provided, which will enable comparability of research across different settings. Finally, a set of features is presented, which in accordance with current knowledge, increases the likelihood of the presence of preclinical AD in individuals with SCD. This list is referred to as SCD plus. PMID:24798886

  17. Traditional used Plants against Cognitive Decline and Alzheimer Disease

    PubMed Central

    Eckert, Gunter Peter

    2010-01-01

    Alzheimer's disease (AD) is a neurodegenerative disorder characterized clinically by progressive memory deficits, impaired cognitive function, and altered and inappropriate behavior. Aging represents the most important risk factor for AD and the global trend in the phenomenon of population aging has dramatic consequences for public health, healthcare financing, and delivery systems in the word and, especially in developing countries. Mounting evidence obtained in in vitro and in vivo studies, suggests that various traditionally used plants in Asia, India, and Europe significantly affect key metabolic alterations culminating in AD-typical neurodegeneration. The present article aims to bring the reader up-to-date on the most recent studies and advances describing the direct and indirect activities of traditional used plants and its constituents possibly relieving features of AD. A variety of traditional used plants and its extracts exerted activities on AD related drug targets including AChE activity, antioxidative activity, modulation of Aβ-producing secretase activities, Aβ-degradation, heavy metal chelating, induction of neurotrophic factors, and cell death mechanisms. Although pre-clinical investigations identified promising drug candidates for AD, clinical evidences are still pending. PMID:21833177

  18. Military risk factors for cognitive decline, dementia and Alzheimer's disease.

    PubMed

    Veitch, Dallas P; Friedl, Karl E; Weiner, Michael W

    2013-11-01

    Delayed neurological health consequences of environmental exposures during military service have been generally underappreciated. The rapidly expanding understanding of Alzheimer's disease (AD) pathogenesis now makes it possible to quantitate some of the likely long-term health risks associated with military service. Military risk factors for AD include both factors elevated in military personnel such as tobacco use, traumatic brain injury (TBI), depression, and post-traumatic stress disorder (PTSD) and other nonspecific risk factors for AD including, vascular risk factors such as obesity and obesity-related diseases (e.g., metabolic syndrome), education and physical fitness. The degree of combat exposure, Vietnam era Agent Orange exposure and Gulf War Illness may also influence risk for AD. Using available data on the association of AD and specific exposures and risk factors, the authors have conservatively estimated 423,000 new cases of AD in veterans by 2020, including 140,000 excess cases associated with specific military exposures. The cost associated with these excess cases is approximately $5.8 billion to $7.8 billion. Mitigation of the potential impact of military exposures on the cognitive function of veterans and management of modifiable risk factors through specifically designed programs will be instrumental in minimizing the impact of AD in veterans in the future decades. PMID:23906002

  19. Perception and Cognition in the Ageing Brain: A Brief Review of the Short- and Long-Term Links between Perceptual and Cognitive Decline

    PubMed Central

    Roberts, Katherine L.; Allen, Harriet A.

    2016-01-01

    Ageing is associated with declines in both perception and cognition. We review evidence for an interaction between perceptual and cognitive decline in old age. Impoverished perceptual input can increase the cognitive difficulty of tasks, while changes to cognitive strategies can compensate, to some extent, for impaired perception. While there is strong evidence from cross-sectional studies for a link between sensory acuity and cognitive performance in old age, there is not yet compelling evidence from longitudinal studies to suggest that poor perception causes cognitive decline, nor to demonstrate that correcting sensory impairment can improve cognition in the longer term. Most studies have focused on relatively simple measures of sensory (visual and auditory) acuity, but more complex measures of suprathreshold perceptual processes, such as temporal processing, can show a stronger link with cognition. The reviewed evidence underlines the importance of fully accounting for perceptual deficits when investigating cognitive decline in old age. PMID:26973514

  20. Development and validation of risk index for cognitive decline using blood-derived markers

    PubMed Central

    Ayonayon, Hilsa; Harris, Tamara; Phillips, Caroline; Rosano, Caterina; Satterfield, Suzanne; Yaffe, Kristine

    2015-01-01

    Objective: We sought to develop and validate a risk index for prospective cognitive decline in older adults based on blood-derived markers. Methods: The index was based on 8 markers that have been previously associated with cognitive aging: APOE genotype, plasma β-amyloid 42/40 ratio, telomere length, cystatin C, glucose, C-reactive protein, interleukin-6, and albumin. The outcome was person-specific cognitive slopes (Modified Mini-Mental State Examination) from 11 years of follow-up. A total of 1,445 older adults comprised the development sample. An index based on dichotomized markers was divided into low-, medium-, and high-risk categories; the risk categories were validated with the remaining sample (n = 739) using linear regression. Amyloid was measured on a subsample (n = 865) and was included only in a secondary index. Results: The risk categories showed significant differences from each other and were predictive of prospective cognitive decline in the validation sample, even after adjustment for age and baseline cognitive score: the low-risk group (24.8%) declined 0.32 points/y (95% confidence interval [CI]: −0.46, −0.19), the medium-risk group (58.7%) declined 0.55 points/y (95% CI: −0.65, 0.45), and the high-risk group (16.6%) declined 0.69 points/y (95% CI: −0.85, −0.54). Using the secondary index, which included β-amyloid 42/40 (validation n = 279), the low-risk group (26.9%) declined 0.20 points/y (95% CI: −0.42, 0.01), the medium-risk group (61.3%) declined 0.55 points/y (95% CI: −0.72, −0.38), and the high-risk group (11.8%) declined 0.83 points/y (95% CI: −1.14, −0.51). Conclusions: A risk index based on 8 blood-based markers was modestly able to predict cognitive decline over an 11-year follow-up. Further validation in other cohorts is necessary. PMID:25609760

  1. Adherence to a Mediterranean-type dietary pattern and cognitive decline in a community population123

    PubMed Central

    Tangney, Christine C; Kwasny, Mary J; Li, Hong; Wilson, Robert S; Evans, Denis A; Morris, Martha Clare

    2011-01-01

    Background: Many of the foods abundant in the traditional Mediterranean diet, such as vegetables and fish, have been associated with slower cognitive decline. Objective: We investigated whether adherence to a Mediterranean dietary pattern or to the Healthy Eating Index–2005 (HEI-2005) is associated with cognitive change in older adults. Design: This article is based on analyses of data from an ongoing longitudinal study in adults aged ≥65 y known as the Chicago Health and Aging Project (CHAP). CHAP participants (2280 blacks and 1510 whites) with ≥2 cognitive assessments were evaluated for adherence to 1) the Mediterranean dietary pattern (MedDiet; maximum score: 55) and 2) the HEI-2005 (maximum score: 100). For both scoring systems, higher scores connote greater adherence. Cognitive function was assessed at 3-y intervals on the basis of a composite measure of global cognition. Linear mixed models were used to examine the association of dietary scores to change in cognitive function. Mean follow-up time was 7.6 y. Results: Mean (±SD) scores for participants were 28.2 ± 0.1 for the MedDiet and 61.2 ± 9.6 for the HEI-2005. White participants had higher energy-adjusted MedDiet scores but lower HEI-2005 scores than did black participants. Higher MedDiet scores were associated with slower rates of cognitive decline (β = +0.0014 per 1-point increase, SEE = 0.0004, P = 0.0004) after adjustment for age, sex, race, education, participation in cognitive activities, and energy. No such associations were observed for HEI-2005 scores. Conclusion: The Mediterranean dietary pattern as captured by the MedDiet scoring system may reduce the rate of cognitive decline with older age. PMID:21177796

  2. Fasting Insulin Levels and Cognitive Decline in Older Women without Diabetes

    PubMed Central

    van Oijen, Marieke; Okereke, Olivia I.; Kang, Jae Hee; Pollak, Michael N.; Hu, Frank B.; Hankinson, Susan E.; Grodstein, Francine

    2008-01-01

    Background Type 2 diabetes has been associated with an increased risk of dementia. To assess possible independent effects of insulin, we investigated the relation of insulin levels to cognitive decline in nondiabetic women. Methods Fasting plasma insulin levels were measured in mid-life in 1,416 nondiabetic Nurses’ Health Study participants, who also completed cognitive testing that began 10 years later (current age: 70–75 years). Over 4 years, 3 assessments of general cognition, verbal memory, category fluency and attention were administered. Primary outcomes were the Telephone Interview for Cognitive Status (TICS) performance, the global score (average of all tests) and verbal memory (average of verbal recall tests). Linear mixed-effects models were used to calculate the association between insulin and cognitive decline. Results Higher insulin levels were associated with a faster decline on the TICS and verbal memory. For analysis, batch-specific quartiles of insulin levels were constructed. Compared to the lowest quartile, adjusted differences in the annual rates of decline (with 95% CI values in parentheses) for the second, third and fourth quartiles were: TICS, −0.06 (−0.16, 0.03), −0.14 (−0.24, −0.04), and −0.09 (−0.19, 0.01) points (p trend = 0.04); verbal memory, −0.01 (−0.04, 0.02), −0.05 (−0.08, −0.02), and −0.02 (−0.05, 0.01) units (p trend = 0.02). These associations remained after multivariable adjustment. Conclusions Our study provides evidence for a potential role of higher fasting insulin levels in cognitive decline, possibly independent of diabetes. PMID:18421217

  3. Vitamin B₁₂ status, cognitive decline and dementia: a systematic review of prospective cohort studies.

    PubMed

    O'Leary, Fiona; Allman-Farinelli, Margaret; Samman, Samir

    2012-12-14

    Poor vitamin B₁₂ status may lead to the development of cognitive decline and dementia but there is a large variation in the quality, design of and results reported from these investigations. We have undertaken a systematic review of the evidence for the association between vitamin B₁₂ status and cognitive decline in older adults. A database search of the literature to 2011 was undertaken, using keywords related to vitamin B₁₂ and cognition. All prospective cohort studies assessing the association of serum vitamin B₁₂ or biomarkers were included. Quality assessment and extraction of the data were undertaken by two researchers. The quality assessment tool assigns a positive, neutral or negative rating. Of 3772 published articles, thirty-five cohort studies (n 14 325 subjects) were identified and evaluated. No association between serum vitamin B₁₂ concentrations and cognitive decline or dementia was found. However, four studies that used newer biomarkers of vitamin B₁₂ status (methylmalonic acid and holotranscobalamin (holoTC)) showed associations between poor vitamin B₁₂ status and the increased risk of cognitive decline or dementia diagnosis. In general, the studies were of reasonable quality (twenty-one positive, ten neutral and four negative quality) but of short duration and inadequate subject numbers to determine whether an effect exists. Future studies should be of adequate duration (at least 6 years), recruit subjects from the seventh decade, choose markers of vitamin B₁₂ status with adequate specificity such as holoTC and/or methylmalonic acid and employ standardised neurocognitive assessment tools and not screening tests in order to ascertain any relationship between vitamin B₁₂ status and cognitive decline. PMID:23084026

  4. Plasma fibrinogen is associated with cognitive decline and risk for dementia in patients with mild cognitive impairment.

    PubMed

    Xu, G; Zhang, H; Zhang, S; Fan, X; Liu, X

    2008-07-01

    This study was aimed to investigate the relationship between plasma fibrinogen level and risk for cognitive decline and dementia in patients with mild cognitive impairment (MCI). Elderly patients with suspected cognitive impairment were screened and evaluated periodically. One hundred and eighty-five patients who met the criteria for MCI were enrolled. Blood coagulation functions and plasma fibrinogen levels were measured at baseline. Hyperfibrinogenaemia was defined as plasma fibrinogen > or =3.0 g/l. Global cognitive function was assessed serially with Mini-Mental State Examination (MMSE). The enrolled patients were followed for 2 years to observe if dementia was developed. There were 185 patients diagnosed as MCI, of which 17 (9.2%) deceased, 15 (8.1%) lost to follow-up, and 68 (36.8%) developed dementia during follow-up. Mean of MMSE score of the enrolled patients declined significantly during follow-up (22.0 +/- 3.0 vs. 18.1 +/- 5.8, p < 0.001). Patients with hyperfibrinogenaemia at baseline had greater MMSE decrement during follow-up than patients with normal fibrinogen level (-5.4 +/- 5.4 vs. -3.5 +/- 4.5, p < 0.05). Linear regression indicated that plasma fibrinogen level was associated with cognitive decline (R = 0.17, p < 0.05). Patients with hyperfibrinogenaemia had an increased risk for dementia and vascular dementia compared with patients with normal level of plasma fibrinogen (log rank test, p < 0.05). There was a trend that hyperfibrinogenaemia also increased risk for dementia of Alzheimer's type (p = 0.061). It can be concluded that plasma fibrinogen level may be associated with cognitive decline, and hyperfibrinogenaemia may increase risk for dementia in patients with MCI. PMID:17916180

  5. Automated Semantic Indices Related to Cognitive Function and Rate of Cognitive Decline

    ERIC Educational Resources Information Center

    Pakhomov, Serguei V. S.; Hemmy, Laura S.; Lim, Kelvin O.

    2012-01-01

    The objective of our study is to introduce a fully automated, computational linguistic technique to quantify semantic relations between words generated on a standard semantic verbal fluency test and to determine its cognitive and clinical correlates. Cognitive differences between patients with Alzheimer's disease and mild cognitive impairment are…

  6. APOE and BDNF polymorphisms moderate amyloid β-related cognitive decline in preclinical Alzheimer's disease

    PubMed Central

    Lim, Y Y; Villemagne, V L; Laws, S M; Pietrzak, R H; Snyder, P J; Ames, D; Ellis, K A; Harrington, K; Rembach, A; Martins, R N; Rowe, C C; Masters, C L; Maruff, P

    2015-01-01

    Accumulation of β-amyloid (Aβ) in the brain is associated with memory decline in healthy individuals as a prelude to Alzheimer's disease (AD). Genetic factors may moderate this decline. We examined the role of apolipoprotein E (ɛ4 carrier[ɛ4+], ɛ4 non-carrier[ɛ4−]) and brain-derived neurotrophic factor (BDNFVal/Val, BDNFMet) in the extent to which they moderate Aβ-related memory decline. Healthy adults (n=333, Mage=70 years) enrolled in the Australian Imaging, Biomarkers and Lifestyle study underwent Aβ neuroimaging. Neuropsychological assessments were conducted at baseline, 18-, 36- and 54-month follow-ups. Aβ positron emission tomography neuroimaging was used to classify participants as Aβ− or Aβ+. Relative to Aβ−ɛ4−, Aβ+ɛ4+ individuals showed significantly faster rates of cognitive decline over 54 months across all domains (d=0.40–1.22), while Aβ+ɛ4− individuals showed significantly faster decline only on verbal episodic memory (EM). There were no differences in rates of cognitive change between Aβ−ɛ4− and Aβ−ɛ4+ groups. Among Aβ+ individuals, ɛ4+/BDNFMet participants showed a significantly faster rate of decline on verbal and visual EM, and language over 54 months compared with ɛ4−/BDNFVal/Val participants (d=0.90–1.02). At least two genetic loci affect the rate of Aβ-related cognitive decline. Aβ+ɛ4+/BDNFMet individuals can expect to show clinically significant memory impairment after 3 years, whereas Aβ+ɛ4+/BDNFVal/Val individuals can expect a similar degree of impairment after 10 years. Little decline over 54 months was observed in the Aβ− and Aβ+ ɛ4− groups, irrespective of BDNF status. These data raise important prognostic issues in managing preclinical AD, and should be considered in designing secondary preventative clinical trials. PMID:25288138

  7. APOE GENOTYPE AND COGNITIVE DECLINE IN A MIDDLE-AGED COHORT

    Technology Transfer Automated Retrieval System (TEKTRAN)

    BACKGROUND: Most longitudinal studies of nondemented persons have reported greater cognitive decline among APOE epsilon4 carriers vs noncarriers. However, most studies involved elderly samples (aged 65+) and were not large enough to examine the three APOE alleles separately. METHODS: Change in cogni...

  8. Omega-3 Fatty Acid Status Enhances the Prevention of Cognitive Decline by B Vitamins in Mild Cognitive Impairment.

    PubMed

    Oulhaj, Abderrahim; Jernerén, Fredrik; Refsum, Helga; Smith, A David; de Jager, Celeste A

    2015-01-01

    A randomized trial (VITACOG) in people with mild cognitive impairment (MCI) found that B vitamin treatment to lower homocysteine slowed the rate of cognitive and clinical decline. We have used data from this trial to see whether baseline omega-3 fatty acid status interacts with the effects of B vitamin treatment. 266 participants with MCI aged ≥70 years were randomized to B vitamins (folic acid, vitamins B6 and B12) or placebo for 2 years. Baseline cognitive test performance, clinical dementia rating (CDR) scale, and plasma concentrations of total homocysteine, total docosahexaenoic and eicosapentaenoic acids (omega-3 fatty acids) were measured. Final scores for verbal delayed recall, global cognition, and CDR sum-of-boxes were better in the B vitamin-treated group according to increasing baseline concentrations of omega-3 fatty acids, whereas scores in the placebo group were similar across these concentrations. Among those with good omega-3 status, 33% of those on B vitamin treatment had global CDR scores >0 compared with 59% among those on placebo. For all three outcome measures, higher concentrations of docosahexaenoic acid alone significantly enhanced the cognitive effects of B vitamins, while eicosapentaenoic acid appeared less effective. When omega-3 fatty acid concentrations are low, B vitamin treatment has no effect on cognitive decline in MCI, but when omega-3 levels are in the upper normal range, B vitamins interact to slow cognitive decline. A clinical trial of B vitamins combined with omega-3 fatty acids is needed to see whether it is possible to slow the conversion from MCI to AD. PMID:26757190

  9. Epidemiologic Evidence of a Relationship between Tea, Coffee, or Caffeine Consumption and Cognitive Decline12

    PubMed Central

    Arab, Lenore; Khan, Faraz; Lam, Helen

    2013-01-01

    A systematic literature review of human studies relating caffeine or caffeine-rich beverages to cognitive decline reveals only 6 studies that have collected and analyzed cognition data in a prospective fashion that enables study of decline across the spectrum of cognition. These 6 studies, in general, evaluate cognitive function using the Mini Mental State Exam and base their beverage data on FFQs. Studies included in our review differed in their source populations, duration of study, and most dramatically in how their analyses were done, disallowing direct quantitative comparisons of their effect estimates. Only one of the studies reported on all 3 exposures, coffee, tea, and caffeine, making comparisons of findings across studies more difficult. However, in general, it can be stated that for all studies of tea and most studies of coffee and caffeine, the estimates of cognitive decline were lower among consumers, although there is a lack of a distinct dose response. Only a few measures showed a quantitative significance and, interestingly, studies indicate a stronger effect among women than men. PMID:23319129

  10. Environmental enrichment attenuates the age-related decline in the mRNA expression of steroidogenic enzymes and reduces the methylation state of the steroid 5α-reductase type 1 gene in the rat hippocampus.

    PubMed

    Rossetti, María F; Varayoud, Jorgelina; Moreno-Piovano, Guillermo S; Luque, Enrique H; Ramos, Jorge G

    2015-09-01

    We analyzed the effects of aging and environmental enrichment on the mRNA expression and DNA methylation state of steroidogenic enzymes in the hippocampus. The effects of aging were evaluated by comparing young adult (90-day-old) and middle-aged (450-day-old) female Wistar rats. To elucidate the effects of environmental enrichment, a subgroup of middle-aged rats exposed to sensory and social stimulation for 105 days was compared to rats housed under standard laboratory conditions. Aging decreased the transcription of neurosteroidogenic-related genes and increased the promoter methylation state of cytochrome P450 side chain cleavage, 3α-hydroxysteroid dehydrogenase (3α-HSD) and 5α-reductase-1. Exposure of middle-aged rats to environmental enrichment increased mRNA levels of 5α-reductase-1, 3α-HSD and cytochrome P450 17α-hydroxylase/c17,20-lyase and decreased the methylation state of the 5α-reductase-1 gene. Thus, sensory and social stimulation attenuate the age-related decline in the mRNA expression of hippocampal steroidogenic enzymes. Epigenetic mechanisms associated with differential promoter methylation could be involved. PMID:26021641

  11. Florbetapir F 18 amyloid PET and 36-month cognitive decline:a prospective multicenter study

    PubMed Central

    Doraiswamy, P M; Sperling, R A; Johnson, K; Reiman, E M; Wong, T Z; Sabbagh, M N; Sadowsky, C H; Fleisher, A S; Carpenter, A; Joshi, A D; Lu, M; Grundman, M; Mintun, M A; Skovronsky, D M; Pontecorvo, M J; Duara, Ranjan; Sabbagh, Marwan; Lawrence Ahern, Geoffrey; Holub, Richard F; Farmer, Mildred V; Safirstein, Beth Emmie; Alva, Gustavo; Longmire, Crystal F; Jewell, George; Johnson, Keith A; Korn, Ron; Reiman, Eric M; Wendt, Jeanette K; Wong, Dean; Doraiswamy, P Murali; Coleman, R Edward; Devous, Michael; Jennings, Danna; Weiner, Michael W; Murphy, Cynthia A; Kovnat, Karel D; Williamson, Jeff D; Sadowsky, Carl H

    2014-01-01

    This study was designed to evaluate whether subjects with amyloid beta (Aβ) pathology, detected using florbetapir positron emission tomorgraphy (PET), demonstrated greater cognitive decline than subjects without Aβ pathology. Sixty-nine cognitively normal (CN) controls, 52 with recently diagnosed mild cognitive impairment (MCI) and 31 with probable Alzheimer's disease (AD) dementia were included in the study. PET images obtained in these subjects were visually rated as positive (Aβ+) or negative (Aβ−), blind to diagnosis. Fourteen percent (10/69) of CN, 37% (19/52) of MCI and 68% (21/31) of AD were Aβ+. The primary outcome was change in ADAS-Cog score in MCI subjects after 36 months; however, additional outcomes included change on measures of cognition, function and diagnostic status. Aβ+ MCI subjects demonstrated greater worsening compared with Aβ− subjects on the ADAS-Cog over 36 months (5.66±1.47 vs −0.71±1.09, P=0.0014) as well as on the mini-mental state exam (MMSE), digit symbol substitution  (DSS) test, and a verbal fluency test (P<0.05). Similar to MCI subjects, Aβ+ CN subjects showed greater decline on the ADAS-Cog, digit-symbol-substitution test and verbal fluency (P<0.05), whereas Aβ+ AD patients showed greater declines in verbal fluency and the MMSE (P<0.05). Aβ+ subjects in all diagnostic groups also showed greater decline on the CDR-SB (P<0.04), a global clinical assessment. Aβ+ subjects did not show significantly greater declines on the ADCS-ADL or Wechsler Memory Scale. Overall, these findings suggest that in CN, MCI and AD subjects, florbetapir PET Aβ+ subjects show greater cognitive and global deterioration over a 3-year follow-up than Aβ− subjects do. PMID:24614494

  12. Gender Differences in Tea, Coffee, and Cognitive Decline in the Elderly: The Cardiovascular Health Study

    PubMed Central

    Arab, Lenore; Biggs, Mary L.; O’Meara, Ellen S.; Longstreth, W.T.; Crane, Paul K.; Fitzpatrick, Annette L.

    2013-01-01

    Although caffeine can enhance cognitive function acutely, long-term effects of consumption of caffeine-containing beverages such as tea and coffee are uncertain. Data on 4,809 participants aged 65 and older from the Cardiovascular Health Study (CHS) were used to examine the relationship of consumption of tea and coffee, assessed by food frequency questionnaire, on change in cognitive function by gender. Cognitive performance was assessed using serial Modified Mini-Mental State (3MS) examinations, which were administered annually up to 9 times. Linear mixed models were used to estimate rates of change in standard 3MS scores and scores modeled using item response theory (IRT). Models were adjusted for age, education, smoking status, clinic site, diabetes, hypertension, stroke, coronary heart disease, depression score, and APOE genotype. Over the median 7.9 years of follow-up, participants who did not consume tea or coffee declined annually by an average of 1.30 points (women) and 1.11 points (men) on standard 3MS scores. In fully adjusted models using either standard or IRT 3MS scores, we found modestly reduced rates of cognitive decline for some, but not all, levels of coffee and tea consumption for women, with no consistent effect for men. Caffeine consumption was also associated with attenuation in cognitive decline in women. Dose-response relationships were not linear. These longitudinal analyses suggest a somewhat attenuated rate of cognitive decline among tea and coffee consumers compared to non-consumers in women but not in men. Whether this association is causal or due to unmeasured confounding requires further study. PMID:21841254

  13. Alzheimer's disease pattern of brain atrophy predicts cognitive decline in Parkinson's disease

    PubMed Central

    Dietz, Nicole; Duda, John E.; Wolk, David A.; Doshi, Jimit; Xie, Sharon X.; Davatzikos, Christos; Clark, Christopher M.; Siderowf, Andrew

    2012-01-01

    Research suggests overlap in brain regions undergoing neurodegeneration in Parkinson's and Alzheimer's disease. To assess the clinical significance of this, we applied a validated Alzheimer's disease-spatial pattern of brain atrophy to patients with Parkinson's disease with a range of cognitive abilities to determine its association with cognitive performance and decline. At baseline, 84 subjects received structural magnetic resonance imaging brain scans and completed the Dementia Rating Scale-2, and new robust and expanded Dementia Rating Scale-2 norms were applied to cognitively classify participants. Fifty-nine non-demented subjects were assessed annually with the Dementia Rating Scale-2 for two additional years. Magnetic resonance imaging scans were quantified using both a region of interest approach and voxel-based morphometry analysis, and a method for quantifying the presence of an Alzheimer's disease spatial pattern of brain atrophy was applied to each scan. In multivariate models, higher Alzheimer's disease pattern of atrophy score was associated with worse global cognitive performance (β = −0.31, P = 0.007), including in non-demented patients (β = −0.28, P = 0.05). In linear mixed model analyses, higher baseline Alzheimer's disease pattern of atrophy score predicted long-term global cognitive decline in non-demented patients [F(1, 110) = 9.72, P = 0.002], remarkably even in those with normal cognition at baseline [F(1, 80) = 4.71, P = 0.03]. In contrast, in cross-sectional and longitudinal analyses there was no association between region of interest brain volumes and cognitive performance in patients with Parkinson's disease with normal cognition. These findings support involvement of the hippocampus and parietal–temporal cortex with cognitive impairment and long-term decline in Parkinson's disease. In addition, an Alzheimer's disease pattern of brain atrophy may be a preclinical biomarker of cognitive decline

  14. Working memory and executive function decline across normal aging, mild cognitive impairment, and Alzheimer's disease.

    PubMed

    Kirova, Anna-Mariya; Bays, Rebecca B; Lagalwar, Sarita

    2015-01-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disease marked by deficits in episodic memory, working memory (WM), and executive function. Examples of executive dysfunction in AD include poor selective and divided attention, failed inhibition of interfering stimuli, and poor manipulation skills. Although episodic deficits during disease progression have been widely studied and are the benchmark of a probable AD diagnosis, more recent research has investigated WM and executive function decline during mild cognitive impairment (MCI), also referred to as the preclinical stage of AD. MCI is a critical period during which cognitive restructuring and neuroplasticity such as compensation still occur; therefore, cognitive therapies could have a beneficial effect on decreasing the likelihood of AD progression during MCI. Monitoring performance on working memory and executive function tasks to track cognitive function may signal progression from normal cognition to MCI to AD. The present review tracks WM decline through normal aging, MCI, and AD to highlight the behavioral and neurological differences that distinguish these three stages in an effort to guide future research on MCI diagnosis, cognitive therapy, and AD prevention. PMID:26550575

  15. Vitamin D as a marker of cognitive decline in elderly Indian population

    PubMed Central

    Vedak, Tejal Kanhaiya; Ganwir, Vaishali; Shah, Arun B.; Pinto, Charles; Lele, Vikram R.; Subramanyam, Alka; Shah, Hina; Deo, Sudha Shrikant

    2015-01-01

    Objectives: Very few studies in India have addressed the role of vitamin D in cognitive function. The present study was conducted to assess the serum levels of 25-hydroxyvitamin D (25(OH)D) and its association with markers of cognitive impairment and homocysteine levels in the elderly Indian population. Materials and Methods: The study population consisted of patients with dementia (Group A, n = 32), mild cognitive impairment (MCI; Group B, n = 24), and elderly age-matched controls (Group C, n = 30). Measurement of serum levels of 25(OH)D and total homocysteine were done. Results: Significant decreased concentration of 25(OH)D and increased concentration of homocysteine was observed. Association of serum levels of vitamin D with markers of cognitive decline as well as serum homocysteine levels was observed in patients with dementia and MCI when compared to controls. Conclusion: Correlation of vitamin D with markers of cognitive decline and homocysteine opens a new door for early diagnosis of cognitive impairment. PMID:26425010

  16. Preventing cognitive decline in older African Americans with mild cognitive impairment: design and methods of a randomized clinical trial.

    PubMed

    Rovner, Barry W; Casten, Robin J; Hegel, Mark T; Leiby, Benjamin E

    2012-07-01

    Mild Cognitive Impairment (MCI) affects 25% of older African Americans and predicts progression to Alzheimer's disease. An extensive epidemiologic literature suggests that cognitive, physical, and/or social activities may prevent cognitive decline. We describe the methods of a randomized clinical trial to test the efficacy of Behavior Activation to prevent cognitive decline in older African Americans with the amnestic multiple domain subtype of MCI. Community Health Workers deliver 6 initial in-home treatment sessions over 2-3 months and then 6 subsequent in-home booster sessions using language, materials, and concepts that are culturally relevant to older African Americans during this 24 month clinical trial. We are randomizing 200 subjects who are recruited from churches, senior centers, and medical clinics to Behavior Activation or Supportive Therapy, which controls for attention. The primary outcome is episodic memory as measured by the Hopkins Verbal Learning Test-Revised at baseline and at months 3, 12, 18, and 24. The secondary outcomes are general and domain-specific neuropsychological function, activities of daily living, depression, and quality-of-life. The negative results of recent clinical trials of drug treatments for MCI and Alzheimer's disease suggest that behavioral interventions may provide an alternative treatment approach to preserve cognition in an aging society. PMID:22406101

  17. Prospective memory in subjective cognitive decline: a preliminary study on the role of early cognitive marker in dementia.

    PubMed

    Hsu, Yen-Hsuan; Huang, Ching-Feng; Tu, Min-Chien; Hua, Mau-Sun

    2015-01-01

    Accumulating evidence shows that subjective cognitive decline (SCD) without impairment on conventional neuropsychological tests may indicate increased risk for Alzheimer disease. Previous studies of mild cognitive impairment have demonstrated the potential role of prospective memory (PM) in the early detection of cognitive decline. We thus aimed to investigate the performance of people with SCD on PM tasks relative to their healthy controls (HCs). Forty-one participants with SCD and demographically matched HCs received regular cognitive testing as well as 2 single-trial naturalistic time-based and event-based PM tasks. Statistical analyses showed that the individuals with SCD performed worse on the time-based PM task, especially on the prospective component, when compared with their HCs. Our findings suggest that PM, especially the time-based one on the prospective component, may be an early cognitive marker of dementia. This implies an underlying difficulty among subjects with SCD in self-initiation that exacerbates their memory difficulties. Further investigation on a large scale is needed. PMID:25187222

  18. Dietary patterns and cognitive decline in an Australian study of ageing.

    PubMed

    Gardener, S L; Rainey-Smith, S R; Barnes, M B; Sohrabi, H R; Weinborn, M; Lim, Y Y; Harrington, K; Taddei, K; Gu, Y; Rembach, A; Szoeke, C; Ellis, K A; Masters, C L; Macaulay, S L; Rowe, C C; Ames, D; Keogh, J B; Scarmeas, N; Martins, R N

    2015-07-01

    The aim of this paper was to investigate the association of three well-recognised dietary patterns with cognitive change over a 3-year period. Five hundred and twenty-seven healthy participants from the Australian Imaging, Biomarkers and Lifestyle study of ageing completed the Cancer Council of Victoria food frequency questionnaire at baseline and underwent a comprehensive neuropsychological assessment at baseline, 18 and 36 months follow-up. Individual neuropsychological test scores were used to construct composite scores for six cognitive domains and a global cognitive score. Based on self-reported consumption, scores for three dietary patterns, (1) Australian-style Mediterranean diet (AusMeDi), (2) western diet and (3) prudent diet were generated for each individual. Linear mixed model analyses were conducted to examine the relationship between diet scores and cognitive change in each cognitive domain and for the global score. Higher baseline adherence to the AusMeDi was associated with better performance in the executive function cognitive domain after 36 months in apolipoprotein E (APOE) ɛ4 allele carriers (P<0.01). Higher baseline western diet adherence was associated with greater cognitive decline after 36 months in the visuospatial cognitive domain in APOE ɛ4 allele non-carriers (P<0.01). All other results were not significant. Our findings in this well-characterised Australian cohort indicate that adherence to a healthy diet is important to reduce risk for cognitive decline, with the converse being true for the western diet. Executive function and visuospatial functioning appear to be particularly susceptible to the influence of diet. PMID:25070537

  19. Reduction of Endogenous Melatonin Accelerates Cognitive Decline in Mice in a Simulated Occupational Formaldehyde Exposure Environment

    PubMed Central

    Mei, Yufei; Duan, Chunli; Li, Xiaoxiao; Zhao, Yun; Cao, Fenghua; Shang, Shuai; Ding, Shumao; Yue, Xiangpei; Gao, Ge; Yang, Hui; Shen, Luxi; Feng, Xueyan; Jia, Jianping; Tong, Zhiqian; Yang, Xu

    2016-01-01

    Individuals afflicted with occupational formaldehyde (FA) exposure often suffer from abnormal behaviors such as aggression, depression, anxiety, sleep disorders, and in particular, cognitive impairments. Coincidentally, clinical patients with melatonin (MT) deficiency also complain of cognitive problems associated with the above mental disorders. Whether and how FA affects endogenous MT metabolism and induces cognitive decline need to be elucidated. To mimic occupational FA exposure environment, 16 healthy adult male mice were exposed to gaseous FA (3 mg/m3) for 7 consecutive days. Results showed that FA exposure impaired spatial memory associated with hippocampal neuronal death. Biochemical analysis revealed that FA exposure elicited an intensive oxidative stress by reducing systemic glutathione levels, in particular, decreasing brain MT concentrations. Inversely, intraperitoneal injection of MT markedly attenuated FA-induced hippocampal neuronal death, restored brain MT levels, and reversed memory decline. At tissue levels, injection of FA into the hippocampus distinctly reduced brain MT concentrations. Furthermore, at cellular and molecular levels, we found that FA directly inactivated MT in vitro and in vivo. These findings suggest that MT supplementation contributes to the rescue of cognitive decline, and may alleviate mental disorders in the occupational FA-exposed human populations. PMID:26938543

  20. Regional Multiple Pathology Scores Are Associated with Cognitive Decline in Lewy Body Dementias.

    PubMed

    Howlett, David R; Whitfield, David; Johnson, Mary; Attems, Johannes; O'Brien, John T; Aarsland, Dag; Lai, Mitchell K P; Lee, Jasinda H; Chen, Christopher; Ballard, Clive; Hortobágyi, Tibor; Francis, Paul T

    2015-07-01

    Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) are characterized by the presence of α-synuclein-containing Lewy bodies and Lewy neurites. However, both dementias also show variable degrees of Alzheimer's disease (AD) pathology (senile plaques and neurofibrillary tangles), particularly in areas of the cortex associated with higher cognitive functions. This study investigates the contribution of the individual and combined pathologies in determining the rate of cognitive decline. Cortical α-synuclein, phosphorylated tau (phosphotau) and Aβ plaque pathology in 34 PDD and 55 DLB patients was assessed semi-quantitatively in four regions of the neocortex. The decline in cognition, assessed by Mini Mental State Examination, correlated positively with the cortical α-synuclein load. Patients also had varying degrees of senile Aβ plaque and phosphotau pathology. Regression analyses pointed to a combined pathology (Aβ plaque plus phosphotau plus α-synuclein-positive features), particularly in the prefrontal cortex (BA9) and temporal lobe neocortex with the superior and middle temporal gyrus (BA21, 22), being a major determining factor in the development of dementia. Thus, cognitive decline in Lewy body dementias is not a consequence of α-synuclein-induced neurodegeneration alone but senile plaque and phosphorylated tau pathology also contribute to the overall deficits. PMID:25103200

  1. Brain structural connectivity distinguishes patients at risk for cognitive decline after carotid interventions.

    PubMed

    Soman, Salil; Prasad, Gautam; Hitchner, Elizabeth; Massaband, Payam; Moseley, Michael E; Zhou, Wei; Rosen, Allyson C

    2016-06-01

    While brain connectivity analyses have been demonstrated to identify ill patients for a number of diseases, their ability to predict cognitive impairment after brain injury is not well established. Traditional post brain injury models, such as stroke, are limited for this evaluation because pre-injury brain connectivity patterns are infrequently available. Patients with severe carotid stenosis, in contrast, often undergo non-emergent revascularization surgery, allowing the collection of pre and post-operative imaging, may experience brain insult due to perioperative thrombotic/embolic infarcts or hypoperfusion, and can suffer post-operative cognitive decline. We hypothesized that a distributed function such as memory would be more resilient in patients with brains demonstrating higher degrees of modularity. To test this hypothesis, we analyzed preoperative structural connectivity graphs (using T1 and DWI MRI) for 34 patients that underwent carotid intervention, and evaluated differences in graph metrics using the Brain Connectivity Toolbox. We found that patients with lower binary component number, binary community number and weighted community number prior to surgery were at greater risk for developing cognitive decline. These findings highlight the promise of brain connectivity analyses to predict cognitive decline following brain injury and serve as a clinical decision support tool. Hum Brain Mapp 37:2185-2194, 2016. © 2016 Wiley Periodicals, Inc. PMID:27028955

  2. Aging exacerbates obesity-induced cerebromicrovascular rarefaction, neurovascular uncoupling, and cognitive decline in mice.

    PubMed

    Tucsek, Zsuzsanna; Toth, Peter; Tarantini, Stefano; Sosnowska, Danuta; Gautam, Tripti; Warrington, Junie P; Giles, Cory B; Wren, Jonathan D; Koller, Akos; Ballabh, Praveen; Sonntag, William E; Ungvari, Zoltan; Csiszar, Anna

    2014-11-01

    Epidemiological studies show that obesity has deleterious effects on the brain and cognitive function in the elderly population. However, the specific mechanisms through which aging and obesity interact to promote cognitive decline remain unclear. To test the hypothesis that aging exacerbates obesity-induced cerebromicrovascular impairment, we compared young (7 months) and aged (24 months) high-fat diet-fed obese C57BL/6 mice. We found that aging exacerbates the obesity-induced decline in microvascular density both in the hippocampus and in the cortex. The extent of hippocampal microvascular rarefaction and the extent of impairment of hippocampal-dependent cognitive function positively correlate. Aging exacerbates obesity-induced loss of pericyte coverage on cerebral microvessels and alters hippocampal angiogenic gene expression signature, which likely contributes to microvascular rarefaction. Aging also exacerbates obesity-induced oxidative stress and induction of NADPH oxidase and impairs cerebral blood flow responses to whisker stimulation. Collectively, obesity exerts deleterious cerebrovascular effects in aged mice, promoting cerebromicrovascular rarefaction and neurovascular uncoupling. The morphological and functional impairment of the cerebral microvasculature in association with increased blood-brain barrier disruption and neuroinflammation (Tucsek Z, Toth P, Sosnowsk D, et al. Obesity in aging exacerbates blood-brain barrier disruption, neuroinflammation and oxidative stress in the mouse hippocampus: effects on expression of genes involved in beta-amyloid generation and Alzheimer's disease. J Gerontol Biol Med Sci. 2013. In press, PMID: 24269929) likely contribute to obesity-induced cognitive decline in aging. PMID:24895269

  3. The mismatch negativity as an index of cognitive decline for the early detection of Alzheimer's disease.

    PubMed

    Ruzzoli, Manuela; Pirulli, Cornelia; Mazza, Veronica; Miniussi, Carlo; Brignani, Debora

    2016-01-01

    Evidence suggests that Alzheimer's disease (AD) is part of a continuum, characterized by long preclinical phases before the onset of clinical symptoms. In several cases, this continuum starts with a syndrome, defined as mild cognitive impairment (MCI), in which daily activities are preserved despite the presence of cognitive decline. The possibility of having a reliable and sensitive neurophysiological marker that can be used for early detection of AD is extremely valuable because of the incidence of this type of dementia. In this study, we aimed to investigate the reliability of auditory mismatch negativity (aMMN) as a marker of cognitive decline from normal ageing progressing from MCI to AD. We compared aMMN elicited in the frontal and temporal locations by duration deviant sounds in short (400 ms) and long (4000 ms) inter-trial intervals (ITI) in three groups. We found that at a short ITI, MCI showed only the temporal component of aMMN and AD the frontal component compared to healthy elderly who presented both. At a longer ITI, aMMN was elicited only in normal ageing subjects at the temporal locations. Our study provides empirical evidence for the possibility to adopt aMMN as an index for assessing cognitive decline in pathological ageing. PMID:27616726

  4. 25-Hydroxyvitamin D levels and cognitive performance and decline in elderly men

    PubMed Central

    Slinin, Y; Paudel, M L.; Taylor, B C.; Fink, H A.; Ishani, A; Canales, M T.; Yaffe, K; Barrett-Connor, E; Orwoll, E S.; Shikany, J M.; LeBlanc, E S.; Cauley, J A.; Ensrud, K E.

    2010-01-01

    Objective: To test the hypothesis that lower 25-hydroxyvitamin D [25(OH)D] levels are associated with a greater likelihood of cognitive impairment and risk of cognitive decline. Methods: We measured 25(OH)D and assessed cognitive function using the Modified Mini-Mental State Examination (3MS) and Trail Making Test Part B (Trails B) in a cohort of 1,604 men enrolled in the Osteoporotic Fractures in Men Study and followed them for an average of 4.6 years for changes in cognitive function. Results: In a model adjusted for age, season, and site, men with lower 25(OH)D levels seemed to have a higher odds of cognitive impairment, but the test for trend did not reach significance (impairment by 3MS: odds ratio [OR] 1.84, 95% confidence interval [CI] 0.81–4.19 for quartile [Q] 1; 1.41, 0.61–3.28 for Q2; and 1.18, 0.50–2.81 for Q3, compared with Q4 [referent group; p trend = 0.12]; and impairment by Trails B: OR 1.66, 95% CI 0.98–2.82 for Q1; 0.96, 0.54–1.69 for Q2; and 1.30, 0.76–2.22 for Q3, compared with Q4 [p trend = 0.12]). Adjustment for age and education further attenuated the relationships. There was a trend for an independent association between lower 25(OH)D levels and odds of cognitive decline by 3MS performance (multivariable OR 1.41, 95% CI 0.89–2.23 for Q1; 1.28, 0.84–1.95 for Q2; and 1.06, 0.70–1.62 for Q3, compared with Q4 [p = 0.10]), but no association with cognitive decline by Trails B. Conclusion: We found little evidence of independent associations between lower 25-hydroxyvitamin D level and baseline global and executive cognitive function or incident cognitive decline. GLOSSARY 3MS = Modified Mini-Mental State Examination; 25(OH)D = 25-hydroxyvitamin D; BMI = body mass index; CI = confidence interval; IADL = instrumental activities of daily living; MrOS = Osteoporotic Fractures in Men; OR = odds ratio; PASE = Physical Activity Scale for the Elderly; Q = quartile; Trails B = Trail Making Test Part B. PMID:19940271

  5. Rate of cognitive decline during the premotor phase of essential tremor

    PubMed Central

    Louis, Elan D.; Sánchez-Ferro, Álvaro; Bermejo-Pareja, Félix

    2013-01-01

    Objective: To characterize the rate of cognitive decline during the premotor phase of essential tremor (ET) in comparison to prevalent ET cases and controls. Methods: In this population-based, prospective study of people aged 65 years and older (Neurological Disorders in Central Spain), a 37-item version of the Mini-Mental State Examination was administered at 2 visits (baseline and follow-up, approximately 3 years later). We compared the rate of cognitive decline in 3 groups: prevalent ET cases (i.e., participants diagnosed with ET at baseline and at follow-up), “premotor” ET cases (i.e., participants diagnosed with incident ET at follow-up, but not at baseline), and controls (i.e., participants not diagnosed with ET at baseline or follow-up). Results: The 2,375 participants included 135 prevalent ET cases, 56 premotor ET cases, and 2,184 controls. During the follow-up period of 3.4 ± 0.5 years (mean ± SD), the 37-item version of the Mini-Mental State Examination declined by 0.7 ± 3.3 points (0.2 ± 1.0 points/year) in prevalent ET cases, 1.1 ± 3.5 points (0.3 ± 1.0 points/year) in premotor ET cases, and 0.1 ± 3.9 points (0.0 ± 1.2 points/year) in controls (p = 0.014). The difference between premotor ET cases and controls was significant (p = 0.046), as was the difference between prevalent ET cases and controls (p = 0.027). Conclusions: In this prospective cohort, cognitive test scores in premotor and prevalent ET cases declined at a faster rate than in elders without this disease. A decline in global cognitive function may occur in a premotor phase of ET. PMID:23700331

  6. Reduced Cognitive Function Predicts Functional Decline in Patients with Heart Failure over 12 months

    PubMed Central

    Alosco, Michael L.; Spitznagel, Mary Beth; Cohen, Ronald; Sweet, Lawrence H.; Colbert, Lisa H.; Josephson, Richard; Hughes, Joel; Rosneck, Jim; Gunstad, John

    2016-01-01

    Background Impaired activities of daily living (ADL) are common in heart failure (HF) patients and contribute to the elevated mortality and hospitalization rates in this population. Cognitive impairment is also prevalent in HF, though its ability to predict functional decline over time is unknown. Aims This study examined the longitudinal pattern of activities of daily living in HF persons and whether reduced baseline cognitive status predicts functional decline in this population. Methods 110 persons with HF completed the Lawton-Brody Activities of Daily Living Scale and were administered the Modified Mini-Mental Status Examination (3MS) at baseline and a 12-month follow-up. Three composite scores were derived from the Lawton-Brody, including total, instrumental, and basic ADLs. Results HF patients reported high rates of baseline impairments in instrumental ADLs, including shopping, food preparation, housekeeping duties, laundry, among others. Repeated measures analyses showed significant declines in total and instrumental ADLs from baseline to the 12-month follow-up in HF (p < .05). Hierarchical regression analyses showed that poorer baseline performance on the 3MS predicted worse total ADL performance at 12-months (β = .15, p = .049), including greater dependence in shopping, driving, feeding, and physical ambulation (p < .05 for all). Conclusion The current results show that HF patients report significant functional decline over a 12-month period and brief cognitive tests can identify those patients at highest risk for decline. If replicated, such findings encourage the use of cognitive screening measures to identify HF patients most likely to require assistance with ADL tasks. PMID:23754840

  7. Association Between the Mediterranean Diet and Cognitive Decline in a Biracial Population

    PubMed Central

    Houston, Denise K.; Simonsick, Eleanor M.; Lee, Jung Sun; Ayonayon, Hilsa N.; Shahar, Danit R.; Rosano, Caterina; Satterfield, Suzanne; Yaffe, Kristine

    2015-01-01

    Background. Results from numerous studies suggest protective effects of the Mediterranean diet for cardiovascular disease, cancer, and mortality. Evidence for an association with a decreased risk of cognitive decline is less consistent and studies are limited by a lack of diversity in their populations. Methods. We followed 2,326 older adults (38.2% black, 51.3% female, aged 70–79 at baseline) over 8 years in a prospective cohort study in the United States (Health, Aging and Body Composition study). To measure adherence to a Mediterranean diet, we calculated race-specific tertiles of the MedDiet score (range: 0–55) using baseline food frequency questionnaires. Cognitive decline was assessed using repeated Modified Mini Mental State Examination scores over the study. We used linear mixed models to assess the association between MedDiet score and trajectory of cognitive decline. Results. Among blacks, participants with high MedDiet scores had a significantly lower mean rate of decline on the Modified Mini Mental State Examination score compared with participants with lower MedDiet scores (middle and bottom tertiles). The mean difference in points per year was 0.22 (95% confidence interval: 0.05–0.39; p = .01) after adjustment for age, sex, education, body mass index, current smoking, physical activity, depression, diabetes, total energy intake, and socioeconomic status. No association between MedDiet scores and change in Modified Mini Mental State Examination score was seen among white participants (p = .14). Conclusions. Stronger adherence to the Mediterranean diet may reduce the rate of cognitive decline among black, but not white older adults. Further studies in diverse populations are needed to confirm this association and pinpoint mechanisms that may explain these results. PMID:24994847

  8. Optimizing Cognitive Development over the Life Course and Preventing Cognitive Decline: Introducing the Cognitive Health Environment Life Course Model (CHELM)

    ERIC Educational Resources Information Center

    Anstey, Kaarin J.

    2014-01-01

    Optimal cognitive development is defined in this article as the highest level of cognitive function reached in each cognitive domain given a person's biological and genetic disposition, and the highest possible maintenance of cognitive function over the adult life course. Theoretical perspectives underpinning the development of a framework…

  9. Compensatory larger cortical thickness in healthy elderly individuals with electroencephalographic risk for cognitive decline.

    PubMed

    Castro-Chavira, Susana A; Barrios, Fernando A; Pasaye, Erick H; Alatorre-Cruz, Graciela C; Fernández, Thalía

    2016-06-15

    Excess theta electroencephalographic (EEG) activity has been described as an accurate predictor for cognitive decline at least 7 years before symptom presentation. To test whether this predictor for cognitive decline correlates with structural changes in the brains of healthy elderly individuals, we compared the magnetic resonance structural images of healthy individuals with excess of theta activity [group with a risk for cognitive decline, risk group (RG); n=14] with healthy controls with normal EEG activity (control group; n=14). Neuropsychological and epidemiological analyses showed significant differences in only two features: more years of education and better performance in the visuospatial process task in the control group. Voxel-based morphometry results were not conclusive, but showed tendencies toward larger volumes in the prefrontal and parietal lobes, and smaller volumes in the right temporal lobe, right occipital lobe, and left cerebellum for the RG; these tendencies are in agreement with those proposed by the posterior-anterior shift in an aging model. Cortical-thickness analyses yielded a significant correlation between cortical thickness and years of education in the prefrontal and inferior-temporal regions, and larger cortical thickness in the RG, independent of age and years of education, in the right superior temporal region. These results suggest changes in the cortical thickness of structures related to memory and visuospatial functions in healthy, cognitively normal individuals before the appearance of cognitive decline. Thus, the performance of healthy elderly individuals with EEG risk may only be slightly different from normal because of compensation mechanisms allowing them to fulfill daily-life tasks, masking structural changes during preclinical neurocognitive disorders. PMID:27171033

  10. Cognitive decline in dementia with Lewy bodies: a 5-year prospective cohort study

    PubMed Central

    Rongve, A; Soennesyn, H; Skogseth, Ragnhild; Oesterhus, Ragnhild; Hortobágyi, T; Ballard, Clive; Auestad, B H; Aarsland, D

    2016-01-01

    Objectives We report the cognitive decline in persons diagnosed with mild dementia with Lewy bodies (DLB) and mild Alzheimer's disease (AD) during 5 years of annual follow-ups. Methods Patients were recruited into the study from geriatric, psychiatric and neurology clinics in Western Norway during 2005–2013. They were diagnosed according to clinical consensus criteria, based on standardised clinical rating scales. Autopsy-based diagnoses were available for 20 cases. Cognitive decline for up to 5 years was assessed using the Clinical Dementia Rating (CDR) scale and the Mini-Mental State Examination (MMSE). Survival analysis including Cox regression (time to reach severe dementia) and linear mixed-effects (lme) modelling were used to model the decline on MMSE. Results At least one follow-up assessment was available for 67 patients with DLB and 107 patients with AD, with a median follow-up time of 4.3 years. The time to reach severe dementia was significantly shorter in DLB (median 1793 days) compared with AD (1947 days; p=0.033), and the difference remained significant in the multiple Cox regression analysis (HR=2.0, p<0.02). In the adjusted lme model, MMSE decline was faster in DLB (annual decline 4.4 points) compared with AD (3.2 points; p<0.008). Conclusions Our findings show that from the mild dementia stage, patients with DLB have a more rapid cognitive decline than in AD. Such prognostic information is vital for patients and families and crucial for planning clinical trials and enabling health economic modelling. PMID:26928028

  11. Decreased Self-Appraisal Accuracy on Cognitive Tests of Executive Functioning Is a Predictor of Decline in Mild Cognitive Impairment

    PubMed Central

    Scherling, Carole S.; Wilkins, Sarah E.; Zakrezewski, Jessica; Kramer, Joel H.; Miller, Bruce L.; Weiner, Michael W.; Rosen, Howard J.

    2016-01-01

    Objective: Mild cognitive impairment (MCI) in older individuals is associated with increased risk of progression to dementia. The factors predicting progression are not yet well established, yet cognitive performance, particularly for memory, is known to be important. Anosognosia, meaning lack of awareness of one’s impaired function, is commonly reported in dementia and is often also a feature of MCI, but its association with risk of progression is not well understood. In particular, self-appraisal measures provide an autonomous measure of insight abilities, without the need of an informant. Methods: The present study examined the utility of self-appraisal accuracy at baseline for predicting cognitive decline in 51 patients using an informant-free assessment method. Baseline task performance scores were compared to self-assessments of performance to yield a discrimination score (DS) for tasks tapping into memory and executive functions. Results: Linear regression revealed that a larger DS for executive function tasks in MCI predicted functional decline, independent of age, education, and baseline memory and executive task scores. Conclusion: These findings indicate that objective estimates of self-appraisal can be used to quantify anosognosia and increase predictive accuracy for decline in MCI. PMID:27458368

  12. A lipid storage–like disorder contributes to cognitive decline in HIV-infected subjects

    PubMed Central

    Bandaru, Veera Venkata Ratnam; Mielke, Michelle M.; Sacktor, Ned; McArthur, Justin C.; Grant, Igor; Letendre, Scott; Chang, Linda; Wojna, Valerie; Pardo, Carlos; Calabresi, Peter; Munsaka, Sody

    2013-01-01

    Objective: In this multicenter cohort study, we sought to identify prognostic and associative metabolic indicators for HIV-associated neurocognitive disorders (HAND). Methods: A quantitative lipidomic analysis was conducted on 524 longitudinal CSF samples collected from 7 different performance sites across the mainland United States, Hawaii, and Puerto Rico. Subjects included HIV-infected individuals with longitudinal clinical and cognitive testing data and cognitively normal HIV-negative healthy controls. Results: At baseline, HIV+ subjects could be differentiated from HIV− controls by reductions in a single ceramide species and increases in multiple forms of cholesterol. Perturbations in cholesterol metabolism and ceramide were influenced by combined antiretroviral therapy (cART) use. There were no cross-sectional baseline differences in any lipid metabolite when HIV+ subjects were grouped according to cognitive status. However, a single sphingolipid metabolite and reduced levels of esterified cholesterols were prognostic indicators of incident cognitive decline. Longitudinal patterns of these disturbances in sphingolipid and sterol metabolism suggest that a progressive disorder of lipid metabolism that is similar to disorders of lipid storage may contribute to the pathogenesis of HAND. Conclusions: These findings suggest that HIV infection and cART are independently associated with a CNS metabolic disturbance, identify surrogate markers that are prognostic for cognitive decline, and implicate a lipid storage–like disorder in the progression of HAND. PMID:24027056

  13. Sex-specific risk of cardiovascular disease and cognitive decline: pregnancy and menopause

    PubMed Central

    2013-01-01

    Understanding the biology of sex differences is integral to personalized medicine. Cardiovascular disease and cognitive decline are two related conditions, with distinct sex differences in morbidity and clinical manifestations, response to treatments, and mortality. Although mortality from all-cause cardiovascular diseases has declined in women over the past five years, due in part to increased educational campaigns regarding the recognition of symptoms and application of treatment guidelines, the mortality in women still exceeds that of men. The physiological basis for these differences requires further research, with particular attention to two physiological conditions which are unique to women and associated with hormonal changes: pregnancy and menopause. Both conditions have the potential to impact life-long cardiovascular risk, including cerebrovascular function and cognition in women. This review draws on epidemiological, translational, clinical, and basic science studies to assess the impact of hypertensive pregnancy disorders on cardiovascular disease and cognitive function later in life, and examines the effects of post-menopausal hormone treatments on cardiovascular risk and cognition in midlife women. We suggest that hypertensive pregnancy disorders and menopause activate vascular components, i.e., vascular endothelium and blood elements, including platelets and leukocytes, to release cell-membrane derived microvesicles that are potential mediators of changes in cerebral blood flow, and may ultimately affect cognition in women as they age. Research into specific sex differences for these disease processes with attention to an individual’s sex chromosomal complement and hormonal status is important and timely. PMID:23537114

  14. Neuropsychological Markers of Cognitive Decline in Persons With Alzheimer Disease Neuropathology.

    PubMed

    Hassenstab, Jason; Monsell, Sarah E; Mock, Charles; Roe, Catherine M; Cairns, Nigel J; Morris, John C; Kukull, Walter

    2015-11-01

    To evaluate cognitive performance among persons who did and did not develop clinical Alzheimer disease (AD) but had AD neuropathology at autopsy, we examined neuropsychological performance in cognitively healthy (Clinical Dementia Rating [CDR] = 0) participants who returned for at least 1 follow-up and died within 2 years of their last assessment. Nonprogressors remained at CDR = 0 until death; progressors developed symptomatic AD during life (CDR > 0). Cognitive performance at baseline was compared between progressors and nonprogressors on a global cognitive composite and 4 domain-specific composites (episodic memory, language, attention/working memory, and executive function). Models adjusted for age, education, sex, and non-AD neuropathology. Progressors (n = 173) had worse performance than nonprogressors (n = 141) in nearly all cognitive domains. Progressors scored lower on composites of global cognition (P < 0.001), executive function (P = 0.0006), language (P < 0.0001), and episodic memory (P = 0.0006) but not on attention/working memory (P = 0.91). These data indicate that individuals with underlying AD neuropathology who are clinically healthy but who later develop symptomatic AD have worse performance in a wide range of domains versus individuals with underlying AD neuropathology who are clinically healthy but do not become symptomatic during life. Therefore, subtle cognitive decline at baseline may indicate an increased risk of progression to symptomatic AD. PMID:26469250

  15. Psychometrically matched measures of global cognition, memory, and executive function for assessment of cognitive decline in older persons.

    PubMed

    Mungas, Dan; Reed, Bruce R; Kramer, Joel H

    2003-07-01

    Item response theory methods were used to derive psychometrically sophisticated measures of global cognition, memory, and executive function. Goals were that these measures (a) could be derived from commonly used neuropsychological tests, (b) would have linear measurement properties, and (c) would be psychometrically matched. Scale development was based on a sample of 400 older individuals with cognitive function ranging from normal to demented. Scales were reasonably matched with linear measurement over an ability range relevant to many important clinical applications. Cognitively normal, mild impairment, and dementia participant groups differed on baseline measures and rate of decline. Association of measures with quantitative structural magnetic resonance imaging variables followed expected patterns. This approach to scale development may have applications for other neuropsychological assessment problems. PMID:12959504

  16. The recency ratio as an index of cognitive performance and decline in elderly individuals.

    PubMed

    Bruno, Davide; Reichert, Chelsea; Pomara, Nunzio

    2016-11-01

    Individuals with Alzheimer's disease have been found to present a typical serial position curve in immediate recall tests, showing poor primacy performance and exaggerated recency recall. However, the recency advantage is usually lost after a delay. On this basis, we examined whether the recency ratio (Rr), calculated by dividing recency performance in an immediate memory task by recency performance in a delayed task, was a useful risk marker of cognitive decline. We tested whether change in Mini-Mental State Examination (MMSE) performance between baseline and follow-up was predicted by baseline Rr and found this to be the case (N = 245). From these analyses, we conclude that participants with high Rr scores, who show disproportionate recency recall in the immediate test compared to the delayed test, present signs of being at risk for cognitive decline or dysfunction. PMID:27187491

  17. Methodological Challenges in Determining Longitudinal Associations Between Anticholinergic Drug Use and Incident Cognitive Decline

    PubMed Central

    Kashyap, Mandavi; Belleville, Sylvie; Mulsant, Benoit H; Hilmer, Sarah N; Paquette, Amelie; Tu, Le Mai; Tannenbaum, Cara

    2014-01-01

    Objectives To compare the effect of using different anticholinergic drug scales and different models of cognitive decline in longitudinal studies. Design Longitudinal cohort study. Setting Outpatient clinics, Quebec, Canada. Participants Individuals aged 60 and older without dementia or depression (n = 102). Measurements Using baseline and 1-year follow-up data, four measures of anticholinergic burden (anticholinergic component of the Drug Burden Index (DBI-Ach), Anticholinergic Cognitive Burden (ACB), Anticholinergic Drug Scale (ADS), and Anticholinergic Risk Scale (ARS)) were applied. Three models of cognitive decline (worsening of raw neuropsychological test scores, Reliable Change Index (RCI), and a standardized regression based measure (SRB)) were compared in relation to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) criteria for the onset of a new mild neurocognitive disorder. The consistency of associations was examined using logistic regression. Results The frequency of identifying individuals with an increase in anticholinergic burden over 1 year varied from 18% with the DBI-Ach to 23% with the ACB. The frequency of identifying cognitive decline ranged from 8% to 86% using different models. The raw change score had the highest sensitivity (0.91), and the RCI the highest specificity (0.93) against DSM-V criteria. Memory decline using the SRB method was associated with an increase in ACB (odds ratio (OR) = 5.3, 95% confidence interval (CI) = 1.1–25.8), ADS (OR = 5.7, 95% CI = 1.1–27.7), and ARS (OR = 6.5, 95% CI = 1.34–32.3). An increase in the DBI-Ach was associated with a decline on memory testing using the raw change score method (OR = 4.2, 95% CI = 1.8–15.4) and on the Trail-Making Test Part B using SRB (OR = 2.9, 95% CI = 1.1–8.0). No associations were observed using the DSM-V criteria or RCI method. Conclusion The choice of different methods for defining drug exposure and cognitive decline

  18. Comparison of cognitive decline between dementia with Lewy bodies and Alzheimer's disease: a cohort study

    PubMed Central

    McKeith, Ian; Rodda, Joanne; Qassem, Tarik; Tatsch, Klaus; Booij, Jan; Darcourt, Jacques; O'Brien, John

    2012-01-01

    Objectives Dementia with Lewy bodies (DLB) accounts for 10%–15% of dementia cases at autopsy and has distinct clinical features associated with earlier institutionalisation and a higher level of carer distress than are seen in Alzheimer's disease (AD). At present, there is on-going debate as to whether DLB is associated with a more rapid cognitive decline than AD. An understanding of the rate of decline of cognitive and non-cognitive symptoms in DLB may help patients and carers to plan for the future. Design In this cohort study, the authors compared 100 AD and 58 DLB subjects at baseline and at 12-month follow-up on cognitive and neuropsychiatric measures. Setting Patients were recruited from 40 European centres. Participants Subjects with mild–moderate dementia. Diagnosis of DLB or AD required agreement between consensus panel clinical diagnosis and visual rating of 123I-FP-CIT (dopamine transporter) single photon emission computed tomography neuroimaging. Outcome measures The Cambridge Cognitive Examination including Mini-Mental State Examination and Neuropsychiatric Inventory (NPI). Results The AD and DLB groups did not differ at baseline in terms of age, gender, Clinical Dementia Rating score and use of cholinesterase inhibitors or memantine. NPI and NPI carer distress scores were statistically significantly higher for DLB subjects at baseline and at follow-up, and there were no differences between AD and DLB in cognitive scores at baseline or at follow-up. There was no significant difference in rate of progression of any of the variables analysed. Conclusions DLB subjects had more neuropsychiatric features at baseline and at follow-up than AD, but the authors did not find any statistically significant difference in rate of progression between the mild–moderate AD and DLB groups on cognitive or neuropsychiatric measures over a 12-month follow-up period. PMID:22318660

  19. The relationship between long-term sunlight radiation and cognitive decline in the REGARDS cohort study

    NASA Astrophysics Data System (ADS)

    Kent, Shia T.; Kabagambe, Edmond K.; Wadley, Virginia G.; Howard, Virginia J.; Crosson, William L.; Al-Hamdan, Mohammad Z.; Judd, Suzanne E.; Peace, Fredrick; McClure, Leslie A.

    2014-04-01

    Sunlight may be related to cognitive function through vitamin D metabolism or circadian rhythm regulation. The analysis presented here sought to test whether ground and satellite measures of solar radiation are associated with cognitive decline. The study used a 15-year residential history merged with satellite and ground monitor data to determine sunlight (solar radiation) and air temperature exposure for a cohort of 19,896 cognitively intact black and white participants aged 45+ from the 48 contiguous United States. Exposures of 15, 10, 5, 2, and 1-year were used to predict cognitive status at the most recent assessment in logistic regression models; 1-year insolation and maximum temperatures were chosen as exposure measures. Solar radiation interacted with temperature, age, and gender in its relationships with incident cognitive impairment. After adjustment for covariates, the odds ratio (OR) of cognitive decline for solar radiation exposure below the median vs above the median in the 3rd tertile of maximum temperatures was 1.88 (95 % CI: 1.24, 2.85), that in the 2nd tertile was 1.33 (95 % CI: 1.09, 1.62), and that in the 1st tertile was 1.22 (95 % CI: 0.92, 1.60). We also found that participants under 60 years old had an OR = 1.63 (95 % CI: 1.20, 2.22), those 60-80 years old had an OR = 1.18 (95 % CI: 1.02, 1.36), and those over 80 years old had an OR = 1.05 (0.80, 1.37). Lastly, we found that males had an OR = 1.43 (95 % CI: 1.22, 1.69), and females had an OR = 1.02 (0.87, 1.20). We found that lower levels of solar radiation were associated with increased odds of incident cognitive impairment.

  20. Dissociations in numerical abilities revealed by progressive cognitive decline in a patient with semantic dementia.

    PubMed

    Cappelletti, Marinella; Kopelman, Michael D; Morton, John; Butterworth, Brian

    2005-10-01

    This study describes a 3-year follow-up investigation of the deterioration of number abilities in a semantic dementia patient (IH). A few studies have previously reported the decline of number knowledge in patients with degenerative disorders, although almost never in semantic dementia (Diesfeldt, 1993; Girelli, Luzzatti, Annoni, & Vecchi, 1999; Grafman, Kempen, Rosenberg, Salazar, & Boller, 1989). These studies described the change of the patients' performance mainly in terms of increased errors in number tasks. On the other hand, dissociations between different types of number abilities, or different arithmetical operations, have been reported in patients with focal lesions. In the present investigation, the cognitive basis of number processing was revealed throughout the patient's cognitive decline. Two major results emerged from a longitudinal study: First, the patient's conceptual knowledge of arithmetic was well preserved despite severe impairment of nonarithmetic conceptual knowledge. Second, the patient's progressive decline revealed patterns of dissociations between different number abilities. These were between (1) multiplication and other arithmetical operations, which particularly emerged in the use of algorithms; (2) impaired knowledge of number facts and procedures on one hand, and conceptual knowledge of arithmetic on the other; and (3) different types of transcoding skills. The implications of these dissociations for the cognitive architecture of number processing are discussed. PMID:21038276

  1. Cerebral small vessel disease: Capillary pathways to stroke and cognitive decline

    PubMed Central

    Engedal, Thorbjørn S; Moreton, Fiona; Hansen, Mikkel B; Wardlaw, Joanna M; Dalkara, Turgay; Markus, Hugh S; Muir, Keith W

    2015-01-01

    Cerebral small vessel disease (SVD) gives rise to one in five strokes worldwide and constitutes a major source of cognitive decline in the elderly. SVD is known to occur in relation to hypertension, diabetes, smoking, radiation therapy and in a range of inherited and genetic disorders, autoimmune disorders, connective tissue disorders, and infections. Until recently, changes in capillary patency and blood viscosity have received little attention in the aetiopathogenesis of SVD and the high risk of subsequent stroke and cognitive decline. Capillary flow patterns were, however, recently shown to limit the extraction efficacy of oxygen in tissue and capillary dysfunction therefore proposed as a source of stroke-like symptoms and neurodegeneration, even in the absence of physical flow-limiting vascular pathology. In this review, we examine whether capillary flow disturbances may be a shared feature of conditions that represent risk factors for SVD. We then discuss aspects of capillary dysfunction that could be prevented or alleviated and therefore might be of general benefit to patients at risk of SVD, stroke or cognitive decline. PMID:26661176

  2. Faster Rate of Cognitive Decline in Essential Tremor Cases than Controls: A Prospective Study

    PubMed Central

    Louis, Elan D.; Benito-León, Julián; Vega-Quiroga, Saturio; Bermejo-Pareja, Félix

    2010-01-01

    Background Mild cognitive deficits have been reported in essential tremor (ET); however, these cognitive deficits have been assessed in cross-sectional rather than longitudinal analyses. Objective To determine whether decline in cognitive test scores occurs at a faster rate in ET cases than controls. Methods In a population-based study of older people (≥65 years) in central Spain (Neurological Disorders in Central Spain, NEDICES), non-demented ET cases and controls were followed prospectively. Participants with baseline or incident Parkinson’s disease or dementia were excluded, as were participants who developed incident ET. At baseline (1994–1995) and at follow-up (1997–1998), a 37-item version of the Mini-Mental State Examination (37-MMSE) was administered. Results 2,319 participants (72.4 ± 5.8 years) included 135 prevalent ET cases and 2,184 controls. At baseline, the mean 37-MMSE in cases was 28.8 ± 5.8 vs. 30.2 ± 4.8 in controls (p = 0.02). During the three year follow-up period, the 37-MMSE declined by 0.70 ± 3.2 points in cases vs. 0.11 ± 3.8 points in controls (p = 0.03). In analyses that adjusted for age, education and other potential confounders, the case-control difference remained robust. Discussion In this population-based, prospective study of non-demented elders, baseline cognitive test scores were lower in ET cases than controls; moreover, during the three-year follow-up period, these scores declined at a rate that was seven-times faster in ET cases. This study provides evidence that cognitive deficits in ET are not static and they appear to be progressing at a faster rate than in elders without this disease. PMID:20561042

  3. Early-Stage White Matter Lesions Detected by Multispectral MRI Segmentation Predict Progressive Cognitive Decline

    PubMed Central

    Jokinen, Hanna; Gonçalves, Nicolau; Vigário, Ricardo; Lipsanen, Jari; Fazekas, Franz; Schmidt, Reinhold; Barkhof, Frederik; Madureira, Sofia; Verdelho, Ana; Inzitari, Domenico; Pantoni, Leonardo; Erkinjuntti, Timo

    2015-01-01

    White matter lesions (WML) are the main brain imaging surrogate of cerebral small-vessel disease. A new MRI tissue segmentation method, based on a discriminative clustering approach without explicit model-based added prior, detects partial WML volumes, likely representing very early-stage changes in normal-appearing brain tissue. This study investigated how the different stages of WML, from a “pre-visible” stage to fully developed lesions, predict future cognitive decline. MRI scans of 78 subjects, aged 65–84 years, from the Leukoaraiosis and Disability (LADIS) study were analyzed using a self-supervised multispectral segmentation algorithm to identify tissue types and partial WML volumes. Each lesion voxel was classified as having a small (33%), intermediate (66%), or high (100%) proportion of lesion tissue. The subjects were evaluated with detailed clinical and neuropsychological assessments at baseline and at three annual follow-up visits. We found that voxels with small partial WML predicted lower executive function compound scores at baseline, and steeper decline of executive scores in follow-up, independently of the demographics and the conventionally estimated hyperintensity volume on fluid-attenuated inversion recovery images. The intermediate and fully developed lesions were related to impairments in multiple cognitive domains including executive functions, processing speed, memory, and global cognitive function. In conclusion, early-stage partial WML, still too faint to be clearly detectable on conventional MRI, already predict executive dysfunction and progressive cognitive decline regardless of the conventionally evaluated WML load. These findings advance early recognition of small vessel disease and incipient vascular cognitive impairment. PMID:26696814

  4. Impaired Olfaction and Risk for Delirium or Cognitive Decline After Cardiac Surgery

    PubMed Central

    Brown, Charles H.; Morrissey, Candice; Ono, Masahiro; Yenokyan, Gayane; Selnes, Ola A.; Walston, Jeremy; Max, Laura; LaFlam, Andrew; Neufeld, Karin; Gottesman, Rebecca F.; Hogue, Charles W.

    2014-01-01

    Summary Statement Impaired olfaction, identified in 33% of patients undergoing cardiac surgery, was associated with the adjusted risk for postoperative delirium but not cognitive decline. Objectives The prevalence and significance of impaired olfaction is not well characterized in patients undergoing cardiac surgery. Because impaired olfaction has been associated with underlying neurologic disease, impaired olfaction may identify patients who are vulnerable to poor neurological outcomes in the perioperative period. The objective of this study was to determine the prevalence of impaired olfaction among patients presenting for cardiac surgery and the independent association of impaired olfaction with postoperative delirium and cognitive decline. Design Nested prospective cohort study Setting Academic hospital Participants 165 patients undergoing coronary artery bypass and/or valve surgery Measurements Olfaction was measured using the Brief Smell Identification Test, with impaired olfaction defined as an olfactory score < 5th percentile of normative data. Delirium was assessed using a validated chart-review method. Cognitive performance was assessed using a neuropsychological testing battery at baseline and 4–6 weeks after surgery. Results Impaired olfaction was identified in 54 of 165 patients (33%) prior to surgery. Impaired olfaction was associated with increased adjusted risk for postoperative delirium (relative risk [RR] 1.90, 95% CI 1.17–3.09; P=0.009). There was no association between impaired olfaction and change in composite cognitive score in the overall study population. Conclusion Impaired olfaction is prevalent in patients undergoing cardiac surgery and is associated with increased adjusted risk for postoperative delirium, but not cognitive decline. Impaired olfaction may identify unrecognized vulnerability for postoperative delirium among patients undergoing cardiac surgery. PMID:25597555

  5. Cognitive experience and its effect on age-dependent cognitive decline in beagle dogs.

    PubMed

    Milgram, Norton W

    2003-11-01

    Test-sophisticated beagle dogs show marked age sensitivity in a size discrimination learning task, with old and senior dogs performing significantly more poorly than young dogs. By contrast, age differences in learning were not seen in dogs naive with respect to neuropsychological test experience. These results indicate that old animals benefit less from prior cognitive experience than young animals, which is an example of an age-dependent loss in plasticity. This finding also suggests that behaviorally experienced animals are a more useful model of human cognitive aging than behaviorally naïve animals. We also looked at the effect of a program of behavioral enrichment in aged dogs. One year of enrichment did not lead to significant differences, but after 2 years the behaviorally enriched group performed significantly better than the control group. The effect after 2 years indicates that a prolonged program of cognitive enrichment can serve as an effective intervention in aged dogs. These findings demonstrate that cognitive abilities in aged animals can be modified by providing behavioral experience, indicating that cognitive abilities remain moderately plastic, even in very old animals. PMID:14584821

  6. Attenuation of oxidative damage-associated cognitive decline by Withania somnifera in rat model of streptozotocin-induced cognitive impairment.

    PubMed

    Ahmed, Md Ejaz; Javed, Hayate; Khan, Mohd Moshahid; Vaibhav, Kumar; Ahmad, Ajmal; Khan, Andleeb; Tabassum, Rizwana; Islam, Farah; Safhi, Mohammed M; Islam, Fakhrul

    2013-10-01

    Oxidative stress is a critical contributing factor to age-related neurodegenerative disorders. Therefore, the inhibition of oxidative damage, responsible for chronic detrimental neurodegeneration, is an important strategy for neuroprotective therapy. Withania somnifera (WS) extract has been reported to have potent antioxidant and free radical quenching properties in various disease conditions. The present study evaluated the hypothesis that WS extract would reduce oxidative stress-associated neurodegeneration after intracerebroventricular injection of streptozotocin (ICV-STZ) in rats. To test this hypothesis, male Wistar rats were pretreated with WS extract at doses of 100, 200, and 300 mg/kg body weight once daily for 3 weeks. On day 22nd, the rats were infused bilaterally with ICV-STZ injection (3 mg/kg body weight) in normal saline while sham group received only saline. Two weeks after the lesioning, STZ-infused rats showed cognitive impairment in the Morris water maze test. The rats were sacrificed after 3 weeks of the lesioning for the estimation of the contents of lipid peroxidation, reduced glutathione, and activities of glutathione reductase, glutathione peroxidase, and catalase. Pretreatment with WS extract attenuated behavioral, biochemical, and histological alterations significantly in dose-dependent manner in the hippocampus and cerebral cortex of ICV-STZ-infused rats. These results suggest that WS affords a beneficial effect on cognitive deficit by ameliorating oxidative damage induced by streptozotocin in a model of cognitive impairment. PMID:23340606

  7. Daily stress magnifies the association between cognitive decline and everyday memory problems: an integration of longitudinal and diary methods.

    PubMed

    Rickenbach, Elizabeth Hahn; Almeida, David M; Seeman, Teresa E; Lachman, Margie E

    2014-12-01

    We examined whether long-term fluid cognitive decline was associated with memory problems in everyday life, and whether stress plays a moderating role. We expected that the association between cognitive decline and everyday memory problems would be magnified in the context of self-reported and physiological stress. Data are from the Boston Longitudinal Study, a subsample of the Midlife in the United States study. Participants in the current study (n = 112) completed a battery of tests measuring fluid cognitive functioning at Time 1 (T1) and 2 (T2) over 10 years. At T2, participants completed weekly diaries of self-reported daily stressors and everyday memory problems for 12 consecutive weeks. Also at T2, participants provided 4 saliva samples over the course of 1 day to assess physiological stress using diurnal cortisol profiles [cortisol awakening response (CAR) and diurnal cortisol slope (DCS)]. Self-reported daily stressors and a less healthy DCS were associated with more everyday memory problems, and participants with greater cognitive decline reported more memory problems compared to those with less or no decline. Self-reported daily stressors and CAR moderated the relationship of cognitive decline and memory problems. As expected, more cognitive decline was associated with greater increases in memory problems on weeks when individuals reported more daily stressors and for individuals with a less healthy CAR. The current findings can inform interventions aimed to identify factors, such as daily stress, that contribute to daily functioning in the context of cognitive decline. PMID:25365691

  8. The role of B vitamins in preventing and treating cognitive impairment and decline.

    PubMed

    Morris, Martha Savaria

    2012-11-01

    Many epidemiologic studies have considered whether markers of B-vitamin status are associated with cognitive function and cognitive decline. This avenue of research was sparked by the homocysteine (Hcy) theory of cardiovascular disease, which was extended to Alzheimer's disease when a link between vascular dementia and Alzheimer's disease was discovered. Hcy could cause cognitive impairment via direct neurotoxicity. However, decreased remethylation of Hcy to methionine might also compromise cognitive function by means other than mere Hcy lowering. Folate and vitamin B-12 participate in Hcy remethylation and largely determine Hcy status. Consequently, much of the relevant research has focused on these 2 B vitamins. The many subtly different hypotheses that investigators have addressed by attempting to link several B-vitamin status indicators to diverse cognition-related outcomes have created a confusing body of conflicting studies that seems to defy summarization. Nevertheless, themes are discernible that aid interpretation, foster hypothesis generation, and inform future study design. For example, despite a shared metabolic pathway, Hcy, vitamin B-12, and folate are differently related to specific cognitive outcomes. Although consistency of findings across studies is often touted as essential to distinguishing causal from coincidental relationships, discrepancies among study findings can be even more informative. PMID:23153734

  9. Relationship between Inflammation and Oxidative Stress and Cognitive Decline in the Institutionalized Elderly

    PubMed Central

    Baierle, Marília; Nascimento, Sabrina N.; Moro, Angela M.; Brucker, Natália; Freitas, Fernando; Gauer, Bruna; Durgante, Juliano; Bordignon, Suelen; Zibetti, Murilo; Trentini, Clarissa M.; Duarte, Marta M. M. F.; Grune, Tilman; Breusing, Nicolle; Garcia, Solange C.

    2015-01-01

    Objective. Cognitive impairment reduces quality of life and is related to vascular and neurodegenerative disorders. However, there is also a close relationship between these diseases and oxidative stress. Thus, the purpose of this study was to assess whether inflammation and oxidative damage are associated with low cognitive performance in the elderly with different housing conditions. Methods. The study groups consisted of 32 institutionalized and 25 noninstitutionalized Brazilian elderly subjects. Oxidative damage, inflammation markers, and cognitive function were evaluated. Results. The results demonstrated pronounced oxidative stress in the institutionalized elderly group, which also had a lower antioxidant status compared to noninstitutionalized subjects. High levels of proinflammatory cytokines were also observed in the institutionalized elderly. Furthermore, the raised levels of inflammatory markers were correlated with increased oxidative stress, and both were associated with low cognitive performance. However, based on multiple linear regression analysis, oxidative stress appears to be the main factor responsible for the cognitive decline. Conclusions. The findings suggest that individuals with lower antioxidant status are more vulnerable to oxidative stress, which is associated with cognitive function, leading to reduced life quality and expectancy. PMID:25874023

  10. Inside the Diabetic Brain: Role of Different Players Involved in Cognitive Decline.

    PubMed

    Gaspar, Joana M; Baptista, Filipa I; Macedo, M Paula; Ambrósio, António F

    2016-02-17

    Diabetes mellitus is the most common metabolic disease, and its prevalence is increasing. A growing body of evidence, both in animal models and epidemiological studies, has demonstrated that metabolic diseases like obesity, insulin resistance, and diabetes are associated with alterations in the central nervous system (CNS), being linked with development of cognitive and memory impairments and presenting a higher risk for dementia and Alzheimer's disease. The rising prevalence of diabetes together with its increasing earlier onset suggests that diabetes-related cognitive dysfunction will increase in the near future, causing substantial socioeconomic impact. Decreased insulin secretion or action, dysregulation of glucose homeostasis, impairment in the hypothalamic-pituitary-adrenal axis, obesity, hyperleptinemia, and inflammation may act independently or synergistically to disrupt neuronal homeostasis and cause diabetes-associated cognitive decline. However, the crosstalk between those factors and the mechanisms underlying the diabetes-related CNS complications is still elusive. During the past few years, different strategies (neuroprotective and antioxidant drugs) have emerged as promising therapies for this complication, which still remains to be preventable or treatable. This Review summarizes fundamental past and ongoing research on diabetes-associated cognitive decline, highlighting potential contributors, mechanistic mediators, and new pharmacological approaches to prevent and/or delay this complication. PMID:26667832

  11. Senescent-induced dysregulation of cAMP/CREB signaling and correlations with cognitive decline.

    PubMed

    Hansen, Rolf T; Zhang, Han-Ting

    2013-06-21

    It is well known that alongside senescence there is a gradual decline in cognitive ability, most noticeably certain kinds of memory such as working, episodic, spatial, and long term memory. However, until recently, not much has been known regarding the specific mechanisms responsible for the decline in cognitive ability with age. Over the past decades, researchers have become more interested in cAMP signaling, and its downstream transcription factor cAMP response element binding protein (CREB) in the context of senescence. However, there is still a lack of understanding on what ultimately causes the cognitive deficits observed with senescence. This review will focus on the changes in intracellular signaling in the brain, more specifically, alterations in cAMP/CREB signaling in aging. In addition, the downstream effects of altered cAMP signaling on cognitive ability with age will be further discussed. Overall, understanding the senescent-related changes that occur in cAMP/CREB signaling could be important for the development of novel drug targets for both healthy aging, and pathological aging such as Alzheimer's disease. PMID:23623816

  12. Chronical sleep interruption-induced cognitive decline assessed by a metabolomics method.

    PubMed

    Feng, Li; Wu, Hong-wei; Song, Guang-qing; Lu, Cong; Li, Ying-hui; Qu, Li-na; Chen, Shan-guang; Liu, Xin-min; Chang, Qi

    2016-04-01

    Good sleep is necessary for optimal health, especially for mental health. Insomnia, sleep deprivation will make your ability to learn and memory impaired. Nevertheless, the underlying pathophysiological mechanism of sleep disorders-induced cognitive decline is still largely unknown. In this study, the sleep deprivation of animal model was induced by chronical sleep interruption (CSI), the behavioral tests, biochemical index determinations, and a liquid chromatography-mass spectrometry (LC-MS) based serum metabolic profiling analysis were performed to explore the effects of CSI on cognitive function and the underlying mechanisms. After 14-days CSI, the cognitive function of the mice was evaluated by new objects preference (NOP) task and temporal order judgment (TOJ) task. Serum corticosterone (CORT), and brain Malondialdehyde (MDA), Superoxide Dismutase (SOD), and Catalase (CAT) levels were determined by ELISA kits. Data were analyzed by Principal Component Analysis (PCA), Partial Least Squares project to latent structures-Discriminant Analysis (PLS-DA), and Student's t-test. We found that the cognitive function of the mice was significantly affected by CSI. Besides, levels of CORT and MDA were higher, and SOD and CAT were lower in CSI mice than those of control. Obvious body weight loss of CSI mice was also observed. Thirteen potential serum biomarkers including choline, valine, uric acid, allantoic acid, carnitines, and retinoids were identified. Affected metabolic pathways involve metabolism of purine, retinoid, lipids, and amino acid. These results showed that CSI can damage the cognitive performance notably. The cognitive decline may ascribe to excessive oxidative stress and a series of disturbed metabolic pathways. PMID:26747207

  13. Guanfacine is an effective countermeasure for hypobaric hypoxia-induced cognitive decline.

    PubMed

    Kauser, H; Sahu, S; Kumar, S; Panjwani, U

    2013-12-19

    Hypobaric hypoxia (HH), an environmental stress resulting from ascent to high altitude, affects perception, memory, judgment, and attention, resulting in degradation of many aspects of normal functioning. Alpha 2A adrenergic agonist, guanfacine proved to be beneficial in the amelioration of neurological outcomes of many neuropsychiatric disorders involving adrenergic imbalance and neurodegeneration. Adrenergic dysregulation and neuronal damage have been implicated in hypoxia-induced cognitive deficits, however, efficacy of guanfacine as a countermeasure for HH-induced cognitive decline remains to be evaluated. We, therefore, have studied the effect of this drug on the HH-induced cognitive deficits, adrenergic dysfunction and neuronal damage. Rats were exposed to HH at a simulated altitude of 25,000 feet for 7days and received an IM injection of either saline or guanfacine at a dose of 1mg/kg. Adrenergic transmission was evaluated by biomarkers i.e. norepinephrine (NE), dopamine (DA) and tyrosine hydroxylase (TH) in medial prefrontal cortex (PFC) by biochemical and immunohistochemical assays. Spine and dendritic morphology of pyramidal neurons in layer II of medial PFC was studied using Golgi-Cox staining and Neurolucida neuronal tracing. The cognitive performance was assessed by Delayed Alternation Task using a T-Maze. There was a significant reduction in HH-induced increases in NE, DA and TH levels with guanfacine treatment. Guanfacine rescued HH-induced dendritic atrophy and mushroom type spine loss. The spatial working memory deficits induced by HH were significantly ameliorated with guanfacine treatment. Furthermore, the cognitive performance showed a positive correlation with dendritic arbors and spine numbers. These results showed that the HH-induced cognitive decline is associated with adrenergic dysregulation and neuronal damage in layer II of medial PFC, and that guanfacine treatment during HH ameliorated these functional and morphological deficits. The

  14. Empirically Defining Trajectories of Late-Life Cognitive and Functional Decline

    PubMed Central

    Hochstetler, Helen; Trzepacz, Paula T.; Wang, Shufang; Yu, Peng; Case, Michael; Henley, David B.; Degenhardt, Elisabeth; Leoutsakos, Jeannie-Marie; Lyketsos, Constantine G.

    2015-01-01

    Background: Alzheimer’s disease (AD) is associated with variable cognitive and functional decline, and it is difficult to predict who will develop the disease and how they will progress. Objective: This exploratory study aimed to define latent classes from participants in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database who had similar growth patterns of both cognitive and functional change using Growth Mixture Modeling (GMM), identify characteristics associated with those trajectories, and develop a decision tree using clinical predictors to determine which trajectory, as determined by GMM, individuals will most likely follow. Methods: We used ADNI early mild cognitive impairment (EMCI), late MCI (LMCI), AD dementia, and healthy control (HC) participants with known amyloid-β status and follow-up assessments on the Alzheimer’s Disease Assessment Scale - Cognitive Subscale or the Functional Activities Questionnaire (FAQ) up to 24 months postbaseline. GMM defined trajectories. Classification and Regression Tree (CART) used certain baseline variables to predict likely trajectory path. Results: GMM identified three trajectory classes (C): C1 (n = 162, 13.6%) highest baseline impairment and steepest pattern of cognitive/functional decline; C3 (n = 819, 68.7%) lowest baseline impairment and minimal change on both; C2 (n = 211, 17.7%) intermediate pattern, worsening on both, but less steep than C1. C3 had fewer amyloid- or apolipoprotein-E ɛ4 (APOE4) positive and more healthy controls (HC) or EMCI cases. CART analysis identified two decision nodes using the FAQ to predict likely class with 82.3% estimated accuracy. Conclusions: Cognitive/functional change followed three trajectories with greater baseline impairment and amyloid and APOE4 positivity associated with greater progression. FAQ may predict trajectory class. PMID:26639960

  15. Monocyte Phenotype and Polyfunctionality Are Associated With Elevated Soluble Inflammatory Markers, Cytomegalovirus Infection, and Functional and Cognitive Decline in Elderly Adults.

    PubMed

    de Pablo-Bernal, Rebeca Sara; Cañizares, Julio; Rosado, Isaac; Galvá, María Isabel; Alvarez-Ríos, Ana Isabel; Carrillo-Vico, Antonio; Ferrando-Martínez, Sara; Muñoz-Fernández, María Ángeles; Rafii-El-Idrissi Benhnia, Mohammed; Pacheco, Yolanda María; Ramos, Raquel; Leal, Manuel; Ruiz-Mateos, Ezequiel

    2016-05-01

    Monocytes are mediators of the inflammatory response and include three subsets: classical, intermediate, and nonclassical. Little is known about the phenotypical and functional age-related changes in monocytes and their association with soluble inflammatory biomarkers, cytomegalovirus infection, and functional and mental decline. We assayed the activation ex vivo and the responsiveness to TLR2 and TLR4 agonists in vitro in the three subsets and assessed the intracellular production of IL1-alpha (α), IL1-beta (β), IL-6, IL-8, TNF-α, and IL-10 of elderly adults (median 83 [67-90] years old;n= 20) compared with young controls (median 35 [27-40] years old;n= 20). Ex vivo, the elderly adults showed a higher percentage of classical monocytes that expressed intracellular IL1-α (p= .001), IL1-β (p= .001), IL-6 (p= .002), and IL-8 (p= .007). Similar results were obtained both for the intermediate and nonclassical subsets and in vitro. Polyfunctionality was higher in the elderly adults. The functionality ex vivo was strongly associated with soluble inflammatory markers. The activation phenotype was independently associated with the anti-cytomegalovirus IgG levels and with functional and cognitive decline. These data demonstrate that monocytes are key cell candidates for the source of the high soluble inflammatory levels. Our findings suggest that cytomegalovirus infection might be a driving force in the activation of monocytes and is associated with the functional and cognitive decline. PMID:26286603

  16. Plasma c-peptide levels and rates of cognitive decline in older, community-dwelling women without diabetes

    PubMed Central

    Okereke, Olivia I.; Pollak, Michael N.; Hu, Frank B.; Hankinson, Susan E.; Selkoe, Dennis J.; Grodstein, Francine

    2008-01-01

    SUMMARY Background Both type 2 diabetes and hyperinsulinemia have been related to diminished cognition. To address independent effects of increasing mid-life insulin secretion on late-life cognition, we prospectively examined the relation of plasma c-peptide levels to cognitive decline in a large sample of older women without diabetes or stroke. Methods Plasma c-peptide levels were measured in 1,187 “young-old” women (mean age=64 years) without diabetes in the Nurses’ Health Study. Cognitive decline was assessed approximately 10 years later. Three repeated cognitive batteries were administered over an average of 4.4 years using telephone-based tests of general cognition, verbal memory, category fluency, and attention. Primary outcomes were general cognition (measured by the Telephone interview for Cognitive Status [TICS], as well as a global score averaging all tests) and a verbal memory score averaging 4 tests of word-list and paragraph recall. Linear mixed effects models were used to compute associations between c-peptide levels and rates of cognitive decline. Results Higher c-peptide levels were associated with faster decline in global cognition and verbal memory. Compared to those in the lowest c-peptide quartile, multivariable-adjusted mean differences (95% CI) in rates of decline for women in the highest quartile were −0.03 (−0.06, − 0.00) units/year for the global score, and −0.05 (−0.09, −0.02) units/year for verbal memory. Each one standard-deviation increase in c-peptide was associated with significantly faster decline on the TICS (p-trend=0.05), global score (p-trend=0.04) and verbal memory (p-trend=0.006). Conclusions Higher levels of insulin secretion in those without diabetes may be related to decline in general cognition and verbal memory. PMID:18261857

  17. Cognitive decline in short and long sleepers: A prospective population-based study (NEDICES)

    PubMed Central

    Benito-León, Julián; Louis, Elan D.; Bermejo-Pareja, Félix

    2013-01-01

    Background It is not clear whether cognitive decline progresses more quickly in long sleepers than in short sleepers or than in participants with usual sleep duration. We assessed cognitive decline as a function of self-reported sleep duration in a prospective population-based cohort (NEDICES). Methods Participants were evaluated at baseline and 3 years later. Baseline demographic variables were recorded and participants indicated their daily sleep usual duration as the sum of nighttime sleep and daytime napping. The average daily total usual sleep duration was grouped into three categories: ≤5 hours (short sleepers), 6 to 8 hours (reference category), and ≥9 hours (long sleepers). At baseline and at follow-up, a 37-item version of the Mini-Mental State Examination (37-MMSE) was administered. Results The final sample, 2,715 participants (72.9±6.1 years), comprised 298 (11%) short sleepers, 1,086 (40%) long sleepers, and 1,331 (49%) in the reference group (6 to 8 hours). During the three year follow-up period, the 37-MMSE declined by 0.5±4.0 points in short sleepers, 0.6±4.3 points in long sleepers, and 0.2±3.8 points in the reference group (p=0.08). The difference between short sleepers and the reference group was not significant (p=0.142); however, the difference between long sleepers and the reference group was significant (p=0.040). In analyses adjusted for baseline age and other potential confounders, this difference remained robust. Conclusions In this study, cognitive test scores among long sleepers declined more rapidly than observed in a reference group. Additional studies are needed to confirm these results. PMID:24094933

  18. Computerized Assessment of Communication for Cognitive Stimulation for People with Cognitive Decline Using Spectral-Distortion Measures and Phylogenetic Inference

    PubMed Central

    Pham, Tuan D.; Oyama-Higa, Mayumi; Truong, Cong-Thang; Okamoto, Kazushi; Futaba, Terufumi; Kanemoto, Shigeru; Sugiyama, Masahide; Lampe, Lisa

    2015-01-01

    Therapeutic communication and interpersonal relationships in care homes can help people to improve their mental wellbeing. Assessment of the efficacy of these dynamic and complex processes are necessary for psychosocial planning and management. This paper presents a pilot application of photoplethysmography in synchronized physiological measurements of communications between the care-giver and people with dementia. Signal-based evaluations of the therapy can be carried out using the measures of spectral distortion and the inference of phylogenetic trees. The proposed computational models can be of assistance and cost-effectiveness in caring for and monitoring people with cognitive decline. PMID:25803586

  19. Computerized assessment of communication for cognitive stimulation for people with cognitive decline using spectral-distortion measures and phylogenetic inference.

    PubMed

    Pham, Tuan D; Oyama-Higa, Mayumi; Truong, Cong-Thang; Okamoto, Kazushi; Futaba, Terufumi; Kanemoto, Shigeru; Sugiyama, Masahide; Lampe, Lisa

    2015-01-01

    Therapeutic communication and interpersonal relationships in care homes can help people to improve their mental wellbeing. Assessment of the efficacy of these dynamic and complex processes are necessary for psychosocial planning and management. This paper presents a pilot application of photoplethysmography in synchronized physiological measurements of communications between the care-giver and people with dementia. Signal-based evaluations of the therapy can be carried out using the measures of spectral distortion and the inference of phylogenetic trees. The proposed computational models can be of assistance and cost-effectiveness in caring for and monitoring people with cognitive decline. PMID:25803586

  20. Hippocampal volume and integrity as predictors of cognitive decline in intact elderly.

    PubMed

    Bruno, Davide; Ciarleglio, Adam; Grothe, Michel J; Nierenberg, Jay; Bachman, Alvin H; Teipel, Stefan J; Petkova, Eva; Ardekani, Babak A; Pomara, Nunzio

    2016-08-01

    The risk of Alzheimer's disease can be predicted by volumetric analyses of MRI data in the medial temporal lobe. The present study compared a volumetric measurement of the hippocampus with a novel measure of hippocampal integrity (HI) derived from the ratio of parenchyma volume over total volume. Participants were cognitively intact and aged 60 years or older at baseline, and were tested twice, roughly 3 years apart. Participants had been recruited for a study on late-life major depression (LLMD) and were evenly split between depressed patients and controls. Linear regression models were applied to the data with a cognitive composite score as the outcome, and HI and volume, together or separately, as predictors. Subsequent cognitive performance was predicted well by models that included an interaction between HI and LLMD status, such that lower HI scores predicted more cognitive decline in depressed patients. More research is needed, but tentative results from this study appear to suggest that the newly introduced measure HI is an effective tool for the purpose of predicting future changes in general cognitive ability, and especially so in individuals with LLMD. PMID:27306593

  1. Cerebrospinal fluid α-synuclein predicts cognitive decline in Parkinson disease progression in the DATATOP cohort.

    PubMed

    Stewart, Tessandra; Liu, Changqin; Ginghina, Carmen; Cain, Kevin C; Auinger, Peggy; Cholerton, Brenna; Shi, Min; Zhang, Jing

    2014-04-01

    Most patients with Parkinson disease (PD) develop both cognitive and motor impairment, and biomarkers for progression are urgently needed. Although α-synuclein is altered in cerebrospinal fluid of patients with PD, it is not known whether it predicts motor or cognitive deterioration. We examined clinical data and α-synuclein in >300 unmedicated patients with PD who participated in the deprenyl and tocopherol antioxidative therapy of parkinsonism (DATATOP) study, with up to 8 years of follow-up. Longitudinal measures of motor and cognitive function were studied before (phase 1) and during (phase 2) levodopa therapy; cerebrospinal fluid was collected at the beginning of each phase. Correlations and linear mixed models were used to assess α-synuclein association with disease severity and prediction of progression in the subsequent follow-up period. Despite decreasing α-synuclein (phase 1 to phase 2 change of -0.05 ± 0.21 log-transformed values, P < 0.001), no correlations were observed between α-synuclein and motor symptoms. Longitudinally, lower α-synuclein predicted better preservation of cognitive function by several measures [Selective Reminding Test total recall α-synuclein × time interaction effect coefficient, -0.12 (P = 0.037); delayed recall, -0.05 (P = 0.002); New Dot Test, -0.03 (P = 0.002)]. Thus, α-synuclein, although not clinically useful for motor progression, might predict cognitive decline, and future longitudinal studies should include this outcome for further validation. PMID:24625392

  2. Biomarker clusters are differentially associated with longitudinal cognitive decline in late midlife.

    PubMed

    Racine, Annie M; Koscik, Rebecca L; Berman, Sara E; Nicholas, Christopher R; Clark, Lindsay R; Okonkwo, Ozioma C; Rowley, Howard A; Asthana, Sanjay; Bendlin, Barbara B; Blennow, Kaj; Zetterberg, Henrik; Gleason, Carey E; Carlsson, Cynthia M; Johnson, Sterling C

    2016-08-01

    The ability to detect preclinical Alzheimer's disease is of great importance, as this stage of the Alzheimer's continuum is believed to provide a key window for intervention and prevention. As Alzheimer's disease is characterized by multiple pathological changes, a biomarker panel reflecting co-occurring pathology will likely be most useful for early detection. Towards this end, 175 late middle-aged participants (mean age 55.9 ± 5.7 years at first cognitive assessment, 70% female) were recruited from two longitudinally followed cohorts to undergo magnetic resonance imaging and lumbar puncture. Cluster analysis was used to group individuals based on biomarkers of amyloid pathology (cerebrospinal fluid amyloid-β42/amyloid-β40 assay levels), magnetic resonance imaging-derived measures of neurodegeneration/atrophy (cerebrospinal fluid-to-brain volume ratio, and hippocampal volume), neurofibrillary tangles (cerebrospinal fluid phosphorylated tau181 assay levels), and a brain-based marker of vascular risk (total white matter hyperintensity lesion volume). Four biomarker clusters emerged consistent with preclinical features of (i) Alzheimer's disease; (ii) mixed Alzheimer's disease and vascular aetiology; (iii) suspected non-Alzheimer's disease aetiology; and (iv) healthy ageing. Cognitive decline was then analysed between clusters using longitudinal assessments of episodic memory, semantic memory, executive function, and global cognitive function with linear mixed effects modelling. Cluster 1 exhibited a higher intercept and greater rates of decline on tests of episodic memory. Cluster 2 had a lower intercept on a test of semantic memory and both Cluster 2 and Cluster 3 had steeper rates of decline on a test of global cognition. Additional analyses on Cluster 3, which had the smallest hippocampal volume, suggest that its biomarker profile is more likely due to hippocampal vulnerability and not to detectable specific volume loss exceeding the rate of normal ageing. Our

  3. Predicting loss of employment over three years in multiple sclerosis: clinically meaningful cognitive decline.

    PubMed

    Morrow, Sarah A; Drake, Allison; Zivadinov, Robert; Munschauer, Frederick; Weinstock-Guttman, Bianca; Benedict, Ralph H B

    2010-10-01

    Cognitive dysfunction is common in multiple sclerosis (MS), yet the magnitude of change on objective neuropsychological (NP) tests that is clinically meaningful is unclear. We endeavored to determine NP markers of the transition from employment to work disability in MS, as indicated by degree of decline on individual tests. Participants were 97 employed MS patients followed over 41.3 ± 17.6 months with a NP battery covering six domains of cognitive function. Deterioration at follow-up was designated as documented and paid disability benefits (conservative definition) or a reduction in hours/work responsibilities (liberal definition). Using the conservative definition, 28.9% reported deteriorated employment status and for the liberal definition, 45.4%. The Symbol Digit Modalities Test (SDMT) and California Verbal Learning Test, Total Learning (CVLT2-TL) measures distinguished employed and disabled patients at follow-up. Controlling for demographic and MS characteristics, the odds ratio of a deterioration based on a change of 2.0 on the CVLT2-TL was 3.7 (95% CI 1.2-11.4 and SDMT by 4.0 was 4.2 (95% CI 1.2-14.8), accounting for 86.7% of the area under the ROC curve. We conclude that decline on NP testing over time is predictive of deterioration in vocational status, establishing a magnitude of decline on NP tests that is clinically meaningful. PMID:20830649

  4. Problems meeting basic needs predict cognitive decline in community-dwelling Hispanic older adults.

    PubMed

    Sachs-Ericsson, Natalie; Corsentino, Elizabeth; Cougle, Jesse R

    2009-09-01

    Objectives. Indices of low socioeconomic status (SES) have been found to predict negative health outcomes. However, problems meeting basic needs (e.g., not having enough money for health care, adequate food, etc.) may be a more potent measure of negative health outcomes than other more typically assessed indices of SES, such as income. This article examined the association between problems meeting basic needs and cognitive decline in a sample of community-dwelling Hispanic older adults (N = 1,964). Method. The authors used a prospective design to study the influence of problems meeting basic needs on cognitive functioning. Analyses controlled for demographics, health problems, and depressive symptoms. Results. The authors found problems meeting basic needs to be a more potent predictor of cognitive decline than income. Discussion. Interventions focused on providing older adults with resources for meeting basic needs, such as adequate food and health care, may substantially reduce the subsequent level of stress and health problems in this population. PMID:19571183

  5. Biochemical and neuroimaging studies in subjective cognitive decline: progress and perspectives.

    PubMed

    Sun, Yu; Yang, Fu-Chi; Lin, Ching-Po; Han, Ying

    2015-10-01

    Neurodegeneration due to Alzheimer's disease (AD) can progress over decades before dementia becomes apparent. Indeed, patients with mild cognitive impairment (MCI) already demonstrate significant lesion loads. In most cases, MCI is preceded by subjective cognitive decline (SCD), which is applied to individuals who have self-reported memory-related complaints and has been associated with a higher risk of future cognitive decline and conversion to dementia. Based on the schema of a well-received model of biomarker dynamics in AD pathogenesis, it has been postulated that SCD symptoms may result from compensatory changes in response to β-amyloid accumulation and neurodegeneration. Although SCD is considered a prodromal stage of MCI, it is also a common manifestation in old age, independent of AD, and the predictive value of SCD for AD pathology remains controversial. Here, we provide a review focused on the contributions of cross-sectional and longitudinal analogical studies of biomarkers and neuroimaging evidence in disentangling under what conditions SCD may be attributable to AD pathology. In conclusion, there is promising evidence indicating that clinicians should be able to differentiate pre-AD SCD based on the presence of pathophysiological biomarkers in cerebrospinal fluid (CSF) and neuroimaging. However, this neuroimaging approach is still at an immature stage without an established rubric of standards. A substantial amount of work remains in terms of replicating recent findings and validating the clinical utility of identifying SCD. PMID:25864576

  6. Compensatory mechanisms in higher-educated subjects with Alzheimer's disease: a study of 20 years of cognitive decline.

    PubMed

    Amieva, Hélène; Mokri, Hind; Le Goff, Mélanie; Meillon, Céline; Jacqmin-Gadda, Hélène; Foubert-Samier, Alexandra; Orgogozo, Jean-Marc; Stern, Yaakov; Dartigues, Jean-François

    2014-04-01

    A better knowledge of long-term trajectories of cognitive decline is a central feature of the study of the process leading to Alzheimer's dementia. Several factors may mitigate such decline, among which is education, a major risk factor for Alzheimer's disease. The aim of our work was to compare the pattern and duration of clinical trajectories before Alzheimer's dementia in individuals with low and high education within the PAQUID cohort involving 20 years of follow-up. The sample comprises 442 participants with incident Alzheimer's disease (27.2% were male)--171 with low education (mean age=86.2 years; standard deviation=5.3 years) and 271 with higher education (mean age=86.5; standard deviation=5.4)--and 442 control subjects matched according to age, sex and education. At each visit and up to the 20-year follow-up visit, several cognitive and clinical measures were collected and incident cases of Alzheimer's disease clinically diagnosed. The evolution of clinical measures in pre-demented subjects and matched controls was analysed with a semi-parametric extension of the mixed effects linear model. The results show that the first signs of cognitive decline occurred 15 to 16 years before achieving dementia threshold in higher-educated subjects whereas signs occurred at 7 years before dementia in low-educated subjects. There seemed to be two successive periods of decline in higher-educated subjects. Decline started ∼15 to 16 years before dementia with subtle impairment restricted to some cognitive tests and with no impact during the first 7 to 8 years on global cognition, cognitive complaints, or activities of daily living scales. Then, ∼7 years before dementia, global cognitive abilities begin to deteriorate, along with difficulties dealing with complex activities of daily living, the increase in self-perceived difficulties and depressive symptoms. By contrast, lower-educated subjects presented a single period of decline lasting ∼7 years, characterized by

  7. The relationship between long-term sunlight radiation and cognitive decline in the REGARDS cohort study.

    PubMed

    Kent, Shia T; Kabagambe, Edmond K; Wadley, Virginia G; Howard, Virginia J; Crosson, William L; Al-Hamdan, Mohammad Z; Judd, Suzanne E; Peace, Fredrick; McClure, Leslie A

    2014-04-01

    Sunlight may be related to cognitive function through vitamin D metabolism or circadian rhythm regulation. The analysis presented here sought to test whether ground and satellite measures of solar radiation are associated with cognitive decline. The study used a 15-year residential history merged with satellite and ground monitor data to determine sunlight (solar radiation) and air temperature exposure for a cohort of 19,896 cognitively intact black and white participants aged 45+ from the 48 contiguous United States. Exposures of 15, 10, 5, 2, and 1-year were used to predict cognitive status at the most recent assessment in logistic regression models; 1-year insolation and maximum temperatures were chosen as exposure measures. Solar radiation interacted with temperature, age, and gender in its relationships with incident cognitive impairment. After adjustment for covariates, the odds ratio (OR) of cognitive decline for solar radiation exposure below the median vs above the median in the 3rd tertile of maximum temperatures was 1.88 (95 % CI: 1.24, 2.85), that in the 2nd tertile was 1.33 (95 % CI: 1.09, 1.62), and that in the 1st tertile was 1.22 (95 % CI: 0.92, 1.60). We also found that participants under 60 years old had an OR = 1.63 (95 % CI: 1.20, 2.22), those 60-80 years old had an OR = 1.18 (95 % CI: 1.02, 1.36), and those over 80 years old had an OR = 1.05 (0.80, 1.37). Lastly, we found that males had an OR = 1.43 (95 % CI: 1.22, 1.69), and females had an OR = 1.02 (0.87, 1.20). We found that lower levels of solar radiation were associated with increased odds of incident cognitive impairment. PMID:23340910

  8. Cognitive decline impairs financial and health literacy among community-based older persons without dementia

    PubMed Central

    Boyle, Patricia A.; Yu, Lei; Wilson, Robert S.; Segawa, Eisuke; Buchman, Aron S.; Bennett, David A.

    2013-01-01

    Literacy is an important determinant of health and well-being across the lifespan but is critical in aging, when many influential health and financial decisions are made. Prior studies suggest that older persons exhibit lower literacy than younger persons, particularly in the domains of financial and health literacy, but the reasons why remain unknown. The objectives of this study were to: a) examine pathways linking diverse resources (i.e., education, word knowledge, cognitive function, and decision making style) to health and financial literacy among older persons and determine the extent to which the relation of age with literacy represents a direct effect versus an indirect effect due to decrements in specific cognitive functions (i.e., executive functions and episodic memory), and b) test the hypothesis that declines in executive function and episodic memory are associated with lower literacy among older persons without dementia. 645 community-based older persons without dementia underwent detailed assessments of diverse resources, including education, word knowledge, cognitive function (i.e., executive function, episodic memory) and decision making style (i.e., risk aversion), and completed a measure of literacy that included items similar to those assessed in the Health and Retirement Study, such as numeracy, financial concepts such as compound inflation and knowledge of stocks and bonds, and important health concepts such as understanding of drug risk and Medicare Part D. Path analysis revealed a strong effect of age on literacy, with about half of the effect of age on literacy due to decrements in executive functions and episodic memory. In addition, executive function had an indirect effect on literacy via decision making style (i.e., risk aversion), and education and word knowledge had independent effects on literacy. Finally, among (n=447) persons with repeated cognitive assessments available for up to 14 years, regression analysis supported the

  9. Exploring Experiences and Perceptions of Aging and Cognitive Decline Across Diverse Racial and Ethnic Groups

    PubMed Central

    Roberts, Lisa R.; Schuh, Holly; Sherzai, Dean; Belliard, Juan Carlos; Montgomery, Susanne B.

    2015-01-01

    Objective To explore how older adults from three prominent ethnoracial groups experience cognitive decline and aging. Method Semistructured key informant interviews (KIIs) and focus groups (FGs) were conducted with caregivers, experts, and older adults. Results (N = 75). Fifteen KIIs regarding cognitive aging issues were conducted among health care professionals and community-based agencies serving older adults. Eight FGs included family caregivers and physicians, and six FGs with Latino, African American, and White older adult community members. Major themes included (a) personal expectations about aging, (b) societal value of older adults, (c) model of care preferred, and (d) community concerns. An overarching theme was a sense of loss associated with aging; however, how this loss was experienced and dealt with varied. Discussion Distinct patterns of concerns and views are important to understand for the development of programs aimed at meeting the needs of diverse older adult community members to improve health outcomes. PMID:26925436

  10. Diabetes and cognitive decline in a French cohort of patients infected with HIV-1

    PubMed Central

    Richert, Laura; Thiébaut, Rodolphe; Bruyand, Mathias; Amieva, Hélène; Dauchy, Frédéric-Antoine; Dartigues, Jean-François; Neau, Didier; Morlat, Philippe; Dehail, Patrick; Dabis, François; Bonnet, Fabrice; Chêne, Geneviève

    2015-01-01

    Objective: We investigated the relationship of diabetes and prediabetes with cognitive performances, assessed through raw test and z scores and according to neurocognitive impairment (NCI) classification in a cohort of individuals infected with HIV. Methods: The ANRS CO3 Aquitaine cohort is a prospective hospital-based cohort of HIV-1–infected patients under routine clinical management in 6 public hospitals in southwestern France. Between 2007 and 2009, an ancillary study consisted of a neuropsychological battery of 10 tests at baseline and 2-year follow-up. The severity of NCI (normal, asymptomatic, mild, HIV dementia) was assessed according to international guidelines. Results: At baseline (400 patients, 33 with prediabetes, 39 with diabetes), in cross-sectional multivariable analyses, patients with diabetes performed significantly worse on 9 neuropsychological tests that assessed memory, executive functions, attention, psychomotor speed, language, and manual dexterity. Participants with prediabetes had worse performances compared with those who had normal glycemia in 5 tests. The longitudinal analysis of the association between glycemia status at baseline and change in cognitive performances over 2-year follow-up (n = 283) suggested that patients with diabetes also showed a slightly higher decline on 5 of the 10 tests, those involving executive functions and memory functioning. Glycemia status at baseline was not significantly associated with NCI severity in cross-sectional (p = 0.44) and longitudinal (p = 0.64) analyses. Conclusions: In this hospital-based cohort of people living with HIV, diabetes, but not the other cardiovascular risk factors, is associated with worse cognitive performances in several cognitive domains and with larger decline in fewer domains over the short term. PMID:26156515

  11. Monitoring the Early Signs of Cognitive Decline in Elderly by Computer Games: An MRI Study

    PubMed Central

    Sirály, Enikő; Szabó, Ádám; Szita, Bernadett; Kovács, Vivienne; Fodor, Zsuzsanna; Marosi, Csilla; Salacz, Pál; Hidasi, Zoltán; Maros, Viktor; Hanák, Péter; Csibri, Éva; Csukly, Gábor

    2015-01-01

    Background It is anticipated that current and future preventive therapies will likely be more effective in the early stages of dementia, when everyday functioning is not affected. Accordingly the early identification of people at risk is particularly important. In most cases, when subjects visit an expert and are examined using neuropsychological tests, the disease has already been developed. Contrary to this cognitive games are played by healthy, well functioning elderly people, subjects who should be monitored for early signs. Further advantages of cognitive games are their accessibility and their cost-effectiveness. Purpose The aim of the investigation was to show that computer games can help to identify those who are at risk. In order to validate games analysis was completed which measured the correlations between results of the 'Find the Pairs' memory game and the volumes of the temporal brain regions previously found to be good predictors of later cognitive decline. Participants and Methods 34 healthy elderly subjects were enrolled in the study. The volume of the cerebral structures was measured by MRI. Cortical reconstruction and volumetric segmentation were performed by Freesurfer. Results There was a correlation between the number of attempts and the time required to complete the memory game and the volume of the entorhinal cortex, the temporal pole, and the hippocampus. There was also a correlation between the results of the Paired Associates Learning (PAL) test and the memory game. Conclusions The results gathered support the initial hypothesis that healthy elderly subjects achieving lower scores in the memory game have increased level of atrophy in the temporal brain structures and showed a decreased performance in the PAL test. Based on these results it can be concluded that memory games may be useful in early screening for cognitive decline. PMID:25706380

  12. Disrupted White Matter Network and Cognitive Decline in Type 2 Diabetes Patients.

    PubMed

    Zhang, Junying; Liu, Zhen; Li, Zixiao; Wang, Yunxia; Chen, Yaojing; Li, Xin; Chen, Kewei; Shu, Ni; Zhang, Zhanjun

    2016-05-01

    Type 2 diabetes mellitus is accompanied by cognitive impairment and is associated with an increased risk of dementia. Damage to brain structures such as white matter network disruption may underlie this cognitive disturbance. In the present study, 886 non-diabetic and 163 type 2 diabetic participants completed a battery of neuropsychological tests. Among them, 38 diabetic patients and 34 non-diabetic participants that matched the patients for age/sex/education received a magnetic resonance imaging-based diffusion tensor imaging. Then we calculated the topological properties of the white matter network using a graph theoretical method to investigate network efficiency differences between groups. We found that type 2 diabetic patients had inferior performances compared to the non-diabetic controls, in several cognitive domains involving executive function, spatial processing, memory, and attention. We also found that diabetic patients exhibited a disrupted topological organization of the white matter network (including the global network properties, i.e., network strength, global efficiency, local efficiency and shortest path length, and the nodal efficiency of the right rolandic operculum) in the brain. Moreover, those global network properties and the nodal efficiency of the right rolandic operculum both had positive correlations with executive function in the patient group. The results suggest that type 2 diabetes mellitus leads to an alteration in the topological organization of the cortical white matter network and this alteration may account for the observed cognitive decline. PMID:27163818

  13. Prospective Study of Arterial Stiffness and Subsequent Cognitive Decline Among Community-Dwelling Older Japanese

    PubMed Central

    Taniguchi, Yu; Fujiwara, Yoshinori; Nofuji, Yu; Nishi, Mariko; Murayama, Hiroshi; Seino, Satoshi; Tajima, Rika; Matsuyama, Yutaka; Shinkai, Shoji

    2015-01-01

    Background Brachial-ankle pulse wave velocity (baPWV) is inversely associated with cognitive function. However, it is not known whether baPWV predicts cognitive decline (CD) in later life. We examined whether or not baPWV is an independent risk marker of subsequent CD in a population of older Japanese. Methods Among 982 adults aged 65 years or older who participated in a baseline survey, 526 cognitively intact adults (Mini-Mental State Examination [MMSE] score ≥24; mean [SD] age, 71.7 [5.6] years; women, 57.8%) were followed for a period of up to 5 years. Pulse wave velocity was determined using an automated waveform analyser. Cognition was assessed by the MMSE, and CD was defined as a decrease of two points or more on the MMSE. Results During an average follow-up of 3.4 years, 85 participants (16.2%) developed CD. After controlling for important confounders, the odds ratios for CD in the highest and middle tertiles of baPWV, as compared with the lowest tertile, were 2.95 (95% confidence interval, 1.29–6.74) and 2.39 (95% confidence interval, 1.11–5.15), respectively. Conclusions High baPWV was an independent predictor of CD in a general population of older adults and may be useful in the clinical evaluation of elders. PMID:26235455

  14. The Neural Consequences of Age-Related Hearing Loss.

    PubMed

    Peelle, Jonathan E; Wingfield, Arthur

    2016-07-01

    During hearing, acoustic signals travel up the ascending auditory pathway from the cochlea to auditory cortex; efferent connections provide descending feedback. In human listeners, although auditory and cognitive processing have sometimes been viewed as separate domains, a growing body of work suggests they are intimately coupled. Here, we review the effects of hearing loss on neural systems supporting spoken language comprehension, beginning with age-related physiological decline. We suggest that listeners recruit domain general executive systems to maintain successful communication when the auditory signal is degraded, but that this compensatory processing has behavioral consequences: even relatively mild levels of hearing loss can lead to cascading cognitive effects that impact perception, comprehension, and memory, leading to increased listening effort during speech comprehension. PMID:27262177

  15. Predictors of Postoperative Cognitive Decline in Very Old Patients With Hip Fracture

    PubMed Central

    Müller, Stephan; Kammerlander, Christian; Gosch, Markus

    2014-01-01

    Background: To investigate incidence and predictors of the various postoperative cognitive declines in old patients with hip fracture. Methods: This retrospective chart study evaluated 411 patients (age ≥80 years, follow-up 5 years). After exclusion of 82 patients (preexisting dementia or delirium), 70 patients showing either diagnosed postoperative delirium (POD; group 1; N = 18, 5.5%) or an unspecified cognitive dysfunction and behavior (group 2; N = 52, 15.8%) were analyzed and compared with those without any acute postoperative cerebral impairment (control group; N = 259, 78.7%). Medical history, anesthesiological, orthopedic, and rehabilitation data were assessed using the medical database of the hospital information system. Relative ratio was calculated with Fisher exact test: P value Bonferroni corrected ≤.003. Results: Acute cognitive complications were observed in 70 (21.3%) patients. Our data in group 1 showed that patients with a medical history of stroke (relative risk [RR] = 16.2, P = .0001) or nicotine abuse (RR = 14.4, P = .001) and perioperative surgical bleeding (RR = 6.54, P = .002) are more likely to develop POD. Unspecified cognitive dysfunction and behavior (group 2) was significantly associated with a medical history of stroke (RR = 12.5, P = .0001) and postoperatively with depression (RR = 3.32, P = .001). In the follow-up, significantly more patients in group 1 (55.6%, RR = 21.8, P = .0001) and group 2 (13.5%, RR = 3.88, P = .001) developed dementia as compared to controls (1.9%). Mortality did not differ significantly between the groups (group 1: RR = 1.75, P = .5 and group 2: RR = 0.66, P = 1.0). Conclusion: These data show that various predictors can identify a greater likelihood of developing postoperative cognitive decline in very old patients with hip fracture. Not identifying or labeling of POD limits the opportunity for evaluation, treatment, and planning. Thus, routine cognitive assessments need to be performed in the scope of

  16. Supporting Family Carers of Community-Dwelling Elder with Cognitive Decline: A Randomized Controlled Trial

    PubMed Central

    Schoenmakers, Birgitte; Buntinx, Frank; Delepeleire, Jan

    2010-01-01

    Objective. Caring for a patient with cognitive decline has an important impact on the general well-being of family caregivers. Although highly appreciated, interventions in dementia home care remain mainly ineffective in terms of well-being. Consequently, in spite of an extensive support system, abrupt ending of home care remains more rule than exception. Method. The hypothesis was that the intervention of a care counselor, coordinating care in quasi-unstructured way during one year, will alleviate caregivers' feelings of depression. The study population was composed of community-dwelling patients with cognitive decline. A care counselor was at the exclusive disposal of the intervention group. Primary outcome measure was caregiver depression. Results. Finally, depression was 6.25 times less frequent in the intervention group. The actual intervention appeared minimal with only ten applications for more support followed by only three interventions effectively carried out. Although caregivers felt burdened and depressed, formal support remained stable. On the other hand, the availability of the care counselor made caregivers feel less depressed with the same amount of support. Conclusion. Carers do not always need to be surrounded with more professionals, but they want to feel more supported. In terms of policy, this could have some important implications. PMID:22332005

  17. Predictors of cognitive decline in the early stage of probable Alzheimer's disease.

    PubMed

    Marra, C; Silveri, M C; Gainotti, G

    2000-01-01

    Several papers have attempted to find neurological and neuropsychological predictors of progression in Alzheimer's disease (AD) till now. Despite this quite large amount of works, different and not univocal conclusions have been reported in this field. Different study samples, different end-points and differences in statistical methods can explain much of the inconsistency in the results obtained. In our study, AD patients were examined in a very early stage of the disease to avoid any possible risk to examine subjects at different times of evolution. All the patients underwent an extensive neuropsychological test battery twice (baseline and follow-up) spaced out over about 1 year and were divided into two groups of fast decliners (FD) and slow decliners (SD) on the basis of their rate of decay at the MMSE score. Verbal memory tests, mental control abilities and attention-demanding tasks seem to play a pivotal role in distinguishing the two groups of subjects in the early stage of the disease. Moreover, FD patients show a worse performance than SD at the baseline in most of the cognitive domains explored. In conclusion, different subtypes of AD do exist and an important predictor of progression is represented by the severity of the cognitive impairment at the onset. PMID:10867447

  18. Longitudinal Protein Changes in Blood Plasma Associated with the Rate of Cognitive Decline in Alzheimer's Disease.

    PubMed

    Sattlecker, Martina; Khondoker, Mizanur; Proitsi, Petroula; Williams, Stephen; Soininen, Hilkka; Kłoszewska, Iwona; Mecocci, Patrizia; Tsolaki, Magda; Vellas, Bruno; Lovestone, Simon; Dobson, Richard Jb

    2015-01-01

    Biomarkers of Alzheimer's disease (AD) progression are needed to support the development of urgently needed disease modifying drugs. We employed a SOMAscan assay for quantifying 1,001 proteins in blood samples from 90 AD subjects, 37 stable mild cognitive impaired (MCI) subjects, 39 MCI subjects converting to AD within a year and 69 controls at baseline and one year follow up. We used linear mixed effects models to identify proteins changing significantly over one year with the rate of cognitive decline, which was quantified as the reduction in Mini Mental State Examination (MMSE) scores. Additionally, we investigated proteins changing differently across disease groups and during the conversion from MCI to AD. We found that levels of proteins belonging to the complement cascade increase significantly in fast declining AD patients. Longitudinal changes in the complement cascade might be a surrogate biomarker for disease progression. We also found that members of the cytokine-cytokine receptor interaction pathway change during AD when compared to healthy aging subjects. PMID:26599049

  19. Hyperamylinemia as a risk factor for accelerated cognitive decline in diabetes

    PubMed Central

    Ly, Han

    2016-01-01

    Type II diabetes increases the risk for cognitive decline via multiple traits. Amylin is a pancreatic hormone that has amyloidogenic and cytotoxic properties similar to the amyloid-β peptide. The amylin hormone is overexpressed in individuals with pre-diabetic insulin resistance or obesity leading to amylin oligomerization and deposition in pancreatic islets. Amylin oligomerization was implicated in the apoptosis of the insulin-producing β-cells. Recent studies showed that brain tissue from diabetic patients with cerebrovascular dementia or Alzheimer’s disease contains significant deposits of oligomerized amylin. It has also been reported that the brain amylin deposition reduced exploratory drive, recognition memory and vestibulomotor function in a rat model that overexpresses human amylin in the pancreas. These novel findings are reviewed here and the hypothesis that type II diabetes is linked with cognitive decline by amylin accumulation in the brain is proposed. Deciphering the impact of hyperamylinemia on the brain is critical for both etiology and treatment of dementia. PMID:26503000

  20. Effects of education and race on cognitive decline: An integrative study of generalizability versus study-specific results.

    PubMed

    Gross, Alden L; Mungas, Dan M; Crane, Paul K; Gibbons, Laura E; MacKay-Brandt, Anna; Manly, Jennifer J; Mukherjee, Shubhabrata; Romero, Heather; Sachs, Bonnie; Thomas, Michael; Potter, Guy G; Jones, Richard N

    2015-12-01

    The objective of the study was to examine variability across multiple prospective cohort studies in level and rate of cognitive decline by race/ethnicity and years of education. We compare data across studies, we harmonized estimates of common latent factors representing overall or general cognitive performance, memory, and executive function derived from the: (a) Washington Heights, Hamilton Heights, Inwood Columbia Aging Project (N = 4,115), (b) Spanish and English Neuropsychological Assessment Scales (N = 525), (c) Duke Memory, Health, and Aging study (N = 578), and (d) Neurocognitive Outcomes of Depression in the Elderly (N = 585). We modeled cognitive change over age for cognitive outcomes by race, education, and study. We adjusted models for sex, dementia status, and study-specific characteristics. The results found that for baseline levels of overall cognitive performance, memory, and executive function, differences in race and education tended to be larger than between-study differences and consistent across studies. This pattern did not hold for rate of cognitive decline: effects of education and race/ethnicity on cognitive change were not consistently observed across studies, and when present were small, with racial/ethnic minorities and those with lower education declining at faster rates. In this diverse set of datasets, non-Hispanic Whites and those with higher education had substantially higher baseline cognitive test scores. However, differences in the rate of cognitive decline by race/ethnicity and education did not follow this pattern. This study suggests that baseline test scores and longitudinal change have different determinants, and future studies to examine similarities and differences of causes of cognitive decline in racially/ethnically and educationally diverse older groups is needed. PMID:26523693

  1. Motor Control and Aging: Links to Age-Related Brain Structural, Functional, and Biochemical Effects

    PubMed Central

    Seidler, Rachael D.; Bernard, Jessica A.; Burutolu, Taritonye B.; Fling, Brett W.; Gordon, Mark T.; Gwin, Joseph T.; Kwak, Youngbin; Lipps, David B.

    2009-01-01

    Although connections between cognitive deficits and age-associated brain differences have been elucidated, relationships with motor performance are less well understood. Here, we broadly review age-related brain differences and motor deficits in older adults in addition to cognition-action theories. Age-related atrophy of the motor cortical regions and corpus callosum may precipitate or coincide with motor declines such as balance and gait deficits, coordination deficits, and movement slowing. Correspondingly, degeneration of neurotransmitter systems—primarily the dopaminergic system—may contribute to age-related gross and fine motor declines, as well as to higher cognitive deficits. In general, older adults exhibit involvement of more widespread brain regions for motor control than young adults, particularly the prefrontal cortex and basal ganglia networks. Unfortunately these same regions are the most vulnerable to age-related effects, resulting in an imbalance of “supply and demand”. Existing exercise, pharmaceutical, and motor training interventions may ameliorate motor deficits in older adults. PMID:19850077

  2. Relative value of diverse brain MRI and blood-based biomarkers for predicting cognitive decline in the elderly

    NASA Astrophysics Data System (ADS)

    Madsen, Sarah K.; Ver Steeg, Greg; Daianu, Madelaine; Mezher, Adam; Jahanshad, Neda; Nir, Talia M.; Hua, Xue; Gutman, Boris A.; Galstyan, Aram; Thompson, Paul M.

    2016-03-01

    Cognitive decline accompanies many debilitating illnesses, including Alzheimer's disease (AD). In old age, brain tissue loss also occurs along with cognitive decline. Although blood tests are easier to perform than brain MRI, few studies compare brain scans to standard blood tests to see which kinds of information best predict future decline. In 504 older adults from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we first used linear regression to assess the relative value of different types of data to predict cognitive decline, including 196 blood panel biomarkers, 249 MRI biomarkers obtained from the FreeSurfer software, demographics, and the AD-risk gene APOE. A subset of MRI biomarkers was the strongest predictor. There was no specific blood marker that increased predictive accuracy on its own, we found that a novel unsupervised learning method, CorEx, captured weak correlations among blood markers, and the resulting clusters offered unique predictive power.

  3. Cerebrospinal Fluid α-Synuclein Predicts Cognitive Decline in Parkinson Disease Progression in the DATATOP Cohort

    PubMed Central

    Stewart, Tessandra; Liu, Changqin; Ginghina, Carmen; Cain, Kevin C.; Auinger, Peggy; Cholerton, Brenna; Shi, Min; Zhang, Jing

    2015-01-01

    Most patients with Parkinson disease (PD) develop both cognitive and motor impairment, and biomarkers for progression are urgently needed. Although α-synuclein is altered in cerebrospinal fluid of patients with PD, it is not known whether it predicts motor or cognitive deterioration. We examined clinical data and α-synuclein in >300 unmedicated patients with PD who participated in the deprenyl and tocopherol antioxidative therapy of parkinsonism (DATATOP) study, with up to 8 years of follow-up. Longitudinal measures of motor and cognitive function were studied before (phase 1) and during (phase 2) levodopa therapy; cerebrospinal fluid was collected at the beginning of each phase. Correlations and linear mixed models were used to assess α-synuclein association with disease severity and prediction of progression in the subsequent follow-up period. Despite decreasing α-synuclein (phase 1 to phase 2 change of −0.05 ± 0.21 log-transformed values, P < 0.001), no correlations were observed between α-synuclein and motor symptoms. Longitudinally, lower α-synuclein predicted better preservation of cognitive function by several measures [Selective Reminding Test total recall α-synuclein × time interaction effect coefficient, −0.12 (P = 0.037); delayed recall, −0.05 (P = 0.002); New Dot Test, −0.03 (P = 0.002)]. Thus, α-synuclein, although not clinically useful for motor progression, might predict cognitive decline, and future longitudinal studies should include this outcome for further validation. PMID:24625392

  4. Faster cognitive decline in elders without dementia and decreased risk of cancer mortality

    PubMed Central

    Romero, Juan Pablo; Louis, Elan D.; Bermejo-Pareja, Félix

    2014-01-01

    Objective: To assess whether faster cognitive decline in elders without dementia is associated with decreased risk of cancer mortality. Methods: In this population-based, prospective study of 2,627 people without dementia aged 65 years and older (Neurological Disorders in Central Spain), a 37-item version of the Mini-Mental State Examination (37-MMSE) was administered at 2 visits (baseline and follow-up, approximately 3 years later). We divided change in 37-MMSE into tertiles (lower tertile ≥2 point improvement in score, higher tertile ≥2 point decline in score). Community-dwelling elders were followed for a median of 12.9 years, after which the death certificates of those who died were examined. Results: A total of 1,003 (38.2%) died, including 339 (33.8%) deaths among participants who were in the higher tertile of 37-MMSE change and 664 (66.2%) deaths among those in the remaining tertiles. Cancer was reported significantly less often in those in the higher tertile of MMSE change (20.6%) than in those in the remaining tertiles (28.6%): in an unadjusted Cox model, hazard ratio for cancer mortality in participants within the higher tertile = 0.75 (p = 0.04) compared with the participants within the remaining tertiles. In a Cox model that adjusted for a variety of demographic factors and comorbidities, hazard ratio for cancer mortality in participants within the higher tertile = 0.70 (p = 0.01). Conclusion: In this population-based, prospective study of community-dwelling elders without dementia, faster cognitive decline was associated with a decreased risk of cancer mortality. Further studies are required to elucidate this inverse association in elders without dementia. PMID:24719490

  5. Late-Onset Alzheimer Risk Variants in Memory Decline, Incident Mild Cognitive Impairment and Alzheimer Disease

    PubMed Central

    Carrasquillo, Minerva M.; Crook, Julia E.; Pedraza, Otto; Thomas, Colleen S.; Pankratz, V. Shane; Allen, Mariet; Nguyen, Thuy; Malphrus, Kimberly G.; Ma, Li; Bisceglio, Gina D.; Roberts, Rosebud O.; Lucas, John A.; Smith, Glenn E.; Ivnik, Robert J.; Machulda, Mary M.; Graff-Radford, Neill R.; Petersen, Ronald C.; Younkin, Steven G.; Ertekin-Taner, Nilüfer

    2014-01-01

    Background Genome-wide association studies (GWAS) of late-onset Alzheimer's disease (LOAD) identified risk variants. We assessed the association of nine variants with memory and progression to mild cognitive impairment (MCI) or LOAD (MCI/LOAD). Methods Older Caucasians, cognitively normal at baseline and longitudinally evaluated at Mayo Clinic Rochester and Jacksonville, were assessed for associations of genetic variants with memory decline (n=2,262) using linear mixed models and for incident MCI/LOAD (n=2,674) with Cox proportional hazards models. Each variant was tested both individually and collectively using a single weighted risk score. Results APOE-ε4 was significantly associated with worse memory at baseline (β=-0.88, p=2.78E-03) and increased rate of 5-year decline (β=-1.43, p=3.71E-06) with highly significant overall effect on memory (p=3.88E-09). CLU-locus risk allele rs11136000-G was associated with worse memory at baseline (β=-0.51, p=0.012), but not with increased rate of decline. CLU allele was also associated with incident MCI/LOAD (hazard ratio=HR=1.14, p=0.049) in sensitivity analysis. MS4A6A-locus risk allele rs610932-C was associated with increased incident MCI/LOAD in primary analysis (HR=1.17, p=0.016) and had suggestive association with lower baseline memory (β=-0.35, p=0.08). PICALM-locus risk allele rs3851179-G had nominally significant HR in both primary and sensitivity analysis, but with a protective estimate. LOAD risk alleles ABCA7-rs3764650-C and EPHA1-rs11767557-A associated with increased rates of memory decline in the subset of subjects with a final diagnosis of MCI/LOAD. Risk scores excluding APOE were not significant, whereas APOE-inclusive risk scores associated with worse memory and incident MCI/LOAD. Conclusions The collective influence of the nine top LOAD GWAS variants on memory decline and progression to MCI/LOAD appears limited. Given the significant associations observed with APOE-ε4, discovery of the biologically

  6. Long-term post-operative cognitive decline in the elderly: the effects of anesthesia type, apolipoprotein E genotype, and clinical antecedents

    PubMed Central

    Ancelin, Marie-Laure; De Roquefeuil, Guilhem; Scali, Jacqueline; Bonnel, François; Adam, Jean-François; Cheminal, Jean-Claude; Cristol, Jean-Paul; Dupuy, Anne-Marie; Carrière, Isabelle; Ritchie, Karen

    2010-01-01

    Cognitive dysfunction in the elderly commonly observed following anesthesia has been attributed to age-related neuronal changes exacerbated by pharmacotoxic effects. However, the extent to which these changes may persist following recovery from surgery is still largely unknown. This study investigates the long-term effects of anesthesia on cognitive functioning after orthopedic surgery in 270 elderly patients over the age of 65 who completed a computerized cognitive battery before and 8 days, 4 and 13 months after surgery. Their performance was compared to that of 310 elderly controls who completed the same neuro-psychiatric evaluation at baseline and one-year interval. Multivariate analyses adjusted for socio-demographic variables, depressive symptomatology, vascular pathology as well as baseline cognitive performance. We found early and transient post-operative decline in reaction time and constructional praxis. With regard to long-term changes we observed improvement compared to controls in most verbal tasks (probably due to learning effects). On the other hand, a clear dissociation effect was observed for several areas of visuospatial functioning which persisted up to the 13-month follow-up. This specific pattern of visuospatial deficit was found to be independent of apolipoprotein E genotype and closely resembles what has recently been termed vascular mild cognitive impairment, in turn associated with subtle sub-cortical vascular changes. The observation of only minor differences between persons operated by general and regional anesthesia makes it difficult to attribute these changes directly to the anesthetic agents themselves, suggesting that cognitive dysfunction may be attributable at least in part to peri-operative conditions, notably stress and glucocorticoid exposure. PMID:20858969

  7. Psychosocial Risk Factors for Cognitive Decline in Late-Life Depression: Findings from the MTLD-III Study

    PubMed Central

    Rej, Soham; Begley, Amy; Gildengers, Ariel; Dew, Mary Amanda; Reynolds, Charles F.; Butters, Meryl A.

    2015-01-01

    Background Cognitive impairment and depression frequently co-occur in late life. There remains a need to better characterize psychosocial risk factors of cognitive decline in older adults with depression. We hypothesized that certain psychosocial factors would be associated with higher risk of cognitive decline in individuals with late-life depression. Methods 130 individuals aged ≥ 65 years who had achieved remission from a major depressive episode were randomized to donepezil or placebo and then closely followed for two years. Using Cox proportional hazard models, we examined the association between baseline median household income, education level, race, marital status, and social support and cognitive decline over the follow-up. Results Lower interpersonal support (OR = 0.86 [0.74–0.99], p = .04) and lower baseline global neuropsychological score (OR = 0.56 [0.36–0.87], p = .001) predicted shorter time to conversion to MCI or dementia in univariate models. These exposures did not remain significant in multivariate analyses. Neither socioeconomic status nor other psychosocial factors independently predicted cognitive diagnostic conversion (p > .05). Conclusions We did not find reliable associations between cognitive outcome and any of the psychosocial factors examined. Future large-scale, epidemiological studies, ideally using well-validated subjective measures, should better characterize psychosocial risk factors for cognitive decline in late-life depression. PMID:26180559

  8. Longitudinal Changes in Clock Drawing Test (CDT) Performance before and after Cognitive Decline

    PubMed Central

    Zhao, Qianhua; Hong, Zhen; Guo, Qihao

    2014-01-01

    Background Many scoring systems exist for clock drawing task variants. However, none of them are reliable in evaluating longitudinal changes of cognitive function. The purpose of this study is to create a simple yet optimal scoring procedure to evaluate cognitive decline using a clinic-based sample. Methods Clock-drawings from 121 participants (76 individuals with no dementia and later did not develop dementia after a mean 41.2-month follow-up, 45 individuals with no dementia became demented after a mean 42.3-month follow-up) were analyzed using t-test to determine a new and simplified CDT scoring system. The new scoring method was then compared with other commonly used systems. Results In the converters, there were only 7 items that are significantly different between the initial visits and the second visits. We propose a new scoring system that includes the seven critical items: numbers are equally spaced (12–3–6–9) (p = 0.031), the other eight numbers are marked (p = 0.022), numbers are clockwise (p = 0.002), all numbers are correct (p = 0.030), distance between numbers is constant (p = 0.016), clock has two hands (p = 0.000), arrows are drawn (p = 0.003). Compared with other traditionally used scoring methods, this based change clock drawing test (BCCDT) has one of the most balanced sensitivities/specificities with a clinic-based sample. Conclusions The new CDT scoring system provides further evidence in support of a simple and reliable clock-drawing scoring system in follow-up studies to evaluate cognitive decline, which can be used in assessing the efficacy of medicine. PMID:24874454

  9. Life-Space and Cognitive Decline in a Community-Based Sample of African American and Caucasian Older Adults

    PubMed Central

    Crowe, Michael; Andel, Ross; Wadley, Virginia G.; Okonkwo, Ozioma C.; Sawyer, Patricia; Allman, Richard M.

    2010-01-01

    Background Life-space, a measure of movement through one’s environment, may be viewed as one aspect of environmental complexity for older adults. We examined the relationship between life-space and subsequent change in cognitive function. Methods Participants were 624 community-dwelling Medicare beneficiaries (49% African American) who completed in-home assessments at baseline and follow-up 4 years later. The Life-Space Assessment was used at baseline to measure extent, frequency, and independence of participants’ movement within and outside the home. Cognitive decline was measured with the Mini-Mental State Examination (MMSE). Results In a regression model adjusted for baseline MMSE, age, gender, race, residence (rural/urban), and education, greater life-space at baseline predicted reduced cognitive decline (β = −.177, p < .001). This association remained statistically significant in subsequent models that examined what proportion of the observed association was explained by baseline physical activity, physical function, vascular risk factors, comorbidity, and psychosocial factors. Physical function accounted for the largest proportion (37.3%) of the association between life-space and cognitive decline. There was no significant interaction between life-space and race, gender, or age in predicting cognitive decline. In a logistic regression analysis, participants in the highest quartile of life-space had 53% reduced odds of substantial cognitive decline (≥4 points on MMSE) compared to those in the lowest quartile. Conclusions These preliminary findings suggest that life-space may be a useful identifier of older adults at risk for cognitive decline. Future research should investigate the potential reciprocal relationship between life-space and cognitive function as well as the interrelationship between these factors and physical function. PMID:19038840

  10. Benzodiazepine use and risk of incident dementia or cognitive decline: prospective population based study

    PubMed Central

    Dublin, Sascha; Yu, Onchee; Walker, Rod; Anderson, Melissa; Hubbard, Rebecca A; Crane, Paul K; Larson, Eric B

    2016-01-01

    Objective To determine whether higher cumulative use of benzodiazepines is associated with a higher risk of dementia or more rapid cognitive decline. Design Prospective population based cohort. Setting Integrated healthcare delivery system, Seattle, Washington. Participants 3434 participants aged ≥65 without dementia at study entry. There were two rounds of recruitment (1994-96 and 2000-03) followed by continuous enrollment beginning in 2004. Main outcomes measures The cognitive abilities screening instrument (CASI) was administered every two years to screen for dementia and was used to examine cognitive trajectory. Incident dementia and Alzheimer’s disease were determined with standard diagnostic criteria. Benzodiazepine exposure was defined from computerized pharmacy data and consisted of the total standardized daily doses (TSDDs) dispensed over a 10 year period (a rolling window that moved forward in time during follow-up). The most recent year was excluded because of possible use for prodromal symptoms. Multivariable Cox proportional hazard models were used to examine time varying use of benzodiazepine and dementia risk. Analyses of cognitive trajectory used linear regression models with generalized estimating equations. Results Over a mean follow-up of 7.3 years, 797 participants (23.2%) developed dementia, of whom 637 developed Alzheimer’s disease. For dementia, the adjusted hazard ratios associated with cumulative benzodiazepine use compared with non-use were 1.25 (95% confidence interval 1.03 to 1.51) for 1-30 TSDDs; 1.31 (1.00 to 1.71) for 31-120 TSDDs; and 1.07 (0.82 to 1.39) for ≥121 TSDDs. Results were similar for Alzheimer’s disease. Higher benzodiazepine use was not associated with more rapid cognitive decline. Conclusion The risk of dementia is slightly higher in people with minimal exposure to benzodiazepines but not with the highest level of exposure. These results do not support a causal association between benzodiazepine use and

  11. The Relationship between Cognitive Decline and Psychopathology in Patients with Schizophrenia and Bipolar Disorder

    PubMed Central

    Kim, Moon-Doo; Seo, Hye-Jin; Yun, Hyunju; Jung, Young-Eun; Park, Joon Hyuk; Lee, Chang-In; Moon, Ji Hyun; Hong, Seong-Chul; Yoon, Bo-Hyun; Bahk, Won-Myong

    2015-01-01

    Objective The primary goals of the present study were to assess intellectual function in participants with schizophrenia or bipolar disorder (BD) and to investigate the relationships between cognitive decline and the severity of each type of psychopathology. Methods The present study included 51 patients with schizophrenia and 42 with BD who were recruited from the psychiatry outpatient clinic of Jeju University Hospital between March 2011 and March 2014. The Korean Wechsler Adult Intelligence Scale (K-WAIS) was administered to each of the 93 participants, and they were categorized into two groups based on their current intelligence quotient (IQ) and their estimated premorbid IQ: severely impaired group (SIG) and mildly impaired group (MIG). The Minnesota Multiple Personality Inventory (MMPI) and the Brief Psychiatric Rating Scale (BPRS) were used to assess psychopathology. Results The SIG schizophrenia participants exhibited significantly higher scores on the frequent (F) and schizophrenia (Sc) subscales of the MMPI, but significantly lower scores on the correction (K) and psychopathic deviate (Pd) subscales compared with the MIG schizophrenia participants. Furthermore, the BPRS scores were significantly higher in the SIG schizophrenia participants relative to the MIG schizophrenia participants. The SIG BD participants had significantly higher F, masculinity-femininity (Mf), paranoia (Pa), and Sc but significantly lower Pd scores compared with the MIG BD participants. Conclusion The present findings revealed a significant discrepancy between the estimated premorbid levels of cognitive function and current cognitive function in participants with schizophrenia or BD. Moreover, this discrepancy was correlated with severity of psychopathology in both groups. PMID:25912543

  12. Neutrophils promote Alzheimer's disease-like pathology and cognitive decline via LFA-1 integrin.

    PubMed

    Zenaro, Elena; Pietronigro, Enrica; Della Bianca, Vittorina; Piacentino, Gennj; Marongiu, Laura; Budui, Simona; Turano, Ermanna; Rossi, Barbara; Angiari, Stefano; Dusi, Silvia; Montresor, Alessio; Carlucci, Tommaso; Nanì, Sara; Tosadori, Gabriele; Calciano, Lucia; Catalucci, Daniele; Berton, Giorgio; Bonetti, Bruno; Constantin, Gabriela

    2015-08-01

    Inflammation is a pathological hallmark of Alzheimer's disease, and innate immune cells have been shown to contribute to disease pathogenesis. In two transgenic models of Alzheimer's disease (5xFAD and 3xTg-AD mice), neutrophils extravasated and were present in areas with amyloid-β (Aβ) deposits, where they released neutrophil extracellular traps (NETs) and IL-17. Aβ42 peptide triggered the LFA-1 integrin high-affinity state and rapid neutrophil adhesion to integrin ligands. In vivo, LFA-1 integrin controlled neutrophil extravasation into the CNS and intraparenchymal motility. In transgenic Alzheimer's disease models, neutrophil depletion or inhibition of neutrophil trafficking via LFA-1 blockade reduced Alzheimer's disease-like neuropathology and improved memory in mice already showing cognitive dysfunction. Temporary depletion of neutrophils for 1 month at early stages of disease led to sustained improvements in memory. Transgenic Alzheimer's disease model mice lacking LFA-1 were protected from cognitive decline and had reduced gliosis. In humans with Alzheimer's disease, neutrophils adhered to and spread inside brain venules and were present in the parenchyma, along with NETs. Our results demonstrate that neutrophils contribute to Alzheimer's disease pathogenesis and cognitive impairment and suggest that the inhibition of neutrophil trafficking may be beneficial in Alzheimer's disease. PMID:26214837

  13. Cardiovascular Risk Factors Promote Brain Hypoperfusion Leading to Cognitive Decline and Dementia

    PubMed Central

    de la Torre, Jack C.

    2012-01-01

    Heart disease is the major leading cause of death and disability in the world. Mainly affecting the elderly population, heart disease and its main outcome, cardiovascular disease, have become an important risk factor in the development of cognitive decline and Alzheimer's disease (AD). This paper examines the evidence linking chronic brain hypoperfusion induced by a variety of cardiovascular deficits in the development of cognitive impairment preceding AD. The evidence indicates a strong association between AD and cardiovascular risk factors, including ApoE4, atrial fibrillation, thrombotic events, hypertension, hypotension, heart failure, high serum markers of inflammation, coronary artery disease, low cardiac index, and valvular pathology. In elderly people whose cerebral perfusion is already diminished by their advanced age, additional reduction of cerebral blood flow stemming from abnormalities in the heart-brain vascular loop ostensibly increases the probability of developing AD. Evidence also suggests that a neuronal energy crisis brought on by relentless brain hypoperfusion may be responsible for protein synthesis abnormalities that later result in the classic neurodegenerative lesions involving the formation of amyloid-beta plaques and neurofibrillary tangles. Insight into how cardiovascular risk factors can induce progressive cognitive impairment offers an enhanced understanding of the multifactorial pathophysiology characterizing AD and ways at preventing or managing the cardiovascular precursors of this dementia. PMID:23243502

  14. Glia and zinc in ageing and Alzheimer’s disease: a mechanism for cognitive decline?

    PubMed Central

    Hancock, Sara M.; Finkelstein, David I.; Adlard, Paul A.

    2014-01-01

    Normal ageing is characterized by cognitive decline across a range of neurological functions, which are further impaired in Alzheimer’s disease (AD). Recently, alterations in zinc (Zn) concentrations, particularly at the synapse, have emerged as a potential mechanism underlying the cognitive changes that occur in both ageing and AD. Zn is now accepted as a potent neuromodulator, affecting a variety of signaling pathways at the synapse that are critical to normal cognition. While the focus has principally been on the neuron: Zn interaction, there is a growing literature suggesting that glia may also play a modulatory role in maintaining both Zn ion homeostasis and the normal function of the synapse. Indeed, zinc transporters (ZnT’s) have been demonstrated in glial cells where Zn has also been shown to have a role in signaling. Furthermore, there is increasing evidence that the pathogenesis of AD critically involves glial cells (such as astrocytes), which have been reported to contribute to amyloid-beta (Aβ) neurotoxicity. This review discusses the current evidence supporting a complex interplay of glia, Zn dyshomeostasis and synaptic function in ageing and AD. PMID:25009495

  15. Braak stage and trajectory of cognitive decline in noncognitively impaired elders.

    PubMed

    Mufson, Elliott J; Malek-Ahmadi, Michael; Snyder, Noelle; Ausdemore, Jake; Chen, Kewei; Perez, Sylvia E

    2016-07-01

    In a previous cross-sectional study, we found that nondemented elderly participants from the Rush Religious Orders Study (RROS) displayed a wide range of Braak neurofibrillary tangle and amyloid plaque pathology similar to that seen in prodromal and frank Alzheimer's disease. Here, we examined longitudinal changes in cognitive domains in subjects from this cohort grouped by Braak stage using linear mixed effects models. We found that the trajectory of episodic memory composite (EMC), executive function composite (EFC), and global cognitive composite scores (GCS: average of EMC and EFC scores) was significantly associated with age at visit over time, but not with Braak stage, apolipoprotein E (APOE) ε4 status or plaque pathology alone. By contrast, the combined effects of Braak stage, APOE status, and age at visit were strongly correlated with the trajectory of EMC, EFC and GCS performance over time. These data suggest that age and APOE ε4 status, rather than Alzheimer's disease-related pathology, play a more prominent role in the trajectory of cognitive decline over time in this elderly nondemented population. However, the findings reported require confirmation in a larger cohort of cases. PMID:27255819

  16. The involvement of homocysteine in stress-induced Aβ precursor protein misprocessing and related cognitive decline in rats.

    PubMed

    Xie, Fang; Zhao, Yun; Ma, Jing; Gong, Jing-Bo; Wang, Shi-Da; Zhang, Liang; Gao, Xiu-Jie; Qian, Ling-Jia

    2016-09-01

    Chronic stress is a risk factor in the development of cognitive decline and even Alzheimer's disease (AD), although its underlying mechanism is not fully understood. Our previous data demonstrated that the level of homocysteine (Hcy) was significantly elevated in the plasma of stressed animals, which suggests the possibility that Hcy is a link between stress and cognitive decline. To test this hypothesis, we compared the cognitive function, plasma concentrations of Hcy, and the brain beta-amyloid (Aβ) level between rats with or without chronic unexpected mild stress (CUMS). A lower performance by rats in behavioral tests indicated that a significant cognitive decline was induced by CUMS. Stress also disturbed the normal processing of Aβ precursor protein (APP) and resulted in the accumulation of Aβ in the brains of rats, which showed a positive correlation with the hyperhomocysteinemia (HHcy) that appeared in stressed rats. Hcy-targeting intervention experiments were used to verify further the involvement of Hcy in stress-induced APP misprocessing and related cognitive decline. The results showed that diet-induced HHcy could mimic the cognitive impairment and APP misprocessing in the same manner as CUMS, while Hcy reduction by means of vitamin B complex supplements and betaine could alleviate the cognitive deficits and dysregulation of Aβ metabolism in CUMS rats. Taken together, the novel evidence from our present study suggests that Hcy is likely to be involved in chronic stress-evoked APP misprocessing and related cognitive deficits. Our results also suggested the possibility of Hcy as a target for therapy and the potential value of vitamin B and betaine intake in the prevention of stress-induced cognitive decline. PMID:27435080

  17. Exploratory Decision-Making as a Function of Lifelong Experience, Not Cognitive Decline

    PubMed Central

    2016-01-01

    Older adults perform worse than younger adults in some complex decision-making scenarios, which is commonly attributed to age-related declines in striatal and frontostriatal processing. Recently, this popular account has been challenged by work that considered how older adults’ performance may differ as a function of greater knowledge and experience, and by work showing that, in some cases, older adults outperform younger adults in complex decision-making tasks. In light of this controversy, we examined the performance of older and younger adults in an exploratory choice task that is amenable to model-based analyses and ostensibly not reliant on prior knowledge. Exploration is a critical aspect of decision-making poorly understood across the life span. Across 2 experiments, we addressed (a) how older and younger adults differ in exploratory choice and (b) to what extent observed differences reflect processing capacity declines. Model-based analyses suggested that the strategies used by the 2 groups were qualitatively different, resulting in relatively worse performance for older adults in 1 decision-making environment but equal performance in another. Little evidence was found that differences in processing capacity drove performance differences. Rather the results suggested that older adults’ performance might result from applying a strategy that may have been shaped by their wealth of real-word decision-making experience. While this strategy is likely to be effective in the real world, it is ill suited to some decision environments. These results underscore the importance of taking into account effects of experience in aging studies, even for tasks that do not obviously tap past experiences. PMID:26726916

  18. A Method for Investigating Age-related Differences in the Functional Connectivity of Cognitive Control Networks Associated with Dimensional Change Card Sort Performance

    PubMed Central

    DeBenedictis, Bianca; Morton, J. Bruce

    2014-01-01

    The ability to adjust behavior to sudden changes in the environment develops gradually in childhood and adolescence. For example, in the Dimensional Change Card Sort task, participants switch from sorting cards one way, such as shape, to sorting them a different way, such as color. Adjusting behavior in this way exacts a small performance cost, or switch cost, such that responses are typically slower and more error-prone on switch trials in which the sorting rule changes as compared to repeat trials in which the sorting rule remains the same. The ability to flexibly adjust behavior is often said to develop gradually, in part because behavioral costs such as switch costs typically decrease with increasing age. Why aspects of higher-order cognition, such as behavioral flexibility, develop so gradually remains an open question. One hypothesis is that these changes occur in association with functional changes in broad-scale cognitive control networks. On this view, complex mental operations, such as switching, involve rapid interactions between several distributed brain regions, including those that update and maintain task rules, re-orient attention, and select behaviors. With development, functional connections between these regions strengthen, leading to faster and more efficient switching operations. The current video describes a method of testing this hypothesis through the collection and multivariate analysis of fMRI data from participants of different ages. PMID:24837515

  19. Correlations among central serotonergic parameters and age-related emotional and cognitive changes assessed through the elevated T-maze and the Morris water maze

    PubMed Central

    Oliveira, Luciana; Graeff, Frederico G.; Pereira, Silvia R. C.; Oliveira-Silva, Ieda F.; Franco, Glaura C.

    2010-01-01

    Emotion and spatial cognitive aspects were assessed in adult and middle-aged rats using the elevated T-maze (ETM) and the Morris water maze (MWM) tasks. Both adult and middle-aged rats were able to acquire inhibitory avoidance behaviour, though the middle-aged subjects showed larger latencies along the trials, including the baseline, which was significantly longer than that showed by adult rats. Further, compared to adult rats, middle-aged rats had longer escape latency. In spite of the worse performance in the second session of the spatial cognitive task, the middle-aged rats were able to learn the task and remember the information along the whole probe trial test. Both thalamic serotonin (5-HT) concentration and amygdala serotonergic activity (5-HIAA/5-HT) are significantly correlated, respectively, to escape latency and behavioural extinction in the MWM only for middle-aged rats. A significant correlation between the 5-HIAA/5-HT ratio in the amygdala and behavioural extinction for middle-aged, but not for adult, rats was observed. This result suggests that serotonergic activity in the amygdala may regulate behavioural flexibility in aged animals. In addition, a significant negative correlation was found between hippocampal 5-HIAA/5-HT ratio and the path length at the second training session of the MWM task, although only for adult subjects. This was the only session where a significant difference between the performance of middle-aged and adult rats has occurred. Although the involvement of the hippocampus in learning and memory is well established, the present work shows, for the first time, a correlation between a serotonergic hippocampal parameter and performance of a spatial task, which is lost with ageing. PMID:20431986

  20. Age-related changes in prefrontal norepinephrine transporter density: The basis for improved cognitive flexibility after low doses of atomoxetine in adolescent rats.

    PubMed

    Bradshaw, Sarah E; Agster, Kara L; Waterhouse, Barry D; McGaughy, Jill A

    2016-06-15

    Adolescence is a period of major behavioral and brain reorganization. As diagnoses and treatment of disorders like attention deficit hyperactivity disorder (ADHD) often occur during adolescence, it is important to understand how the prefrontal cortices change and how these changes may influence the response to drugs during development. The current study uses an adolescent rat model to study the effect of standard ADHD treatments, atomoxetine and methylphenidate on attentional set shifting and reversal learning. While both of these drugs act as norepinephrine reuptake inhibitors, higher doses of atomoxetine and all doses of methylphenidate also block dopamine transporters (DAT). Low doses of atomoxetine, were effective at remediating cognitive rigidity found in adolescents. In contrast, methylphenidate improved performance in rats unable to form an attentional set due to distractibility but was without effect in normal subjects. We also assessed the effects of GBR 12909, a selective DAT inhibitor, but found no effect of any dose on behavior. A second study in adolescent rats investigated changes in norepinephrine transporter (NET) and dopamine beta hydroxylase (DBH) density in five functionally distinct sub-regions of the prefrontal cortex: infralimbic, prelimbic, anterior cingulate, medial and lateral orbitofrontal cortices. These regions are implicated in impulsivity and distractibility. We found that NET, but not DBH, changed across adolescence in a regionally selective manner. The prelimbic cortex, which is critical to cognitive rigidity, and the lateral orbitofrontal cortex, critical to reversal learning and some forms of response inhibition, showed higher levels of NET at early than mid- to late adolescence. This article is part of a Special Issue entitled SI: Noradrenergic System. PMID:26774596

  1. An Application of Pavlovian Principles to the Problems of Obesity and Cognitive Decline

    PubMed Central

    Davidson, T. L.; Sample, C. H.; Swithers, S. E.

    2013-01-01

    An enormous amount of research has been aimed at identifying biological and environmental factors that are contributing to the current global obesity pandemic. The present paper reviews recent findings which suggest that obesity is attributable, at least in part, to a disruption of the Pavlovian control of energy regulation. Within our framework, this disruption occurs when (a) consumption of sweet-tasting, but low calorie or noncaloric, foods and beverages reduces the ability of sweet tastes to predict the postingestive caloric consequences of intake and (b) consuming diets high in saturated fat and sugar (a.k.a., Western diet) impairs hippocampal-dependent learning and memory processes that are involved with the use of interoceptive “satiety” signals to anticipate when food and eating are not followed by appetitive postingestive outcomes. The paper concludes with discussion of a “vicious-cycle’ model which links obesity to cognitive decline. PMID:23887140

  2. Shared Neuropathological Characteristics of Obesity, Type 2 Diabetes and Alzheimer's Disease: Impacts on Cognitive Decline.

    PubMed

    Walker, Jennifer M; Harrison, Fiona E

    2015-09-01

    In the past few decades, the prevalence of obesity and type 2 diabetes mellitus (T2DM), as well as older individuals at risk for Alzheimer's disease (AD), has increased. While the consumption of diets high in fat (total and saturated) have been linked to increased risk of AD, diets rich in antioxidants, polyunsaturated fats, and omega-3 fatty acids are associated with decreased risk. Additionally, AD patients are at increased risk for developing T2DM. Recent research suggests that there are stronger similarities between AD and T2DM than have previously been considered. Here we review the neurocognitive and inflammatory effects of high-fat diet consumption, its relationship to AD, and the treatment potential of dietary interventions that may decrease risk of cognitive decline and other associated neuropathological changes, such as insulin resistance, oxidative stress, and chronic inflammatory processes. PMID:26340637

  3. Age-Related Macular Degeneration

    MedlinePlus

    ... this page please turn Javascript on. Age-related Macular Degeneration What is AMD? Click for more information Age-related macular degeneration, ... the macula allows you to see fine detail. AMD Blurs Central Vision AMD blurs the sharp central ...

  4. Alcohol Consumption, Dementia and Cognitive Decline: An Overview of Systematic Reviews.

    PubMed

    Ilomaki, Jenni; Jokanovic, Natali; Tan, Edwin C K; Lonnroos, Eija

    2015-01-01

    There is uncertainty in relation to the effect of alcohol consumption on the incidence of dementia and cognitive decline. This review critically evaluated published systematic reviews on the epidemiology of alcohol consumption and the risk of dementia or cognitive decline. MEDLINE, EMBASE and PsycINFO were searched from inception to February 2014. Systematic reviews of longitudinal observational studies were considered. Two reviewers independently completed the 11-item Assessment of Multiple Systematic Reviews (AMSTAR) tool to assess the quality. We identified three moderate quality systematic reviews (AMSTAR score 4-6) that included a total of 45 unique studies. Two of the systematic reviews encompassed a meta-analysis. Light to moderate drinking may decrease the risk of Alzheimer's disease (AD) (pooled risk ratio [RR] 0.72; 95% confidence interval [CI] 0.61-0.86) and dementia (RR 0.74; 95%CI 0.61-0.91) whereas heavy to excessive drinking does not affect the risk (RR 0.92; 95%CI 0.59-1.45 and RR 1.04; 95%CI 0.69-1.56, respectively). One systematic review identified two studies that reported a link between alcohol consumption and the development of AD. No systematic review categorised former drinkers separately from lifetime abstainers in their analysis. Definitions of alcohol consumption, light to moderate drinking and heavy-excessive drinking varied and drinking patterns were not considered. Moderate quality (AMSTAR score 4-6) systematic reviews indicate that light to moderate alcohol consumption may protect against AD and dementia. However, the importance of drinking patterns and specific beverages remain unknown. There is insufficient evidence to suggest abstainers should initiate alcohol consumption to protect against dementia. PMID:26338173

  5. Cognitive Impairment and Age-Related Vision Disorders: Their Possible Relationship and the Evaluation of the Use of Aspirin and Statins in a 65 Years-and-Over Sardinian Population.

    PubMed

    Mandas, Antonella; Mereu, Rosa Maria; Catte, Olga; Saba, Antonio; Serchisu, Luca; Costaggiu, Diego; Peiretti, Enrico; Caminiti, Giulia; Vinci, Michela; Casu, Maura; Piludu, Stefania; Fossarello, Maurizio; Manconi, Paolo Emilio; Dessí, Sandra

    2014-01-01

    Neurological disorders (Alzheimer's disease, vascular and mixed dementia) and visual loss (cataract, age-related macular degeneration, glaucoma, and diabetic retinopathy) are among the most common conditions that afflict people of at least 65 years of age. An increasing body of evidence is emerging, which demonstrates that memory and vision impairment are closely, significantly, and positively linked and that statins and aspirin may lessen the risk of developing age-related visual and neurological problems. However, clinical studies have produced contradictory results. Thus, the intent of the present study was to reliably establish whether a relationship exist between various types of dementia and age-related vision disorders, and to establish whether statins and aspirin may or may not have beneficial effects on these two types of disorders. We found that participants with dementia and/or vision problems were more likely to be depressed and displayed worse functional ability in basic and instrumental activities of daily living than controls. Mini mental state examination scores were significantly lower in patients with vision disorders compared to subjects without vision disorders. A closer association with macular degeneration was found in subjects with Alzheimer's disease than in subjects without dementia or with vascular dementia, mixed dementia, or other types of age-related vision disorders. When we considered the associations between different types of dementia and vision disorders and the use of statins and aspirin, we found a significant positive association between Alzhe