Impaired sequential and partially compensated probabilistic skill learning in Parkinson's disease.

PubMed

Kemény, Ferenc; Demeter, Gyula; Racsmány, Mihály; Valálik, István; Lukács, Ágnes

2018-06-08

The striatal dopaminergic dysfunction in Parkinson's disease (PD) has been associated with deficits in skill learning in numerous studies, but some of the findings remain controversial. Our aim was to explore the generality of the learning deficit using two widely reported skill learning tasks in the same group of Parkinson's patients. Thirty-four patients with PD (mean age: 62.83 years, SD: 7.67) were compared to age-matched healthy adults. Two tasks were employed: the Serial Reaction Time Task (SRT), testing the learning of motor sequences, and the Weather Prediction (WP) task, testing non-sequential probabilistic category learning. On the SRT task, patients with PD showed no significant evidence for sequence learning. These results support and also extend previous findings, suggesting that motor skill learning is vulnerable in PD. On the WP task, the PD group showed the same amount of learning as controls, but they exploited qualitatively different strategies in predicting the target categories. While controls typically combined probabilities from multiple predicting cues, patients with PD instead focused on individual cues. We also found moderate to high correlations between the different measures of skill learning. These findings support our hypothesis that skill learning is generally impaired in PD, and can in some cases be compensated by relying on alternative learning strategies. © 2018 The Authors. Journal of Neuropsychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.

UNDERNUTRITION IN EARLY LIFE DOES NOT IMPAIR LEARNING IN YOUNG OR AGING RATS.

EPA Science Inventory

Prenatal undernutrition is associated with increased incidence of obesity, heart disease, diabetes. Effects of pre- and post-natal undernutrition on nervous system function in middle-aged and aging male SD rats were examined. Intrauterine growth retardation (IUGR) was induced by ...

77 FR 55099 - National Prostate Cancer Awareness Month, 2012

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-06

... be more likely to develop the disease. Most men who suffer from prostate cancer are over the age of... learn the warning signs of this disease. My Administration will continue to stand with men and their...

Independent effects of age and levodopa on reversal learning in healthy volunteers.

PubMed

Vo, Andrew; Seergobin, Ken N; MacDonald, Penny A

2018-05-18

The dopamine overdose hypothesis has provided an important theoretical framework for understanding cognition in Parkinson's disease. It posits that effects of dopaminergic therapy on cognition in Parkinson's disease depend on baseline dopamine levels in brain regions that support different functions. Although functions performed by more severely dopamine-depleted brain regions improve with medication, those associated with less dopamine deficient areas are actually worsened. It is presumed that medication-related worsening of cognition owes to dopamine overdose. We investigated whether age-related changes in baseline dopamine levels would modulate effects of dopaminergic therapy on reward learning in healthy volunteers. In a double-blind, crossover design, healthy younger and older adults completed a probabilistic reversal learning task after treatment with 100/25 mg of levodopa/carbidopa versus placebo. Older adults learned more poorly than younger adults at baseline, being more likely to shift responses after misleading punishment. Levodopa worsened stimulus-reward learning relative to placebo to the same extent in both groups, irrespective of differences in baseline performance and expected dopamine levels. When order effects were eliminated, levodopa induced response shifts after reward more often than placebo. Our results reveal independent deleterious effects of age group and exogenous dopamine on reward learning, suggesting a more complex scenario than predicted by the dopamine overdose hypothesis. Copyright © 2018 Elsevier Inc. All rights reserved.

Quantitative evaluation of human cerebellum-dependent motor learning through prism adaptation of hand-reaching movement.

PubMed

Hashimoto, Yuji; Honda, Takeru; Matsumura, Ken; Nakao, Makoto; Soga, Kazumasa; Katano, Kazuhiko; Yokota, Takanori; Mizusawa, Hidehiro; Nagao, Soichi; Ishikawa, Kinya

2015-01-01

The cerebellum plays important roles in motor coordination and learning. However, motor learning has not been quantitatively evaluated clinically. It thus remains unclear how motor learning is influenced by cerebellar diseases or aging, and is related with incoordination. Here, we present a new application for testing human cerebellum-dependent motor learning using prism adaptation. In our paradigm, the participant wearing prism-equipped goggles touches their index finger to the target presented on a touchscreen in every trial. The whole test consisted of three consecutive sessions: (1) 50 trials with normal vision (BASELINE), (2) 100 trials wearing the prism that shifts the visual field 25° rightward (PRISM), and (3) 50 trials without the prism (REMOVAL). In healthy subjects, the prism-induced finger-touch error, i.e., the distance between touch and target positions, was decreased gradually by motor learning through repetition of trials. We found that such motor learning could be quantified using the "adaptability index (AI)", which was calculated by multiplying each probability of [acquisition in the last 10 trials of PRISM], [retention in the initial five trials of REMOVAL], and [extinction in the last 10 trials of REMOVAL]. The AI of cerebellar patients less than 70 years old (mean, 0.227; n = 62) was lower than that of age-matched healthy subjects (0.867, n = 21; p < 0.0001). While AI did not correlate with the magnitude of dysmetria in ataxic patients, it declined in parallel with disease progression, suggesting a close correlation between the impaired cerebellar motor leaning and the dysmetria. Furthermore, AI decreased with aging in the healthy subjects over 70 years old compared with that in the healthy subjects less than 70 years old. We suggest that our paradigm of prism adaptation may allow us to quantitatively assess cerebellar motor learning in both normal and diseased conditions.

Quantitative Evaluation of Human Cerebellum-Dependent Motor Learning through Prism Adaptation of Hand-Reaching Movement

PubMed Central

Hashimoto, Yuji; Honda, Takeru; Matsumura, Ken; Nakao, Makoto; Soga, Kazumasa; Katano, Kazuhiko; Yokota, Takanori; Mizusawa, Hidehiro; Nagao, Soichi; Ishikawa, Kinya

2015-01-01

The cerebellum plays important roles in motor coordination and learning. However, motor learning has not been quantitatively evaluated clinically. It thus remains unclear how motor learning is influenced by cerebellar diseases or aging, and is related with incoordination. Here, we present a new application for testing human cerebellum-dependent motor learning using prism adaptation. In our paradigm, the participant wearing prism-equipped goggles touches their index finger to the target presented on a touchscreen in every trial. The whole test consisted of three consecutive sessions: (1) 50 trials with normal vision (BASELINE), (2) 100 trials wearing the prism that shifts the visual field 25° rightward (PRISM), and (3) 50 trials without the prism (REMOVAL). In healthy subjects, the prism-induced finger-touch error, i.e., the distance between touch and target positions, was decreased gradually by motor learning through repetition of trials. We found that such motor learning could be quantified using the “adaptability index (AI)”, which was calculated by multiplying each probability of [acquisition in the last 10 trials of PRISM], [retention in the initial five trials of REMOVAL], and [extinction in the last 10 trials of REMOVAL]. The AI of cerebellar patients less than 70 years old (mean, 0.227; n = 62) was lower than that of age-matched healthy subjects (0.867, n = 21; p < 0.0001). While AI did not correlate with the magnitude of dysmetria in ataxic patients, it declined in parallel with disease progression, suggesting a close correlation between the impaired cerebellar motor leaning and the dysmetria. Furthermore, AI decreased with aging in the healthy subjects over 70 years old compared with that in the healthy subjects less than 70 years old. We suggest that our paradigm of prism adaptation may allow us to quantitatively assess cerebellar motor learning in both normal and diseased conditions. PMID:25785588

Speech Motor Sequence Learning: Effect of Parkinson Disease and Normal Aging on Dual-Task Performance.

PubMed

Whitfield, Jason A; Goberman, Alexander M

2017-06-22

Everyday communication is carried out concurrently with other tasks. Therefore, determining how dual tasks interfere with newly learned speech motor skills can offer insight into the cognitive mechanisms underlying speech motor learning in Parkinson disease (PD). The current investigation examines a recently learned speech motor sequence under dual-task conditions. A previously learned sequence of 6 monosyllabic nonwords was examined using a dual-task paradigm. Participants repeated the sequence while concurrently performing a visuomotor task, and performance on both tasks was measured in single- and dual-task conditions. The younger adult group exhibited little to no dual-task interference on the accuracy and duration of the sequence. The older adult group exhibited variability in dual-task costs, with the group as a whole exhibiting an intermediate, though significant, amount of dual-task interference. The PD group exhibited the largest degree of bidirectional dual-task interference among all the groups. These data suggest that PD affects the later stages of speech motor learning, as the dual-task condition interfered with production of the recently learned sequence beyond the effect of normal aging. Because the basal ganglia is critical for the later stages of motor sequence learning, the observed deficits may result from the underlying neural dysfunction associated with PD.

Motivational modes and learning in Parkinson's disease.

PubMed

Foerde, Karin; Braun, Erin Kendall; Higgins, E Tory; Shohamy, Daphna

2015-08-01

Learning and motivation are intrinsically related, and both have been linked to dopamine. Parkinson's disease results from a progressive loss of dopaminergic inputs to the striatum and leads to impairments in motivation and learning from feedback. However, the link between motivation and learning in Parkinson's disease is not well understood. To address this gap, we leverage a well-established psychological theory of motivation, regulatory mode theory, which distinguishes between two functionally independent motivational concerns in regulating behavior: a concern with having an effect by initiating and maintaining movement (Locomotion) and a concern with establishing what is correct by critically evaluating goal pursuit means and outcomes (Assessment). We examined Locomotion and Assessment in patients with Parkinson's disease and age-matched controls. Parkinson's disease patients demonstrated a selective decrease in Assessment motivation but no change in Locomotion motivation, suggesting that Parkinson's disease leads to a reduced tendency to evaluate and monitor outcomes. Moreover, weaker Assessment motivation was correlated with poorer performance on a feedback-based learning task previously shown to depend on the striatum. Together, these findings link a questionnaire-based personality inventory with performance on a well-characterized experimental task, advancing our understanding of how Parkinson's disease affects motivation with implications for well-being and treatment outcomes. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Motivational modes and learning in Parkinson’s disease

PubMed Central

Braun, Erin Kendall; Higgins, E. Tory; Shohamy, Daphna

2015-01-01

Learning and motivation are intrinsically related, and both have been linked to dopamine. Parkinson’s disease results from a progressive loss of dopaminergic inputs to the striatum and leads to impairments in motivation and learning from feedback. However, the link between motivation and learning in Parkinson’s disease is not well understood. To address this gap, we leverage a well-established psychological theory of motivation, regulatory mode theory, which distinguishes between two functionally independent motivational concerns in regulating behavior: a concern with having an effect by initiating and maintaining movement (Locomotion) and a concern with establishing what is correct by critically evaluating goal pursuit means and outcomes (Assessment). We examined Locomotion and Assessment in patients with Parkinson’s disease and age-matched controls. Parkinson’s disease patients demonstrated a selective decrease in Assessment motivation but no change in Locomotion motivation, suggesting that Parkinson’s disease leads to a reduced tendency to evaluate and monitor outcomes. Moreover, weaker Assessment motivation was correlated with poorer performance on a feedback-based learning task previously shown to depend on the striatum. Together, these findings link a questionnaire-based personality inventory with performance on a well-characterized experimental task, advancing our understanding of how Parkinson’s disease affects motivation with implications for well-being and treatment outcomes. PMID:25552569

Anti-amyloid beta protein antibody passage across the blood-brain barrier in the SAMP8 mouse model of Alzheimer's disease: an age-related selective uptake with reversal of learning impairment.

PubMed

Banks, William A; Farr, Susan A; Morley, John E; Wolf, Kathy M; Geylis, Valeria; Steinitz, Michael

2007-08-01

Amyloid beta protein (Abeta) levels are elevated in the brain of Alzheimer's disease patients. Anti-Abeta antibodies can reverse the histologic and cognitive impairments in mice which overexpress Abeta. Passive immunization appears safer than vaccination and treatment of patients will likely require human rather than xenogenic antibodies. Effective treatment will likely require antibody to cross the blood-brain barrier (BBB). Unfortunately, antibodies typically cross the BBB very poorly and accumulate less well in brain than even albumin, a substance nearly totally excluded from the brain. We compared the ability of two anti-Abeta human monoclonal IgM antibodies, L11.3 and HyL5, to cross the BBB of young CD-1 mice to that of young and aged SAMP8 mice. The SAMP8 mouse has a spontaneous mutation that induces an age-related, Abeta-dependent cognitive deficit. There was preferential uptake of intravenously administered L11.3 in comparison to HyL5, albumin, and a control human monoclonal IgM (RF), especially by hippocampus and olfactory bulb in aged SAMP8 mice. Injection of L11.3 into the brains of aged SAMP8 mice reversed both learning and memory impairments in aged SAMP8 mice, whereas IgG and IgM controls were ineffective. Pharmacokinetic analysis predicted that an intravenous dose 1000 times higher than the brain injection dose would reverse cognitive impairments. This predicted intravenous dose reversed the impairment in learning, but not memory, in aged SAMP8 mice. In conclusion, an IgM antibody was produced that crosses the BBB to reverse cognitive impairment in a murine model of Alzheimer's disease.

Learning about an Undiagosed Condition in an Adult

MedlinePlus

... of the public with current information on clinical research studies. For example, the study entitled "Studies of Children with Metabolic and Other Genetic Diseases" evaluates individuals of all ages (despite its title) with known or suspected genetic diseases. You can ...

Arterial spin labeling reveals relationships between resting cerebral perfusion and motor learning in Parkinson's disease.

PubMed

Barzgari, Amy; Sojkova, Jitka; Maritza Dowling, N; Pozorski, Vincent; Okonkwo, Ozioma C; Starks, Erika J; Oh, Jennifer; Thiesen, Frances; Wey, Alexandra; Nicholas, Christopher R; Johnson, Sterling; Gallagher, Catherine L

2018-05-09

Parkinson's disease (PD) is an age-related neurodegenerative disease that produces changes in movement, cognition, sleep, and autonomic function. Motor learning involves acquisition of new motor skills through practice, and is affected by PD. The purpose of the present study was to evaluate regional differences in resting cerebral blood flow (rCBF), measured using arterial spin labeling (ASL) MRI, during a finger-typing task of motor skill acquisition in PD patients compared to age- and gender-matched controls. Voxel-wise multiple linear regression models were used to examine the relationship between rCBF and several task variables, including initial speed, proficiency gain, and accuracy. In these models, a task-by-disease group interaction term was included to investigate where the relationship between rCBF and task performance was influenced by PD. At baseline, perfusion was lower in PD subjects than controls in the right occipital cortex. The task-by-disease group interaction for initial speed was significantly related to rCBF (p < 0.05, corrected) in several brain regions involved in motor learning, including the occipital, parietal, and temporal cortices, cerebellum, anterior cingulate, and the superior and middle frontal gyri. In these regions, PD patients showed higher rCBF, and controls lower rCBF, with improved performance. Within the control group, proficiency gain over 12 typing trials was related to greater rCBF in cerebellar, occipital, and temporal cortices. These results suggest that higher rCBF within networks involved in motor learning enable PD patients to compensate for disease-related deficits.

Speech Motor Sequence Learning: Acquisition and Retention in Parkinson Disease and Normal Aging.

PubMed

Whitfield, Jason A; Goberman, Alexander M

2017-06-10

The aim of the current investigation was to examine speech motor sequence learning in neurologically healthy younger adults, neurologically healthy older adults, and individuals with Parkinson disease (PD) over a 2-day period. A sequential nonword repetition task was used to examine learning over 2 days. Participants practiced a sequence of 6 monosyllabic nonwords that was retested following nighttime sleep. The speed and accuracy of the nonword sequence were measured, and learning was inferred by examining performance within and between sessions. Though all groups exhibited comparable improvements of the nonword sequence performance during the initial session, between-session retention of the nonword sequence differed between groups. Younger adult controls exhibited offline gains, characterized by an increase in the speed and accuracy of nonword sequence performance across sessions, whereas older adults exhibited stable between-session performance. Individuals with PD exhibited offline losses, marked by an increase in sequence duration between sessions. The current results demonstrate that both PD and normal aging affect retention of speech motor learning. Furthermore, these data suggest that basal ganglia dysfunction associated with PD may affect the later stages of speech motor learning. Findings from the current investigation are discussed in relation to studies examining consolidation of nonspeech motor learning.

Educational and Service Outcomes of a Service Integration Effort.

ERIC Educational Resources Information Center

Greene, David; Diehm, Gwen

1995-01-01

Study investigated the effects of a service-learning component in an undergraduate occupational therapy course. Comparisons were made between students involved in service-learning and those not involved of how they perceived institutionalized older adults' perspectives on disease and aging. Also evaluated were weekly journal entries of the…

Extra virgin olive oil improves learning and memory in SAMP8 mice.

PubMed

Farr, Susan A; Price, Tulin O; Dominguez, Ligia J; Motisi, Antonio; Saiano, Filippo; Niehoff, Michael L; Morley, John E; Banks, William A; Ercal, Nuran; Barbagallo, Mario

2012-01-01

Polyphenols are potent antioxidants found in extra virgin olive oil (EVOO); antioxidants have been shown to reverse age- and disease-related learning and memory deficits. We examined the effects of EVOO on learning and memory in SAMP8 mice, an age-related learning/memory impairment model associated with increased amyloid-β protein and brain oxidative damage. We administered EVOO, coconut oil, or butter to 11 month old SAMP8 mice for 6 weeks. Mice were tested in T-maze foot shock avoidance and one-trial novel object recognition with a 24 h delay. Mice which received EVOO had improved acquisition in the T-maze and spent more time with the novel object in one-trial novel object recognition versus mice which received coconut oil or butter. Mice that received EVOO had improve T-maze retention compared to the mice that received butter. EVOO increased brain glutathione levels suggesting reduced oxidative stress as a possible mechanism. These effects plus increased glutathione reductase activity, superoxide dismutase activity, and decreased tissue levels of 4-hydroxynoneal and 3-nitrotyrosine were enhanced with enriched EVOO (3 × and 5 × polyphenols concentration). Our findings suggest that EVOO has beneficial effects on learning and memory deficits found in aging and diseases, such as those related to the overproduction of amyloid-β protein, by reversing oxidative damage in the brain, effects that are augmented with increasing concentrations of polyphenols in EVOO.

Internet-Based Resources for Disease Self-Care Among Middle-Aged and Older Women with Chronic Conditions.

PubMed

Pettus, Amanda J; Mendez-Luck, Carolyn A; Bergeron, Caroline D; Ahn, SangNam; Towne, Samuel D; Ory, Marcia G; Smith, Matthew Lee

2017-03-01

This two-part study analyzed data collected from middle-aged (age 44-64) and older women (age 65+) with one or more chronic conditions who completed the National Council on Aging Chronic Care Survey. Part One analyzed data from 418 women to describe sociodemographics, disease types, and healthcare utilization associated with Internet use among middle-aged and older women with 1 or more chronic diseases. Part Two analyzed data from the 251 Internet-using women to identify the online self-care resources they are using (format, host organization) and for what purposes. Approximately 31% of participants were age 65 years or older, 30% reported having three or more chronic condition types, and 65% reported using the Internet. A significantly larger proportion of older women reported multiple chronic conditions, and a significantly fewer number of older women reported using the Internet. A significantly smaller proportion of Internet users were non-Hispanic white, more educated, and employed. A significantly larger proportion of non-Internet users reported needing help learning what to do to manage their health conditions and needing help learning how to care for their health conditions. Among only Internet-using women, 18.7% participated in online discussions/chatrooms/listserv and 45.2% read about the experiences of others with chronic diseases. Interest in websites and online courses varied. Understanding Internet use among women with chronic conditions can inform targeted efforts to increase Internet availability, educate potential users about the benefits of online resources, and effectively tailor Internet-based materials to self-care needs.

Automated detection of age-related macular degeneration in OCT images using multiple instance learning

NASA Astrophysics Data System (ADS)

Sun, Weiwei; Liu, Xiaoming; Yang, Zhou

2017-07-01

Age-related Macular Degeneration (AMD) is a kind of macular disease which mostly occurs in old people，and it may cause decreased vision or even lead to permanent blindness. Drusen is an important clinical indicator for AMD which can help doctor diagnose disease and decide the strategy of treatment. Optical Coherence Tomography (OCT) is widely used in the diagnosis of ophthalmic diseases, include AMD. In this paper, we propose a classification method based on Multiple Instance Learning (MIL) to detect AMD. Drusen can exist in a few slices of OCT images, and MIL is utilized in our method. We divided the method into two phases: training phase and testing phase. We train the initial features and clustered to create a codebook, and employ the trained classifier in the test set. Experiment results show that our method achieved high accuracy and effectiveness.

Neuroimaging Studies Illustrate the Commonalities Between Ageing and Brain Diseases.

PubMed

Cole, James H

2018-07-01

The lack of specificity in neuroimaging studies of neurological and psychiatric diseases suggests that these different diseases have more in common than is generally considered. Potentially, features that are secondary effects of different pathological processes may share common neurobiological underpinnings. Intriguingly, many of these mechanisms are also observed in studies of normal (i.e., non-pathological) brain ageing. Different brain diseases may be causing premature or accelerated ageing to the brain, an idea that is supported by a line of "brain ageing" research that combines neuroimaging data with machine learning analysis. In reviewing this field, I conclude that such observations could have important implications, suggesting that we should shift experimental paradigm: away from characterizing the average case-control brain differences resulting from a disease toward methods that place individuals in their age-appropriate context. This will also lead naturally to clinical applications, whereby neuroimaging can contribute to a personalized-medicine approach to improve brain health. © 2018 WILEY Periodicals, Inc.

Context-Dependent Learning in People With Parkinson's Disease.

PubMed

Lee, Ya-Yun; Winstein, Carolee J; Gordon, James; Petzinger, Giselle M; Zelinski, Elizabeth M; Fisher, Beth E

2016-01-01

Context-dependent learning is a phenomenon in which people demonstrate superior performance in the context in which they originally learned a skill but perform less well in a novel context. This study investigated context-dependent learning in people with Parkinson's disease (PD) and age-matched nondisabled adults. All participants practiced 3 finger sequences, each embedded within a unique context (colors and locations on a computer screen). One day after practice, the participants were tested either under the sequence-context associations remained the same as during practice, or the sequence-context associations were changed (SWITCH). Compared with nondisabled adults, people with PD demonstrated significantly greater decrement in performance (especially movement time) under the SWITCH condition, suggesting that individuals with PD are more context dependent than nondisabled adults.

Nutrients and ageing: what can we learn about ageing interactions from animal biology?

PubMed

Stenvinkel, Peter; Kooman, Jeroen P; Shiels, Paul G

2016-01-01

Many prevalent clinical conditions, such as chronic kidney disease, diabetes mellitus, chronic obstructive pulmonary, and cardiovascular disease associate with features of premature ageing, such as muscle wasting, hypogonadism, osteoporosis, and arteriosclerosis. Studies on various animal models have shown that caloric restriction prolongs lifespan. Studies of animals with unusual long or short life for their body size may also contribute to better understanding of ageing processes. The aim of the present article is to review what we can learn about nutritional modulations and ageing interactions from animal biology. Caloric restriction is a powerful intervention that increases longevity in animals ranging from short-lived species, such as worms and flies, to primates. As long-term studies on caloric restriction are not feasible to conduct in humans, much interest has focused on the impact of caloric restriction mimetics, such as resveratrol, on ageing processes. Recent data from studies on the long-lived naked mole rat have provided important novel information on metabolic alterations and antioxidative defense mechanisms that characterize longevity. Better understanding of the biology of exceptionally long-lived animals will contribute to better understanding of ageing processes and novel interventions to extend lifespan also in humans.

Deep learning applications in ophthalmology.

PubMed

Rahimy, Ehsan

2018-05-01

To describe the emerging applications of deep learning in ophthalmology. Recent studies have shown that various deep learning models are capable of detecting and diagnosing various diseases afflicting the posterior segment of the eye with high accuracy. Most of the initial studies have centered around detection of referable diabetic retinopathy, age-related macular degeneration, and glaucoma. Deep learning has shown promising results in automated image analysis of fundus photographs and optical coherence tomography images. Additional testing and research is required to clinically validate this technology.

Automated Grading of Age-Related Macular Degeneration From Color Fundus Images Using Deep Convolutional Neural Networks.

PubMed

Burlina, Philippe M; Joshi, Neil; Pekala, Michael; Pacheco, Katia D; Freund, David E; Bressler, Neil M

2017-11-01

Age-related macular degeneration (AMD) affects millions of people throughout the world. The intermediate stage may go undetected, as it typically is asymptomatic. However, the preferred practice patterns for AMD recommend identifying individuals with this stage of the disease to educate how to monitor for the early detection of the choroidal neovascular stage before substantial vision loss has occurred and to consider dietary supplements that might reduce the risk of the disease progressing from the intermediate to the advanced stage. Identification, though, can be time-intensive and requires expertly trained individuals. To develop methods for automatically detecting AMD from fundus images using a novel application of deep learning methods to the automated assessment of these images and to leverage artificial intelligence advances. Deep convolutional neural networks that are explicitly trained for performing automated AMD grading were compared with an alternate deep learning method that used transfer learning and universal features and with a trained clinical grader. Age-related macular degeneration automated detection was applied to a 2-class classification problem in which the task was to distinguish the disease-free/early stages from the referable intermediate/advanced stages. Using several experiments that entailed different data partitioning, the performance of the machine algorithms and human graders in evaluating over 130 000 images that were deidentified with respect to age, sex, and race/ethnicity from 4613 patients against a gold standard included in the National Institutes of Health Age-related Eye Disease Study data set was evaluated. Accuracy, receiver operating characteristics and area under the curve, and kappa score. The deep convolutional neural network method yielded accuracy (SD) that ranged between 88.4% (0.5%) and 91.6% (0.1%), the area under the receiver operating characteristic curve was between 0.94 and 0.96, and kappa coefficient (SD) between 0.764 (0.010) and 0.829 (0.003), which indicated a substantial agreement with the gold standard Age-related Eye Disease Study data set. Applying a deep learning-based automated assessment of AMD from fundus images can produce results that are similar to human performance levels. This study demonstrates that automated algorithms could play a role that is independent of expert human graders in the current management of AMD and could address the costs of screening or monitoring, access to health care, and the assessment of novel treatments that address the development or progression of AMD.

Predicting Age Using Neuroimaging: Innovative Brain Ageing Biomarkers.

PubMed

Cole, James H; Franke, Katja

2017-12-01

The brain changes as we age and these changes are associated with functional deterioration and neurodegenerative disease. It is vital that we better understand individual differences in the brain ageing process; hence, techniques for making individualised predictions of brain ageing have been developed. We present evidence supporting the use of neuroimaging-based 'brain age' as a biomarker of an individual's brain health. Increasingly, research is showing how brain disease or poor physical health negatively impacts brain age. Importantly, recent evidence shows that having an 'older'-appearing brain relates to advanced physiological and cognitive ageing and the risk of mortality. We discuss controversies surrounding brain age and highlight emerging trends such as the use of multimodality neuroimaging and the employment of 'deep learning' methods. Copyright © 2017 Elsevier Ltd. All rights reserved.

Evaluation of Learned Helplessness, Perceived Self-efficacy, and Functional Capacity in Patients With Fibromyalgia and Rheumatoid Arthritis.

PubMed

Moyano, Sebastián; Scolnik, Marina; Vergara, Facundo; García, María Victoria; Sabelli, Mirtha Rosa; Rosa, Javier Eduardo; Catoggio, Luis José; Soriano, Enrique Roberto

2018-03-19

The aims of this study were to compare learned helplessness (LH) and perceived self-efficacy (SE) in patients with fibromyalgia (FM) and rheumatoid arthritis (RA) and to assess their correlation with functional disability, level of perceived pain, and fatigue. This multicenter, cross-sectional study included consecutive patients (aged ≥18 years) with RA, according to the 2010 American College of Rheumatology/European League Against Rheumatism criteria, and FM, according to 2010 American College of Rheumatology criteria. Learned helplessness was measured by the Rheumatology Attitude Index, Spanish version; SE with the Arthritis Self-efficacy Scale, Spanish version; functional capacity with the Health Assessment Questionnaire (HAQ), Argentine version; depression with Center for Epidemiological Studies-Depression Scale 7-item version and perceived pain and fatigue by the visual analog scale. Disease activity was measured by the Clinical Disease Activity Index (CDAI) and disease impact with the Fibromyalgia Impact Questionnaire (FIQ). A total of 215 patients, 100 with FM and 115 with RA, were included. Mean age was 59 (SD, 14) years and 58 (SD, 13) years for FM and RA, patients respectively. Whereas LH and depression were significantly higher, SE was significantly lower in FM patients. We found a positive correlation between LH and HAQ, pain, depression, fatigue, FIQ, and CDAI in FM and RA patients. We observed a negative correlation between SE and HAQ, pain, depression, fatigue, FIQ (FM), and CDAI (RA) in both groups. Both LH and SE correlate significantly with functional capacity, perceived pain, disease activity, and disease impact in RA and FM patients. Learned helplessness was higher in patients with active disease or high disease impact, as opposed to those in remission or with low disease impact, and the reverse was true for SE. Patients with FM had significantly more LH, pain, fatigue, and depression and less SE compared with those with RA.

Female Adolescents with Chronic or End-Stage Kidney Disease and Strategies for their Care.

PubMed

Diaz-Gonzalez De Ferris, Maria E; Alvarez-Elías, Ana Catalina; Ferris, Michael Ted; Medeiros, Mara

2017-07-01

The prevalence of chronic or end-stage kidney disease in pediatric girls is lower than in boys, however, girls have unique morbidities that can have great effect on their quality of life. For female adolescents, creatinine excretion peaks at approximately 14 years of age and is significantly less than males, owing to lower muscle mass. Females have higher nitric oxide activity, and estrogens may contribute to lower blood pressure. Females excrete less growth hormone during the prepubertal and pubertal years. Females between the ages of 8 and 10 years show increased levels of parathyroid hormone and vitamin D, however, female adolescents with chronic kidney disease have less estrogen and loss of the luteinizing hormone pulsatile pattern. These biological, hormonal, and physical changes affect the psychosocial aspects of female adolescents with chronic kidney disease/end-stage kidney disease, and they must learn to manage their health to achieve good outcomes. Patients and their parents must learn disease management through a customized health care transition preparation in both the pediatric- and adult-focused settings. Clinical strategies are suggested for the care of these special patients. Copyright © 2017. Published by Elsevier Inc.

Machine Learning Techniques in Clinical Vision Sciences.

PubMed

Caixinha, Miguel; Nunes, Sandrina

2017-01-01

This review presents and discusses the contribution of machine learning techniques for diagnosis and disease monitoring in the context of clinical vision science. Many ocular diseases leading to blindness can be halted or delayed when detected and treated at its earliest stages. With the recent developments in diagnostic devices, imaging and genomics, new sources of data for early disease detection and patients' management are now available. Machine learning techniques emerged in the biomedical sciences as clinical decision-support techniques to improve sensitivity and specificity of disease detection and monitoring, increasing objectively the clinical decision-making process. This manuscript presents a review in multimodal ocular disease diagnosis and monitoring based on machine learning approaches. In the first section, the technical issues related to the different machine learning approaches will be present. Machine learning techniques are used to automatically recognize complex patterns in a given dataset. These techniques allows creating homogeneous groups (unsupervised learning), or creating a classifier predicting group membership of new cases (supervised learning), when a group label is available for each case. To ensure a good performance of the machine learning techniques in a given dataset, all possible sources of bias should be removed or minimized. For that, the representativeness of the input dataset for the true population should be confirmed, the noise should be removed, the missing data should be treated and the data dimensionally (i.e., the number of parameters/features and the number of cases in the dataset) should be adjusted. The application of machine learning techniques in ocular disease diagnosis and monitoring will be presented and discussed in the second section of this manuscript. To show the clinical benefits of machine learning in clinical vision sciences, several examples will be presented in glaucoma, age-related macular degeneration, and diabetic retinopathy, these ocular pathologies being the major causes of irreversible visual impairment.

Practice Effects on Story Memory and List Learning Tests in the Neuropsychological Assessment of Older Adults

PubMed Central

Gurnani, Ashita S.; Saurman, Jessica L.; Chapman, Kimberly R.; Steinberg, Eric G.; Martin, Brett; Chaisson, Christine E.; Mez, Jesse; Tripodis, Yorghos; Stern, Robert A.

2016-01-01

Two of the most commonly used methods to assess memory functioning in studies of cognitive aging and dementia are story memory and list learning tests. We hypothesized that the most commonly used story memory test, Wechsler's Logical Memory, would generate more pronounced practice effects than a well validated but less common list learning test, the Neuropsychological Assessment Battery (NAB) List Learning test. Two hundred eighty-seven older adults, ages 51 to 100 at baseline, completed both tests as part of a larger neuropsychological test battery on an annual basis. Up to five years of recall scores from participants who were diagnosed as cognitively normal (n = 96) or with mild cognitive impairment (MCI; n = 72) or Alzheimer's disease (AD; n = 121) at their most recent visit were analyzed with linear mixed effects regression to examine the interaction between the type of test and the number of times exposed to the test. Other variables, including age at baseline, sex, education, race, time (years) since baseline, and clinical diagnosis were also entered as fixed effects predictor variables. The results indicated that both tests produced significant practice effects in controls and MCI participants; in contrast, participants with AD declined or remained stable. However, for the delayed—but not the immediate—recall condition, Logical Memory generated more pronounced practice effects than NAB List Learning (b = 0.16, p < .01 for controls). These differential practice effects were moderated by clinical diagnosis, such that controls and MCI participants—but not participants with AD—improved more on Logical Memory delayed recall than on delayed NAB List Learning delayed recall over five annual assessments. Because the Logical Memory test is ubiquitous in cognitive aging and neurodegenerative disease research, its tendency to produce marked practice effects—especially on the delayed recall condition—suggests a threat to its validity as a measure of new learning, an essential construct for dementia diagnosis. PMID:27711147

A Deep Learning Algorithm for Prediction of Age-Related Eye Disease Study Severity Scale for Age-Related Macular Degeneration from Color Fundus Photography.

PubMed

Grassmann, Felix; Mengelkamp, Judith; Brandl, Caroline; Harsch, Sebastian; Zimmermann, Martina E; Linkohr, Birgit; Peters, Annette; Heid, Iris M; Palm, Christoph; Weber, Bernhard H F

2018-04-10

Age-related macular degeneration (AMD) is a common threat to vision. While classification of disease stages is critical to understanding disease risk and progression, several systems based on color fundus photographs are known. Most of these require in-depth and time-consuming analysis of fundus images. Herein, we present an automated computer-based classification algorithm. Algorithm development for AMD classification based on a large collection of color fundus images. Validation is performed on a cross-sectional, population-based study. We included 120 656 manually graded color fundus images from 3654 Age-Related Eye Disease Study (AREDS) participants. AREDS participants were >55 years of age, and non-AMD sight-threatening diseases were excluded at recruitment. In addition, performance of our algorithm was evaluated in 5555 fundus images from the population-based Kooperative Gesundheitsforschung in der Region Augsburg (KORA; Cooperative Health Research in the Region of Augsburg) study. We defined 13 classes (9 AREDS steps, 3 late AMD stages, and 1 for ungradable images) and trained several convolution deep learning architectures. An ensemble of network architectures improved prediction accuracy. An independent dataset was used to evaluate the performance of our algorithm in a population-based study. κ Statistics and accuracy to evaluate the concordance between predicted and expert human grader classification. A network ensemble of 6 different neural net architectures predicted the 13 classes in the AREDS test set with a quadratic weighted κ of 92% (95% confidence interval, 89%-92%) and an overall accuracy of 63.3%. In the independent KORA dataset, images wrongly classified as AMD were mainly the result of a macular reflex observed in young individuals. By restricting the KORA analysis to individuals >55 years of age and prior exclusion of other retinopathies, the weighted and unweighted κ increased to 50% and 63%, respectively. Importantly, the algorithm detected 84.2% of all fundus images with definite signs of early or late AMD. Overall, 94.3% of healthy fundus images were classified correctly. Our deep learning algoritm revealed a weighted κ outperforming human graders in the AREDS study and is suitable to classify AMD fundus images in other datasets using individuals >55 years of age. Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Age-dependent cognitive impairment in a Drosophila fragile X model and its pharmacological rescue.

PubMed

Choi, Catherine H; McBride, Sean M J; Schoenfeld, Brian P; Liebelt, David A; Ferreiro, David; Ferrick, Neal J; Hinchey, Paul; Kollaros, Maria; Rudominer, Rebecca L; Terlizzi, Allison M; Koenigsberg, Eric; Wang, Yan; Sumida, Ai; Nguyen, Hanh T; Bell, Aaron J; McDonald, Thomas V; Jongens, Thomas A

2010-06-01

Fragile X syndrome afflicts 1 in 2,500 individuals and is the leading heritable cause of mental retardation worldwide. The overriding clinical manifestation of this disease is mild to severe cognitive impairment. Age-dependent cognitive decline has been identified in Fragile X patients, although it has not been fully characterized nor examined in animal models. A Drosophila model of this disease has been shown to display phenotypes bearing similarity to Fragile X symptoms. Most notably, we previously identified naive courtship and memory deficits in young adults with this model that appear to be due to enhanced metabotropic glutamate receptor (mGluR) signaling. Herein we have examined age-related cognitive decline in the Drosophila Fragile X model and found an age-dependent loss of learning during training. We demonstrate that treatment with mGluR antagonists or lithium can prevent this age-dependent cognitive impairment. We also show that treatment with mGluR antagonists or lithium during development alone displays differential efficacy in its ability to rescue naive courtship, learning during training and memory in aged flies. Furthermore, we show that continuous treatment during aging effectively rescues all of these phenotypes. These results indicate that the Drosophila model recapitulates the age-dependent cognitive decline observed in humans. This places Fragile X in a category with several other diseases that result in age-dependent cognitive decline. This demonstrates a role for the Drosophila Fragile X Mental Retardation Protein (dFMR1) in neuronal physiology with regard to cognition during the aging process. Our results indicate that misregulation of mGluR activity may be causative of this age onset decline and strengthens the possibility that mGluR antagonists and lithium may be potential pharmacologic compounds for counteracting several Fragile X symptoms.

Neuropathologic Studies of the Baltimore Longitudinal Study of Aging (BLSA)

PubMed Central

O’Brien, Richard J.; Resnick, Susan M.; Zonderman, Alan B.; Ferrucci, Luigi; Crain, Barbara J.; Pletnikova, Olga; Rudow, Gay; Iacono, Diego; Riudavets, Miguel A.; Driscoll, Ira; Price, Donald L.; Martin, Lee J.; Troncoso, Juan C.

2010-01-01

The Baltimore Longitudinal Study of Aging (BLSA) was established in 1958 and is one the oldest prospective studies of aging in the USA and the world. The BLSA is supported by the National Institute of Aging (NIA) and its mission is to learn what happens to people as they get old and how to sort out changes due to aging and from those due to disease or other causes. In 1986, an autopsy program combined with comprehensive neurologic and cognitive evaluations was established in collaboration with the Johns Hopkins University Alzheimer’s Disease Research Center (ADRC). Since then, 211 subjects have undergone autopsy. Here we review the key clinical neuropathological correlations from this autopsy series. The focus is on the morphological and biochemical changes that occur in normal aging, and the early neuropathological changes of neurodegenerative diseases, especially Alzheimer’s disease (AD). We highlight the combined clinical, pathologic, morphometric, and biochemical evidence of asymptomatic AD, a state characterized by normal clinical evaluations in subjects with abundant AD pathology. We conclude that in some individuals, successful cognitive aging results from compensatory mechanisms that occur at the neuronal level (i.e., neuronal hypertrophy and synaptic plasticity) whereas a failure of compensation may culminate in disease. PMID:19661626

Design and Analysis of Blast Induced Traumatic Brain Injury Mechanism Using a Surrogate Headform: Instrumentation and Outcomes

DTIC Science & Technology

2011-05-01

51 4.5.1: FABRY -PÉROT FIBER OPTIC GAUGES...aggressive social behavior, impaired thinking, language, learning, emotions, behavior, sensation, and neuro-degenerative diseases such as epilepsy...Alzheimer’s disease , Parkinson’s disease , and other brain disorders that become more prevalent with age [9, Figure 2.1: Causes of TBI- A diagram of

Associations between Verbal Learning Slope and Neuroimaging Markers across the Cognitive Aging Spectrum.

PubMed

Gifford, Katherine A; Phillips, Jeffrey S; Samuels, Lauren R; Lane, Elizabeth M; Bell, Susan P; Liu, Dandan; Hohman, Timothy J; Romano, Raymond R; Fritzsche, Laura R; Lu, Zengqi; Jefferson, Angela L

2015-07-01

A symptom of mild cognitive impairment (MCI) and Alzheimer's disease (AD) is a flat learning profile. Learning slope calculation methods vary, and the optimal method for capturing neuroanatomical changes associated with MCI and early AD pathology is unclear. This study cross-sectionally compared four different learning slope measures from the Rey Auditory Verbal Learning Test (simple slope, regression-based slope, two-slope method, peak slope) to structural neuroimaging markers of early AD neurodegeneration (hippocampal volume, cortical thickness in parahippocampal gyrus, precuneus, and lateral prefrontal cortex) across the cognitive aging spectrum [normal control (NC); (n=198; age=76±5), MCI (n=370; age=75±7), and AD (n=171; age=76±7)] in ADNI. Within diagnostic group, general linear models related slope methods individually to neuroimaging variables, adjusting for age, sex, education, and APOE4 status. Among MCI, better learning performance on simple slope, regression-based slope, and late slope (Trial 2-5) from the two-slope method related to larger parahippocampal thickness (all p-values<.01) and hippocampal volume (p<.01). Better regression-based slope (p<.01) and late slope (p<.01) were related to larger ventrolateral prefrontal cortex in MCI. No significant associations emerged between any slope and neuroimaging variables for NC (p-values ≥.05) or AD (p-values ≥.02). Better learning performances related to larger medial temporal lobe (i.e., hippocampal volume, parahippocampal gyrus thickness) and ventrolateral prefrontal cortex in MCI only. Regression-based and late slope were most highly correlated with neuroimaging markers and explained more variance above and beyond other common memory indices, such as total learning. Simple slope may offer an acceptable alternative given its ease of calculation.

Effect of Exercise Training on Hippocampal Volume in Humans: A Pilot Study

ERIC Educational Resources Information Center

Parker, Beth A.; Thompson, Paul D.; Jordan, Kathryn C.; Grimaldi, Adam S.; Assaf, Michal; Jagannathan, Kanchana; Pearlson, Godfrey D.

2011-01-01

The hippocampus is the primary site of memory and learning in the brain. Both normal aging and various disease pathologies (e.g., alcoholism, schizophrenia, and major depressive disorder) are associated with lower hippocampal volumes in humans and hippocampal atrophy predicts progression of Alzheimers disease. In animals, there is convincing…

Sign language aphasia from a neurodegenerative disease.

PubMed

Falchook, Adam D; Mayberry, Rachel I; Poizner, Howard; Burtis, David Brandon; Doty, Leilani; Heilman, Kenneth M

2013-01-01

While Alois Alzheimer recognized the effects of the disease he described on speech and language in his original description of the disease in 1907, the effects of Alzheimer's disease (AD) on language in deaf signers has not previously been reported. We evaluated a 55-year-old right-handed congenitally deaf woman with a 2-year history of progressive memory loss and a deterioration of her ability to communicate in American Sign Language, which she learned at the age of eight. Examination revealed that she had impaired episodic memory as well as marked impairments in the production and comprehension of fingerspelling and grammatically complex sentences. She also had signs of anomia as well as an ideomotor apraxia and visual-spatial dysfunction. This report illustrates the challenges in evaluation of a patient for the presence of degenerative dementia when the person is deaf from birth, uses sign language, and has a late age of primary language acquisition. Although our patient could neither speak nor hear, in many respects her cognitive disorders mirror those of patients with AD who had normally learned to speak.

Striatal degeneration impairs language learning: evidence from Huntington's disease.

PubMed

De Diego-Balaguer, R; Couette, M; Dolbeau, G; Dürr, A; Youssov, K; Bachoud-Lévi, A-C

2008-11-01

Although the role of the striatum in language processing is still largely unclear, a number of recent proposals have outlined its specific contribution. Different studies report evidence converging to a picture where the striatum may be involved in those aspects of rule-application requiring non-automatized behaviour. This is the main characteristic of the earliest phases of language acquisition that require the online detection of distant dependencies and the creation of syntactic categories by means of rule learning. Learning of sequences and categorization processes in non-language domains has been known to require striatal recruitment. Thus, we hypothesized that the striatum should play a prominent role in the extraction of rules in learning a language. We studied 13 pre-symptomatic gene-carriers and 22 early stage patients of Huntington's disease (pre-HD), both characterized by a progressive degeneration of the striatum and 21 late stage patients Huntington's disease (18 stage II, two stage III and one stage IV) where cortical degeneration accompanies striatal degeneration. When presented with a simplified artificial language where words and rules could be extracted, early stage Huntington's disease patients (stage I) were impaired in the learning test, demonstrating a greater impairment in rule than word learning compared to the 20 age- and education-matched controls. Huntington's disease patients at later stages were impaired both on word and rule learning. While spared in their overall performance, gene-carriers having learned a set of abstract artificial language rules were then impaired in the transfer of those rules to similar artificial language structures. The correlation analyses among several neuropsychological tests assessing executive function showed that rule learning correlated with tests requiring working memory and attentional control, while word learning correlated with a test involving episodic memory. These learning impairments significantly correlated with the bicaudate ratio. The overall results support striatal involvement in rule extraction from speech and suggest that language acquisition requires several aspects of memory and executive functions for word and rule learning.

Galantamine Facilitates Acquisition of Hippocampus-Dependent Trace Eyeblink Conditioning in Aged Rabbits

ERIC Educational Resources Information Center

Weible, Aldis P.; Oh, M. Matthew; Lee, Grace; Disterhoft, John F.

2004-01-01

Cholinergic systems are critical to the neural mechanisms mediating learning. Reduced nicotinic cholinergic receptor (nAChR) binding is a hallmark of normal aging. These reductions are markedly more severe in some dementias, such as Alzheimer's disease. Pharmacological central nervous system therapies are a means to ameliorate the cognitive…

Evaluation of nootropic potential of Ocimum sanctum Linn. in mice.

PubMed

Joshi, Hanumanthachar; Parle, Milind

2006-02-01

Dementia is one of the age related mental problems and a characteristic symptom of various neurodegenerative disorders including Alzheimer's disease. Certain drugs like diazepam, barbiturates and alcohol disrupt learning and memory in animals and man. However, a new class of drugs known as nootropic agents is now used in situations where there is organic disorder in learning abilities. The present work was undertaken to assess the potential of O. sanctum extract as a nootropic and anti-amnesic agent in mice. Aqueous extract of dried whole plant of O. sanctum ameliorated the amnesic effect of scopolamine (0.4 mg/kg), diazepam (1 mg/kg) and aging induced memory deficits in mice. Elevated plus maze and passive avoidance paradigm served as the exteroceptive behavioral models. O. sanctum extract decreased transfer latency and increased step down latency, when compared to control (piracetam treated), scopolamine and aged groups of mice significantly. O. sanctum preparations could of beneficial in the treatment of cognitive disorders such as dementia and Alzheimer's disease.

Learning cooking skills at different ages: a cross-sectional study.

PubMed

Lavelle, Fiona; Spence, Michelle; Hollywood, Lynsey; McGowan, Laura; Surgenor, Dawn; McCloat, Amanda; Mooney, Elaine; Caraher, Martin; Raats, Monique; Dean, Moira

2016-11-14

Cooking skills are increasingly included in strategies to prevent and reduce chronic diet-related diseases and obesity. While cooking interventions target all age groups (Child, Teen and Adult), the optimal age for learning these skills on: 1) skills retention, 2) cooking practices, 3) cooking attitudes, 4) diet quality and 5) health is unknown. Similarly, although the source of learning cooking skills has been previously studied, the differences in learning from these different sources has not been considered. This research investigated the associations of the age and source of learning with the aforementioned five factors. A nationally representative (Northern/Republic of Ireland) cross-sectional survey was undertaken with 1049 adults aged between 20-60 years. The survey included both measures developed and tested by the researchers as well as validated measures of cooking (e.g. chopping) and food skills (e.g. budgeting), cooking practices (e.g. food safety), cooking attitudes, diet quality and health. Respondents also stated when they learnt the majority of their skills and their sources of learning. The data was analysed using ANOVAs with post-hoc analysis and Chi 2 crosstabs with a significance level of 0.05. Results showed that child (<12 years) and/or teen (13-18 years) learners had significantly greater numbers of, and confidence in, their cooking and food skills, cooking practices, cooking attitudes, diet quality (with the exception of fibre intake where adult learners were higher) and health. Mother was the primary source of learning and those who learnt only from this source had significantly better outcomes on 12 of the 23 measures. This research highlights the importance of learning cooking skills at an early age for skill retention, confidence, cooking practices, cooking attitude and diet quality. Mother remained the primary source of learning, however, as there is a reported deskilling of domestic cooks, mothers may no longer have the ability to teach cooking skills to the next generation. A focus on alternative sources including practical cooking skills education starting at an early age is required. This study also highlights the need for further longitudinal research on the impact of age and source of learning on cooking skills.

Fluoxetine attenuates the impairment of spatial learning ability and prevents neuron loss in middle-aged APPswe/PSEN1dE9 double transgenic Alzheimer's disease mice.

PubMed

Ma, Jing; Gao, Yuan; Jiang, Lin; Chao, Feng-Lei; Huang, Wei; Zhou, Chun-Ni; Tang, Wei; Zhang, Lei; Huang, Chun-Xia; Zhang, Yi; Luo, Yan-Min; Xiao, Qian; Yu, Hua-Rong; Jiang, Rong; Tang, Yong

2017-04-25

Selective serotonin reuptake inhibitors (SSRIs) have been reported to increase cognitive performance in some clinical studies of Alzheimer's disease (AD). However, there is a lack of evidence supporting the efficacy of SSRIs as cognition enhancers in AD, and the role of SSRIs as a treatment for AD remains largely unclear. Here, we characterized the impact of fluoxetine (FLX), a well-known SSRI, on neurons in the dentate gyrus (DG) and in CA1 and CA3 of the hippocampus of middle-aged (16 to 17 months old) APPswe/PSEN1dE9 (APP/PS1) transgenic AD model mice. We found that intraperitoneal (i.p.) injection of FLX (10 mg/kg/day) for 5 weeks effectively alleviated the impairment of spatial learning ability in middle-aged APP/PS1 mice as evaluated using the Morris water maze. More importantly, the number of neurons in the hippocampal DG was significantly increased by FLX. Additionally, FLX reduced the deposition of beta amyloid, inhibited GSK-3β activity and increased the level of β-catenin in middle-aged APP/PS1 mice. Collectively, the results of this study indicate that FLX delayed the progression of neuronal loss in the hippocampal DG in middle-aged AD mice, and this effect may underlie the FLX-induced improvement in learning ability. FLX may therefore serve as a promising therapeutic drug for AD.

Fluoxetine attenuates the impairment of spatial learning ability and prevents neuron loss in middle-aged APPswe/PSEN1dE9 double transgenic Alzheimer's disease mice

PubMed Central

Ma, Jing; Gao, Yuan; Jiang, Lin; Chao, Feng-lei; Huang, Wei; Zhou, Chun-ni; Tang, Wei; Zhang, Lei; Huang, Chun-xia; Zhang, Yi; Luo, Yan-min; Xiao, Qian; Yu, Hua-rong; Jiang, Rong; Tang, Yong

2017-01-01

Selective serotonin reuptake inhibitors (SSRIs) have been reported to increase cognitive performance in some clinical studies of Alzheimer’s disease (AD). However, there is a lack of evidence supporting the efficacy of SSRIs as cognition enhancers in AD, and the role of SSRIs as a treatment for AD remains largely unclear. Here, we characterized the impact of fluoxetine (FLX), a well-known SSRI, on neurons in the dentate gyrus (DG) and in CA1 and CA3 of the hippocampus of middle-aged (16 to 17 months old) APPswe/PSEN1dE9 (APP/PS1) transgenic AD model mice. We found that intraperitoneal (i.p.) injection of FLX (10 mg/kg/day) for 5 weeks effectively alleviated the impairment of spatial learning ability in middle-aged APP/PS1 mice as evaluated using the Morris water maze. More importantly, the number of neurons in the hippocampal DG was significantly increased by FLX. Additionally, FLX reduced the deposition of beta amyloid, inhibited GSK-3β activity and increased the level of β-catenin in middle-aged APP/PS1 mice. Collectively, the results of this study indicate that FLX delayed the progression of neuronal loss in the hippocampal DG in middle-aged AD mice, and this effect may underlie the FLX-induced improvement in learning ability. FLX may therefore serve as a promising therapeutic drug for AD. PMID:28430602

Multi-categorical deep learning neural network to classify retinal images: A pilot study employing small database.

PubMed

Choi, Joon Yul; Yoo, Tae Keun; Seo, Jeong Gi; Kwak, Jiyong; Um, Terry Taewoong; Rim, Tyler Hyungtaek

2017-01-01

Deep learning emerges as a powerful tool for analyzing medical images. Retinal disease detection by using computer-aided diagnosis from fundus image has emerged as a new method. We applied deep learning convolutional neural network by using MatConvNet for an automated detection of multiple retinal diseases with fundus photographs involved in STructured Analysis of the REtina (STARE) database. Dataset was built by expanding data on 10 categories, including normal retina and nine retinal diseases. The optimal outcomes were acquired by using a random forest transfer learning based on VGG-19 architecture. The classification results depended greatly on the number of categories. As the number of categories increased, the performance of deep learning models was diminished. When all 10 categories were included, we obtained results with an accuracy of 30.5%, relative classifier information (RCI) of 0.052, and Cohen's kappa of 0.224. Considering three integrated normal, background diabetic retinopathy, and dry age-related macular degeneration, the multi-categorical classifier showed accuracy of 72.8%, 0.283 RCI, and 0.577 kappa. In addition, several ensemble classifiers enhanced the multi-categorical classification performance. The transfer learning incorporated with ensemble classifier of clustering and voting approach presented the best performance with accuracy of 36.7%, 0.053 RCI, and 0.225 kappa in the 10 retinal diseases classification problem. First, due to the small size of datasets, the deep learning techniques in this study were ineffective to be applied in clinics where numerous patients suffering from various types of retinal disorders visit for diagnosis and treatment. Second, we found that the transfer learning incorporated with ensemble classifiers can improve the classification performance in order to detect multi-categorical retinal diseases. Further studies should confirm the effectiveness of algorithms with large datasets obtained from hospitals.

Cardiovascular Event Prediction by Machine Learning: The Multi-Ethnic Study of Atherosclerosis.

PubMed

Ambale-Venkatesh, Bharath; Yang, Xiaoying; Wu, Colin O; Liu, Kiang; Hundley, W Gregory; McClelland, Robyn; Gomes, Antoinette S; Folsom, Aaron R; Shea, Steven; Guallar, Eliseo; Bluemke, David A; Lima, João A C

2017-10-13

Machine learning may be useful to characterize cardiovascular risk, predict outcomes, and identify biomarkers in population studies. To test the ability of random survival forests, a machine learning technique, to predict 6 cardiovascular outcomes in comparison to standard cardiovascular risk scores. We included participants from the MESA (Multi-Ethnic Study of Atherosclerosis). Baseline measurements were used to predict cardiovascular outcomes over 12 years of follow-up. MESA was designed to study progression of subclinical disease to cardiovascular events where participants were initially free of cardiovascular disease. All 6814 participants from MESA, aged 45 to 84 years, from 4 ethnicities, and 6 centers across the United States were included. Seven-hundred thirty-five variables from imaging and noninvasive tests, questionnaires, and biomarker panels were obtained. We used the random survival forests technique to identify the top-20 predictors of each outcome. Imaging, electrocardiography, and serum biomarkers featured heavily on the top-20 lists as opposed to traditional cardiovascular risk factors. Age was the most important predictor for all-cause mortality. Fasting glucose levels and carotid ultrasonography measures were important predictors of stroke. Coronary Artery Calcium score was the most important predictor of coronary heart disease and all atherosclerotic cardiovascular disease combined outcomes. Left ventricular structure and function and cardiac troponin-T were among the top predictors for incident heart failure. Creatinine, age, and ankle-brachial index were among the top predictors of atrial fibrillation. TNF-α (tissue necrosis factor-α) and IL (interleukin)-2 soluble receptors and NT-proBNP (N-Terminal Pro-B-Type Natriuretic Peptide) levels were important across all outcomes. The random survival forests technique performed better than established risk scores with increased prediction accuracy (decreased Brier score by 10%-25%). Machine learning in conjunction with deep phenotyping improves prediction accuracy in cardiovascular event prediction in an initially asymptomatic population. These methods may lead to greater insights on subclinical disease markers without apriori assumptions of causality. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00005487. © 2017 American Heart Association, Inc.

Education for Self-Responsibility III: Prevention of HIV/AIDS and Other Communicable Diseases. Curriculum Guide. Grades 4-6.

ERIC Educational Resources Information Center

Texas Education Agency, Austin.

This curriculum guide encourages students to learn behaviors that will reduce the potential for HIV infection when confronted with choices at a later age. The curriculum is designed for integration within a comprehensive program of school health education (lessons on communicable disease, including Human Immunodeficiency Virus (HIV), can be…

Neuroprotective effect and mechanism of daucosterol palmitate in ameliorating learning and memory impairment in a rat model of Alzheimer's disease.

PubMed

Ji, Zhi-Hong; Xu, Zhong-Qi; Zhao, Hong; Yu, Xin-Yu

2017-03-01

Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by progressive memory decline and cognitive impairment. Amyloid beta (Aβ) has been proposed as the causative role for the pathogenesis of AD. Accumulating evidence demonstrates that Aβ neurotoxicity is mediated by glutamate excitotoxicity. Daucosterol palmitate (DSP), a plant steroid with anti-glutamate excitotoxicity effect, was isolated from the anti-aging traditional Chinese medicinal herb Alpinia oxyphylla Miq. in our previous study. Based on the anti-glutamate excitotoxicity effect of DSP, in this study we investigated potential benefit and mechanism of DSP in ameliorating learning and memory impairment in AD model rats. Results from this study showed that DSP administration effectively ameliorated Aβ-induced learning and memory impairment in rats, markedly inhibited Aβ-induced hippocampal ROS production, effectively prevented Aβ-induced hippocampal neuronal damage and significantly restored hippocampal synaptophysin expression level. This study suggests that DSP may be a potential candidate for development as a therapeutic agent for AD cognitive decline. Copyright © 2017 Elsevier Inc. All rights reserved.

Education for Self-Responsibility III: Prevention of HIV/AIDS and Other Communicable Diseases. Curriculum Guide. Prekindergarten-Grade 3.

ERIC Educational Resources Information Center

Texas Education Agency, Austin.

This curriculum guide encourages students to learn behaviors that will reduce the potential for HIV infection when confronted with choices at a later age. The curriculum is designed for integration within a comprehensive program of school health education (lessons on communicable disease, including HIV, can be integrated at the preschool through…

Infectious disease burden and cognitive function in young to middle-aged adults.

PubMed

Gale, Shawn D; Erickson, Lance D; Berrett, Andrew; Brown, Bruce L; Hedges, Dawson W

2016-02-01

Prior research has suggested an association between exposure to infectious disease and neurocognitive function in humans. While most of these studies have explored individual viral, bacterial, and even parasitic sources of infection, few have considered the potential neurocognitive burden associated with multiple infections. In this study, we utilized publically available data from a large dataset produced by the Centers for Disease Control and Prevention that included measures of neurocognitive function, sociodemographic variables, and serum antibody data for several infectious diseases. Specifically, immunoglobulin G antibodies for toxocariasis, toxoplasmosis, hepatitis A, hepatitis B, and hepatitis C, cytomegalovirus, and herpes 1 and 2 were available in 5662 subjects. We calculated an overall index of infectious-disease burden to determine if an aggregate measure of exposure to infectious disease would be associated with neurocognitive function in adults aged 20-59 years. The index predicted processing speed and learning and memory but not reaction time after controlling for age, sex, race-ethnicity, immigration status, education, and the poverty-to-income ratio. Interactions between the infectious-disease index and some sociodemographic variables were also associated with neurocognitive function. In summary, an index aggregating exposure to several infectious diseases was associated with neurocognitive function in young- to middle-aged adults. Copyright © 2015 Elsevier Inc. All rights reserved.

[White House Conference on Aging, 1981: Health-Related and Medical Care Issues of the Elderly. Eighteen Reports.

ERIC Educational Resources Information Center

White House Conference on Aging, Washington, DC.

This document contains the 18 papers on health-related and medical care issues of the elderly that were presented at the 1981 White House Conference on Aging. The materials focus on the following topics: physical mobility, death, heart disease, nutrition, injury, senile dementia, post-menopausaul women, gerontological nursing, learning and memory,…

Aging, practice effects, and genetic risk in the Wisconsin Registry for Alzheimer’s Prevention

PubMed Central

Jonaitis, Erin M.; Koscik, Rebecca L.; La Rue, Asenath; Johnson, Sterling C.; Hermann, Bruce; Sager, Mark A.

2015-01-01

BACKGROUND In the last five years, a consensus has developed that Alzheimer’s disease (AD) may begin years before overt cognitive impairment (Sperling et al., 2011). Accordingly, the focus has shifted to identifying preclinical disease in order to match treatments to those most likely to benefit. Subtle cognitive changes, including reduced benefit from practice, may be one such preclinical sign. In this paper, we explore cognitive aging trajectories within a large cohort of clinically intact late-middle-aged adults. METHOD Longitudinal cognitive data were analyzed from 594 participants in the Wisconsin Registry for Alzheimer’s Prevention. Mixed models were used to examine trajectories, adjusting for prior exposure, and the moderation thereof by markers of dementia risk, APOE-ε4 status, and family history of AD. RESULTS Practice effects were observed for Verbal Learning & Memory, Working Memory, Speed & Flexibility, and Visual Learning. However, for Working Memory and Speed & Flexibility, these effects were attenuated for FH+ subjects. CONCLUSION Reduced practice effects have previously been observed in clinical groups (Cooper et al., 2001; Machulda et al., 2013). These results in middle-aged adults suggest that they may also indicate preclinical changes on the path to AD. PMID:26012360

The M-current inhibitor XE991 decreases the stimulation threshold for long-term synaptic plasticity in healthy mice and in models of cognitive disease.

PubMed

Fontán-Lozano, Angela; Suárez-Pereira, Irene; Delgado-García, José María; Carrión, Angel Manuel

2011-01-01

Aging, mental retardation, number of psychiatric and neurological disorders are all associated with learning and memory impairments. As the underlying causes of such conditions are very heterogeneous, manipulations that can enhance learning and memory in mice under different circumstances might be able to overcome the cognitive deficits in patients. The M-current regulates neuronal excitability and action potential firing, suggesting that its inhibition may increase cognitive capacities. We demonstrate that XE991, a specific M-current blocker, enhances learning and memory in healthy mice. This effect may be achieved by altering basal hippocampal synaptic activity and by diminishing the stimulation threshold for long-term changes in synaptic efficacy and learning-related gene expression. We also show that training sessions regulate the M-current by transiently decreasing the levels of KCNQ/Kv7.3 protein, a pivotal subunit for the M-current. Furthermore, we found that XE991 can revert the cognitive impairment associated with acetylcholine depletion and the neurodegeneration induced by kainic acid. Together, these results show that inhibition of the M-current as a general strategy may be useful to enhance cognitive capacities in healthy and aging individuals, as well as in those with neurodegenerative diseases. Copyright © 2010 Wiley-Liss, Inc.

Beneficial effects of dietary EGCG and voluntary exercise on behavior in an Alzheimer's disease mouse model.

PubMed

Walker, Jennifer M; Klakotskaia, Diana; Ajit, Deepa; Weisman, Gary A; Wood, W Gibson; Sun, Grace Y; Serfozo, Peter; Simonyi, Agnes; Schachtman, Todd R

2015-01-01

Alzheimer's disease (AD) is a progressive, age-dependent neurodegenerative disorder affecting specific brain regions that control memory and cognitive functions. Epidemiological studies suggest that exercise and dietary antioxidants are beneficial in reducing AD risk. To date, botanical flavonoids are consistently associated with the prevention of age-related diseases. The present study investigated the effects of 4 months of wheel-running exercise, initiated at 2-months of age, in conjunction with the effects of the green tea catechin (-)-epigallocatechin-3-gallate (EGCG) administered orally in the drinking water (50 mg/kg daily) on: (1) behavioral measures: learning and memory performance in the Barnes maze, nest building, open-field, anxiety in the light-dark box; and (2) soluble amyloid-β (Aβ) levels in the cortex and hippocampus in TgCRND8 (Tg) mice. Untreated Tg mice showed hyperactivity, relatively poor nest building behaviors, and deficits in spatial learning in the Barnes maze. Both EGCG and voluntary exercise, separately and in combination, were able to attenuate nest building and Barnes maze performance deficits. Additionally, these interventions lowered soluble Aβ1-42 levels in the cortex and hippocampus. These results, together with epidemiological and clinical studies in humans, suggest that dietary polyphenols and exercise may have beneficial effects on brain health and slow the progression of AD.

Multi-modal imaging predicts memory performance in normal aging and cognitive decline.

PubMed

Walhovd, K B; Fjell, A M; Dale, A M; McEvoy, L K; Brewer, J; Karow, D S; Salmon, D P; Fennema-Notestine, C

2010-07-01

This study (n=161) related morphometric MR imaging, FDG-PET and APOE genotype to memory scores in normal controls (NC), mild cognitive impairment (MCI) and Alzheimer's disease (AD). Stepwise regression analyses focused on morphometric and metabolic characteristics of the episodic memory network: hippocampus, entorhinal, parahippocampal, retrosplenial, posterior cingulate, precuneus, inferior parietal, and lateral orbitofrontal cortices. In NC, hippocampal metabolism predicted learning; entorhinal metabolism predicted recognition; and hippocampal metabolism predicted recall. In MCI, thickness of the entorhinal and precuneus cortices predicted learning, while parahippocampal metabolism predicted recognition. In AD, posterior cingulate cortical thickness predicted learning, while APOE genotype predicted recognition. In the total sample, hippocampal volume and metabolism, cortical thickness of the precuneus, and inferior parietal metabolism predicted learning; hippocampal volume and metabolism, parahippocampal thickness and APOE genotype predicted recognition. Imaging methods appear complementary and differentially sensitive to memory in health and disease. Medial temporal and parietal metabolism and morphometry best explained memory variance. Medial temporal characteristics were related to learning, recall and recognition, while parietal structures only predicted learning. Copyright 2008. Published by Elsevier Inc.

What's Your Stroke I.Q.?

MedlinePlus

What's Your Stroke I.Q.? Often, it is believed that stroke is a disease of old age. You may be surprised to learn that stroke ... to help prevent it. Test your stroke I.Q. by answering these six questions. By knowing the ...

Repeated cognitive stimulation alleviates memory impairments in an Alzheimer's disease mouse model.

PubMed

Martinez-Coria, Hilda; Yeung, Stephen T; Ager, Rahasson R; Rodriguez-Ortiz, Carlos J; Baglietto-Vargas, David; LaFerla, Frank M

2015-08-01

Alzheimer's disease is a neurodegenerative disease associated with progressive memory and cognitive decline. Previous studies have identified the benefits of cognitive enrichment on reducing disease pathology. Additionally, epidemiological and clinical data suggest that repeated exercise, and cognitive and social enrichment, can improve and/or delay the cognitive deficiencies associated with aging and neurodegenerative diseases. In the present study, 3xTg-AD mice were exposed to a rigorous training routine beginning at 3 months of age, which consisted of repeated training in the Morris water maze spatial recognition task every 3 months, ending at 18 months of age. At the conclusion of the final Morris water maze training session, animals subsequently underwent testing in another hippocampus-dependent spatial task, the Barnes maze task, and on the more cortical-dependent novel object recognition memory task. Our data show that periodic cognitive enrichment throughout aging, via multiple learning episodes in the Morris water maze task, can improve the memory performance of aged 3xTg-AD mice in a separate spatial recognition task, and in a preference memory task, when compared to naïve aged matched 3xTg-AD mice. Furthermore, we observed that the cognitive enrichment properties of Morris water maze exposer, was detectable in repeatedly trained animals as early as 6 months of age. These findings suggest early repeated cognitive enrichment can mitigate the diverse cognitive deficits observed in Alzheimer's disease. Published by Elsevier Inc.

“Dividends” From Research on Aging—Can Biogerontologists, at Long Last, Find Something Useful to Do?

PubMed Central

2009-01-01

Biogerontologists and demographers have argued that the fastest, most cost-effective strategies for prevention of the medical problems that afflict those older than 60 years are likely to emerge from a deeper understanding of what factors time the aging process and how aging leads, in rough synchrony, to the many diseases and disabilities of aging. Biologists can support and refine this discussion by studies of slow-aging mice, of mice with disease-promoting mutations, of mice in which specific cellular responses have been abrogated by genetic or pharmaceutical interventions, of slow-aging dog and horse breeds, and of the factors, genetic and physiological, that coordinate lethal and nonlethal consequences of aging in people. More work is also needed to learn how timing of antiaging interventions can be used to optimize the balance between beneficial and undesirable effects. PMID:19225032

Preserved Fronto-Striatal Plasticity and Enhanced Procedural Learning in a Transgenic Mouse Model of Alzheimer's Disease Overexpressing Mutant "hAPPswe"

ERIC Educational Resources Information Center

Middei, Silvia; Geracitano, Raffaella; Caprioli, Antonio; Mercuri, Nicola; Ammassari-Teule, Martine

2004-01-01

Mutations in the amyloid precursor protein (APP) gene inducing abnormal processing and deposition of [beta]-amyloid protein in the brain have been implicated in the pathogenesis of Alzheimer's disease (AD). Although Tg2576 mice with the Swedish mutation ("hAPPswe") exhibit age-related [Alpha][beta]-plaque formation in brain regions like the…

Multi-categorical deep learning neural network to classify retinal images: A pilot study employing small database

PubMed Central

Seo, Jeong Gi; Kwak, Jiyong; Um, Terry Taewoong; Rim, Tyler Hyungtaek

2017-01-01

Deep learning emerges as a powerful tool for analyzing medical images. Retinal disease detection by using computer-aided diagnosis from fundus image has emerged as a new method. We applied deep learning convolutional neural network by using MatConvNet for an automated detection of multiple retinal diseases with fundus photographs involved in STructured Analysis of the REtina (STARE) database. Dataset was built by expanding data on 10 categories, including normal retina and nine retinal diseases. The optimal outcomes were acquired by using a random forest transfer learning based on VGG-19 architecture. The classification results depended greatly on the number of categories. As the number of categories increased, the performance of deep learning models was diminished. When all 10 categories were included, we obtained results with an accuracy of 30.5%, relative classifier information (RCI) of 0.052, and Cohen’s kappa of 0.224. Considering three integrated normal, background diabetic retinopathy, and dry age-related macular degeneration, the multi-categorical classifier showed accuracy of 72.8%, 0.283 RCI, and 0.577 kappa. In addition, several ensemble classifiers enhanced the multi-categorical classification performance. The transfer learning incorporated with ensemble classifier of clustering and voting approach presented the best performance with accuracy of 36.7%, 0.053 RCI, and 0.225 kappa in the 10 retinal diseases classification problem. First, due to the small size of datasets, the deep learning techniques in this study were ineffective to be applied in clinics where numerous patients suffering from various types of retinal disorders visit for diagnosis and treatment. Second, we found that the transfer learning incorporated with ensemble classifiers can improve the classification performance in order to detect multi-categorical retinal diseases. Further studies should confirm the effectiveness of algorithms with large datasets obtained from hospitals. PMID:29095872

Motor Decline in Clinically Presymptomatic Spinocerebellar Ataxia Type 2 Gene Carriers

PubMed Central

Velázquez-Perez, Luis; Díaz, Rosalinda; Pérez-González, Ruth; Canales, Nalia; Rodríguez-Labrada, Roberto; Medrano, Jacquelín; Sánchez, Gilberto; Almaguer-Mederos, Luis; Torres, Cira; Fernandez-Ruiz, Juan

2009-01-01

Background Motor deficits are a critical component of the clinical characteristics of patients with spinocerebellar ataxia type 2. However, there is no current information on the preclinical manifestation of those motor deficits in presymptomatic gene carriers. To further understand and characterize the onset of the clinical manifestation in this disease, we tested presymptomatic spinocerebellar ataxia type 2 gene carriers, and volunteers, in a task that evaluates their motor performance and their motor learning capabilities. Methods and Findings 28 presymptomatic spinocerebellar ataxia type 2 gene carriers and an equal number of control volunteers matched for age and gender participated in the study. Both groups were tested in a prism adaptation task known to be sensible to both motor performance and visuomotor learning deficits. Our results clearly show that although motor learning capabilities are intact, motor performance deficits are present even years before the clinical manifestation of the disease start. Conclusions The results show a clear deficit in motor performance that can be detected years before the clinical onset of the disease. This motor performance deficit appears before any motor learning or clinical manifestations of the disease. These observations identify the performance coefficient as an objective and quantitative physiological biomarker that could be useful to assess the efficiency of different therapeutic agents. PMID:19401771

A Longitudinal Item Response Theory Model to Characterize Cognition Over Time in Elderly Subjects

PubMed Central

Bornkamp, Björn; Krahnke, Tillmann; Mielke, Johanna; Monsch, Andreas; Quarg, Peter

2017-01-01

For drug development in neurodegenerative diseases such as Alzheimer's disease, it is important to understand which cognitive domains carry the most information on the earliest signs of cognitive decline, and which subject characteristics are associated with a faster decline. A longitudinal Item Response Theory (IRT) model was developed for the Basel Study on the Elderly, in which the Consortium to Establish a Registry for Alzheimer's Disease – Neuropsychological Assessment Battery (with additions) and the California Verbal Learning Test were measured on 1,750 elderly subjects for up to 13.9 years. The model jointly captured the multifaceted nature of cognition and its longitudinal trajectory. The word list learning and delayed recall tasks carried the most information. Greater age at baseline, fewer years of education, and positive APOEɛ4 carrier status were associated with a faster cognitive decline. Longitudinal IRT modeling is a powerful approach for progressive diseases with multifaceted endpoints. PMID:28643388

Effects of Cumulative Frequency, but Not of Frequency Trajectory, in Lexical Decision Times of Older Adults and Patients with Alzheimer's Disease

ERIC Educational Resources Information Center

Caza, Nicole; Moscovitch, Morris

2005-01-01

The purpose of this study was to investigate the issue of age-limited learning effects on visual lexical decision in normal and pathological aging, by using words with different frequency trajectories and cumulative frequencies. We selected words that objectively changed in frequency trajectory from an early word count (Thorndike, 1921, 1932;…

Probabilistic reversal learning is impaired in Parkinson's disease

PubMed Central

Peterson, David A.; Elliott, Christian; Song, David D.; Makeig, Scott; Sejnowski, Terrence J.; Poizner, Howard

2009-01-01

In many everyday settings, the relationship between our choices and their potentially rewarding outcomes is probabilistic and dynamic. In addition, the difficulty of the choices can vary widely. Although a large body of theoretical and empirical evidence suggests that dopamine mediates rewarded learning, the influence of dopamine in probabilistic and dynamic rewarded learning remains unclear. We adapted a probabilistic rewarded learning task originally used to study firing rates of dopamine cells in primate substantia nigra pars compacta (Morris et al. 2006) for use as a reversal learning task with humans. We sought to investigate how the dopamine depletion in Parkinson's disease (PD) affects probabilistic reward learning and adaptation to a reversal in reward contingencies. Over the course of 256 trials subjects learned to choose the more favorable from among pairs of images with small or large differences in reward probabilities. During a subsequent otherwise identical reversal phase, the reward probability contingencies for the stimuli were reversed. Seventeen Parkinson's disease (PD) patients of mild to moderate severity were studied off of their dopaminergic medications and compared to 15 age-matched controls. Compared to controls, PD patients had distinct pre- and post-reversal deficiencies depending upon the difficulty of the choices they had to learn. The patients also exhibited compromised adaptability to the reversal. A computational model of the subjects’ trial-by-trial choices demonstrated that the adaptability was sensitive to the gain with which patients weighted pre-reversal feedback. Collectively, the results implicate the nigral dopaminergic system in learning to make choices in environments with probabilistic and dynamic reward contingencies. PMID:19628022

Copernicus revisited: amyloid beta in Alzheimer's disease.

PubMed

Joseph, J; Shukitt-Hale, B; Denisova, N A; Martin, A; Perry, G; Smith, M A

2001-01-01

The beta-amyloid hypothesis of Alzheimer's Disease (AD) has dominated the thinking and research in this area for over a decade and a half. While there has been a great deal of effort in attempting to prove its centrality in this devastating disease, and while an enormous amount has been learned about its properties (e.g., putative toxicity, processing and signaling), Abeta has not proven to be both necessary and sufficient for the development, neurotoxicity, and cognitive deficits associated with this disease. Instead, the few treatments that are available have emerged from aging research and are primarily directed toward modification of acetylcholine levels. Clearly, it is time to rethink this position and to propose instead that future approaches should focus upon altering the age-related sensitivity of the neuronal environment to insults involving such factors as inflammation and oxidative stress. In other words "solve the problems of aging and by extension those of AD will also be reduced." This review is being submitted as a rather Lutherian attempt to "nail an alternative thesis" to the gate of the Church of the Holy Amyloid to open its doors to the idea that aging is the most pervasive element in this disease and Abeta is merely one of the planets.

Age and Age-Related Diseases: Role of Inflammation Triggers and Cytokines

PubMed Central

Rea, Irene Maeve; Gibson, David S.; McGilligan, Victoria; McNerlan, Susan E.; Alexander, H. Denis; Ross, Owen A.

2018-01-01

Cytokine dysregulation is believed to play a key role in the remodeling of the immune system at older age, with evidence pointing to an inability to fine-control systemic inflammation, which seems to be a marker of unsuccessful aging. This reshaping of cytokine expression pattern, with a progressive tendency toward a pro-inflammatory phenotype has been called “inflamm-aging.” Despite research there is no clear understanding about the causes of “inflamm-aging” that underpin most major age-related diseases, including atherosclerosis, diabetes, Alzheimer’s disease, rheumatoid arthritis, cancer, and aging itself. While inflammation is part of the normal repair response for healing, and essential in keeping us safe from bacterial and viral infections and noxious environmental agents, not all inflammation is good. When inflammation becomes prolonged and persists, it can become damaging and destructive. Several common molecular pathways have been identified that are associated with both aging and low-grade inflammation. The age-related change in redox balance, the increase in age-related senescent cells, the senescence-associated secretory phenotype (SASP) and the decline in effective autophagy that can trigger the inflammasome, suggest that it may be possible to delay age-related diseases and aging itself by suppressing pro-inflammatory molecular mechanisms or improving the timely resolution of inflammation. Conversely there may be learning from molecular or genetic pathways from long-lived cohorts who exemplify good quality aging. Here, we will discuss some of the current ideas and highlight molecular pathways that appear to contribute to the immune imbalance and the cytokine dysregulation, which is associated with “inflammageing” or parainflammation. Evidence of these findings will be drawn from research in cardiovascular disease, cancer, neurological inflammation and rheumatoid arthritis. PMID:29686666

The impact of educational experiences on nursing students' knowledge and attitudes toward people with Alzheimer's disease: A mixed method study.

PubMed

Kimzey, Michelle; Mastel-Smith, Beth; Alfred, Danita

2016-11-01

As the population ages, the effects of Alzheimer's disease will be felt by all nurses. Providing proper care for people with Alzheimer's disease is difficult and requires specific skills, attitudes, and knowledge. Limited data exists regarding nursing students' attitudes and knowledge toward people with Alzheimer's disease, whether undergraduate education prepares students to care for this population, or the best methods to support students in learning in an innovative and interactive environment. The aim of this study was to determine the effect of different educational experiences on nursing students' knowledge and attitudes toward people with Alzheimer's disease and to explore nursing students' knowledge and attitudes surrounding the care of people with Alzheimer's disease. A convergent mixed method design. A three group (Alzheimer's disease clinical experience, online learning module, and no dementia-specific intervention), pretest and posttest design served as the quantitative arm of the study. A focus group discussion with themes extracted served as the qualitative piece of the study. College of Nursing in North Texas. Convenience sample of 94 senior level nursing students enrolled in the undergraduate nursing program's Community Health course. Students completed pre and posttest surveys which included Alzheimer's Disease Knowledge Scale, Dementia Attitudes Scale, and demographic questionnaire. Content analysis was conducted on focus group responses to qualitative interview questions. The Alzheimer's disease clinical group experienced increased knowledge and improved attitudes toward people with Alzheimer's disease compared with students who completed the online module or had no dementia-specific intervention. Four themes emerged from focus group data: Basic Alzheimer's disease knowledge, need for Alzheimer's disease experiential learning, negative feelings related to behaviors, and appropriate responses to behavioral and psychological symptoms of dementia. Experiential learning in the form of clinical placements increased knowledge and improved attitudes about Alzheimer's disease compared with an online module and no dementia-specific intervention. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

Early Intervention with a Multi-Ingredient Dietary Supplement Improves Mood and Spatial Memory in a Triple Transgenic Mouse Model of Alzheimer's Disease.

PubMed

Hutton, Craig P; Lemon, Jennifer A; Sakic, Boris; Rollo, C David; Boreham, Douglas R; Fahnestock, Margaret; Wojtowicz, J Martin; Becker, Suzanna

2018-06-09

The increasing global burden of Alzheimer's disease (AD) and failure of conventional treatments to stop neurodegeneration necessitates an alternative approach. Evidence of inflammation, mitochondrial dysfunction, and oxidative stress prior to the accumulation of amyloid-β in the prodromal stage of AD (mild cognitive impairment; MCI) suggests that early interventions which counteract these features, such as dietary supplements, may ameliorate the onset of MCI-like behavioral symptoms. We administered a polyphenol-containing multiple ingredient dietary supplement (MDS), or vehicle, to both sexes of triple transgenic (3xTg-AD) mice and wildtype mice for 2 months from 2-4 months of age. We hypothesized that the MDS would preserve spatial learning, which is known to be impaired in untreated 3xTg-AD mice by 4 months of age. Behavioral phenotyping of animals was done at 1-2 and 3-4 months of age using a comprehensive battery of tests. As previously reported in males, both sexes of 3xTg-AD mice exhibited increased anxiety-like behavior at 1-2 months of age, prior to deficits in learning and memory, which did not appear until 3-4 months of age. The MDS did not reduce this anxiety or prevent impairments in novel object recognition (both sexes) or on the water maze probe trial (females only). Strikingly, the MDS specifically prevented 3xTg-AD mice (both sexes) from developing impairments (exhibited by untreated 3xTg-AD controls) in working memory and spatial learning. The MDS also increased sucrose preference, an indicator of hedonic tone. These data show that the MDS can prevent some, but not all, psychopathology in an AD model.

Physical Therapy for Neurological Conditions in Geriatric Populations.

PubMed

Carmeli, Eli

2017-01-01

With more of the world's population surviving longer, individuals often face age-related neurology disorders and decline of function that can affect lifestyle and well-being. Despite neurophysiological changes affecting the brain function and structure, the aged brain, in some degree, can learn and relearn due to neuroplasticity. Recent advances in rehabilitation techniques have produced better functional outcomes in age-related neurological conditions. Physical therapy (PT) of the elderly individual focuses in particular on sensory-motor impairments, postural control coordination, and prevention of sarcopenia. Geriatric PT has a significant influence on quality of life, independent living, and life expectancy. However, in many developed and developing countries, the profession of PT is underfunded and understaffed. This article provides a brief overview on (a) age-related disease of central nervous system and (b) the principles, approaches, and doctrines of motor skill learning and point out the most common treatment models that PTs use for neurological patients.

Physical Therapy for Neurological Conditions in Geriatric Populations

PubMed Central

Carmeli, Eli

2017-01-01

With more of the world’s population surviving longer, individuals often face age-related neurology disorders and decline of function that can affect lifestyle and well-being. Despite neurophysiological changes affecting the brain function and structure, the aged brain, in some degree, can learn and relearn due to neuroplasticity. Recent advances in rehabilitation techniques have produced better functional outcomes in age-related neurological conditions. Physical therapy (PT) of the elderly individual focuses in particular on sensory–motor impairments, postural control coordination, and prevention of sarcopenia. Geriatric PT has a significant influence on quality of life, independent living, and life expectancy. However, in many developed and developing countries, the profession of PT is underfunded and understaffed. This article provides a brief overview on (a) age-related disease of central nervous system and (b) the principles, approaches, and doctrines of motor skill learning and point out the most common treatment models that PTs use for neurological patients. PMID:29270402

Loss of quinone reductase 2 function selectively facilitates learning behaviors.

PubMed

Benoit, Charles-Etienne; Bastianetto, Stephane; Brouillette, Jonathan; Tse, YiuChung; Boutin, Jean A; Delagrange, Philippe; Wong, TakPan; Sarret, Philippe; Quirion, Rémi

2010-09-22

High levels of reactive oxygen species (ROS) are associated with deficits in learning and memory with age as well as in Alzheimer's disease. Using DNA microarray, we demonstrated the overexpression of quinone reductase 2 (QR2) in the hippocampus in two models of learning deficits, namely the aged memory impaired rats and the scopolamine-induced amnesia model. QR2 is a cytosolic flavoprotein that catalyzes the reduction of its substrate and enhances the production of damaging activated quinone and ROS. QR2-like immunostaining is enriched in cerebral structures associated with learning behaviors, such as the hippocampal formation and the temporofrontal cortex of rat, mouse, and human brains. In cultured rat embryonic hippocampal neurons, selective inhibitors of QR2, namely S26695 and S29434, protected against menadione-induced cell death by reversing its proapoptotic action. S26695 (8 mg/kg) also significantly inhibited scopolamine-induced amnesia. Interestingly, adult QR2 knock-out mice demonstrated enhanced learning abilities in various tasks, including Morris water maze, object recognition, and rotarod performance test. Other behaviors related to anxiety (elevated plus maze), depression (forced swim), and schizophrenia (prepulse inhibition) were not affected in QR2-deficient mice. Together, these data suggest a role for QR2 in cognitive behaviors with QR2 inhibitors possibly representing a novel therapeutic strategy toward the treatment of learning deficits especially observed in the aged brain.

White matter hyperintensities and imaging patterns of brain ageing in the general population.

PubMed

Habes, Mohamad; Erus, Guray; Toledo, Jon B; Zhang, Tianhao; Bryan, Nick; Launer, Lenore J; Rosseel, Yves; Janowitz, Deborah; Doshi, Jimit; Van der Auwera, Sandra; von Sarnowski, Bettina; Hegenscheid, Katrin; Hosten, Norbert; Homuth, Georg; Völzke, Henry; Schminke, Ulf; Hoffmann, Wolfgang; Grabe, Hans J; Davatzikos, Christos

2016-04-01

White matter hyperintensities are associated with increased risk of dementia and cognitive decline. The current study investigates the relationship between white matter hyperintensities burden and patterns of brain atrophy associated with brain ageing and Alzheimer's disease in a large populatison-based sample (n = 2367) encompassing a wide age range (20-90 years), from the Study of Health in Pomerania. We quantified white matter hyperintensities using automated segmentation and summarized atrophy patterns using machine learning methods resulting in two indices: the SPARE-BA index (capturing age-related brain atrophy), and the SPARE-AD index (previously developed to capture patterns of atrophy found in patients with Alzheimer's disease). A characteristic pattern of age-related accumulation of white matter hyperintensities in both periventricular and deep white matter areas was found. Individuals with high white matter hyperintensities burden showed significantly (P < 0.0001) lower SPARE-BA and higher SPARE-AD values compared to those with low white matter hyperintensities burden, indicating that the former had more patterns of atrophy in brain regions typically affected by ageing and Alzheimer's disease dementia. To investigate a possibly causal role of white matter hyperintensities, structural equation modelling was used to quantify the effect of Framingham cardiovascular disease risk score and white matter hyperintensities burden on SPARE-BA, revealing a statistically significant (P < 0.0001) causal relationship between them. Structural equation modelling showed that the age effect on SPARE-BA was mediated by white matter hyperintensities and cardiovascular risk score each explaining 10.4% and 21.6% of the variance, respectively. The direct age effect explained 70.2% of the SPARE-BA variance. Only white matter hyperintensities significantly mediated the age effect on SPARE-AD explaining 32.8% of the variance. The direct age effect explained 66.0% of the SPARE-AD variance. Multivariable regression showed significant relationship between white matter hyperintensities volume and hypertension (P = 0.001), diabetes mellitus (P = 0.023), smoking (P = 0.002) and education level (P = 0.003). The only significant association with cognitive tests was with the immediate recall of the California verbal and learning memory test. No significant association was present with the APOE genotype. These results support the hypothesis that white matter hyperintensities contribute to patterns of brain atrophy found in beyond-normal brain ageing in the general population. White matter hyperintensities also contribute to brain atrophy patterns in regions related to Alzheimer's disease dementia, in agreement with their known additive role to the likelihood of dementia. Preventive strategies reducing the odds to develop cardiovascular disease and white matter hyperintensities could decrease the incidence or delay the onset of dementia. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

White matter hyperintensities and imaging patterns of brain ageing in the general population

PubMed Central

Erus, Guray; Toledo, Jon B.; Zhang, Tianhao; Bryan, Nick; Launer, Lenore J.; Rosseel, Yves; Janowitz, Deborah; Doshi, Jimit; Van der Auwera, Sandra; von Sarnowski, Bettina; Hegenscheid, Katrin; Hosten, Norbert; Homuth, Georg; Völzke, Henry; Schminke, Ulf; Hoffmann, Wolfgang; Grabe, Hans J.; Davatzikos, Christos

2016-01-01

Abstract White matter hyperintensities are associated with increased risk of dementia and cognitive decline. The current study investigates the relationship between white matter hyperintensities burden and patterns of brain atrophy associated with brain ageing and Alzheimer’s disease in a large populatison-based sample ( n = 2367) encompassing a wide age range (20–90 years), from the Study of Health in Pomerania. We quantified white matter hyperintensities using automated segmentation and summarized atrophy patterns using machine learning methods resulting in two indices: the SPARE-BA index (capturing age-related brain atrophy), and the SPARE-AD index (previously developed to capture patterns of atrophy found in patients with Alzheimer’s disease). A characteristic pattern of age-related accumulation of white matter hyperintensities in both periventricular and deep white matter areas was found. Individuals with high white matter hyperintensities burden showed significantly ( P < 0.0001) lower SPARE-BA and higher SPARE-AD values compared to those with low white matter hyperintensities burden, indicating that the former had more patterns of atrophy in brain regions typically affected by ageing and Alzheimer’s disease dementia. To investigate a possibly causal role of white matter hyperintensities, structural equation modelling was used to quantify the effect of Framingham cardiovascular disease risk score and white matter hyperintensities burden on SPARE-BA, revealing a statistically significant ( P < 0.0001) causal relationship between them. Structural equation modelling showed that the age effect on SPARE-BA was mediated by white matter hyperintensities and cardiovascular risk score each explaining 10.4% and 21.6% of the variance, respectively. The direct age effect explained 70.2% of the SPARE-BA variance. Only white matter hyperintensities significantly mediated the age effect on SPARE-AD explaining 32.8% of the variance. The direct age effect explained 66.0% of the SPARE-AD variance. Multivariable regression showed significant relationship between white matter hyperintensities volume and hypertension ( P = 0.001), diabetes mellitus ( P = 0.023), smoking ( P = 0.002) and education level ( P = 0.003). The only significant association with cognitive tests was with the immediate recall of the California verbal and learning memory test. No significant association was present with the APOE genotype. These results support the hypothesis that white matter hyperintensities contribute to patterns of brain atrophy found in beyond-normal brain ageing in the general population. White matter hyperintensities also contribute to brain atrophy patterns in regions related to Alzheimer’s disease dementia, in agreement with their known additive role to the likelihood of dementia. Preventive strategies reducing the odds to develop cardiovascular disease and white matter hyperintensities could decrease the incidence or delay the onset of dementia. PMID:26912649

Verbal and visual memory in patients with early Parkinson's disease: effect of levodopa.

PubMed

Singh, Sumit; Behari, Madhuri

2006-03-01

The effect of initiation of levodopa therapy on the memory functions in patients with Parkinson's disease remains poorly understood. To evaluate the effect of initiation of levodopa therapy on memory, in patients with early Parkinson's disease. Prospective case control study. Seventeen patients with early Parkinson's disease were evaluated for verbal memory using Rey's auditory verbal learning test, and visual memory using the Benton's visual retention test and Form sequence learning test. UPDRS scores, Hoehn and Yahr's Staging and Schwab and England scores of Activities of daily living. Hamilton's depression rating scale and MMSE were also evaluated. Six controls were also evaluated according to similar study protocol. Levodopa was then prescribed to the cases. Same tests were repeated on all the subjects after 12 weeks. The mean age of the patients was 59.8 (+ 12.9 yrs); mean disease duration of 3.26 (+ 2.06 yrs). The mean UPDRS scores of patients were 36.52 (+ 15.84). Controls were of a similar age and sex distribution. A statistically significant improvement in the scores on the UPDRS, Hamilton's depression scale, Schwab and England scale, and a statistically significant deterioration in the scores of visual memory was observed in patients with PD after starting levodopa, as compared to their baseline scores. There was no correlation between degree of deterioration and the dose of levodopa. Initiation of levodopa therapy in patients with early and stable Parkinson's disease is associated with deterioration in visual memory functions, with relative preservation of the verbal memory.

Translations from Kommunist No. 16, November 1977

DTIC Science & Technology

1978-01-06

circlement. We had to come out of age -old backwardness. We had to surmount the tremendous force of historical inertia and learn how to live according to...invariably manifested toward the Soviet state by our class brothers abroad. Their firm actions frequently helped to defeat the ag - gressive intents of...decent life. Yet, hunger, poverty, disease, illiteracy, right- lessness, fear of the future, and impoverished old age remain the share of huge

Semi-supervised manifold learning with affinity regularization for Alzheimer's disease identification using positron emission tomography imaging.

PubMed

Lu, Shen; Xia, Yong; Cai, Tom Weidong; Feng, David Dagan

2015-01-01

Dementia, Alzheimer's disease (AD) in particular is a global problem and big threat to the aging population. An image based computer-aided dementia diagnosis method is needed to providing doctors help during medical image examination. Many machine learning based dementia classification methods using medical imaging have been proposed and most of them achieve accurate results. However, most of these methods make use of supervised learning requiring fully labeled image dataset, which usually is not practical in real clinical environment. Using large amount of unlabeled images can improve the dementia classification performance. In this study we propose a new semi-supervised dementia classification method based on random manifold learning with affinity regularization. Three groups of spatial features are extracted from positron emission tomography (PET) images to construct an unsupervised random forest which is then used to regularize the manifold learning objective function. The proposed method, stat-of-the-art Laplacian support vector machine (LapSVM) and supervised SVM are applied to classify AD and normal controls (NC). The experiment results show that learning with unlabeled images indeed improves the classification performance. And our method outperforms LapSVM on the same dataset.

A Separable Two-Dimensional Random Field Model of Binary Response Data from Multi-Day Behavioral Experiments.

PubMed

Malem-Shinitski, Noa; Zhang, Yingzhuo; Gray, Daniel T; Burke, Sara N; Smith, Anne C; Barnes, Carol A; Ba, Demba

2018-04-18

The study of learning in populations of subjects can provide insights into the changes that occur in the brain with aging, drug intervention, and psychiatric disease. We introduce a separable two-dimensional (2D) random field (RF) model for analyzing binary response data acquired during the learning of object-reward associations across multiple days. The method can quantify the variability of performance within a day and across days, and can capture abrupt changes in learning. We apply the method to data from young and aged macaque monkeys performing a reversal-learning task. The method provides an estimate of performance within a day for each age group, and a learning rate across days for each monkey. We find that, as a group, the older monkeys require more trials to learn the object discriminations than do the young monkeys, and that the cognitive flexibility of the younger group is higher. We also use the model estimates of performance as features for clustering the monkeys into two groups. The clustering results in two groups that, for the most part, coincide with those formed by the age groups. Simulation studies suggest that clustering captures inter-individual differences in performance levels. In comparison with generalized linear models, this method is better able to capture the inherent two-dimensional nature of the data and find between group differences. Applied to binary response data from groups of individuals performing multi-day behavioral experiments, the model discriminates between-group differences and identifies subgroups. Copyright © 2018. Published by Elsevier B.V.

Mechanisms of n-3 fatty acid-mediated development and maintenance of learning memory performance.

PubMed

Su, Hui-Min

2010-05-01

Docosahexaenoic acid (DHA, 22:6n-3) is specifically enriched in the brain and mainly anchored in the neuronal membrane, where it is involved in the maintenance of normal neurological function. Most DHA accumulation in the brain takes place during brain development in the perinatal period. However, hippocampal DHA levels decrease with age and in the brain disorder Alzheimer's disease (AD), and this decrease is associated with reduced hippocampal-dependent spatial learning memory ability. A potential mechanism is proposed by which the n-3 fatty acids DHA and eicosapentaenoic acid (20:5n-3) aid the development and maintenance of spatial learning memory performance. The developing brain or hippocampal neurons can synthesize and take up DHA and incorporate it into membrane phospholipids, especially phosphatidylethanolamine, resulting in enhanced neurite outgrowth, synaptogenesis and neurogenesis. Exposure to n-3 fatty acids enhances synaptic plasticity by increasing long-term potentiation and synaptic protein expression to increase the dendritic spine density, number of c-Fos-positive neurons and neurogenesis in the hippocampus for learning memory processing. In aged rats, n-3 fatty acid supplementation reverses age-related changes and maintains learning memory performance. n-3 fatty acids have anti-oxidative stress, anti-inflammation, and anti-apoptosis effects, leading to neuron protection in the aged, damaged, and AD brain. Retinoid signaling may be involved in the effects of DHA on learning memory performance. Estrogen has similar effects to n-3 fatty acids on hippocampal function. It would be interesting to know if there is any interaction between DHA and estrogen so as to provide a better strategy for the development and maintenance of learning memory. Copyright 2010 Elsevier Inc. All rights reserved.

Survey on diagnosis of diseases from retinal images

NASA Astrophysics Data System (ADS)

Das, Sneha; Malathy, C.

2018-04-01

Retina is a thin membranous layer of tissue that occupies at the back of the eye which provides central vision needed for daily routines. Identifying retinal diseases at the early stage is a challenging task since healthy retina is required for central vision. Several retinal diseases affect the eye such as retinal tear, retinal detachment, glaucoma, macular hole and macular degeneration etc. These maladies will encounter a secondary growth in the close future as the age of the person increases. A survey is made which tells about the diagnosis of the retinal diseases from the retinal images using machine learning techniques.

Ankle brachial index and cognitive function among Hispanics/Latinos: Results from the Hispanic Community Health Study/Study of Latinos.

PubMed

Tarraf, Wassim; Criqui, Michael H; Allison, Matthew A; Wright, Clinton B; Fornage, Myriam; Daviglus, Martha; Kaplan, Robert C; Davis, Sonia; Conceicao, Alan S; González, Hector M

2018-04-01

The Ankle-Brachial index (ABI) is a well-accepted measure of peripheral artery disease (arterial stenosis and stiffness) and has been shown to be associated with cognitive function and disorders; however, these associations have not been examined in Hispanics/Latinos. Therefore, we sought to examine relationships between ABI and cognitive function among diverse middle-age and older Hispanics/Latinos. We used cross-sectional data on n = 7991 participants aged 45-74 years, without stroke or coronary heart disease, from the Hispanic Community Health Study/Study of Latinos. Our primary outcome, global cognition (GC), was a continuous composite score of four cognitive domains (verbal learning and memory, verbal fluency, executive function, and mental status). Secondary outcomes were the individual tests representing these domains. The ABI was analyzed continuously and categorically with standard clinical cut-points. We tested associations using generalized survey regression models incrementally adjusting for confounding factors. Age, sex, hypertension, diabetes, and dyslipidemia moderations were examined through interactions with the primary exposure. In age, sex, and education adjusted models, continuous ABI had an inverse u-shape association with worse GC. We found similar associations with measures of verbal learning and memory, verbal fluency, executive function, but not with low mental status. The associations were attenuated, but not completely explained, by accounting for the confounders and not modified by age, sex, education, and vascular disease risks. In addition to being a robust indicator of arterial compromise, our study suggests that abnormal ABI readings may also be useful for early signaling of subtle cognitive deficits. Copyright © 2018 Elsevier B.V. All rights reserved.

Accelerated age-related cognitive decline and neurodegeneration, caused by deficient DNA repair.

PubMed

Borgesius, Nils Z; de Waard, Monique C; van der Pluijm, Ingrid; Omrani, Azar; Zondag, Gerben C M; van der Horst, Gijsbertus T J; Melton, David W; Hoeijmakers, Jan H J; Jaarsma, Dick; Elgersma, Ype

2011-08-31

Age-related cognitive decline and neurodegenerative diseases are a growing challenge for our societies with their aging populations. Accumulation of DNA damage has been proposed to contribute to these impairments, but direct proof that DNA damage results in impaired neuronal plasticity and memory is lacking. Here we take advantage of Ercc1(Δ/-) mutant mice, which are impaired in DNA nucleotide excision repair, interstrand crosslink repair, and double-strand break repair. We show that these mice exhibit an age-dependent decrease in neuronal plasticity and progressive neuronal pathology, suggestive of neurodegenerative processes. A similar phenotype is observed in mice where the mutation is restricted to excitatory forebrain neurons. Moreover, these neuron-specific mutants develop a learning impairment. Together, these results suggest a causal relationship between unrepaired, accumulating DNA damage, and age-dependent cognitive decline and neurodegeneration. Hence, accumulated DNA damage could therefore be an important factor in the onset and progression of age-related cognitive decline and neurodegenerative diseases.

Proteomic analysis of specific brain proteins in aged SAMP8 mice treated with alpha-lipoic acid: implications for aging and age-related neurodegenerative disorders.

PubMed

Poon, H Fai; Farr, Susan A; Thongboonkerd, Visith; Lynn, Bert C; Banks, William A; Morley, John E; Klein, Jon B; Butterfield, D Allan

2005-01-01

Free radical-mediated damage to neuronal membrane components has been implicated in the etiology of Alzheimer's disease (AD) and aging. The senescence accelerated prone mouse strain 8 (SAMP8) exhibits age-related deterioration in memory and learning along with increased oxidative markers. Therefore, SAMP8 is a suitable model to study brain aging and, since aging is the major risk factor for AD and SAMP8 exhibits many of the biochemical findings of AD, perhaps as a model for and the early phase of AD. Our previous studies reported higher oxidative stress markers in brains of 12-month-old SAMP8 mice when compared to that of 4-month-old SAMP8 mice. Further, we have previously shown that injecting the mice with alpha-lipoic acid (LA) reversed brain lipid peroxidation, protein oxidation, as well as the learning and memory impairments in SAMP8 mice. Recently, we reported the use of proteomics to identify proteins that are expressed differently and/or modified oxidatively in aged SAMP8 brains. In order to understand how LA reverses the learning and memory deficits of aged SAMP8 mice, in the current study, we used proteomics to compare the expression levels and specific carbonyl levels of proteins in brains from 12-month-old SAMP8 mice treated or not treated with LA. We found that the expressions of the three brain proteins (neurofilament triplet L protein, alpha-enolase, and ubiquitous mitochondrial creatine kinase) were increased significantly and that the specific carbonyl levels of the three brain proteins (lactate dehydrogenase B, dihydropyrimidinase-like protein 2, and alpha-enolase) were significantly decreased in the aged SAMP8 mice treated with LA. These findings suggest that the improved learning and memory observed in LA-injected SAMP8 mice may be related to the restoration of the normal condition of specific proteins in aged SAMP8 mouse brain. Moreover, our current study implicates neurofilament triplet L protein, alpha-enolase, ubiquitous mitochondrial creatine kinase, lactate dehydrogenase B, and dihydropyrimidinase-like protein 2 in process associated with learning and memory of SAMP8 mice.

Enhanced Cognition and Hypoglutamatergic Signaling in a Growth Hormone Receptor Knockout Mouse Model of Successful Aging.

PubMed

Hascup, Kevin N; Lynn, Mary K; Fitzgerald, Patrick J; Randall, Shari; Kopchick, John J; Boger, Heather A; Bartke, Andrzej; Hascup, Erin R

2017-03-01

Growth hormone receptor knockout (GHR-KO) mice are long lived with improved health span, making this an excellent model system for understanding biochemical mechanisms important to cognitive reserve. The purpose of the present study was to elucidate differences in cognition and glutamatergic dynamics between aged (20- to 24-month-old) GHR-KO and littermate controls. Glutamate plays a critical role in hippocampal learning and memory and is implicated in several neurodegenerative disorders, including Alzheimer's disease. Spatial learning and memory were assessed using the Morris water maze (MWM), whereas independent dentate gyrus (DG), CA3, and CA1 basal glutamate, release, and uptake measurements were conducted in isoflurane anesthetized mice utilizing an enzyme-based microelectrode array (MEA) coupled with constant potential amperometry. These MEAs have high temporal and low spatial resolution while causing minimal damage to the surrounding parenchyma. Littermate controls performed worse on the memory portion of the MWM behavioral task and had elevated DG, CA3, and CA1 basal glutamate and stimulus-evoked release compared with age-matched GHR-KO mice. CA3 basal glutamate negatively correlated with MWM performance. These results support glutamatergic regulation in learning and memory and may have implications for therapeutic targets to delay the onset of, or reduce cognitive decline, in Alzheimer's disease. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Cholinesterase Inhibitors Improve Both Memory and Complex Learning in Aged Beagle Dogs

PubMed Central

Araujo, Joseph A.; Greig, Nigel H.; Ingram, Donald K.; Sandin, Johan; de Rivera, Christina; Milgram, Norton W.

2016-01-01

Similar to patients with Alzheimer’s disease (AD), dogs exhibit age-dependent cognitive decline, amyloid-β (Aβ) pathology, and evidence of cholinergic hypofunction. The present study sought to further investigate the role of cholinergic hypofunction in the canine model by examining the effect of the cholinesterase inhibitors phenserine and donepezil on performance of two tasks, a delayed non-matching-to-position task (DNMP) designed to assess working memory, and an oddity discrimination learning task designed to assess complex learning, in aged dogs. Phenserine (0.5 mg/kg; PO) significantly improved performance on the DNMP at the longest delay compared to wash-out and partially attenuated scopolamine-induced deficits (15 μg/kg; SC). Phenserine also improved learning on a difficult version of an oddity discrimination task compared to placebo, but had no effect on an easier version. We also examined the effects of three doses of donepezil (0.75, 1.5, and 6 mg/kg; PO) on performance of the DNMP. Similar to the results with phenserine, 1.5 mg/kg of donepezil improved performance at the longest delay compared to baseline and wash-out, indicative of memory enhancement. These results further extend the findings of cholinergic hypofunction in aged dogs and provide pharmacological validation of the canine model with a cholinesterase inhibitor approved for use in AD. Collectively, these studies support utilizing the aged dog in future screening of therapeutics for AD, as well as for investigating the links among cholinergic function, Aβ pathology, and cognitive decline. PMID:21593569

Comparison between the story recall test and the word-list learning test in Korean patients with mild cognitive impairment and early stage of Alzheimer's disease.

PubMed

Baek, Min Jae; Kim, Hyun Jung; Kim, Sangyun

2012-01-01

Among verbal memory tests, two that are commonly used to measure the ability of verbal memory function in cognitive impairment are story recall tests and word-list learning tests. However, research is limited regarding which test might be more sensitive in discriminating between normal cognitive aging and patients with Alzheimer's disease (AD) in the Korean population. The purpose of the current study was to compare the word-list learning test (Seoul Verbal Learning Test; SVLT) and the story recall test (Korean Story Recall Test; KSRT) to determine which test is more sensitive in discriminating between individuals with normal cognitive aging and patients with mild cognitive impairment (MCI) and early stage of AD in Korea. A total of 53 healthy adults, 127 patients with MCI, and 72 patients with early stage of AD participated in this study. The receiver-operating characteristic (ROC) curve and area under the curve (AUC) were evaluated to compare these two tests. The results showed that the AUC of the SVLT was significantly larger than the AUC of the KSRT in all three groups (healthy adults vs. MCI and early stage of AD; healthy adults vs. MCI; healthy adults vs. early stage of AD). However, in comparison of patients with MCI and early stage of AD, the AUC of SVLT and the AUC of KSRT were not significant. The word-list learning test is a more useful tool for examining verbal memory function for older adults in Korea than the story recall test.

Phospholipase A2 - nexus of aging, oxidative stress, neuronal excitability, and functional decline of the aging nervous system? Insights from a snail model system of neuronal aging and age-associated memory impairment.

PubMed

Hermann, Petra M; Watson, Shawn N; Wildering, Willem C

2014-01-01

The aging brain undergoes a range of changes varying from subtle structural and physiological changes causing only minor functional decline under healthy normal aging conditions, to severe cognitive or neurological impairment associated with extensive loss of neurons and circuits due to age-associated neurodegenerative disease conditions. Understanding how biological aging processes affect the brain and how they contribute to the onset and progress of age-associated neurodegenerative diseases is a core research goal in contemporary neuroscience. This review focuses on the idea that changes in intrinsic neuronal electrical excitability associated with (per)oxidation of membrane lipids and activation of phospholipase A2 (PLA2) enzymes are an important mechanism of learning and memory failure under normal aging conditions. Specifically, in the context of this special issue on the biology of cognitive aging we portray the opportunities offered by the identifiable neurons and behaviorally characterized neural circuits of the freshwater snail Lymnaea stagnalis in neuronal aging research and recapitulate recent insights indicating a key role of lipid peroxidation-induced PLA2 as instruments of aging, oxidative stress and inflammation in age-associated neuronal and memory impairment in this model system. The findings are discussed in view of accumulating evidence suggesting involvement of analogous mechanisms in the etiology of age-associated dysfunction and disease of the human and mammalian brain.

Cuba's Aging and Alzheimer Longitudinal Study.

PubMed

Llibre-Rodríguez, Juan de Jesús; Valhuerdi-Cepero, Adolfo; López-Medina, Ana M; Noriega-Fernández, Lisseth; Porto-Álvarez, Rutbeskia; Guerra-Hernández, Milagros A; Bosch-Bayard, Rodolfo I; Zayas-Llerena, Tania; Hernandez-Ulloa, Elaine; Rodríguez-Blanco, Ana L; Salazar-Pérez, Enrique; Llibre-Guerra, Juan C; Llibre-Guerra, Jorge J; Marcheco-Teruel, Beatriz

2017-01-01

Aging and Alzheimer is a prospective, longitudinal cohort study involving 2944 adults aged ≥65 years from selected areas in Cuba's Havana and Matanzas Provinces. This door-to-door study, which began in 2003, includes periodic assessments of the cohort based on an interview; physical exam; anthropometric measurements; and diagnosis of dementia and its subtypes, other mental disorders, and other chronic non-communicable diseases and their risk factors. Information was gathered on sociodemographic characteristics; disability, dependency and frailty; use of health services; and characteristics of care and caregiver burden. The first assessment also included blood tests: complete blood count, blood glucose, kidney and liver function, lipid profile and ApoE4 genotype (a susceptibility marker). In 2007-2011, the second assessment was done of 2010 study subjects aged ≥65 years who were still alive. The study provides data on prevalence and incidence of dementia and its risk factors, and of related conditions that affect the health of older adults. It also contributes valuable experiences from field work and interactions with older adults and their families. Building on lessons learned, a third assessment to be done in 2016-2018 will incorporate a community intervention strategy to respond to diseases and conditions that predispose to dementia, frailty and dependency in older adults. KEYWORDS Dementia, Alzheimer disease, chronic disease, aging, chronic illness, frailty, dependency, cohort studies, Cuba.

Generation to Generation: The Heart of Family Medicine

ERIC Educational Resources Information Center

Winter, Robin O.

2012-01-01

According to the American Board of Family Medicine, "The scope of family medicine encompasses all ages, both sexes, each organ system and every disease entity." What makes the seemingly daunting task of practicing family medicine possible is that family physicians learn to utilize similar clinical reasoning for all of their patients…

Age-Related Differences in Associative Learning of Landmarks and Heading Directions in a Virtual Navigation Task.

PubMed

Zhong, Jimmy Y; Moffat, Scott D

2016-01-01

Previous studies have showed that spatial memory declines with age but have not clarified the relevance of different landmark cues for specifying heading directions among different age groups. This study examined differences between younger, middle-aged and older adults in route learning and memory tasks after they navigated a virtual maze that contained: (a) critical landmarks that were located at decision points (i.e., intersections) and (b) non-critical landmarks that were located at non-decision points (i.e., the sides of the route). Participants were given a recognition memory test for critical and non-critical landmarks and also given a landmark-direction associative learning task. Compared to younger adults, older adults committed more navigation errors during route learning and were poorer at associating the correct heading directions with both critical and non-critical landmarks. Notably, older adults exhibited a landmark-direction associative memory deficit at decision points; this was the first finding to show that an associative memory deficit exist among older adults in a navigational context for landmarks that are pertinent for reaching a goal, and suggest that older adults may expend more cognitive resources on the encoding of landmark/object features than on the binding of landmark and directional information. This study is also the first to show that older adults did not have a tendency to process non-critical landmarks, which were regarded as distractors/irrelevant cues for specifying the directions to reach the goal, to an equivalent or larger extent than younger adults. We explain this finding in view of the low number of non-critical cues in our virtual maze (relative to a real-world urban environment) that might not have evoked older adults' usual tendency toward processing or encoding distractors. We explain the age differences in navigational and cognitive performance with regards to functional and structural changes in the hippocampus and parahippocampus, and recommend further investigations into the functional connectivity between the prefrontal cortex and hippocampus for a better understanding of the landmark-direction associative learning among the elderly. Finally, it is hoped that the current behavioral findings will facilitate efforts to identify the neural markers of Alzheimer's disease, a disease that commonly involves navigational deficits.

Differential Memory Test Sensitivity for Diagnosing Amnestic Mild Cognitive Impairment and Predicting Conversion to Alzheimer's Disease

PubMed Central

Rabin, Laura A.; Paré, Nadia; Saykin, Andrew J.; Brown, Michael J.; Wishart, Heather A.; Flashman, Laura A.; Santulli, Robert B.

2011-01-01

Episodic memory is the first and most severely affected cognitive domain in Alzheimer's disease (AD), and it is also the key early marker in prodromal stages including amnestic mild cognitive impairment (MCI). The relative ability of memory tests to discriminate between MCI and normal aging has not been well characterized. We compared the classification value of widely used verbal memory tests in distinguishing healthy older adults (n = 51) from those with MCI (n = 38). Univariate logistic regression indicated that the total learning score from the California Verbal Learning Test-II (CVLT-II) ranked highest in terms of distinguishing MCI from normal aging (sensitivity = 90.2; specificity = 84.2). Inclusion of the delayed recall condition of a story memory task (i.e., WMS-III Logical Memory, Story A) enhanced the overall accuracy of classification (sensitivity = 92.2; specificity = 94.7). Combining Logical Memory recognition and CVLT-II long delay best predicted progression from MCI to AD over a 4-year period (accurate classification = 87.5%). Learning across multiple trials may provide the most sensitive index for initial diagnosis of MCI, but inclusion of additional variables may enhance overall accuracy and may represent the optimal strategy for identifying individuals most likely to progress to dementia. PMID:19353345

Beneficial effects of docosahexaenoic acid on cognition in age-related cognitive decline.

PubMed

Yurko-Mauro, Karin; McCarthy, Deanna; Rom, Dror; Nelson, Edward B; Ryan, Alan S; Blackwell, Andrew; Salem, Norman; Stedman, Mary

2010-11-01

Docosahexaenoic acid (DHA) plays an important role in neural function. Decreases in plasma DHA are associated with cognitive decline in healthy elderly adults and in patients with Alzheimer's disease. Higher DHA intake is inversely correlated with relative risk of Alzheimer's disease. The potential benefits of DHA supplementation in age-related cognitive decline (ARCD) have not been fully examined. Determine effects of DHA administration on improving cognitive functions in healthy older adults with ARCD. Randomized, double-blind, placebo-controlled, clinical study was conducted at 19 U.S. clinical sites. A total of 485 healthy subjects, aged ≥55 with Mini-Mental State Examination >26 and a Logical Memory (Wechsler Memory Scale III) baseline score ≥1 standard deviation below younger adults, were randomly assigned to 900 mg/d of DHA orally or matching placebo for 24 weeks. The primary outcome was the CANTAB Paired Associate Learning (PAL), a visuospatial learning and episodic memory test. Intention-to-treat analysis demonstrated significantly fewer PAL six pattern errors with DHA versus placebo at 24 weeks (difference score, -1.63 ± 0.76 [-3.1, -0.14, 95% CI], P = .03). DHA supplementation was also associated with improved immediate and delayed Verbal Recognition Memory scores (P < .02), but not working memory or executive function tests. Plasma DHA levels doubled and correlated with improved PAL scores (P < .02) in the DHA group. DHA was well tolerated with no reported treatment-related serious adverse events. Twenty-four week supplementation with 900 mg/d DHA improved learning and memory function in ARCD and is a beneficial supplement that supports cognitive health with aging. Clinicaltrials.gov, Identifier: NCT0027813. Copyright © 2010 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Effect of parental family history of Alzheimer's disease on serial position profiles.

PubMed

La Rue, Asenath; Hermann, Bruce; Jones, Jana E; Johnson, Sterling; Asthana, Sanjay; Sager, Mark A

2008-07-01

An exaggerated recency effect (ie, disproportionate recall of last-presented items) has been consistently observed in the word list learning of patients with Alzheimer's disease (AD). Our study sought to determine whether there were similar alterations in serial position learning among asymptomatic persons at risk for AD as a result of parental family history. Subjects included 623 asymptomatic middle-aged children of patients with AD (median, 53 years) and 157 control participants whose parents survived to at least age 70 without AD or other memory disorders. All participants were administered the Rey Auditory Verbal Learning Test, which requires learning and recall of 15 unrelated nouns. There was no significant difference in total words recalled between the AD children and control groups. However, compared with controls, AD children exhibited a significantly greater tendency to recall words from the end (recency) versus beginning (primacy) of the list. Serial position effects were unrelated to apolipoprotein allele epsilon 4 or depressive symptoms. Asymptomatic persons at risk for AD by virtue of family history do not show a difference in total words recalled compared with controls, but they exhibit a distinctly different serial position curve, suggesting greater reliance on immediate as opposed to episodic memory. This is the same serial position pattern observed in mild AD, seen here in reduced severity. Longitudinal follow-up is planned to determine whether changes in serial position patterns are a meaningful marker for preclinical detection of AD.

Learning to predict is spared in mild cognitive impairment due to Alzheimer's disease.

PubMed

Baker, Rosalind; Bentham, Peter; Kourtzi, Zoe

2015-10-01

Learning the statistics of the environment is critical for predicting upcoming events. However, little is known about how we translate previous knowledge about scene regularities to sensory predictions. Here, we ask whether patients with mild cognitive impairment due to Alzheimer's disease (MCI-AD) that are known to have spared implicit but impaired explicit recognition memory are able to learn temporal regularities and predict upcoming events. We tested the ability of MCI-AD patients and age-matched controls to predict the orientation of a test stimulus following exposure to sequences of leftwards or rightwards oriented gratings. Our results demonstrate that exposure to temporal sequences without feedback facilitates the ability to predict an upcoming stimulus in both MCI-AD patients and controls. Further, we show that executive cognitive control may account for individual variability in predictive learning. That is, we observed significant positive correlations of performance in attentional and working memory tasks with post-training performance in the prediction task. Taken together, these results suggest a mediating role of circuits involved in cognitive control (i.e. frontal circuits) that may support the ability for predictive learning in MCI-AD.

Can physical exercise in old age improve memory and hippocampal function?

PubMed Central

van Praag, Henriette; Sendtner, Michael

2016-01-01

Abstract Physical exercise can convey a protective effect against cognitive decline in ageing and Alzheimer’s disease. While the long-term health-promoting and protective effects of exercise are encouraging, it’s potential to induce neuronal and vascular plasticity in the ageing brain is still poorly understood. It remains unclear whether exercise slows the trajectory of normal ageing by modifying vascular and metabolic risk factors and/or consistently boosts brain function by inducing structural and neurochemical changes in the hippocampus and related medial temporal lobe circuitry—brain areas that are important for learning and memory. Hence, it remains to be established to what extent exercise interventions in old age can improve brain plasticity above and beyond preservation of function. Existing data suggest that exercise trials aiming for improvement and preservation may require different outcome measures and that the balance between the two may depend on exercise intensity and duration, the presence of preclinical Alzheimer’s disease pathology, vascular and metabolic risk factors and genetic variability. PMID:26912638

A combination cocktail improves spatial attention in a canine model of human aging and Alzheimer's disease.

PubMed

Head, Elizabeth; Murphey, Heather L; Dowling, Amy L S; McCarty, Katie L; Bethel, Samuel R; Nitz, Jonathan A; Pleiss, Melanie; Vanrooyen, Jenna; Grossheim, Mike; Smiley, Jeffery R; Murphy, M Paul; Beckett, Tina L; Pagani, Dieter; Bresch, Frederick; Hendrix, Curt

2012-01-01

Alzheimer's disease (AD) involves multiple pathological processes in the brain, including increased inflammation and oxidative damage, as well as the accumulation of amyloid-β (Aβ) plaques. We hypothesized that a combinatorial therapeutic approach to target these multiple pathways may provide cognitive and neuropathological benefits for AD patients. To test this hypothesis, we used a canine model of human aging and AD. Aged dogs naturally develop learning and memory impairments, human-type Aβ deposits, and oxidative damage in the brain. Thus, 9 aged beagles (98-115 months) were treated with a medical food cocktail containing (1) an extract of turmeric containing 95% curcuminoids; (2) an extract of green tea containing 50% epigallocatechingallate; (3) N-acetyl cysteine; (4) R-alpha lipoic acid; and (5) an extract of black pepper containing 95% piperine. Nine similarly aged dogs served as placebo-treated controls. After 3 months of treatment, 13 dogs completed a variable distance landmark task used as a measure of spatial attention. As compared to placebo-treated animals, dogs receiving the medical food cocktail had significantly lower error scores (t11 = 4.3, p = 0.001) and were more accurate across all distances (F(1,9) = 20.7, p = 0.001), suggesting an overall improvement in spatial attention. Measures of visual discrimination learning, executive function and spatial memory, and levels of brain and cerebrospinal fluid Aβ were unaffected by the cocktail. Our results indicate that this medical food cocktail may be beneficial for improving spatial attention and motivation deficits associated with impaired cognition in aging and AD.

Cognitive states influence dopamine-driven aberrant learning in Parkinson’s disease

PubMed Central

Cavanagh, James F.; Mueller, Andrea A.; Brown, Darin R.; Janowich, Jacqueline R.; Story-Remer, Jacqueline H.; Wegele, Ashley; Richardson, Sarah Pirio

2017-01-01

Individual differences in dopaminergic tone underlie tendencies to learn from reward versus punishment. These effects are well documented in Parkinson’s patients, who vacillate between low and high tonic dopaminergic states as a function of medication. Yet very few studies have investigated the influence of higher-level cognitive states known to affect downstream dopaminergic learning in Parkinson’s patients. A dopamine-dependent cognitive influence over learning would provide a candidate mechanism for declining cognitive integrity and motivation in Parkinson’s patients. In this report we tested the influence of two high-level cognitive states (cost of conflict and value of volition) that have recently been shown to cause predictable learning biases in healthy young adults as a function of dopamine receptor subtype and dopaminergic challenge. It was hypothesized that Parkinson’s patients OFF medication would have an enhanced cost of conflict and a decreased value of volition, and that these effects would be remediated or reversed ON medication. Participants included N=28 Parkinson’s disease patients who were each tested ON and OFF dopaminergic medication and 28 age- and sex-matched controls. The expected cost of conflict effect was observed in Parkinson’s patients OFF versus ON medication, but only in those that were more recently diagnosed (<5 years). We found an unexpected effect in the value of volition task: medication compromised the ability to learn from difficult a-volitional (instructed) choices. This novel finding was also enhanced in recently diagnosed patients. The difference in learning biases ON vs. OFF medication between these two tasks was strongly correlated, bolstering the idea that they tapped into a common underlying imbalance in dopaminergic tone that is particularly variable in earlier stage Parkinsonism. The finding that these decision biases are specific to earlier but not later stage disease may offer a chance for future studies to quantify phenotypic expressions of idiosyncratic disease progression. PMID:28384481

Cognitive states influence dopamine-driven aberrant learning in Parkinson's disease.

PubMed

Cavanagh, James F; Mueller, Andrea A; Brown, Darin R; Janowich, Jacqueline R; Story-Remer, Jacqueline H; Wegele, Ashley; Richardson, Sarah Pirio

2017-05-01

Individual differences in dopaminergic tone underlie tendencies to learn from reward versus punishment. These effects are well documented in Parkinson's patients, who vacillate between low and high tonic dopaminergic states as a function of medication. Yet very few studies have investigated the influence of higher-level cognitive states known to affect downstream dopaminergic learning in Parkinson's patients. A dopamine-dependent cognitive influence over learning would provide a candidate mechanism for declining cognitive integrity and motivation in Parkinson's patients. In this report we tested the influence of two high-level cognitive states (cost of conflict and value of volition) that have recently been shown to cause predictable learning biases in healthy young adults as a function of dopamine receptor subtype and dopaminergic challenge. It was hypothesized that Parkinson's patients OFF medication would have an enhanced cost of conflict and a decreased value of volition, and that these effects would be remediated or reversed ON medication. Participants included N = 28 Parkinson's disease patients who were each tested ON and OFF dopaminergic medication and 28 age- and sex-matched controls. The expected cost of conflict effect was observed in Parkinson's patients OFF versus ON medication, but only in those that were more recently diagnosed (<5 years). We found an unexpected effect in the value of volition task: medication compromised the ability to learn from difficult a-volitional (instructed) choices. This novel finding was also enhanced in recently diagnosed patients. The difference in learning biases ON versus OFF medication between these two tasks was strongly correlated, bolstering the idea that they tapped into a common underlying imbalance in dopaminergic tone that is particularly variable in earlier stage Parkinsonism. The finding that these decision biases are specific to earlier but not later stage disease may offer a chance for future studies to quantify phenotypic expressions of idiosyncratic disease progression. Copyright © 2017 Elsevier Ltd. All rights reserved.

Classification of optical coherence tomography images for diagnosing different ocular diseases

NASA Astrophysics Data System (ADS)

Gholami, Peyman; Sheikh Hassani, Mohsen; Kuppuswamy Parthasarathy, Mohana; Zelek, John S.; Lakshminarayanan, Vasudevan

2018-03-01

Optical Coherence tomography (OCT) images provide several indicators, e.g., the shape and the thickness of different retinal layers, which can be used for various clinical and non-clinical purposes. We propose an automated classification method to identify different ocular diseases, based on the local binary pattern features. The database consists of normal and diseased human eye SD-OCT images. We use a multiphase approach for building our classifier, including preprocessing, Meta learning, and active learning. Pre-processing is applied to the data to handle missing features from images and replace them with the mean or median of the corresponding feature. All the features are run through a Correlation-based Feature Subset Selection algorithm to detect the most informative features and omit the less informative ones. A Meta learning approach is applied to the data, in which a SVM and random forest are combined to obtain a more robust classifier. Active learning is also applied to strengthen our classifier around the decision boundary. The primary experimental results indicate that our method is able to differentiate between the normal and non-normal retina with an area under the ROC curve (AUC) of 98.6% and also to diagnose the three common retina-related diseases, i.e., Age-related Macular Degeneration, Diabetic Retinopathy, and Macular Hole, with an AUC of 100%, 95% and 83.8% respectively. These results indicate a better performance of the proposed method compared to most of the previous works in the literature.

QTL mapping and candidate gene analysis of telomere length control factors in maize (Zea mays L.)

USDA-ARS?s Scientific Manuscript database

Telomere length is under genetic control and important for essential telomere functions. Failure to regulate telomere length homeostasis contributes to cancers and aging-related diseases in animals, but the effects of telomere length defects in plants remains poorly understood. To learn more about t...

New Learning Programs in Cognitive Vitality, Alzheimer's Disease, and Related Dementias

ERIC Educational Resources Information Center

Kovacich, Joann; Garrett, Ruth; Forti, Esther M.

2006-01-01

As the population continues to age there remains an unmet need in preventing, identifying, treating, and managing mental/behavioral health problems among older adults. The purpose of this paper is to describe educational and training programs offered through three Geriatric Education Centers: (1) the Meharry Consortium Geriatric Education Center,…

Evaluation of learned helplessness, self-efficacy and disease activity, functional capacity and pain in Argentinian patients with rheumatoid arthritis.

PubMed

Vergara, F; Rosa, J; Orozco, C; Bertiller, E; Gallardo, M A; Bravo, M; Catay, E; Collado, V; Gómez, G; Sabelli, M; García, M V; Rosemffet, M G; Citera, G; Schneeberger, E E; Catoggio, L J; Soriano, E R

2017-01-01

To evaluate the association between learned helplessness (LH) and self-efficacy (SE) with disease activity, functional capacity, and level of pain in patients with rheumatoid arthritis (RA) and to compare LH and SE between patients in remission and patients with active disease. This multicentre, cross-sectional study included consecutive patients (aged ≥ 18 years) with RA according to 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria. LH was measured by the Rheumatology Attitude Index (RAI), Spanish version; SE with the Arthritis Self-efficacy Scale (ASES), Spanish version; functional capacity with the Health Assessment Questionnaire, Argentinian version (HAQ-A); and perceived pain by the visual analogue scale (VAS). Disease activity was measured by the Clinical Disease Activity Index (CDAI). A total of 115 patients (82% females) with a mean (± sd) age of 58 ± 13 years were included. We found a significantly positive correlation between LH and perceived pain (p < 0.001), HAQ-A score (p < 0.001), and CDAI (p < 0.001) and a significantly negative correlation between SE and perceived pain (p < 0.001), HAQ-A score (p < 0.001), and CDAI (p < 0.001). We found greater levels of SE and lower grades of LH in patients in remission compared to those with active disease (median 76 vs. 58; p < 0.001 and 6 vs. 11; p < 0.001, respectively). LH and SE correlated significantly with disease activity, functional capacity, and perceived pain. Levels of SE were higher in patients in remission compared to those with active disease as opposed to levels of LH, which were lower in patients in remission compared to those with active disease. These results show that cognitive factors are related to disease activity and their modifications may have importance in the management of RA.

All about running: synaptic plasticity, growth factors and adult hippocampal neurogenesis.

PubMed

Vivar, Carmen; Potter, Michelle C; van Praag, Henriette

2013-01-01

Accumulating evidence from animal and human research shows exercise benefits learning and memory, which may reduce the risk of neurodegenerative diseases, and could delay age-related cognitive decline. Exercise-induced improvements in learning and memory are correlated with enhanced adult hippocampal neurogenesis and increased activity-dependent synaptic plasticity. In this present chapter we will highlight the effects of physical activity on cognition in rodents, as well as on dentate gyrus (DG) neurogenesis, synaptic plasticity, spine density, neurotransmission and growth factors, in particular brain-derived nerve growth factor (BDNF).

E-Learning Model in Chronic Kidney Disease Management: a Controlled Clinical Trial.

PubMed

Barahimi, Hamid; Zolfaghari, Mitra; Abolhassani, Farid; Rahimi Foroushani, Abass; Mohammadi, Aeen; Rajaee, Farahnaz

2017-07-01

Chronic kidney disease (CKD) is a challenging health problem. The present study examined impact of self-care education through e-learning on improving kidney function among individuals with CKD. The studied population consisted of CKD patients receiving care at 10 centers for treating noncommunicable diseases in Tehran. Three centers were randomly selected and 39 patients with a glomerular filtration rate (GFR) less than 60 mL/min/1.73 m2, minimum education of grade 9, minimum of 2 years of referrals, and computer literacy of the individual or a first-degree relative were included in the study, while 92 patients were assigned into the control group. Changes in GFR were compared after 6 months following an e-learning program for the patients in the intervention group. The mean change in GFR was 7.5 ± 8.9 mL/min/1.73 m2 for the intervention group after the e-learning intervention, while this was -2.3 ± 8.5 mL/min/1.73 m2. The two groups were also significantly different in terms of age, marital status, education level, mean arterial pressure, and serum high-density lipoprotein level, and therefore, multivariable comparison of GFR was made incorporating these factor into the analysis and showed a significant improvement of GFR in the intervention group. According to the results of this study, effects of the e-learning educational intervention on improvement in kidney function and CKD treatment were established.

Impaired insulin signaling and spatial learning in middle-aged rats: The role of PTP1B.

PubMed

Kuga, Gabriel Keine; Muñoz, Vitor Rosetto; Gaspar, Rafael Calais; Nakandakari, Susana Castelo Branco Ramos; da Silva, Adelino Sanchez Ramos; Botezelli, José Diego; Leme, José Alexandre Curiacos de Almeida; Gomes, Ricardo José; de Moura, Leandro Pereira; Cintra, Dennys Esper; Ropelle, Eduardo Rochete; Pauli, José Rodrigo

2018-04-01

The insulin and Brain-Derived Neurotrophic Factor (BDNF) signaling in the hippocampus promotes synaptic plasticity and memory formation. On the other hand, aging is related to the cognitive decline and is the main risk factor for Alzheimer's Disease (AD). The Protein-Tyrosine Phosphatase 1B (PTP1B) is related to several deleterious processes in neurons and emerges as a promising target for new therapies. In this context, our study aims to investigate the age-related changes in PTP1B content, insulin signaling, β-amyloid content, and Tau phosphorylation in the hippocampus of middle-aged rats. Young (3 months) and middle-aged (17 months) Wistar rats were submitted to Morris-water maze (MWM) test, insulin tolerance test, and molecular analysis in the hippocampus. Aging resulted in increased body weight, and insulin resistance and decreases learning process in MWM. Interestingly, the middle-aged rats have higher levels of PTP-1B, lower phosphorylation of IRS-1, Akt, GSK3β, mTOR, and TrkB. Also, the aging process increased Tau phosphorylation and β-amyloid content in the hippocampus region. In summary, this study provides new evidence that aging-related PTP1B increasing, contributing to insulin resistance and the onset of the AD. Copyright © 2018 Elsevier Inc. All rights reserved.

Identifying Medical Diagnoses and Treatable Diseases by Image-Based Deep Learning.

PubMed

Kermany, Daniel S; Goldbaum, Michael; Cai, Wenjia; Valentim, Carolina C S; Liang, Huiying; Baxter, Sally L; McKeown, Alex; Yang, Ge; Wu, Xiaokang; Yan, Fangbing; Dong, Justin; Prasadha, Made K; Pei, Jacqueline; Ting, Magdalene Y L; Zhu, Jie; Li, Christina; Hewett, Sierra; Dong, Jason; Ziyar, Ian; Shi, Alexander; Zhang, Runze; Zheng, Lianghong; Hou, Rui; Shi, William; Fu, Xin; Duan, Yaou; Huu, Viet A N; Wen, Cindy; Zhang, Edward D; Zhang, Charlotte L; Li, Oulan; Wang, Xiaobo; Singer, Michael A; Sun, Xiaodong; Xu, Jie; Tafreshi, Ali; Lewis, M Anthony; Xia, Huimin; Zhang, Kang

2018-02-22

The implementation of clinical-decision support algorithms for medical imaging faces challenges with reliability and interpretability. Here, we establish a diagnostic tool based on a deep-learning framework for the screening of patients with common treatable blinding retinal diseases. Our framework utilizes transfer learning, which trains a neural network with a fraction of the data of conventional approaches. Applying this approach to a dataset of optical coherence tomography images, we demonstrate performance comparable to that of human experts in classifying age-related macular degeneration and diabetic macular edema. We also provide a more transparent and interpretable diagnosis by highlighting the regions recognized by the neural network. We further demonstrate the general applicability of our AI system for diagnosis of pediatric pneumonia using chest X-ray images. This tool may ultimately aid in expediting the diagnosis and referral of these treatable conditions, thereby facilitating earlier treatment, resulting in improved clinical outcomes. VIDEO ABSTRACT. Copyright © 2018 Elsevier Inc. All rights reserved.

The educational impact of the Specialty Care Access Network-Extension of Community Healthcare Outcomes program.

PubMed

Salgia, Reena J; Mullan, Patricia B; McCurdy, Heather; Sales, Anne; Moseley, Richard H; Su, Grace L

2014-11-01

With the aging hepatitis C cohort and increasing prevalence of fatty liver disease, the burden on primary care providers (PCPs) to care for patients with liver disease is growing. In response, the Veterans Administration implemented initiatives for primary care-specialty referral to increase PCP competency in complex disease management. The Specialty Care Access Network-Extension of Community Healthcare Outcomes (SCAN-ECHO) program initiative was designed to transfer subspecialty knowledge to PCPs through case-based distance learning combined with real-time consultation. There is limited information regarding the initiative's ability to engage PCPs to learn and influence their practice. We surveyed PCPs to determine the factors that led to their participation in this program and the educational impact of participation. Of 51 potential participants, 24 responded to an anonymous survey. More than 75% of respondents participated more than one time in a SCAN-ECHO clinic. Providers were motivated to participate by a desire to learn more about liver disease, to apply the knowledge gained to future patients, and to save their patients time traveling to another center for specialty consultation. Seventy-one percent responded that the didactic component and case-based discussion were equally important. It is important that participation changed clinical practice: 75% of providers indicated they had personally discussed the information they learned from the case presentations with their colleague(s), and 42% indicated they helped a colleague care for their patient with the knowledge learned during discussions of other participants' cases. This study shows that the SCAN-ECHO videoconferencing program between PCPs and specialists can educate providers in the delivery of specialty care from a distance and potentially improve healthcare delivery.

Emerging technologies to support independent living of older adults at risk.

PubMed

Hanson, Gregory J; Takahashi, Paul Y; Pecina, Jennifer L

2013-01-01

The aging of the population is expected to place an unprecedented strain on health care systems over the next two decades and beyond. Emerging electronic monitoring technologies provide opportunities to learn about the aging process, age-related diseases, and contribute to new, cost effective care models that preserve independence at home for older adults at risk. The goals of this article are to familiarize the reader with emerging technologies and potential applications to older adults' at-risk, review the current literature about the clinical and economic outcomes of emerging technologies, and to outline future directions and challenges.

Genetic architecture of learning and delayed recall: a twin study of episodic memory.

PubMed

Panizzon, Matthew S; Lyons, Michael J; Jacobson, Kristen C; Franz, Carol E; Grant, Michael D; Eisen, Seth A; Xian, Hong; Kremen, William S

2011-07-01

Although episodic memory is often conceptualized as consisting of multiple component processes, there is a lack of understanding as to whether these processes are influenced by the same or different genetic determinants. The aim of the present study was to utilize multivariate twin analyses to elucidate the degree to which learning and delayed recall, two critical measures of episodic memory performance, have common or different genetic and environmental influences. Participants from the Vietnam Era Twin Study of Aging (314 monozygotic twin pairs, 259 dizygotic twin pairs, and 47 unpaired twins) were assessed using the second edition of the California Verbal Learning Test. Mean age at the time of the evaluation was 55.4 years (SD = 2.5). Model fitting revealed the presence of a higher-order latent factor influencing learning, short- and long-delay free recall, with a heritability of .36. The best-fitting model also indicated specific genetic influences on learning, which accounted for 10% of the overall variance. Given that learning involves the acquisition and retrieval of information, whereas delayed recall involves only retrieval, we conclude that these specific effects are likely to reflect genes that are specific to acquisition processes. These results demonstrate that even in nonclinical populations, it is possible to differentiate component processes in episodic memory. These different genetic influences may have implications for gene association studies, as well as other genetic studies of cognitive aging and disorders of episodic memory such as Alzheimer's disease or mild cognitive impairment. PsycINFO Database Record (c) 2011 APA, all rights reserved.

Reward processing in neurodegenerative disease

PubMed Central

Perry, David C.; Kramer, Joel H.

2015-01-01

Representation of reward value involves a distributed network including cortical and subcortical structures. Because neurodegenerative illnesses target specific anatomic networks that partially overlap with the reward circuit they would be predicted to have distinct impairments in reward processing. This review presents the existing evidence of reward processing changes in neurodegenerative diseases including mild cognitive impairment, Alzheimer's disease, frontotemporal dementia, amyotrophic lateral sclerosis, Parkinson's disease, and Huntington's disease, as well as in healthy aging. Carefully distinguishing the different aspects of reward processing (primary rewards, secondary rewards, reward-based learning, and reward-based decision-making) and using tasks that differentiate the stages of processing reward will lead to improved understanding of this fundamental process and clarify a contributing cause of behavioral change in these illnesses. PMID:24417286

Increased brain-predicted aging in treated HIV disease

PubMed Central

Underwood, Jonathan; Caan, Matthan W.A.; De Francesco, Davide; van Zoest, Rosan A.; Leech, Robert; Wit, Ferdinand W.N.M.; Portegies, Peter; Geurtsen, Gert J.; Schmand, Ben A.; Schim van der Loeff, Maarten F.; Franceschi, Claudio; Sabin, Caroline A.; Majoie, Charles B.L.M.; Winston, Alan; Reiss, Peter; Sharp, David J.

2017-01-01

Objective: To establish whether HIV disease is associated with abnormal levels of age-related brain atrophy, by estimating apparent brain age using neuroimaging and exploring whether these estimates related to HIV status, age, cognitive performance, and HIV-related clinical parameters. Methods: A large sample of virologically suppressed HIV-positive adults (n = 162, age 45–82 years) and highly comparable HIV-negative controls (n = 105) were recruited as part of the Comorbidity in Relation to AIDS (COBRA) collaboration. Using T1-weighted MRI scans, a machine-learning model of healthy brain aging was defined in an independent cohort (n = 2,001, aged 18–90 years). Neuroimaging data from HIV-positive and HIV-negative individuals were then used to estimate brain-predicted age; then brain-predicted age difference (brain-PAD = brain-predicted brain age − chronological age) scores were calculated. Neuropsychological and clinical assessments were also carried out. Results: HIV-positive individuals had greater brain-PAD score (mean ± SD 2.15 ± 7.79 years) compared to HIV-negative individuals (−0.87 ± 8.40 years; b = 3.48, p < 0.01). Increased brain-PAD score was associated with decreased performance in multiple cognitive domains (information processing speed, executive function, memory) and general cognitive performance across all participants. Brain-PAD score was not associated with age, duration of HIV infection, or other HIV-related measures. Conclusion: Increased apparent brain aging, predicted using neuroimaging, was observed in HIV-positive adults, despite effective viral suppression. Furthermore, the magnitude of increased apparent brain aging related to cognitive deficits. However, predicted brain age difference did not correlate with chronological age or duration of HIV infection, suggesting that HIV disease may accentuate rather than accelerate brain aging. PMID:28258081

Increased brain-predicted aging in treated HIV disease.

PubMed

Cole, James H; Underwood, Jonathan; Caan, Matthan W A; De Francesco, Davide; van Zoest, Rosan A; Leech, Robert; Wit, Ferdinand W N M; Portegies, Peter; Geurtsen, Gert J; Schmand, Ben A; Schim van der Loeff, Maarten F; Franceschi, Claudio; Sabin, Caroline A; Majoie, Charles B L M; Winston, Alan; Reiss, Peter; Sharp, David J

2017-04-04

To establish whether HIV disease is associated with abnormal levels of age-related brain atrophy, by estimating apparent brain age using neuroimaging and exploring whether these estimates related to HIV status, age, cognitive performance, and HIV-related clinical parameters. A large sample of virologically suppressed HIV-positive adults (n = 162, age 45-82 years) and highly comparable HIV-negative controls (n = 105) were recruited as part of the Comorbidity in Relation to AIDS (COBRA) collaboration. Using T1-weighted MRI scans, a machine-learning model of healthy brain aging was defined in an independent cohort (n = 2,001, aged 18-90 years). Neuroimaging data from HIV-positive and HIV-negative individuals were then used to estimate brain-predicted age; then brain-predicted age difference (brain-PAD = brain-predicted brain age - chronological age) scores were calculated. Neuropsychological and clinical assessments were also carried out. HIV-positive individuals had greater brain-PAD score (mean ± SD 2.15 ± 7.79 years) compared to HIV-negative individuals (-0.87 ± 8.40 years; b = 3.48, p < 0.01). Increased brain-PAD score was associated with decreased performance in multiple cognitive domains (information processing speed, executive function, memory) and general cognitive performance across all participants. Brain-PAD score was not associated with age, duration of HIV infection, or other HIV-related measures. Increased apparent brain aging, predicted using neuroimaging, was observed in HIV-positive adults, despite effective viral suppression. Furthermore, the magnitude of increased apparent brain aging related to cognitive deficits. However, predicted brain age difference did not correlate with chronological age or duration of HIV infection, suggesting that HIV disease may accentuate rather than accelerate brain aging. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Machine learning and social network analysis applied to Alzheimer's disease biomarkers.

PubMed

Di Deco, Javier; González, Ana M; Díaz, Julia; Mato, Virginia; García-Frank, Daniel; Álvarez-Linera, Juan; Frank, Ana; Hernández-Tamames, Juan A

2013-01-01

Due to the fact that the number of deaths due Alzheimer is increasing, the scientists have a strong interest in early stage diagnostic of this disease. Alzheimer's patients show different kind of brain alterations, such as morphological, biochemical, functional, etc. Currently, using magnetic resonance imaging techniques is possible to obtain a huge amount of biomarkers; being difficult to appraise which of them can explain more properly how the pathology evolves instead of the normal ageing. Machine Learning methods facilitate an efficient analysis of complex data and can be used to discover which biomarkers are more informative. Moreover, automatic models can learn from historical data to suggest the diagnostic of new patients. Social Network Analysis (SNA) views social relationships in terms of network theory consisting of nodes and connections. The resulting graph-based structures are often very complex; there can be many kinds of connections between the nodes. SNA has emerged as a key technique in modern sociology. It has also gained a significant following in medicine, anthropology, biology, information science, etc., and has become a popular topic of speculation and study. This paper presents a review of machine learning and SNA techniques and then, a new approach to analyze the magnetic resonance imaging biomarkers with these techniques, obtaining relevant relationships that can explain the different phenotypes in dementia, in particular, different stages of Alzheimer's disease.

Casting a Wide Net: Role of Perineuronal Nets in Neural Plasticity.

PubMed

Sorg, Barbara A; Berretta, Sabina; Blacktop, Jordan M; Fawcett, James W; Kitagawa, Hiroshi; Kwok, Jessica C F; Miquel, Marta

2016-11-09

Perineuronal nets (PNNs) are unique extracellular matrix structures that wrap around certain neurons in the CNS during development and control plasticity in the adult CNS. They appear to contribute to a wide range of diseases/disorders of the brain, are involved in recovery from spinal cord injury, and are altered during aging, learning and memory, and after exposure to drugs of abuse. Here the focus is on how a major component of PNNs, chondroitin sulfate proteoglycans, control plasticity, and on the role of PNNs in memory in normal aging, in a tauopathy model of Alzheimer's disease, and in drug addiction. Also discussed is how altered extracellular matrix/PNN formation during development may produce synaptic pathology associated with schizophrenia, bipolar disorder, major depression, and autism spectrum disorders. Understanding the molecular underpinnings of how PNNs are altered in normal physiology and disease will offer insights into new treatment approaches for these diseases. Copyright © 2016 the authors 0270-6474/16/3611459-10$15.00/0.

Oxidative stress, aging, and central nervous system disease in the canine model of human brain aging.

PubMed

Head, Elizabeth; Rofina, Jaime; Zicker, Steven

2008-01-01

Decline in cognitive functions that accompany aging in dogs may have a biologic basis, and many of the disorders associated with aging in dogs may be mitigated through dietary modifications that incorporate specific nutraceuticals. Based on previous research and the results of laboratory and clinical studies, antioxidants may be one class of nutraceutical that provides benefits to aged dogs. Brains of aged dogs accumulate oxidative damage to proteins and lipids, which may lead to dysfunction of neuronal cells. The production of free radicals and lack of increase in compensatory antioxidant enzymes may lead to detrimental modifications to important macromolecules within neurons. Reducing oxidative damage through food ingredients rich in a broad spectrum of antioxidants significantly improves, or slows the decline of, learning and memory in aged dogs.

Basic life support skills: assessment and education of spouse and first degree relatives of patients with coronary disease.

PubMed

Khan, Javaid Arif; Shafquat, Azam; Kundi, Asadullah

2010-05-01

To assess the knowledge of basic cardiac life support (BCLS) before and after the institution of training among first degree relatives and spouses of patients with coronary disease. Quasi-experimental study. National Institute of Cardiovascular Diseases, Karachi, from April 2007 to May 2008. A total of 300 relatives of patients with coronary heart disease undertook a one day CPR course. Questionnaire assessing knowledge of CPR was administered before and after the course. Patients were studied in groups of 10-20 at a time. Proportion of correct knowledge was compared using chi-square test with significance at p < 0.05. Mean age of participants was 31.08+10.53 years. Two hundred and twenty (73.34%) were males. On the average for all 31 questions, 37.09% of participants had correct responses before the training and 68.16% after the training of BCLS (p < 0.001). There was statistically significant improvement across all age groups, gender and educational levels (p < 0.01). There was significant improvement in relatives' knowledge of BCLS after training. Different age groups, both genders and all educational groups showed equal learning abilities.

Adaptation of postural recovery responses to a vestibular sensory illusion in individuals with Parkinson disease and healthy controls.

PubMed

Lester, Mark E; Cavanaugh, James T; Foreman, K Bo; Shaffer, Scott W; Marcus, Robin; Dibble, Leland E

2017-10-01

The ability to adapt postural responses to sensory illusions diminishes with age and is further impaired by Parkinson disease. However, limited information exists regarding training-related adaptions of sensory reweighting in these populations. This study sought to determine whether Parkinson disease or age would differentially affect acute postural recovery or adaptive postural responses to novel or repeated exposure to sensory illusions using galvanic vestibular stimulation during quiet stance. Acutely, individuals with Parkinson disease demonstrated larger center of pressure coefficient of variation compared to controls. Unlike individuals with Parkinson disease and asymptomatic older adults, healthy young adults acutely demonstrated a reduction in Sample Entropy to the sensory illusion. Following a period of consolidation Sample Entropy increased in the healthy young group, which coincided with a decreased center of pressure coefficient of variation. Similar changes were not observed in the Parkinson disease or older adult groups. Taken together, these results suggest that young adults learn to adapt to vestibular illusion in a more robust manner than older adults or those with Parkinson disease. Further investigation into the nature of this adaptive difference is warranted. Published by Elsevier Ltd.

CHRONIC DEVELOPMENTAL LEAD EXPOSURE REDUCES NEUROGENESIS IN ADULT RAT HIPPOCAMPUS BUT DOES NOT IMPAIR SPATIAL LEARNING.

EPA Science Inventory

It has long been heralded that the mature brain does not generate new neurons, it only loses them as a function of injury, disease and age. An exciting recent finding in neuroscience has been that the dentate granule cell layer of the hippocampus has the distinctive property of ...

Developmental origins of disruptive behaviour problems: the 'original sin' hypothesis, epigenetics and their consequences for prevention.

PubMed

Tremblay, Richard E

2010-04-01

This paper reviews publications on developmental trajectories of disruptive behaviour (DB) problems (aggression, opposition-defiance, rule breaking, and stealing-vandalism) over the past decade. Prior to these studies two theoretical models had strongly influenced research on DB: social learning and disease onset. According to these developmental perspectives, children learn DB from their environment and onset of the disease is triggered by accumulated exposition to disruptive models in the environment, including the media. Most of the evidence came from studies of school age children and adolescents. Longitudinal studies tracing developmental trajectories of DB from early childhood onwards suggest an inversed developmental process. DB are universal during early childhood. With age, children learn socially acceptable behaviours from interactions with their environment. A 'disease' status is given to children who fail to learn the socially acceptable behaviours. The mechanisms that lead to deficits in using socially accepted behaviours are strongly intergenerational, based on complex genetic and environmental contributions, including epigenetic mechanisms. Prevention of these deficits requires early, intensive and long-term support to parents and child. Newly discovered epigenetic mechanisms suggest that intensive perinatal interventions will have impacts on numerous aspects of physical and mental health, including DB. This review also concludes that: a) subtypes of disruptive behaviours should not be aggregated because they have different developmental trajectories and require specific corrective interventions; b) the overt-covert and destructive-nondestructive dimensions appear the most useful to create DB subtypes; c) overt DB onset before covert DB because the latter require more brain maturation; d) DB subtype taxonomies are more useful for clinicians than developmental taxonomies because the latter are post mortem diagnoses and clinicians' retrospective information is unreliable; e) we need large-scale collaborative preventive experimental interventions starting during early pregnancy to advance knowledge on causes and prevention of DB problems.

From Entry to Practice to Advanced Nurse Practitioner - The Progression of Competencies and How They Assist in Delivery of eHealth Programs for Healthy Ageing.

PubMed

Rodger, Daragh; Hussey, Pamela

2017-01-01

Most of the health issues encountered in persons of older age are the result of one or more chronic diseases. The evidence base reports that chronic diseases can be prevented or delayed by engaging in healthy behaviors. Education provides a cost effective intervention on both economic grounds in addition to delivery of optimal patient outcomes. Information and Communication Technology (ICT) increasingly is viewed as a critical utility in eHealth delivery, providing scope for expanding online education facilities for older persons. Developing nursing competencies in the delivery of eHealth solutions to deliver user education programs therefore makes sense. This chapter discusses nursing competencies on the development of targeted eHealth programs for healthy ageing. The role of Advanced Nurse Practitioner in Ireland and its associated competency set identifies how a strong action learning model can be designed to deliver eHealth educational programs for effective delivery of healthy ageing in place.

Patients with Parkinson's disease learn to control complex systems-an indication for intact implicit cognitive skill learning.

PubMed

Witt, Karsten; Daniels, Christine; Daniel, Victoria; Schmitt-Eliassen, Julia; Volkmann, Jens; Deuschl, Günther

2006-01-01

Implicit memory and learning mechanisms are composed of multiple processes and systems. Previous studies demonstrated a basal ganglia involvement in purely cognitive tasks that form stimulus response habits by reinforcement learning such as implicit classification learning. We will test the basal ganglia influence on two cognitive implicit tasks previously described by Berry and Broadbent, the sugar production task and the personal interaction task. Furthermore, we will investigate the relationship between certain aspects of an executive dysfunction and implicit learning. To this end, we have tested 22 Parkinsonian patients and 22 age-matched controls on two implicit cognitive tasks, in which participants learned to control a complex system. They interacted with the system by choosing an input value and obtaining an output that was related in a complex manner to the input. The objective was to reach and maintain a specific target value across trials (dynamic system learning). The two tasks followed the same underlying complex rule but had different surface appearances. Subsequently, participants performed an executive test battery including the Stroop test, verbal fluency and the Wisconsin card sorting test (WCST). The results demonstrate intact implicit learning in patients, despite an executive dysfunction in the Parkinsonian group. They lead to the conclusion that the basal ganglia system affected in Parkinson's disease does not contribute to the implicit acquisition of a new cognitive skill. Furthermore, the Parkinsonian patients were able to reach a specific goal in an implicit learning context despite impaired goal directed behaviour in the WCST, a classic test of executive functions. These results demonstrate a functional independence of implicit cognitive skill learning and certain aspects of executive functions.

Automated detection of exudative age-related macular degeneration in spectral domain optical coherence tomography using deep learning.

PubMed

Treder, Maximilian; Lauermann, Jost Lennart; Eter, Nicole

2018-02-01

Our purpose was to use deep learning for the automated detection of age-related macular degeneration (AMD) in spectral domain optical coherence tomography (SD-OCT). A total of 1112 cross-section SD-OCT images of patients with exudative AMD and a healthy control group were used for this study. In the first step, an open-source multi-layer deep convolutional neural network (DCNN), which was pretrained with 1.2 million images from ImageNet, was trained and validated with 1012 cross-section SD-OCT scans (AMD: 701; healthy: 311). During this procedure training accuracy, validation accuracy and cross-entropy were computed. The open-source deep learning framework TensorFlow™ (Google Inc., Mountain View, CA, USA) was used to accelerate the deep learning process. In the last step, a created DCNN classifier, using the information of the above mentioned deep learning process, was tested in detecting 100 untrained cross-section SD-OCT images (AMD: 50; healthy: 50). Therefore, an AMD testing score was computed: 0.98 or higher was presumed for AMD. After an iteration of 500 training steps, the training accuracy and validation accuracies were 100%, and the cross-entropy was 0.005. The average AMD scores were 0.997 ± 0.003 in the AMD testing group and 0.9203 ± 0.085 in the healthy comparison group. The difference between the two groups was highly significant (p < 0.001). With a deep learning-based approach using TensorFlow™, it is possible to detect AMD in SD-OCT with high sensitivity and specificity. With more image data, an expansion of this classifier for other macular diseases or further details in AMD is possible, suggesting an application for this model as a support in clinical decisions. Another possible future application would involve the individual prediction of the progress and success of therapy for different diseases by automatically detecting hidden image information.

Juvenile neuronal ceroid lipofuscinosis and education.

PubMed

von Tetzchner, Stephen; Fosse, Per; Elmerskog, Bengt

2013-11-01

Juvenile neuronal ceroid lipofuscinosis (JNCL) is characterized by severe visual impairment with onset around age 4-8 years, and a developmental course that includes blindness, epilepsy, speech problems, dementia, motor coordination problems, and emotional reactions. There is presently no cure and the disease leads to premature death. There have been few studies of non-medical intervention for individuals with JNCL, probably because of the negative prognosis. The present chapter discusses the education of children and adolescents with JNCL on the basis of current knowledge about the variation in perceptual, cognitive and language abilities through the course of the disease, and the possibilities that exist for supporting coping and learning within and outside the classroom. Adapted and special needs education may contribute significantly to improved learning conditions, better maintenance of skills and less frustration for individuals with JNCL. This article is part of a Special Issue entitled: The Neuronal Ceroid Lipofuscinoses or Batten Disease. Copyright © 2013 Elsevier B.V. All rights reserved.

Limb deficiency and prosthetic management. 2. Aging with limb loss.

PubMed

Flood, Katherine M; Huang, Mark E; Roberts, Toni L; Pasquina, Paul F; Nelson, Virginia S; Bryant, Phillip R

2006-03-01

This self-directed learning module highlights the issues faced by people aging with limb loss. It is part of the study guide on limb deficiency and vascular rehabilitation in the Self-Directed Physiatric Education Program for practitioners and trainees in physical medicine and rehabilitation. This article specifically focuses on the impact that limb loss has on health and physical function throughout the life span. Case examples are used to illustrate what effect limb loss in childhood or young adulthood has on the incidence and management of new impairments or disease processes commonly associated with aging. To discuss the impact of early-life limb loss on the incidence and management of physiologic and functional changes associated with aging.

Sirtuins in the Cardiovascular System: Potential Targets in Pediatric Cardiology.

PubMed

Ianni, Alessandro; Yuan, Xuejun; Bober, Eva; Braun, Thomas

2018-06-01

Cardiovascular diseases represent a major cause of death and morbidity. Cardiac and vascular pathologies develop predominantly in the aged population in part due to lifelong exposure to numerous risk factors but are also found in children and during adolescence. In comparison to adults, much has to be learned about the molecular pathways driving cardiovascular diseases in the pediatric population. Sirtuins are highly conserved enzymes that play pivotal roles in ensuring cardiac homeostasis under physiological and stress conditions. In this review, we discuss novel findings about the biological functions of these molecules in the cardiovascular system and their possible involvement in pediatric cardiovascular diseases.

Presenilin-1 familial Alzheimer’s disease mutation alters hippocampal neurogenesis and memory function in CCL2 null mice

PubMed Central

Kiyota, Tomomi; Morrison, Christine M; Tu, Guihua; Dyavarshetty, Bhagyalaxmi; Weir, Robert A; Zhang, Gang; Xiong, Huangui; Gendelman, Howard E

2015-01-01

Aberrations in hippocampal neurogenesis are associated with learning and memory, synaptic plasticity and neurodegeneration in Alzheimer’s disease (AD). However, the linkage between them, β-amyloidosis and neuroinflammation is not well understood. To this end, we generated a mouse overexpressing familial AD (FAD) mutant human presenilin-1 (PS1) crossed with a knockout (KO) of the CC-chemokine ligand 2 (CCL2) gene. The PS1/CCL2KO mice developed robust age-dependent deficits in hippocampal neurogenesis associated with impairments in learning and memory, synaptic plasticity and long-term potentiation. Neurogliogenesis gene profiling supported β-amyloid independent pathways for FAD-associated deficits in hippocampal neurogenesis. We conclude that these PS1/CCL2KO mice are suitable for studies linking host genetics, immunity and hippocampal function. PMID:26112421

Evolutionary model with genetics, aging, and knowledge

NASA Astrophysics Data System (ADS)

Bustillos, Armando Ticona; de Oliveira, Paulo Murilo

2004-02-01

We represent a process of learning by using bit strings, where 1 bits represent the knowledge acquired by individuals. Two ways of learning are considered: individual learning by trial and error, and social learning by copying knowledge from other individuals or from parents in the case of species with parental care. The age-structured bit string allows us to study how knowledge is accumulated during life and its influence over the genetic pool of a population after many generations. We use the Penna model to represent the genetic inheritance of each individual. In order to study how the accumulated knowledge influences the survival process, we include it to help individuals to avoid the various death situations. Modifications in the Verhulst factor do not show any special feature due to its random nature. However, by adding years to life as a function of the accumulated knowledge, we observe an improvement of the survival rates while the genetic fitness of the population becomes worse. In this latter case, knowledge becomes more important in the last years of life where individuals are threatened by diseases. Effects of offspring overprotection and differences between individual and social learning can also be observed. Sexual selection as a function of knowledge shows some effects when fidelity is imposed.

Autophagy and cardiovascular aging: lesson learned from rapamycin.

PubMed

Nair, Sreejayan; Ren, Jun

2012-06-01

The biological aging process is commonly associated with increased risk of cardiovascular diseases. Several theories have been put forward for aging-associated deterioration in ventricular function, including attenuation of growth hormone (insulin-like growth factors and insulin) signaling, loss of DNA replication and repair, histone acetylation and accumulation of reactive oxygen species. Recent evidence has depicted a rather unique role of autophagy as another important pathway in the regulation of longevity and senescence. Autophagy is a predominant cytoprotective (rather than self-destructive) process. It carries a prominent role in determination of lifespan. Reduced autophagy has been associated with aging, leading to accumulation of dysfunctional or damaged proteins and organelles. To the contrary, measures such as caloric restriction and exercise may promote autophagy to delay aging and associated comorbidities. Stimulation of autophagy using rapamycin may represent a novel strategy to prolong lifespan and combat aging-associated diseases. Rapamycin regulates autophagy through inhibition of the nutrient-sensing molecule mammalian target of rapamycin (mTOR). Inhibition of mTOR through rapamycin and caloric restriction promotes longevity. The purpose of this review is to recapitulate some of the recent advances in an effort to better understand the interplay between rapamycin-induced autophagy and decelerating cardiovascular aging.

Emotional Intelligence: A Novel Outcome Associated with Wellbeing and Self-Management in Chronic Obstructive Pulmonary Disease

PubMed Central

Kirsch, Janae L.; Dulohery, Megan M.; Abascal-Bolado, Beatriz

2016-01-01

Rationale: Individuals with chronic obstructive pulmonary disease (COPD) often struggle with diminished autonomy and quality of life. Emotional factors play a crucial role in the well-being of patients with COPD; they are independently associated with critical outcomes such as dyspnea, quality of life, and health care use. Emotional intelligence is the capacity to understand and manage personal thoughts and feelings, as well as to positively influence interpersonal communication and social well-being. Emotional intelligence is a trainable skill that is extensively used in corporate business to improve well-being and performance, and it may also be significant in the self-management of emotions in patients with chronic disease. Importantly, research supports the proposition that emotional intelligence may be developed and learned at any time or any age, and training programs have been associated with increased well-being and better emotional regulation in patients with chronic disease. However, to date, no research has been done to investigate its value in patients with COPD. Objectives: We aimed to investigate the association between emotional intelligence and two meaningful outcomes in COPD: quality of life and self-management abilities. Methods: Participants with moderate to severe COPD completed a disease-specific quality of life tool (Chronic Respiratory Questionnaire), the Trait Emotional Intelligence Questionnaire, the Self-Management Abilities Scale, the modified Medical Research Council Dyspnea Scale, and pulmonary function tests, and also provided information about living conditions and self-reported health care use. Measurements and Main Results: A total of 310 patients with COPD (mean age, 69 ± 9 yr; 40% female; mean FEV1%, 42.4 ± 15.8) participated in the study. Emotional intelligence was significantly and independently associated with self-management abilities (P < 0.0001) and all domains of quality of life assessed (dyspnea, fatigue, emotions, and mastery; P < 0.0001) after adjusting for age, degree of bronchial obstruction, breathlessness, and other significant confounders. Conclusions: Emotional intelligence may represent an important attribute in COPD, as it is associated with self-management abilities and all domains of quality of life, regardless of age or disease severity. Emotional intelligence can be learned and may complement existing rehabilitation efforts. Attention to it may address the current gap that exists in the treatment of emotional components of COPD responsible for decreased quality of life and increased health care use. PMID:26501370

Emotional Intelligence: A Novel Outcome Associated with Wellbeing and Self-Management in Chronic Obstructive Pulmonary Disease.

PubMed

Benzo, Roberto P; Kirsch, Janae L; Dulohery, Megan M; Abascal-Bolado, Beatriz

2016-01-01

Individuals with chronic obstructive pulmonary disease (COPD) often struggle with diminished autonomy and quality of life. Emotional factors play a crucial role in the well-being of patients with COPD; they are independently associated with critical outcomes such as dyspnea, quality of life, and health care use. Emotional intelligence is the capacity to understand and manage personal thoughts and feelings, as well as to positively influence interpersonal communication and social well-being. Emotional intelligence is a trainable skill that is extensively used in corporate business to improve well-being and performance, and it may also be significant in the self-management of emotions in patients with chronic disease. Importantly, research supports the proposition that emotional intelligence may be developed and learned at any time or any age, and training programs have been associated with increased well-being and better emotional regulation in patients with chronic disease. However, to date, no research has been done to investigate its value in patients with COPD. We aimed to investigate the association between emotional intelligence and two meaningful outcomes in COPD: quality of life and self-management abilities. Participants with moderate to severe COPD completed a disease-specific quality of life tool (Chronic Respiratory Questionnaire), the Trait Emotional Intelligence Questionnaire, the Self-Management Abilities Scale, the modified Medical Research Council Dyspnea Scale, and pulmonary function tests, and also provided information about living conditions and self-reported health care use. A total of 310 patients with COPD (mean age, 69 ± 9 yr; 40% female; mean FEV1%, 42.4 ± 15.8) participated in the study. Emotional intelligence was significantly and independently associated with self-management abilities (P < 0.0001) and all domains of quality of life assessed (dyspnea, fatigue, emotions, and mastery; P < 0.0001) after adjusting for age, degree of bronchial obstruction, breathlessness, and other significant confounders. Emotional intelligence may represent an important attribute in COPD, as it is associated with self-management abilities and all domains of quality of life, regardless of age or disease severity. Emotional intelligence can be learned and may complement existing rehabilitation efforts. Attention to it may address the current gap that exists in the treatment of emotional components of COPD responsible for decreased quality of life and increased health care use.

Perceptions of Asian American men about tobacco cigarette consumption: a social learning theory framework.

PubMed

Spigner, Clarence; Shigaki, Alison; Tu, Shin-Ping

2005-10-01

Little information exists regarding the perceptions that ethnic-specific groups of Asian American men have about tobacco cigarette smoking. Thirty Asian American men of immigrant status living in Seattle, Washington, were stratified by ethnicity (Chinese and Vietnamese), language (Mandarin, Cantonese, Vietnamese) and age to comprise six focus groups (two Mandarin speaking men aged 20-40 years and 10 aged 41-65+ years; three Cantonese men aged 20-40 years and another six aged 41-65+ years; four Vietnamese men aged 20-40 years and another five aged 41-65+ years). All group interviews were audio-taped and six separate hard-copy transcripts were produced, independently theme-coded by three investigators to ensure inter-rater reliability, and analyzed with QRS NUD*IST ethnographic software. Bandura (1969, 1986) categorized emergent contextual themes within the constructs of "predisposing, enabling, and reinforcing" behavioral determinants from Social Learning Theory. Smoking to be sociable emerged as the most salient theme. Awareness of tobacco-related diseases other than lung cancer was less evident, as was a self-perceived lack of will-power to quit. Concerns about side-stream smoking affecting family members, along with smoking to alleviate stress, were key findings. Further tobacco-related research is needed that incorporates considerations for cultural dynamics.

Learning Radiological Appearances of Diseases: Does Comparison Help?

ERIC Educational Resources Information Center

Kok, Ellen M.; de Bruin, Anique B. H.; Robben, Simon G. F.; van Merrienboer, Jeroen J. G.

2013-01-01

Comparison learning is a promising approach for learning complex real-life visual tasks. When medical students study radiological appearances of diseases, comparison of images showing diseases with images showing no abnormalities could help them learn to discriminate relevant, disease-related information. Medical students studied 12 diseases on…

Age-dependent phenotypic characteristics of a triple transgenic mouse model of Alzheimer disease.

PubMed

Pietropaolo, Susanna; Feldon, Joram; Yee, Benjamin K

2008-08-01

The triple-transgenic mouse line (3 x Tg-AD) harboring PS1M146V, APPSwe, and taup301L transgenes represents the only transgenic model for Alzheimer's disease (AD) to date capturing both beta-amyloid and tau neuropathology. The present study provides an extensive behavioral characterization of the 3 x Tg-AD mouse line, evaluating the emergence of noncognitive and cognitive AD-like symptoms at two ages corresponding to the early (6-7 months) and advanced (12-13 months) stages of AD-pathology. Enhanced responsiveness to aversive stimulation was detected in mutant mice at both ages: the 3 x Tg-AD genotype enhanced acoustic startle response and facilitated performance in the cued-version of the water maze. These noncognitive phenotypes were accompanied by hyperactivity and reduced locomotor habituation in the open field at the older age. Signs of cognitive aberrations were also detected at both ages, but they were limited to associative learning. The present study suggests that this popular transgenic mouse model of AD has clear phenotypes beyond the cognitive domain, and their potential relationship to the cognitive phenotypes should be further explored.

Spatial navigation in young versus older adults

PubMed Central

Gazova, Ivana; Laczó, Jan; Rubinova, Eva; Mokrisova, Ivana; Hyncicova, Eva; Andel, Ross; Vyhnalek, Martin; Sheardova, Katerina; Coulson, Elizabeth J.; Hort, Jakub

2013-01-01

Older age is associated with changes in the brain, including the medial temporal lobe, which may result in mild spatial navigation deficits, especially in allocentric navigation. The aim of the study was to characterize the profile of real-space allocentric (world-centered, hippocampus-dependent) and egocentric (body-centered, parietal lobe dependent) navigation and learning in young vs. older adults, and to assess a possible influence of gender. We recruited healthy participants without cognitive deficits on standard neuropsychological testing, white matter lesions or pronounced hippocampal atrophy: 24 young participants (18–26 years old) and 44 older participants stratified as participants 60–70 years old (n = 24) and participants 71–84 years old (n = 20). All underwent spatial navigation testing in the real-space human analog of the Morris Water Maze, which has the advantage of assessing separately allocentric and egocentric navigation and learning. Of the eight consecutive trials, trials 2–8 were used to reduce bias by a rebound effect (more dramatic changes in performance between trials 1 and 2 relative to subsequent trials). The participants who were 71–84 years old (p < 0.001), but not those 60–70 years old, showed deficits in allocentric navigation compared to the young participants. There were no differences in egocentric navigation. All three groups showed spatial learning effect (p’ s ≤ 0.01). There were no gender differences in spatial navigation and learning. Linear regression limited to older participants showed linear (β = 0.30, p = 0.045) and quadratic (β = 0.30, p = 0.046) effect of age on allocentric navigation. There was no effect of age on egocentric navigation. These results demonstrate that navigation deficits in older age may be limited to allocentric navigation, whereas egocentric navigation and learning may remain preserved. This specific pattern of spatial navigation impairment may help differentiate normal aging from prodromal Alzheimer’s disease. PMID:24391585

Dynamic Brains and the Changing Rules of Neuroplasticity: Implications for Learning and Recovery

PubMed Central

Voss, Patrice; Thomas, Maryse E.; Cisneros-Franco, J. Miguel; de Villers-Sidani, Étienne

2017-01-01

A growing number of research publications have illustrated the remarkable ability of the brain to reorganize itself in response to various sensory experiences. A traditional view of this plastic nature of the brain is that it is predominantly limited to short epochs during early development. Although examples showing that neuroplasticity exists outside of these finite time-windows have existed for some time, it is only recently that we have started to develop a fuller understanding of the different regulators that modulate and underlie plasticity. In this article, we will provide several lines of evidence indicating that mechanisms of neuroplasticity are extremely variable across individuals and throughout the lifetime. This variability is attributable to several factors including inhibitory network function, neuromodulator systems, age, sex, brain disease, and psychological traits. We will also provide evidence of how neuroplasticity can be manipulated in both the healthy and diseased brain, including recent data in both young and aged rats demonstrating how plasticity within auditory cortex can be manipulated pharmacologically and by varying the quality of sensory inputs. We propose that a better understanding of the individual differences that exist within the various mechanisms that govern experience-dependent neuroplasticity will improve our ability to harness brain plasticity for the development of personalized translational strategies for learning and recovery following brain injury or disease. PMID:29085312

Effects of Curculigoside on Memory Impairment and Bone Loss via Anti-Oxidative Character in APP/PS1 Mutated Transgenic Mice.

PubMed

Zhao, Lu; Liu, Sha; Wang, Yin; Zhang, Qiaoyan; Zhao, Wenjuan; Wang, Zejian; Yin, Ming

2015-01-01

Alzheimer's disease (AD) and osteoporosis are two closely related multifactorial progressively degenerative diseases that predominantly affect aged people. These two diseases share many common risk factors, including old age, being female, smoking, excessive drinking, low estrogen, and vitamin D3 levels. Additionally, oxidative damage and the dysfunction of the antioxidant system play important roles in the pathogenesis of osteoporosis and AD. Aβ not only leads to impaired memory but also plays a crucial role in the demineralization process of bone tissues of older people and women with menopause. Curculigoside can promote calcium deposition and increase the levels of ALP and Runx2 in osteoblasts under oxidative stress via anti-oxidative character. Therefore, we investigated the effects of CUR on the spatial learning and memory by the Morris water maze and brain immunohistochemistry, and bone microstructure and material properties of femurs by micro-computed tomography and mechanical testing in APP/PS1 mutated transgenic mice. Oral administration of CUR can significantly enhance learning performance and ameliorate bone loss in APP/PS1 mutated transgenic mice, and the mechanism may be related to its antioxidant effect. Based on these results, CUR has real potential as a new natural resource for developing medicines or dietary supplements for the prevention and treatment of the two closely linked multifactorial progressive degenerative disorders, AD and osteoporosis.

Learning temporal statistics for sensory predictions in mild cognitive impairment.

PubMed

Di Bernardi Luft, Caroline; Baker, Rosalind; Bentham, Peter; Kourtzi, Zoe

2015-08-01

Training is known to improve performance in a variety of perceptual and cognitive skills. However, there is accumulating evidence that mere exposure (i.e. without supervised training) to regularities (i.e. patterns that co-occur in the environment) facilitates our ability to learn contingencies that allow us to interpret the current scene and make predictions about future events. Recent neuroimaging studies have implicated fronto-striatal and medial temporal lobe brain regions in the learning of spatial and temporal statistics. Here, we ask whether patients with mild cognitive impairment due to Alzheimer's disease (MCI-AD) that are characterized by hippocampal dysfunction are able to learn temporal regularities and predict upcoming events. We tested the ability of MCI-AD patients and age-matched controls to predict the orientation of a test stimulus following exposure to sequences of leftwards or rightwards orientated gratings. Our results demonstrate that exposure to temporal sequences without feedback facilitates the ability to predict an upcoming stimulus in both MCI-AD patients and controls. However, our fMRI results demonstrate that MCI-AD patients recruit an alternate circuit to hippocampus to succeed in learning of predictive structures. In particular, we observed stronger learning-dependent activations for structured sequences in frontal, subcortical and cerebellar regions for patients compared to age-matched controls. Thus, our findings suggest a cortico-striatal-cerebellar network that may mediate the ability for predictive learning despite hippocampal dysfunction in MCI-AD. Copyright © 2015 Elsevier Ltd. All rights reserved.

Verbal memory in drug-naive, newly diagnosed Parkinson's disease. The retrieval deficit hypothesis revisited.

PubMed

Brønnick, Kolbjørn; Alves, Guido; Aarsland, Dag; Tysnes, Ole-Bjørn; Larsen, Jan Petter

2011-01-01

The retrieval deficit hypothesis on memory impairment in patients with Parkinson's disease (PD) implies a selective impairment in recall of learned material with normal encoding, retention, and recognition. This hypothesis has been challenged by new data. We have therefore investigated verbal memory and learning in a large sample of newly diagnosed, drug naïve, non-demented patients with PD. From a sample of patients with PD from the Norwegian ParkWest study, 133 PD patients and 133 controls matched on sex, age, and education were included. The California Verbal Learning Test-2 (CVLT-2) was used to assess verbal memory. Patients performed significantly worse than controls on free and cued recall as well as on recognition memory. Patients used the semantic clustering learning strategy significantly less extensively than the controls and the learning slope of the PD patients was significantly less steep. There was no difference in retention when controlling for encoding. Patients did not perform better on the recognition measure or on cued recall (d-prime), as compared to free recall. Executive functions explained a substantial part of the memory deficits. This study suggests that memory impairment in drug naïve early PD to a large degree is a deficit of learning/ encoding and not of retention or retrieval. An implication is that the retrieval deficit hypothesis should be moderated in its general form. Executive deficits and less extensive use of the efficient semantic clustering learning strategy had a strong impact on learning and memory. (c) 2010 APA, all rights reserved.

Epigenetic mechanisms during ageing and neurogenesis as novel therapeutic avenues in human brain disorders.

PubMed

Delgado-Morales, Raúl; Agís-Balboa, Roberto Carlos; Esteller, Manel; Berdasco, María

2017-01-01

Ageing is the main risk factor for human neurological disorders. Among the diverse molecular pathways that govern ageing, epigenetics can guide age-associated decline in part by regulating gene expression and also through the modulation of genomic instability and high-order chromatin architecture. Epigenetic mechanisms are involved in the regulation of neural differentiation as well as in functional processes related to memory consolidation, learning or cognition during healthy lifespan. On the other side of the coin, many neurodegenerative diseases are associated with epigenetic dysregulation. The reversible nature of epigenetic factors and, especially, their role as mediators between the genome and the environment make them exciting candidates as therapeutic targets. Rather than providing a broad description of the pathways epigenetically deregulated in human neurological disorders, in this review, we have focused on the potential use of epigenetic enzymes as druggable targets to ameliorate neural decline during normal ageing and especially in neurological disorders. We will firstly discuss recent progress that supports a key role of epigenetic regulation during healthy ageing with an emphasis on the role of epigenetic regulation in adult neurogenesis. Then, we will focus on epigenetic alterations associated with ageing-related human disorders of the central nervous system. We will discuss examples in the context of psychiatric disorders, including schizophrenia and posttraumatic stress disorders, and also dementia or Alzheimer's disease as the most frequent neurodegenerative disease. Finally, methodological limitations and future perspectives are discussed.

[The professional learning website needs of hospital nursing stations: a needs assessment].

PubMed

Yu, Tsui-Mien; Hsu, Li-Ling; Hsieh, Suh-Ing

2011-12-01

Healthcare must face the challenges of the information era. Changes in the medical sciences and increasing disease complexity have given rise to many professional learning websites designed to aid nurse learning. However, nurses in Taiwan have only a few poorly designed websites from which to choose. Language barriers and cultural differences often prevent nurses from making the best use of learning websites designed outside of Taiwan. This situation necessitates an investigation into the type of learning website content most needed by professional nurses in Taiwan. This study aimed to investigate the types of content in a professional learning website most needed by a group of nurses and to examine factors affecting nurses' content demand. Researchers used descriptive and correlational study designs. Random cluster sampling was used to select 43 of the total 70 nursing wards at one hospital in northern Taiwan. Subjects agreed to participate in a cross-sectional survey using a self-structured questionnaire. A total 571 questionnaires (96%) were returned out of 600 sent. The average professional learning website demand score was 4.03 (SD = 0.70). The top three content categories were, respectively, instructions on nursing routines for common diseases, common medication information, and instructions on preparing for common physical examinations. The bottom three content categories were, respectively, description of website purpose, post-learning tests, and online forum. Subject age, marital status, education, hospital department, Clinical Nursing Ladder status, and work experience all significantly affected subjects' content demand profile. Study findings identified the content categories in highest demand from professional nurses, which can help guide professional learning website design work in the future. Different website versions may be developed to suit different nurse needs and help nurses save time searching for information on such topics as nursing procedures and standard introductions to medical-surgical wards.

Strategic value-directed learning and memory in Alzheimer's disease and behavioural-variant frontotemporal dementia.

PubMed

Wong, Stephanie; Irish, Muireann; Savage, Greg; Hodges, John R; Piguet, Olivier; Hornberger, Michael

2018-02-12

In healthy adults, the ability to prioritize learning of highly valued information is supported by executive functions and enhances subsequent memory retrieval for this information. In Alzheimer's disease (AD) and behavioural-variant frontotemporal dementia (bvFTD), marked deficits are evident in learning and memory, presenting in the context of executive dysfunction. It is unclear whether these patients show a typical memory bias for higher valued stimuli. We administered a value-directed word-list learning task to AD (n = 10) and bvFTD (n = 21) patients and age-matched healthy controls (n = 22). Each word was assigned a low, medium or high point value, and participants were instructed to maximize the number of points earned across three learning trials. Participants' memory for the words was assessed on a delayed recall trial, followed by a recognition test for the words and corresponding point values. Relative to controls, both patient groups showed poorer overall learning, delayed recall and recognition. Despite these impairments, patients with AD preferentially recalled high-value words on learning trials and showed significant value-directed enhancement of recognition memory for the words and points. Conversely, bvFTD patients did not prioritize recall of high-value words during learning trials, and this reduced selectivity was related to inhibitory dysfunction. Nonetheless, bvFTD patients showed value-directed enhancement of recognition memory for the point values, suggesting a mismatch between memory of high-value information and the ability to apply this in a motivationally salient context. Our findings demonstrate that value-directed enhancement of memory may persist to some degree in patients with dementia, despite pronounced deficits in learning and memory. © 2018 The British Psychological Society.

Chronic sorrow in caregivers of school age children with sickle cell disease: a grounded theory approach.

PubMed

Northington, L

2000-01-01

Chronic illness affects over 1 million children in the United States annually. One such illness prominent in the African-American population is sickle cell disease (SCD), which affects approximately 1 in 375 African Americans in the United States. This potentially life-threatening disease requires caregivers to carefully monitor and supervise children with SCD. Monitoring and caring for children with SCD places heavy burdens, demands, and responsibilities on these caregivers. The psychological stressors and unpredictable nature of the disease could cause caregivers to experience a variety of emotions, with one being chronic sorrow. The purposes of this study were to examine the process of chronic sorrow in caregivers of school age children with SCD, identify the characteristics of chronic sorrow, and generate a substantive theory of chronic sorrow. The methodology used was grounded theory, and data were generated through two interview sessions, a demographic questionnaire, field notes, and memos. Data analyses were performed following the principles of grounded theory. Data suggested these caregivers move through three overlapping stages: learning about and incorporating SCD into their daily lives; experiencing the sorrow; and doing what one has to do and moving on. The diagnosis was the initial trigger to evoke feelings, including sorrow. As time progressed, other internal and external triggers began to evoke feelings of sorrow that eventually became chronic. A process of repatterning began as caregivers learned to live with the unpredictable consequences of SCD, which produced the feelings of chronic sorrow. Repatterning behaviors enabled caregivers to "do what you have to do and move on."

Periodontal Disease Awareness and Knowledge among Nigerian Primary School Teachers

PubMed Central

Azodo, CC; Umoh, AO

2015-01-01

Background: Teacher-led oral health education is equally effective in improving the oral health knowledge and oral hygiene status of adolescents as dentist-led and peer-led strategies. Aim: The aim was to determine periodontal disease awareness and knowledge among Nigerian primary school teachers. Subjects and Methods: This cross-sectional study was conducted among primary school teachers in Edo State, Nigeria. A self-administered questionnaire which elicited information on demography, awareness of the periodontal disease and source of information, knowledge of etiology, and symptoms of the periodontal disease, was the data collection tool.. The test of association was done using either Chi-square or Fisher's exact statistics. P value was set at 0.05 for significance level. Results: Out of 180 teachers recruited from seven public primary schools in Benin City, Edo State, Nigeria, 151 of them fully participated by filling the study questionnaires giving a 83.9% (151/180) response rate. The majority 74.2% (112/151) of the participants reported having heard of the periodontal disease and the leading source of information was television. A total of 29.8% (45/151) of participants considered periodontal disease as the main cause of tooth loss among adult Nigerian. Only 12.6% (19/151) of the participants knew dental plaque as soft debris on teeth and 29.1% (44/151) attested that plaque can cause periodontal disease. The majority of the participants were not aware of age 81.5% (123/151) and gender 96.7% (146/151) predisposition to periodontal disease. The perceived manifestations of the periodontal disease reported by were mainly gum bleeding 35.1% (53/151) and swollen gum 20.5% (31/151). A total of 70.2% (106/151) of the participants considered periodontal disease as a preventable disease and about half 49.0% (74/151) of the participants considered daily mouth cleaning as the best preventive method. The majority 95.4% (144/151) of the participants expressed interest in learning about the periodontal disease and the most preferred methods were workshops and lectures. Conclusion: A significant proportion of the participants heard about periodontal disease from nondental clinic sources. There existed a poor awareness of etiology, age and gender predispositions, manifestation, complications, and the preventable nature of periodontal disease among the participants. However, the majority of them indicated interest in learning about periodontal disease which should be utilized in optimizing their knowledge. PMID:26500791

Periodontal Disease Awareness and Knowledge among Nigerian Primary School Teachers.

PubMed

Azodo, C C; Umoh, A O

2015-01-01

Teacher-led oral health education is equally effective in improving the oral health knowledge and oral hygiene status of adolescents as dentist-led and peer-led strategies. The aim was to determine periodontal disease awareness and knowledge among Nigerian primary school teachers. This cross-sectional study was conducted among primary school teachers in Edo State, Nigeria. A self-administered questionnaire which elicited information on demography, awareness of the periodontal disease and source of information, knowledge of etiology, and symptoms of the periodontal disease, was the data collection tool.. The test of association was done using either Chi-square or Fisher's exact statistics. P value was set at 0.05 for significance level. Out of 180 teachers recruited from seven public primary schools in Benin City, Edo State, Nigeria, 151 of them fully participated by filling the study questionnaires giving a 83.9% (151/180) response rate. The majority 74.2% (112/151) of the participants reported having heard of the periodontal disease and the leading source of information was television. A total of 29.8% (45/151) of participants considered periodontal disease as the main cause of tooth loss among adult Nigerian. Only 12.6% (19/151) of the participants knew dental plaque as soft debris on teeth and 29.1% (44/151) attested that plaque can cause periodontal disease. The majority of the participants were not aware of age 81.5% (123/151) and gender 96.7% (146/151) predisposition to periodontal disease. The perceived manifestations of the periodontal disease reported by were mainly gum bleeding 35.1% (53/151) and swollen gum 20.5% (31/151). A total of 70.2% (106/151) of the participants considered periodontal disease as a preventable disease and about half 49.0% (74/151) of the participants considered daily mouth cleaning as the best preventive method. The majority 95.4% (144/151) of the participants expressed interest in learning about the periodontal disease and the most preferred methods were workshops and lectures. A significant proportion of the participants heard about periodontal disease from nondental clinic sources. There existed a poor awareness of etiology, age and gender predispositions, manifestation, complications, and the preventable nature of periodontal disease among the participants. However, the majority of them indicated interest in learning about periodontal disease which should be utilized in optimizing their knowledge.

Neuroprotective Effects of Herbal Extract (Rosa canina, Tanacetum vulgare and Urtica dioica) on Rat Model of Sporadic Alzheimer's Disease.

PubMed

Daneshmand, Parvaneh; Saliminejad, Kioomars; Dehghan Shasaltaneh, Marzieh; Kamali, Koorosh; Riazi, Gholam Hossein; Nazari, Reza; Azimzadeh, Pedram; Khorram Khorshid, Hamid Reza

2016-01-01

Sporadic Alzheimer's Disease (SAD) is caused by genetic risk factors, aging and oxidative stresses. The herbal extract of Rosa canina (R. canina), Tanacetum vulgare (T. vulgare) and Urtica dioica (U. dioica) has a beneficial role in aging, as an anti-inflammatory and anti-oxidative agent. In this study, the neuroprotective effects of this herbal extract in the rat model of SAD was investigated. The rats were divided into control, sham, model, herbal extract -treated and ethanol-treated groups. Drug interventions were started on the 21(st) day after modeling and each treatment group was given the drugs by intraperitoneal (I.P.) route for 21 days. The expression levels of the five important genes for pathogenesis of SAD including Syp, Psen1, Mapk3, Map2 and Tnf-α were measured by qPCR between the hippocampi of SAD model which were treated by this herbal extract and control groups. The Morris Water Maze was adapted to test spatial learning and memory ability of the rats. Treatment of the rat model of SAD with herbal extract induced a significant change in expression of Syp (p=0.001) and Psen1 (p=0.029). In Morris Water Maze, significant changes in spatial learning seen in the rat model group were improved in herbal-treated group. This herbal extract could have anti-dementia properties and improve spatial learning and memory in SAD rat model.

Automated Detection of Diabetic Retinopathy using Deep Learning.

PubMed

Lam, Carson; Yi, Darvin; Guo, Margaret; Lindsey, Tony

2018-01-01

Diabetic retinopathy is a leading cause of blindness among working-age adults. Early detection of this condition is critical for good prognosis. In this paper, we demonstrate the use of convolutional neural networks (CNNs) on color fundus images for the recognition task of diabetic retinopathy staging. Our network models achieved test metric performance comparable to baseline literature results, with validation sensitivity of 95%. We additionally explored multinomial classification models, and demonstrate that errors primarily occur in the misclassification of mild disease as normal due to the CNNs inability to detect subtle disease features. We discovered that preprocessing with contrast limited adaptive histogram equalization and ensuring dataset fidelity by expert verification of class labels improves recognition of subtle features. Transfer learning on pretrained GoogLeNet and AlexNet models from ImageNet improved peak test set accuracies to 74.5%, 68.8%, and 57.2% on 2-ary, 3-ary, and 4-ary classification models, respectively.

Brain properties predict proximity to symptom onset in sporadic Alzheimer's disease.

PubMed

Vogel, Jacob W; Vachon-Presseau, Etienne; Pichet Binette, Alexa; Tam, Angela; Orban, Pierre; La Joie, Renaud; Savard, Mélissa; Picard, Cynthia; Poirier, Judes; Bellec, Pierre; Breitner, John C S; Villeneuve, Sylvia

2018-06-01

See Tijms and Visser (doi:10.1093/brain/awy113) for a scientific commentary on this article.Alzheimer's disease is preceded by a lengthy 'preclinical' stage spanning many years, during which subtle brain changes occur in the absence of overt cognitive symptoms. Predicting when the onset of disease symptoms will occur is an unsolved challenge in individuals with sporadic Alzheimer's disease. In individuals with autosomal dominant genetic Alzheimer's disease, the age of symptom onset is similar across generations, allowing the prediction of individual onset times with some accuracy. We extend this concept to persons with a parental history of sporadic Alzheimer's disease to test whether an individual's symptom onset age can be informed by the onset age of their affected parent, and whether this estimated onset age can be predicted using only MRI. Structural and functional MRIs were acquired from 255 ageing cognitively healthy subjects with a parental history of sporadic Alzheimer's disease from the PREVENT-AD cohort. Years to estimated symptom onset was calculated as participant age minus age of parental symptom onset. Grey matter volume was extracted from T1-weighted images and whole-brain resting state functional connectivity was evaluated using degree count. Both modalities were summarized using a 444-region cortical-subcortical atlas. The entire sample was divided into training (n = 138) and testing (n = 68) sets. Within the training set, individuals closer to or beyond their parent's symptom onset demonstrated reduced grey matter volume and altered functional connectivity, specifically in regions known to be vulnerable in Alzheimer's disease. Machine learning was used to identify a weighted set of imaging features trained to predict years to estimated symptom onset. This feature set alone significantly predicted years to estimated symptom onset in the unseen testing data. This model, using only neuroimaging features, significantly outperformed a similar model instead trained with cognitive, genetic, imaging and demographic features used in a traditional clinical setting. We next tested if these brain properties could be generalized to predict time to clinical progression in a subgroup of 26 individuals from the Alzheimer's Disease Neuroimaging Initiative, who eventually converted either to mild cognitive impairment or to Alzheimer's dementia. The feature set trained on years to estimated symptom onset in the PREVENT-AD predicted variance in time to clinical conversion in this separate longitudinal dataset. Adjusting for participant age did not impact any of the results. These findings demonstrate that years to estimated symptom onset or similar measures can be predicted from brain features and may help estimate presymptomatic disease progression in at-risk individuals.

Ensemble positive unlabeled learning for disease gene identification.

PubMed

Yang, Peng; Li, Xiaoli; Chua, Hon-Nian; Kwoh, Chee-Keong; Ng, See-Kiong

2014-01-01

An increasing number of genes have been experimentally confirmed in recent years as causative genes to various human diseases. The newly available knowledge can be exploited by machine learning methods to discover additional unknown genes that are likely to be associated with diseases. In particular, positive unlabeled learning (PU learning) methods, which require only a positive training set P (confirmed disease genes) and an unlabeled set U (the unknown candidate genes) instead of a negative training set N, have been shown to be effective in uncovering new disease genes in the current scenario. Using only a single source of data for prediction can be susceptible to bias due to incompleteness and noise in the genomic data and a single machine learning predictor prone to bias caused by inherent limitations of individual methods. In this paper, we propose an effective PU learning framework that integrates multiple biological data sources and an ensemble of powerful machine learning classifiers for disease gene identification. Our proposed method integrates data from multiple biological sources for training PU learning classifiers. A novel ensemble-based PU learning method EPU is then used to integrate multiple PU learning classifiers to achieve accurate and robust disease gene predictions. Our evaluation experiments across six disease groups showed that EPU achieved significantly better results compared with various state-of-the-art prediction methods as well as ensemble learning classifiers. Through integrating multiple biological data sources for training and the outputs of an ensemble of PU learning classifiers for prediction, we are able to minimize the potential bias and errors in individual data sources and machine learning algorithms to achieve more accurate and robust disease gene predictions. In the future, our EPU method provides an effective framework to integrate the additional biological and computational resources for better disease gene predictions.

Considerations in the Design of Clinical Trials for Cognitive Aging

PubMed Central

Brinton, Roberta Diaz; Katz, Russell; Petersen, Ronald C.; Negash, Selam; Mungas, Dan; Aisen, Paul S.

2012-01-01

What will it take to develop interventions for the treatment of age-related cognitive decline? Session V of the Summit provided perspectives on the design of clinical trials to evaluate promising but unproven interventions, and some of the steps needed to accelerate the discovery and evaluation of promising treatments. It considered strategies to further characterize the biological and cognitive changes associated with normal aging and their translation into the development of new treatments. It provided regulatory, scientific, and clinical perspectives about neurocognitive aging treatments, their potential benefits and risks, and the strategies and endpoints needed to evaluate them in the most rapid, rigorous, and clinically meaningful way. It considered lessons learned from the study of Alzheimer's disease, the promising roles of biomarkers in neurocognitive aging research, and ways to help galvanize the scientific study and treatment of neurocognitive aging. PMID:22573913

Considerations in the design of clinical trials for cognitive aging.

PubMed

Reiman, Eric M; Brinton, Roberta Diaz; Katz, Russell; Petersen, Ronald C; Negash, Selam; Mungas, Dan; Aisen, Paul S

2012-06-01

What will it take to develop interventions for the treatment of age-related cognitive decline? Session V of the Summit provided perspectives on the design of clinical trials to evaluate promising but unproven interventions, and some of the steps needed to accelerate the discovery and evaluation of promising treatments. It considered strategies to further characterize the biological and cognitive changes associated with normal aging and their translation into the development of new treatments. It provided regulatory, scientific, and clinical perspectives about neurocognitive aging treatments, their potential benefits and risks, and the strategies and endpoints needed to evaluate them in the most rapid, rigorous, and clinically meaningful way. It considered lessons learned from the study of Alzheimer's disease, the promising roles of biomarkers in neurocognitive aging research, and ways to help galvanize the scientific study and treatment of neurocognitive aging.

Using Smartphones and Machine Learning to Quantify Parkinson Disease Severity: The Mobile Parkinson Disease Score.

PubMed

Zhan, Andong; Mohan, Srihari; Tarolli, Christopher; Schneider, Ruth B; Adams, Jamie L; Sharma, Saloni; Elson, Molly J; Spear, Kelsey L; Glidden, Alistair M; Little, Max A; Terzis, Andreas; Dorsey, E Ray; Saria, Suchi

2018-03-26

Current Parkinson disease (PD) measures are subjective, rater-dependent, and assessed in clinic. Smartphones can measure PD features, yet no smartphone-derived rating score exists to assess motor symptom severity in real-world settings. To develop an objective measure of PD severity and test construct validity by evaluating the ability of the measure to capture intraday symptom fluctuations, correlate with current standard PD outcome measures, and respond to dopaminergic therapy. This observational study assessed individuals with PD who remotely completed 5 tasks (voice, finger tapping, gait, balance, and reaction time) on the smartphone application. We used a novel machine-learning-based approach to generate a mobile Parkinson disease score (mPDS) that objectively weighs features derived from each smartphone activity (eg, stride length from the gait activity) and is scaled from 0 to 100 (where higher scores indicate greater severity). Individuals with and without PD additionally completed standard in-person assessments of PD with smartphone assessments during a period of 6 months. Ability of the mPDS to detect intraday symptom fluctuations, the correlation between the mPDS and standard measures, and the ability of the mPDS to respond to dopaminergic medication. The mPDS was derived from 6148 smartphone activity assessments from 129 individuals (mean [SD] age, 58.7 [8.6] years; 56 [43.4%] women). Gait features contributed most to the total mPDS (33.4%). In addition, 23 individuals with PD (mean [SD] age, 64.6 [11.5] years; 11 [48%] women) and 17 without PD (mean [SD] age 54.2 [16.5] years; 12 [71%] women) completed in-clinic assessments. The mPDS detected symptom fluctuations with a mean (SD) intraday change of 13.9 (10.3) points on a scale of 0 to 100. The measure correlated well with the Movement Disorder Society Unified Parkinson Disease's Rating Scale total (r = 0.81; P < .001) and part III only (r = 0.88; P < .001), the Timed Up and Go assessment (r = 0.72; P = .002), and the Hoehn and Yahr stage (r = 0.91; P < .001). The mPDS improved by a mean (SD) of 16.3 (5.6) points in response to dopaminergic therapy. Using a novel machine-learning approach, we created and demonstrated construct validity of an objective PD severity score derived from smartphone assessments. This score complements standard PD measures by providing frequent, objective, real-world assessments that could enhance clinical care and evaluation of novel therapeutics.

Growth of Malignant Non-CNS Tumors Alters Brain Metabolome

PubMed Central

Kovalchuk, Anna; Nersisyan, Lilit; Mandal, Rupasri; Wishart, David; Mancini, Maria; Sidransky, David; Kolb, Bryan; Kovalchuk, Olga

2018-01-01

Cancer survivors experience numerous treatment side effects that negatively affect their quality of life. Cognitive side effects are especially insidious, as they affect memory, cognition, and learning. Neurocognitive deficits occur prior to cancer treatment, arising even before cancer diagnosis, and we refer to them as “tumor brain.” Metabolomics is a new area of research that focuses on metabolome profiles and provides important mechanistic insights into various human diseases, including cancer, neurodegenerative diseases, and aging. Many neurological diseases and conditions affect metabolic processes in the brain. However, the tumor brain metabolome has never been analyzed. In our study we used direct flow injection/mass spectrometry (DI-MS) analysis to establish the effects of the growth of lung cancer, pancreatic cancer, and sarcoma on the brain metabolome of TumorGraft™ mice. We found that the growth of malignant non-CNS tumors impacted metabolic processes in the brain, affecting protein biosynthesis, and amino acid and sphingolipid metabolism. The observed metabolic changes were similar to those reported for neurodegenerative diseases and brain aging, and may have potential mechanistic value for future analysis of the tumor brain phenomenon. PMID:29515623

Behavioural characterisation of the alpha-mannosidosis guinea pig.

PubMed

Robinson, A J; Crawley, A C; Auclair, D; Weston, P F; Hirte, C; Hemsley, K M; Hopwood, J J

2008-01-25

alpha-Mannosidosis is a lysosomal storage disorder resulting from a functional deficiency of the lysosomal enzyme alpha-mannosidase. This deficiency results in the accumulation of various oligosaccharides in the lysosomes of affected individuals, causing somatic pathology and progressive neurological degeneration that results in cognitive deficits, ataxia, and other neurological symptoms. We have a naturally occurring guinea pig model of this disease which exhibits a deficiency of lysosomal alpha-mannosidase and has a similar clinical presentation to human alpha-mannosidosis. Various tests were developed in the present study to characterise and quantitate the loss of neurological function in alpha-mannosidosis guinea pigs and to follow closely the progression of the disease. General neurological examinations showed progressive differences in alpha-mannosidosis animals from approximately 1 month of age. Significant differences were observed in hind limb gait width from 2 months of age and significant cognitive (memory and learning) deficits were observed from 3 months of age. Evoked response tests showed an increase in somatosensory P1 peak latency in alpha-mannosidosis guinea pigs from approximately 2 months of age, as well as progressive hearing loss using auditory brainstem evoked responses. The alpha-mannosidosis guinea pig therefore appears to exhibit many of the characteristics of the human disease, and will be useful in evaluating therapies for treatment of central nervous system pathology.

Extracting and summarizing white matter hyperintensities using supervised segmentation methods in Alzheimer's disease risk and aging studies.

PubMed

Ithapu, Vamsi; Singh, Vikas; Lindner, Christopher; Austin, Benjamin P; Hinrichs, Chris; Carlsson, Cynthia M; Bendlin, Barbara B; Johnson, Sterling C

2014-08-01

Precise detection and quantification of white matter hyperintensities (WMH) observed in T2-weighted Fluid Attenuated Inversion Recovery (FLAIR) Magnetic Resonance Images (MRI) is of substantial interest in aging, and age-related neurological disorders such as Alzheimer's disease (AD). This is mainly because WMH may reflect co-morbid neural injury or cerebral vascular disease burden. WMH in the older population may be small, diffuse, and irregular in shape, and sufficiently heterogeneous within and across subjects. Here, we pose hyperintensity detection as a supervised inference problem and adapt two learning models, specifically, Support Vector Machines and Random Forests, for this task. Using texture features engineered by texton filter banks, we provide a suite of effective segmentation methods for this problem. Through extensive evaluations on healthy middle-aged and older adults who vary in AD risk, we show that our methods are reliable and robust in segmenting hyperintense regions. A measure of hyperintensity accumulation, referred to as normalized effective WMH volume, is shown to be associated with dementia in older adults and parental family history in cognitively normal subjects. We provide an open source library for hyperintensity detection and accumulation (interfaced with existing neuroimaging tools), that can be adapted for segmentation problems in other neuroimaging studies. Copyright © 2014 Wiley Periodicals, Inc.

Preferences for learning different types of genome sequencing results among young breast cancer patients: Role of psychological and clinical factors.

PubMed

Kaphingst, Kimberly A; Ivanovich, Jennifer; Lyons, Sarah; Biesecker, Barbara; Dresser, Rebecca; Elrick, Ashley; Matsen, Cindy; Goodman, Melody

2018-01-29

The growing importance of genome sequencing means that patients will increasingly face decisions regarding what results they would like to learn. The present study examined psychological and clinical factors that might affect these preferences. 1,080 women diagnosed with breast cancer at age 40 or younger completed an online survey. We assessed their interest in learning various types of genome sequencing results: risk of preventable disease or unpreventable disease, cancer treatment response, uncertain meaning, risk to relatives' health, and ancestry/physical traits. Multivariable logistic regression was used to examine whether being "very" interested in each result type was associated with clinical factors: BRCA1/2 mutation status, prior genetic testing, family history of breast cancer, and psychological factors: cancer recurrence worry, genetic risk worry, future orientation, health information orientation, and genome sequencing knowledge. The proportion of respondents who were very interested in learning each type of result ranged from 16% to 77%. In all multivariable models, those who were very interested in learning a result type had significantly higher knowledge about sequencing benefits, greater genetic risks worry, and stronger health information orientation compared to those with less interest (p-values < .05). Our findings indicate that high interest in return of various types of genome sequencing results was more closely related to psychological factors. Shared decision-making approaches that increase knowledge about genome sequencing and incorporate patient preferences for health information and learning about genetic risks may help support patients' informed choices about learning different types of sequencing results. © Society of Behavioral Medicine 2018.

Reversal Learning and Associative Memory Impairments in a BACHD Rat Model for Huntington Disease

PubMed Central

Abada, Yah-se K.; Nguyen, Huu Phuc; Ellenbroek, Bart; Schreiber, Rudy

2013-01-01

Chorea and psychiatric symptoms are hallmarks of Huntington disease (HD), a neurodegenerative disorder, genetically characterized by the presence of expanded CAG repeats (>35) in the HUNTINGTIN (HTT) gene. HD patients present psychiatric symptoms prior to the onset of motor symptoms and we recently found a similar emergence of non motor and motor deficits in BACHD rats carrying the human full length mutated HTT (97 CAG-CAA repeats). We evaluated cognitive performance in reversal learning and associative memory tests in different age cohorts of BACHD rats. Male wild type (WT) and transgenic (TG) rats between 2 and 12 months of age were tested. Learning and strategy shifting were assessed in a cross-maze test. Associative memory was evaluated in different fear conditioning paradigms (context, delay and trace). The possible confound of a fear conditioning phenotype by altered sensitivity to a ‘painful’ stimulus was assessed in a flinch-jump test. In the cross maze, 6 months old TG rats showed a mild impairment in reversal learning. In the fear conditioning tasks, 4, 6 and 12 months old TG rats showed a marked reduction in contextual fear conditioning. In addition, TG rats showed impaired delay conditioning (9 months) and trace fear conditioning (3 months). This phenotype was unlikely to be affected by a change in ‘pain’ sensitivity as WT and TG rats showed no difference in their threshold response in the flinch-jump test. Our results suggest that BACHD rats have a profound associative memory deficit and, possibly, a deficit in reversal learning as assessed in a cross maze task. The time course for the emergence of these symptoms (i.e., before the occurrence of motor symptoms) in this rat model for HD appears similar to the time course in patients. These data suggest that BACHD rats may be a useful model for preclinical drug discovery. PMID:24223692

Assessment of health status by molecular measures in adults ranging from middle-aged to old: Ready for clinical use?

PubMed

Waaijer, M E C; Westendorp, R G J; Goldeck, D; Gunn, D A; Pawelec, G; Stijntjes, M; Slagboom, P E; Maier, A B

2017-01-01

In addition to measures already used in clinical practice, molecular measures have been proposed to assess health status, but these have not yet been introduced into clinical practice. We aimed to test the association of functional capacity measures used in current practice and molecular measures with age and health status. The cohort consisted of 178 middle-aged to old participants of the Leiden Longevity Study (range 42-82years). We tested associations between functional capacity measures (physical tests: grip strength, 4-meter walk, chair stand test; cognitive tests: Stroop test, digit symbol substitution test and 15-picture learning test) with age and with cardiovascular or metabolic disease as a measure of the health status. These associations with age and health status were also tested for molecular measures (C reactive protein (CRP), numbers of senescent p16INK4a positive cells in the epidermis and dermis and putative immunosenescence (presence of CD57+ T cells)). All functional capacity measures were associated with age. CRP and epidermal p16INK4a positivity were also associated with age, but with smaller estimates. Grip strength and the Stroop test were associated with cardiovascular or metabolic disease, as was epidermal p16INK4a positivity. All associations with cardiovascular or metabolic disease attenuated when adjusting for age. In conclusion, in middle-aged to old persons, the molecular measures tested here were more weakly associated with age and health status than functional capacity measures. Whether these molecular measures associate more closely with health status in the elderly or in specific groups of patients needs to be explored further. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Cognitive Mechanisms in Decision-Making in Patients With Mild Alzheimer Disease.

PubMed

Alameda-Bailen, Jose Ramon; Salguero-Alcaniz, Maria Pilar; Merchan-Clavellino, Ana; Paino-Quesada, Susana

2017-01-01

Alzheimer's dementia is characterized by significant cortical and subcortical atrophy, causing diverse neuropsychological deficits. According to the somatic marker hypothesis, the areas responsible for generating the somatic markers that anticipate the consequences of a decision and thereby optimize the process would be affected in these patients. The aim of this experiment is to study the decision-making processes in Alzheimer type dementia patients to determine potential deficits in these processes as a result of the disease, aside from the cognitive impairment that is typical of aging. In addition, we wish to determine the defining characteristics of decision-making in these patients, on the basis of the prospect valence-learning parameters. We evaluated 30 patients with Alzheimer's disease and a control group of 30 healthy subjects. A short version of the Iowa Gambling Task was used. The results showed that patients made less advantageous choices than did controls. Group differences were quantitative and qualitative, as significant differences in cognitive mechanisms identified in the prospect valence-learning decisions were observed. These results are consistent with evidence from neuroimaging studies as well as with work carried out with amnesic patients. That problems in our patients' decision-making could be due to the characteristic memory deficits of this disease, which prevents them from establishing new stimulus-reward relationships and eliminating previously learned responses as a result of the parietal and temporal atrophy they present. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Cherry Featured in NCI’s Spotlight on Scientists Video Series | Poster

Cancer.gov

James Cherry, Ph.D., learned at an early age that education is crucial to success. He credits his mentors, some of whom include his grandmother, Shepherd University professor Burton Lidgerding, Ph.D., David Munroe, Ph.D., Frederick National Lab, and Robert J. Hohman, Ph.D., National Institute of Allergy and Infectious Diseases, for guiding him to the career he has today.

Exploring the Impact of the Design of the Physical Classroom Environment on Young Children with Autism Spectrum Disorder (ASD)

ERIC Educational Resources Information Center

Martin, Caren S.

2016-01-01

In 2010, the Centers for Disease Control (CDC) reported a 1600% increase in the number of individuals between the ages of 6 and 22 years with autism spectrum disorder (ASD). Knowledge about educational interventions for children with ASD is substantial; however, less is known about the design of supportive classroom environments where they learn.…

Effects of a Cognitive Behavioral Therapy Intervention Trial to Improve Disease Outcomes in Children with Inflammatory Bowel Disease.

PubMed

Levy, Rona L; van Tilburg, Miranda A L; Langer, Shelby L; Romano, Joan M; Walker, Lynn S; Mancl, Lloyd A; Murphy, Tasha B; Claar, Robyn L; Feld, Shara I; Christie, Dennis L; Abdullah, Bisher; DuPen, Melissa M; Swanson, Kimberly S; Baker, Melissa D; Stoner, Susan A; Whitehead, William E

2016-09-01

Studies testing the efficacy of behavioral interventions to modify psychosocial sequelae of inflammatory bowel disease in children are limited. This report presents outcomes through a 6-month follow-up from a large randomized controlled trial testing the efficacy of a cognitive behavioral intervention for children with inflammatory bowel disease and their parents. One hundred eighty-five children aged 8 to 17 years with a diagnosis of Crohn's disease or ulcerative colitis and their parents were randomized to one of two 3-session conditions: (1) a social learning and cognitive behavioral therapy condition or (2) an education support condition designed to control for time and attention. There was a significant overall treatment effect for school absences due to Crohn's disease or ulcerative colitis (P < 0.05) at 6 months after treatment. There was also a significant overall effect after treatment for child-reported quality of life (P < 0.05), parent-reported increases in adaptive child coping (P < 0.001), and reductions in parents' maladaptive responses to children's symptoms (P < 0.05). Finally, exploratory analyses indicated that for children with a higher level of flares (2 or more) prebaseline, those in social learning and cognitive behavioral therapy condition experienced a greater reduction in flares after treatment. This trial suggests that a brief cognitive behavioral intervention for children with inflammatory bowel disease and their parents can result in improved child functioning and quality of life, and for some children may decrease disease activity.

PENN neurodegenerative disease research - in the spirit of Benjamin Franklin.

PubMed

Trojanowski, John Q

2008-01-01

Benjamin Franklin (1706-1790) was entrepreneur, statesman, supporter of the public good as well as inventor, and his most significant invention was the University of Pennsylvania (PENN). Franklin outlined his plans for a college providing practical and classical instruction to prepare youth for real-world pursuits in his 'Proposals Relating to the Education of Youth in Pensilvania' (1749), and Franklin's spirit of learning to serve society guides PENN to the present day. This is evidenced by the series of articles in this special issue of Neurosignals, describing research conducted by seasoned and newly recruited PENN faculty, addressing consequences of the longevity revolution which defines our epoch at the dawn of this millennium. While aging affects all organ systems, the nervous system is most critical to successful aging. Thus, the articles in this special issue of Neurosignals focus on research at PENN that is designed to prevent or ameliorate aging-related neurodegenerative disorders such as Alzheimer's and Parkinson's disease, amyotrophic lateral sclerosis and frontotemporal dementia. This research could enhance our chances of aging successfully in the continuing longevity revolution, and the essay here provides context and background on this research.

Exercise counteracts declining hippocampal function in aging and Alzheimer's disease.

PubMed

Intlekofer, Karlie A; Cotman, Carl W

2013-09-01

Alzheimer's disease (AD) afflicts more than 5.4 million Americans and ranks as the most common type of dementia (Thies and Bleiler, 2011), yet effective pharmacological treatments have not been identified. Substantial evidence indicates that physical activity enhances learning and memory for people of all ages, including individuals that suffer from cognitive impairment. The mechanisms that underlie these benefits have been explored using animal models, including transgenic models of AD. Accumulating research shows that physical activity reinstates hippocampal function by enhancing the expression of brain-derived neurotrophic factor (BDNF) and other growth factors that promote neurogenesis, angiogenesis, and synaptic plasticity. In addition, several studies have found that physical activity counteracts age- and AD-associated declines in mitochondrial and immune system function. A growing body of evidence also suggests that exercise interventions hold the potential to reduce the pathological features associated with AD. Taken together, animal and human studies indicate that exercise provides a powerful stimulus that can countervail the molecular changes that underlie the progressive loss of hippocampal function in advanced age and AD. 2012 Published by Elsevier Inc

The use of public health e-learning resources by pharmacists in Wales: a quantitative evaluation.

PubMed

Evans, Andrew; Evans, Sian; Roberts, Debra

2016-08-01

The aim of this study was to examine how communicable disease e-learning resources were utilised by pharmacy professionals and to identify whether uptake of the resources was influenced by disease outbreaks. Retrospective analysis of routine data regarding the number of individuals completing e-learning resources and statutory notifications of communicable disease. A high proportion of pharmacy professionals in Wales (38.8%, n = 915/2357) accessed the resources; around one in six completed multiple resources (n = 156). The most commonly accessed were those where there had been a disease outbreak during the study period. There was a strong positive correlation between e-learning uptake and number of disease cases; this was observed both for measles and scarlet fever. Communicable disease e-learning appears to be an acceptable method for providing communicable disease information to pharmacy professionals. Study findings suggest that e-learning uptake is positively influenced by disease outbreaks this reflects well both on pharmacy professionals and on the e-learning resources themselves. © 2016 Royal Pharmaceutical Society.

Aging and Learning.

ERIC Educational Resources Information Center

Mayor's Office for Senior Citizens, Chicago, IL.

The process of learning with respect to age is discussed. Learning may be defined as the acquisition of information or skills. Three non-cognitive factors varying with age are loss of speed, health, and motivation. Studies on learning in relation to age have not controlled for non-learning factors. Perceptual and psychomotor studies are not…

Testing communication strategies to convey genomic concepts using virtual reality technology.

PubMed

Kaphingst, Kimberly A; Persky, Susan; McCall, Cade; Lachance, Christina; Beall, Andrew C; Blascovich, Jim

2009-06-01

Health professionals need to be able to communicate information about genomic susceptibility in understandable and usable ways, but substantial challenges are involved. We developed four learning modules that varied along two factors: (1) learning mode (active learning vs. didactic learning) and (2) metaphor (risk elevator vs. bridge) and tested them using a 2 x 2 between-subjects, repeated measures design. The study used an innovative virtual reality technology experimental platform; four virtual worlds were designed to convey the concept that genetic and behavioral factors interact to affect common disease risk. The primary outcome was comprehension (recall, transfer). Study participants were 42 undergraduates aged 19-23. The results indicated that the elevator metaphor better supported learning of the concept than the bridge metaphor. Mean transfer score was significantly higher for the elevator metaphor (p < 0.05). Mean change in recall was significantly higher for didactic learning than active learning (p < 0.05). Mean ratings for variables posited to be associated with better learning (e.g., motivation), however, were generally higher for the active learning worlds. The results suggested that active learning might not always be more effective than didactic learning in increasing comprehension of health information. The findings also indicated that less complex metaphors might convey abstract concepts more effectively.

Testing Communication Strategies to Convey Genomic Concepts Using Virtual Reality Technology

PubMed Central

Kaphingst, Kimberly A.; Persky, Susan; McCall, Cade; Lachance, Christina; Beall, Andrew C.; Blascovich, Jim

2009-01-01

Health professionals need to be able to communicate information about genomic susceptibility in understandable and usable ways, but substantial challenges are involved. We developed four learning modules that varied along two factors: (1) learning mode (active learning vs. didactic learning) and (2) metaphor (risk elevator vs. bridge) and tested them using a 2×2 between-subjects, repeated measures design. The study used an innovative virtual reality technology experimental platform; four virtual worlds were designed to convey the concept that genetic and behavioral factors interact to affect common disease risk. The primary outcome was comprehension (recall, transfer). Study participants were 42 undergraduates aged 19–23. The results indicated that the elevator metaphor better supported learning of the concept than the bridge metaphor. Mean transfer score was significantly higher for the elevator metaphor (p<0.05). Mean change in recall was significantly higher for didactic learning than active learning (p<0.05). However, mean ratings for variables posited to be associated with better learning (e.g., motivation) were generally higher for the active learning worlds. The results suggested that active learning might not always be more effective than didactic learning in increasing comprehension of health information. The findings also indicated that less complex metaphors might convey abstract concepts more effectively. PMID:19466649

The learning curve of laparoendoscopic single-Site (LESS) fundoplication: definable, short, and safe.

PubMed

Ross, Sharona B; Choung, Edward; Teta, Anthony F; Colibao, Lotiffa; Luberice, Kenneth; Paul, Harold; Rosemurgy, Alexander S

2013-01-01

This study of laparoendoscopic single-site (LESS) fundoplication for gastroesophageal reflux disease was undertaken to determine the "learning curve" for implementing LESS fundoplication. One hundred patients, 38% men, with a median age of 61 years and median body mass index of 26 kg/m(2) , underwent LESS fundoplications. The operative times, placement of additional trocars, conversions to "open" operations, and complications were compared among patient quartiles to establish a learning curve. Median data are reported. The median operative times and complications did not differ among 25-patient cohorts. Additional trocars were placed in 27% of patients, 67% of whom were in the first 25-patient cohort. Patients undergoing LESS fundoplication had a dramatic relief in the frequency and severity of all symptoms of reflux across all cohorts equally (P < .05), particularly for heartburn and regurgitation, without causing dysphagia. LESS fundoplication ameliorates symptoms of gastroesophageal reflux disease without apparent scarring. Notably, few operations required additional trocars after the first 25-patient cohort. Patient selection became more inclusive (eg, more "redo" fundoplications) with increasing experience, whereas operative times and complications remained relatively unchanged. The learning curve of LESS fundoplication is definable, short, and safe. We believe that patients will seek LESS fundoplication because of the efficacy and superior cosmetic outcomes; surgeons will need to meet this demand.

Neuroprotective effects of the polyphenolic antioxidant agent, Curcumin, against homocysteine-induced cognitive impairment and oxidative stress in the rat.

PubMed

Ataie, Amin; Sabetkasaei, Masoumeh; Haghparast, Abbas; Moghaddam, Akbar Hajizadeh; Kazeminejad, Behrang

2010-10-01

Aging is the major risk factor for neurodegenerative diseases and oxidative stress is involved in the pathophysiology of these diseases. In this study, the possible antioxidant and neuroprotective properties of the polyphenolic antioxidant compound, Curcumin against homocysteine (Hcy) neurotoxicity was investigated. Curcumin (5 and 50mg/kg) was injected intraperitoneally once daily for a period of 10 days beginning 5 days prior to Hcy (0.2 micromol/microl) intrahippocampal injection in rats. Biochemical and behavioral studies, including passive avoidance learning and locomotor activity tests were studied 24h after the last Curcumin or its vehicle injection. We detected Malondialdehyde (MDA) and Super oxide anion (SOA) in rats' hippocampi. Results indicated that Hcy could induce lipid peroxidation and increase MDA and SOA levels in rats' hippocampi. Additionally, Hcy impaired memory retention in passive avoidance learning test. However, Curcumin treatment decreased MDA and SOA levels significantly as well as improved learning and memory in rats. Histopathological analysis also indicated that Hcy could decrease hippocampus cell count and Curcumin inhibited this toxic effect. These results suggest that Hcy may induce lipid peroxidation in rats' hippocampi and polyphenol treatment (Curcumin) improved learning and memory deficits by protecting the nervous system against Hcy toxicity. (c) 2010 Elsevier Inc. All rights reserved.

Compensatory processing during rule-based category learning in older adults.

PubMed

Bharani, Krishna L; Paller, Ken A; Reber, Paul J; Weintraub, Sandra; Yanar, Jorge; Morrison, Robert G

2016-01-01

Healthy older adults typically perform worse than younger adults at rule-based category learning, but better than patients with Alzheimer's or Parkinson's disease. To further investigate aging's effect on rule-based category learning, we monitored event-related potentials (ERPs) while younger and neuropsychologically typical older adults performed a visual category-learning task with a rule-based category structure and trial-by-trial feedback. Using these procedures, we previously identified ERPs sensitive to categorization strategy and accuracy in young participants. In addition, previous studies have demonstrated the importance of neural processing in the prefrontal cortex and the medial temporal lobe for this task. In this study, older adults showed lower accuracy and longer response times than younger adults, but there were two distinct subgroups of older adults. One subgroup showed near-chance performance throughout the procedure, never categorizing accurately. The other subgroup reached asymptotic accuracy that was equivalent to that in younger adults, although they categorized more slowly. These two subgroups were further distinguished via ERPs. Consistent with the compensation theory of cognitive aging, older adults who successfully learned showed larger frontal ERPs when compared with younger adults. Recruitment of prefrontal resources may have improved performance while slowing response times. Additionally, correlations of feedback-locked P300 amplitudes with category-learning accuracy differentiated successful younger and older adults. Overall, the results suggest that the ability to adapt one's behavior in response to feedback during learning varies across older individuals, and that the failure of some to adapt their behavior may reflect inadequate engagement of prefrontal cortex.

Compensatory Processing During Rule-Based Category Learning in Older Adults

PubMed Central

Bharani, Krishna L.; Paller, Ken A.; Reber, Paul J.; Weintraub, Sandra; Yanar, Jorge; Morrison, Robert G.

2016-01-01

Healthy older adults typically perform worse than younger adults at rule-based category learning, but better than patients with Alzheimer's or Parkinson's disease. To further investigate aging's effect on rule-based category learning, we monitored event-related potentials (ERPs) while younger and neuropsychologically typical older adults performed a visual category-learning task with a rule-based category structure and trial-by-trial feedback. Using these procedures, we previously identified ERPs sensitive to categorization strategy and accuracy in young participants. In addition, previous studies have demonstrated the importance of neural processing in the prefrontal cortex and the medial temporal lobe for this task. In this study, older adults showed lower accuracy and longer response times than younger adults, but there were two distinct subgroups of older adults. One subgroup showed near-chance performance throughout the procedure, never categorizing accurately. The other subgroup reached asymptotic accuracy that was equivalent to that in younger adults, although they categorized more slowly. These two subgroups were further distinguished via ERPs. Consistent with the compensation theory of cognitive aging, older adults who successfully learned showed larger frontal ERPs when compared with younger adults. Recruitment of prefrontal resources may have improved performance while slowing response times. Additionally, correlations of feedback-locked P300 amplitudes with category-learning accuracy differentiated successful younger and older adults. Overall, the results suggest that the ability to adapt one's behavior in response to feedback during learning varies across older individuals, and that the failure of some to adapt their behavior may reflect inadequate engagement of prefrontal cortex. PMID:26422522

Age-Associated Perceptions of Physical Activity Facilitators and Barriers Among Women in Rural Southernmost Illinois

PubMed Central

Carnahan, Leslie R.; Peacock, Nadine R.

2016-01-01

Introduction Women living in rural areas in the United States experience disproportionately high rates of diseases such as obesity and heart disease and are less likely than women living in urban areas to meet daily physical activity (PA) recommendations. The purpose of our research was to understand age-specific perceptions of barriers and facilitators to rural women engaging in PA and to identify strategies to promote PA among these women. Methods As part of a community health assessment to learn about women’s health issues, 110 adult women participated in 14 focus groups. The women were divided into 4 age groups, and focus groups were held in various community settings. We used qualitative analysis methods to explore themes in the women’s narratives, including themes related to PA knowledge, PA behavior, and access to PA facilities. Results Participants described multiple and often conflicting individual, social, and environmental barriers and facilitators to PA. Several barriers and facilitators were shared across age groups (eg, competing priorities and inadequate knowledge about PA’s role in disease prevention and disease management). Other barriers (eg, illness and injury) and facilitators (eg, PA as a social opportunity) differed by age group. Conclusion Rural women in southernmost Illinois have often contradictory barriers and facilitators to PA, and those barriers and facilitators are different at different points in a woman’s life. Our findings suggest the need for multilevel, multisector approaches to promote PA. Additionally, this research supports the need for tailored PA promotion programs for rural women to address the barriers these women face across their lifespan. PMID:27685431

[A historical survey of diphtheria in the Western World, China and Japan. Part II: Modern age (from sixteenth century to the beginning of nineteenth century)].

PubMed

Nakamura, A

1996-09-01

In Europe and North America, literatures on diphtheritic diseases was increasing from sixteenth to eighteenth century. In New England of North America, diphtheria and scarlet fever occurred epidemically in mingled form from 1735 to the succeeding year. Thereafter, many physicians in Europe and America treated patients of diphtheria and had different opinions about the nature of croup and diphtheria. In China, its own clinical medicine progressed extraordinarily during the modern age. Laryngeal specialists appeared and wrote special monographs about the pharynx and larynx. A physician wrote about "epidemic exanthem", which the author presumes to be a complicated form of scarlet fever and diphtheria. In Japan, diphtheria occurred in sporadic form usually, and in epidemic form occasionally. Japanese physicians studied medicine from China since the ancient age, and also introduced European medicine through the Netherlands in the eighteenth century. So Japanese physicians learned knowledge about throat diseases and diphtheria from Chinese and European medicine.

Nutrition, Genes, and Age-Related Macular Degeneration: What Have We Learned from the Trials?

PubMed

Chew, Emily Y

2017-01-01

The Age-Related Eye Disease Study (AREDS) and AREDS2 provided evidence for treating persons with age-related macular degeneration (AMD) with antioxidant vitamins and minerals to reduce the risk of development of late AMD. The AREDS2 data suggest that the beta-carotene in the original AREDS supplements be replaced by lutein and zeaxanthin, providing a safer drug for those who are smokers or former smokers. Even though consuming fish reduced the risk of AMD in observational studies, the AREDS2 results showed that omega-3 long-chain polyunsaturated fatty acids (docosahexaenoic acid/eicosapentaenoic acid) had no beneficial effect on AMD. Despite the major progress in the discovery of gene variants associated with AMD, the use of genetic testing to predict disease has not been clinically useful. The use of genetic testing prior to AMD therapies such as administering AREDS supplements is not recommended by the American Academy of Ophthalmology and other organizations. © 2017 S. Karger AG, Basel.

Stereological Investigation of the Effects of Treadmill Running Exercise on the Hippocampal Neurons in Middle-Aged APP/PS1 Transgenic Mice.

PubMed

Chao, Fenglei; Jiang, Lin; Zhang, Yi; Zhou, Chunni; Zhang, Lei; Tang, Jing; Liang, Xin; Qi, Yingqiang; Zhu, Yanqing; Ma, Jing; Tang, Yong

2018-01-01

The risk of cognitive decline during Alzheimer's disease (AD) can be reduced if physical activity is maintained; however, the specific neural events underlying this beneficial effect are still uncertain. To quantitatively investigate the neural events underlying the effect of running exercise on middle-aged AD subjects, 12-month-old male APP/PS1 mice were randomly assigned to a control group or running group, and age-matched non-transgenic littermates were used as a wild-type group. AD running group mice were subjected to a treadmill running protocol (regular and moderate intensity) for four months. Spatial learning and memory abilities were assessed using the Morris water maze. Hippocampal amyloid plaques were observed using Thioflavin S staining and immunohistochemistry. Hippocampal volume, number of neurons, and number of newborn cells (BrdU+ cells) in the hippocampus were estimated using stereological techniques, and newborn neurons were observed using double-labelling immunofluorescence. Marked neuronal loss in both the CA1 field and dentate gyrus (DG) and deficits in both the neurogenesis and survival of new neurons in the DG of middle-aged APP/PS1 mice were observed. Running exercise could improve the spatial learning and memory abilities, reduce amyloid plaques in the hippocampi, delay neuronal loss, induce neurogenesis, and promote the survival of newborn neurons in the DG of middle-aged APP/PS1 mice. Exercise-induced protection of neurons and adult neurogenesis within the DG might be part of the important structural basis of the improved spatial learning and memory abilities observed in AD mice.

Repetition priming of words and nonwords in Alzheimer's disease and normal aging

PubMed Central

Ober, Beth A.; Shenaut, Gregory K.

2014-01-01

Objective This study examines the magnitude and direction of nonword and word lexical decision repetition priming effects in Alzheimer’s disease (AD) and normal aging, focusing specifically on the negative priming effect sometimes observed with repeated nonwords. Method Probable Alzheimer's disease (AD) patients (30), elderly normal controls (34), and young normal controls (49) participated in a repetition priming experiment using low-frequency words and word-like nonwords with a letter-level orthographic orienting task at study followed by a lexical decision test phase. Results Although participants' reaction times were longer in AD compared to elderly normal, and elderly normal compared to young normal, the repetition priming effect and the degree to which the repetition priming effect was reversed for nonwords compared to words was unaffected by AD or normal aging. Conclusion AD patients, like young and elderly normal participants, are able to modify (in the case of words) and create (in the case of nonwords) long-term memory traces for lexical stimuli, based on a single orthographic processing trial. The nonword repetition results are discussed from the perspective of new vocabulary learning commencing with a provisional lexical memory trace created after orthographic encoding of a novel word-like letter string. PMID:25000325

High dietary advanced glycation end products are associated with poorer spatial learning and accelerated Aβ deposition in an Alzheimer mouse model.

PubMed

Lubitz, Irit; Ricny, Jan; Atrakchi-Baranes, Dana; Shemesh, Chen; Kravitz, Efrat; Liraz-Zaltsman, Sigal; Maksin-Matveev, Anna; Cooper, Itzik; Leibowitz, Avshalom; Uribarri, Jaime; Schmeidler, James; Cai, Weijing; Kristofikova, Zdena; Ripova, Daniela; LeRoith, Derek; Schnaider-Beeri, Michal

2016-04-01

There is growing evidence of the involvement of advanced glycation end products (AGEs) in the pathogenesis of neurodegenerative processes including Alzheimer's disease (AD) and their function as a seed for the aggregation of Aβ, a hallmark feature of AD. AGEs are formed endogenously and exogenously during heating and irradiation of foods. We here examined the effect of a diet high in AGEs in the context of an irradiated diet on memory, insoluble Aβ42 , AGEs levels in hippocampus, on expression of the receptor for AGEs (RAGE), and on oxidative stress in the vasculature. We found that AD-like model mice on high-AGE diet due to irradiation had significantly poorer memory, higher hippocampal levels of insoluble Aβ42 and AGEs as well as higher levels of oxidative stress on vascular walls, compared to littermates fed an isocaloric diet. These differences were not due to weight gain. The data were further supported by the overexpression of RAGE, which binds to Aβ42 and regulates its transport across the blood-brain barrier, suggesting a mediating pathway. Because exposure to AGEs can be diminished, these insights provide an important simple noninvasive potential therapeutic strategy for alleviating a major lifestyle-linked disease epidemic. © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Age-Related Alterations in the Metabolic Profile in the Hippocampus of the Senescence-Accelerated Mouse Prone 8: A Spontaneous Alzheimer's Disease Mouse Model

PubMed Central

Wang, Hualong; Lian, Kaoqi; Han, Bing; Wang, Yanyong; Kuo, Sheng-Han; Geng, Yuan; Qiang, Jing; Sun, Meiyu; Wang, Mingwei

2015-01-01

Alzheimer's disease (AD), the most common age-dependent neurodegenerative disorder, produces a progressive decline in cognitive function. The metabolic mechanism of AD has emerged in recent years. In this study, we used multivariate analyses of gas chromatography-mass spectrometry measurements to determine that learning and retention-related metabolic profiles are altered during aging in the hippocampus of the senescence-accelerated mouse prone 8 (SAMP8). Alterations in 17 metabolites were detected in mature and aged mice compared to young mice (13 decreased and 4 increased metabolites), including metabolites related to dysfunctional lipid metabolism (significantly increased cholesterol, oleic acid, and phosphoglyceride levels), decreased amino acid (alanine, serine, glycine, aspartic acid, glutamate, and gamma-aminobutyric acid), and energy-related metabolite levels (malic acid, butanedioic acid, fumaric acid, and citric acid), and other altered metabolites (increased N-acetyl-aspartic acid and decreased pyroglutamic acid, urea, and lactic acid) in the hippocampus. All of these alterations indicated that the metabolic mechanisms of age-related cognitive impairment in SAMP8 mice were related to multiple pathways and networks. Lipid metabolism, especially cholesterol metabolism, appears to play a distinct role in the hippocampus in AD. PMID:24284365

Parental substance abuse, reports of chronic pain and coping in adult patients with sickle cell disease.

PubMed Central

Edwards, Christopher; Whitfield, Keith; Sudhakar, Shiv; Pearce, Michele; Byrd, Goldie; Wood, Mary; Feliu, Miriam; Leach-Beale, Brittani; DeCastro, Laura; Whitworth, Elaine; Abrams, Mary; Jonassaint, Jude; Harrison, M. Ojinga; Mathis, Markece; Scott, Lydia; Johnson, Stephanie; Durant, Lauren; Holmes, Anita; Presnell, Katherine; Bennett, Gary; Shelby, Rebecca; Robinson, Elwood

2006-01-01

There is increasing interest from a social learning perspective in understanding the role of parental factors on adult health behaviors and health outcomes. Our review revealed no studies, to date, that have evaluated the effects of parental substance abuse on reports of chronic pain and coping in adult patients with sickle cell disease (SCD). We explored the effects of parental substance (alcohol or drug) abuse on reports of the sensory, affective and summary indices of pain in 67 adult patients, mean age 38.9 (13.5), with SCD. We also explored the effects of parental substance abuse on psychopathology associated with pain and active coping. Twenty-four percent of patients reported that their parent(s) abused substances. Patients whose parent(s) were characterized as substance abusers reported greater sensory (p=0.02), affective (p=0.01) and summary (VAS; p=0.02) indices of pain as compared to their counterparts, whose parent(s) were not characterized as substance abusers. Patients did not differ in average age, education or the propensity to respond in a socially acceptable manner. There was a significant trend towards patients who characterized their parents as abusers scoring higher than their counterparts on active coping. We propose a Social Learning Theory to explain the current findings and suggest a need for additional prospective research to simultaneously explore biological (genetic) and social factors that influence the interpretation, experience and reporting of chronic pain in adult patients with chronic disease. PMID:16573309

Is "Learning" episodic memory? Distinct cognitive and neuroanatomic correlates of immediate recall during learning trials in neurologically normal aging and neurodegenerative cohorts.

PubMed

Casaletto, K B; Marx, G; Dutt, S; Neuhaus, J; Saloner, R; Kritikos, L; Miller, B; Kramer, J H

2017-07-28

Although commonly interpreted as a marker of episodic memory during neuropsychological exams, relatively little is known regarding the neurobehavior of "total learning" immediate recall scores. Medial temporal lobes are clearly associated with delayed recall performances, yet immediate recall may necessitate networks beyond traditional episodic memory. We aimed to operationalize cognitive and neuroanatomic correlates of total immediate recall in several aging syndromes. Demographically-matched neurologically normal adults (n=91), individuals with Alzheimer's disease (n=566), logopenic variant primary progressive aphasia (PPA) (n=34), behavioral variant frontotemporal dementia (n=97), semantic variant PPA (n=71), or nonfluent/agrammatic variant PPA (n=39) completed a neurocognitive battery, including the CVLT-Short Form trials 1-4 Total Immediate Recall; a majority subset also completed a brain MRI. Regressions covaried for age and sex, and MMSE in cognitive and total intracranial volume in neuroanatomic models. Neurologically normal adults demonstrated a heterogeneous pattern of cognitive associations with total immediate recall (executive, speed, delayed recall), such that no singular cognitive or neuroanatomic correlate uniquely predicted performance. Within the clinical cohorts, there were syndrome-specific cognitive and neural associations with total immediate recall; e.g., semantic processing was the strongest cognitive correlate in svPPA (partial r=0.41), while frontal volumes was the only meaningful neural correlate in bvFTD (partial r=0.20). Medial temporal lobes were not independently associated with total immediate recall in any group (ps>0.05). Multiple neurobehavioral systems are associated with "total learning" immediate recall scores that importantly differ across distinct clinical syndromes. Conventional memory networks may not be sufficient or even importantly contribute to total immediate recall in many syndromes. Interpreting learning scores as equivalent to episodic memory may be erroneous. Copyright © 2017 Elsevier Ltd. All rights reserved.

Can donated media placements reach intended audiences?

PubMed

Cooper, Crystale Purvis; Gelb, Cynthia A; Chu, Jennifer; Polonec, Lindsey

2013-09-01

Donated media placements for public service announcements (PSAs) can be difficult to secure, and may not always reach intended audiences. Strategies used by the Centers for Disease Control and Prevention's (CDC) Screen for Life: National Colorectal Cancer Action Campaign (SFL) to obtain donated media placements include producing a diverse mix of high-quality PSAs, co-branding with state and tribal health agencies, securing celebrity involvement, monitoring media trends to identify new distribution opportunities, and strategically timing the release of PSAs. To investigate open-ended recall of PSAs promoting colorectal cancer screening, CDC conducted 12 focus groups in three U.S. cities with men and women either nearing age 50 years, when screening is recommended to begin, or aged 50-75 years who were not in compliance with screening guidelines. In most focus groups, multiple participants recalled exposure to PSAs promoting colorectal cancer screening, and most of these individuals reported having seen SFL PSAs on television, in transit stations, or on the sides of public buses. Some participants reported exposure to SFL PSAs without prompting from the moderator, as they explained how they learned about the disease. Several participants reported learning key campaign messages from PSAs, including that colorectal cancer screening should begin at age 50 years and screening can find polyps so they can be removed before becoming cancerous. Donated media placements can reach and educate mass audiences, including millions of U.S. adults who have not been screened appropriately for colorectal cancer.

Subjective memory complaint only relates to verbal episodic memory performance in mild cognitive impairment.

PubMed

Gifford, Katherine A; Liu, Dandan; Damon, Stephen M; Chapman, William G; Romano Iii, Raymond R; Samuels, Lauren R; Lu, Zengqi; Jefferson, Angela L

2015-01-01

A cognitive concern from the patient, informant, or clinician is required for the diagnosis of mild cognitive impairment (MCI); however, the cognitive and neuroanatomical correlates of complaint are poorly understood. We assessed how self-complaint relates to cognitive and neuroimaging measures in older adults with MCI. MCI participants were drawn from the Alzheimer's Disease Neuroimaging Initiative and dichotomized into two groups based on the presence of self-reported memory complaint (no complaint n = 191, 77 ± 7 years; complaint n = 206, 73 ± 8 years). Cognitive outcomes included episodic memory, executive functioning, information processing speed, and language. Imaging outcomes included regional lobar volumes (frontal, parietal, temporal, cingulate) and specific medial temporal lobe structures (hippocampal volume, entorhinal cortex thickness, parahippocampal gyrus thickness). Linear regressions, adjusting for age, gender, race, education, Mini-Mental State Examination score, mood, and apolipoprotein E4 status, found that cognitive complaint related to immediate (β = -1.07, p < 0.001) and delayed episodic memory performances assessed on a serial list learning task (β = -1.06, p = 0.001) but no other cognitive measures or neuroimaging markers. Self-reported memory concern was unrelated to structural neuroimaging markers of atrophy and measures of information processing speed, executive functioning, or language. In contrast, subjective memory complaint related to objective verbal episodic learning performance. Future research is warranted to better understand the relation between cognitive complaint and surrogate markers of abnormal brain aging, including Alzheimer's disease, across the cognitive aging spectrum.

Interaction of ApoE3 and ApoE4 isoforms with an ITM2b/BRI2 mutation linked to the Alzheimer disease-like Danish dementia: Effects on learning and memory

PubMed Central

Biundo, Fabrizio; Ishiwari, Keita; Del Prete, Dolores; D’Adamio, Luciano

2015-01-01

Mutations in Amyloid β Precursor Protein (APP) and in genes that regulate APP processing – such as PSEN1/2 and ITM2b/BRI2 – cause familial dementia, such Familial Alzheimer disease (FAD), Familial Danish (FDD) and British (FBD) dementias. The ApoE gene is the major genetic risk factor for sporadic AD. Three major variants of ApoE exist in humans (ApoE2, ApoE3, and ApoE4), with the ApoE4 allele being strongly associated with AD. ITM2b/BRI2 is also a candidate regulatory node genes predicted to mediate the common patterns of gene expression shared by healthy ApoE4 carriers and late-onset AD patients not carrying ApoE4. This evidence provides a direct link between ITM2b/BRI2 and ApoE4. To test whether ApoE4 and pathogenic ITM2b/BRI2 interact to modulate learning and memory, we crossed a mouse carrying the ITM2b/BRI2 mutations that causes FDD knocked-in the endogenous mouse Itm2b/Bri2 gene (FDDKI mice) with human ApoE3 and ApoE4 targeted replacement mice. The resultant ApoE3, FDDKI/ApoE3, ApoE4, FDDKI/ApoE4 male mice were assessed longitudinally for learning and memory at 4, 6, 12, and 16– 17 months of age. The results showed that ApoE4-carrying mice displayed spatial working/short-term memory deficits relative to ApoE3-carrying mice starting in early middle age, while long-term spatial memory of ApoE4 mice was not adversely affected even at 16–17 months, and that the FDD mutation impaired working/short-term spatial memory in ApoE3-carrying mice and produced impaired long-term spatial memory in ApoE4-carrying mice in middle age. The present results suggest that the FDD mutation may differentially affect learning and memory in ApoE4 carriers and non-carriers. PMID:26528887

Interaction of ApoE3 and ApoE4 isoforms with an ITM2b/BRI2 mutation linked to the Alzheimer disease-like Danish dementia: Effects on learning and memory.

PubMed

Biundo, Fabrizio; Ishiwari, Keita; Del Prete, Dolores; D'Adamio, Luciano

2015-12-01

Mutations in Amyloid β Precursor Protein (APP) and in genes that regulate APP processing--such as PSEN1/2 and ITM2b/BRI2--cause familial dementia, such Familial Alzheimer disease (FAD), Familial Danish (FDD) and British (FBD) dementias. The ApoE gene is the major genetic risk factor for sporadic AD. Three major variants of ApoE exist in humans (ApoE2, ApoE3, and ApoE4), with the ApoE4 allele being strongly associated with AD. ITM2b/BRI2 is also a candidate regulatory node genes predicted to mediate the common patterns of gene expression shared by healthy ApoE4 carriers and late-onset AD patients not carrying ApoE4. This evidence provides a direct link between ITM2b/BRI2 and ApoE4. To test whether ApoE4 and pathogenic ITM2b/BRI2 interact to modulate learning and memory, we crossed a mouse carrying the ITM2b/BRI2 mutations that causes FDD knocked-in the endogenous mouse Itm2b/Bri2 gene (FDDKI mice) with human ApoE3 and ApoE4 targeted replacement mice. The resultant ApoE3, FDDKI/ApoE3, ApoE4, FDDKI/ApoE4 male mice were assessed longitudinally for learning and memory at 4, 6, 12, and 16-17 months of age. The results showed that ApoE4-carrying mice displayed spatial working/short-term memory deficits relative to ApoE3-carrying mice starting in early middle age, while long-term spatial memory of ApoE4 mice was not adversely affected even at 16-17 months, and that the FDD mutation impaired working/short-term spatial memory in ApoE3-carrying mice and produced impaired long-term spatial memory in ApoE4-carrying mice in middle age. The present results suggest that the FDD mutation may differentially affect learning and memory in ApoE4 carriers and non-carriers. Copyright © 2015 Elsevier Inc. All rights reserved.

Diet rich in date palm fruits improves memory, learning and reduces beta amyloid in transgenic mouse model of Alzheimer's disease.

PubMed

Subash, Selvaraju; Essa, Musthafa Mohamed; Braidy, Nady; Awlad-Thani, Kathyia; Vaishnav, Ragini; Al-Adawi, Samir; Al-Asmi, Abdullah; Guillemin, Gilles J

2015-01-01

At present, the treatment options available to delay the onset or slow down the progression of Alzheimer's disease (AD) are not effective. Recent studies have suggested that diet and lifestyle factors may represent protective strategies to minimize the risk of developing AD. Date palm fruits are a good source of dietary fiber and are rich in total phenolics and natural antioxidants, such as anthocyanins, ferulic acid, protocatechuic acid and caffeic acid. These polyphenolic compounds have been shown to be neuroprotective in different model systems. We investigated whether dietary supplementation with 2% and 4% date palm fruits (grown in Oman) could reduce cognitive and behavioral deficits in a transgenic mouse model for AD (amyloid precursor protein [APPsw]/Tg2576). The experimental groups of APP-transgenic mice from the age of 4 months were fed custom-mix diets (pellets) containing 2% and 4% date fruits. We assessed spatial memory and learning ability, psychomotor coordination, and anxiety-related behavior in all the animals at the age of 4 months and after 14 months of treatment using the Morris water maze test, rota-rod test, elevated plus maze test, and open-field test. We have also analyzed the levels of amyloid beta (Aβ) protein (1-40 and 1-42) in plasma of control and experimental animals. Standard diet-fed Tg mice showed significant memory deficits, increased anxiety-related behavior, and severe impairment in spatial learning ability, position discrimination learning ability and motor coordination when compared to wild-type on the same diet and Tg mice fed 2% and 4% date supplementation at the age of 18 months. The levels of both Aβ proteins were significantly lowered in date fruits supplemented groups than the Tg mice without the diet supplement. The neuroprotective effect offered by 4% date fruits diet to AD mice is higher than 2% date fruits diet. Our results suggest that date fruits dietary supplementation may have beneficial effects in lowering the risk, delaying the onset or slowing down the progression of AD.

Neuropsychological Profiles Differentiate Alzheimer Disease from Subcortical Ischemic Vascular Dementia in an Autopsy-Defined Cohort.

PubMed

Ramirez-Gomez, Liliana; Zheng, Ling; Reed, Bruce; Kramer, Joel; Mungas, Dan; Zarow, Chris; Vinters, Harry; Ringman, John M; Chui, Helena

2017-01-01

The aim of this study was to assess the ability of neuropsychological tests to differentiate autopsy-defined Alzheimer disease (AD) from subcortical ischemic vascular dementia (SIVD). From a sample of 175 cases followed longitudinally that underwent autopsy, we selected 23 normal controls (NC), 20 SIVD, 69 AD, and 10 mixed cases of dementia. Baseline neuropsychological tests, including Memory Assessment Scale word list learning test, control oral word association test, and animal fluency, were compared between the three autopsy-defined groups. The NC, SIVD, and AD groups did not differ by age or education. The SIVD and AD groups did not differ by the Global Clinical Dementia Rating Scale. Subjects with AD performed worse on delayed recall (p < 0.01). A receiver operating characteristics analysis comparing the SIVD and AD groups including age, education, difference between categorical (animals) versus phonemic fluency (letter F), and the first recall from the word learning test distinguished the two groups with a sensitivity of 85%, specificity of 67%, and positive likelihood ratio of 2.57 (AUC = 0.789, 95% CI 0.69-0.88, p < 0.0001). In neuropathologically defined subgroups, neuropsychological profiles have modest ability to distinguish patients with AD from those with SIVD. © 2017 S. Karger AG, Basel.

Neuropsychological Profiles Differentiate Alzheimer Disease from Subcortical Ischemic Vascular Dementia in an Autopsy-Defined Cohort

PubMed Central

Ramirez-Gomez, Liliana; Zheng, Ling; Reed, Bruce; Kramer, Joel; Mungas, Dan; Zarow, Chris; Vinters, Harry; Ringman, John M.; Chui, Helena

2018-01-01

Background/Aims The aim of this study was to assess the ability of neuropsychological tests to differentiate autopsy-defined Alzheimer disease (AD) from subcortical ischemic vascular dementia (SIVD). Methods From a sample of 175 cases followed longitudinally that underwent autopsy, we selected 23 normal controls (NC), 20 SIVD, 69 AD, and 10 mixed cases of dementia. Baseline neuropsychological tests, including Memory Assessment Scale word list learning test, control oral word association test, and animal fluency, were compared between the three autopsy-defined groups. Results The NC, SIVD, and AD groups did not differ by age or education. The SIVD and AD groups did not differ by the Global Clinical Dementia Rating Scale. Subjects with AD performed worse on delayed recall (p < 0.01). A receiver operating characteristics analysis comparing the SIVD and AD groups including age, education, difference between categorical (animals) versus phonemic fluency (letter F), and the first recall from the word learning test distinguished the two groups with a sensitivity of 85%, specificity of 67%, and positive likelihood ratio of 2.57 (AUC = 0.789, 95% CI 0.69–0.88, p < 0.0001). Conclusion In neuropathologically defined subgroups, neuropsychological profiles have modest ability to distinguish patients with AD from those with SIVD. PMID:28595184

Verbal memory declines more in female patients with Parkinson's disease: the importance of gender-corrected normative data.

PubMed

Fengler, S; Roeske, S; Heber, I; Reetz, K; Schulz, J B; Riedel, O; Wittchen, H U; Storch, A; Linse, K; Baudrexel, S; Hilker, R; Mollenhauer, B; Witt, K; Schmidt, N; Balzer-Geldsetzer, M; Dams, J; Dodel, R; Gräber, S; Pilotto, A; Petrelli, A; Fünkele, S; Kassubek, J; Kalbe, E

2016-08-01

Data on gender-specific profiles of cognitive functions in patients with Parkinson's disease (PD) are rare and inconsistent, and possible disease-confounding factors have been insufficiently considered. The LANDSCAPE study on cognition in PD enrolled 656 PD patients (267 without cognitive impairment, 66% male; 292 with mild cognitive impairment, 69% male; 97 with PD dementia, 69% male). Raw values and age-, education-, and gender-corrected Z scores of a neuropsychological test battery (CERAD-Plus) were compared between genders. Motor symptoms, disease duration, l-dopa equivalent daily dose, depression - and additionally age and education for the raw value analysis - were taken as covariates. Raw-score analysis replicated results of previous studies in that female PD patients were superior in verbal memory (word list learning, p = 0.02; recall, p = 0.03), while men outperformed women in visuoconstruction (p = 0.002) and figural memory (p = 0.005). In contrast, gender-corrected Z scores showed that men were superior in verbal memory (word list learning, p = 0.02; recall, p = 0.02; recognition, p = 0.04), while no difference was found for visuospatial tests. This picture could be observed both in the overall analysis of PD patients as well as in a differentiated group analysis. Normative data corrected for gender and other sociodemographic variables are relevant, since they may elucidate a markedly different cognitive profile compared to raw scores. Our study also suggests that verbal memory decline is stronger in women than in men with PD. Future studies are needed to replicate these findings, examine the progression of gender-specific cognitive decline in PD and define different underlying mechanisms of this dysfunction.

Sleep-dependent memory consolidation in healthy aging and mild cognitive impairment.

PubMed

Pace-Schott, Edward F; Spencer, Rebecca M C

2015-01-01

Sleep quality and architecture as well as sleep's homeostatic and circadian controls change with healthy aging. Changes include reductions in slow-wave sleep's (SWS) percent and spectral power in the sleep electroencephalogram (EEG), number and amplitude of sleep spindles, rapid eye movement (REM) density and the amplitude of circadian rhythms, as well as a phase advance (moved earlier in time) of the brain's circadian clock. With mild cognitive impairment (MCI) there are further reductions of sleep quality, SWS, spindles, and percent REM, all of which further diminish, along with a profound disruption of circadian rhythmicity, with the conversion to Alzheimer's disease (AD). Sleep disorders may represent risk factors for dementias (e.g., REM Behavior Disorder presages Parkinson's disease) and sleep disorders are themselves extremely prevalent in neurodegenerative diseases. Working memory , formation of new episodic memories, and processing speed all decline with healthy aging whereas semantic, recognition, and emotional declarative memory are spared. In MCI, episodic and working memory further decline along with declines in semantic memory. In young adults, sleep-dependent memory consolidation (SDC) is widely observed for both declarative and procedural memory tasks. However, with healthy aging, although SDC for declarative memory is preserved, certain procedural tasks, such as motor-sequence learning, do not show SDC. In younger adults, fragmentation of sleep can reduce SDC, and a normative increase in sleep fragmentation may account for reduced SDC with healthy aging. Whereas sleep disorders such as insomnia, obstructive sleep apnea, and narcolepsy can impair SDC in the absence of neurodegenerative changes, the incidence of sleep disorders increases both with normal aging and, further, with neurodegenerative disease. Specific features of sleep architecture, such as sleep spindles and SWS are strongly linked to SDC. Diminution of these features with healthy aging and their further decline with MCI may account for concomitant declines in SDC. Notably these same sleep features further markedly decline, in concert with declining cognitive function, with the progression to AD. Therefore, progressive changes in sleep quality, architecture, and neural regulation may constitute a contributing factor to cognitive decline that is seen both with healthy aging and, to a much greater extent, with neurodegenerative disease.

Facilitating the use of implicit memory and learning in the physical therapy management of individuals with Alzheimer disease: a case series.

PubMed

White, Laura; Ford, Matthew P; Brown, Cynthia J; Peel, Claire; Triebel, Kristen L

2014-01-01

Physical rehabilitation of individuals with Alzheimer disease (AD) is often complicated by impairments in explicit memory and learning. Rehabilitation strategies that facilitate the use of the preserved implicit memory system may be effective in treating patients with AD. The purpose of this case series is to describe the application of these strategies, including high-repetition practice, errorless learning (EL), and spaced retrieval, to the physical therapy management of individuals with moderate AD. Three women aged 89 to 95 years with moderate AD who resided in an assisted living facility participated in physical therapy to address their mobility limitations. Twelve physical therapy sessions were scheduled over a period of 4 weeks. Interventions were individually designed to address the mobility needs of each patient, and rehabilitation strategies based on implicit learning principles were integrated into the interventions. All patients participated in at least 10 of the 12 physical therapy sessions. Improvements in performance of objective measures of balance were observed in all patients, although only 1 patient's balance score exceeded the minimal detectable change. No significant clinical change was observed in any patients on the Timed Up and Go Test or self-selected gait speed. Principles of implicit learning were integrated into the interventions for these patients with moderate AD. However, the feasibility of applying the EL paradigm was limited. Further research on the effectiveness of EL, spaced retrieval, and other rehabilitation strategies that facilitate implicit learning of mobility skills in patients with AD is needed to promote optimal physical therapy outcomes in this patient population.

The pattern of verbal, visuospatial and procedural learning in Richardson variant of progressive supranuclear palsy in comparison to Parkinson's disease.

PubMed

Sitek, Emilia J; Wieczorek, Dariusz; Konkel, Agnieszka; Dąbrowska, Magda; Sławek, Jarosław

2017-08-29

Progressive supranuclear palsy (PSP) is regarded either within spectrum of atypical parkinsonian syndromes or frontotemporal lobar degeneration. We compared the verbal, visuospatial and procedural learning profiles in patients with PSP and Parkinson's disease (PD). Furthermore, the relationship between executive factors (initiation and inhibition) and learning outcomes was analyzed. Thirty-three patients with the clinical diagnosis of PSP-Richardson's syndrome (PSP-RS), 39 patients with PD and 29 age -and education -matched controls were administered Mini-Mental State Examination (MMSE), phonemic and semantic fluency tasks, Auditory Verbal Learning Test (AVLT), Visual Learning and Memory Test for Neuropsychological Assessment by Lamberti and Weidlich (Diagnosticum für Cerebralschädigung, DCS), Tower of Toronto (ToT) and two motor sequencing tasks. Patients with PSP-RS and PD were matched in terms of MMSE scores and mood. Performance on DCS was lower in PSP-RS than in PD. AVLT delayed recall was better in PSP-RS than PD. Motor sequencing task did not differentiate between patients. Scores on AVLT correlated positively with phonemic fluency scores in both PSP-RS and PD. ToT rule violation scores were negatively associated with DCS performance in PSP-RS and PD as well as with AVLT performance in PD. Global memory performance is relatively similar in PSP-RS and PD. Executive factors (initiation and inhibition) are closely related to memory performance in PSP-RS and PD. Visuospatial learning impairment in PSP-RS is possibly linked to impulsivity and failure to inhibit automatic responses.

Andrographolide recovers cognitive impairment in a natural model of Alzheimer's disease (Octodon degus).

PubMed

Rivera, Daniela S; Lindsay, Carolina; Codocedo, Juan Francisco; Morel, Isidora; Pinto, Claudio; Cisternas, Pedro; Bozinovic, Francisco; Inestrosa, Nibaldo C

2016-10-01

The social species Octodon degus (degu) is the only wild-type South American rodent that develops Alzheimer's-like pathology with age. Here, we evaluated the ability of a natural product (Andrographolide, ANDRO), a diterpene of the labdane family obtained from the Asian plant Andrographis paniculata, to recover the cognitive decline in this long-lived animal model. We administered ANDRO to aged degus (56-month old) for 3 months. In addition, in 2 control groups (young degus: 12-month old and aged degus: 56-month old), we administrated saline solution as a vehicle. We evaluated cognitive performance through several behavioral tests. We also performed a series of physiological and biochemical analyses (e.g., electrophysiological and immunoblotting assessment) to identify possible mechanisms underlying cognitive performance associated with age. Our results suggest that there is an effect of aging on the loss of cognitive function, and this decrease in cognitive function was also related to a decrease in the synaptic functions and an increase in the main hallmarks of Alzheimer's disease (AD). More importantly, ANDRO treatments showed the following beneficial effects: (1) recovery of spatial memory and learning performance; (2) recovery of synaptic basal transmission; (3) partial or complete protection of certain synaptic proteins; and (4) a specific neuroprotective effect, including the reduction of phosphorylated tau protein and amyloid beta aggregate maturation in aged degus. Taken together, our results suggest that ANDRO could be used as a potential therapy for AD and support the use of O. degus as a natural model in which to study both neural damage associated with aging processes and the behavioral and neuropathological hallmarks of aging-related diseases such as AD. Copyright © 2016 Elsevier Inc. All rights reserved.

Lessons learned and applied

PubMed Central

Hebert, Corey Joseph; Hall, Corey M.; Odoms, La’ Nyia J.

2012-01-01

Most vaccines available in the United States (US) have been incorporated into vaccination schedules for infants and young children, age groups particularly at risk of contracting infectious diseases. High universal vaccination coverage is responsible for substantially reducing or nearly eliminating many of the diseases that once killed thousands of children each year in the US. Despite the success of infant vaccinations, periods of low vaccination coverage and the limited immunogenicity and duration of protection of certain vaccines have resulted in sporadic outbreaks, allowing some diseases to spread in communities. These challenges suggest that expanded vaccination coverage to younger infants and adolescents, and more immunogenic vaccines, may be needed in some instances. This review focuses on the importance of infant immunization and explores the successes and challenges of current early childhood vaccination programs and how these lessons may be applied to other invasive diseases, such as meningococcal disease. PMID:22617834

Rescue from excitotoxicity and axonal degeneration accompanied by age-dependent behavioral and neuroanatomical alterations in caspase-6-deficient mice.

PubMed

Uribe, Valeria; Wong, Bibiana K Y; Graham, Rona K; Cusack, Corey L; Skotte, Niels H; Pouladi, Mahmoud A; Xie, Yuanyun; Feinberg, Konstantin; Ou, Yimiao; Ouyang, Yingbin; Deng, Yu; Franciosi, Sonia; Bissada, Nagat; Spreeuw, Amanda; Zhang, Weining; Ehrnhoefer, Dagmar E; Vaid, Kuljeet; Miller, Freda D; Deshmukh, Mohanish; Howland, David; Hayden, Michael R

2012-05-01

Apoptosis, or programmed cell death, is a cellular pathway involved in normal cell turnover, developmental tissue remodeling, embryonic development, cellular homeostasis maintenance and chemical-induced cell death. Caspases are a family of intracellular proteases that play a key role in apoptosis. Aberrant activation of caspases has been implicated in human diseases. In particular, numerous findings implicate Caspase-6 (Casp6) in neurodegenerative diseases, including Alzheimer disease (AD) and Huntington disease (HD), highlighting the need for a deeper understanding of Casp6 biology and its role in brain development. The use of targeted caspase-deficient mice has been instrumental for studying the involvement of caspases in apoptosis. The goal of this study was to perform an in-depth neuroanatomical and behavioral characterization of constitutive Casp6-deficient (Casp6-/-) mice in order to understand the physiological function of Casp6 in brain development, structure and function. We demonstrate that Casp6-/- neurons are protected against excitotoxicity, nerve growth factor deprivation and myelin-induced axonal degeneration. Furthermore, Casp6-deficient mice show an age-dependent increase in cortical and striatal volume. In addition, these mice show a hypoactive phenotype and display learning deficits. The age-dependent behavioral and region-specific neuroanatomical changes observed in the Casp6-/- mice suggest that Casp6 deficiency has a more pronounced effect in brain regions that are involved in neurodegenerative diseases, such as the striatum in HD and the cortex in AD.

Brain properties predict proximity to symptom onset in sporadic Alzheimer’s disease

PubMed Central

Vogel, Jacob W; Vachon-Presseau, Etienne; Pichet Binette, Alexa; Tam, Angela; Orban, Pierre; La Joie, Renaud; Savard, Mélissa; Picard, Cynthia; Poirier, Judes; Bellec, Pierre; Breitner, John C S; Villeneuve, Sylvia

2018-01-01

Abstract See Tijms and Visser (doi:10.1093/brain/awy113) for a scientific commentary on this article. Alzheimer’s disease is preceded by a lengthy ‘preclinical’ stage spanning many years, during which subtle brain changes occur in the absence of overt cognitive symptoms. Predicting when the onset of disease symptoms will occur is an unsolved challenge in individuals with sporadic Alzheimer’s disease. In individuals with autosomal dominant genetic Alzheimer’s disease, the age of symptom onset is similar across generations, allowing the prediction of individual onset times with some accuracy. We extend this concept to persons with a parental history of sporadic Alzheimer’s disease to test whether an individual’s symptom onset age can be informed by the onset age of their affected parent, and whether this estimated onset age can be predicted using only MRI. Structural and functional MRIs were acquired from 255 ageing cognitively healthy subjects with a parental history of sporadic Alzheimer’s disease from the PREVENT-AD cohort. Years to estimated symptom onset was calculated as participant age minus age of parental symptom onset. Grey matter volume was extracted from T1-weighted images and whole-brain resting state functional connectivity was evaluated using degree count. Both modalities were summarized using a 444-region cortical-subcortical atlas. The entire sample was divided into training (n = 138) and testing (n = 68) sets. Within the training set, individuals closer to or beyond their parent’s symptom onset demonstrated reduced grey matter volume and altered functional connectivity, specifically in regions known to be vulnerable in Alzheimer’s disease. Machine learning was used to identify a weighted set of imaging features trained to predict years to estimated symptom onset. This feature set alone significantly predicted years to estimated symptom onset in the unseen testing data. This model, using only neuroimaging features, significantly outperformed a similar model instead trained with cognitive, genetic, imaging and demographic features used in a traditional clinical setting. We next tested if these brain properties could be generalized to predict time to clinical progression in a subgroup of 26 individuals from the Alzheimer’s Disease Neuroimaging Initiative, who eventually converted either to mild cognitive impairment or to Alzheimer’s dementia. The feature set trained on years to estimated symptom onset in the PREVENT-AD predicted variance in time to clinical conversion in this separate longitudinal dataset. Adjusting for participant age did not impact any of the results. These findings demonstrate that years to estimated symptom onset or similar measures can be predicted from brain features and may help estimate presymptomatic disease progression in at-risk individuals. PMID:29688388

Active Ageing, Active Learning: Policy and Provision in Hong Kong

ERIC Educational Resources Information Center

Tam, M.

2011-01-01

This paper discusses the relationship between ageing and learning, previous literature having confirmed that participation in continued learning in old age contributes to good health, satisfaction with life, independence and self-esteem. Realizing that learning is vital to active ageing, the Hong Kong government has implemented policies and…

Creating Contexts for Middle-Age Learning.

ERIC Educational Resources Information Center

Stone, Sandra J.

1998-01-01

Presents the theories of Vygotsky and Bandura that provide the foundation for research on cross-age learning in multiple-age groupings. Discusses the cognitive, social, and emotional benefits children derive from mixed-age groupings. Outlines social learning contexts, such as learning centers and projects, and structural contexts, such as multiage…

Combining macula clinical signs and patient characteristics for age-related macular degeneration diagnosis: a machine learning approach.

PubMed

Fraccaro, Paolo; Nicolo, Massimo; Bonetto, Monica; Giacomini, Mauro; Weller, Peter; Traverso, Carlo Enrico; Prosperi, Mattia; OSullivan, Dympna

2015-01-27

To investigate machine learning methods, ranging from simpler interpretable techniques to complex (non-linear) "black-box" approaches, for automated diagnosis of Age-related Macular Degeneration (AMD). Data from healthy subjects and patients diagnosed with AMD or other retinal diseases were collected during routine visits via an Electronic Health Record (EHR) system. Patients' attributes included demographics and, for each eye, presence/absence of major AMD-related clinical signs (soft drusen, retinal pigment epitelium, defects/pigment mottling, depigmentation area, subretinal haemorrhage, subretinal fluid, macula thickness, macular scar, subretinal fibrosis). Interpretable techniques known as white box methods including logistic regression and decision trees as well as less interpreitable techniques known as black box methods, such as support vector machines (SVM), random forests and AdaBoost, were used to develop models (trained and validated on unseen data) to diagnose AMD. The gold standard was confirmed diagnosis of AMD by physicians. Sensitivity, specificity and area under the receiver operating characteristic (AUC) were used to assess performance. Study population included 487 patients (912 eyes). In terms of AUC, random forests, logistic regression and adaboost showed a mean performance of (0.92), followed by SVM and decision trees (0.90). All machine learning models identified soft drusen and age as the most discriminating variables in clinicians' decision pathways to diagnose AMD. Both black-box and white box methods performed well in identifying diagnoses of AMD and their decision pathways. Machine learning models developed through the proposed approach, relying on clinical signs identified by retinal specialists, could be embedded into EHR to provide physicians with real time (interpretable) support.

Learners' Starting Age of Learning EFL and Use of Language Learning Strategies

ERIC Educational Resources Information Center

Sadeghi, Karim; Khonbi, Zainab Abolfazli

2013-01-01

This study investigated the use of language learning strategies (LLS) and reasons for learning English among Iranian EFL students who began learning English at different ages. The participants (N = 33, both male and female) were divided into two groups of younger beginners (who began learning English before age 9; N = 16) and older beginners (who…

Are Children the Better Placebo Analgesia Responders? An Experimental Approach.

PubMed

Wrobel, Nathalie; Fadai, Tahmine; Sprenger, Christian; Hebebrand, Johannes; Wiech, Katja; Bingel, Ulrike

2015-10-01

There is little information regarding changes in placebo responsiveness with age, although first predictors of placebo responders such as psychological and physiological processes have been identified. Reviews and meta-analyses indicate that placebo response rates in randomized controlled trials (RCTs) are higher in children and adolescents compared with adults. As these studies cannot control for age-dependent differences in the natural course of the disease, biases might contribute to different placebo rates in RCTs. To avoid these biases, this study investigated age-related differences in placebo responsiveness between children and adults in a well-established experimental model of placebo analgesia combining classic conditioning and expectation. Our data confirm placebo analgesic responses in children, which did not differ in magnitude from those of adults. The influence of previous experience on subsequent treatment outcome was stronger in children than in adults, indicating an increased relevance of learning processes for treatment outcomes in children. Further studies are needed to understand the influence of treatment-related learning processes in children and adolescents, which might critically determine treatment responsiveness during adulthood. This study is the first to experimentally explore placebo analgesia and influences of previous experience on placebo responses in children compared with adults. We found comparable placebo responses in both groups and an increased relevance of learning processes for treatment outcomes in children. Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.

Learning to Live Well with Celiac Disease

MedlinePlus

... Foundation Celiac Disease Foundation Read More "Celiac Disease" Articles Celiac Disease Changes Everything / What is Celiac Disease? / Symptoms, Diagnosis & Treatment / Four Inches and Seven Pounds… / Learning to Live Well with Celiac Disease / Living Gluten- ...

Comparison of machine learning and semi-quantification algorithms for (I123)FP-CIT classification: the beginning of the end for semi-quantification?

PubMed

Taylor, Jonathan Christopher; Fenner, John Wesley

2017-11-29

Semi-quantification methods are well established in the clinic for assisted reporting of (I123) Ioflupane images. Arguably, these are limited diagnostic tools. Recent research has demonstrated the potential for improved classification performance offered by machine learning algorithms. A direct comparison between methods is required to establish whether a move towards widespread clinical adoption of machine learning algorithms is justified. This study compared three machine learning algorithms with that of a range of semi-quantification methods, using the Parkinson's Progression Markers Initiative (PPMI) research database and a locally derived clinical database for validation. Machine learning algorithms were based on support vector machine classifiers with three different sets of features: Voxel intensities Principal components of image voxel intensities Striatal binding radios from the putamen and caudate. Semi-quantification methods were based on striatal binding ratios (SBRs) from both putamina, with and without consideration of the caudates. Normal limits for the SBRs were defined through four different methods: Minimum of age-matched controls Mean minus 1/1.5/2 standard deviations from age-matched controls Linear regression of normal patient data against age (minus 1/1.5/2 standard errors) Selection of the optimum operating point on the receiver operator characteristic curve from normal and abnormal training data Each machine learning and semi-quantification technique was evaluated with stratified, nested 10-fold cross-validation, repeated 10 times. The mean accuracy of the semi-quantitative methods for classification of local data into Parkinsonian and non-Parkinsonian groups varied from 0.78 to 0.87, contrasting with 0.89 to 0.95 for classifying PPMI data into healthy controls and Parkinson's disease groups. The machine learning algorithms gave mean accuracies between 0.88 to 0.92 and 0.95 to 0.97 for local and PPMI data respectively. Classification performance was lower for the local database than the research database for both semi-quantitative and machine learning algorithms. However, for both databases, the machine learning methods generated equal or higher mean accuracies (with lower variance) than any of the semi-quantification approaches. The gain in performance from using machine learning algorithms as compared to semi-quantification was relatively small and may be insufficient, when considered in isolation, to offer significant advantages in the clinical context.

Age differences in learning emerge from an insufficient representation of uncertainty in older adults

PubMed Central

Nassar, Matthew R.; Bruckner, Rasmus; Gold, Joshua I.; Li, Shu-Chen; Heekeren, Hauke R.; Eppinger, Ben

2016-01-01

Healthy aging can lead to impairments in learning that affect many laboratory and real-life tasks. These tasks often involve the acquisition of dynamic contingencies, which requires adjusting the rate of learning to environmental statistics. For example, learning rate should increase when expectations are uncertain (uncertainty), outcomes are surprising (surprise) or contingencies are more likely to change (hazard rate). In this study, we combine computational modelling with an age-comparative behavioural study to test whether age-related learning deficits emerge from a failure to optimize learning according to the three factors mentioned above. Our results suggest that learning deficits observed in healthy older adults are driven by a diminished capacity to represent and use uncertainty to guide learning. These findings provide insight into age-related cognitive changes and demonstrate how learning deficits can emerge from a failure to accurately assess how much should be learned. PMID:27282467

Alzheimer's disease and natural cognitive aging may represent adaptive metabolism reduction programs

PubMed Central

2009-01-01

The present article examines several lines of converging evidence suggesting that the slow and insidious brain changes that accumulate over the lifespan, resulting in both natural cognitive aging and Alzheimer's disease (AD), represent a metabolism reduction program. A number of such adaptive programs are known to accompany aging and are thought to have decreased energy requirements for ancestral hunter-gatherers in their 30s, 40s and 50s. Foraging ability in modern hunter-gatherers declines rapidly, more than a decade before the average terminal age of 55 years. Given this, the human brain would have been a tremendous metabolic liability that must have been advantageously tempered by the early cellular and molecular changes of AD which begin to accumulate in all humans during early adulthood. Before the recent lengthening of life span, individuals in the ancestral environment died well before this metabolism reduction program resulted in clinical AD, thus there was never any selective pressure to keep adaptive changes from progressing to a maladaptive extent. Aging foragers may not have needed the same cognitive capacities as their younger counterparts because of the benefits of accumulated learning and life experience. It is known that during both childhood and adulthood metabolic rate in the brain decreases linearly with age. This trend is thought to reflect the fact that children have more to learn. AD "pathology" may be a natural continuation of this trend. It is characterized by decreasing cerebral metabolism, selective elimination of synapses and reliance on accumulating knowledge (especially implicit and procedural) over raw brain power (working memory). Over decades of subsistence, the behaviors of aging foragers became routinized, their motor movements automated and their expertise ingrained to a point where they no longer necessitated the first-rate working memory they possessed when younger and learning actively. Alzheimer changes selectively and precisely mediate an adaptation to this major life-history transition. AD symptomatology shares close similarities with deprivation syndromes in other animals including the starvation response. Both molecular and anatomical features of AD imitate brain changes that have been conceptualized as adaptive responses to low food availability in mammals and birds. Alzheimer's patients are known to express low overall metabolic rates and are genetically inclined to exhibit physiologically thrifty traits widely thought to allow mammals to subsist under conditions of nutritional scarcity. Additionally, AD is examined here in the contexts of anthropology, comparative neuroscience, evolutionary medicine, expertise, gerontology, neural Darwinism, neuroecology and the thrifty genotype. PMID:19250550

Alzheimer's disease and natural cognitive aging may represent adaptive metabolism reduction programs.

PubMed

Reser, Jared Edward

2009-02-28

The present article examines several lines of converging evidence suggesting that the slow and insidious brain changes that accumulate over the lifespan, resulting in both natural cognitive aging and Alzheimer's disease (AD), represent a metabolism reduction program. A number of such adaptive programs are known to accompany aging and are thought to have decreased energy requirements for ancestral hunter-gatherers in their 30s, 40s and 50s. Foraging ability in modern hunter-gatherers declines rapidly, more than a decade before the average terminal age of 55 years. Given this, the human brain would have been a tremendous metabolic liability that must have been advantageously tempered by the early cellular and molecular changes of AD which begin to accumulate in all humans during early adulthood. Before the recent lengthening of life span, individuals in the ancestral environment died well before this metabolism reduction program resulted in clinical AD, thus there was never any selective pressure to keep adaptive changes from progressing to a maladaptive extent.Aging foragers may not have needed the same cognitive capacities as their younger counterparts because of the benefits of accumulated learning and life experience. It is known that during both childhood and adulthood metabolic rate in the brain decreases linearly with age. This trend is thought to reflect the fact that children have more to learn. AD "pathology" may be a natural continuation of this trend. It is characterized by decreasing cerebral metabolism, selective elimination of synapses and reliance on accumulating knowledge (especially implicit and procedural) over raw brain power (working memory). Over decades of subsistence, the behaviors of aging foragers became routinized, their motor movements automated and their expertise ingrained to a point where they no longer necessitated the first-rate working memory they possessed when younger and learning actively. Alzheimer changes selectively and precisely mediate an adaptation to this major life-history transition.AD symptomatology shares close similarities with deprivation syndromes in other animals including the starvation response. Both molecular and anatomical features of AD imitate brain changes that have been conceptualized as adaptive responses to low food availability in mammals and birds. Alzheimer's patients are known to express low overall metabolic rates and are genetically inclined to exhibit physiologically thrifty traits widely thought to allow mammals to subsist under conditions of nutritional scarcity. Additionally, AD is examined here in the contexts of anthropology, comparative neuroscience, evolutionary medicine, expertise, gerontology, neural Darwinism, neuroecology and the thrifty genotype.

Progression of multiple behavioral deficits with various ages of onset in a murine model of Hurler syndrome.

PubMed

Pan, Dao; Sciascia, Anthony; Vorhees, Charles V; Williams, Michael T

2008-01-10

Mucopolysaccharidosis type I (MPS I) is one of the most common lysosomal storage diseases with progressive neurological dysfunction. To characterize the chronological behavioral profiles and identify the onset of functional deficits in a MPS I mouse model (IDUA(-/-)), we evaluated anxiety, locomotor behavior, startle, spatial learning and memory with mice at 2, 4, 6 and 8 months of age. In automated open-field test, IDUA(-/-) mice showed hypoactivity as early as 2 months of age and altered anxiety starting from 6 months of age during the initial exploratory phase, even though normal habituation was observed at all ages. In the marble-burying task, the anxiety-like compulsive behavior was normal in IDUA(-/-) mice at almost all tested ages, but significantly reduced in 8-month old male IDUA(-/-) mice which coincided with the rapid death of IDUA(-/-) males starting from 7 months of age. In the Morris water maze, IDUA(-/-) mice exhibited impaired proficient learning only at 4 months of age during the acquisition phase. Spatial memory deficits were observed in IDUA(-/-) mice during both 1 and 7 days probe trials at 4 and 8 months of age. The IDUA(-/-) mice performed normally in a novel object recognition task at younger ages until 8 months old when reduced visual cognitive memory retention was noted in the IDUA(-/-) mice. In addition, 8-month-old IDUA(-/-) mice failed to habituate to repeated open-field exposure, suggesting deficits in non-aversive and non-associative memory. In acoustic startle assessment, significantly more non-responders were found in IDUA(-/-) mice, but normal performance was seen in those that did show a response. These results presented a temporal evaluation of phenotypic behavioral dysfunctions in IDUA(-/-) mice from adolescence to maturity, indicating the impairments, with different ages of onset, in locomotor and anxiety-like compulsive behaviors, spatial learning and memory, visual recognition and short-term non-associative memory retention. This study would also provide guidelines for the experimental designs of behavioral evaluation on innovative therapies for the treatment of MPS type I.

PhenoLines: Phenotype Comparison Visualizations for Disease Subtyping via Topic Models.

PubMed

Glueck, Michael; Naeini, Mahdi Pakdaman; Doshi-Velez, Finale; Chevalier, Fanny; Khan, Azam; Wigdor, Daniel; Brudno, Michael

2018-01-01

PhenoLines is a visual analysis tool for the interpretation of disease subtypes, derived from the application of topic models to clinical data. Topic models enable one to mine cross-sectional patient comorbidity data (e.g., electronic health records) and construct disease subtypes-each with its own temporally evolving prevalence and co-occurrence of phenotypes-without requiring aligned longitudinal phenotype data for all patients. However, the dimensionality of topic models makes interpretation challenging, and de facto analyses provide little intuition regarding phenotype relevance or phenotype interrelationships. PhenoLines enables one to compare phenotype prevalence within and across disease subtype topics, thus supporting subtype characterization, a task that involves identifying a proposed subtype's dominant phenotypes, ages of effect, and clinical validity. We contribute a data transformation workflow that employs the Human Phenotype Ontology to hierarchically organize phenotypes and aggregate the evolving probabilities produced by topic models. We introduce a novel measure of phenotype relevance that can be used to simplify the resulting topology. The design of PhenoLines was motivated by formative interviews with machine learning and clinical experts. We describe the collaborative design process, distill high-level tasks, and report on initial evaluations with machine learning experts and a medical domain expert. These results suggest that PhenoLines demonstrates promising approaches to support the characterization and optimization of topic models.

Multivariate prediction of motor diagnosis in Huntington's disease: 12 years of PREDICT‐HD

PubMed Central

Long, Jeffrey D.

2015-01-01

Abstract Background It is well known in Huntington's disease that cytosine‐adenine‐guanine expansion and age at study entry are predictive of the timing of motor diagnosis. The goal of this study was to assess whether additional motor, imaging, cognitive, functional, psychiatric, and demographic variables measured at study entry increased the ability to predict the risk of motor diagnosis over 12 years. Methods One thousand seventy‐eight Huntington's disease gene–expanded carriers (64% female) from the Neurobiological Predictors of Huntington's Disease study were followed up for up to 12 y (mean = 5, standard deviation = 3.3) covering 2002 to 2014. No one had a motor diagnosis at study entry, but 225 (21%) carriers prospectively received a motor diagnosis. Analysis was performed with random survival forests, which is a machine learning method for right‐censored data. Results Adding 34 variables along with cytosine‐adenine‐guanine and age substantially increased predictive accuracy relative to cytosine‐adenine‐guanine and age alone. Adding six of the common motor and cognitive variables (total motor score, diagnostic confidence level, Symbol Digit Modalities Test, three Stroop tests) resulted in lower predictive accuracy than the full set, but still had twice the 5‐y predictive accuracy than when using cytosine‐adenine‐guanine and age alone. Additional analysis suggested interactions and nonlinear effects that were characterized in a post hoc Cox regression model. Conclusions Measurement of clinical variables can substantially increase the accuracy of predicting motor diagnosis over and above cytosine‐adenine‐guanine and age (and their interaction). Estimated probabilities can be used to characterize progression level and aid in future studies' sample selection. © 2015 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society PMID:26340420

Multivariate prediction of motor diagnosis in Huntington's disease: 12 years of PREDICT-HD.

PubMed

Long, Jeffrey D; Paulsen, Jane S

2015-10-01

It is well known in Huntington's disease that cytosine-adenine-guanine expansion and age at study entry are predictive of the timing of motor diagnosis. The goal of this study was to assess whether additional motor, imaging, cognitive, functional, psychiatric, and demographic variables measured at study entry increased the ability to predict the risk of motor diagnosis over 12 years. One thousand seventy-eight Huntington's disease gene-expanded carriers (64% female) from the Neurobiological Predictors of Huntington's Disease study were followed up for up to 12 y (mean = 5, standard deviation = 3.3) covering 2002 to 2014. No one had a motor diagnosis at study entry, but 225 (21%) carriers prospectively received a motor diagnosis. Analysis was performed with random survival forests, which is a machine learning method for right-censored data. Adding 34 variables along with cytosine-adenine-guanine and age substantially increased predictive accuracy relative to cytosine-adenine-guanine and age alone. Adding six of the common motor and cognitive variables (total motor score, diagnostic confidence level, Symbol Digit Modalities Test, three Stroop tests) resulted in lower predictive accuracy than the full set, but still had twice the 5-y predictive accuracy than when using cytosine-adenine-guanine and age alone. Additional analysis suggested interactions and nonlinear effects that were characterized in a post hoc Cox regression model. Measurement of clinical variables can substantially increase the accuracy of predicting motor diagnosis over and above cytosine-adenine-guanine and age (and their interaction). Estimated probabilities can be used to characterize progression level and aid in future studies' sample selection. © 2015 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Association between socioeconomic status, learned helplessness, and disease outcome in patients with inflammatory polyarthritis.

PubMed

Camacho, E M; Verstappen, S M M; Symmons, D P M

2012-08-01

Independent investigations have shown that socioeconomic status (SES) and learned helplessness (LH) are associated with poor disease outcome in patients with rheumatoid arthritis (RA). Our aim was to investigate the cross-sectional relationship between SES, LH, and disease outcome in patients with recent-onset inflammatory polyarthritis (IP), the broader group of conditions of which RA is the major constituent. SES was measured using the Index of Multiple Deprivation 2007 for 553 patients consecutively recruited to the Norfolk Arthritis Register. Patients also completed the Rheumatology Attitudes Index, a measure of LH. SES and LH were investigated as predictors of disease outcome (functional disability [Health Assessment Questionnaire (HAQ)] and disease activity [Disease Activity Score in 28 joints]) in a regression analysis, adjusted for age, sex, and symptom duration. The role of LH in the relationship between SES and disease outcome was then investigated. Compared to patients of the highest SES, those of the lowest SES had a significantly worse outcome (median difference in HAQ score 0.42; 95% confidence interval [95% CI] 0.08, 0.75). Compared to patients with normal LH, patients with low LH had a significantly better outcome and patients with high LH had a significantly worse outcome (median difference in HAQ score 1.12; 95% CI 0.82, 1.41). There was a significant likelihood that LH mediated the association between SES and disease outcome (P = 0.04). LH is robustly associated with cross-sectional disease outcome in patients with IP, and appears to mediate the relationship between SES and disease outcome. As LH is potentially modifiable, these findings have potential clinical implications. Copyright © 2012 by the American College of Rheumatology.

Association between socioeconomic status, learned helplessness, and disease outcome in patients with inflammatory polyarthritis

PubMed Central

Camacho, E M; Verstappen, S M M; Symmons, D P M

2012-01-01

Objective Independent investigations have shown that socioeconomic status (SES) and learned helplessness (LH) are associated with poor disease outcome in patients with rheumatoid arthritis (RA). Our aim was to investigate the cross-sectional relationship between SES, LH, and disease outcome in patients with recent-onset inflammatory polyarthritis (IP), the broader group of conditions of which RA is the major constituent. Methods SES was measured using the Index of Multiple Deprivation 2007 for 553 patients consecutively recruited to the Norfolk Arthritis Register. Patients also completed the Rheumatology Attitudes Index, a measure of LH. SES and LH were investigated as predictors of disease outcome (functional disability [Health Assessment Questionnaire (HAQ)] and disease activity [Disease Activity Score in 28 joints]) in a regression analysis, adjusted for age, sex, and symptom duration. The role of LH in the relationship between SES and disease outcome was then investigated. Results Compared to patients of the highest SES, those of the lowest SES had a significantly worse outcome (median difference in HAQ score 0.42; 95% confidence interval [95% CI] 0.08, 0.75). Compared to patients with normal LH, patients with low LH had a significantly better outcome and patients with high LH had a significantly worse outcome (median difference in HAQ score 1.12; 95% CI 0.82, 1.41). There was a significant likelihood that LH mediated the association between SES and disease outcome (P = 0.04). Conclusion LH is robustly associated with cross-sectional disease outcome in patients with IP, and appears to mediate the relationship between SES and disease outcome. As LH is potentially modifiable, these findings have potential clinical implications. PMID:22438290

Locomotor activity, emotionality, sensori-motor gating, learning and memory in the APPswe/PS1dE9 mouse model of Alzheimer's disease.

PubMed

O'Leary, Timothy P; Hussin, Ahmed T; Gunn, Rhian K; Brown, Richard E

2018-06-02

The APPswe/PS1dE9 mouse (line 85) is a double transgenic model of Alzheimer's disease (AD) with familial amyloid precursor protein and presenilin-1 mutations. These mice develop age-related behavioral changes reflective of the neuropsychiatric symptoms (altered anxiety-like behaviour, hyperactivity) and cognitive dysfunction (impaired learning and memory) observed in AD. The APPswe/PS1dE9 mouse has been used to examine the efficacy of therapeutic interventions on behaviour, despite previous difficulties in replicating behavioural phenotypes. Therefore, the purpose of this study was to establish the reliability of these phenotypes by further characterizing the behaviour of male APPswe/PS1dE9 and wild-type mice between 7 and 14 months of age. Mice were tested on the open-field over 5-days to examine emotionality, locomotor activity and inter-session habituation. Mice were also tested on the repeated-reversal water maze task and spontaneous alternation on the Y-maze to assess working memory. Sensori-motor gating was examined with acoustic startle and pre-pulse inhibition. Lastly contextual and cued (trace) memory was assessed with fear conditioning. The results show that among non-cognitive behaviours, APPswe/PS1dE9 mice have normal locomotor activity, anxiety-like behavior, habituation and sensori-motor gating. However, APPswe/PS1dE9 mice show impaired working memory on the repeated-reversal water-maze and impaired memory in contextual but not trace-cued fear conditioning. These results indicate that the APPswe/PS1dE9 (line 85) mice have deficits in some types of hippocampal-dependent learning and memory and, at the ages tested, APPswe/PS1dE9 mice model cognitive dysfunction but not neuropsychiatric symptoms. Copyright © 2018. Published by Elsevier Inc.

Age-related cognitive decline coincides with accelerated volume loss of the dorsal but not ventral hippocampus in mice.

PubMed

Reichel, J M; Bedenk, B T; Czisch, M; Wotjak, C T

2017-01-01

Even in the absence of neurodegenerative diseases, progressing age often coincides with cognitive decline and morphological changes. However, longitudinal studies that directly link these two processes are missing. In this proof-of-concept study we therefore performed repeated within-subject testing of healthy male R26R mice in a spatial learning task in combination with manganese-enhanced volumetric MRI analyses at the ages of 8, 16, and 24 months. We grouped the mice into good and poor performers (n = 6, each), based on their spatial learning abilities at the age of 24 months. Using this stratification, we failed to detect a priori volume differences, but observed a significant decrease in total hippocampal volume over time for both groups. Interestingly, this volume decrease was specific for the dorsal hippocampus and significantly accelerated in poor performers between 16 and 24 months of age. This is the first time that individual changes in hippocampal volume were traced alongside cognitive performance within the same subjects over 1½ years. Our study points to a causal link between volume loss of the dorsal hippocampus and cognitive impairments. In addition, it suggests accelerated degenerative processes rather than a priori volume differences as determining trajectories of age-related cognitive decline. Despite the relatively small sample sizes, the strong behavioral and moderate morphological alterations demonstrate the general feasibility of longitudinal studies of age-related decline in cognition and hippocampus integrity. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Brahmi rasayana Improves Learning and Memory in Mice

PubMed Central

Joshi, Hanumanthachar; Parle, Milind

2006-01-01

Cure of cognitive disorders such as amnesia, attention deficit and Alzheimer's disease is still a nightmare in the field of medicine. Nootropic agents such as piracetam, aniracetam and choline esterase inhibitors like Donepezil® are being used to improve memory, mood and behavior, but the resulting side effects associated with these agents have made their use limited. The present study was undertaken to assess the potential of Brahmi rasayana (BR) as a memory enhancer. BR (100 and 200 mg kg−1 p.o.) was administered for eight successive days to both young and aged mice. Elevated plus maze and passive-avoidance paradigm were employed to evaluate learning and memory parameters. Scopolamine (0.4 mg kg−1 i.p.) was used to induce amnesia in mice. The effect of BR on whole brain AChE activity was also assessed. Piracetam (200 mg kg−1 i.p.) was used as a standard nootropic agent. BR significantly improved learning and memory in young mice and reversed the amnesia induced by both scopolamine (0.4 mg kg−1 i.p.) and natural aging. BR significantly decreased whole brain acetyl cholinesterase activity. BR might prove to be a useful memory restorative agent in the treatment of dementia seen in elderly. PMID:16550227

Towards a clinically informed, data-driven definition of elderly onset epilepsy.

PubMed

Josephson, Colin B; Engbers, Jordan D T; Sajobi, Tolulope T; Jette, Nathalie; Agha-Khani, Yahya; Federico, Paolo; Murphy, William; Pillay, Neelan; Wiebe, Samuel

2016-02-01

Elderly onset epilepsy represents a distinct subpopulation that has received considerable attention due to the unique features of the disease in this age group. Research into this particular patient group has been limited by a lack of a standardized definition and understanding of the attributes associated with elderly onset epilepsy. We used a prospective cohort database to examine differences in patients stratified according to age of onset. Linear support vector machine learning incorporating all significant variables was used to predict age of onset according to prespecified thresholds. Sensitivity and specificity were calculated and plotted in receiver-operating characteristic (ROC) space. Feature coefficients achieving an absolute value of 0.25 or greater were graphed by age of onset to define how they vary with time. We identified 2,449 patients, of whom 149 (6%) had an age of seizure onset of 65 or older. Fourteen clinical variables had an absolute predictive value of at least 0.25 at some point over the age of epilepsy-onset spectrum. Area under the curve in ROC space was maximized between ages of onset of 65 and 70. Features identified through machine learning were frequently threshold specific and were similar, but not identical, to those revealed through simple univariable and multivariable comparisons. This study provides an empirical, clinically informed definition of "elderly onset epilepsy." If validated, an age threshold of 65-70 years can be used for future studies of elderly onset epilepsy and permits targeted interventions according to the patient's age of onset. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Analysis of epidemiological studies: facts and artifacts.

PubMed

Wright, Anne L

2002-09-01

Cohort studies have provided the foundation for much of our knowledge of childhood asthma. Four important lessons have been learned from these longitudinal studies: that asthma is a complex disease, encompassing many phenotypes; that it is linked to the development of the immune system and respiratory tract in the first years of life; that early life events strongly affect the development of asthma risk and that relationships between certain exposures and asthma risk are age dependent. The Tucson Children's Respiratory Study is used to exemplify these lessons and to illustrate the advantages of cohort studies in investigating a complex disease. Copyright 2002 Elsevier Science Ltd.

Age effects shrink when motor learning is predominantly supported by nondeclarative, automatic memory processes: evidence from golf putting.

PubMed

Chauvel, Guillaume; Maquestiaux, François; Hartley, Alan A; Joubert, Sven; Didierjean, André; Masters, Rich S W

2012-01-01

Can motor learning be equivalent in younger and older adults? To address this question, 48 younger (M = 23.5 years) and 48 older (M = 65.0 years) participants learned to perform a golf-putting task in two different motor learning situations: one that resulted in infrequent errors or one that resulted in frequent errors. The results demonstrated that infrequent-error learning predominantly relied on nondeclarative, automatic memory processes whereas frequent-error learning predominantly relied on declarative, effortful memory processes: After learning, infrequent-error learners verbalized fewer strategies than frequent-error learners; at transfer, a concurrent, attention-demanding secondary task (tone counting) left motor performance of infrequent-error learners unaffected but impaired that of frequent-error learners. The results showed age-equivalent motor performance in infrequent-error learning but age deficits in frequent-error learning. Motor performance of frequent-error learners required more attention with age, as evidenced by an age deficit on the attention-demanding secondary task. The disappearance of age effects when nondeclarative, automatic memory processes predominated suggests that these processes are preserved with age and are available even early in motor learning.

Age and education adjusted normative data and discriminative validity for Rey's Auditory Verbal Learning Test in the elderly Greek population.

PubMed

Messinis, Lambros; Nasios, Grigorios; Mougias, Antonios; Politis, Antonis; Zampakis, Petros; Tsiamaki, Eirini; Malefaki, Sonia; Gourzis, Phillipos; Papathanasopoulos, Panagiotis

2016-01-01

Rey's Auditory Verbal Learning Test (RAVLT) is a widely used neuropsychological test to assess episodic memory. In the present study we sought to establish normative and discriminative validity data for the RAVLT in the elderly population using previously adapted learning lists for the Greek adult population. We administered the test to 258 cognitively healthy elderly participants, aged 60-89 years, and two patient groups (192 with amnestic mild cognitive impairment, aMCI, and 65 with Alzheimer's disease, AD). From the statistical analyses, we found that age and education contributed significantly to most trials of the RAVLT, whereas the influence of gender was not significant. Younger elderly participants with higher education outperformed the older elderly with lower education levels. Moreover, both clinical groups performed significantly worse on most RAVLT trials and composite measures than matched cognitively healthy controls. Furthermore, the AD group performed more poorly than the aMCI group on most RAVLT variables. Receiver operating characteristic (ROC) analysis was used to examine the utility of the RAVLT trials to discriminate cognitively healthy controls from aMCI and AD patients. Area under the curve (AUC), an index of effect size, showed that most of the RAVLT measures (individual and composite) included in this study adequately differentiated between the performance of healthy elders and aMCI/AD patients. We also provide cutoff scores in discriminating cognitively healthy controls from aMCI and AD patients, based on the sensitivity and specificity of the prescribed scores. Moreover, we present age- and education-specific normative data for individual and composite scores for the Greek adapted RAVLT in elderly subjects aged between 60 and 89 years for use in clinical and research settings.

Frontostriatal white matter integrity mediates adult age differences in probabilistic reward learning.

PubMed

Samanez-Larkin, Gregory R; Levens, Sara M; Perry, Lee M; Dougherty, Robert F; Knutson, Brian

2012-04-11

Frontostriatal circuits have been implicated in reward learning, and emerging findings suggest that frontal white matter structural integrity and probabilistic reward learning are reduced in older age. This cross-sectional study examined whether age differences in frontostriatal white matter integrity could account for age differences in reward learning in a community life span sample of human adults. By combining diffusion tensor imaging with a probabilistic reward learning task, we found that older age was associated with decreased reward learning and decreased white matter integrity in specific pathways running from the thalamus to the medial prefrontal cortex and from the medial prefrontal cortex to the ventral striatum. Further, white matter integrity in these thalamocorticostriatal paths could statistically account for age differences in learning. These findings suggest that the integrity of frontostriatal white matter pathways critically supports reward learning. The findings also raise the possibility that interventions that bolster frontostriatal integrity might improve reward learning and decision making.

Active-learning implementation in an advanced elective course on infectious diseases.

PubMed

Hidayat, Levita; Patel, Shreya; Veltri, Keith

2012-06-18

To describe the development, implementation, and assessment of an advanced elective course on infectious diseases using active-learning strategies. Pedagogy for active learning was incorporated by means of mini-lecture, journal club, and debate with follow-up discussion. Forty-eight students were enrolled in this 4-week elective course, in which 30% of course time was allocated for active-learning exercises. All activities were fundamentally designed as a stepwise approach in complementing each active-learning exercise. Achievement of the course learning objectives was assessed using a 5-point Likert scale survey instrument. Students' awareness of the significance of antimicrobial resistance was improved (p ≤ 0.05). Students' ability to critically evaluate the infectious-disease literature and its application in informed clinical judgments was also enhanced through these active-learning exercises (p ≤ 0.05). Students agreed that active learning should be part of the pharmacy curriculum and that active-learning exercises improved their critical-thinking, literature-evaluation, and self-learning skills. An elective course using active-learning strategies allowed students to combine information gained from the evaluation of infectious-disease literature, critical thinking, and informed clinical judgment. This blended approach ultimately resulted in an increased knowledge and awareness of infectious diseases.

Topics of internal medicine for undergraduate dental education: a qualitative study.

PubMed

Kunde, A; Harendza, S

2015-08-01

Due to the ageing population, internal medicine has become increasingly important for dental education. Although several studies have reported dentists' dissatisfaction with their internal medicine training, no guidelines exist for internal medicine learning objectives in dental education. The aim of this study was to identify topics of internal medicine considered to be relevant for dental education by dentists and internists. Eight dentists from private dental practices in Hamburg and eight experienced internal medicine consultants from Hamburg University Hospital were recruited for semi-structured interviews about internal medicine topics relevant for dentists. Internal diseases were clustered into representative subspecialties. Dentists and internists were also asked to rate medical diseases or emergencies compiled from the literature by their relevance to dental education. Coagulopathy and endocarditis were rated highest by dentists, whilst anaphylaxis was rated highest by internists. Dentists rated hepatitis, HIV, organ transplantation and head/neck neoplasm significantly higher than internists. The largest number of different internal diseases mentioned by dentists or internists could be clustered under cardiovascular diseases. The number of specific diseases dentists considered to be relevant for dental education was higher in the subspecialties cardiovascular diseases, haematology/oncology and infectiology. We identified the internal medicine topics most relevant for dental education by surveying practising dentists and internists. The relevance of these topics should be confirmed by larger quantitative studies to develop guidelines how to design specific learning objectives for internal medicine in the dental curriculum. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Consumption of fig fruits grown in Oman can improve memory, anxiety, and learning skills in a transgenic mice model of Alzheimer's disease.

PubMed

Subash, Selvaraju; Essa, Musthafa Mohamed; Braidy, Nady; Al-Jabri, Ahood; Vaishnav, Ragini; Al-Adawi, Samir; Al-Asmi, Abdullah; Guillemin, Gilles J

2016-12-01

Alzheimer disease (AD) is one of the most common forms of dementia in the elderly. Several reports have suggested neurotoxic effects of amyloid beta protein (Aβ) and role of oxidative stress in AD. Figs are rich in fiber, copper, iron, manganese, magnesium, potassium, calcium, vitamin K, and are a good source of proanthocyanidins and quercetin which demonstrate potent antioxidant properties. We studied the effect of dietary supplementation with 4% figs grown in Oman on the memory, anxiety, and learning skills in APPsw/Tg2576 (Tg mice) mice model for AD. We assessed spatial memory and learning ability, psychomotor coordination, and anxiety-related behavior in Tg and wild-type mice at the age of 4 months and after 15 months using the Morris water maze test, rota-rod test, elevated plus maze test, and open-field test. Tg mice that were fed a control diet without figs showed significant memory deficits, increased anxiety-related behavior, and severe impairment in spatial, position discrimination learning ability, and motor coordination compared to the wild-type control mice on the same diet, and Tg mice fed on 4% fig diet supplementation for 15 months. Our results suggest that dietary supplementation of figs may be useful for the improvement of cognitive and behavioral deficits in AD.

Effect of normal aging and of Alzheimer's disease on, episodic memory.

PubMed

Le Moal, S; Reymann, J M; Thomas, V; Cattenoz, C; Lieury, A; Allain, H

1997-01-01

Performances of 12 patients with Alzheimer's disease (AD), 15 healthy elderly subjects and 20 young healthy volunteers were compared on two episodic memory tests. The first, a learning test of semantically related words, enabled an assessment of the effect of semantic relationships on word learning by controlling the encoding and retrieval processes. The second, a dual coding test, is about the assessment of automatic processes operating during drawings encoding. The results obtained demonstrated quantitative and qualitative differences between the population. Manifestations of episodic memory deficit in AD patients were shown not only by lower performance scores than in elderly controls, but also by the lack of any effect of semantic cues and the production of a large number of extra-list intrusions. Automatic processes underlying dual coding appear to be spared in AD, although more time is needed to process information than in young or elderly subjects. These findings confirm former data and emphasize the preservation of certain memory processes (dual coding) in AD which could be used in future therapeutic approaches.

Family and child-care provider influences on preschool children's fruit, juice, and vegetable consumption.

PubMed

Nicklas, T A; Baranowski, T; Baranowski, J C; Cullen, K; Rittenberry, L; Olvera, N

2001-07-01

Children's intakes of fruit, juice, and vegetables (FJV) do not meet the recommended minimum of five daily servings, placing them at increased risk for development of cancer and other diseases. Because children's food preferences and practices are initiated early in life (e.g., 2-5 years of age), early dietary intervention programs may have immediate nutritional benefit, as well as reduce chronic disease risk when learned healthful habits and preferences are carried into adulthood. Families and child-care settings are important social environments within which food-related behaviors among young children are developed. FJV preferences, the primary predictor of FJV consumption in children, are influenced by availability, variety, and repeated exposure. Caregivers (parents and child-care providers) can influence children's eating practices by controlling availability and accessibility of foods, meal structure, food modeling, food socialization practices, and food-related parenting style. Much remains to be learned about how these influences and practices affect the development of FJV preferences and consumption early in life.

Accurate Monitoring Leads to Effective Control and Greater Learning of Patient Education Materials

ERIC Educational Resources Information Center

Rawson, Katherine A.; O'Neil, Rochelle; Dunlosky, John

2011-01-01

Effective management of chronic diseases (e.g., diabetes) can depend on the extent to which patients can learn and remember disease-relevant information. In two experiments, we explored a technique motivated by theories of self-regulated learning for improving people's learning of information relevant to managing a chronic disease. Materials were…

Neurodegenerative disease and cognitive retest learning.

PubMed

Wilson, Robert S; Capuano, Ana W; Yu, Lei; Yang, Jingyun; Kim, Namhee; Leurgans, Sue E; Lamar, Melissa; Schneider, Julie A; Bennett, David A; Boyle, Patricia A

2018-06-01

Retest learning impacts estimates of cognitive aging, but its bases are uncertain. Here, we test the hypothesis that dementia-related neurodegeneration impairs retest learning. Older persons without cognitive impairment at enrollment (n = 567) had annual cognitive testing for a mean of 11 years, died, and had a neuropathologic examination to quantify 5 neurodegenerative pathologies. Change point models were used to divide cognitive trajectories into an early retest sensitive component and a later component less sensitive to retest. Performance on a global cognitive measure (baseline mean = 0.227, standard deviation = 0.382) increased an estimated mean of 0.142-unit per year for a mean of 1.5 years and declined an estimated mean of 0.123-unit per year thereafter. No pathologic marker was related to cognitive change before the change point; each was related to cognitive decline after the change point. Results were comparable in analyses that used specific cognitive outcomes, included 220 individuals with mild cognitive impairment at enrollment, or allowed a longer retest learning period. The findings suggest that neurodegeneration does not impact cognitive retest learning. Copyright © 2018 Elsevier Inc. All rights reserved.

Dopamine selectively remediates ‘model-based’ reward learning: a computational approach

PubMed Central

Sharp, Madeleine E.; Foerde, Karin; Daw, Nathaniel D.

2016-01-01

Patients with loss of dopamine due to Parkinson’s disease are impaired at learning from reward. However, it remains unknown precisely which aspect of learning is impaired. In particular, learning from reward, or reinforcement learning, can be driven by two distinct computational processes. One involves habitual stamping-in of stimulus-response associations, hypothesized to arise computationally from ‘model-free’ learning. The other, ‘model-based’ learning, involves learning a model of the world that is believed to support goal-directed behaviour. Much work has pointed to a role for dopamine in model-free learning. But recent work suggests model-based learning may also involve dopamine modulation, raising the possibility that model-based learning may contribute to the learning impairment in Parkinson’s disease. To directly test this, we used a two-step reward-learning task which dissociates model-free versus model-based learning. We evaluated learning in patients with Parkinson’s disease tested ON versus OFF their dopamine replacement medication and in healthy controls. Surprisingly, we found no effect of disease or medication on model-free learning. Instead, we found that patients tested OFF medication showed a marked impairment in model-based learning, and that this impairment was remediated by dopaminergic medication. Moreover, model-based learning was positively correlated with a separate measure of working memory performance, raising the possibility of common neural substrates. Our results suggest that some learning deficits in Parkinson’s disease may be related to an inability to pursue reward based on complete representations of the environment. PMID:26685155

Personalized Age Progression with Bi-Level Aging Dictionary Learning.

PubMed

Shu, Xiangbo; Tang, Jinhui; Li, Zechao; Lai, Hanjiang; Zhang, Liyan; Yan, Shuicheng

2018-04-01

Age progression is defined as aesthetically re-rendering the aging face at any future age for an individual face. In this work, we aim to automatically render aging faces in a personalized way. Basically, for each age group, we learn an aging dictionary to reveal its aging characteristics (e.g., wrinkles), where the dictionary bases corresponding to the same index yet from two neighboring aging dictionaries form a particular aging pattern cross these two age groups, and a linear combination of all these patterns expresses a particular personalized aging process. Moreover, two factors are taken into consideration in the dictionary learning process. First, beyond the aging dictionaries, each person may have extra personalized facial characteristics, e.g., mole, which are invariant in the aging process. Second, it is challenging or even impossible to collect faces of all age groups for a particular person, yet much easier and more practical to get face pairs from neighboring age groups. To this end, we propose a novel Bi-level Dictionary Learning based Personalized Age Progression (BDL-PAP) method. Here, bi-level dictionary learning is formulated to learn the aging dictionaries based on face pairs from neighboring age groups. Extensive experiments well demonstrate the advantages of the proposed BDL-PAP over other state-of-the-arts in term of personalized age progression, as well as the performance gain for cross-age face verification by synthesizing aging faces.

77 FR 14446 - Changes to the Generic Aging Lessons Learned (GALL) Report Revision 2 AMP XI.M41, “Buried and...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-09

... NUCLEAR REGULATORY COMMISSION [NRC-2012-0055] Changes to the Generic Aging Lessons Learned (GALL... Aging Lessons Learned (GALL) Report,'' and the NRC staff's aging management review procedure and... into ADAMS. II. Background The NRC issues LR-ISGs to communicate insights and lessons learned and to...

Neurobiology of the aging dog.

PubMed

Head, Elizabeth

2011-09-01

Aged canines naturally accumulate several types of neuropathology that may have links to cognitive decline. On a gross level, significant cortical atrophy occurs with age along with an increase in ventricular volume based on magnetic resonance imaging studies. Microscopically, there is evidence of select neuron loss and reduced neurogenesis in the hippocampus of aged dogs, an area critical for intact learning and memory. The cause of neuronal loss and dysfunction may be related to the progressive accumulation of toxic proteins, oxidative damage, cerebrovascular pathology, and changes in gene expression. For example, aged dogs naturally accumulate human-type beta-amyloid peptide, a protein critically involved with the development of Alzheimer's disease in humans. Further, oxidative damage to proteins, DNA/RNA and lipids occurs with age in dogs. Although less well explored in the aged canine brain, neuron loss, and cerebrovascular pathology observed with age are similar to human brain aging and may also be linked to cognitive decline. Interestingly, the prefrontal cortex appears to be particularly vulnerable early in the aging process in dogs and this may be reflected in dysfunction in specific cognitive domains with age.

Automated analysis of retinal imaging using machine learning techniques for computer vision.

PubMed

De Fauw, Jeffrey; Keane, Pearse; Tomasev, Nenad; Visentin, Daniel; van den Driessche, George; Johnson, Mike; Hughes, Cian O; Chu, Carlton; Ledsam, Joseph; Back, Trevor; Peto, Tunde; Rees, Geraint; Montgomery, Hugh; Raine, Rosalind; Ronneberger, Olaf; Cornebise, Julien

2016-01-01

There are almost two million people in the United Kingdom living with sight loss, including around 360,000 people who are registered as blind or partially sighted. Sight threatening diseases, such as diabetic retinopathy and age related macular degeneration have contributed to the 40% increase in outpatient attendances in the last decade but are amenable to early detection and monitoring. With early and appropriate intervention, blindness may be prevented in many cases. Ophthalmic imaging provides a way to diagnose and objectively assess the progression of a number of pathologies including neovascular ("wet") age-related macular degeneration (wet AMD) and diabetic retinopathy. Two methods of imaging are commonly used: digital photographs of the fundus (the 'back' of the eye) and Optical Coherence Tomography (OCT, a modality that uses light waves in a similar way to how ultrasound uses sound waves). Changes in population demographics and expectations and the changing pattern of chronic diseases creates a rising demand for such imaging. Meanwhile, interrogation of such images is time consuming, costly, and prone to human error. The application of novel analysis methods may provide a solution to these challenges. This research will focus on applying novel machine learning algorithms to automatic analysis of both digital fundus photographs and OCT in Moorfields Eye Hospital NHS Foundation Trust patients. Through analysis of the images used in ophthalmology, along with relevant clinical and demographic information, DeepMind Health will investigate the feasibility of automated grading of digital fundus photographs and OCT and provide novel quantitative measures for specific disease features and for monitoring the therapeutic success.

Oxidative Stress, Aging and CNS disease in the Canine Model of Human Brain Aging

PubMed Central

Head, Elizabeth; Rofina, Jaime; Zicker, Steven

2008-01-01

SYNOPSIS Decline in cognitive functions that accompany aging in dogs may have a biological basis, and many of the disorders associated with aging in canines may be mitigated through dietary modifications that incorporate specific nutraceuticals. Based on previous research and the results of both laboratory and clinical studies – antioxidants may be one class of nutraceutical that provides benefits to aged dogs. Brains of aged dogs accumulate oxidative damage to proteins and lipids, which may lead to dysfunction of neuronal cells. The production of free radicals and lack of increase in compensatory antioxidant enzymes may lead to detrimental modifications to important macromolecules within neurons. Reducing oxidative damage through food ingredients rich in a broad spectrum of antioxidants significantly improves, or slows the decline of, learning and memory in aged dogs. However, determining all effective compounds and combinations, dosage ranges, as well as when to initiate intervention and long term effects constitute gaps in our current knowledge. PMID:18249248

Longitudinal Study-Based Dementia Prediction for Public Health

PubMed Central

Kim, HeeChel; Chun, Hong-Woo; Kim, Seonho; Coh, Byoung-Youl; Kwon, Oh-Jin; Moon, Yeong-Ho

2017-01-01

The issue of public health in Korea has attracted significant attention given the aging of the country’s population, which has created many types of social problems. The approach proposed in this article aims to address dementia, one of the most significant symptoms of aging and a public health care issue in Korea. The Korean National Health Insurance Service Senior Cohort Database contains personal medical data of every citizen in Korea. There are many different medical history patterns between individuals with dementia and normal controls. The approach used in this study involved examination of personal medical history features from personal disease history, sociodemographic data, and personal health examinations to develop a prediction model. The prediction model used a support-vector machine learning technique to perform a 10-fold cross-validation analysis. The experimental results demonstrated promising performance (80.9% F-measure). The proposed approach supported the significant influence of personal medical history features during an optimal observation period. It is anticipated that a biomedical “big data”-based disease prediction model may assist the diagnosis of any disease more correctly. PMID:28867810

Positivity effect in healthy aging in observational but not active feedback-learning.

PubMed

Bellebaum, Christian; Rustemeier, Martina; Daum, Irene

2012-01-01

The present study investigated the impact of healthy aging on the bias to learn from positive or negative performance feedback in observational and active feedback learning. In active learning, a previous study had already shown a negative learning bias in healthy seniors older than 75 years, while no bias was found for younger seniors. However, healthy aging is accompanied by a 'positivity effect', a tendency to primarily attend to stimuli with positive valence. Based on recent findings of dissociable neural mechanisms in active and observational feedback learning, the positivity effect was hypothesized to influence older participants' observational feedback learning in particular. In two separate experiments, groups of young (mean age 27) and older participants (mean age 60 years) completed an observational or active learning task designed to differentially assess positive and negative learning. Older but not younger observational learners showed a significant bias to learn better from positive than negative feedback. In accordance with previous findings, no bias was found for active learning. This pattern of results is discussed in terms of differences in the neural underpinnings of active and observational learning from performance feedback.

Effects of curcumin (Curcuma longa) on learning and spatial memory as well as cell proliferation and neuroblast differentiation in adult and aged mice by upregulating brain-derived neurotrophic factor and CREB signaling.

PubMed

Nam, Sung Min; Choi, Jung Hoon; Yoo, Dae Young; Kim, Woosuk; Jung, Hyo Young; Kim, Jong Whi; Yoo, Miyoung; Lee, Sanghee; Kim, Chul Jung; Yoon, Yeo Sung; Hwang, In Koo

2014-06-01

Aging is a progressive process, and it may lead to the initiation of neurological diseases. In this study, we investigated the effects of wild Indian Curcuma longa using a Morris water maze paradigm on learning and spatial memory in adult and D-galactose-induced aged mice. In addition, the effects on cell proliferation and neuroblast differentiation were assessed by immunohistochemistry for Ki67 and doublecortin (DCX) respectively. The aging model in mice was induced through the subcutaneous administration of D-galactose (100 mg/kg) for 10 weeks. C. longa (300 mg/kg) or its vehicle (physiological saline) was administered orally to adult and D-galactose-treated mice for the last three weeks before sacrifice. The administration of C. longa significantly shortened the escape latency in both adult and D-galactose-induced aged mice and significantly ameliorated D-galactose-induced reduction of cell proliferation and neuroblast differentiation in the subgranular zone of hippocampal dentate gyrus. In addition, the administration of C. longa significantly increased the levels of phosphorylated CREB and brain-derived neurotrophic factor in the subgranular zone of dentate gyrus. These results indicate that C. longa mitigates D-galactose-induced cognitive impairment, associated with decreased cell proliferation and neuroblast differentiation, by activating CREB signaling in the hippocampal dentate gyrus.

Effects of Curcumin (Curcuma longa) on Learning and Spatial Memory as Well as Cell Proliferation and Neuroblast Differentiation in Adult and Aged Mice by Upregulating Brain-Derived Neurotrophic Factor and CREB Signaling

PubMed Central

Nam, Sung Min; Choi, Jung Hoon; Yoo, Dae Young; Kim, Woosuk; Jung, Hyo Young; Kim, Jong Whi; Yoo, Miyoung; Lee, Sanghee; Kim, Chul Jung; Yoon, Yeo Sung

2014-01-01

Abstract Aging is a progressive process, and it may lead to the initiation of neurological diseases. In this study, we investigated the effects of wild Indian Curcuma longa using a Morris water maze paradigm on learning and spatial memory in adult and D-galactose-induced aged mice. In addition, the effects on cell proliferation and neuroblast differentiation were assessed by immunohistochemistry for Ki67 and doublecortin (DCX) respectively. The aging model in mice was induced through the subcutaneous administration of D-galactose (100 mg/kg) for 10 weeks. C. longa (300 mg/kg) or its vehicle (physiological saline) was administered orally to adult and D-galactose-treated mice for the last three weeks before sacrifice. The administration of C. longa significantly shortened the escape latency in both adult and D-galactose-induced aged mice and significantly ameliorated D-galactose-induced reduction of cell proliferation and neuroblast differentiation in the subgranular zone of hippocampal dentate gyrus. In addition, the administration of C. longa significantly increased the levels of phosphorylated CREB and brain-derived neurotrophic factor in the subgranular zone of dentate gyrus. These results indicate that C. longa mitigates D-galactose-induced cognitive impairment, associated with decreased cell proliferation and neuroblast differentiation, by activating CREB signaling in the hippocampal dentate gyrus. PMID:24712702

Factors associated with experiences of genetic discrimination among individuals at risk for Huntington disease

PubMed Central

Bombard, Yvonne; Palin, JoAnne; Friedman, Jan M.; Veenstra, Gerry; Creighton, Susan; Paulsen, Jane S.; Bottorff, Joan L.; Hayden, Michael R.

2013-01-01

The purpose of this study was to identify factors that are associated with experiencing genetic discrimination (GD) among individuals at risk for Huntington disease (HD). Multivariable logistic regression analysis was used to examine factors associated with experiencing GD in data from a cross-sectional, self-report survey of 293 individuals at risk for HD. The study sample comprised 167 genetically tested respondents, and 66 who were not tested (80% response rate). Overall, individuals who learn they are at risk for HD at a younger age (OR = 3.1; 95% CI: 1.5–6.2; P = 0.002), are mutation-positive (OR = 2.8; 95% CI: 1.4–6.0; P = 0.006), or are highly educated (OR = 2.7; 95% CI: 1.4–5.1; P = 0.002) are more likely to experience GD, particularly in insurance, family, and social settings. Further, younger age was associated with discrimination in insurance (OR = 0.97; 95% CI: 0.94–1.00; P = 0.038). This study provides evidence that some people who are at risk for HD were more likely to experience GD than others. Individuals who learned they are at risk for HD at a younger age and those who are mutation-positive were more likely to experience GD, particularly in insurance, family, and social settings. Younger individuals were more likely to experience discrimination in the insurance setting. Overall, highly educated individuals were also more likely to report discrimination. These results provide direction for clinical and family discussions, counseling practice, and policy aimed at mitigating experiences of GD. PMID:21184581

Subjective memory complaint only relates to verbal episodic memory performance in mild cognitive impairment

PubMed Central

Gifford, Katherine A.; Liu, Dandan; Damon, Stephen M.; Chapman, William G.; Romano, Raymond R.; Samuels, Lauren R.; Lu, Zengqi; Jefferson, Angela L.

2015-01-01

Background A cognitive concern from the patient, informant, or clinician is required for the diagnosis of mild cognitive impairment (MCI); however, the cognitive and neuroanatomical correlates of complaint are poorly understood. Objective We assessed how self-complaint relates to cognitive and neuroimaging measures in older adults with MCI. Method MCI participants were drawn from the Alzheimer’s Disease Neuroimaging Initiative and dichotomized into two groups based on the presence of self-reported memory complaint (no complaint n=191, 77±7 years; complaint n=206, 73±8 years). Cognitive outcomes included episodic memory, executive functioning, information processing speed, and language. Imaging outcomes included regional lobar volumes (frontal, parietal, temporal, cingulate) and specific medial temporal lobe structures (hippocampal volume, entorhinal cortex thickness, parahippocampal gyrus thickness). Results Linear regressions, adjusting for age, gender, race, education, Mini-Mental State Examination score, mood, and apolipoprotein E-4 status, found that cognitive complaint related to immediate (β=−1.07, p<0.001) and delayed episodic memory performances assessed on a serial list learning task (β=−1.06, p=0.001) but no other cognitive measures or neuroimaging markers. Conclusions Self-reported memory concern was unrelated to structural neuroimaging markers of atrophy and measures of information processing speed, executive functioning, or language. In contrast, subjective memory complaint related to objective verbal episodic learning performance. Future research is warranted to better understand the relation between cognitive complaint and surrogate markers of abnormal brain aging, including Alzheimer’s disease, across the cognitive aging spectrum. PMID:25281602

Role of kinin B1 and B2 receptors in memory consolidation during the aging process of mice.

PubMed

Lemos, Mayra Tolentino Resk; Amaral, Fabio Agostini; Dong, Karis Ester; Bittencourt, Maria Fernanda Queiroz Prado; Caetano, Ariadiny Lima; Pesquero, João Bosco; Viel, Tania Araujo; Buck, Hudson Sousa

2010-04-01

Under physiological conditions, elderly people present memory deficit associated with neuronal loss. This pattern is also associated with Alzheimer's disease but, in this case, in a dramatically intensified level. Kinin receptors have been involved in neurodegeneration and increase of amyloid-beta concentration, associated with Alzheimer's disease (AD). Considering these findings, this work evaluated the role of kinin receptors in memory consolidation during the aging process. Male C57Bl/6 (wt), knock-out B1 (koB1) or B2 (koB2) mice (3, 6, 12 and 18-month-old - mo; n=10 per group) were submitted to an acquisition session, reinforcement to learning (24h later: test 1) and final test (7days later: test 2), in an active avoidance apparatus, to evaluate memory. Conditioned avoidance responses (CAR, % of 50 trials) were registered. In acquisition sessions, similar CAR were obtained among age matched animals from all strains. However, a significant decrease in CAR was observed throughout the aging process (3mo: 8.8+/-2.3%; 6mo: 4.1+/-0.6%; 12mo: 2.2+/-0.6%, 18mo: 3.6+/-0.6%, P<0.01), indicating a reduction in the learning process. In test 1, as expected, memory retention increased significantly (P<0.05) in all 3- and 6-month-old animals as well as in 12-month-old-wt and 12-month-old-koB1 (P<0.01), compared to the training session. However, 12-month-old-koB2 and all 18-month-old animals did not show an increase in memory retention. In test 2, 3- and 6-month-old wt and koB1 mice of all ages showed a significant improvement in memory (P<0.05) compared to test 1. However, 12-month-old wt and koB2 mice of all ages showed no difference in memory retention. We suggest that, during the aging process, the B1 receptor could be involved in neurodegeneration and memory loss. Nevertheless, the B2 receptor is apparently acting as a neuroprotective factor. Copyright 2009 Elsevier Ltd. All rights reserved.

Strategic Decision-Making Learning from Label Distributions: An Approach for Facial Age Estimation.

PubMed

Zhao, Wei; Wang, Han

2016-06-28

Nowadays, label distribution learning is among the state-of-the-art methodologies in facial age estimation. It takes the age of each facial image instance as a label distribution with a series of age labels rather than the single chronological age label that is commonly used. However, this methodology is deficient in its simple decision-making criterion: the final predicted age is only selected at the one with maximum description degree. In many cases, different age labels may have very similar description degrees. Consequently, blindly deciding the estimated age by virtue of the highest description degree would miss or neglect other valuable age labels that may contribute a lot to the final predicted age. In this paper, we propose a strategic decision-making label distribution learning algorithm (SDM-LDL) with a series of strategies specialized for different types of age label distribution. Experimental results from the most popular aging face database, FG-NET, show the superiority and validity of all the proposed strategic decision-making learning algorithms over the existing label distribution learning and other single-label learning algorithms for facial age estimation. The inner properties of SDM-LDL are further explored with more advantages.

Strategic Decision-Making Learning from Label Distributions: An Approach for Facial Age Estimation

PubMed Central

Zhao, Wei; Wang, Han

2016-01-01

Nowadays, label distribution learning is among the state-of-the-art methodologies in facial age estimation. It takes the age of each facial image instance as a label distribution with a series of age labels rather than the single chronological age label that is commonly used. However, this methodology is deficient in its simple decision-making criterion: the final predicted age is only selected at the one with maximum description degree. In many cases, different age labels may have very similar description degrees. Consequently, blindly deciding the estimated age by virtue of the highest description degree would miss or neglect other valuable age labels that may contribute a lot to the final predicted age. In this paper, we propose a strategic decision-making label distribution learning algorithm (SDM-LDL) with a series of strategies specialized for different types of age label distribution. Experimental results from the most popular aging face database, FG-NET, show the superiority and validity of all the proposed strategic decision-making learning algorithms over the existing label distribution learning and other single-label learning algorithms for facial age estimation. The inner properties of SDM-LDL are further explored with more advantages. PMID:27367691

Preservation of musical memory and engagement in healthy aging and Alzheimer's disease.

PubMed

Cuddy, Lola L; Sikka, Ritu; Vanstone, Ashley

2015-03-01

In striking contrast to the difficulties with new learning and episodic memories in aging and especially in Alzheimer's disease (AD), musical long-term memories appear to be largely preserved. Evidence for spared musical memories in aging and AD is reviewed here. New data involve the development of a Musical Engagement Questionnaire especially designed for use with AD patients. The questionnaire assesses behavioral responses to music and is answered by the care partner. Current results show that, despite cognitive loss, persons with mild to moderate AD preserve musical engagement and music seeking. Familiar music evokes personal autobiographical memories for healthy younger and older adults as well and for those with mild to moderate AD. It is argued that music is a prime candidate for being a stimulus for cognitive stimulation because musical memories and associated emotions may be readily evoked; that is, they are strong and do not need to be repaired. Working with and through music as a resource may enhance social and communication functions. © 2015 New York Academy of Sciences.

[Rational balanced nutrition of schoolchildren of various age groups].

PubMed

Kulikova, N V; Samolyuk, N G; Fedotov, A S; Krotenko, N M

2013-01-01

The problem of nutrition of schoolchildren as the main index of health status is considered. Recommendations for implementation of correction system of school feeding in conditions of Siberia will be presented. The purpose of work: on the basis of the results of monitoring living activity and assessment of the health of schoolchildren of different age groups in Siberia to develop guidelines on the rational balanced nutrition. Studies bear witness to inadequate diet and regimen of feeding of schoolchildren. In Siberia a progressive deterioration in the health of students during the years of learning is observed, part of diseases is associated with an unbalanced diet. We offer the project, in course of realization of which study in schools are carried out, scientifically grounded recommendations on appropriate diet and regimen of feeding for schoolchildren of different age groups in the Siberia in the cold and warm period of the year are developed. Implementation of recommendations will result in the general improvement of children health and reduction in medical aid appealability due to diseases of the gastrointestinal tract.

Cognitive components underpinning the development of model-based learning.

PubMed

Potter, Tracey C S; Bryce, Nessa V; Hartley, Catherine A

2017-06-01

Reinforcement learning theory distinguishes "model-free" learning, which fosters reflexive repetition of previously rewarded actions, from "model-based" learning, which recruits a mental model of the environment to flexibly select goal-directed actions. Whereas model-free learning is evident across development, recruitment of model-based learning appears to increase with age. However, the cognitive processes underlying the development of model-based learning remain poorly characterized. Here, we examined whether age-related differences in cognitive processes underlying the construction and flexible recruitment of mental models predict developmental increases in model-based choice. In a cohort of participants aged 9-25, we examined whether the abilities to infer sequential regularities in the environment ("statistical learning"), maintain information in an active state ("working memory") and integrate distant concepts to solve problems ("fluid reasoning") predicted age-related improvements in model-based choice. We found that age-related improvements in statistical learning performance did not mediate the relationship between age and model-based choice. Ceiling performance on our working memory assay prevented examination of its contribution to model-based learning. However, age-related improvements in fluid reasoning statistically mediated the developmental increase in the recruitment of a model-based strategy. These findings suggest that gradual development of fluid reasoning may be a critical component process underlying the emergence of model-based learning. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Active-Learning Implementation in an Advanced Elective Course on Infectious Diseases

PubMed Central

Patel, Shreya; Veltri, Keith

2012-01-01

Objectives. To describe the development, implementation, and assessment of an advanced elective course on infectious diseases using active-learning strategies. Design. Pedagogy for active learning was incorporated by means of mini-lecture, journal club, and debate with follow-up discussion. Forty-eight students were enrolled in this 4-week elective course, in which 30% of course time was allocated for active-learning exercises. All activities were fundamentally designed as a stepwise approach in complementing each active-learning exercise. Assessment. Achievement of the course learning objectives was assessed using a 5-point Likert scale survey instrument. Students’ awareness of the significance of antimicrobial resistance was improved (p ≤ 0.05). Students’ ability to critically evaluate the infectious-disease literature and its application in informed clinical judgments was also enhanced through these active-learning exercises (p ≤ 0.05). Students agreed that active learning should be part of the pharmacy curriculum and that active-learning exercises improved their critical-thinking, literature-evaluation, and self-learning skills. Conclusion. An elective course using active-learning strategies allowed students to combine information gained from the evaluation of infectious-disease literature, critical thinking, and informed clinical judgment. This blended approach ultimately resulted in an increased knowledge and awareness of infectious diseases. PMID:22761528

Dopamine selectively remediates 'model-based' reward learning: a computational approach.

PubMed

Sharp, Madeleine E; Foerde, Karin; Daw, Nathaniel D; Shohamy, Daphna

2016-02-01

Patients with loss of dopamine due to Parkinson's disease are impaired at learning from reward. However, it remains unknown precisely which aspect of learning is impaired. In particular, learning from reward, or reinforcement learning, can be driven by two distinct computational processes. One involves habitual stamping-in of stimulus-response associations, hypothesized to arise computationally from 'model-free' learning. The other, 'model-based' learning, involves learning a model of the world that is believed to support goal-directed behaviour. Much work has pointed to a role for dopamine in model-free learning. But recent work suggests model-based learning may also involve dopamine modulation, raising the possibility that model-based learning may contribute to the learning impairment in Parkinson's disease. To directly test this, we used a two-step reward-learning task which dissociates model-free versus model-based learning. We evaluated learning in patients with Parkinson's disease tested ON versus OFF their dopamine replacement medication and in healthy controls. Surprisingly, we found no effect of disease or medication on model-free learning. Instead, we found that patients tested OFF medication showed a marked impairment in model-based learning, and that this impairment was remediated by dopaminergic medication. Moreover, model-based learning was positively correlated with a separate measure of working memory performance, raising the possibility of common neural substrates. Our results suggest that some learning deficits in Parkinson's disease may be related to an inability to pursue reward based on complete representations of the environment. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Learning about Your Disease

MedlinePlus

... del paciente Transplant process Diseases treated by transplant Acute myeloid leukemia Adrenoleukodystrophy (ALD) Chronic Lymphocytic Leukemia (CLL) ... SCID) Sickle cell disease (SCD) Wiskott-Aldrich syndrome Acute lymphoblastic leukemia (ALL) Other diseases Treatment decisions Learn ...

Motor Sequence Learning Performance in Parkinson's Disease Patients Depends on the Stage of Disease

ERIC Educational Resources Information Center

Stephan, Marianne A.; Meier, Beat; Zaugg, Sabine Weber; Kaelin-Lang, Alain

2011-01-01

It is still unclear, whether patients with Parkinson's disease (PD) are impaired in the incidental learning of different motor sequences in short succession, although such a deficit might greatly impact their daily life. The aim of this study was thus to clarify the relation between disease parameters of PD and incidental motor learning of two…

The surgical learning and instructional portfolio: what residents at a single institution are learning.

PubMed

Webb, Travis P; Merkley, Taylor R

2011-03-01

The Accreditation Council for Graduate Medical Education (ACGME) Learning Portfolio is recommended as a tool to develop and document reflective, practice-based learning and improvement. There is no consensus regarding the appropriate content of a learning portfolio in medical education. Studying lessons selected for inclusion in their learning portfolios by surgical trainees could help identify useful subject matter for this purpose. Each month, all residents in our surgery residency program submit entries into their individual Surgical Learning and Instructional Portfolio (SLIP). The SLIP entries from July 2008 to 2009 (n = 420) were deidentified and randomized using a random number generator. We conducted a thematic content analysis of 50 random portfolio entries to identify lessons learned. Two independent raters analyzed the "3 lessons learned" portion of the portfolio entries and identified themes and subthemes using the constant comparative method used in grounded theory. The collaborative coding process resulted in theme saturation after the identification of 7 themes and their subthemes. Themes in decreasing order of frequency included complications, disease epidemiology, disease presentation, surgical management of disease, medical management of disease, operative techniques, and pathophysiology. Junior residents chose to focus on a broad array of foundational topics including disease presentation, epidemiology, and overall management of diseases, whereas postgraduate year-4 (PGY-4) and PGY-5 residents most frequently chose to focus on complications as learning points. Lessons learned reflect perceived needs of the trainees based on training year. When given a template to follow, junior and senior residents choose to reflect on different subject matter to meet their learning goals.

Optimizing associated liver partition and portal vein ligation for staged hepatectomy outcomes: Surgical experience or appropriate patient selection?

PubMed Central

Al Hasan, Ibrahim; Tun-Abraham, Mauro Enrique; Wanis, Kerollos N.; Garcia-Ochoa, Carlos; Levstik, Mark A.; Al-Judaibi, Bandar; Hernandez-Alejandro, Roberto

2017-01-01

Background Early reports of associated liver partition and portal vein ligation for staged hepatectomy (ALPPS) outcomes have been suboptimal. The literature has confirmed that learning curves influence surgical outcomes. We have 54 months of continuous experience performing ALPPS with strict selection criteria. This study aimed to evaluate the impact of the learning curve on ALPPS outcomes. Methods We retrospectively compared patients who underwent ALPPS between April 2012 and March 2016. Patients were grouped into 2 24-month (early and late) periods. All candidates had a high tumour load requiring staged hepatectomy after chemotherapy response, a predicted future liver remnant (FLR) less than 30% and good performance status. Results Thirty-three patients underwent ALPPS during the study period: 16 in the early group (median age 65 yr, mean body mass index [BMI] 27) and 17 in the late group (median age 60 yr, mean BMI 25). Bilobar disease was comparable in both groups (94% v. 88%, p > 0.99). Duration of surgery was not statistically different. Intraoperative blood loss and need for transfusion were significantly lower in the late group (200 ± 109 mL v. 100 ± 43 mL, p < 0.05). The late group had a higher proportion of monosegment ALPPS (4:1). There were no deaths within 90 days in either cohort. Rates of postoperative complications were not statistically significant between groups. The R0 resection rate was similar. The entire 1-year disease-free and overall survival were 52% and 84%, respectively. Conclusion Excellent results can be obtained in innovative complex surgery with careful patient selection and good technical skills. Additionally, the learning curve brought confidence to perform more complex procedures while maintaining good outcomes. PMID:29173259

The selective positive allosteric M1 muscarinic receptor modulator PQCA attenuates learning and memory deficits in the Tg2576 Alzheimer's disease mouse model.

PubMed

Puri, Vanita; Wang, Xiaohai; Vardigan, Joshua D; Kuduk, Scott D; Uslaner, Jason M

2015-01-01

We have recently shown that the M1 muscarinic receptor positive allosteric modulator, PQCA, improves cognitive performance in rodents and non-human primates administered the muscarinic receptor antagonist scopolamine. The purpose of the present experiments was to characterize the effects of PQCA in a model more relevant to the disease pathology of Alzheimer's disease. Tg2576 transgenic mice that have elevated Aβ were tested in the novel object recognition task to characterize recognition memory as a function of age and treatment with the PQCA. The effects of PQCA were compared to the acetylcholinesterase inhibitor donepezil, the standard of care for Alzheimer's disease. In addition, the effect of co-administering PQCA and donepezil was evaluated. Aged Tg2576 mice demonstrated a deficit in recognition memory that was significantly attenuated by PQCA. The positive control donepezil also reversed the deficit. Furthermore, doses of PQCA and donepezil that were inactive on their own were found to improve recognition memory when given together. These studies suggest that M1 muscarinic receptor positive allosteric modulation can ameliorate memory deficits in disease relevant models of Alzheimer's disease. These data, combined with our previous findings demonstrating PQCA improves scopolamine-induced cognitive deficits in both rodents and non-human primates, suggest that M1 positive allosteric modulators have therapeutic potential for the treatment of Alzheimer's disease. Copyright © 2015 Elsevier B.V. All rights reserved.

Are There Age-Related Differences in the Ability to Learn Configural Responses?

PubMed Central

Clark, Rachel; Freedberg, Michael; Hazeltine, Eliot; Voss, Michelle W.

2015-01-01

Age is often associated with a decline in cognitive abilities that are important for maintaining functional independence, such as learning new skills. Many forms of motor learning appear to be relatively well preserved with age, while learning tasks that involve associative binding tend to be negatively affected. The current study aimed to determine whether age differences exist on a configural response learning task, which includes aspects of motor learning and associative binding. Young (M = 24 years) and older adults (M = 66.5 years) completed a modified version of a configural learning task. Given the requirement of associative binding in the configural relationships between responses, we predicted older adults would show significantly less learning than young adults. Older adults demonstrated lower performance (slower reaction time and lower accuracy). However, contrary to our prediction, older adults showed similar rates of learning as indexed by a configural learning score compared to young adults. These results suggest that the ability to acquire knowledge incidentally about configural response relationships is largely unaffected by cognitive aging. The configural response learning task provides insight into the task demands that constrain learning abilities in older adults. PMID:26317773

Calorie Restriction and Aging in Nonhuman Primates

PubMed Central

Kemnitz, Joseph W.

2012-01-01

In the 75 years since the seminal observation of Clive McCay that restriction of calorie intake extends the lifespan of rats, a great deal has been learned about the effects of calorie restriction (CR; reduced intake of a nutritious diet) on aging in various short-lived animal models. Studies have demonstrated many beneficial effects of CR on health, the rate of aging, and longevity. Two prospective investigations of the effects of CR on long-lived nonhuman primate (NHP) species began nearly 25 years ago and are still under way. This review presents the design, methods, and main findings of these and other important contributing studies, which have generally revealed beneficial effects of CR on physiological function and the retardation of disease consistent with studies in other species. Specifically, prolonged CR appears to extend the lifespan of rhesus monkeys, which exhibited lower body fat; slower rate of muscle loss with age; lower incidence of neoplasia, cardiovascular disease, type 2 diabetes mellitus, and endometriosis; improved insulin sensitivity and glucose tolerance; and no apparent adverse effect on bone health, as well as a reduction in total energy expenditure. In addition, there are no reports of deleterious effects of CR on reproductive endpoints, and brain morphology is preserved by CR. Adrenal and thyroid hormone profiles are inconsistently affected. More research is needed to delineate the mechanisms of the desirable outcomes of CR and to develop interventions that can produce similar beneficial outcomes for humans. This research offers tremendous potential for producing novel insights into aging and risk of disease. PMID:21411859

Curcuma longa L. extract improves the cortical neural connectivity during the aging process

PubMed Central

Flores, Gonzalo

2017-01-01

Turmeric or Curcuma is a natural product that has anti-inflammatory, antioxidant and anti-apoptotic pharmacological properties. It can be used in the control of the aging process that involves oxidative stress, inflammation, and apoptosis. Aging is a physiological process that affects higher cortical and cognitive functions with a reduction in learning and memory, limited judgment and deficits in emotional control and social behavior. Moreover, aging is a major risk factor for the appearance of several disorders such as cerebrovascular disease, diabetes mellitus, and hypertension. At the brain level, the aging process alters the synaptic intercommunication by a reduction in the dendritic arbor as well as the number of the dendritic spine in the pyramidal neurons of the prefrontal cortex, hippocampus and basolateral amygdala, consequently reducing the size of these regions. The present review discusses the synaptic changes caused by the aging process and the neuroprotective role the Curcuma has through its anti-inflammatory, antioxidant and anti-apoptotic actions PMID:28761413

Suitability of asthma education materials for school-age children: Implications for health literacy.

PubMed

Tzeng, Yu-Fen; Gau, Bih-Shya

2018-03-01

To investigate the suitability of asthma education materials for school-age children with asthma and elucidate how these children used their health-literacy abilities to identify whether the materials can be accepted, comprehended and applied. Effective asthma self-management education is influenced by the suitability of materials and an individual's health literacy. A mixed-method research design was developed using quantitative and qualitative surveys. The suitability of the materials was assessed on the basis of the Chinese version of the Suitability Assessment of Materials by five experts. In addition, five school-age children (age: 8-12 years) were recruited and interviewed. In total, 25 pieces of asthma education material for children were collected. On the basis of their type, the materials were categorised as nine brochures, 11 leaflets and five videos. Of the 25 materials, 17 were rated as superior materials, whereas eight were rated as adequate materials. The suitability scores of the video-based materials were significantly higher than those of the brochures and leaflets (p = .006). One print material was considered to have a reading level suitable for fifth-grade or younger children, whereas the remaining materials were considered suitable for sixth-grade or older children. The following six health-literacy domains were identified: recognising asthma through body knowledge, posing reflective questions, identifying self-care difficulties, receiving adult guidance, learning with enjoyment and addressing learning requirements. The video-based materials had integrated content and were appealing to children. Cartoon animations, interactive computer games, and skill demonstrations may enhance learning stimulation and motivation and increase learning effects in children. The present results may help healthcare providers to understand children's capacities to manage their disease, effectively address children's requirements and function as a key resource for children to strengthen their literacy in asthma management. © 2017 John Wiley & Sons Ltd.

Adult Age Differences in Learning from Positive and Negative Probabilistic Feedback

PubMed Central

Simon, Jessica R.; Howard, James H.; Howard, Darlene V.

2010-01-01

Objective Past research has investigated age differences in frontal-based decision making, but few studies have focused on the behavioral effects of striatal-based changes in healthy aging. Feedback learning has been found to vary with dopamine levels; increases in dopamine facilitate learning from positive feedback, whereas decreases facilitate learning from negative feedback. Given previous evidence of striatal dopamine depletion in healthy aging, we investigated behavioral differences between college-aged and healthy old adults using a feedback learning task that is sensitive to both frontal and striatal processes. Method Seventeen college-aged (M = 18.9 years) and 24 healthy, older adults (M = 70.3 years) completed the Probabilistic selection task, in which participants are trained on probabilistic stimulus-outcome information and then tested to determine whether they learned more from positive or negative feedback. Results As a group, the old adults learned equally well from positive and negative feedback, whereas the college-aged group learned more from positive than negative feedback, F(1, 39) = 4.10, p < .05, reffect = .3. However, these group differences were not due to the older individuals being more balanced learners. Most individuals of both ages were balanced learners, but while all of the remaining young learners had a positive bias, the remaining older learners were split between those with positive and negative learning biases (χ2(2) = 6.12, p<.047). Conclusions These behavioral results are consistent with the dopamine theory of striatal aging, and suggest there might be adult age differences in the kinds of information people use when faced with a current choice. PMID:20604627

Learning and memory in disease vector insects

PubMed Central

Vinauger, Clément; Lahondère, Chloé; Cohuet, Anna; Lazzari, Claudio R.; Riffell, Jeffrey A.

2016-01-01

Learning and memory plays an important role in host preference and parasite transmission by disease vector insects. Historically there has been a dearth of standardized protocols that permit testing their learning abilities, thus limiting discussion on the potential epidemiological consequences of learning and memory to a largely speculative extent. However, with increasing evidence that individual experience and associative learning can affect processes such as oviposition site selection and host preference, it is timely to review the recently acquired knowledge, identify research gaps and discuss the implication of learning in disease vector insects in perspective with control strategies. PMID:27450224

Cognitive Components Underpinning the Development of Model-Based Learning

PubMed Central

Potter, Tracey C.S.; Bryce, Nessa V.; Hartley, Catherine A.

2016-01-01

Reinforcement learning theory distinguishes “model-free” learning, which fosters reflexive repetition of previously rewarded actions, from “model-based” learning, which recruits a mental model of the environment to flexibly select goal-directed actions. Whereas model-free learning is evident across development, recruitment of model-based learning appears to increase with age. However, the cognitive processes underlying the development of model-based learning remain poorly characterized. Here, we examined whether age-related differences in cognitive processes underlying the construction and flexible recruitment of mental models predict developmental increases in model-based choice. In a cohort of participants aged 9–25, we examined whether the abilities to infer sequential regularities in the environment (“statistical learning”), maintain information in an active state (“working memory”) and integrate distant concepts to solve problems (“fluid reasoning”) predicted age-related improvements in model-based choice. We found that age-related improvements in statistical learning performance did not mediate the relationship between age and model-based choice. Ceiling performance on our working memory assay prevented examination of its contribution to model-based learning. However, age-related improvements in fluid reasoning statistically mediated the developmental increase in the recruitment of a model-based strategy. These findings suggest that gradual development of fluid reasoning may be a critical component process underlying the emergence of model-based learning. PMID:27825732

Dual-modality impairment of implicit learning of letter-strings versus color-patterns in patients with schizophrenia.

PubMed

Chiu, Ming-Jang; Liu, Kristina; Hsieh, Ming H; Hwu, Hai-Gwo

2005-12-12

Implicit learning was reported to be intact in schizophrenia using artificial grammar learning. However, emerging evidence indicates that artificial grammar learning is not a unitary process. The authors used dual coding stimuli and schizophrenia clinical symptom dimensions to re-evaluate the effect of schizophrenia on various components of artificial grammar learning. Letter string and color pattern artificial grammar learning performances were compared between 63 schizophrenic patients and 27 comparison subjects. Four symptom dimensions derived from a Chinese Positive and Negative Symptom Scale ratings were correlated with patients' artificial grammar implicit learning performances along the two stimulus dimensions. Patients' explicit memory performances were assessed by verbal paired associates and visual reproduction subtests of the Wechsler Memory Scales Revised Version to provide a contrast to their implicit memory function. Schizophrenia severely hindered color pattern artificial grammar learning while the disease affected lexical string artificial grammar learning to a lesser degree after correcting the influences from age, education and the performance of explicit memory function of both verbal and visual modalities. Both learning performances correlated significantly with the severity of patients' schizophrenic clinical symptom dimensions that reflect poor abstract thinking, disorganized thinking, and stereotyped thinking. The results of this study suggested that schizophrenia affects various mechanisms of artificial grammar learning differently. Implicit learning, knowledge acquisition in the absence of conscious awareness, is not entirely intact in patients with schizophrenia. Schizophrenia affects implicit learning through an impairment of the ability of making abstractions from rules and at least in part decreasing the capacity for perceptual learning.

The Surgical Learning and Instructional Portfolio: What Residents at a Single Institution Are Learning

PubMed Central

Webb, Travis P; Merkley, Taylor R

2011-01-01

Background The Accreditation Council for Graduate Medical Education (ACGME) Learning Portfolio is recommended as a tool to develop and document reflective, practice-based learning and improvement. There is no consensus regarding the appropriate content of a learning portfolio in medical education. Studying lessons selected for inclusion in their learning portfolios by surgical trainees could help identify useful subject matter for this purpose. Methods Each month, all residents in our surgery residency program submit entries into their individual Surgical Learning and Instructional Portfolio (SLIP). The SLIP entries from July 2008 to 2009 (n = 420) were deidentified and randomized using a random number generator. We conducted a thematic content analysis of 50 random portfolio entries to identify lessons learned. Two independent raters analyzed the “3 lessons learned” portion of the portfolio entries and identified themes and subthemes using the constant comparative method used in grounded theory. Results The collaborative coding process resulted in theme saturation after the identification of 7 themes and their subthemes. Themes in decreasing order of frequency included complications, disease epidemiology, disease presentation, surgical management of disease, medical management of disease, operative techniques, and pathophysiology. Junior residents chose to focus on a broad array of foundational topics including disease presentation, epidemiology, and overall management of diseases, whereas postgraduate year-4 (PGY-4) and PGY-5 residents most frequently chose to focus on complications as learning points. Conclusions Lessons learned reflect perceived needs of the trainees based on training year. When given a template to follow, junior and senior residents choose to reflect on different subject matter to meet their learning goals. PMID:22379531

Rapamycin rescues vascular, metabolic and learning deficits in apolipoprotein E4 transgenic mice with pre-symptomatic Alzheimer's disease.

PubMed

Lin, Ai-Ling; Jahrling, Jordan B; Zhang, Wei; DeRosa, Nicholas; Bakshi, Vikas; Romero, Peter; Galvan, Veronica; Richardson, Arlan

2017-01-01

Apolipoprotein E ɛ4 allele is a common susceptibility gene for late-onset Alzheimer's disease. Brain vascular and metabolic deficits can occur in cognitively normal apolipoprotein E ɛ4 carriers decades before the onset of Alzheimer's disease. The goal of this study was to determine whether early intervention using rapamycin could restore neurovascular and neurometabolic functions, and thus impede pathological progression of Alzheimer's disease-like symptoms in pre-symptomatic Apolipoprotein E ɛ4 transgenic mice. Using in vivo, multimodal neuroimaging, we found that apolipoprotein E ɛ4 mice treated with rapamycin had restored cerebral blood flow, blood-brain barrier integrity and glucose metabolism, compared to age- and gender-matched wild-type controls. The preserved vasculature and metabolism were associated with amelioration of incipient learning deficits. We also found that rapamycin restored the levels of the proinflammatory cyclophilin A in vasculature, which may contribute to the preservation of cerebrovascular function in the apolipoprotein E ɛ4 transgenics. Our results show that rapamycin improves functional outcomes in this mouse model and may have potential as an effective intervention to block progression of vascular, metabolic and early cognitive deficits in human Apolipoprotein E ɛ4 carriers. As rapamycin is FDA-approved and neuroimaging is readily used in humans, the results of the present study may provide the basis for future Alzheimer's disease intervention studies in human subjects. © The Author(s) 2015.

Application of Machine Learning in Postural Control Kinematics for the Diagnosis of Alzheimer's Disease

PubMed Central

Yelshyna, Darya; Bicho, Estela

2016-01-01

The use of wearable devices to study gait and postural control is a growing field on neurodegenerative disorders such as Alzheimer's disease (AD). In this paper, we investigate if machine-learning classifiers offer the discriminative power for the diagnosis of AD based on postural control kinematics. We compared Support Vector Machines (SVMs), Multiple Layer Perceptrons (MLPs), Radial Basis Function Neural Networks (RBNs), and Deep Belief Networks (DBNs) on 72 participants (36 AD patients and 36 healthy subjects) exposed to seven increasingly difficult postural tasks. The decisional space was composed of 18 kinematic variables (adjusted for age, education, height, and weight), with or without neuropsychological evaluation (Montreal cognitive assessment (MoCA) score), top ranked in an error incremental analysis. Classification results were based on threefold cross validation of 50 independent and randomized runs sets: training (50%), test (40%), and validation (10%). Having a decisional space relying solely on postural kinematics, accuracy of AD diagnosis ranged from 71.7 to 86.1%. Adding the MoCA variable, the accuracy ranged between 91 and 96.6%. MLP classifier achieved top performance in both decisional spaces. Having comprehended the interdynamic interaction between postural stability and cognitive performance, our results endorse machine-learning models as a useful tool for computer-aided diagnosis of AD based on postural control kinematics. PMID:28074090

Application of Machine Learning in Postural Control Kinematics for the Diagnosis of Alzheimer's Disease.

PubMed

Costa, Luís; Gago, Miguel F; Yelshyna, Darya; Ferreira, Jaime; David Silva, Hélder; Rocha, Luís; Sousa, Nuno; Bicho, Estela

2016-01-01

The use of wearable devices to study gait and postural control is a growing field on neurodegenerative disorders such as Alzheimer's disease (AD). In this paper, we investigate if machine-learning classifiers offer the discriminative power for the diagnosis of AD based on postural control kinematics. We compared Support Vector Machines (SVMs), Multiple Layer Perceptrons (MLPs), Radial Basis Function Neural Networks (RBNs), and Deep Belief Networks (DBNs) on 72 participants (36 AD patients and 36 healthy subjects) exposed to seven increasingly difficult postural tasks. The decisional space was composed of 18 kinematic variables (adjusted for age, education, height, and weight), with or without neuropsychological evaluation (Montreal cognitive assessment (MoCA) score), top ranked in an error incremental analysis. Classification results were based on threefold cross validation of 50 independent and randomized runs sets: training (50%), test (40%), and validation (10%). Having a decisional space relying solely on postural kinematics, accuracy of AD diagnosis ranged from 71.7 to 86.1%. Adding the MoCA variable, the accuracy ranged between 91 and 96.6%. MLP classifier achieved top performance in both decisional spaces. Having comprehended the interdynamic interaction between postural stability and cognitive performance, our results endorse machine-learning models as a useful tool for computer-aided diagnosis of AD based on postural control kinematics.

Examining the Effects of Age on Health Outcomes of Chronic Obstructive Pulmonary Disease: Results From the Genetic Epidemiology of Chronic Obstructive Pulmonary Disease Study and Evaluation of Chronic Obstructive Pulmonary Disease Longitudinally to Identify Predictive Surrogate Endpoints Cohorts.

PubMed

Parulekar, Amit D; Martinez, Carlos; Tsai, Chu-Lin; Locantore, Nicholas; Atik, Mustafa; Yohannes, Abebaw M; Kao, Christina C; Al-Azzawi, Hassan; Mohsin, Ali; Wise, Robert A; Foreman, Marilyn G; Demeo, Dawn L; Regan, Elizabeth A; Make, Barry J; Boriek, Aladin M; Wiener, Laura E; Hanania, Nicola A

2017-12-01

The prevalence of chronic obstructive pulmonary disease (COPD) and its associated comorbidities increase with age. However, little is understood about differences in the disease in patients over 65 years of age compared with younger patients. To determine disease characteristics of COPD and its impact in older patients compared with younger patients. We examined baseline characteristics of patients with COPD (global obstructive lung disease stage II-IV) in 2 large cohorts: Genetic Epidemiology of COPD Study (COPDGene) and Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE). We compared demographics, indices of disease severity, prevalence of comorbidities, exacerbation frequency, and quality of life scores in patients ≥65 years of age vs patients <65 years of age. We also tested for associations of age with disease characteristics and health outcomes. In the COPDGene cohort, older patients (n = 1663) had more severe disease as measured by forced expiratory volume in 1 second (1.22 vs 1.52 L, P < .001), use of long-term oxygen therapy (35% vs 22%, P < .001), 6-minute walk distance (355 vs 375 m, P < .001), and radiographic evidence of emphysema (14% vs 8%, P < .001) and air trapping (47% vs 36%, P < .001) and were more likely to have comorbidities compared with younger patients (n = 2027). Similarly, in the ECLIPSE cohort, older patients (n = 1030) had lower forced expiratory volume in 1 second (1.22 vs 1.34 L, P < .001), greater use of long-term oxygen therapy (7% vs 5%, P = .02), shorter 6- minute walk distance (360 vs 389 m, P < .001), and more radiographic evidence of emphysema (17% vs 14%, P = .009) than younger patients (n = 1131). In adjusted analyses of both cohorts, older age was associated with decreased frequency of exacerbations [odds ratio = 0.52, 95% confidence interval (CI) = 0.43-0.64 in COPDGene, odds ratio = 0.79, 95% CI = 0.64-0.99 in ECLIPSE] and a better quality of life (lower St. Georges respiratory questionnaire score) (β = -8.7, 95% CI = -10.0 to -7.4 in COPDGene, β = -4.4, 95% CI = -6.1 to -3.2 in ECLIPSE). Despite greater severity of illness, older patients with COPD had better quality of life and reported fewer exacerbations than younger patients. Although this observation needs to be explored further, it may be related to the fact that older patients change their expectations and learn to adapt to their disease. Copyright © 2017 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

How Explicit and Implicit Test Instructions in an Implicit Learning Task Affect Performance

PubMed Central

Witt, Arnaud; Puspitawati, Ira; Vinter, Annie

2013-01-01

Typically developing children aged 5 to 8 years were exposed to artificial grammar learning. Following an implicit exposure phase, half of the participants received neutral instructions at test while the other half received instructions making a direct, explicit reference to the training phase. We first aimed to assess whether implicit learning operated in the two test conditions. We then evaluated the differential impact of age on learning performances as a function of test instructions. The results showed that performance did not vary as a function of age in the implicit instructions condition, while age effects emerged when explicit instructions were employed at test. However, performance was affected differently by age and the instructions given at test, depending on whether the implicit learning of short or long units was assessed. These results suggest that the claim that the implicit learning process is independent of age needs to be revised. PMID:23326409

A Mapping Study on Mobile Games for Patients of Chronic Diseases.

PubMed

de Sá, Kévin Cardoso; Martins, Márcio Garcia; da Costa, Cristiano André; Barbosa, Jorge Luis Victoria; da Rosa Righi, Rodrigo

2017-09-01

There is a growing interest of using technologies to propose solutions for healthcare issues. One of such issues is the incidence of chronic diseases, which are responsible for a considerable proportion of worldwide mortality. It is possible to prevent the development of such diseases using tools and methods that instruct the population. To achieve this, mobile games provide a powerful environment for teaching different subjects to user, without them actively knowing that they are learning new concepts. Despite the growing interest of using mobile games in healthcare, more specifically by patients with chronic diseases, in the best of our knowledge there are no studies that address the current research being published in the area. To close this gap, we carried out a systematic mapping study to synthesize an overview of the area. Five databases were searched and more than 1200 studies were analyzed and filtered. Among them, 17 met the the inclusion and exclusion criteria defined in this work. The results show that there is still room for research in this area, since the studies focus on a younger audience rather than proposing solutions for all ages. Furthermore, the number of chronic conditions being addressed is still small, obesity and diabetes are prevalent. Besides, the full capacity of game features that foster learning through games are not being employed, the majority of games proposed by the articles encompass less than half of these features.

Do written mandatory accreditation standards for residential care positively model learning organizations? Textual and critical discourse analysis.

PubMed

Bell, Erica; Robinson, Andrew; See, Catherine

2013-11-01

Unprecedented global population ageing accompanied by increasing complexity of aged care present major challenges of quality in aged care. In the business literature, Senge's theory of adaptive learning organisations offers a model of organisational quality. However, while accreditation of national standards is an increasing mechanism for achieving quality in aged care, there are anecdotal concerns it creates a 'minimum standards compliance mentality' and no evidence about whether it reinforces learning organisations. The research question was 'Do mandatory national accreditation standards for residential aged care, as they are written, positively model learning organisations?'. Automatic text analysis was combined with critical discourse analysis to analyse the presence of learning concepts from Senge's learning organisation theory in an exhaustive sample of national accreditation standards from 7 countries. The two stages of analysis were: (1) quantitative mapping of the presence of learning organisation concepts in standards using Bayesian-based textual analytics software and (2) qualitative critical discourse analysis to further examine how the language of standards so identified may be modelling learning organisation concepts. The learning concepts 'training', 'development', 'knowledge', and 'systems' are present with relative frequencies of 19%, 11%, 10%, and 10% respectively in the 1944 instances, in paragraph-sized text blocks, considered. Concepts such as 'team', 'integration', 'learning', 'change' and 'innovation' occur with 7%, 6%, 5%, 5%, and 1% relative frequencies respectively. Learning concepts tend to co-occur with negative rather than positive sentiment language in the 3176 instances in text blocks containing sentiment language. Critical discourse analysis suggested that standards generally use the language of organisational change and learning in limited ways that appear to model 'learning averse' communities of practice and organisational cultures. The aged care quality challenge and the role of standards need rethinking. All standards implicitly or explicitly model an organisation of some type. If standards can model a limited and negative learning organisation language, they could model a well-developed and positive learning organisation language. In the context of the global aged care crisis, the modelling of learning organisations is probably critical for minimal competence in residential aged care and certainly achievable in the language of standards. Copyright © 2013 Elsevier Ltd. All rights reserved.

[Use of nondeclarative and automatic memory processes in motor learning: how to mitigate the effects of aging].

PubMed

Chauvel, Guillaume; Maquestiaux, François; Didierjean, André; Joubert, Sven; Dieudonné, Bénédicte; Verny, Marc

2011-12-01

Does normal aging inexorably lead to diminished motor learning abilities? This article provides an overview of the literature on the question, with particular emphasis on the functional dissociation between two sets of memory processes: declarative, effortful processes, and non-declarative, automatic processes. There is abundant evidence suggesting that aging does impair learning when past memories of former actions are required (episodic memory) and recollected through controlled processing (working memory). However, other studies have shown that aging does not impair learning when motor actions are performed non verbally and automatically (tapping procedural memory). These findings led us to hypothesize that one can minimize the impact of aging on the ability to learn new motor actions by favouring procedural learning. Recent data validating this hypothesis are presented. Our findings underline the importance of developing new motor learning strategies, which "bypass" declarative, effortful memory processes.

Gene-based association study of genes linked to hippocampal sclerosis of aging neuropathology: GRN, TMEM106B, ABCC9, and KCNMB2

PubMed Central

Katsumata, Yuriko; Nelson, Peter T.; Ellingson, Sally R.; Fardo, David W.

2017-01-01

Hippocampal sclerosis of aging (HS-Aging) is a common neurodegenerative condition associated with dementia. To learn more about genetic risk of HS-Aging pathology, we tested gene-based associations of the GRN, TMEM106B, ABCC9, and KCNMB2 genes, which were reported to be associated with HS-Aging pathology in previous studies. Genetic data were obtained from the Alzheimer’s Disease Genetics Consortium (ADGC), linked to autopsy-derived neuropathological outcomes from the National Alzheimer’s Coordinating Center (NACC). Of the 3,251 subjects included in the study, 271 (8.3%) were identified as an HS-Aging case. The significant gene-based association between the ABCC9 gene and HS-Aging appeared to be driven by a region in which a significant haplotype-based association was found. We tested this haplotype as an expression Quantitative Trait Locus (eQTL) using two different public-access brain gene expression databases. The HS-Aging pathology protective ABCC9 haplotype was associated with decreased ABCC9 expression, indicating a possible toxic gain of function. PMID:28131462

Autoimmune Manifestations in the 3xTg-AD Model of Alzheimer's Disease

PubMed Central

Marchese, Monica; Cowan, David; Head, Elizabeth; Ma, Donglai; Karimi, Khalil; Ashthorpe, Vanessa; Kapadia, Minesh; Zhao, Hui; Davis, Paulina; Sakic, Boris

2015-01-01

Background Immune system activation is frequently reported in patients with Alzheimer's disease (AD). However, it remains unknown whether this is a cause, a consequence, or an epiphenomenon of brain degeneration. Objective The present study examines whether immunological abnormalities occur in a well-established murine AD model and if so, how they relate temporally to behavioral deficits and neuropathology. Methods A broad battery of tests was employed to assess behavioral performance and autoimmune/inflammatory markers in 3xTg-AD (AD) mice and wild type controls from 1.5 to 12 months of age. Results Aged AD mice displayed severe manifestations of systemic autoimmune/inflammatory disease, as evidenced by splenomegaly, hepatomegaly, elevated serum levels of anti-nuclear/anti-dsDNA antibodies, low hematocrit, and increased number of double-negative T splenocytes. However, anxiety-related behavior and altered spleen function were evident as early as 2 months of age, thus preceding typical AD-like brain pathology. Moreover, AD mice showed altered olfaction and impaired “cognitive” flexibility in the first 6 months of life, suggesting mild cognitive impairment-like manifestations before general learning/memory impairments emerged at an older age. Interestingly, all of these features were present in 3xTg-AD mice prior to significant amyloid-β or tau pathology. Conclusion The results indicate that behavioral deficits in AD mice develop in parallel with systemic autoimmune/inflammatory disease. These changes antedate AD-like neuropathology, thus supporting a causal link between autoimmunity and aberrant behavior. Consequently, 3xTg-AD mice may be a useful model in elucidating the role of immune system in the etiology of AD. PMID:24150111

Distinct discrimination learning strategies and their relation with spatial memory and attentional control in 4- to 14-year-olds.

PubMed

Schmittmann, Verena D; van der Maas, Han L J; Raijmakers, Maartje E J

2012-04-01

Behavioral, psychophysiological, and neuropsychological studies have revealed large developmental differences in various learning paradigms where learning from positive and negative feedback is essential. The differences are possibly due to the use of distinct strategies that may be related to spatial working memory and attentional control. In this study, strategies in performing a discrimination learning task were distinguished in a cross-sectional sample of 302 children from 4 to 14 years of age. The trial-by-trial accuracy data were analyzed with mathematical learning models. The best-fitting model revealed three learning strategies: hypothesis testing, slow abrupt learning, and nonlearning. The proportion of hypothesis-testing children increased with age. Nonlearners were present only in the youngest age group. Feature preferences for the irrelevant dimension had a detrimental effect on performance in the youngest age group. The executive functions spatial working memory and attentional control significantly predicted posterior learning strategy probabilities after controlling for age. Copyright © 2011 Elsevier Inc. All rights reserved.

Apolipoprotein E4 Causes Age- and Sex-Dependent Impairments of Hilar GABAergic Interneurons and Learning and Memory Deficits in Mice

PubMed Central

Leung, Laura; Andrews-Zwilling, Yaisa; Yoon, Seo Yeon; Jain, Sachi; Ring, Karen; Dai, Jessica; Wang, Max Mu; Tong, Leslie; Walker, David; Huang, Yadong

2012-01-01

Apolipoprotein (apo) E4 is the major genetic risk factor for Alzheimer's disease (AD). ApoE4 has sex-dependent effects, whereby the risk of developing AD is higher in apoE4-expressing females than males. However, the mechanism underlying the sex difference, in relation to apoE4, is unknown. Previous findings indicate that apoE4 causes age-dependent impairments of hilar GABAergic interneurons in female mice, leading to learning and memory deficits. Here, we investigate whether the detrimental effects of apoE4 on hilar GABAergic interneurons are sex-dependent using apoE knock-in (KI) mice across different ages. We found that in female apoE-KI mice, there was an age-dependent depletion of hilar GABAergic interneurons, whereby GAD67- or somatostatin-positive–but not NPY- or parvalbumin-positive–interneuron loss was exacerbated by apoE4. Loss of these neuronal populations was correlated with the severity of spatial learning deficits at 16 months of age in female apoE4-KI mice; however, this effect was not observed in female apoE3-KI mice. In contrast, we found an increase in the numbers of hilar GABAergic interneurons with advancing age in male apoE-KI mice, regardless of apoE genotype. Moreover, male apoE-KI mice showed a consistent ratio of hilar inhibitory GABAergic interneurons to excitatory mossy cells approximating 1.5 that is independent of apoE genotype and age, whereas female apoE-KI mice exhibited an age-dependent decrease in this ratio, which was exacerbated by apoE4. Interestingly, there are no apoE genotype effects on GABAergic interneurons in the CA1 and CA3 subregions of the hippocampus as well as the entorhinal and auditory cortexes. These findings suggest that the sex-dependent effects of apoE4 on developing AD is in part attributable to inherent sex-based differences in the numbers of hilar GABAergic interneurons, which is further modulated by apoE genotype. PMID:23300939

A review of supervised machine learning applied to ageing research.

PubMed

Fabris, Fabio; Magalhães, João Pedro de; Freitas, Alex A

2017-04-01

Broadly speaking, supervised machine learning is the computational task of learning correlations between variables in annotated data (the training set), and using this information to create a predictive model capable of inferring annotations for new data, whose annotations are not known. Ageing is a complex process that affects nearly all animal species. This process can be studied at several levels of abstraction, in different organisms and with different objectives in mind. Not surprisingly, the diversity of the supervised machine learning algorithms applied to answer biological questions reflects the complexities of the underlying ageing processes being studied. Many works using supervised machine learning to study the ageing process have been recently published, so it is timely to review these works, to discuss their main findings and weaknesses. In summary, the main findings of the reviewed papers are: the link between specific types of DNA repair and ageing; ageing-related proteins tend to be highly connected and seem to play a central role in molecular pathways; ageing/longevity is linked with autophagy and apoptosis, nutrient receptor genes, and copper and iron ion transport. Additionally, several biomarkers of ageing were found by machine learning. Despite some interesting machine learning results, we also identified a weakness of current works on this topic: only one of the reviewed papers has corroborated the computational results of machine learning algorithms through wet-lab experiments. In conclusion, supervised machine learning has contributed to advance our knowledge and has provided novel insights on ageing, yet future work should have a greater emphasis in validating the predictions.

Broad-based visual benefits from training with an integrated perceptual-learning video game.

PubMed

Deveau, Jenni; Lovcik, Gary; Seitz, Aaron R

2014-06-01

Perception is the window through which we understand all information about our environment, and therefore deficits in perception due to disease, injury, stroke or aging can have significant negative impacts on individuals' lives. Research in the field of perceptual learning has demonstrated that vision can be improved in both normally seeing and visually impaired individuals, however, a limitation of most perceptual learning approaches is their emphasis on isolating particular mechanisms. In the current study, we adopted an integrative approach where the goal is not to achieve highly specific learning but instead to achieve general improvements to vision. We combined multiple perceptual learning approaches that have individually contributed to increasing the speed, magnitude and generality of learning into a perceptual-learning based video-game. Our results demonstrate broad-based benefits of vision in a healthy adult population. Transfer from the game includes; improvements in acuity (measured with self-paced standard eye-charts), improvement along the full contrast sensitivity function, and improvements in peripheral acuity and contrast thresholds. The use of this type of this custom video game framework built up from psychophysical approaches takes advantage of the benefits found from video game training while maintaining a tight link to psychophysical designs that enable understanding of mechanisms of perceptual learning and has great potential both as a scientific tool and as therapy to help improve vision. Copyright © 2014 Elsevier B.V. All rights reserved.

Amyloid-Related Memory Decline in Preclinical Alzheimer's Disease Is Dependent on APOE ε4 and Is Detectable over 18-Months.

PubMed

Thai, Christine; Lim, Yen Ying; Villemagne, Victor L; Laws, Simon M; Ames, David; Ellis, Kathryn A; Rainey-Smith, Stephanie R; Martins, Ralph N; Masters, Colin L; Rowe, Christopher C; Maruff, Paul

2015-01-01

High levels of β-amyloid (Aβ) in the brain and carriage of the APOE ε4 allele have each been linked to cognitive impairment in cognitively normal (CN) older adults. However, the relationship between these two biomarkers and cognitive decline is unclear. The aim of this study was to investigate the relationship between cerebral Aβ level, APOE ε4 carrier status, and cognitive decline over 18 months, in 317 cognitively healthy (CN) older adults (47.6% males, 52.4% females) aged between 60 and 89 years (Mean = 69.9, SD = 6.8). Cognition was assessed using the Cogstate Brief Battery (CBB) and the California Verbal Learning Test, Second Edition (CVLT-II). Planned comparisons indicated that CN older adults with high Aβ who were also APOE ε4 carriers demonstrated the most pronounced decline in learning and working memory. In CN older adults who were APOE ε4 non-carriers, high Aβ was unrelated to cognitive decline in learning and working memory. Carriage of APOE ε4 in CN older adults with low Aβ was associated with a significantly increased rate of decline in learning and unexpectedly, improved cognitive performance on measures of verbal episodic memory over 18 months. These results suggest that Aβ and APOE ε4 interact to increase the rate of cognitive decline in CN older adults and provide further support for the use of Aβ and APOE ε4 as biomarkers of early Alzheimer's disease.

Imidafenacin has no influence on learning in nucleus basalis of Meynert-lesioned rats.

PubMed

Yamazaki, Takanobu; Fukata, Ayako

2013-12-01

The prevalence of overactive bladder (OAB) and Alzheimer's disease (AD) increases with age, and much attention has been paid to the risk of cognitive impairment which may be induced by antimuscarinics used for OAB in patients with AD. Imidafenacin, an antimuscarinic agent for OAB treatment, has been reported not to affect learning in normal animals. However, under the condition in which sensitivity to learning impairment by antimuscarinics is increased, it remains unclear whether imidafenacin still does not impair the learning. Therefore, the influences of imidafenacin on passive avoidance response were investigated in sham-operated and nucleus basalis of Meynert (nbM)-lesioned rats and compared with oxybutynin hydrochloride and tolterodine tartrate. The learning-inhibitory doses of intravenous oxybutynin hydrochloride and tolterodine tartrate were 0.3 and 3 mg/kg in sham-operated rats and 0.1 and 1 mg/kg in nbM-lesioned rats, respectively. Thus, the learning impairments by those antimuscarinics were more sensitive in nbM-lesioned rats than in sham-operated rats. On the other hand, intravenous administration of imidafenacin had no influence on learning in either case of the rats. In normal rats, however, intracerebroventricular administration of imidafenacin impaired learning to the same degree as that of oxybutynin hydrochloride. Thus, the present study suggests that imidafenacin, unlike the other antimuscarinics used, has no significant risk of enhancing learning impairment even in models whose sensitivity to learning impairment by antimuscarinics is commonly increased, probably because of its low brain penetration.

The Impact of Age on Using Language Learning Strategies

ERIC Educational Resources Information Center

Sepasdar, Mansoreh; Soori, Afshin

2014-01-01

Since age plays an important role in learning a second or foreign language, the present study investigated how different students in different age groups used language learning strategies. The participants of this study were 94 Iranian EFL students from four educational levels and different age groups as, primary (10-12), guidance (13-15), high…

Learning Objects and Gerontology

ERIC Educational Resources Information Center

Weinreich, Donna M.; Tompkins, Catherine J.

2006-01-01

Virtual AGE (vAGE) is an asynchronous educational environment that utilizes learning objects focused on gerontology and a learning anytime/anywhere philosophy. This paper discusses the benefits of asynchronous instruction and the process of creating learning objects. Learning objects are "small, reusable chunks of instructional media" Wiley…

New twist on neuronal insulin receptor signaling in health, disease, and therapeutics.

PubMed

Wada, Akihiko; Yokoo, Hiroki; Yanagita, Toshihiko; Kobayashi, Hideyuki

2005-10-01

Long after the pioneering studies documenting the existence of insulin (year 1967) and insulin receptor (year 1978) in brain, the last decade has witnessed extraordinary progress in the understanding of brain region-specific multiple roles of insulin receptor signalings in health and disease. In the hypothalamus, insulin regulates food intake, body weight, peripheral fat deposition, hepatic gluconeogenesis, reproductive endocrine axis, and compensatory secretion of counter-regulatory hormones to hypoglycemia. In the hippocampus, insulin promotes learning and memory, independent of the glucoregulatory effect of insulin. Defective insulin receptor signalings are associated with the dementia in normal aging and patients with age-related neurodegenerative diseases (e.g., Alzheimer's disease); the cognitive impairment can be reversed with systemic administration of insulin in the euglycemic condition. Intranasal administration of insulin enhances memory and mood and decreases body weight in healthy humans, without causing hypoglycemia. In the hypothalamus, insulin-induced activation of the phosphoinositide 3-kinase pathway followed by opening of ATP-sensitive K+ channel has been shown to be related to multiple effects of insulin. However, the precise molecular mechanisms of insulin's pleiotropic effects still remain obscure. More importantly, much remains unknown about the quality control mechanisms ensuring correct conformational maturation of the insulin receptor, and the cellular mechanisms regulating density of cell surface functional insulin receptors.

Implicit learning in children and adults with Williams syndrome.

PubMed

Don, Audrey J; Schellenberg, E Glenn; Reber, Arthur S; DiGirolamo, Kristen M; Wang, Paul P

2003-01-01

In comparison to explicit learning, implicit learning is hypothesized to be a phylogenetically older form of learning that is important in early developmental processes (e.g., natural language acquisition, socialization)and relatively impervious to individual differences in age and IQ. We examined implicit learning in a group of children and adults (9.49 years of age)with Williams syndrome (WS)and in a comparison group of typically developing individuals matched for chronological age. Participants were tested in an artificial-grammar learning paradigm and in a rotor-pursuit task. For both groups, implicit learning was largely independent of age. Both groups showed evidence of implicit learning but the comparison group outperformed the WS group on both tasks. Performance advantages for the comparison group were no longer significant when group differences in working memory or nonverbal intelligence were held constant.

Subtle cognitive impairments in patients with long-term cure of Cushing's disease.

PubMed

Tiemensma, Jitske; Kokshoorn, Nieke E; Biermasz, Nienke R; Keijser, Bart-Jan S A; Wassenaar, Moniek J E; Middelkoop, Huub A M; Pereira, Alberto M; Romijn, Johannes A

2010-06-01

Active Cushing's disease is associated with cognitive impairments. We hypothesized that previous hypercortisolism in patients with Cushing's disease results in irreversible impairments in cognitive functioning. Therefore, our aim was to assess cognitive functioning after long-term cure of Cushing's disease. Cognitive assessment consisted of 11 tests, which evaluated global cognitive functioning, memory, and executive functioning. We included 74 patients cured of Cushing's disease and 74 controls matched for age, gender, and education. Furthermore, we included 54 patients previously treated for nonfunctioning pituitary macroadenomas (NFMA) and 54 controls matched for age, gender, and education. Compared with NFMA patients, patients cured from Cushing's disease had lower scores on the Mini Mental State Examination (P = 0.001), and on the memory quotient of the Wechsler Memory Scale (P = 0.050). Furthermore, patients cured from Cushing's disease tended to recall fewer words on the imprinting (P = 0.013), immediate recall (P = 0.012), and delayed recall (P = 0.003) trials of the Verbal Learning Test of Rey. On the Rey Complex Figure Test, patients cured from Cushing's disease had lower scores on both trials (P = 0.002 and P = 0.007) compared with NFMA patients. Patients cured from Cushing's disease also made fewer correct substitutions on the Letter-Digit Substitution Test (P = 0.039) and came up with fewer correct patterns on the Figure Fluency Test (P = 0.003) compared with treated NFMA patients. Cognitive function, reflecting memory and executive functions, is impaired in patients despite long-term cure of Cushing's disease. These observations indicate irreversible effects of previous hypercortisolism on cognitive function and, thus, on the central nervous system. These observations may also be of relevance for patients treated with high-dose exogenous glucocorticoids.

Isidore of Seville on the origins and meanings of medical terms.

PubMed

Dirckx, John H

2007-12-01

Early in the 7th century of our era, the prelate and scholar Isidore of Seville compiled a Latin encyclopedia of classical learning that retained its popularity throughout the Middle Ages and into early modern times. This work, called Origines seu Etymologiae, treats many of its topics by tracing (often fancifully and incorrectly) the histories of their terms. From Book IV, which deals with medicine, 3 chapters containing glossaries of acute, chronic, and cutaneous diseases are here translated.

Influence of Cognitive Functioning on Age-Related Performance Declines in Visuospatial Sequence Learning.

PubMed

Krüger, Melanie; Hinder, Mark R; Puri, Rohan; Summers, Jeffery J

2017-01-01

Objectives: The aim of this study was to investigate how age-related performance differences in a visuospatial sequence learning task relate to age-related declines in cognitive functioning. Method: Cognitive functioning of 18 younger and 18 older participants was assessed using a standardized test battery. Participants then undertook a perceptual visuospatial sequence learning task. Various relationships between sequence learning and participants' cognitive functioning were examined through correlation and factor analysis. Results: Older participants exhibited significantly lower performance than their younger counterparts in the sequence learning task as well as in multiple cognitive functions. Factor analysis revealed two independent subsets of cognitive functions associated with performance in the sequence learning task, related to either the processing and storage of sequence information (first subset) or problem solving (second subset). Age-related declines were only found for the first subset of cognitive functions, which also explained a significant degree of the performance differences in the sequence learning task between age-groups. Discussion: The results suggest that age-related performance differences in perceptual visuospatial sequence learning can be explained by declines in the ability to process and store sequence information in older adults, while a set of cognitive functions related to problem solving mediates performance differences independent of age.

Ameliorating effects of aged garlic extracts against Aβ-induced neurotoxicity and cognitive impairment

PubMed Central

2013-01-01

Background In vitro antioxidant activities and neuron-like PC12 cell protective effects of solvent fractions from aged garlic extracts were investigated to evaluate their anti-amnesic functions. Ethyl acetate fractions of aged garlic had higher total phenolics than other fractions. Methods Antioxidant activities of ethyl acetate fractions from aged garlic were examined using 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) diammonium salt (ABTS) and malondialdehyde (MDA) inhibitory effect using mouse whole brain homogenates. Levels of cellular oxidative stress as reactive oxygen species (ROS) accumulation were measured using 2',7'-dichlorofluorescein diacetate (DCF-DA). PC12 cell viability was investigated by 3-[4,5-dimethythiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and lactate dehydtrogenase (LDH) assay. The learning and memory impairment in institute of cancer research (ICR) mice was induced by neurotoxic amyloid beta protein (Aβ) to investigate in vivo anti-amnesic effects of aged garlic extracts by using Y-maze and passive avoidance tests. Results We discovered that ethyl acetate fractions showed the highest ABTS radical scavenging activity and MDA inhibitory effect. Intracellular ROS accumulation resulting from Aβ treatment in PC12 cells was significantly reduced when ethyl acetate fractions were presented in the medium compare to PC12 cells which was only treated with Aβ only. Ethyl acetate fractions from aged garlic extracts showed protection against Aβ-induced neurotoxicity. Pre-administration with aged garlic extracts attenuated Aβ-induced learning and memory deficits in both in vivo tests. Conclusions Our findings suggest that aged garlic extracts with antioxidant activities may improve cognitive impairment against Aβ-induced neuronal deficit, and possess a wide range of beneficial activities for neurodegenerative disorders, notably Alzheimer's disease (AD). PMID:24134394

Influence of schooling and age on cognitive performance in healthy older adults

PubMed Central

Bento-Torres, N.V.O.; Bento-Torres, J.; Tomás, A.M.; Costa, V.O.; Corrêa, P.G.R.; Costa, C.N.M.; Jardim, N.Y.V.; Picanço-Diniz, C.W.

2017-01-01

Few studies have examined the influence of a low level of schooling on age-related cognitive decline in countries with wide social and economic inequalities by using the Cambridge Automated Neuropsychological Test Battery (CANTAB). The aim of the present study was to assess the influence of schooling on age-related cognitive decline using unbiased cognitive tests. CANTAB allows cognitive assessment across cultures and education levels with reduced interference of the examiner during data acquisition. Using two-way ANOVA, we assessed the influences of age and education on test scores of old adults (61–84 years of age). CANTAB tests included: Visual Sustained Attention, Reaction Time, Spatial Working Memory, Learning and Episodic Memory. All subjects had a minimum visual acuity of 20/30 (Snellen Test), no previous or current history of traumatic brain/head trauma, stroke, language impairment, chronic alcoholism, neurological diseases, memory problems or depressive symptoms, and normal scores on the Mini Mental State Examination (MMSE). Subjects were grouped according to education level (1 to 7 and ≥8 years of schooling) and age (60–69 and ≥70 years). Low schooling level was associated with significantly lower performance on visual sustained attention, learning and episodic memory, reaction time, and spatial working memory. Although reaction time was influenced by age, no significant results on post hoc analysis were detected. Our findings showed a significantly worse cognitive performance in volunteers with lower levels of schooling and suggested that formal education in early life must be included in the preventive public health agenda. In addition, we suggest that CANTAB may be useful to detect subtle cognitive changes in healthy aging. PMID:28355353

The neuropsychological differentiation of patients with very mild Alzheimer's disease and/or major depression.

PubMed

desRosiers, G; Hodges, J R; Berrios, G

1995-11-01

To evaluate the usefulness of standardized neuropsychological tests in the psychometric differentiation of patients with very mild or mild Alzheimer's Disease (AD) and/or major depression presenting in a tertiary clinic with memory/attention complaints. Controlled prospective clinicoexperimental design. Multidisciplinary Memory Clinic at Addenbroke's Hospital, Cambridge, England. Twenty-four patients with a clinical diagnosis of Alzheimer's disease (12 with major depression and 12 without), 12 patients with major depressive illness but without AD, and 12 healthy control subjects, all matched for age, sex, education levels, and estimates of premorbid intellectual potential. Mini-Mental State Examination (MMSE), Wechsler's Logical Memory (WLM) and Visual Reproduction (WVR), immediate and delayed reproduction, Wechsler's paired Associate Learning (WPAL), including the Easy and Hard subsets. Warrington's Recognition Memory for Faces (WRMF), Kendrick's Object Learning (KOLT) and Digit Copying (KDCT) Tests. Minimum 2-year follow-up diagnosis. Statistically, patients with very mild AD were distinguished clearly from those without AD on most tests of memory functions. Psychometrically, only KOLT and an index of retention on WLM and WVR were specific enough to avoid false positives, a requirement for second-stage tools. They also proved sensitive enough to suggest their role as first-stage instruments when screening for primary dementia in high-functioning patients scoring above the cut-point on MMSE. As efforts intensify to develop more powerful means to identify patients with Alzheimer's disease in its earliest stages, inclusion of specialist tests posing greater cognitive challenge than standard mental status scales has been one strategy. Our study explored how some of these neuropsychological tools behave psychometrically when analyzed on a single-case basis, and the results suggest a few are sensitive enough to boost detection above base rates alone while also being specific enough to reduce false alarms. Retention on Wechsler's Logical Memory and Visual Reproduction tasks and scores on Kendrick's Object Learning Test helped decrease the degree of ambiguity when cognitive profiles were used to distinguish depressed patients with Alzheimer disease from those without.

The Geropathology Research Network: An Interdisciplinary Approach for Integrating Pathology Into Research on Aging

PubMed Central

Ikeno, Yuji; Niedernhofer, Laura; McIndoe, Richard A.; Ciol, Marcia A.; Ritchey, Jerry; Liggitt, Denny

2016-01-01

Geropathology is the study of aging and age-related lesions and diseases in the form of whole necropsies/autopsies, surgical biopsies, histology, and molecular biomarkers. It encompasses multiple subspecialties of geriatrics, anatomic pathology, molecular pathology, clinical pathology, and gerontology. In order to increase the consistency and scope of communication in the histologic and molecular pathology assessment of tissues from preclinical and clinical aging studies, a Geropathology Research Network has been established consisting of pathologists and scientists with expertise in the comparative pathology of aging, the design of aging research studies, biostatistical methods for analysis of aging data, and bioinformatics for compiling and annotating large sets of data generated from aging studies. The network provides an environment to promote learning and exchange of scientific information and ideas for the aging research community through a series of symposia, the development of uniform ways of integrating pathology into aging studies, and the statistical analysis of pathology data. The efforts of the network are ultimately expected to lead to a refined set of sentinel biomarkers of molecular and anatomic pathology that could be incorporated into preclinical and clinical aging intervention studies to increase the relevance and productivity of these types of investigations. PMID:26243216

Mechanisms of Oxidative Stress Resistance in The Brain: Lessons Learned From Hypoxia Tolerant Extremophilic Vertebrates

PubMed Central

Garbarino, Valentina R.; Orr, Miranda E.; Rodriguez, Karl A.; Buffenstein, Rochelle

2016-01-01

The Oxidative Stress Theory of Aging has had tremendous impact in research involving aging and age-associated diseases including those that affect the nervous system. With over half a century of accrued data showing both strong support for and against this theory, there is a need to critically evaluate the data acquired from common biomedical research models, and to also diversify the species used in studies involving this proximate theory. One approach is to follow Orgel’s second axiom that “evolution is smarter than we are” and judiciously choose species that may have evolved to live with chronic or seasonal oxidative stressors. Vertebrates that have naturally evolved to live under extreme conditions (e.g., anoxia or hypoxia), as well as those that undergo daily or seasonal torpor encounter both decreased oxygen availability and subsequent reoxygenation, with concomitant increased oxidative stress. Due to its high metabolic activity, the brain may be particularly vulnerable to oxidative stress. Here, we focus on oxidative stress responses in the brains of certain mouse models as well as extremophilic vertebrates. Exploring the naturally evolved biological tools utilized to cope with seasonal or environmentally variable oxygen availability may yield key information pertinent for how to deal with oxidative stress and thereby mitigate its propagation of age-associated diseases. PMID:25841340

Adverse events and dropouts in Alzheimer's disease studies: what can we learn?

PubMed

Henley, David B; Sundell, Karen L; Sethuraman, Gopalan; Schneider, Lon S

2015-01-01

Interpreting Alzheimer's disease (AD) clinical trial (CT) outcomes is complicated by treatment dropouts and adverse events (AEs). In elderly participants, AE rates, dropouts, and deaths are important considerations as they may undermine the validity of clinical trials. Published discontinuation and safety data are limited. Safety data from 1054 placebo-treated participants in IDENTITY and IDENTITY-2, 76-week, Phase 3 AD studies conducted in 31 countries, were pooled, annualized, and summarized overall, by country and age group. Median age was 74.2 (interquartile range 67.9-79.5) years; 57.4% were female; and median observation time was 63.2 (interquartile range 41.6-77.4) weeks when study drug dosing was halted. Overall annualized rates for discontinuations, discontinuations due to AEs, serious adverse events (SAEs), and deaths were 21.6% (range 19.6%-24.0%), 8.2% (range 8.1%-8.3%), 12.0%, and 1.7%, respectively. AE and discontinuation rates varied by country and age groups. Fall, pneumonia, and atrial fibrillation AEs were more frequent in the oldest age group. These annualized placebo safety data provide insight into the course of enrolled patients with mild-to-moderate AD, and are useful in planning longer term trials and in monitoring safety. Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Reducing cardiovascular disease risk in mid-life and older African Americans: A church-based longitudinal intervention project at baseline

PubMed Central

Lemacks, Jennifer L.; Wickrama, Kandauda (K.A.S.); Young-Clark, Iris; Coccia, Catherine; Ilich, Jasminka Z.; Harris, Cynthia M.; Hart, Celeste B.; Battle, Arrie M.; O’Neal, Catherine Walker

2014-01-01

Introduction African Americans (AAs) experience higher age-adjusted morbidity and mortality than Whites for cardiovascular disease (CVD). Church-based health programs can reduce risk factors for CVD, including elevated blood pressure [BP], excess body weight, sedentary lifestyle and diet. Yet few studies have incorporated older adults and longitudinal designs. Purposes The aims of this study are to: a) describe a theory-driven longitudinal intervention study to reduce CVD risk in mid-life and older AAs; b) compare selected dietary (fruit and vegetable servings/day, fat consumption), physical activity (PA) and clinical variables (BMI, girth circumferences, systolic and diastolic BP, LDL, HDL, total cholesterol [CHOL] and HDL/CHOL) between treatment and comparison churches at baseline; c) identify selected background characteristics (life satisfaction, social support, age, gender, educational level, marital status, living arrangement and medication use) at baseline that may confound results; and d) share the lessons learned. Methods This study incorporated a longitudinal pre/post with comparison group quasi-experimental design. Community-based participatory research (CBPR) was used to discover ideas for the study, identify community advisors, recruit churches (three treatment, three comparison) in two-counties in North Florida, and randomly select 221 mid-life and older AAs (45+) (n = 104 in clinical subsample), stratifying for age and gender. Data were collected through self-report questionnaires and clinical assessments. Results and conclusions Dietary, PA and clinical results were similar to the literature. Treatment and comparison groups were similar in background characteristics and health behaviors but differed in selected clinical factors. For the total sample, relationships were noted for most of the background characteristics. Lessons learned focused on community relationships and participant recruitment. PMID:24685998

77 FR 46127 - Interim Staff Guidance on Changes to the Generic Aging Lessons Learned (GALL) Report Revision 2...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-02

... Aging Lessons Learned (GALL) Report Revision 2 AMP XI.M41, ``Buried and Underground Piping and Tanks... AMPs in NUREG-1801, Revision 2, ``Generic Aging Lessons Learned (GALL) Report,'' and the NRC staff's... issues LR-ISG to communicate insights and lessons learned and to address emergent issues not covered in...

Cost-Sensitive Local Binary Feature Learning for Facial Age Estimation.

PubMed

Lu, Jiwen; Liong, Venice Erin; Zhou, Jie

2015-12-01

In this paper, we propose a cost-sensitive local binary feature learning (CS-LBFL) method for facial age estimation. Unlike the conventional facial age estimation methods that employ hand-crafted descriptors or holistically learned descriptors for feature representation, our CS-LBFL method learns discriminative local features directly from raw pixels for face representation. Motivated by the fact that facial age estimation is a cost-sensitive computer vision problem and local binary features are more robust to illumination and expression variations than holistic features, we learn a series of hashing functions to project raw pixel values extracted from face patches into low-dimensional binary codes, where binary codes with similar chronological ages are projected as close as possible, and those with dissimilar chronological ages are projected as far as possible. Then, we pool and encode these local binary codes within each face image as a real-valued histogram feature for face representation. Moreover, we propose a cost-sensitive local binary multi-feature learning method to jointly learn multiple sets of hashing functions using face patches extracted from different scales to exploit complementary information. Our methods achieve competitive performance on four widely used face aging data sets.

Older adults get episodic memory boosting from noninvasive stimulation of prefrontal cortex during learning

PubMed Central

Brambilla, Michela; Cobelli, Chiara; Cohen, Leonardo G.; Cotelli, Maria

2016-01-01

Episodic memory displays the largest degree of age-related decline, a process that is accelerated in pathological conditions such as amnestic mild cognitive impairment and Alzheimer's disease. Previous studies have shown that the left lateral prefrontal cortex (PFC) contributes to the encoding of episodic memories along the life span. The aim of this randomized, double-blind, placebo-controlled study was to test the hypothesis that anodal trascranial direct current stimulation (tDCS) over the left lateral PFC during the learning phase would enhance delayed recall of verbal episodic memories in elderly individuals. Older adults learned a list of words while receiving anodal or placebo (sham) tDCS. Memory recall was tested 48 hours and 1 month later. The results showed that anodal tDCS strengthened episodic memories, an effect indicated by enhanced delayed recall (48 hours) compared to placebo stimulation (Cohen's d effect size = 1.01). The observation that PFC-tDCS during learning can boost verbal episodic memory in the elderly opens up the possibility to design-specific neurorehabilitation protocols targeted to conditions that affect episodic memory such as mild cognitive impairment. PMID:26923418

Incidental Sequence Learning across the Lifespan

ERIC Educational Resources Information Center

Weiermann, Brigitte; Meier, Beat

2012-01-01

The purpose of the present study was to investigate incidental sequence learning across the lifespan. We tested 50 children (aged 7-16), 50 young adults (aged 20-30), and 50 older adults (aged >65) with a sequence learning paradigm that involved both a task and a response sequence. After several blocks of practice, all age groups slowed down…

77 FR 21813 - Changes to the Generic Aging Lessons Learned (GALL) Report Revision 2 AMP XI.M41, “Buried and...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-11

... NUCLEAR REGULATORY COMMISSION [NRC-2012-0055] Changes to the Generic Aging Lessons Learned (GALL) Report Revision 2 AMP XI.M41, ``Buried and Underground Piping and Tanks'' AGENCY: Nuclear Regulatory... NUREG-1801, Revision 2, ``Generic Aging Lessons Learned (GALL) Report,'' and the NRC staff's aging...

Does Language Help Regularity Learning? The Influence of Verbalizations on Implicit Sequential Regularity Learning and the Emergence of Explicit Knowledge in Children, Younger and Older Adults

ERIC Educational Resources Information Center

Ferdinand, Nicola K.; Kray, Jutta

2017-01-01

This study aimed at investigating the ability to learn regularities across the life span and examine whether this learning process can be supported or hampered by verbalizations. For this purpose, children (aged 8-10 years) and younger (aged 19-30 years) and older (aged 70-80 years) adults took part in a sequence learning experiment. We found that…

Long-term neurodevelopmental outcome of children born to prospectively followed pregnancies of women with systemic lupus erythematosus and/or antiphospholipid syndrome.

PubMed

Nalli, C; Iodice, A; Andreoli, L; Galli, J; Lojacono, A; Motta, M; Fazzi, E; Tincani, A

2017-04-01

Background Systemic lupus erythematosus (SLE) and antiphospholipid antibody syndrome (APS) are autoimmune diseases that affect women of childbearing age. Maternal IgG antiphospholipid antibodies (aPL) can cross the placenta during pregnancy and theoretically reach the fetal brain. Some studies showed an increased number of learning disabilities in these children. Objectives To evaluate the long-term neurodevelopmental outcome of 40 children (median age 7.4 years) born to mothers with SLE and/or APS carrying positive IgG aPL during the third trimester of pregnancy. Methods Children were checked for neurological physical exam and intellectual/cognitive functioning by the Wechsler scale for corrected age. We submitted to the mothers the Child Behavior CheckList (CBCL) and a homemade set of questions created by pediatric neurologists. Results In all children neurological physical exam and intelligence levels were found to be normal. A cognitive impairment or a discrepant cognitive profile was found in 3 (7%) and 11 (28%) children, respectively. Learning disabilities were diagnosed in 3 children (19% of school-age children), all born to mothers with triple aPL positivity. A history of epilepsy was shown in four children (10%). Children born to women with SLE and/or APS may need a long-term follow-up focusing on milestones of neurodevelopment in order to detect and correct any alteration as early as possible.

Gene Network Construction from Microarray Data Identifies a Key Network Module and Several Candidate Hub Genes in Age-Associated Spatial Learning Impairment

PubMed Central

Uddin, Raihan; Singh, Shiva M.

2017-01-01

As humans age many suffer from a decrease in normal brain functions including spatial learning impairments. This study aimed to better understand the molecular mechanisms in age-associated spatial learning impairment (ASLI). We used a mathematical modeling approach implemented in Weighted Gene Co-expression Network Analysis (WGCNA) to create and compare gene network models of young (learning unimpaired) and aged (predominantly learning impaired) brains from a set of exploratory datasets in rats in the context of ASLI. The major goal was to overcome some of the limitations previously observed in the traditional meta- and pathway analysis using these data, and identify novel ASLI related genes and their networks based on co-expression relationship of genes. This analysis identified a set of network modules in the young, each of which is highly enriched with genes functioning in broad but distinct GO functional categories or biological pathways. Interestingly, the analysis pointed to a single module that was highly enriched with genes functioning in “learning and memory” related functions and pathways. Subsequent differential network analysis of this “learning and memory” module in the aged (predominantly learning impaired) rats compared to the young learning unimpaired rats allowed us to identify a set of novel ASLI candidate hub genes. Some of these genes show significant repeatability in networks generated from independent young and aged validation datasets. These hub genes are highly co-expressed with other genes in the network, which not only show differential expression but also differential co-expression and differential connectivity across age and learning impairment. The known function of these hub genes indicate that they play key roles in critical pathways, including kinase and phosphatase signaling, in functions related to various ion channels, and in maintaining neuronal integrity relating to synaptic plasticity and memory formation. Taken together, they provide a new insight and generate new hypotheses into the molecular mechanisms responsible for age associated learning impairment, including spatial learning. PMID:29066959

Gene Network Construction from Microarray Data Identifies a Key Network Module and Several Candidate Hub Genes in Age-Associated Spatial Learning Impairment.

PubMed

Uddin, Raihan; Singh, Shiva M

2017-01-01

As humans age many suffer from a decrease in normal brain functions including spatial learning impairments. This study aimed to better understand the molecular mechanisms in age-associated spatial learning impairment (ASLI). We used a mathematical modeling approach implemented in Weighted Gene Co-expression Network Analysis (WGCNA) to create and compare gene network models of young (learning unimpaired) and aged (predominantly learning impaired) brains from a set of exploratory datasets in rats in the context of ASLI. The major goal was to overcome some of the limitations previously observed in the traditional meta- and pathway analysis using these data, and identify novel ASLI related genes and their networks based on co-expression relationship of genes. This analysis identified a set of network modules in the young, each of which is highly enriched with genes functioning in broad but distinct GO functional categories or biological pathways. Interestingly, the analysis pointed to a single module that was highly enriched with genes functioning in "learning and memory" related functions and pathways. Subsequent differential network analysis of this "learning and memory" module in the aged (predominantly learning impaired) rats compared to the young learning unimpaired rats allowed us to identify a set of novel ASLI candidate hub genes. Some of these genes show significant repeatability in networks generated from independent young and aged validation datasets. These hub genes are highly co-expressed with other genes in the network, which not only show differential expression but also differential co-expression and differential connectivity across age and learning impairment. The known function of these hub genes indicate that they play key roles in critical pathways, including kinase and phosphatase signaling, in functions related to various ion channels, and in maintaining neuronal integrity relating to synaptic plasticity and memory formation. Taken together, they provide a new insight and generate new hypotheses into the molecular mechanisms responsible for age associated learning impairment, including spatial learning.

Aging, Estrogens, and Episodic Memory in Women

PubMed Central

Henderson, Victor W.

2009-01-01

Objective To review the relation in midlife and beyond between estrogen exposures and episodic memory in women. Background Episodic memory performance declines with usual aging, and impairments in episodic memory often portend the development of Alzheimer's disease. In the laboratory, estradiol influences hippocampal function and animal learning. However, it is controversial whether estrogens affect memory after a woman's reproductive years. Method Focused literature review, including a summary of a systematic search of clinical trials of estrogens in which outcomes included an objective measure of episodic memory. Results The natural menopause transition is not associated with objective changes in episodic memory. Strong clinical trial evidence indicates that initiating estrogen-containing hormone therapy after about age 60 years does not benefit episodic memory. Clinical trial findings in middle-age women before age 60 are limited by smaller sample sizes and shorter treatment durations, but these also do not indicate substantial memory effects. Limited short-term evidence, however, suggests that estrogens may improve verbal memory after surgical menopause. Although hormone therapy initiation in old age increases dementia risk, observational studies raise the question of an early critical window during which midlife estrogen therapy reduces late-life Alzheimer's disease. However, almost no data address whether midlife estrogen therapy affects episodic memory in old age. Conclusions Episodic memory is not substantially impacted by the natural menopause transition or improved by use of estrogen-containing hormone therapy after age 60. Further research is needed to determine whether outcomes differ after surgical menopause or whether episodic memory later in life is modified by midlife estrogenic exposures. PMID:19996872

Intellectual enrichment lessens the effect of brain atrophy on learning and memory in multiple sclerosis

PubMed Central

Sumowski, James F.; Wylie, Glenn R.; Chiaravalloti, Nancy; DeLuca, John

2010-01-01

Objective: Learning and memory impairments are prevalent among persons with multiple sclerosis (MS); however, such deficits are only weakly associated with MS disease severity (brain atrophy). The cognitive reserve hypothesis states that greater lifetime intellectual enrichment lessens the negative impact of brain disease on cognition, thereby helping to explain the incomplete relationship between brain disease and cognitive status in neurologic populations. The literature on cognitive reserve has focused mainly on Alzheimer disease. The current research examines whether greater intellectual enrichment lessens the negative effect of brain atrophy on learning and memory in patients with MS. Methods: Forty-four persons with MS completed neuropsychological measures of verbal learning and memory, and a vocabulary-based estimate of lifetime intellectual enrichment. Brain atrophy was estimated with third ventricle width measured from 3-T magnetization-prepared rapid gradient echo MRIs. Hierarchical regression was used to predict learning and memory with brain atrophy, intellectual enrichment, and the interaction between brain atrophy and intellectual enrichment. Results: Brain atrophy predicted worse learning and memory, and intellectual enrichment predicted better learning; however, these effects were moderated by interactions between brain atrophy and intellectual enrichment. Specifically, higher intellectual enrichment lessened the negative impact of brain atrophy on both learning and memory. Conclusion: These findings help to explain the incomplete relationship between multiple sclerosis disease severity and cognition, as the effect of disease on cognition is attenuated among patients with higher intellectual enrichment. As such, intellectual enrichment is supported as a protective factor against disease-related cognitive impairment in persons with multiple sclerosis. GLOSSARY AD = Alzheimer disease; ANOVA = analysis of variance; MPRAGE = magnetization-prepared rapid gradient echo; MS = multiple sclerosis; SRT = Selective Reminding Test; TVW = third ventricle width; WASI = Wechsler Abbreviated Scale of Intelligence. PMID:20548040

Access to oral health care services among adults with learning disabilities: a scoping review.

PubMed

Naseem, Mustafa; Shah, Altaf H; Khiyani, Muhammad Faheem; Khurshid, Zohaib; Zafar, Muhammad Sohail; Gulzar, Shabnam; AlJameel, AlBandary H; Khalil, Hesham S

2016-01-01

The prevalence of oral diseases including dental caries and periodontal conditions is remarkably higher in people with disabilities. The provision of accessible oral health services for people with learning disabilities may be challenging. The objectives of the review were to identify barriers in accessing oral health care that persists within society, enabling or disabling people with learning disabilities. Using the Arksey O'Malley framework, a scoping review was conducted on PubMed/Medline, OVIDSP, and EMBASE. Studies were evaluated and short-listed based on the inclusion criteria, which consisted of: (1) study participants or population with learning disabilities, (2) aged 16 years or over, (3) reporting on access to oral health services, (4) published in the English language. Those that justified the inclusion criteria were carefully chosen after a blind peer-reviewed process when relevance and quality were debated. Nine studies were eventually included from searches. Tabulation of data was done under the heading of study type, outcomes, the year of publication and patient selection. The majority of studies provided a biomedical overview of access for adults with learning disabilities. The concept of access for people with disability is still ill-defined and obscure. Access to oral health care and needs of people with learning disabilities are complex and multi-facet.

Contribution of neuroinflammation and immunity to brain aging and the mitigating effects of physical and cognitive interventions.

PubMed

Di Benedetto, Svetlana; Müller, Ludmila; Wenger, Elisabeth; Düzel, Sandra; Pawelec, Graham

2017-04-01

It is widely accepted that the brain and the immune system continuously interact during normal as well as pathological functioning. Human aging is commonly accompanied by low-grade inflammation in both the immune and central nervous systems, thought to contribute to many age-related diseases. This review of the current literature focuses first on the normal neuroimmune interactions occurring in the brain, which promote learning, memory and neuroplasticity. Further, we discuss the protective and dynamic role of barriers to neuroimmune interactions, which have become clearer with the recent discovery of the meningeal lymphatic system. Next, we consider age-related changes of the immune system and possible deleterious influences of immunosenescence and low-grade inflammation (inflammaging) on neurodegenerative processes in the normally aging brain. We survey the major immunomodulators and neuroregulators in the aging brain and their highly tuned dynamic and reciprocal interactions. Finally, we consider our current understanding of how physical activity, as well as a combination of physical and cognitive interventions, may mediate anti-inflammatory effects and thus positively impact brain aging. Copyright © 2017 Elsevier Ltd. All rights reserved.

The effect of red grape juice on Alzheimer's disease in rats

PubMed Central

Siahmard, Zahra; Alaei, Hojjatollah; Reisi, Parham; Pilehvarian, Ali Asghar

2012-01-01

Background: Alzheimer's disease is a neurodegenerative disease appearing as a result of free radicals and oxidative stress. Antioxidants agents boost memory and control Alzheimer's disease. Since red grape juice contains antioxidant agents, its effects on speed of learning and improvement of memory was studied in Alzheimer's rats. Materials and Methods: Alzheimer's model was induced by bilateral infusion of streptozocine into lateral ventricles of brain of male rats. Rats drank 10% red grape juice for 21 days. Passive avoidance learning test was used for measuring memory and learning in rats. Results: Our results showed that learning and memory in STZ-group decreased significantly compared to Sham group. However, intake of red grape juice increased speed of learning and improvement of memory in Alzheimer's rats. Conclusions: Our results suggest that there are active ingredients in red grape juice, which probably have therapeutic and preventive effects on cognitive impairments in Alzheimer's disease. PMID:23326794

The effect of red grape juice on Alzheimer's disease in rats.

PubMed

Siahmard, Zahra; Alaei, Hojjatollah; Reisi, Parham; Pilehvarian, Ali Asghar

2012-01-01

Alzheimer's disease is a neurodegenerative disease appearing as a result of free radicals and oxidative stress. Antioxidants agents boost memory and control Alzheimer's disease. Since red grape juice contains antioxidant agents, its effects on speed of learning and improvement of memory was studied in Alzheimer's rats. Alzheimer's model was induced by bilateral infusion of streptozocine into lateral ventricles of brain of male rats. Rats drank 10% red grape juice for 21 days. Passive avoidance learning test was used for measuring memory and learning in rats. Our results showed that learning and memory in STZ-group decreased significantly compared to Sham group. However, intake of red grape juice increased speed of learning and improvement of memory in Alzheimer's rats. Our results suggest that there are active ingredients in red grape juice, which probably have therapeutic and preventive effects on cognitive impairments in Alzheimer's disease.

Colostomy irrigation in the elderly. Effective recovery regardless of age.

PubMed

Venturini, M; Bertelli, G; Forno, G; Grandi, G; Dini, D

1990-12-01

One hundred forty elderly cancer outpatients with colostomy in the authors' rehabilitation department were included in an analysis of the feasibility, effectiveness, and safety of periodic irrigation of remaining colon with lukewarm tap water with the aim of regaining full continence. Sixteen patients did not have a sufficiently long remaining bowel (cecostomy, transverse colostomy) and 17 were considered unsuitable to learn the technique because of advanced neoplastic disease with poor life expectancy, intercurrent disease, or stomal problems. One hundred seven patients were proposed to perform the irrigation: 17 refused to do so with the remaining 90 able to learn the method without problems. Nearly all patients achieved full continence for at least 24 hours. Three patients refused to continue, and nine interrupted for minor complications. The median duration of irrigation in the whole group is 257 days (range, 1 to 2669 days): 32 patients have been irrigating from one to five years, and 9 patients for more than 5 years. Based on these results, we recommend irrigation as standard rehabilitative treatment for elderly patients.

Aging Affects Motor Learning but Not Savings at Transfer of Learning

ERIC Educational Resources Information Center

Seidler, Rachael D.

2007-01-01

Two important components of skill learning are the learning process itself (motor acquisition) and the ability to transfer what has been learned to new task variants (motor transfer). Many studies have documented age-related declines in the ability to learn new manual motor skills. In this study, I tested whether the degree of savings at transfer…

In-Depth Characterization and Validation of Human Urine Metabolomes Reveal Novel Metabolic Signatures of Lower Urinary Tract Symptoms

NASA Astrophysics Data System (ADS)

Hao, Ling; Greer, Tyler; Page, David; Shi, Yatao; Vezina, Chad M.; Macoska, Jill A.; Marker, Paul C.; Bjorling, Dale E.; Bushman, Wade; Ricke, William A.; Li, Lingjun

2016-08-01

Lower urinary tract symptoms (LUTS) are a range of irritative or obstructive symptoms that commonly afflict aging population. The diagnosis is mostly based on patient-reported symptoms, and current medication often fails to completely eliminate these symptoms. There is a pressing need for objective non-invasive approaches to measure symptoms and understand disease mechanisms. We developed an in-depth workflow combining urine metabolomics analysis and machine learning bioinformatics to characterize metabolic alterations and support objective diagnosis of LUTS. Machine learning feature selection and statistical tests were combined to identify candidate biomarkers, which were statistically validated with leave-one-patient-out cross-validation and absolutely quantified by selected reaction monitoring assay. Receiver operating characteristic analysis showed highly-accurate prediction power of candidate biomarkers to stratify patients into disease or non-diseased categories. The key metabolites and pathways may be possibly correlated with smooth muscle tone changes, increased collagen content, and inflammation, which have been identified as potential contributors to urinary dysfunction in humans and rodents. Periurethral tissue staining revealed a significant increase in collagen content and tissue stiffness in men with LUTS. Together, our study provides the first characterization and validation of LUTS urinary metabolites and pathways to support the future development of a urine-based diagnostic test for LUTS.

Machine Learning, Sentiment Analysis, and Tweets: An Examination of Alzheimer's Disease Stigma on Twitter.

PubMed

Oscar, Nels; Fox, Pamela A; Croucher, Racheal; Wernick, Riana; Keune, Jessica; Hooker, Karen

2017-09-01

Social scientists need practical methods for harnessing large, publicly available datasets that inform the social context of aging. We describe our development of a semi-automated text coding method and use a content analysis of Alzheimer's disease (AD) and dementia portrayal on Twitter to demonstrate its use. The approach improves feasibility of examining large publicly available datasets. Machine learning techniques modeled stigmatization expressed in 31,150 AD-related tweets collected via Twitter's search API based on 9 AD-related keywords. Two researchers manually coded 311 random tweets on 6 dimensions. This input from 1% of the dataset was used to train a classifier against the tweet text and code the remaining 99% of the dataset. Our automated process identified that 21.13% of the AD-related tweets used AD-related keywords to perpetuate public stigma, which could impact stereotypes and negative expectations for individuals with the disease and increase "excess disability". This technique could be applied to questions in social gerontology related to how social media outlets reflect and shape attitudes bearing on other developmental outcomes. Recommendations for the collection and analysis of large Twitter datasets are discussed. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Serum high-density lipoprotein is associated with better cognitive function in a cross-sectional study of aging women.

PubMed

Bates, Kristyn A; Sohrabi, Hamid R; Rainey-Smith, Stephanie R; Weinborn, Michael; Bucks, Romola S; Rodrigues, Mark; Beilby, John; Howard, Matthew; Taddei, Kevin; Martins, Georgia; Paton, Athena; Shah, Tejal; Dhaliwal, Satvinder S; Foster, Jonathan K; Martins, Ian J; Lautenschlager, Nicola T; Mastaglia, Frank L; Gandy, Samuel E; Martins, Ralph N

2017-03-01

Purpose/Aim of the study: Poor cardiovascular health, including obesity and altered lipid profiles at mid-life, are linked to increased risk of Alzheimer's disease (AD). The biological mechanisms linking cardiovascular health and cognitive function are unclear though are likely to be multifactorial. This study examined the association between various lipoproteins and cognitive functioning in ageing women. We investigated the relationship between readily available biomarkers (i.e. serum lipoprotein) and cognitive decline in domains associated with increased risk of AD (e.g. episodic verbal memory performance and subjective memory complaint). We report cross-sectional data investigating the relationship between serum total cholesterol, triglycerides, high-density lipoprotein (HDL-C) and low-density lipoprotein with verbal memory and learning ability in 130 women with and without memory complaints (n = 71 and 59, respectively) drawn from a study investigating cognitively healthy Western Australians (average age 62.5 years old). After statistical modelling that controlled for the effects of age, depression and apolipoprotein E genotype, HDL-C was significantly associated with better verbal learning and memory performance, specifically short and long delay-free recalls (F = 3.062; p < .05 and F = 3.2670; p < .05, respectively). Our cross-sectional findings suggest that the positive effect of HDL-C on verbal memory may be present much earlier than previously reported and provide further support for the role of HDL-C in healthy brain ageing. Further exploration of the protective effect of HDL-C on cognitive function in ageing is warranted through follow-up, longitudinal studies.

Wheel-running in a transgenic mouse model of Alzheimer's disease: protection or symptom?

PubMed

Richter, Helene; Ambrée, Oliver; Lewejohann, Lars; Herring, Arne; Keyvani, Kathy; Paulus, Werner; Palme, Rupert; Touma, Chadi; Schäbitz, Wolf-Rüdiger; Sachser, Norbert

2008-06-26

Several studies on both humans and animals reveal benefits of physical exercise on brain function and health. A previous study on TgCRND8 mice, a transgenic model of Alzheimer's disease, reported beneficial effects of premorbid onset of long-term access to a running wheel on spatial learning and plaque deposition. Our study investigated the effects of access to a running wheel after the onset of Abeta pathology on behavioural, endocrinological, and neuropathological parameters. From day 80 of age, the time when Abeta deposition becomes apparent, TgCRND8 and wildtype mice were kept with or without running wheel. Home cage behaviour was analysed and cognitive abilities regarding object recognition memory and spatial learning in the Barnes maze were assessed. Our results show that, in comparison to Wt mice, Tg mice were characterised by impaired object recognition memory and spatial learning, increased glucocorticoid levels, hyperactivity in the home cage and high levels of stereotypic behaviour. Access to a running wheel had no effects on cognitive or neuropathological parameters, but reduced the amount of stereotypic behaviour in transgenics significantly. Furthermore, wheel-running was inversely correlated with stereotypic behaviour, suggesting that wheel-running may have stereotypic qualities. In addition, wheel-running positively correlated with plaque burden. Thus, in a phase when plaques are already present in the brain, it may be symptomatic of brain pathology, rather than protective. Whether or not access to a running wheel has beneficial effects on Alzheimer-like pathology and symptoms may therefore strongly depend on the exact time when the wheel is provided during development of the disease.

The Copenhagen City Heart Study (Østerbroundersøgelsen)

PubMed Central

Aguib, Yasmine; Al Suwaidi, Jassim

2015-01-01

The Copenhagen City Heart Study, also known as “Østerbroundersøgelsen”, is a large prospective cardio-vascular population study of 20,000 women and men that was launched in 1975 by Dr Peter Schnohr and Dr Gorm Jensen together with statistician Jørgen Nyboe and Prof. A. Tybjærg Hansen. The original purpose of the study was to focus on prevention of coronary heart disease and stroke. During the years many other aspects have been added to the study: pulmonary diseases, heart failure, arrhythmia, alcohol, arthrosis, eye diseases, allergy, epilepsia, dementia, stress, vital exhaustion, social network, sleep-apnoe, ageing and genetics. In this review we highlight unique aspects of the Copenhagen City Heat Study (CCHS) and its outcome in investigations of clinical and molecular aspects of health and disease in the regional and global population. To increase the impact of population studies with a focus on risk and prevention of cardiovascular and related diseases and to maximize the likelihood of identifying disease causes and effective therapeutics, lessons learned from past research should be applied to the design, implementation and interpretation of future studies. PMID:26779513

Age- and Brain Region-Specific Changes of Glucose Metabolic Disorder, Learning, and Memory Dysfunction in Early Alzheimer's Disease Assessed in APP/PS1 Transgenic Mice Using 18F-FDG-PET.

PubMed

Li, Xue-Yuan; Men, Wei-Wei; Zhu, Hua; Lei, Jian-Feng; Zuo, Fu-Xing; Wang, Zhan-Jing; Zhu, Zhao-Hui; Bao, Xin-Jie; Wang, Ren-Zhi

2016-10-18

Alzheimer's disease (AD) is a leading cause of dementia worldwide, associated with cognitive deficits and brain glucose metabolic alteration. However, the associations of glucose metabolic changes with cognitive dysfunction are less detailed. Here, we examined the brains of APP/presenilin 1 (PS1) transgenic (Tg) mice aged 2, 3.5, 5 and 8 months using 18 F-labed fluorodeoxyglucose ( 18 F-FDG) microPET to assess age- and brain region-specific changes of glucose metabolism. FDG uptake was calculated as a relative standardized uptake value (SUVr). Morris water maze (MWM) was used to evaluate learning and memory dysfunction. We showed a glucose utilization increase in multiple brain regions of Tg mice at 2 and 3.5 months but not at 5 and 8 months. Comparisons of SUVrs within brains showed higher glucose utilization than controls in the entorhinal cortex, hippocampus, and frontal cortex of Tg mice at 2 and 3.5 months but in the thalamus and striatum at 3.5, 5 and 8 months. By comparing SUVrs in the entorhinal cortex and hippocampus, Tg mice were distinguished from controls at 2 and 3.5 months. In MWM, Tg mice aged 2 months shared a similar performance to the controls (prodromal-AD). By contrast, Tg mice failed training tests at 3.5 months but failed all MWM tests at 5 and 8 months, suggestive of partial or complete cognitive deficits (symptomatic-AD). Correlation analyses showed that hippocampal SUVrs were significantly correlated with MWM parameters in the symptomatic-AD stage. These data suggest that glucose metabolic disorder occurs before onset of AD signs in APP/PS1 mice with the entorhinal cortex and hippocampus affected first, and that regional FDG uptake increase can be an early biomarker for AD. Furthermore, hippocampal FDG uptake is a possible indicator for progression of Alzheimer's cognition after cognitive decline, at least in animals.

Intellectual enrichment lessens the effect of brain atrophy on learning and memory in multiple sclerosis.

PubMed

Sumowski, James F; Wylie, Glenn R; Chiaravalloti, Nancy; DeLuca, John

2010-06-15

Learning and memory impairments are prevalent among persons with multiple sclerosis (MS); however, such deficits are only weakly associated with MS disease severity (brain atrophy). The cognitive reserve hypothesis states that greater lifetime intellectual enrichment lessens the negative impact of brain disease on cognition, thereby helping to explain the incomplete relationship between brain disease and cognitive status in neurologic populations. The literature on cognitive reserve has focused mainly on Alzheimer disease. The current research examines whether greater intellectual enrichment lessens the negative effect of brain atrophy on learning and memory in patients with MS. Forty-four persons with MS completed neuropsychological measures of verbal learning and memory, and a vocabulary-based estimate of lifetime intellectual enrichment. Brain atrophy was estimated with third ventricle width measured from 3-T magnetization-prepared rapid gradient echo MRIs. Hierarchical regression was used to predict learning and memory with brain atrophy, intellectual enrichment, and the interaction between brain atrophy and intellectual enrichment. Brain atrophy predicted worse learning and memory, and intellectual enrichment predicted better learning; however, these effects were moderated by interactions between brain atrophy and intellectual enrichment. Specifically, higher intellectual enrichment lessened the negative impact of brain atrophy on both learning and memory. These findings help to explain the incomplete relationship between multiple sclerosis disease severity and cognition, as the effect of disease on cognition is attenuated among patients with higher intellectual enrichment. As such, intellectual enrichment is supported as a protective factor against disease-related cognitive impairment in persons with multiple sclerosis.

Investing in organisational culture: nursing students' experience of organisational learning culture in aged care settings following a program of cultural development.

PubMed

Grealish, Laurie; Henderson, Amanda

2016-10-01

Concerns around organisational learning culture limit nursing student placements in aged care settings to first year experiences. Determine the impact of an extended staff capacity building program on students' experiences of the organisational learning culture in the aged care setting. Pre and post-test design. A convenience sample of first, second and third year Bachelor of Nursing students attending placements at three residential aged care facilities completed the Clinical Learning Organisational Culture Survey. Responses between the group that attended placement before the program (n = 17/44; RR 38%) and the group that attended following the program (n = 33/72; RR 45%) were compared. Improvements were noted in the areas of recognition, accomplishment, and influence, with decreases in dissatisfaction. Organisational investment in building staff capacity can produce a positive learning culture. The aged care sector offers a rich learning experience for students when staff capacity to support learning is developed.

Sex differences in cognitive ageing: testing predictions derived from life-history theory in a dioecious nematode.

PubMed

Zwoinska, Martyna K; Kolm, Niclas; Maklakov, Alexei A

2013-12-01

Life-history theory maintains that organisms allocate limited resources to different traits to maximize fitness. Learning ability and memory are costly and known to trade-off with longevity in invertebrates. However, since the relationship between longevity and fitness often differs between the sexes, it is likely that sexes will differentially resolve the trade-off between learning and longevity. We used an established associative learning paradigm in the dioecious nematode Caenorhabditis remanei, which is sexually dimorphic for lifespan, to study age-related learning ability in males and females. In particular, we tested the hypothesis that females (the shorter-lived sex) show higher learning ability than males early in life but senesce faster. Indeed, young females outperformed young males in learning a novel association between an odour (butanone) and food (bacteria). However, while learning ability and offspring production declined rapidly with age in females, males maintained high levels of these traits until mid-age. These results not only demonstrate sexual dimorphism in age-related learning ability but also suggest that it conforms to predictions derived from the life-history theory. © 2013.

Nebraska Early Learning Guidelines for Ages Birth to 3: Nurturing the Development and Learning of Infants and Toddlers through Responsive Caregiving

ERIC Educational Resources Information Center

Nebraska Department of Education, 2006

2006-01-01

This resource provides information to assist parents, family members, early childhood teachers, caregivers, and other adults in promoting the learning and development of young children ages birth to three. It is a companion to the Nebraska Early Learning Guidelines for Ages 3 to 5, and uses the same format and domains of development. This…

Machine learning for prediction of all-cause mortality in patients with suspected coronary artery disease: a 5-year multicentre prospective registry analysis

PubMed Central

Motwani, Manish; Dey, Damini; Berman, Daniel S.; Germano, Guido; Achenbach, Stephan; Al-Mallah, Mouaz H.; Andreini, Daniele; Budoff, Matthew J.; Cademartiri, Filippo; Callister, Tracy Q.; Chang, Hyuk-Jae; Chinnaiyan, Kavitha; Chow, Benjamin J.W.; Cury, Ricardo C.; Delago, Augustin; Gomez, Millie; Gransar, Heidi; Hadamitzky, Martin; Hausleiter, Joerg; Hindoyan, Niree; Feuchtner, Gudrun; Kaufmann, Philipp A.; Kim, Yong-Jin; Leipsic, Jonathon; Lin, Fay Y.; Maffei, Erica; Marques, Hugo; Pontone, Gianluca; Raff, Gilbert; Rubinshtein, Ronen; Shaw, Leslee J.; Stehli, Julia; Villines, Todd C.; Dunning, Allison; Min, James K.; Slomka, Piotr J.

2017-01-01

Aims Traditional prognostic risk assessment in patients undergoing non-invasive imaging is based upon a limited selection of clinical and imaging findings. Machine learning (ML) can consider a greater number and complexity of variables. Therefore, we investigated the feasibility and accuracy of ML to predict 5-year all-cause mortality (ACM) in patients undergoing coronary computed tomographic angiography (CCTA), and compared the performance to existing clinical or CCTA metrics. Methods and results The analysis included 10 030 patients with suspected coronary artery disease and 5-year follow-up from the COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter registry. All patients underwent CCTA as their standard of care. Twenty-five clinical and 44 CCTA parameters were evaluated, including segment stenosis score (SSS), segment involvement score (SIS), modified Duke index (DI), number of segments with non-calcified, mixed or calcified plaques, age, sex, gender, standard cardiovascular risk factors, and Framingham risk score (FRS). Machine learning involved automated feature selection by information gain ranking, model building with a boosted ensemble algorithm, and 10-fold stratified cross-validation. Seven hundred and forty-five patients died during 5-year follow-up. Machine learning exhibited a higher area-under-curve compared with the FRS or CCTA severity scores alone (SSS, SIS, DI) for predicting all-cause mortality (ML: 0.79 vs. FRS: 0.61, SSS: 0.64, SIS: 0.64, DI: 0.62; P< 0.001). Conclusions Machine learning combining clinical and CCTA data was found to predict 5-year ACM significantly better than existing clinical or CCTA metrics alone. PMID:27252451

Machine learning for prediction of all-cause mortality in patients with suspected coronary artery disease: a 5-year multicentre prospective registry analysis.

PubMed

Motwani, Manish; Dey, Damini; Berman, Daniel S; Germano, Guido; Achenbach, Stephan; Al-Mallah, Mouaz H; Andreini, Daniele; Budoff, Matthew J; Cademartiri, Filippo; Callister, Tracy Q; Chang, Hyuk-Jae; Chinnaiyan, Kavitha; Chow, Benjamin J W; Cury, Ricardo C; Delago, Augustin; Gomez, Millie; Gransar, Heidi; Hadamitzky, Martin; Hausleiter, Joerg; Hindoyan, Niree; Feuchtner, Gudrun; Kaufmann, Philipp A; Kim, Yong-Jin; Leipsic, Jonathon; Lin, Fay Y; Maffei, Erica; Marques, Hugo; Pontone, Gianluca; Raff, Gilbert; Rubinshtein, Ronen; Shaw, Leslee J; Stehli, Julia; Villines, Todd C; Dunning, Allison; Min, James K; Slomka, Piotr J

2017-02-14

Traditional prognostic risk assessment in patients undergoing non-invasive imaging is based upon a limited selection of clinical and imaging findings. Machine learning (ML) can consider a greater number and complexity of variables. Therefore, we investigated the feasibility and accuracy of ML to predict 5-year all-cause mortality (ACM) in patients undergoing coronary computed tomographic angiography (CCTA), and compared the performance to existing clinical or CCTA metrics. The analysis included 10 030 patients with suspected coronary artery disease and 5-year follow-up from the COronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicenter registry. All patients underwent CCTA as their standard of care. Twenty-five clinical and 44 CCTA parameters were evaluated, including segment stenosis score (SSS), segment involvement score (SIS), modified Duke index (DI), number of segments with non-calcified, mixed or calcified plaques, age, sex, gender, standard cardiovascular risk factors, and Framingham risk score (FRS). Machine learning involved automated feature selection by information gain ranking, model building with a boosted ensemble algorithm, and 10-fold stratified cross-validation. Seven hundred and forty-five patients died during 5-year follow-up. Machine learning exhibited a higher area-under-curve compared with the FRS or CCTA severity scores alone (SSS, SIS, DI) for predicting all-cause mortality (ML: 0.79 vs. FRS: 0.61, SSS: 0.64, SIS: 0.64, DI: 0.62; P< 0.001). Machine learning combining clinical and CCTA data was found to predict 5-year ACM significantly better than existing clinical or CCTA metrics alone. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.

Experimental evolution of slowed cognitive aging in Drosophila melanogaster.

PubMed

Zwoinska, Martyna K; Maklakov, Alexei A; Kawecki, Tadeusz J; Hollis, Brian

2017-03-01

Reproductive output and cognitive performance decline in parallel during aging, but it is unknown whether this reflects a shared genetic architecture or merely the declining force of natural selection acting independently on both traits. We used experimental evolution in Drosophila melanogaster to test for the presence of genetic variation for slowed cognitive aging, and assess its independence from that responsible for other traits' decline with age. Replicate experimental populations experienced either joint selection on learning and reproduction at old age (Old + Learning), selection on late-life reproduction alone (Old), or a standard two-week culture regime (Young). Within 20 generations, the Old + Learning populations evolved a slower decline in learning with age than both the Old and Young populations, revealing genetic variation for cognitive aging. We found little evidence for a genetic correlation between cognitive and demographic aging: although the Old + Learning populations tended to show higher late-life fecundity than Old populations, they did not live longer. Likewise, selection for late reproduction alone did not result in improved late-life learning. Our results demonstrate that Drosophila harbor genetic variation for cognitive aging that is largely independent from genetic variation for demographic aging and suggest that these two aspects of aging may not necessarily follow the same trajectories. © 2016 The Author(s). Evolution published by Wiley Periodicals, Inc. on behalf of The Society for the Study of Evolution.

Ageing and spatial reversal learning in humans: findings from a virtual water maze.

PubMed

Schoenfeld, R; Foreman, N; Leplow, B

2014-08-15

Deterioration in spatial memory with normal ageing is well accepted. Animal research has shown spatial reversal learning to be most vulnerable to pathological changes in the brain, but this has never been tested in humans. We studied ninety participants (52% females, 20-80 yrs) in a virtual water maze with a reversal learning procedure. Neuropsychological functioning, mood and personality were assessed to control moderator effects. For data analysis, participants were subdivided post hoc into groups aged 20-24, 25-34, 35-44, 45-64 and 65-80 yrs. Initial spatial learning occurred in all age groups but 65-80-yrs-olds never reached the level of younger participants. When tested for delayed recall of spatial memory, younger people frequented the target area but those over 65 yrs did not. In spatial reversal learning, age groups over 45 yrs were deficient and the 65-80-yrs-olds showed no evidence of reversal. Spatial measures were associated with neuropsychological functioning. Extraversion and measures of depression moderated the age effect on the learning index with older introverted and non-depressed individuals showing better results. Measures of anxiety moderated the age effect on reversal learning with older people having higher anxiety scores showing a preserved reversal learning capability. Results confirmed age to be a major factor in spatial tasks but further showed neuropsychological functioning, psycho-affective determinants and personality traits to be significant predictors of individual differences. Copyright © 2014 Elsevier B.V. All rights reserved.

The Effect of Old Age on Supra-Span Learning of Visuo-Spatial Sequences under Incidental and Intentional Encoding Instructions

ERIC Educational Resources Information Center

Gagnon, Sylvain; Bedard, Marie-Josee; Turcotte, Josee

2005-01-01

Recent findings [Turcotte, Gagnon, & Poirier, 2005. The effect of old age on the learning of supra-span sequences. "Psychology and Aging," 20, 251-260.] indicate that incidental learning of visuo-spatial supra-span sequences through immediate serial recall declines with old age (Hebb's paradigm). In this study, we examined whether…

SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer's disease and amyotrophic lateral sclerosis.

PubMed

Kim, Dohoon; Nguyen, Minh Dang; Dobbin, Matthew M; Fischer, Andre; Sananbenesi, Farahnaz; Rodgers, Joseph T; Delalle, Ivana; Baur, Joseph A; Sui, Guangchao; Armour, Sean M; Puigserver, Pere; Sinclair, David A; Tsai, Li-Huei

2007-07-11

A progressive loss of neurons with age underlies a variety of debilitating neurological disorders, including Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS), yet few effective treatments are currently available. The SIR2 gene promotes longevity in a variety of organisms and may underlie the health benefits of caloric restriction, a diet that delays aging and neurodegeneration in mammals. Here, we report that a human homologue of SIR2, SIRT1, is upregulated in mouse models for AD, ALS and in primary neurons challenged with neurotoxic insults. In cell-based models for AD/tauopathies and ALS, SIRT1 and resveratrol, a SIRT1-activating molecule, both promote neuronal survival. In the inducible p25 transgenic mouse, a model of AD and tauopathies, resveratrol reduced neurodegeneration in the hippocampus, prevented learning impairment, and decreased the acetylation of the known SIRT1 substrates PGC-1alpha and p53. Furthermore, injection of SIRT1 lentivirus in the hippocampus of p25 transgenic mice conferred significant protection against neurodegeneration. Thus, SIRT1 constitutes a unique molecular link between aging and human neurodegenerative disorders and provides a promising avenue for therapeutic intervention.

SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer's disease and amyotrophic lateral sclerosis

PubMed Central

Kim, Dohoon; Nguyen, Minh Dang; Dobbin, Matthew M; Fischer, Andre; Sananbenesi, Farahnaz; Rodgers, Joseph T; Delalle, Ivana; Baur, Joseph A; Sui, Guangchao; Armour, Sean M; Puigserver, Pere; Sinclair, David A; Tsai, Li-Huei

2007-01-01

A progressive loss of neurons with age underlies a variety of debilitating neurological disorders, including Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS), yet few effective treatments are currently available. The SIR2 gene promotes longevity in a variety of organisms and may underlie the health benefits of caloric restriction, a diet that delays aging and neurodegeneration in mammals. Here, we report that a human homologue of SIR2, SIRT1, is upregulated in mouse models for AD, ALS and in primary neurons challenged with neurotoxic insults. In cell-based models for AD/tauopathies and ALS, SIRT1 and resveratrol, a SIRT1-activating molecule, both promote neuronal survival. In the inducible p25 transgenic mouse, a model of AD and tauopathies, resveratrol reduced neurodegeneration in the hippocampus, prevented learning impairment, and decreased the acetylation of the known SIRT1 substrates PGC-1alpha and p53. Furthermore, injection of SIRT1 lentivirus in the hippocampus of p25 transgenic mice conferred significant protection against neurodegeneration. Thus, SIRT1 constitutes a unique molecular link between aging and human neurodegenerative disorders and provides a promising avenue for therapeutic intervention. PMID:17581637

Brain age predicts mortality

PubMed Central

Cole, J H; Ritchie, S J; Bastin, M E; Valdés Hernández, M C; Muñoz Maniega, S; Royle, N; Corley, J; Pattie, A; Harris, S E; Zhang, Q; Wray, N R; Redmond, P; Marioni, R E; Starr, J M; Cox, S R; Wardlaw, J M; Sharp, D J; Deary, I J

2018-01-01

Age-associated disease and disability are placing a growing burden on society. However, ageing does not affect people uniformly. Hence, markers of the underlying biological ageing process are needed to help identify people at increased risk of age-associated physical and cognitive impairments and ultimately, death. Here, we present such a biomarker, ‘brain-predicted age’, derived using structural neuroimaging. Brain-predicted age was calculated using machine-learning analysis, trained on neuroimaging data from a large healthy reference sample (N=2001), then tested in the Lothian Birth Cohort 1936 (N=669), to determine relationships with age-associated functional measures and mortality. Having a brain-predicted age indicative of an older-appearing brain was associated with: weaker grip strength, poorer lung function, slower walking speed, lower fluid intelligence, higher allostatic load and increased mortality risk. Furthermore, while combining brain-predicted age with grey matter and cerebrospinal fluid volumes (themselves strong predictors) not did improve mortality risk prediction, the combination of brain-predicted age and DNA-methylation-predicted age did. This indicates that neuroimaging and epigenetics measures of ageing can provide complementary data regarding health outcomes. Our study introduces a clinically-relevant neuroimaging ageing biomarker and demonstrates that combining distinct measurements of biological ageing further helps to determine risk of age-related deterioration and death. PMID:28439103

Integrity of white matter structure is related to episodic memory performance in the low-educated elderly.

PubMed

Resende, Elisa de Paula França; Tovar-Moll, Fernanda Freire; Ferreira, Fernanda Meireles; Bramati, Ivanei; de Souza, Leonardo Cruz; Carmona, Karoline Carvalho; Guimarães, Henrique Cerqueira; Carvalho, Viviane Amaral; Barbosa, Maira Tonidandel; Caramelli, Paulo

2017-11-01

The low-educated elderly are a vulnerable population in whom studying the role of white matter integrity on memory may provide insights for understanding how memory declines with aging and disease. Thirty-one participants (22 women), 23 cognitively healthy and eight with cognitive impairment-no dementia, aged 80.4 ± 3.8 years, with 2.2 ± 1.9 years of education, underwent an MRI scan with diffusion tensor imaging (DTI) acquisition. We verified if there were correlations between the performance on the Brief Cognitive Screening Battery (BCSB) and the Rey Auditory Verbal Learning Test (RAVLT) with DTI parameters. The BCSB delayed recall task correlated with frontotemporoparietal connection bundles, with the hippocampal part of the cingulum bilaterally and with the right superior longitudinal fasciculus. The RAVLT learning and delayed recall scores also correlated with the hippocampal part of the cingulum bilaterally. Although preliminary, our study suggests that the integrity of white matter frontotemporoparietal fasciculi seems to play a role in episodic memory performance in the low-educated elderly. This finding opens opportunities to study potential targets for memory decline prevention in vulnerable populations.

Positive-unlabeled learning for disease gene identification

PubMed Central

Yang, Peng; Li, Xiao-Li; Mei, Jian-Ping; Kwoh, Chee-Keong; Ng, See-Kiong

2012-01-01

Background: Identifying disease genes from human genome is an important but challenging task in biomedical research. Machine learning methods can be applied to discover new disease genes based on the known ones. Existing machine learning methods typically use the known disease genes as the positive training set P and the unknown genes as the negative training set N (non-disease gene set does not exist) to build classifiers to identify new disease genes from the unknown genes. However, such kind of classifiers is actually built from a noisy negative set N as there can be unknown disease genes in N itself. As a result, the classifiers do not perform as well as they could be. Result: Instead of treating the unknown genes as negative examples in N, we treat them as an unlabeled set U. We design a novel positive-unlabeled (PU) learning algorithm PUDI (PU learning for disease gene identification) to build a classifier using P and U. We first partition U into four sets, namely, reliable negative set RN, likely positive set LP, likely negative set LN and weak negative set WN. The weighted support vector machines are then used to build a multi-level classifier based on the four training sets and positive training set P to identify disease genes. Our experimental results demonstrate that our proposed PUDI algorithm outperformed the existing methods significantly. Conclusion: The proposed PUDI algorithm is able to identify disease genes more accurately by treating the unknown data more appropriately as unlabeled set U instead of negative set N. Given that many machine learning problems in biomedical research do involve positive and unlabeled data instead of negative data, it is possible that the machine learning methods for these problems can be further improved by adopting PU learning methods, as we have done here for disease gene identification. Availability and implementation: The executable program and data are available at http://www1.i2r.a-star.edu.sg/∼xlli/PUDI/PUDI.html. Contact: xlli@i2r.a-star.edu.sg or yang0293@e.ntu.edu.sg Supplementary information: Supplementary Data are available at Bioinformatics online. PMID:22923290

Perceptron ensemble of graph-based positive-unlabeled learning for disease gene identification.

PubMed

Jowkar, Gholam-Hossein; Mansoori, Eghbal G

2016-10-01

Identification of disease genes, using computational methods, is an important issue in biomedical and bioinformatics research. According to observations that diseases with the same or similar phenotype have the same biological characteristics, researchers have tried to identify genes by using machine learning tools. In recent attempts, some semi-supervised learning methods, called positive-unlabeled learning, is used for disease gene identification. In this paper, we present a Perceptron ensemble of graph-based positive-unlabeled learning (PEGPUL) on three types of biological attributes: gene ontologies, protein domains and protein-protein interaction networks. In our method, a reliable set of positive and negative genes are extracted using co-training schema. Then, the similarity graph of genes is built using metric learning by concentrating on multi-rank-walk method to perform inference from labeled genes. At last, a Perceptron ensemble is learned from three weighted classifiers: multilevel support vector machine, k-nearest neighbor and decision tree. The main contributions of this paper are: (i) incorporating the statistical properties of gene data through choosing proper metrics, (ii) statistical evaluation of biological features, and (iii) noise robustness characteristic of PEGPUL via using multilevel schema. In order to assess PEGPUL, we have applied it on 12950 disease genes with 949 positive genes from six class of diseases and 12001 unlabeled genes. Compared with some popular disease gene identification methods, the experimental results show that PEGPUL has reasonable performance. Copyright © 2016 Elsevier Ltd. All rights reserved.

Age moderates the effect of acute dopamine depletion on passive avoidance learning.

PubMed

Kelm, Mary Katherine; Boettiger, Charlotte Ann

2015-04-01

Despite extensive links between reinforcement-based learning and dopamine (DA), studies to date have not found consistent effects of acute DA reduction on reinforcement learning in both men and women. Here, we tested the effects of reducing DA on reward- and punishment-based learning using the deterministic passive avoidance learning (PAL) task. We tested 16 (5 female) adults (ages 22-40) in a randomized, cross-over design to determine whether reducing global DA by administering an amino acid beverage deficient in the DA precursors, phenylalanine and tyrosine (P/T[-]), would affect PAL task performance. We found that P/T[-] beverage effects on PAL performance were modulated by age. Specifically, we found that P/T depletion significantly improved learning from punishment with increasing participant age. Participants committed 1.49 fewer passive avoidance errors per additional year of age (95% CI, -0.71 - -2.27, r=-0.74, p=0.001). Moreover, P/T depletion improved learning from punishment in adults (ages 26-40) while it impaired learning from punishment in emerging adults (ages 22-25). We observed similar, but non-significant trends in learning from reward. While there was no overall effect of P/T-depletion on reaction time (RT), there was a relationship between the effect of P/T depletion on PAL performance and RT; those who responded more slowly on the P/T[-] beverage also made more errors on the P/T[-] beverage. When P/T-depletion slowed RT after a correct response, there was a worsening of PAL task performance; there was no similar relationship for the RT after an incorrect response and PAL task performance. Moreover, among emerging adults, changes in mood on the P/T[-] beverage negatively correlated with learning from reward on the P/T[-] beverage. Together, we found that both reward- and punishment-based learning are sensitive to central catecholamine levels, and that these effects of acute DA reduction vary with age. Copyright © 2015 Elsevier Inc. All rights reserved.

Finger agnosia and cognitive deficits in patients with Alzheimer's disease.

PubMed

Davis, Andrew S; Trotter, Jeffrey S; Hertza, Jeremy; Bell, Christopher D; Dean, Raymond S

2012-01-01

The purpose of this study was to examine the presence of finger agnosia in patients with Alzheimer's disease (AD) and to determine if level of finger agnosia was related to cognitive impairment. Finger agnosia is a sensitive measure of cerebral impairment and is associated with neurofunctional areas implicated in AD. Using a standardized and norm-referenced approach, results indicated that patients with AD evidenced significantly decreased performance on tests of bilateral finger agnosia compared with healthy age-matched controls. Finger agnosia was predictive of cognitive dysfunction on four of seven domains, including: Crystallized Language, Fluid Processing, Associative Learning, and Processing Speed. Results suggest that measures of finger agnosia, a short and simple test, may be useful in the early detection of AD.

Human umbilical cord plasma proteins revitalize hippocampal function in aged mice

PubMed Central

Castellano, Joseph M.; Mosher, Kira I.; Abbey, Rachelle J.; McBride, Alisha A.; James, Michelle L.; Berdnik, Daniela; Shen, Jadon C.; Zou, Bende; Xie, Xinmin S.; Tingle, Martha; Hinkson, Izumi V.; Angst, Martin S.; Wyss-Coray, Tony

2017-01-01

Ageing drives changes in neuronal and cognitive function, the decline of which is a major feature of many neurological disorders. The hippocampus, a brain region subserving roles of spatial and episodic memory and learning, is sensitive to the detrimental effects of ageing at morphological and molecular levels. With advancing age, synapses in various hippocampal subfields exhibit impaired long-term potentiation1, an electrophysiological correlate of learning and memory. At the molecular level, immediate early genes are among the synaptic plasticity genes that are both induced by long-term potentiation2, 3, 4 and downregulated in the aged brain5, 6, 7, 8. In addition to revitalizing other aged tissues9, 10, 11, 12, 13, exposure to factors in young blood counteracts age-related changes in these central nervous system parameters14, 15, 16, although the identities of specific cognition-promoting factors or whether such activity exists in human plasma remains unknown17. We hypothesized that plasma of an early developmental stage, namely umbilical cord plasma, provides a reservoir of such plasticity-promoting proteins. Here we show that human cord plasma treatment revitalizes the hippocampus and improves cognitive function in aged mice. Tissue inhibitor of metalloproteinases 2 (TIMP2), a blood-borne factor enriched in human cord plasma, young mouse plasma, and young mouse hippocampi, appears in the brain after systemic administration and increases synaptic plasticity and hippocampal-dependent cognition in aged mice. Depletion experiments in aged mice revealed TIMP2 to be necessary for the cognitive benefits conferred by cord plasma. We find that systemic pools of TIMP2 are necessary for spatial memory in young mice, while treatment of brain slices with TIMP2 antibody prevents long-term potentiation, arguing for previously unknown roles for TIMP2 in normal hippocampal function. Our findings reveal that human cord plasma contains plasticity-enhancing proteins of high translational value for targeting ageing- or disease-associated hippocampal dysfunction. PMID:28424512

Fully Automated Deep Learning System for Bone Age Assessment.

PubMed

Lee, Hyunkwang; Tajmir, Shahein; Lee, Jenny; Zissen, Maurice; Yeshiwas, Bethel Ayele; Alkasab, Tarik K; Choy, Garry; Do, Synho

2017-08-01

Skeletal maturity progresses through discrete phases, a fact that is used routinely in pediatrics where bone age assessments (BAAs) are compared to chronological age in the evaluation of endocrine and metabolic disorders. While central to many disease evaluations, little has changed to improve the tedious process since its introduction in 1950. In this study, we propose a fully automated deep learning pipeline to segment a region of interest, standardize and preprocess input radiographs, and perform BAA. Our models use an ImageNet pretrained, fine-tuned convolutional neural network (CNN) to achieve 57.32 and 61.40% accuracies for the female and male cohorts on our held-out test images. Female test radiographs were assigned a BAA within 1 year 90.39% and within 2 years 98.11% of the time. Male test radiographs were assigned 94.18% within 1 year and 99.00% within 2 years. Using the input occlusion method, attention maps were created which reveal what features the trained model uses to perform BAA. These correspond to what human experts look at when manually performing BAA. Finally, the fully automated BAA system was deployed in the clinical environment as a decision supporting system for more accurate and efficient BAAs at much faster interpretation time (<2 s) than the conventional method.

Intranasal Insulin Prevents Anesthesia-Induced Cognitive Impairment and Chronic Neurobehavioral Changes.

PubMed

Chen, Yanxing; Dai, Chun-Ling; Wu, Zhe; Iqbal, Khalid; Liu, Fei; Zhang, Baorong; Gong, Cheng-Xin

2017-01-01

General anesthesia increases the risk for cognitive impairment post operation, especially in the elderly and vulnerable individuals. Recent animal studies on the impact of anesthesia on postoperative cognitive impairment have provided some valuable insights, but much remains to be understood. Here, by using mice of various ages and conditions, we found that anesthesia with propofol and sevoflurane caused significant deficits in spatial learning and memory, as tested using Morris Water Maze (MWM) 2-6 days after anesthesia exposure, in aged (17-18 months old) wild-type (WT) mice and in adult (7-8 months old) 3xTg-AD mice (a triple transgenic mouse model of Alzheimer's disease (AD)), but not in adult WT mice. Anesthesia resulted in long-term neurobehavioral changes in the fear conditioning task carried out 65 days after exposure to anesthesia in 3xTg-AD mice. Importantly, daily intranasal administration of insulin (1.75 U/mouse/day) for only 3 days prior to anesthesia completely prevented the anesthesia-induced deficits in spatial learning and memory and the long-term neurobehavioral changes tested 65 days after exposure to anesthesia in 3xTg-AD mice. These results indicate that aging and AD-like brain pathology increase the vulnerability to cognitive impairment after anesthesia and that intranasal treatment with insulin can prevent anesthesia-induced cognitive impairment.

Concept Learning and Heuristic Classification in Weak-Theory Domains

DTIC Science & Technology

1990-03-01

age and noise-induced cochlear age..gt.60 noise-induced cochlear air(mild) age-induced cochlear history(noise) norma ]_ear speechpoor)acousticneuroma...Annual review of computer science. Machine Learning, 4, 1990. (to appear). [18] R.T. Duran . Concept learning with incomplete data sets. Master’s thesis

Learning and Active Aging

ERIC Educational Resources Information Center

Boulton-Lewis, Gillian M.; Buys, Laurie; Lovie-Kitchin, Jan

2006-01-01

Learning is an important aspect of aging productively. This paper describes results from 2645 respondents (aged from 50 to 74+ years) to a 165-variable postal survey in Australia. The focus is on learning and its relation to work; social, spiritual, and emotional status; health; vision; home; life events; and demographic details. Clustering…

Teaching and Learning in the Digital Age

ERIC Educational Resources Information Center

Starkey, Louise

2012-01-01

"Teaching and Learning in the Digital Age" is for all those interested in considering the impact of emerging digital technologies on teaching and learning. It explores the concept of a digital age and perspectives of knowledge, pedagogy and practice within a digital context. By examining teaching with digital technologies through new learning…

The Effects of Age Factor on Learning English: A Case Study of Learning English in Saudi Schools, Saudi Arabia

ERIC Educational Resources Information Center

Gawi, Elsadig Mohamed Khalifa

2012-01-01

The purpose of this study is to investigate the effect of age on learning English in Saudi Arabia. It aims at encouraging the learning of English as a foreign language at an early age in KSA. The populations of the study are English language teachers and Saudi students in elementary schools compared with intermediate school students in Dawadmi…

We Still Have a Lot to Learn: Learning Experiences of Individuals Age 80 and Older in Care Facilities in a Midwestern State

ERIC Educational Resources Information Center

Grebert, Sheila

2012-01-01

This qualitative study focused on the learning experiences of individuals, age 80 and older, in care facilities in a Midwestern state. Even with the well documented growth of the over age 85 demographic, there are few studies about learning that included this demographic or considered the wants and needs of this group. Using a phenomenological…

Prediction and Validation of Disease Genes Using HeteSim Scores.

PubMed

Zeng, Xiangxiang; Liao, Yuanlu; Liu, Yuansheng; Zou, Quan

2017-01-01

Deciphering the gene disease association is an important goal in biomedical research. In this paper, we use a novel relevance measure, called HeteSim, to prioritize candidate disease genes. Two methods based on heterogeneous networks constructed using protein-protein interaction, gene-phenotype associations, and phenotype-phenotype similarity, are presented. In HeteSim_MultiPath (HSMP), HeteSim scores of different paths are combined with a constant that dampens the contributions of longer paths. In HeteSim_SVM (HSSVM), HeteSim scores are combined with a machine learning method. The 3-fold experiments show that our non-machine learning method HSMP performs better than the existing non-machine learning methods, our machine learning method HSSVM obtains similar accuracy with the best existing machine learning method CATAPULT. From the analysis of the top 10 predicted genes for different diseases, we found that HSSVM avoid the disadvantage of the existing machine learning based methods, which always predict similar genes for different diseases. The data sets and Matlab code for the two methods are freely available for download at http://lab.malab.cn/data/HeteSim/index.jsp.

Teaching dementia care to physical therapy doctoral students: A multimodal experiential learning approach.

PubMed

Lorio, Anne K; Gore, Jane B; Warthen, Lindsey; Housley, Stephen N; Burgess, Elisabeth O

2017-01-01

As the population aged 65 and older grows, it becomes imperative for health care providers to expand their knowledge regarding geriatric conditions and concerns. Dementia is a devastating degenerative disease process that is affecting millions of individuals in the United States, with significant economic and emotional burden on family and caregivers. The need for further dementia education in physical therapy school is essential to improve attitudes and treatment that affect patient outcomes and quality of care. This physical therapy program implemented a 12-hour multimodal experiential learning module designed to educate their students on the challenges associated with dementia to increase knowledge and confidence when treating these patients. The results of this study showed statistically significant improvements in overall confidence and knowledge of treating patients with dementia. The study finds the addition of experiential learning to traditional didactic coursework improves students' reported confidence in working with patients with dementia and understanding the challenges associated with treating patients with dementia.

The Neural Mechanisms of Meditative Practices: Novel Approaches for Healthy Aging.

PubMed

Acevedo, Bianca P; Pospos, Sarah; Lavretsky, Helen

2016-01-01

Meditation has been shown to have physical, cognitive, and psychological health benefits that can be used to promote healthy aging. However, the common and specific mechanisms of response remain elusive due to the diverse nature of mind-body practices. In this review, we aim to compare the neural circuits implicated in focused-attention meditative practices that focus on present-moment awareness to those involved in active-type meditative practices (e.g., yoga) that combine movement, including chanting, with breath practices and meditation. Recent meta-analyses and individual studies demonstrated common brain effects for attention-based meditative practices and active-based meditations in areas involved in reward processing and learning, attention and memory, awareness and sensory integration, and self-referential processing and emotional control, while deactivation was seen in the amygdala, an area implicated in emotion processing. Unique effects for mindfulness practices were found in brain regions involved in body awareness, attention, and the integration of emotion and sensory processing. Effects specific to active-based meditations appeared in brain areas involved in self-control, social cognition, language, speech, tactile stimulation, sensorimotor integration, and motor function. This review suggests that mind-body practices can target different brain systems that are involved in the regulation of attention, emotional control, mood, and executive cognition that can be used to treat or prevent mood and cognitive disorders of aging, such as depression and caregiver stress, or serve as "brain fitness" exercise. Benefits may include improving brain functional connectivity in brain systems that generally degenerate with Alzheimer's disease, Parkinson's disease, and other aging-related diseases.

Does language help regularity learning? The influence of verbalizations on implicit sequential regularity learning and the emergence of explicit knowledge in children, younger and older adults.

PubMed

Ferdinand, Nicola K; Kray, Jutta

2017-03-01

This study aimed at investigating the ability to learn regularities across the life span and examine whether this learning process can be supported or hampered by verbalizations. For this purpose, children (aged 8-10 years) and younger (aged 19-30 years) and older (aged 70-80 years) adults took part in a sequence learning experiment. We found that verbalizing sequence-congruent information during learning is a powerful tool to generate explicit knowledge and it is especially helpful for younger adults. Although recent research suggests that implicit learning can be influenced by directing the participants' attention to relevant aspects of the task, verbalizations had a much weaker influence on implicit than explicit learning. Our results show that verbalizing during learning slows down reaction times (RTs) but does not influence the amount of implicit learning. Especially older adults were not able to overcome the cost of the dual-task situation. Younger adults, in contrast, show an initial dual-tasking cost that, in the case of a helpful verbalization, is overcome with practice and turns into a RT and learning benefit. However, when the verbalization is omitted this benefit is lost, that is, better implicit learning seems to be confined to situations in which the supporting verbalization is maintained. Additionally, we did not find reliable age differences in implicit learning in the no verbalization groups, which speaks in favor of age-invariant models of implicit learning across the life span. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Pharmacological and genetic reversal of age-dependent cognitive deficits attributable to decreased presenilin function.

PubMed

McBride, Sean M J; Choi, Catherine H; Schoenfeld, Brian P; Bell, Aaron J; Liebelt, David A; Ferreiro, David; Choi, Richard J; Hinchey, Paul; Kollaros, Maria; Terlizzi, Allison M; Ferrick, Neal J; Koenigsberg, Eric; Rudominer, Rebecca L; Sumida, Ai; Chiorean, Stephanie; Siwicki, Kathleen K; Nguyen, Hanh T; Fortini, Mark E; McDonald, Thomas V; Jongens, Thomas A

2010-07-14

Alzheimer's disease (AD) is the leading cause of cognitive loss and neurodegeneration in the developed world. Although its genetic and environmental causes are not generally known, familial forms of the disease (FAD) are attributable to mutations in a single copy of the Presenilin (PS) and amyloid precursor protein genes. The dominant inheritance pattern of FAD indicates that it may be attributable to gain or change of function mutations. Studies of FAD-linked forms of presenilin (psn) in model organisms, however, indicate that they are loss of function, leading to the possibility that a reduction in PS activity might contribute to FAD and that proper psn levels are important for maintaining normal cognition throughout life. To explore this issue further, we have tested the effect of reducing psn activity during aging in Drosophila melanogaster males. We have found that flies in which the dosage of psn function is reduced by 50% display age-onset impairments in learning and memory. Treatment with metabotropic glutamate receptor (mGluR) antagonists or lithium during the aging process prevented the onset of these deficits, and treatment of aged flies reversed the age-dependent deficits. Genetic reduction of Drosophila metabotropic glutamate receptor (DmGluRA), the inositol trisphosphate receptor (InsP(3)R), or inositol polyphosphate 1-phosphatase also prevented these age-onset cognitive deficits. These findings suggest that reduced psn activity may contribute to the age-onset cognitive loss observed with FAD. They also indicate that enhanced mGluR signaling and calcium release regulated by InsP(3)R as underlying causes of the age-dependent cognitive phenotypes observed when psn activity is reduced.

Early brain connectivity alterations and cognitive impairment in a rat model of Alzheimer's disease.

PubMed

Muñoz-Moreno, Emma; Tudela, Raúl; López-Gil, Xavier; Soria, Guadalupe

2018-02-07

Animal models of Alzheimer's disease (AD) are essential to understanding the disease progression and to development of early biomarkers. Because AD has been described as a disconnection syndrome, magnetic resonance imaging (MRI)-based connectomics provides a highly translational approach to characterizing the disruption in connectivity associated with the disease. In this study, a transgenic rat model of AD (TgF344-AD) was analyzed to describe both cognitive performance and brain connectivity at an early stage (5 months of age) before a significant concentration of β-amyloid plaques is present. Cognitive abilities were assessed by a delayed nonmatch-to-sample (DNMS) task preceded by a training phase where the animals learned the task. The number of training sessions required to achieve a learning criterion was recorded and evaluated. After DNMS, MRI acquisition was performed, including diffusion-weighted MRI and resting-state functional MRI, which were processed to obtain the structural and functional connectomes, respectively. Global and regional graph metrics were computed to evaluate network organization in both transgenic and control rats. The results pointed to a delay in learning the working memory-related task in the AD rats, which also completed a lower number of trials in the DNMS task. Regarding connectivity properties, less efficient organization of the structural brain networks of the transgenic rats with respect to controls was observed. Specific regional differences in connectivity were identified in both structural and functional networks. In addition, a strong correlation was observed between cognitive performance and brain networks, including whole-brain structural connectivity as well as functional and structural network metrics of regions related to memory and reward processes. In this study, connectivity and neurocognitive impairments were identified in TgF344-AD rats at a very early stage of the disease when most of the pathological hallmarks have not yet been detected. Structural and functional network metrics of regions related to reward, memory, and sensory performance were strongly correlated with the cognitive outcome. The use of animal models is essential for the early identification of these alterations and can contribute to the development of early biomarkers of the disease based on MRI connectomics.

A pilot project of an online cross-age tutoring program: crescent school virtual learning (vLearning).

PubMed

Chow, Ronald

2016-11-01

Traditional classroom teaching is the standard of education. However, there may be some students who feel uncomfortable approaching their teachers and may feel more at ease if they ask for assistance from their peers. There are two types of student-to-student tutoring methods that are supplements to classroom learning: peer tutoring between same-age students and cross-age tutoring between different-age children. Cross-age tutoring programs in which the tutor is 2-3 years older than the tutee have been reported to be more effective than those between same-age students in promoting student responsibility, empowerment and academic performance. A pilot online cross-age tutoring program was launched in September 2014 at Crescent School. A new website was designed, created and implemented with the permission and regular monitoring of the Student Services faculty for the online program - Crescent School Virtual Learning (vLearning). The program was well received and will undergo evaluation in the future.

Beneficial effects of glycine (bioglycin) on memory and attention in young and middle-aged adults.

PubMed

File, S E; Fluck, E; Fernandes, C

1999-12-01

The N-methyl D-aspartate receptor complex is involved in the mechanism of long-term potentiation, which is thought to be the biological basis of learning and memory. This complex can be manipulated in a number of ways, one of which is through the strychnine-insensitive glycine receptor coagonist site. The effects of Bioglycin(Konapharma, Pratteln, Switzerland), a biologically active form of the amino acid glycine, were therefore studied in healthy students (mean age, 20.7 years) and middle-aged men (mean age, 58.9 years) with tests that measured attention, memory and mood, using a double-blind, randomized, crossover design. Compared with the young group, the middle-aged group had significantly poorer verbal episodic memory, focused, divided, and sustained attention; they also differed in their subjective responses at the end of testing. Bioglycin significantly improved retrieval from episodic memory in both the young and the middle-aged groups, but it did not affect focused or divided attention. However, the middle-aged men significantly benefited from Bioglycin in the sustained-attention task. The effects of Bioglycin differed from those of other cognitive enhancers in that it was without stimulant properties or significant effects on mood, and it primarily improved memory rather than attention. It is likely to be of benefit in young or older people in situations where high retrieval of information is needed or when performance is impaired by jet lag, shift work, or disrupted sleep. It may also benefit the impaired retrieval shown in patients with schizophrenia, Parkinson's disease, and Huntington's disease.

Cognitive procedural learning among children and adolescents with or without spastic cerebral palsy: the differential effect of age.

PubMed

Gofer-Levi, M; Silberg, T; Brezner, A; Vakil, E

2014-09-01

Children learn to engage their surroundings skillfully, adopting implicit knowledge of complex regularities and associations. Probabilistic classification learning (PCL) is a type of cognitive procedural learning in which different cues are probabilistically associated with specific outcomes. Little is known about the effects of developmental disorders on cognitive skill acquisition. Twenty-four children and adolescents with cerebral palsy (CP) were compared to 24 typically developing (TD) youth in their ability to learn probabilistic associations. Performance was examined in relation to general cognitive abilities, level of motor impairment and age. Improvement in PCL was observed for all participants, with no relation to IQ. An age effect was found only among TD children. Learning curves of children with CP on a cognitive procedural learning task differ from those of TD peers and do not appear to be age sensitive. Copyright © 2014 Elsevier Ltd. All rights reserved.

Learning about Parkinson's Disease

MedlinePlus

... having genetic testing can learn more about their risk for Parkinson's disease and the availability and accuracy of genetic testing for this disease by setting up an appointment with a genetics health professional. Genetic professionals work as members of health ...

Down syndrome with end-stage renal disease.

PubMed

Kute, Vivek B; Vanikar, Aruna V; Shah, Pankaj R; Gumber, Manoj R; Patel, Himanshu V; Engineer, Divyesh P; Thakkar, Umang G; Trivedi, Hargovind L

2013-10-01

Down syndrome is one of the most common genetic causes of learning disabilities in children. Although the incidence of renal and urological involvement in Down syndrome is not very common, monitoring of patients with Down syndrome for renal diseases should be done regularly as patient's age into the second and third decades. With increased survival, it appears that a growing number of these patients present with chronic renal failure. Down syndrome patients are apparently not suited for peritoneal dialysis because of lacking cooperation. This procedure can be prone to failure, mainly because of an increased risk of peritonitis. Handling such patients especially those on peritoneal dialysis is challenging. Here we report a case of Down syndrome with end-stage renal disease treated with hemodialysis for 6 months. To the best of our knowledge and current literature review this is the first case report of a patient with Down syndrome undergoing hemodialysis.

[Toxoplasmosis, a parasitic zoonoses prevalent in Chile: count and challenges].

PubMed

Mimica, Francisco; Muñoz-Zanzi, Claudia; Torres, Marisa; Padilla, Oslando

2015-10-01

Toxoplasmosis, cosmopolitan parasitic zoonosis often found in humans, is transmitted mainly by food and water, and is considered a significant risk of morbidity and mortality in pregnant women, newborns and immunocompromised patients. To identify the information about this zoonosis and its first reports in Chile. Review of publications in Pubmed, Mesh search of systematic reviews, case studies, cross-sectional studies, systematic reviews, meta-analysis and specialty publications. In addition, other publications in parasitology journals were analyzed. There are reports of the presence of this disease in Chile for 60 years. During this time several differences in prevalence depending on geographic location, age and education level of the population have been detected. There is low epidemiological vigilance and lack of specific official preventive measures for this disease, despite the possible introduction of new parasite genotypes of an increased virulence and pathogenicity in the country through the importation of meat. New enigmas have arisen in relation to this disease associating it with Alzheimer, Parkinson's disease, autism, learning disabilities, among others.

[Alzheimer's Therapeutic Research Institute].

PubMed

Shimada, Hiroyuki; Kato, Yuichi; Fujii, Hisako; Mori, Hiroshi

2017-07-01

The Alzheimer's Therapeutic Research Institute (ATRI) was established in 2015 after ATRI director, Paul Aisen, and his fellow experts in therapeutic interventions for Alzheimer's disease (AD) moved from the Alzheimer's Disease Cooperative Study (ADCS) at the University of California to the Keck School of Medicine of the University of Southern California. The National Institute on Aging (NIA) decided to commit $14 million to the ATRI via an Alzheimer's Clinical Trials Consortium (ACTC). The ATRI supports various studies such as the Anti-Amyloid Treatment in Asymptomatic Alzheimer's study ("A4 study"), Alzheimer's Disease Neuroimaging Initiative 3 (ADNI3), Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN), and The Alzheimer's Disease Neuroimaging Initiative-Depression Project (ADNI-D). The ATRI will share all relevant data and materials with the academic community, corporations, and government organizations. The ATRI is overseen by a Data and Safety Monitoring Board (DSMB), which comprises of leading experts in the field of Alzheimer's research and acts independently. The ATRI is slated to play a central role in clinical dementia research in the US in near future.

Motor learning, retention and transfer after virtual-reality-based training in Parkinson's disease--effect of motor and cognitive demands of games: a longitudinal, controlled clinical study.

PubMed

dos Santos Mendes, Felipe Augusto; Pompeu, José Eduardo; Modenesi Lobo, Alexandra; Guedes da Silva, Keyte; Oliveira, Tatiana de Paula; Peterson Zomignani, Andrea; Pimentel Piemonte, Maria Elisa

2012-09-01

To evaluate the learning, retention and transfer of performance improvements after Nintendo Wii Fit™ training in patients with Parkinson's disease and healthy elderly people. Longitudinal, controlled clinical study. Sixteen patients with early-stage Parkinson's disease and 11 healthy elderly people. Warm-up exercises and Wii Fit training that involved training motor (shifts centre of gravity and step alternation) and cognitive skills. A follow-up evaluative Wii Fit session was held 60 days after the end of training. Participants performed a functional reach test before and after training as a measure of learning transfer. Learning and retention were determined based on the scores of 10 Wii Fit games over eight sessions. Transfer of learning was assessed after training using the functional reach test. Patients with Parkinson's disease showed no deficit in learning or retention on seven of the 10 games, despite showing poorer performance on five games compared with the healthy elderly group. Patients with Parkinson's disease showed marked learning deficits on three other games, independent of poorer initial performance. This deficit appears to be associated with cognitive demands of the games which require decision-making, response inhibition, divided attention and working memory. Finally, patients with Parkinson's disease were able to transfer motor ability trained on the games to a similar untrained task. The ability of patients with Parkinson's disease to learn, retain and transfer performance improvements after training on the Nintendo Wii Fit depends largely on the demands, particularly cognitive demands, of the games involved, reiterating the importance of game selection for rehabilitation purposes. Copyright © 2012 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

Machine learning based detection of age-related macular degeneration (AMD) and diabetic macular edema (DME) from optical coherence tomography (OCT) images

PubMed Central

Wang, Yu; Zhang, Yaonan; Yao, Zhaomin; Zhao, Ruixue; Zhou, Fengfeng

2016-01-01

Non-lethal macular diseases greatly impact patients’ life quality, and will cause vision loss at the late stages. Visual inspection of the optical coherence tomography (OCT) images by the experienced clinicians is the main diagnosis technique. We proposed a computer-aided diagnosis (CAD) model to discriminate age-related macular degeneration (AMD), diabetic macular edema (DME) and healthy macula. The linear configuration pattern (LCP) based features of the OCT images were screened by the Correlation-based Feature Subset (CFS) selection algorithm. And the best model based on the sequential minimal optimization (SMO) algorithm achieved 99.3% in the overall accuracy for the three classes of samples. PMID:28018716

Longitudinal attentional engagement rescues mice from age-related cognitive declines and cognitive inflexibility

PubMed Central

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 maze task that required the mice to remember and operate on two sets of overlapping guidance (spatial) cues. As previously reported, this training resulted in an immediate (at 4 mo of age) improvement in the animals' aggregate performance across a battery of five learning tasks. Subsequently, these animals received an additional 3 d of working memory training at 3-wk intervals for 15 mo (totaling 66 training sessions), and at 18 mo of age were assessed on a selective attention task, a second set of learning tasks, and variations of those tasks that required the animals to modify the previously learned response. Both attentional and learning abilities (on passive avoidance, active avoidance, and reinforced alternation tasks) were impaired in aged animals that had not received working memory training. Likewise, these aged animals exhibited consistent deficits when required to modify a previously instantiated learned response (in reinforced alternation, active avoidance, and spatial water maze). In contrast, these attentional, learning, and perseverative deficits were attenuated in aged animals that had undergone lifelong working memory exercise. These results suggest that general impairments of learning, attention, and cognitive flexibility may be mitigated by a cognitive exercise regimen that requires chronic attentional engagement. PMID:21521768

Longitudinal attentional engagement rescues mice from age-related cognitive declines and cognitive inflexibility.

PubMed

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 maze task that required the mice to remember and operate on two sets of overlapping guidance (spatial) cues. As previously reported, this training resulted in an immediate (at 4 mo of age) improvement in the animals' aggregate performance across a battery of five learning tasks. Subsequently, these animals received an additional 3 d of working memory training at 3-wk intervals for 15 mo (totaling 66 training sessions), and at 18 mo of age were assessed on a selective attention task, a second set of learning tasks, and variations of those tasks that required the animals to modify the previously learned response. Both attentional and learning abilities (on passive avoidance, active avoidance, and reinforced alternation tasks) were impaired in aged animals that had not received working memory training. Likewise, these aged animals exhibited consistent deficits when required to modify a previously instantiated learned response (in reinforced alternation, active avoidance, and spatial water maze). In contrast, these attentional, learning, and perseverative deficits were attenuated in aged animals that had undergone lifelong working memory exercise. These results suggest that general impairments of learning, attention, and cognitive flexibility may be mitigated by a cognitive exercise regimen that requires chronic attentional engagement.

Longitudinal analysis of the behavioral phenotype in a novel transgenic rat model of early stages of Alzheimer's disease.

PubMed

Galeano, Pablo; Martino Adami, Pamela V; Do Carmo, Sonia; Blanco, Eduardo; Rotondaro, Cecilia; Capani, Francisco; Castaño, Eduardo M; Cuello, A Claudio; Morelli, Laura

2014-01-01

Intraneuronal accumulation of amyloid β (iAβ) has been linked to mild cognitive impairment that may precede Alzheimer's disease (AD) onset. This neuropathological trait was recently mimicked in a novel animal model of AD, the hemizygous transgenic McGill-R-Thy1-APP (Tg(+/-)) rat. The characterization of the behavioral phenotypes in this animal model could provide a baseline of efficacy for earlier therapeutic interventions. The aim of the present study was to undertake a longitudinal study of Aβ accumulation and a comprehensive behavioral evaluation of this transgenic rat model. We assessed exploratory activity, anxiety-related behaviors, recognition memory, working memory, spatial learning and reference memory at 3, 6, and 12 months of age. In parallel, we measured Aβ by ELISA, Western blots and semiquantitative immunohistochemistry in hippocampal samples. SDS-soluble Aβ peptide accumulated at low levels (~9 pg/mg) without differences among ages. However, Western blots showed SDS-resistant Aβ oligomers (~30 kDa) at 6 and 12 months, but not at 3 months. When compared to wild-type (WT), male Tg(+/-) rats exhibited a spatial reference memory deficit in the Morris Water Maze (MWM) as early as 3 months of age, which persisted at 6 and 12 months. In addition, Tg(+/-) rats displayed a working memory impairment in the Y-maze and higher anxiety levels in the Open Field (OF) at 6 and 12 months of age, but not at 3 months. Exploratory activity in the OF was similar to that of WT at all-time points. Spatial learning in the MWM and the recognition memory, as assessed by the Novel Object Recognition Test, were unimpaired at any time point. The data from the present study demonstrate that the hemizygous transgenic McGill-R-Thy1-APP rat has a wide array of behavioral and cognitive impairments from young adulthood to middle-age. The low Aβ burden and early emotional and cognitive deficits in this transgenic rat model supports its potential use for drug discovery purposes in early AD.

Longitudinal analysis of the behavioral phenotype in a novel transgenic rat model of early stages of Alzheimer's disease

PubMed Central

Galeano, Pablo; Martino Adami, Pamela V.; Do Carmo, Sonia; Blanco, Eduardo; Rotondaro, Cecilia; Capani, Francisco; Castaño, Eduardo M.; Cuello, A. Claudio; Morelli, Laura

2014-01-01

Intraneuronal accumulation of amyloid β (iAβ) has been linked to mild cognitive impairment that may precede Alzheimer's disease (AD) onset. This neuropathological trait was recently mimicked in a novel animal model of AD, the hemizygous transgenic McGill-R-Thy1-APP (Tg+/−) rat. The characterization of the behavioral phenotypes in this animal model could provide a baseline of efficacy for earlier therapeutic interventions. The aim of the present study was to undertake a longitudinal study of Aβ accumulation and a comprehensive behavioral evaluation of this transgenic rat model. We assessed exploratory activity, anxiety-related behaviors, recognition memory, working memory, spatial learning and reference memory at 3, 6, and 12 months of age. In parallel, we measured Aβ by ELISA, Western blots and semiquantitative immunohistochemistry in hippocampal samples. SDS-soluble Aβ peptide accumulated at low levels (~9 pg/mg) without differences among ages. However, Western blots showed SDS-resistant Aβ oligomers (~30 kDa) at 6 and 12 months, but not at 3 months. When compared to wild-type (WT), male Tg+/− rats exhibited a spatial reference memory deficit in the Morris Water Maze (MWM) as early as 3 months of age, which persisted at 6 and 12 months. In addition, Tg+/− rats displayed a working memory impairment in the Y-maze and higher anxiety levels in the Open Field (OF) at 6 and 12 months of age, but not at 3 months. Exploratory activity in the OF was similar to that of WT at all-time points. Spatial learning in the MWM and the recognition memory, as assessed by the Novel Object Recognition Test, were unimpaired at any time point. The data from the present study demonstrate that the hemizygous transgenic McGill-R-Thy1-APP rat has a wide array of behavioral and cognitive impairments from young adulthood to middle-age. The low Aβ burden and early emotional and cognitive deficits in this transgenic rat model supports its potential use for drug discovery purposes in early AD. PMID:25278855

Comparison of Conditioning Impairments in Children with Down Syndrome, Autistic Spectrum Disorders and Mental Age-Matched Controls

ERIC Educational Resources Information Center

Reed, P.; Staytom, L.; Stott, S.; Truzoli, R.

2011-01-01

Background: This study investigated the relative ease of learning across four tasks suggested by an adaptation of Thomas's hierarchy of learning in children with Down syndrome, autism spectrum disorders and mental age-matched controls. Methods: Learning trials were carried out to investigate observational learning, instrumental learning, reversal…

Learning Style Preferences of Elderly Coronary Artery Disease Patients.

ERIC Educational Resources Information Center

Theis, Saundra L.; Merritt, Sharon L.

1992-01-01

The Patient Learning Styles Questionnaire derived from Canfield and administered to 134 elderly coronary artery disease patients revealed the following order of learning preferences: structure, iconics, listening, direct experience, reading, achievement, affiliation, and eminence. Level of education significantly influenced preferred learning…

Use of low frequency repetitive transcranial magnetic stimulation to reduce context-dependent learning in people with Parkinson's disease.

PubMed

Lee, Ya-Yun; Fisher, Beth E

2017-05-22

Compared with age-matched non-disabled adults, people with Parkinson's disease (PD) demonstrated greater context-dependent learning, a phenomenon in which an individual shows inferior motor performance when the testing environmental context is different from the original practice context. Additionally, enhanced context- dependency has been shown to be associated with an increased activation of the dorsolateral prefrontal cortex (DLPFC). This study aimed to determine whether context-dependent learning in people with PD could be reduced by decreasing DLPFC activation with low frequency repetitive transcranial magnetic stimulation (rTMS). Quasi-experimental pre-post test controlled study. University laboratory. Twenty-seven participants (18 individuals with PD and 9 age-matched non- disabled adults) were recruited into the PD, PD_rTMS (PD participants who received low frequency rTMS), and Control groups. All participants practiced a finger sequence task containing 3 sequences embedded within specific contexts (colored circles and spatial location on a computer screen) on the first day. On day 2, the participants were tested under the SWITCH and SAME conditions. In the SWITCH condition, the sequence-context association changed from that of practice; in the SAME condition, the sequence-context association remained the same as practice. The PD_rTMS group received 1 Hz rTMS applied over the left DLPFC on the second day before the testing conditions. Switch cost, the performance difference between the SWITCH and SAME conditions, was calculated to indicate context-dependency. All participants improved throughout practice on the first day. Analysis of the switch cost revealed a significant group main effect (p = 0.050). Post-hoc analysis revealed that the PD_rTMS group had significantly smaller switch cost than the PD group (p = 0.031) but not the Control group. Low frequency rTMS applied over DLPFC reduced context-dependency in people with PD. The findings provide a preliminary evidence of using low frequency rTMS as an adjuvant intervention approach to facilitate individuals with PD to generalize a learned motor task from one environmental context to another.

Explicit Instruction, Bilingualism, and the Older Adult Learner

ERIC Educational Resources Information Center

Cox, Jessica G.

2017-01-01

Little is known about older adult language learners and effects of aging on L2 learning. This study investigated learning in older age through interactions of learner-internal and -external variables; specifically, late-learned L2 (bilingualism) and provision of grammar explanation (explicit instruction, EI). Forty-three older adults (age 60+) who…

The Role of Age and Occupational Future Time Perspective in Workers' Motivation to Learn

ERIC Educational Resources Information Center

Kochoian, Nané; Raemdonck, Isabel; Frenay, Mariane; Zacher, Hannes

2017-01-01

The purpose of this paper is to better understand the relationship between employees' chronological age and their motivation to learn, by adopting a lifespan perspective. Based on socioemotional selectivity theory, we suggest that occupational future time perspective mediates the relationship between age and motivation to learn. In accordance with…

The Effects of Age, IQ, and Sentence Mediation Strategy Training on Paired-Associates Learning. Studies in Learning Potential, Volume 3, Number 43.

ERIC Educational Resources Information Center

Stein, Joan Lerner; Budoff, Milton

Compared were performances of 39 educable mentally retarded (EMR) Ss, mean chronological age (CA) 11 1/2 years, mean mental age (MA) 7 3/4 years; 25 fifth graders matched on CA; and 27 second graders matched on MA to determine whether children of different ages and IQ spontaneously demonstrate learning strategies after repeated practice with…

Exploring educational needs and design aspects of internet-enabled patient education for persons with diabetes: a qualitative interview study

PubMed Central

Jafari, Javad; Karimi Moonaghi, Hosein; Zary, Nabil; Masiello, Italo

2016-01-01

Objective The objective of this article is to explore the educational needs and design aspects of personalised internet-enabled education for patients with diabetes in Iran. Design Data were collected using semistructured interviews and then qualitatively analysed using inductive content analysis. Participants 9 patients with type 2 diabetes were included. Inclusion criteria were access to and knowledge on how to use the internet. The selection ensured representation based on gender, age, occupation and educational background. Setting The sample population was patients with diabetes who were admitted to an outpatient diabetes clinic in Mashhad, a large city of Iran with about 3 million inhabitants. Results 4 core categories emerged from the data: (1) seeking knowledge about diabetes, including specific knowledge acquisition, patient's interactions and learning requirements; (2) teaching and learning, including using different teaching methods and different ways to learn about the disease; (3) facilitators, including internet and mobile phone use to learn about the disease; and (4) barriers, including lack of internet access, uncertainty of access to the internet and lack of website in the local language and also perceived cultural barriers, such as patients' fears of the internet, lack of time and awareness. Conclusions This study provides a better understanding of the patient's educational expectations and technical needs in relation to internet-enabled education. This knowledge will inform the development of functional mock-ups in the next research phase using a design-based research approach in order to design internet-enabled patient education for self-management of diabetes. PMID:27799245

Is the Role of External Feedback in Auditory Skill Learning Age Dependent?

PubMed

Zaltz, Yael; Roth, Daphne Ari-Even; Kishon-Rabin, Liat

2017-12-20

The purpose of this study is to investigate the role of external feedback in auditory perceptual learning of school-age children as compared with that of adults. Forty-eight children (7-9 years of age) and 64 adults (20-35 years of age) conducted a training session using an auditory frequency discrimination (difference limen for frequency) task, with external feedback (EF) provided for half of them. Data supported the following findings: (a) Children learned the difference limen for frequency task only when EF was provided. (b) The ability of the children to benefit from EF was associated with better cognitive skills. (c) Adults showed significant learning whether EF was provided or not. (d) In children, within-session learning following training was dependent on the provision of feedback, whereas between-sessions learning occurred irrespective of feedback. EF was found beneficial for auditory skill learning of 7-9-year-old children but not for young adults. The data support the supervised Hebbian model for auditory skill learning, suggesting combined bottom-up internal neural feedback controlled by top-down monitoring. In the case of immature executive functions, EF enhanced auditory skill learning. This study has implications for the design of training protocols in the auditory modality for different age groups, as well as for special populations.

Striatum-medial prefrontal cortex connectivity predicts developmental changes in reinforcement learning.

PubMed

van den Bos, Wouter; Cohen, Michael X; Kahnt, Thorsten; Crone, Eveline A

2012-06-01

During development, children improve in learning from feedback to adapt their behavior. However, it is still unclear which neural mechanisms might underlie these developmental changes. In the current study, we used a reinforcement learning model to investigate neurodevelopmental changes in the representation and processing of learning signals. Sixty-seven healthy volunteers between ages 8 and 22 (children: 8-11 years, adolescents: 13-16 years, and adults: 18-22 years) performed a probabilistic learning task while in a magnetic resonance imaging scanner. The behavioral data demonstrated age differences in learning parameters with a stronger impact of negative feedback on expected value in children. Imaging data revealed that the neural representation of prediction errors was similar across age groups, but functional connectivity between the ventral striatum and the medial prefrontal cortex changed as a function of age. Furthermore, the connectivity strength predicted the tendency to alter expectations after receiving negative feedback. These findings suggest that the underlying mechanisms of developmental changes in learning are not related to differences in the neural representation of learning signals per se but rather in how learning signals are used to guide behavior and expectations.

Learning to Read in the Digital Age

ERIC Educational Resources Information Center

Rose, David; Dalton, Bridget

2009-01-01

The digital age offers transformative opportunities for individualization of learning. First, modern imaging technologies have changed our understanding of learning and the sources and ranges of its diversity. Second, digital technologies make it possible to design learning environments that are responsive to individual differences. We draw on…

Nutrients, Microglia Aging, and Brain Aging.

PubMed

Wu, Zhou; Yu, Janchun; Zhu, Aiqin; Nakanishi, Hiroshi

2016-01-01

As the life expectancy continues to increase, the cognitive decline associated with Alzheimer's disease (AD) becomes a big major issue in the world. After cellular activation upon systemic inflammation, microglia, the resident immune cells in the brain, start to release proinflammatory mediators to trigger neuroinflammation. We have found that chronic systemic inflammatory challenges induce differential age-dependent microglial responses, which are in line with the impairment of learning and memory, even in middle-aged animals. We thus raise the concept of "microglia aging." This concept is based on the fact that microglia are the key contributor to the acceleration of cognitive decline, which is the major sign of brain aging. On the other hand, inflammation induces oxidative stress and DNA damage, which leads to the overproduction of reactive oxygen species by the numerous types of cells, including macrophages and microglia. Oxidative stress-damaged cells successively produce larger amounts of inflammatory mediators to promote microglia aging. Nutrients are necessary for maintaining general health, including the health of brain. The intake of antioxidant nutrients reduces both systemic inflammation and neuroinflammation and thus reduces cognitive decline during aging. We herein review our microglia aging concept and discuss systemic inflammation and microglia aging. We propose that a nutritional approach to controlling microglia aging will open a new window for healthy brain aging.

Nutrients, Microglia Aging, and Brain Aging

PubMed Central

Wu, Zhou; Yu, Janchun; Zhu, Aiqin; Nakanishi, Hiroshi

2016-01-01

As the life expectancy continues to increase, the cognitive decline associated with Alzheimer's disease (AD) becomes a big major issue in the world. After cellular activation upon systemic inflammation, microglia, the resident immune cells in the brain, start to release proinflammatory mediators to trigger neuroinflammation. We have found that chronic systemic inflammatory challenges induce differential age-dependent microglial responses, which are in line with the impairment of learning and memory, even in middle-aged animals. We thus raise the concept of “microglia aging.” This concept is based on the fact that microglia are the key contributor to the acceleration of cognitive decline, which is the major sign of brain aging. On the other hand, inflammation induces oxidative stress and DNA damage, which leads to the overproduction of reactive oxygen species by the numerous types of cells, including macrophages and microglia. Oxidative stress-damaged cells successively produce larger amounts of inflammatory mediators to promote microglia aging. Nutrients are necessary for maintaining general health, including the health of brain. The intake of antioxidant nutrients reduces both systemic inflammation and neuroinflammation and thus reduces cognitive decline during aging. We herein review our microglia aging concept and discuss systemic inflammation and microglia aging. We propose that a nutritional approach to controlling microglia aging will open a new window for healthy brain aging. PMID:26941889

ProDiGe: Prioritization Of Disease Genes with multitask machine learning from positive and unlabeled examples

PubMed Central

2011-01-01

Background Elucidating the genetic basis of human diseases is a central goal of genetics and molecular biology. While traditional linkage analysis and modern high-throughput techniques often provide long lists of tens or hundreds of disease gene candidates, the identification of disease genes among the candidates remains time-consuming and expensive. Efficient computational methods are therefore needed to prioritize genes within the list of candidates, by exploiting the wealth of information available about the genes in various databases. Results We propose ProDiGe, a novel algorithm for Prioritization of Disease Genes. ProDiGe implements a novel machine learning strategy based on learning from positive and unlabeled examples, which allows to integrate various sources of information about the genes, to share information about known disease genes across diseases, and to perform genome-wide searches for new disease genes. Experiments on real data show that ProDiGe outperforms state-of-the-art methods for the prioritization of genes in human diseases. Conclusions ProDiGe implements a new machine learning paradigm for gene prioritization, which could help the identification of new disease genes. It is freely available at http://cbio.ensmp.fr/prodige. PMID:21977986

The beneficial effects of cognitive training with simple calculation and reading aloud in an elderly postsurgical population: study protocol for a randomized controlled trial.

PubMed

Kulason, Kay; Nouchi, Rui; Hoshikawa, Yasushi; Noda, Masafumi; Okada, Yoshinori; Kawashima, Ryuta

2016-07-22

This project proposes a pilot study to investigate the positive healing effects of cognitive training with simple arithmetic and reading aloud on elderly postsurgical patients. Elderly patients undergoing surgery have an increased risk of Postoperative Cognitive Decline (POCD), a condition in which learning, memory, and processing speed is greatly reduced after surgery. Since elderly patients are more likely to exhibit symptoms of POCD, the incidence is increasing as the population receiving surgery has aged. Little effort has been expended, however, to find treatments for POCD. Learning therapy, which consists of a combination of reading aloud and solving simple arithmetic problems, was developed in Japan as a treatment for Alzheimer's Disease to improve cognitive functions. Because patients with Alzheimer's Disease experience similar issues as those with POCD in learning, memory, and processing speed, a cognitive intervention based on the learning-therapy treatments used for Alzheimer's Disease could show advantageous outcomes for those at risk of POCD. Cognitive function will be measured before and after surgery using three different tests (Mini-Mental Status Exam, Frontal Assessment Battery, and Cogstate computerized tests). Subjects will be randomly divided into two groups-one that receives a Simple Calculation and Reading Aloud intervention (SCRA) and a waitlisted control group that does not receive SCRA. To measure cognition before and after the intervention, the previously mentioned three tests will be used. The obtained data will be analyzed using statistical tests such as ANCOVA to indicate whether the cognitive intervention group has made improvements in their cognitive functions. In addition, questionnaires will also be administered to collect data on mental and emotional statuses. This report will be the first pilot study to investigate the beneficial effects of SCRA on elderly surgical patients. Previous studies have shown sufficient evidence on the effectiveness of learning therapy in healthy elderly people and in those with Dementia. Therefore, this study will clarify whether SCRA can improve cognitive function in the more specialized group of elderly surgical patients. University Hospital Medical Information Network Clinical Trial Registry, UMIN000019832 . Registered on 18 November 2015.

Ventral striatal network connectivity reflects reward learning and behavior in patients with Parkinson's disease.

PubMed

Petersen, Kalen; Van Wouwe, Nelleke; Stark, Adam; Lin, Ya-Chen; Kang, Hakmook; Trujillo-Diaz, Paula; Kessler, Robert; Zald, David; Donahue, Manus J; Claassen, Daniel O

2018-01-01

A subgroup of Parkinson's disease (PD) patients treated with dopaminergic therapy develop compulsive reward-driven behaviors, which can result in life-altering morbidity. The mesocorticolimbic dopamine network guides reward-motivated behavior; however, its role in this treatment-related behavioral phenotype is incompletely understood. Here, mesocorticolimbic network function in PD patients who develop impulsive and compulsive behaviors (ICB) in response to dopamine agonists was assessed using BOLD fMRI. The tested hypothesis was that network connectivity between the ventral striatum and the limbic cortex is elevated in patients with ICB and that reward-learning proficiency reflects the extent of mesocorticolimbic network connectivity. To evaluate this hypothesis, 3.0T BOLD-fMRI was applied to measure baseline functional connectivity on and off dopamine agonist therapy in age and sex-matched PD patients with (n = 19) or without (n = 18) ICB. An incentive-based task was administered to a subset of patients (n = 20) to quantify positively or negatively reinforced learning. Whole-brain voxelwise analyses and region-of-interest-based mixed linear effects modeling were performed. Elevated ventral striatal connectivity to the anterior cingulate gyrus (P = 0.013), orbitofrontal cortex (P = 0.034), insula (P = 0.044), putamen (P = 0.014), globus pallidus (P < 0.01), and thalamus (P < 0.01) was observed in patients with ICB. A strong trend for elevated amygdala-to-midbrain connectivity was found in ICB patients on dopamine agonist. Ventral striatum-to-subgenual cingulate connectivity correlated with reward learning (P < 0.01), but not with punishment-avoidance learning. These data indicate that PD-ICB patients have elevated network connectivity in the mesocorticolimbic network. Behaviorally, proficient reward-based learning is related to this enhanced limbic and ventral striatal connectivity. Hum Brain Mapp 39:509-521, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Ageing and learning as conceptualized by senior adults in two cultures: Hong Kong and Australia.

PubMed

Tam, Maureen; Aird, Rosemary; Boulton-Lewis, Gillian; Buys, Laurie

2016-01-01

This paper is about a study aimed to understand what successful ageing and later life learning mean to older adults in two cultures: Hong Kong and Australia. It aims to shed light on (1) the meaning of ageing and learning as conceptualized by elders in Hong Kong and Australia; (2) the reasons for participation in later life learning, as well as, barriers for non-participation; (3) their learning interests and instructional preferences; and (4) the correlation between learning and successful ageing, and between learning and other well-being variables, including health, happiness and satisfaction. Two large samples of elders from Hong Kong (n=519) and Australia (n=421) participated in the study. A self-developed questionnaire, called the "Learning and Ageing Survey 2013", was used. It included a total of 108 structured questions in three sections. Within group analysis of the data from the two locations indicated that there are more similarities, rather than differences, between elders in Hong Kong and Australia with respect to background characteristics, meanings of ageing and learning, reasons for participation, barriers for nonparticipation, learning interests and instructional preferences. The fact that there are more commonalities, rather than differences, between the two samples of elders from two different cultures supports the claim that cultures very often overlap and coincide, and need not be seen as polarized, where becoming bi-cultural is possible. It is therefore important for cross-cultural comparative research to identify cultural differences, while at the same time, to recognize the existence of similarities between cultures.

The Role of Age and Executive Function in Auditory Category Learning

PubMed Central

Reetzke, Rachel; Maddox, W. Todd; Chandrasekaran, Bharath

2015-01-01

Auditory categorization is a natural and adaptive process that allows for the organization of high-dimensional, continuous acoustic information into discrete representations. Studies in the visual domain have identified a rule-based learning system that learns and reasons via a hypothesis-testing process that requires working memory and executive attention. The rule-based learning system in vision shows a protracted development, reflecting the influence of maturing prefrontal function on visual categorization. The aim of the current study is two-fold: (a) to examine the developmental trajectory of rule-based auditory category learning from childhood through adolescence, into early adulthood; and (b) to examine the extent to which individual differences in rule-based category learning relate to individual differences in executive function. Sixty participants with normal hearing, 20 children (age range, 7–12), 21 adolescents (age range, 13–19), and 19 young adults (age range, 20–23), learned to categorize novel dynamic ripple sounds using trial-by-trial feedback. The spectrotemporally modulated ripple sounds are considered the auditory equivalent of the well-studied Gabor patches in the visual domain. Results revealed that auditory categorization accuracy improved with age, with young adults outperforming children and adolescents. Computational modeling analyses indicated that the use of the task-optimal strategy (i.e. a conjunctive rule-based learning strategy) improved with age. Notably, individual differences in executive flexibility significantly predicted auditory category learning success. The current findings demonstrate a protracted development of rule-based auditory categorization. The results further suggest that executive flexibility coupled with perceptual processes play important roles in successful rule-based auditory category learning. PMID:26491987

The use of errorless learning strategies for patients with Alzheimer's disease: a literature review.

PubMed

Li, Ruijie; Liu, Karen P Y

2012-12-01

The aim of this article was to review the evidence of errorless learning on learning outcomes in patients with early-stage Alzheimer's disease. A computer-aided literature search from 1999 to 2011 was carried out using MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO and PsycArticles. Keywords included 'errorless learning or practice' and 'Alzheimer's disease'. Four studies that fulfilled the inclusion criteria were selected and reviewed. Two of the studies were clinical controlled trials: one was a single-group pretest-post-test trial and the other was a multiple single-participant study. Demographic variables, design, treatment and outcome measures were summarized. Recall trials were used as the primary outcome measure. Results indicate that the use of errorless learning promotes better retention of specific types of information. Errorless learning is effective in memory rehabilitation of older adults with Alzheimer's disease. However, it would require more studies with unified outcome measures to allow for the formulation of standardized clinical protocol and recommendations.

The construction of learning objects on communicable diseases for community health agents.

PubMed

Pacheco, Kátia Cilene Ferreira; Azambuja, Marcelo Schenk de; Bonamigo, Andrea Wander

2018-06-07

To describe the creation of a learning object about communicable diseases and their identification, monitoring, and prevention for community health agents. The qualitative, exploratory, case study conducted in the North District Management Zone - Baltazar of the Universidade Federal de Ciências da Saúde de Porto Alegre, from October to January 2015 2016. The study had 58 participants and consisted of the stages field research, Bardin's content analysis, and design of the learning object. The profile of the professionals working in the location was established. These agents identified the most commonly found diseases and stressed their needs in relation to a technological resource. The identified needs were considered to define the content and structure the learning object. The learning object is an alternative method for sharing knowledge on communicable diseases. The tool allows the combination of technology with teaching, which makes the learning process and the work of the community health agents more rewarding and productive.

Older Australians: Structural barriers to learning in later life.

PubMed

Boulton-Lewis, Gillian; Aird, Rosemary; Buys, Laurie

2016-01-01

Learning in older age is associated with benefits including increases in skills, social interactions, self-satisfaction, coping ability, enjoyment, and resilience to age-related changes in the brain. It is also a fundamental component of active ageing and if active ageing objectives are to be met for the growing ageing population, barriers to learning need to be understood and addressed. This study aimed at determining the degree that structural factors deter people aged 55 years and older from engaging in learning activities. The data were obtained from survey (n=421) with a purposive sample of Australian Seniors aged 55 to 75+, and open ended follow up interviews (n=40). The survey responses to the 22 barriers to learning questions were ranked and quantified. The issues identified in the interviews shed further light on the survey data. The analyses revealed that factors related to educational institutions as well as infrastructure were commonly cited as barriers to participation in learning. In particular expense of educational programmes (55.1%), long travelling time (45.6%) other transportation difficulties (38.9%), lack of interest in offered programmes ((36.4) and lack of information about courses (31.1%) were seen as barriers. The interviews revealed and confirmed five main barriers; money, offerings of interest/availability, travel/transport, information, computer skills and being employed. The findings should provide policy makers, institutions, organizations and government with a list of areas where changes might be made so as to improve older people's opportunities for learning as they proceed through older age.

Learning of nature: The curious case of the naked mole rat.

PubMed

Lagunas-Rangel, Francisco Alejandro; Chávez-Valencia, Venice

2017-06-01

Naked mole rats (NMRs) are the longest-living rodents known, living up to approximately 30 years and showing sustained good health. Nowadays, NMRs are considered excellent models for aging and, additionally, for cancer research, due to the evidence of a remarkable cancer resistance demonstrated through thousands of necropsies performed with very few cases that describe this pathology, which is believed to be a disease that unavoidably accompanies aging. Since some years ago, several studies have tried to explain the possible mechanisms underlying longevity and cancer resistance in NMRs through different perspectives and directions, creating new knowledge that subsequently could be used for cancer prevention and delaying aging in humans. Thus, the purpose of this review is to summarize the recent knowledge on naked mole rats with a particular emphasis on the molecular mechanisms associated with their longevity and cancer resistance. Copyright © 2017 Elsevier B.V. All rights reserved.

Unintentional firearm deaths: a comparison of other-inflicted and self-inflicted shootings.

PubMed

Hemenway, David; Barber, Catherine; Miller, Matthew

2010-07-01

This study compares other-inflicted and self-inflicted unintentional firearm fatalities. Data come from the National Violent Death Reporting System, a new surveillance system from the Centers for Disease Control and Prevention. Data are currently available from 16 states and parts of California for various years 2003-2006. Of the 363 unintentional firearm fatalities, about half (49%) were other-inflicted, ranging from 78% of child (aged 0-14) deaths to 19% of older adult (aged 55+) deaths. In other-inflicted shooting deaths, the shooters were overwhelmingly young (81% under age 25). The shooters in the other-inflicted deaths were primarily friends (43%) or family (47%); brothers were the most common family shooter. To learn how to prevent unintentional injuries, it is critical to have information not only on the victim, but also on the person who inflicted the injury. Copyright 2010 Elsevier Ltd. All rights reserved.

Life priorities in the HIV-positive Asians: a text-mining analysis in young vs. old generation.

PubMed

Chen, Wei-Ti; Barbour, Russell

2017-04-01

HIV/AIDS is one of the most urgent and challenging public health issues, especially since it is now considered a chronic disease. In this project, we used text mining techniques to extract meaningful words and word patterns from 45 transcribed in-depth interviews of people living with HIV/AIDS (PLWHA) conducted in Taipei, Beijing, Shanghai, and San Francisco from 2006 to 2013. Text mining analysis can predict whether an emerging field will become a long-lasting source of academic interest or whether it is simply a passing source of interest that will soon disappear. The data were analyzed by age group (45 and older vs. 44 and younger). The highest ranking fragments in the order of frequency were: "care", "daughter", "disease", "family", "HIV", "hospital", "husband", "medicines", "money", "people", "son", "tell/disclosure", "thought", "want", and "years". Participants in the 44-year-old and younger group were focused mainly on disease disclosure, their families, and their financial condition. In older PLWHA, social supports were one of the main concerns. In this study, we learned that different age groups perceive the disease differently. Therefore, when designing intervention, researchers should consider to tailor an intervention to a specific population and to help PLWHA achieve a better quality of life. Promoting self-management can be an effective strategy for every encounter with HIV-positive individuals.

Infants with complex congenital heart diseases show poor short-term memory in the mobile paradigm at 3 months of age.

PubMed

Chen, Chao-Ying; Harrison, Tondi; Heathcock, Jill

2015-08-01

The purpose of this study was to examine learning, short-term memory and general development including cognitive, motor, and language domains in infants with Complex Congenital Heart Defects (CCDH). Ten infants with CCHD (4 males, 6 females) and 14 infants with typical development (TD) were examined at 3 months of age. The mobile paradigm, where an infant's leg is tethered to an overhead mobile, was used to evaluate learning and short-term memory. The Bayley Scales of Infant Development 3rd edition (Bayley-III) was used to evaluate general development in cognitive, motor, and language domains. Infants with CCHD and infants with TD both showed learning with significant increase in kicking rate (p<0.001) across periods of the mobile paradigm, but only infants with TD demonstrated short-term memory (p=0.017) in the mobile paradigm. There were no differences on cognitive, motor, and language development between infants with CCHD and infants with TD on the Bayley-III. Early assessment is necessary to guide targeted treatment in infants with CCHD. One-time assessment may fail to detect potential cognitive impairments during early infancy in infants with CCHD. Supportive intervention programs for infants with CCHD that focuses on enhancing short-term memory are recommended. Copyright © 2015 Elsevier Inc. All rights reserved.

The Role of the University of the Third Age in Meeting Needs of Adult Learners in Victoria, Australia

ERIC Educational Resources Information Center

Hebestreit, Lydia

2008-01-01

Many older adults are interested in learning long past the age dictated by social norms. Some want to learn simply for the joy of learning, others because of the social contacts made by joining a community of learners, and still others want to learn so that they have a purpose in life. The University of the Third Age (U3A) is one of several models…

The Laparoscopic Approach in the Treatment of Diverticular Colon Disease

PubMed Central

del Olmo, J. C. Martin; Blanco, J. I.; de la Cuesta, C.; Atienza, R.

1998-01-01

Background and Objectives: The experience with treatment of diverticular colon disease (DCD) by the laparoscopic method is analyzed. Methods: Between January 1994 and July 1997, a group of 22 patients with criteria for symptomatic diverticular disease in the descending and sigmoid colon underwent laparoscopy with average resections of 40 cm. Intra-abdominal mechanical anastomosis completed the procedure. Results: The operative morbidity was 28%. Two cases, in acute diverticulitis phase, were reconverted to open surgery, and three cases presented postoperative rectorrhagia which ceased spontaneously. No long-term complications have been found. Postoperative hospitalization was 4-8 days (mean 5.5) and mean operative time was 165 minutes (range 120-240). Conclusions: Nevertheless, the learning curve precise to practice this type of surgery, the acceptable morbity-mortality rates which the laparoscopic method presents, especially with these high-risk groups of patients (age > 65, high blood pressure, etc), encouraged us to modified the criteria indicating surgery for the disease, offering first choice operative treatment with efficiency and safety. However, we feel that those patients with acute complications of diverticular colon disease must be excluded initially for laparoscopic approach. PMID:9876730

Computer aided decision making for heart disease detection using hybrid neural network-Genetic algorithm.

PubMed

Arabasadi, Zeinab; Alizadehsani, Roohallah; Roshanzamir, Mohamad; Moosaei, Hossein; Yarifard, Ali Asghar

2017-04-01

Cardiovascular disease is one of the most rampant causes of death around the world and was deemed as a major illness in Middle and Old ages. Coronary artery disease, in particular, is a widespread cardiovascular malady entailing high mortality rates. Angiography is, more often than not, regarded as the best method for the diagnosis of coronary artery disease; on the other hand, it is associated with high costs and major side effects. Much research has, therefore, been conducted using machine learning and data mining so as to seek alternative modalities. Accordingly, we herein propose a highly accurate hybrid method for the diagnosis of coronary artery disease. As a matter of fact, the proposed method is able to increase the performance of neural network by approximately 10% through enhancing its initial weights using genetic algorithm which suggests better weights for neural network. Making use of such methodology, we achieved accuracy, sensitivity and specificity rates of 93.85%, 97% and 92% respectively, on Z-Alizadeh Sani dataset. Copyright © 2017 Elsevier B.V. All rights reserved.

Resting-state Functional Connectivity is an Age-dependent Predictor of Motor Learning Abilities.

PubMed

Mary, Alison; Wens, Vincent; Op de Beeck, Marc; Leproult, Rachel; De Tiège, Xavier; Peigneux, Philippe

2017-10-01

This magnetoencephalography study investigates how ageing modulates the relationship between pre-learning resting-state functional connectivity (rsFC) and subsequent learning. Neuromagnetic resting-state activity was recorded 5 min before motor sequence learning in 14 young (19-30 years) and 14 old (66-70 years) participants. We used a seed-based beta-band power envelope correlation approach to estimate rsFC maps, with the seed located in the right primary sensorimotor cortex. In each age group, the relation between individual rsFC and learning performance was investigated using Pearson's correlation analyses. Our results show that rsFC is predictive of subsequent motor sequence learning but involves different cross-network interactions in the two age groups. In young adults, decreased coupling between the sensorimotor network and the cortico-striato-cerebellar network is associated with better motor learning, whereas a similar relation is found in old adults between the sensorimotor, the dorsal-attentional and the DMNs. Additionally, age-related correlational differences were found in the dorsolateral prefrontal cortex, known to subtend attentional and controlled processes. These findings suggest that motor skill learning depends-in an age-dependent manner-on subtle interactions between resting-state networks subtending motor activity on the one hand, and controlled and attentional processes on the other hand. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Exploring the Connection between Age and Strategies for Learning New Technology Related Tasks

ERIC Educational Resources Information Center

Meiselwitz, Gabriele; Chakraborty, Suranjan

2011-01-01

This paper discusses the connection between age and strategies for learning new technology related tasks. Many users have to learn about new devices and applications on a frequent basis and use a variety of strategies to accomplish this learning process. Approaches to learning new technology related tasks vary and can contribute to a user's…

Serum BDNF correlates with connectivity in the (pre)motor hub in the aging human brain--a resting-state fMRI pilot study.

PubMed

Mueller, Karsten; Arelin, Katrin; Möller, Harald E; Sacher, Julia; Kratzsch, Jürgen; Luck, Tobias; Riedel-Heller, Steffi; Villringer, Arno; Schroeter, Matthias L

2016-02-01

Brain-derived neurotrophic factor (BDNF) has been discussed to be involved in plasticity processes in the human brain, in particular during aging. Recently, aging and its (neurodegenerative) diseases have increasingly been conceptualized as disconnection syndromes. Here, connectivity changes in neural networks (the connectome) are suggested to be the most relevant and characteristic features for such processes or diseases. To further elucidate the impact of aging on neural networks, we investigated the interaction between plasticity processes, brain connectivity, and healthy aging by measuring levels of serum BDNF and resting-state fMRI data in 25 young (mean age 24.8 ± 2.7 (SD) years) and 23 old healthy participants (mean age, 68.6 ± 4.1 years). To identify neural hubs most essentially related to serum BDNF, we applied graph theory approaches, namely the new data-driven and parameter-free approach eigenvector centrality (EC) mapping. The analysis revealed a positive correlation between serum BDNF and EC in the premotor and motor cortex in older participants in contrast to young volunteers, where we did not detect any association. This positive relationship between serum BDNF and EC appears to be specific for older adults. Our results might indicate that the amount of physical activity and learning capacities, leading to higher BDNF levels, increases brain connectivity in (pre)motor areas in healthy aging in agreement with rodent animal studies. Pilot results have to be replicated in a larger sample including behavioral data to disentangle the cause for the relationship between BDNF levels and connectivity. Copyright © 2016 Elsevier Inc. All rights reserved.

Handedness and language learning disability differentially distribute in progressive aphasia variants.

PubMed

Miller, Zachary A; Mandelli, Maria Luisa; Rankin, Katherine P; Henry, Maya L; Babiak, Miranda C; Frazier, Darvis T; Lobach, Iryna V; Bettcher, Brianne M; Wu, Teresa Q; Rabinovici, Gil D; Graff-Radford, Neill R; Miller, Bruce L; Gorno-Tempini, Maria Luisa

2013-11-01

Primary progressive aphasia is a neurodegenerative clinical syndrome that presents in adulthood with an isolated, progressive language disorder. Three main clinical/anatomical variants have been described, each associated with distinctive pathology. A high frequency of neurodevelopmental learning disability in primary progressive aphasia has been reported. Because the disorder is heterogeneous with different patterns of cognitive, anatomical and biological involvement, we sought to identify whether learning disability had a predilection for one or more of the primary progressive aphasia subtypes. We screened the University of California San Francisco Memory and Aging Center's primary progressive aphasia cohort (n = 198) for history of language-related learning disability as well as hand preference, which has associations with learning disability. The study included logopenic (n = 48), non-fluent (n = 54) and semantic (n = 96) variant primary progressive aphasias. We investigated whether the presence of learning disability or non-right-handedness was associated with differential effects on demographic, neuropsychological and neuroimaging features of primary progressive aphasia. We showed that a high frequency of learning disability was present only in the logopenic group (χ(2) = 15.17, P < 0.001) and (χ(2) = 11.51, P < 0.001) compared with semantic and non-fluent populations. In this group, learning disability was associated with earlier onset of disease, more isolated language symptoms, and more focal pattern of left posterior temporoparietal atrophy. Non-right-handedness was instead over-represented in the semantic group, at nearly twice the prevalence of the general population (χ(2) = 6.34, P = 0.01). Within semantic variant primary progressive aphasia the right-handed and non-right-handed cohorts appeared homogeneous on imaging, cognitive profile, and structural analysis of brain symmetry. Lastly, the non-fluent group showed no increase in learning disability or non-right-handedness. Logopenic variant primary progressive aphasia and developmental dyslexia both manifest with phonological disturbances and posterior temporal involvement. Learning disability might confer vulnerability of this network to early-onset, focal Alzheimer's pathology. Left-handedness has been described as a proxy for atypical brain hemispheric lateralization. As non-right-handedness was increased only in the semantic group, anomalous lateralization mechanisms might instead be related to frontotemporal lobar degeneration with abnormal TARDBP. Taken together, this study suggests that neurodevelopmental signatures impart differential trajectories towards neurodegenerative disease.

Cherry Featured in NCI’s Spotlight on Scientists Video Series | Poster

Cancer.gov

James Cherry, Ph.D., learned at an early age that education is crucial to success. He credits his mentors, some of whom include his grandmother, Shepherd University professor Burton Lidgerding, Ph.D., David Munroe, Ph.D., Frederick National Lab, and Robert J. Hohman, Ph.D., National Institute of Allergy and Infectious Diseases, for guiding him to the career he has today. Cherry, scientific program director, Office of Scientific Operations (OSO), NCI at Frederick, is one of the scientists featured in NCI’s Spotlight on Scientists video series.

The Effects of Aging on the Neural Basis of Implicit Associative Learning in a Probabilistic Triplets Learning Task

ERIC Educational Resources Information Center

Simon, Jessica R.; Vaidya, Chandan J.; Howard, James H., Jr.; Howard, Darlene V.

2012-01-01

Few studies have investigated how aging influences the neural basis of implicit associative learning, and available evidence is inconclusive. One emerging behavioral pattern is that age differences increase with practice, perhaps reflecting the involvement of different brain regions with training. Many studies report hippocampal involvement early…

FUNdamentals: A Research-Based, Phonics Tutorial Learn To Read Program. [Educational Kit].

ERIC Educational Resources Information Center

Eller, Jeanie

FUNdamentals puts the "FUN" back in learning for all age groups. FUNdamentals is an intensive, systematic phonics learn-to-read program that helps improve comprehension, spelling, and penmanship. It is designed for use by every age group. Formulated for use with learners from preschool through adult ages, FUNdamentals is the key to…

Approaches to Learning and Age in Predicting College Students' Academic Achievement

ERIC Educational Resources Information Center

Cetin, Baris

2016-01-01

The aim of this study is to determine whether the approaches to learning and age are significantly correlated to grade point average (GPA) in early childhood education students. In addition, another purpose of this study is to determine whether approaches to learning and age predicted students' GPAs in the Early Childhood Education Department. The…

75 FR 27838 - Notice of Availability of Draft NUREG-1800, Revision 2; “Standard Review Plan for Review of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-18

... Draft NUREG-1801, Revision 2; ``Generic Aging Lessons Learned (GALL) Report'' AGENCY: Nuclear Regulatory... Applications for Nuclear Power Plants ''and draft NUREG-1801, ``Generic Aging Lessons Learned (GALL) Report... Power Plants'' (SRP-LR); and the revised NUREG-1801, ``Generic Aging Lessons Learned (GALL) Report'' for...

Improving diagnostic recognition of primary hyperparathyroidism with machine learning.

PubMed

Somnay, Yash R; Craven, Mark; McCoy, Kelly L; Carty, Sally E; Wang, Tracy S; Greenberg, Caprice C; Schneider, David F

2017-04-01

Parathyroidectomy offers the only cure for primary hyperparathyroidism, but today only 50% of primary hyperparathyroidism patients are referred for operation, in large part, because the condition is widely under-recognized. The diagnosis of primary hyperparathyroidism can be especially challenging with mild biochemical indices. Machine learning is a collection of methods in which computers build predictive algorithms based on labeled examples. With the aim of facilitating diagnosis, we tested the ability of machine learning to distinguish primary hyperparathyroidism from normal physiology using clinical and laboratory data. This retrospective cohort study used a labeled training set and 10-fold cross-validation to evaluate accuracy of the algorithm. Measures of accuracy included area under the receiver operating characteristic curve, precision (sensitivity), and positive and negative predictive value. Several different algorithms and ensembles of algorithms were tested using the Weka platform. Among 11,830 patients managed operatively at 3 high-volume endocrine surgery programs from March 2001 to August 2013, 6,777 underwent parathyroidectomy for confirmed primary hyperparathyroidism, and 5,053 control patients without primary hyperparathyroidism underwent thyroidectomy. Test-set accuracies for machine learning models were determined using 10-fold cross-validation. Age, sex, and serum levels of preoperative calcium, phosphate, parathyroid hormone, vitamin D, and creatinine were defined as potential predictors of primary hyperparathyroidism. Mild primary hyperparathyroidism was defined as primary hyperparathyroidism with normal preoperative calcium or parathyroid hormone levels. After testing a variety of machine learning algorithms, Bayesian network models proved most accurate, classifying correctly 95.2% of all primary hyperparathyroidism patients (area under receiver operating characteristic = 0.989). Omitting parathyroid hormone from the model did not decrease the accuracy significantly (area under receiver operating characteristic = 0.985). In mild disease cases, however, the Bayesian network model classified correctly 71.1% of patients with normal calcium and 92.1% with normal parathyroid hormone levels preoperatively. Bayesian networking and AdaBoost improved the accuracy of all parathyroid hormone patients to 97.2% cases (area under receiver operating characteristic = 0.994), and 91.9% of primary hyperparathyroidism patients with mild disease. This was significantly improved relative to Bayesian networking alone (P < .0001). Machine learning can diagnose accurately primary hyperparathyroidism without human input even in mild disease. Incorporation of this tool into electronic medical record systems may aid in recognition of this under-diagnosed disorder. Copyright © 2016 Elsevier Inc. All rights reserved.

Dissociation between active and observational learning from positive and negative feedback in Parkinsonism.

PubMed

Kobza, Stefan; Ferrea, Stefano; Schnitzler, Alfons; Pollok, Bettina; Südmeyer, Martin; Bellebaum, Christian

2012-01-01

Feedback to both actively performed and observed behaviour allows adaptation of future actions. Positive feedback leads to increased activity of dopamine neurons in the substantia nigra, whereas dopamine neuron activity is decreased following negative feedback. Dopamine level reduction in unmedicated Parkinson's Disease patients has been shown to lead to a negative learning bias, i.e. enhanced learning from negative feedback. Recent findings suggest that the neural mechanisms of active and observational learning from feedback might differ, with the striatum playing a less prominent role in observational learning. Therefore, it was hypothesized that unmedicated Parkinson's Disease patients would show a negative learning bias only in active but not in observational learning. In a between-group design, 19 Parkinson's Disease patients and 40 healthy controls engaged in either an active or an observational probabilistic feedback-learning task. For both tasks, transfer phases aimed to assess the bias to learn better from positive or negative feedback. As expected, actively learning patients showed a negative learning bias, whereas controls learned better from positive feedback. In contrast, no difference between patients and controls emerged for observational learning, with both groups showing better learning from positive feedback. These findings add to neural models of reinforcement-learning by suggesting that dopamine-modulated input to the striatum plays a minor role in observational learning from feedback. Future research will have to elucidate the specific neural underpinnings of observational learning.

Age Moderates the Effect of Acute Dopamine Depletion on Passive Avoidance Learning

PubMed Central

Kelm, Mary Katherine; Boettiger, Charlotte Ann

2015-01-01

Despite extensive links between reinforcement-based learning and dopamine (DA), studies to date have not found consistent effects of acute DA reduction on reinforcement learning in both men and women. Here, we tested the effects of reducing DA on reward- and punishment-based learning using the deterministic passive avoidance learning (PAL) task We tested 16 (5 female) adults (ages 22–40) in a randomized, cross-over design to determine whether reducing global DA by administering an amino acid beverage deficient in the DA precursors, phenylalanine and tyrosine (P/T[−]), would affect performance on the PAL task. We found that P/T[−] beverage effects on PAL performance were modulated by age. In particular, we found that P/T depletion significantly improved learning from punishment with increasing participant age. Participants committed 1.49 fewer passive avoidance errors per additional year of age (95% CI, −0.71 – −2.27, r=−0.74, p=0.001). Moreover, in this small sample, P/T depletion improved learning from punishment in adults (ages 26–40) while it impaired learning from punishment in emerging adults (ages 22–25). We observed similar, but non-significant trends in learning from reward. While there was no overall effect of P/T-depletion on reaction time (RT), there was a relationship between the effect of P/T depletion on PAL performance and RT; those who responded more slowly on the P/T[−] beverage also made more errors on the P/T[−] beverage. When P/T-depletion slowed RT after a correct response, there was a worsening of PAL task performance; there was no similar relationship for the RT after an incorrect response and PAL task performance. Moreover, among emerging adults, changes in mood on the P/T[−] beverage negatively correlated with learning from reward on the P/T[−] beverage. Together, we found that both reward- and punishment-based learning are sensitive to central catecholamine levels, and that these effects of acute DA reduction vary with age. PMID:25636601

Role of antioxidant enzymes in redox regulation of N-methyl-D-aspartate receptor function and memory in middle-aged rats.

PubMed

Lee, Wei-Hua; Kumar, Ashok; Rani, Asha; Foster, Thomas C

2014-06-01

Overexpression of superoxide dismutase 1 (SOD1) in the hippocampus results in age-dependent impaired cognition and altered synaptic plasticity suggesting a possible model for examining the role of oxidative stress in senescent neurophysiology. However, it is unclear if SOD1 overexpression involves an altered redox environment and a decrease in N-methyl-D-aspartate receptor (NMDAR) synaptic function reported for aging animals. Viral vectors were used to express SOD1 and green fluorescent protein (SOD1 + GFP), SOD1 and catalase (SOD1 + CAT), or GFP alone in the hippocampus of middle-aged (17 months) male Fischer 344 rats. We confirm that SOD1 + GFP and SOD1 + CAT reduced lipid peroxidation indicating superoxide metabolites were primarily responsible for lipid peroxidation. SOD1 + GFP impaired learning, decreased glutathione peroxidase activity, decreased glutathione levels, decreased NMDAR-mediated synaptic responses, and impaired long-term potentiation. Co-expression of SOD1 + CAT rescued the effects of SOD1 expression on learning, redox measures, and synaptic function suggesting the effects were mediated by excess hydrogen peroxide. Application of the reducing agent dithiolthreitol to hippocampal slices increased the NMDAR-mediated component of the synaptic response in SOD1 + GFP animals relative to animals that overexpress SOD1 + CAT indicating that the effect of antioxidant enzyme expression on NMDAR function was because of a shift in the redox environment. The results suggest that overexpression of neuronal SOD1 and CAT in middle age may provide a model for examining the role of oxidative stress in senescent physiology and the progression of age-related neurodegenerative diseases. Copyright © 2014 Elsevier Inc. All rights reserved.

Association of bilateral oophorectomy with cognitive function in healthy, postmenopausal women.

PubMed

Kurita, Keiko; Henderson, Victor W; Gatz, Margaret; St John, Jan; Hodis, Howard N; Karim, Roksana; Mack, Wendy J

2016-09-01

To investigate the association between bilateral oophorectomy and cognitive performance in healthy, older women. Retrospective analysis of clinical trial data. Academic research institution. Healthy postmenopausal women without signs or symptoms of cardiovascular disease or diabetes (n = 926). Randomized interventions (not the focus of this analysis) in analyzed trials included B-vitamins, soy isoflavones, oral estradiol, and matching placebos. Measures in five cognitive domains (executive functions, semantic memory, logical memory, visual memory, and verbal learning) and global cognitive function. Using data from three clinical trials conducted under uniform conditions, bilateral oophorectomy and its timing were analyzed cross-sectionally and longitudinally in relation to cognitive function in linear regression models. Covariates included age, education, race/ethnicity, body mass index, trial, and randomized treatment (in longitudinal models). Duration of menopausal hormone use was considered as a possible mediator and effect modifier. Median age of oophorectomy was 45 years. When evaluating baseline cognition, we found that surgical menopause after 45 years of age was associated with lower performance in verbal learning compared with natural menopause. Evaluating the change in cognition over approximately 2.7 years, surgical menopause was associated with performance declines in visual memory for those who had an oophorectomy after 45 years of age and in semantic memory for those who had oophorectomy before 45 years of age compared with natural menopause. Oophorectomy after natural menopause was not associated with cognitive performance. Adjustment for duration of hormone use did not alter these associations. Cognitive associations with ovarian removal vary by timing of surgery relative to both menopause and age. Copyright © 2016. Published by Elsevier Inc.

Cognitive Consequences of Trilingualism

PubMed Central

Schroeder, Scott R.; Marian, Viorica

2017-01-01

Aims and Objectives The objectives of the present research were to examine the cognitive consequences of trilingualism and explain them relative to the cognitive consequences of bilingualism. Approach A comparison of cognitive abilities in trilinguals and bilinguals was conducted. In addition, we proposed a cognitive plasticity framework to account for cognitive differences and similarities between trilinguals and bilinguals. Data and Analysis Three aspects of cognition were analyzed: (1) cognitive reserve in older adults, as measured by age of onset of Alzheimer’s disease and mild cognitive impairment; (2) inhibitory control in children and younger adults, as measured by response times on behavioral Simon and flanker tasks; and (3) memory generalization in infants and toddlers, as measured by accuracy on behavioral deferred imitation tasks. Results were considered within a framework of cognitive plasticity, which took into account several factors that may affect plasticity, including the age of learning a third language and the extent to which additional cognitive resources are needed to learn the third language. Findings A mixed pattern of results was observed. In some cases, such as cognitive reserve in older adults, trilinguals showed larger advantages than bilinguals. On other measures, for example inhibitory control in children and younger adults, trilinguals were found to exhibit the same advantages as bilinguals. In still other cases, like memory generalization in infants and toddlers, trilinguals did not demonstrate the advantages seen in bilinguals. Originality This study is the first comprehensive analysis of how learning a third language affects the cognitive abilities that are modified by bilingual experience, and the first to propose a cognitive plasticity framework that can explain and predict trilingual-bilingual differences. Significance This research shows that the cognitive consequences of trilingualism are not simply an extension of bilingualism’s effects; rather, trilingualism has distinct consequences, with theoretical implications for our understanding of linguistic and cognitive processes and their plasticity, as well as applied-science implications for using second and third language learning in educational and rehabilitative contexts to foster successful cognitive development and aging. PMID:29151803

Encoding changes in orbitofrontal cortex in reversal-impaired aged rats.

PubMed

Schoenbaum, Geoffrey; Setlow, Barry; Saddoris, Michael P; Gallagher, Michela

2006-03-01

Previous work in rats and primates has shown that normal aging can be associated with a decline in cognitive flexibility mediated by prefrontal circuits. For example, aged rats are impaired in rapid reversal learning, which in young rats depends critically on the orbitofrontal cortex. To assess whether aging-related reversal impairments reflect orbitofrontal dysfunction, we identified aged rats with reversal learning deficits and then recorded single units as these rats, along with unimpaired aged cohorts and young control rats, learned and reversed a series of odor discrimination problems. We found that the flexibility of neural correlates in orbitofrontal cortex was markedly diminished in aged rats characterized as reversal-impaired in initial training. In particular, although many cue-selective neurons in young and aged-unimpaired rats reversed odor preference when the odor-outcome associations were reversed, cue-selective neurons in reversal-impaired aged rats did not. In addition, outcome-expectant neurons in aged-impaired rats failed to become active during cue sampling after learning. These altered features of neural encoding could provide a basis for cognitive inflexibility associated with normal aging.

Deep Learning for Image-Based Cassava Disease Detection.

PubMed

Ramcharan, Amanda; Baranowski, Kelsee; McCloskey, Peter; Ahmed, Babuali; Legg, James; Hughes, David P

2017-01-01

Cassava is the third largest source of carbohydrates for human food in the world but is vulnerable to virus diseases, which threaten to destabilize food security in sub-Saharan Africa. Novel methods of cassava disease detection are needed to support improved control which will prevent this crisis. Image recognition offers both a cost effective and scalable technology for disease detection. New deep learning models offer an avenue for this technology to be easily deployed on mobile devices. Using a dataset of cassava disease images taken in the field in Tanzania, we applied transfer learning to train a deep convolutional neural network to identify three diseases and two types of pest damage (or lack thereof). The best trained model accuracies were 98% for brown leaf spot (BLS), 96% for red mite damage (RMD), 95% for green mite damage (GMD), 98% for cassava brown streak disease (CBSD), and 96% for cassava mosaic disease (CMD). The best model achieved an overall accuracy of 93% for data not used in the training process. Our results show that the transfer learning approach for image recognition of field images offers a fast, affordable, and easily deployable strategy for digital plant disease detection.

The Application of Modeling and Simulation to the Behavioral Deficit of Autism

NASA Technical Reports Server (NTRS)

Anton, John J.

2010-01-01

This abstract describes a research effort to apply technological advances in virtual reality simulation and computer-based games to create behavioral modification programs for individuals with Autism Spectrum Disorder (ASD). The research investigates virtual social skills training within a 3D game environment to diminish the impact of ASD social impairments and to increase learning capacity for optimal intellectual capability. Individuals with autism will encounter prototypical social contexts via computer interface and will interact with 3D avatars with predefined roles within a game-like environment. Incremental learning objectives will combine to form a collaborative social environment. A secondary goal of the effort is to begin the research and development of virtual reality exercises aimed at triggering the release of neurotransmitters to promote critical aspects of synaptic maturation at an early age to change the course of the disease.

Mechanisms underlying comprehension of health information in adulthood: the roles of prior knowledge and working memory capacity.

PubMed

Soederberg Miller, Lisa M; Gibson, Tanja N; Applegate, Elizabeth A; de Dios, Jeannette

2011-07-01

Prior knowledge, working memory capacity (WMC), and conceptual integration (attention allocated to integrating concepts in text) are critical within many contexts; however, their impact on the acquisition of health information (i.e. learning) is relatively unexplored.We examined how these factors impact learning about nutrition within a cross-sectional study of adults ages 18 to 81. Results showed that conceptual integration mediated the effects of knowledge and WMC on learning, confirming that attention to concepts while reading is important for learning about health. We also found that when knowledge was controlled, age declines in learning increased, suggesting that knowledge mitigates the effects of age on learning about nutrition.

Access to oral health care services among adults with learning disabilities: a scoping review

PubMed Central

Naseem, Mustafa; Shah, Altaf H; Khiyani, Muhammad Faheem; Khurshid, Zohaib; Zafar, Muhammad Sohail; Gulzar, Shabnam; AlJameel, AlBandary H.; Khalil, Hesham S.

2016-01-01

Summary Background The prevalence of oral diseases including dental caries and periodontal conditions is remarkably higher in people with disabilities. The provision of accessible oral health services for people with learning disabilities may be challenging. Objectives The objectives of the review were to identify barriers in accessing oral health care that persists within society, enabling or disabling people with learning disabilities. Methods Using the Arksey O’Malley framework, a scoping review was conducted on PubMed/Medline, OVIDSP, and EMBASE. Studies were evaluated and short-listed based on the inclusion criteria, which consisted of: (1) study participants or population with learning disabilities, (2) aged 16 years or over, (3) reporting on access to oral health services, (4) published in the English language. Those that justified the inclusion criteria were carefully chosen after a blind peer-reviewed process when relevance and quality were debated. Results Nine studies were eventually included from searches. Tabulation of data was done under the heading of study type, outcomes, the year of publication and patient selection. The majority of studies provided a biomedical overview of access for adults with learning disabilities. Conclusions The concept of access for people with disability is still ill-defined and obscure. Access to oral health care and needs of people with learning disabilities are complex and multi-facet. PMID:28149451

Elevated Risk of Type 2 Diabetes for Development of Alzheimer Disease: a Key Role for Oxidative Stress in Brain

PubMed Central

Butterfield, D. Allan; Di Domenico, Fabio; Barone, Eugenio

2014-01-01

Alzheimer disease (AD) is the most common form of dementia among the elderly and is characterized by progressive loss of memory and cognition. Epidemiological data show that the incidence of AD increases with age and doubles every 5 years after 65 years of age. From a neuropathological point of view, amyloid-β-peptide (Aβ) leads to senile plaques, which, together with hyperphosphorylated tau-based neurofibrillary tangles and synapse loss, are the principal pathological hallmarks of AD. Aβ is associated with the formation of reactive oxygen (ROS) and nitrogen (RNS) species, and induces calcium-dependent excitotoxicity, impairment of cellular respiration, and alteration of synaptic functions associated with learning and memory. Oxidative stress was found to be associated with type 2 diabetes mellitus (T2DM), which (i) represents another prevalent disease associated with obesity and often aging, and (ii) is considered to be a risk factor for AD development. T2DM is characterized by high blood glucose levels resulting from increased hepatic glucose production, impaired insulin production and peripheral insulin resistance, which close resemble to the brain insulin resistance observed in AD patients. Furthermore, growing evidence suggest that oxidative stress play a pivotal role in the development of insulin resistance and vice versa. This review article provides molecular aspects and the pharmacological approaches from both preclinical and clinical data and interpreted from the point of view of oxidative stress with the aim to highlight progresses in this field. PMID:24949886

Learning New Letter-like Writing Patterns Explicitly and Implicitly in Children and Adults.

PubMed

Jongbloed-Pereboom, M; Overvelde, A; Nijhuis-van der Sanden, M W G; Steenbergen, B

2017-12-15

A handwriting task was used to test the assumption that explicit learning is dependent on age and working memory, while implicit learning is not. The effect of age was examined by testing both, typically developing children (5-12 years old, n = 81) and adults (n = 27) in a counterbalanced within-subjects design. Participants were asked to repeatedly write letter-like patterns on a digitizer with a non-inking pen. Reproduction of the pattern was better after explicit learning compared to implicit learning. Age had positive effects on both explicit and implicit learning; working memory did not affect learning in either conditions. These results show that it may be more effective to learn writing new letter-like patterns explicitly and that an explicit teaching method is preferred in mainstream primary education.

Multimodal Learning and Intelligent Prediction of Symptom Development in Individual Parkinson’s Patients

PubMed Central

Przybyszewski, Andrzej W.; Kon, Mark; Szlufik, Stanislaw; Szymanski, Artur; Habela, Piotr; Koziorowski, Dariusz M.

2016-01-01

We still do not know how the brain and its computations are affected by nerve cell deaths and their compensatory learning processes, as these develop in neurodegenerative diseases (ND). Compensatory learning processes are ND symptoms usually observed at a point when the disease has already affected large parts of the brain. We can register symptoms of ND such as motor and/or mental disorders (dementias) and even provide symptomatic relief, though the structural effects of these are in most cases not yet understood. It is very important to obtain early diagnosis, which can provide several years in which we can monitor and partly compensate for the disease’s symptoms, with the help of various therapies. In the case of Parkinson’s disease (PD), in addition to classical neurological tests, measurements of eye movements are diagnostic. We have performed measurements of latency, amplitude, and duration in reflexive saccades (RS) of PD patients. We have compared the results of our measurement-based diagnoses with standard neurological ones. The purpose of our work was to classify how condition attributes predict the neurologist’s diagnosis. For n = 10 patients, the patient age and parameters based on RS gave a global accuracy in predictions of neurological symptoms in individual patients of about 80%. Further, by adding three attributes partly related to patient ‘well-being’ scores, our prediction accuracies increased to 90%. Our predictive algorithms use rough set theory, which we have compared with other classifiers such as Naïve Bayes, Decision Trees/Tables, and Random Forests (implemented in KNIME/WEKA). We have demonstrated that RS are powerful biomarkers for assessment of symptom progression in PD. PMID:27649187

Virtual reality for gait training: can it induce motor learning to enhance complex walking and reduce fall risk in patients with Parkinson's disease?

PubMed

Mirelman, Anat; Maidan, Inbal; Herman, Talia; Deutsch, Judith E; Giladi, Nir; Hausdorff, Jeffrey M

2011-02-01

Gait and cognitive disturbances are common in Parkinson's disease (PD). These deficits exacerbate fall risk and difficulties with mobility, especially during complex or dual-task walking. Traditional gait training generally fails to fully address these complex gait activities. Virtual reality (VR) incorporates principles of motor learning while delivering engaging and challenging training in complex environments. We hypothesized that VR may be applied to address the multifaceted deficits associated with fall risk in PD. Twenty patients received 18 sessions (3 per week) of progressive intensive treadmill training with virtual obstacles (TT + VR). Outcome measures included gait under usual-walking and dual-task conditions and while negotiating physical obstacles. Cognitive function and functional performance were also assessed. Patients were 67.1 ± 6.5 years and had a mean disease duration of 9.8 ± 5.6 years. Posttraining, gait speed significantly improved during usual walking, during dual task, and while negotiating overground obstacles. Dual-task gait variability decreased (ie, improved) and Trail Making Test times (parts A and B) improved. Gains in functional performance measures and retention effects, 1 month later, were also observed. To our knowledge, this is the first time that TT + VR has been used for gait training in PD. The results indicate that TT + VR is viable in PD and may significantly improve physical performance, gait during complex challenging conditions, and even certain aspects of cognitive function. These findings have important implications for understanding motor learning in the presence of PD and for treating fall risk in PD, aging, and others who share a heightened risk of falls.

Keys to successful diabetes self-management for uninsured patients: social support, observational learning, and turning points: a safety net providers' strategic alliance study.

PubMed

Madden, Melissa Hanahan; Tomsik, Philip; Terchek, Joshua; Navracruz, Lisa; Reichsman, Ann; Clark, Terri Clemons; Cella, Peggi; Weirich, Stephen A; Munson, Michelle R; Werner, James J

2011-03-01

To examine how medically uninsured patients who receive health care at federally qualified health centers and free clinics are able to successfully self-manage diabetes compared to patients who are less successful. Two distinct groups of patients with diabetes for 6 months or longer were enrolled: (1) successful, defined as those with glycated hemoglobin (HbA1c) of 7% or less or a recent improvement of at least 2% (n=17); and (2) unsuccessful, defined as patients with HbAlc of at least 9% (n=9) and without recent improvement. Patients were interviewed about enabling factors, motivators, resources, and barriers to diabetes self-management. Data from interviews, chart reviews, and clinician surveys were analyzed using qualitative methods and statistical techniques. African Americans comprised 57.7% of the sample and whites 38.5% (N=26). No significant differences were detected between successful and unsuccessful groups in age, race, education, or employment status. Clinicians rated unsuccessful patients as having more severe diabetes and significantly lower levels of control than successful patients. Compared to unsuccessful patients, successful patients more often reported having friends or family with diabetes, more frequently sought information about the disease, used evidence-based self-management strategies, held more accurate perceptions of their own diabetes control, and experienced "turning point" events that motivated increased efforts in disease management. Patients who successfully managed diabetes learned from diabetic family members and interpreted disease-related events as motivational turning points. It may be beneficial to incorporate social learning and motivational enhancement into diabetes interventions to increase patients' motivation for improved levels of self-management.

Procedural learning: A developmental study of motor sequence learning and probabilistic classification learning in school-aged children.

PubMed

Mayor-Dubois, Claire; Zesiger, Pascal; Van der Linden, Martial; Roulet-Perez, Eliane

2016-01-01

In this study, we investigated motor and cognitive procedural learning in typically developing children aged 8-12 years with a serial reaction time (SRT) task and a probabilistic classification learning (PCL) task. The aims were to replicate and extend the results of previous SRT studies, to investigate PCL in school-aged children, to explore the contribution of declarative knowledge to SRT and PCL performance, to explore the strategies used by children in the PCL task via a mathematical model, and to see whether performances obtained in motor and cognitive tasks correlated. The results showed similar learning effects in the three age groups in the SRT and in the first half of the PCL tasks. Participants did not develop explicit knowledge in the SRT task whereas declarative knowledge of the cue-outcome associations correlated with the performances in the second half of the PCL task, suggesting a participation of explicit knowledge after some time of exposure in PCL. An increasing proportion of the optimal strategy use with increasing age was observed in the PCL task. Finally, no correlation appeared between cognitive and motor performance. In conclusion, we extended the hypothesis of age invariance from motor to cognitive procedural learning, which had not been done previously. The ability to adopt more efficient learning strategies with age may rely on the maturation of the fronto-striatal loops. The lack of correlation between performance in the SRT task and the first part of the PCL task suggests dissociable developmental trajectories within the procedural memory system.

Medication Impairs Probabilistic Classification Learning in Parkinson's Disease

ERIC Educational Resources Information Center

Jahanshahi, Marjan; Wilkinson, Leonora; Gahir, Harpreet; Dharminda, Angeline; Lagnado, David A.

2010-01-01

In Parkinson's disease (PD), it is possible that tonic increase of dopamine associated with levodopa medication overshadows phasic release of dopamine, which is essential for learning. Thus while the motor symptoms of PD are improved with levodopa medication, learning would be disrupted. To test this hypothesis, we investigated the effect of…

Guidance on the Use of Learning Strategies in Distance Education (DE) as a Function of Age and Gender

ERIC Educational Resources Information Center

Alliprandini, Paula Mariza Zedu; Pavesi, Marilza Aparecida; Dayanne, Vicentini; Sekitani, Juliane Tiemi

2015-01-01

This study aims to determine whether there are differences in the use of learning strategies used by students enrolled in courses offered in the format of Distance Learning (DL) by gender and age of participants. A total of 402 students responded to a range of learning strategies evaluations-version adapted for distance learning, containing 49…

Problem based learning in chronic disease management: a review of the research.

PubMed

Williams, Bev; Pace, Ana Emilia

2009-10-01

To determine whether problem based learning (PBL) is an effective educational strategy in chronic disease management. The databases CINAHL, EMBASE, HealthStar, Medline and PubMed were searched for articles which focused on PBL and patient education or patient learning. Individual studies using PBL as an intervention with chronic disease management reflect significant changes in cognitive and clinical outcomes among individuals experiencing diabetes, asthma, arthritis and coronary artery disease. There is a need for more well designed studies that assess the impact of PBL on self-care management of a variety of chronic diseases. There is some evidence that PBL is effective in promoting self-care with individuals experiencing diabetes, arthritis, asthma and coronary artery disease. 2009 Published by Elsevier Ireland Ltd.

Learning and the Brain.

ERIC Educational Resources Information Center

Fishback, Sarah Jane

1999-01-01

Reviews research on the brain and memory, emotions, aging, and learning. Outlines practice implications: connect new learning to personal experiences, make sure learners are paying attention, recognize the role of emotions, and be aware that stimulation influences the aging brain. (SK)

Teaching and Learning about Sexuality and Aging.

ERIC Educational Resources Information Center

Steffl, Bernita M.; Kelly, James J.

1979-01-01

Describes an experience in developing teaching and learning content on aging and sexuality. Suggestions for a course outline and experiential learning for students and a summary of findings, which has implications for educators in gerontology, are included. (Author)

Age and Language Learning

ERIC Educational Resources Information Center

Collard, Lucien

1977-01-01

An investigation of the differences between first and second language acquisition and the relationship between age and second language learning. The stages in native language acquisition and the advantages of an early start in second language learning are discussed. (AMH)

Life-Span Learning: A Developmental Perspective

ERIC Educational Resources Information Center

Thornton, James E.

2003-01-01

The article discusses learning as embedded processes of development and aging, and as social activity over the life course. The concept of life-span learning is proposed and outlined to discuss these processes as aspects of and propositions in life-span development and aging theory. Life-span learning processes arise and continuously develop in a…

Rule-Based and Information-Integration Category Learning in Normal Aging

ERIC Educational Resources Information Center

Maddox, W. Todd; Pacheco, Jennifer; Reeves, Maia; Zhu, Bo; Schnyer, David M.

2010-01-01

The basal ganglia and prefrontal cortex play critical roles in category learning. Both regions evidence age-related structural and functional declines. The current study examined rule-based and information-integration category learning in a group of older and younger adults. Rule-based learning is thought to involve explicit, frontally mediated…

Dopamine modulates striatal response to reward and punishment in patients with Parkinson's disease: a pharmacological challenge fMRI study.

PubMed

Argyelan, Miklos; Herzallah, Mohammad; Sako, Wataru; DeLucia, Ivana; Sarpal, Deepak; Vo, An; Fitzpatrick, Toni; Moustafa, Ahmed A; Eidelberg, David; Gluck, Mark

2018-05-02

It is well established that Parkinson's disease leads to impaired learning from reward and enhanced learning from punishment. The administration of dopaminergic medications reverses this learning pattern. However, few studies have investigated the neural underpinnings of these cognitive processes. In this study, using fMRI, we tested a group of Parkinson's disease patients on and off dopaminergic medications and matched healthy individuals. All individuals completed an fMRI cognitive task that dissociates feedback learning from reward versus punishment. The administration of dopaminergic medications attenuated blood oxygen level dependent (BOLD) responses to punishment in the bilateral putamen, in bilateral dorsolateral prefrontal cortex and the left premotor cortex. Further, the administration of dopaminergic medications resulted in a higher ratio of BOLD activity between reward and punishment trials in these brain areas. BOLD activity in these brain areas was significantly correlated with learning from punishment, but not from reward trials. Furthermore, the administration of dopaminergic medications altered BOLD activity in the right insula and ventromedial prefrontal cortex when Parkinson's disease patients were anticipating feedback. These findings are in agreement with a large body of literature indicating that Parkinson's disease is associated with enhanced learning from punishment. However, it was surprising that dopaminergic medications modulated punishment learning as opposed to reward learning, although reward learning has been directly linked to dopaminergic function. We argue that these results might be attributed to both a change in the balance between direct and indirect pathway activation in the basal ganglia as well as the differential activity of D1 versus D2 dopamine receptors.

Subject-Specific Sparse Dictionary Learning for Atlas-Based Brain MRI Segmentation.

PubMed

Roy, Snehashis; He, Qing; Sweeney, Elizabeth; Carass, Aaron; Reich, Daniel S; Prince, Jerry L; Pham, Dzung L

2015-09-01

Quantitative measurements from segmentations of human brain magnetic resonance (MR) images provide important biomarkers for normal aging and disease progression. In this paper, we propose a patch-based tissue classification method from MR images that uses a sparse dictionary learning approach and atlas priors. Training data for the method consists of an atlas MR image, prior information maps depicting where different tissues are expected to be located, and a hard segmentation. Unlike most atlas-based classification methods that require deformable registration of the atlas priors to the subject, only affine registration is required between the subject and training atlas. A subject-specific patch dictionary is created by learning relevant patches from the atlas. Then the subject patches are modeled as sparse combinations of learned atlas patches leading to tissue memberships at each voxel. The combination of prior information in an example-based framework enables us to distinguish tissues having similar intensities but different spatial locations. We demonstrate the efficacy of the approach on the application of whole-brain tissue segmentation in subjects with healthy anatomy and normal pressure hydrocephalus, as well as lesion segmentation in multiple sclerosis patients. For each application, quantitative comparisons are made against publicly available state-of-the art approaches.

Curcumin exerts neuroprotective effects against homocysteine intracerebroventricular injection-induced cognitive impairment and oxidative stress in rat brain.

PubMed

Ataie, Amin; Sabetkasaei, Masoumeh; Haghparast, Abbas; Moghaddam, Akbar Hajizadeh; Ataee, Ramin; Moghaddam, Shiva Nasiraei

2010-08-01

Aging is the major risk factor for neurodegenerative diseases and oxidative stress and is involved in their pathophysiology. Oxidative stress can induce neuronal damage and modulate intracellular signaling, ultimately leading to neuronal death by apoptosis or necrosis. In this study we investigated the neuroprotective properties of the natural polyphenolic antioxidant compound, curcumin, against homocysteine (Hcy) neurotoxicity. Curcumin (5, 15, or 45 mg/kg) was injected intraperitoneally once daily for a period of 10 days beginning 5 days prior to Hcy (0.2 micromol/microl) intracerebroventricular injection in rats. Biochemical and behavioral studies, including passive avoidance learning and locomotor activity tests, were evaluated 24 hours after the last injection of curcumin or vehicle. Results indicated that Hcy induces lipid peroxidation and increases malondialdehyde (MDA) and superoxide anion (SOA) levels in whole rat brain. In addition, Hcy impaired memory retention in the passive avoidance learning test. However, curcumin treatment significantly decreased MDA and SOA levels and improved learning and memory in rats. These results suggest that Hcy may induce lipid peroxidation in rat brain and that polyphenol treatment (curcumin) improves learning and memory deficits by protecting the nervous system against oxidative stress.

Older adults get episodic memory boosting from noninvasive stimulation of prefrontal cortex during learning.

PubMed

Sandrini, Marco; Manenti, Rosa; Brambilla, Michela; Cobelli, Chiara; Cohen, Leonardo G; Cotelli, Maria

2016-03-01

Episodic memory displays the largest degree of age-related decline, a process that is accelerated in pathological conditions such as amnestic mild cognitive impairment and Alzheimer's disease. Previous studies have shown that the left lateral prefrontal cortex (PFC) contributes to the encoding of episodic memories along the life span. The aim of this randomized, double-blind, placebo-controlled study was to test the hypothesis that anodal trascranial direct current stimulation (tDCS) over the left lateral PFC during the learning phase would enhance delayed recall of verbal episodic memories in elderly individuals. Older adults learned a list of words while receiving anodal or placebo (sham) tDCS. Memory recall was tested 48 hours and 1 month later. The results showed that anodal tDCS strengthened episodic memories, an effect indicated by enhanced delayed recall (48 hours) compared to placebo stimulation (Cohen's d effect size = 1.01). The observation that PFC-tDCS during learning can boost verbal episodic memory in the elderly opens up the possibility to design-specific neurorehabilitation protocols targeted to conditions that affect episodic memory such as mild cognitive impairment. Copyright © 2016 Elsevier Inc. All rights reserved.

Mechanisms of vascular aging: What can we learn from Hutchinson-Gilford progeria syndrome?

PubMed

Del Campo, Lara; Hamczyk, Magda R; Andrés, Vicente; Martínez-González, José; Rodríguez, Cristina

Aging is the main risk factor for cardiovascular disease (CVD). The increased prevalence of CVD is partly due to the global increase in life expectancy. In this context, it is essential to identify the mechanisms by which aging induces CVD, with the ultimate aim of reducing its incidence. Both atherosclerosis and heart failure significantly contribute to age-associated CVD morbidity and mortality. Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder caused by the synthesis of progerin, which is noted for accelerated aging and CVD. This mutant form of prelamin A induces generalised atherosclerosis, vascular calcification, and cardiac electrophysiological abnormalities, leading to premature aging and death, mainly due to myocardial infarction and stroke. This review discusses the main vascular structural and functional abnormalities during physiological and premature aging, as well as the mechanisms involved in the exacerbated CVD and accelerated aging induced by the accumulation of progerin and prelamin A. Both proteins are expressed in non-HGPS individuals, and physiological aging shares many features of progeria. Research into HGPS could therefore shed light on novel mechanisms involved in the physiological aging of the cardiovascular system. Copyright © 2018 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

Ageing and Learning: What Do They Mean to Elders Themselves?

ERIC Educational Resources Information Center

Tam, Maureen; Chui, Ernest

2016-01-01

This paper is about a quantitative study which has examined and elucidated the conceptualizations of ageing and learning by a group of elders in Hong Kong. In more specific terms, the study has investigated how this group of older people understood the meaning of successful ageing and elder learning in the context of their later lives. Based on…

Beyond Online versus Face-to-Face Comparisons: The Interaction of Student Age and Mode of Instruction on Academic Achievement

ERIC Educational Resources Information Center

Slover, Ed; Mandernach, Jean

2018-01-01

While it is well-established that nontraditional students are more likely to take online courses than their traditional-age counterparts, investigations of the learning equivalence between online and campus-based instruction typically fail to consider student age as a mediating factor in the learning experience. To examine learning outcomes as a…

The Benefits of Intergenerational Learning in Higher Education: Lessons Learned from Two Age Friendly University Programs

ERIC Educational Resources Information Center

Pstross, Mikulas; Corrigan, Trudy; Knopf, Richard C.; Sung, HeeKyung; Talmage, Craig A.; Conroy, Carmel; Fowley, Cathy

2017-01-01

This article focuses on the role of universities in the promotion of intergenerational learning and the facilitation of reciprocal sharing of expertise among learners of all ages. The principles of the Age Friendly University are used as a particular lens for interpreting two university programs, one in the United States and one in Ireland. Though…

The Learning Projects of Rural Third Age Women: Enriching a Valuable Community Resource

ERIC Educational Resources Information Center

Lear, Glenna

2011-01-01

As a third age PhD candidate with a passion for learning, I wanted to explore the learning of other rural third age women who live on the Lower Eyre Peninsula (LEP) of South Australia. This reflects the methodological stance of heuristic inquiry, which requires the researcher to have a passionate interest in the phenomena under investigation, and…

The significance of 'facilitator as a change agent'--organisational learning culture in aged care home settings.

PubMed

Grealish, Laurie; Henderson, Amanda; Quero, Fritz; Phillips, Roslyn; Surawski, May

2015-04-01

To explore the impact of an educational programme focused on social behaviours and relationships on organisational learning culture in the residential aged care context. The number of aged care homes will continue to rise as the frail older elderly live longer, requiring more formal care and support. As with other small- to medium-sized health services, aged care homes are faced with the challenge of continuous development of the workforce and depend upon registered nurses to lead staff development. A mixed-method evaluation research design was used to determine the impact of an educational programme focused on social aspects of learning on organisational learning culture. One hundred and fifty-nine (pre) and 143 (post) participants from three aged care homes completed the Clinical Learning Organisational Culture survey, and three participant-researcher registered nurse clinical educators provided regular journal entries for review. While each site received the same educational programme over a six-month period, the change in organisational learning culture at each site was notably different. Two aged care homes had significant improvements in affiliation, one in accomplishment and one in recognition. The educators' journals differed in the types of learning observed and interventions undertaken, with Eucalyptus focused on organisational change, Grevillea focused on group (student) change and the Wattle focused on individual or situational change. Clinical educator activities appear to have a significant effect on organisational learning culture, with a focus on the organisational level having the greatest positive effect on learning culture and on individual or situational level having a limited effect. Clinical educator facilitation that is focused on organisational rather than individual interests may offer a key to improving organisational learning culture. © 2014 John Wiley & Sons Ltd.

Normal Aging and the Dissociable Prototype Learning Systems

PubMed Central

Glass, Brian D.; Chotibut, Tanya; Pacheco, Jennifer; Schnyer, David M.; Maddox, W. Todd

2011-01-01

Dissociable prototype learning systems have been demonstrated behaviorally and with neuroimaging in younger adults as well as with patient populations. In A/not-A (AN) prototype learning, participants are shown members of category A during training, and during test are asked to decide whether novel items are in category A or are not in category A. Research suggests that AN learning is mediated by a perceptual learning system. In A/B (AB) prototype learning, participants are shown members of category A and B during training, and during test are asked to decide whether novel items are in category A or category B. In contrast to AN, research suggests that AB learning is mediated by a declarative memory system. The current study examined the effects of normal aging on AN and AB prototype learning. We observed an age-related deficit in AB learning, but an age-related advantage in AN learning. Computational modeling supports one possible interpretation based on narrower selective attentional focus in older adults in the AB task and broader selective attention in the AN task. Neuropsychological testing in older participants suggested that executive functioning and attentional control were associated with better performance in both tasks. However, nonverbal memory was associated with better AN performance, while visual attention was associated with worse AB performance. The results support an interactive memory systems approach and suggest that age-related declines in one memory system can lead to deficits in some tasks, but to enhanced performance in others. PMID:21875215

Vascular ageing and interventions: lessons and learnings

PubMed Central

Williams, Bryan

2016-01-01

This review discusses the relationship between elevated blood pressure, hypertension, arterial stiffness and hence vascular ageing. This is a complex process and the majority of treatments target the consequences of this, rather than the pathophysiology of ageing itself. This is because preventing vascular ageing from occurring is complex and would require very early intervention and lifelong treatment. The process of arteriosclerosis is known to result from reversible and irreversible functional components, and, together, these are responsible for the increased systolic and decreased diastolic blood pressure seen with advancing age. Indeed, hypertension develops as it becomes more difficult for the heart to drive blood flow around the body, as a result of poor ventricular coupling and increased arterial stiffness. Elevated blood pressure is therefore a clinical manifestation of ageing that continues to increase with advancing years, and is also linked with an increased risk of cardiac, cerebrovascular and chronic kidney disease. These manifestations arise due to changing haemodynamics associated with ageing, and therefore treatments that reduce the development of these conditions or delay their progression have the potential to improve patient outcomes. This may be possible with existing therapies as well as new treatments currently under investigation. PMID:27102114

Predicting the survival of diabetes using neural network

NASA Astrophysics Data System (ADS)

Mamuda, Mamman; Sathasivam, Saratha

2017-08-01

Data mining techniques at the present time are used in predicting diseases of health care industries. Neural Network is one among the prevailing method in data mining techniques of an intelligent field for predicting diseases in health care industries. This paper presents a study on the prediction of the survival of diabetes diseases using different learning algorithms from the supervised learning algorithms of neural network. Three learning algorithms are considered in this study: (i) The levenberg-marquardt learning algorithm (ii) The Bayesian regulation learning algorithm and (iii) The scaled conjugate gradient learning algorithm. The network is trained using the Pima Indian Diabetes Dataset with the help of MATLAB R2014(a) software. The performance of each algorithm is further discussed through regression analysis. The prediction accuracy of the best algorithm is further computed to validate the accurate prediction

Faster forgetting contributes to impaired spatial memory in the PDAPP mouse: Deficit in memory retrieval associated with increased sensitivity to interference?

PubMed Central

Daumas, Stephanie; Sandin, Johan; Chen, Karen S.; Kobayashi, Dione; Tulloch, Jane; Martin, Stephen J.; Games, Dora; Morris, Richard G.M.

2008-01-01

Two experiments were conducted to investigate the possibility of faster forgetting by PDAPP mice (a well-established model of Alzheimer’s disease as reported by Games and colleagues in an earlier paper). Experiment 1, using mice aged 13–16 mo, confirmed the presence of a deficit in a spatial reference memory task in the water maze by hemizygous PDAPP mice relative to littermate controls. However, after overtraining to a criterion of equivalent navigational performance, a series of memory retention tests revealed faster forgetting in the PDAPP group. Very limited retraining was sufficient to reinstate good memory in both groups, indicating that their faster forgetting may be due to retrieval failure rather than trace decay. In Experiment 2, 6-mo-old PDAPP and controls were required to learn each of a series of spatial locations to criterion with their memory assessed 10 min after learning each location. No memory deficit was apparent in the PDAPP mice initially, but a deficit built up through the series of locations suggestive of increased sensitivity to interference. Faster forgetting and increased interference may each reflect a difficulty in accessing memory traces. This interpretation of one aspect of the cognitive deficit in human mutant APP mice has parallels to deficits observed in patients with Alzheimer’s disease, further supporting the validity of transgenic models of the disease. PMID:18772249

The effect of normal aging and age-related macular degeneration on perceptual learning.

PubMed

Astle, Andrew T; Blighe, Alan J; Webb, Ben S; McGraw, Paul V

2015-01-01

We investigated whether perceptual learning could be used to improve peripheral word identification speed. The relationship between the magnitude of learning and age was established in normal participants to determine whether perceptual learning effects are age invariant. We then investigated whether training could lead to improvements in patients with age-related macular degeneration (AMD). Twenty-eight participants with normal vision and five participants with AMD trained on a word identification task. They were required to identify three-letter words, presented 10° from fixation. To standardize crowding across each of the letters that made up the word, words were flanked laterally by randomly chosen letters. Word identification performance was measured psychophysically using a staircase procedure. Significant improvements in peripheral word identification speed were demonstrated following training (71% ± 18%). Initial task performance was correlated with age, with older participants having poorer performance. However, older adults learned more rapidly such that, following training, they reached the same level of performance as their younger counterparts. As a function of number of trials completed, patients with AMD learned at an equivalent rate as age-matched participants with normal vision. Improvements in word identification speed were maintained at least 6 months after training. We have demonstrated that temporal aspects of word recognition can be improved in peripheral vision with training across a range of ages and these learned improvements are relatively enduring. However, training targeted at other bottlenecks to peripheral reading ability, such as visual crowding, may need to be incorporated to optimize this approach.

The effect of normal aging and age-related macular degeneration on perceptual learning

PubMed Central

Astle, Andrew T.; Blighe, Alan J.; Webb, Ben S.; McGraw, Paul V.

2015-01-01

We investigated whether perceptual learning could be used to improve peripheral word identification speed. The relationship between the magnitude of learning and age was established in normal participants to determine whether perceptual learning effects are age invariant. We then investigated whether training could lead to improvements in patients with age-related macular degeneration (AMD). Twenty-eight participants with normal vision and five participants with AMD trained on a word identification task. They were required to identify three-letter words, presented 10° from fixation. To standardize crowding across each of the letters that made up the word, words were flanked laterally by randomly chosen letters. Word identification performance was measured psychophysically using a staircase procedure. Significant improvements in peripheral word identification speed were demonstrated following training (71% ± 18%). Initial task performance was correlated with age, with older participants having poorer performance. However, older adults learned more rapidly such that, following training, they reached the same level of performance as their younger counterparts. As a function of number of trials completed, patients with AMD learned at an equivalent rate as age-matched participants with normal vision. Improvements in word identification speed were maintained at least 6 months after training. We have demonstrated that temporal aspects of word recognition can be improved in peripheral vision with training across a range of ages and these learned improvements are relatively enduring. However, training targeted at other bottlenecks to peripheral reading ability, such as visual crowding, may need to be incorporated to optimize this approach. PMID:26605694

78 FR 33120 - Final Interim Staff Guidance LR-ISG-2011-04; Updated Aging Management Criteria for Reactor Vessel...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-03

..., ``Generic Aging Lessons Learned Report'' (GALL Report), for the aging management of Pressurized Water... communicate insights and lessons learned and to address emergent issues not covered in license renewal... ensure that PWR license renewal applicants will adequately address age-related degradation and aging...

Age-related differences in perceptuomotor procedural learning in children.

PubMed

Lejeune, Caroline; Catale, Corinne; Schmitz, Xavier; Quertemont, Etienne; Meulemans, Thierry

2013-10-01

Procedural learning is generally considered to proceed in a series of phases, with cognitive resources playing an important role during the initial step. From a developmental perspective, little is known about the development of procedural learning or the role played by explicit cognitive processes during learning. The main objectives of this study were (a) to determine whether procedural learning performance improves with age by comparing groups of 7-year-old children, 10-year-old children, and adults and (b) to investigate the role played by executive functions during the acquisition in these three age groups. The 76 participants were assessed on a computerized adaptation of the mirror tracing paradigm. Results revealed that the youngest children had more difficulty in adapting to the task (they were slower and committed more errors at the beginning of the learning process) than 10-year-olds, but despite this age effect observed at the outset, all children improved performance across trials and transferred their skill to a different figure as well as adults. Correlational analyses showed that inhibition abilities play a key role in the performance of 10-year-olds and adults at the beginning of the learning but not in that of 7-year-olds. Overall, our results suggest that the age-related differences observed in our procedural learning task are at least partly due to the differential involvement of inhibition abilities, which may facilitate learning (so long as they are sufficiently developed) during the initial steps of the learning process; however, they would not be a necessary condition for skill learning to occur. Copyright © 2013 Elsevier Inc. All rights reserved.

The location discrimination reversal task in mice is sensitive to deficits in performance caused by aging, pharmacological and other challenges.

PubMed

Graf, Radka; Longo, Jami L; Hughes, Zoë A

2018-06-01

Deficits in hippocampal-mediated pattern separation are one aspect of cognitive function affected in schizophrenia (SZ) or Alzheimer's disease (AD). To develop novel therapies, it is beneficial to explore this specific aspect of cognition preclinically. The location discrimination reversal (LDR) task is a hippocampal-dependent operant paradigm that evaluates spatial learning and cognitive flexibility using touchscreens. Here we assessed baseline performance as well as multimodal disease-relevant manipulations in mice. Mice were trained to discriminate between the locations of two images where the degree of separation impacted performance. Administration of putative pro-cognitive agents was unable to improve performance at narrow separation. Furthermore, a range of disease-relevant manipulations were characterized to assess whether performance could be impaired and restored. Pertinent to the cholinergic loss in AD, scopolamine (0.1 mg/kg) produced a disruption in LDR, which was attenuated by donepezil (1 mg/kg). Consistent with NMDA hypofunction in cognitive impairment associated with SZ, MK-801 (0.1 mg/kg) also disrupted performance; however, this deficit was not modified by rolipram. Microdeletion of genes associated with SZ (22q11) resulted in impaired performance, which was restored by rolipram (0.032 mg/kg). Since aging and inflammation affect cognition and are risk factors for AD, these aspects were also evaluated. Aged mice were slower to acquire the task than young mice and did not reach the same level of performance. A systemic inflammatory challenge (lipopolysaccharide (LPS), 1 mg/kg) produced prolonged (7 days) deficits in the LDR task. These data suggest that LDR task is a valuable platform for evaluating disease-relevant deficits in pattern separation and offers potential for identifying novel therapies.

Subtypes of mild cognitive impairment in patients with Parkinson's disease: evidence from the LANDSCAPE study.

PubMed

Kalbe, Elke; Rehberg, Sarah Petra; Heber, Ines; Kronenbuerger, Martin; Schulz, Jörg B; Storch, Alexander; Linse, Katharina; Schneider, Christine; Gräber, Susanne; Liepelt-Scarfone, Inga; Berg, Daniela; Dams, Judith; Balzer-Geldsetzer, Monika; Hilker, Rüdiger; Oberschmidt, Carola; Witt, Karsten; Schmidt, Nele; Mollenhauer, Brit; Trenkwalder, Claudia; Spottke, Annika; Roeske, Sandra; Wittchen, Hans-Ulrich; Riedel, Oliver; Dodel, Richard

2016-10-01

Inconsistent results exist regarding the cognitive profile in patients with Parkinson's disease with mild cognitive impairment (PD-MCI). We aimed at providing data on this topic from a large cohort of patients with PD-MCI. Sociodemographic, clinical and neuropsychological baseline data from patients with PD-MCI recruited in the multicentre, prospective, observational DEMPARK/LANDSCAPE study were analysed. 269 patients with PD-MCI (age 67.8±7.4, Unified Parkinson's Disease Rating Scale (UPDRS-III) scores 23.2±11.6) were included. PD-MCI subtypes were 39.4% non-amnestic single domain, 30.5% amnestic multiple domain, 23.4% non-amnestic multiple domain and 6.7% amnestic single domain. Executive functions were most frequently impaired. The most sensitive tests to detect cognitive dysfunctions were the Modified Card Sorting Test, digit span backwards and word list learning direct recall. Multiple stepwise regression analyses showed that global cognition, gender and age, but not education or disease-related parameters predicted PD-MCI subtypes. This study with the so far largest number of prospectively recruited patients with PD-MCI indicates that non-amnestic PD-MCI is more frequent than amnestic PD-MCI; executive dysfunctions are the most typical cognitive symptom in PD-MCI; and age, gender and global cognition predict the PD-MCI subtype. Longitudinal data are needed to test the hypothesis that patients with PD-MCI with specific cognitive profiles have different risks to develop dementia. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Internet Use for Health-Care Information by Subjects With COPD.

PubMed

Delgado, Cionéia K; Gazzotti, Mariana R; Santoro, Ilka L; Carvalho, Andrea K; Jardim, José R; Nascimento, Oliver A

2015-09-01

Although the internet is an important tool for entertainment, work, learning, shopping, and communication, it is also a possible source for information on health and disease. The aim of this study was to evaluate the proportion of subjects with COPD in São Paulo, Brazil, who use the internet to obtain information about their disease. Subjects (N = 382) with COPD answered a 17-question survey, including information regarding computer use, internet access, and searching for sites on COPD. Our sample was distributed according to the socioeconomic levels of the Brazilian population (low, 17.8%; medium, 66.5%; and high, 15.7%). Most of the subjects in the sample were male (62.6%), with a mean age of 67.0 ± 9.9 y. According to Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages, 74.3% of the subjects were in stage II or III. In addition, 51.6% of the subjects had a computer, 49.7% accessed the internet, and 13.9% used it to search for information about COPD. The internet was predominantly accessed by male (70.3%) and younger (64.6 ± 9.5 y of age) subjects compared with female (29.7%, P = .04) and older (67.5 ± 9.6 y of age, P < .007) subjects. Searching for information about COPD on the internet was associated with having a computer (5.9-fold), Medical Research Council dyspnea level 1 (5.3-fold), and high social class (8.4-fold). The search for information on COPD was not influenced by GOLD staging. A low percentage of subjects with COPD in São Paulo use the internet as a tool to obtain information about their disease. This search is associated with having a computer, low dyspnea score, and high socioeconomic level. Copyright © 2015 by Daedalus Enterprises.

The design and progress of a multidomain lifestyle intervention to improve brain health in middle-aged persons to reduce later Alzheimer's disease risk: The Gray Matters randomized trial.

PubMed

Norton, Maria C; Clark, Christine J; Tschanz, JoAnn T; Hartin, Phillip; Fauth, Elizabeth B; Gast, Julie A; Dorsch, Travis E; Wengreen, Heidi; Nugent, Chris; Robinson, W David; Lefevre, Michael; McClean, Sally; Cleland, Ian; Schaefer, Sydney Y; Aguilar, Sheryl

2015-06-01

Most Alzheimer's disease (AD) prevention studies focus on older adults or persons with existing cognitive impairment. This study describes the design and progress of a novel pilot intervention, the Gray Matters study. This proof-of-concept randomized controlled trial tests an evidence-based multidomain lifestyle intervention in 146 persons aged 40 to 64 years, in northern Utah. Data collectors were blinded to participants' randomization to treatment (n = 104) or control (n = 42). Intervention targeted physical activity, food choices, social engagement, cognitive simulation, sleep quality, and stress management, and uses a custom smartphone application, activity monitor, and educational materials. Secondary outcomes include biomarkers, body mass index, cognitive testing, and psychological surveys. Midway through the study, achievements include a 98.7% retention rate, a 96% rate of compliance with app data entry, and positive trends in behavioral change. Participants were empowered, learning that lifestyle might impact AD risk, exhibiting positive behavioral changes thus far.

Effects of distinctive encoding on source-based false recognition: further examination of recall-to-reject processes in aging and Alzheimer disease.

PubMed

Pierce, Benton H; Waring, Jill D; Schacter, Daniel L; Budson, Andrew E

2008-09-01

To examine the use of distinctive materials at encoding on recall-to-reject monitoring processes in aging and Alzheimer disease (AD). AD patients, and to a lesser extent older adults, have shown an impaired ability to use recollection-based monitoring processes (eg, recall-to-reject) to avoid various types of false memories, such as source-based false recognition. Younger adults, healthy older adults, and AD patients engaged in an incidental learning task, in which critical category exemplars were either accompanied by a distinctive picture or were presented as only words. Later, participants studied a series of categorized lists in which several typical exemplars were omitted and were then given a source memory test. Both older and younger adults made more accurate source attributions after picture encoding compared with word-only encoding, whereas AD patients did not exhibit this distinctiveness effect. These results extend those of previous studies showing that monitoring in older adults can be enhanced with distinctive encoding, and suggest that such monitoring processes in AD patients many be insensitive to distinctiveness.

Research Synthesis Methods in an Age of Globalized Risks: Lessons from the Global Burden of Foodborne Disease Expert Elicitation.

PubMed

2016-02-01

We live in an age that increasingly calls for national or regional management of global risks. This article discusses the contributions that expert elicitation can bring to efforts to manage global risks and identifies challenges faced in conducting expert elicitation at this scale. In doing so it draws on lessons learned from conducting an expert elicitation as part of the World Health Organizations (WHO) initiative to estimate the global burden of foodborne disease; a study commissioned by the Foodborne Disease Epidemiology Reference Group (FERG). Expert elicitation is designed to fill gaps in data and research using structured, transparent methods. Such gaps are a significant challenge for global risk modeling. Experience with the WHO FERG expert elicitation shows that it is feasible to conduct an expert elicitation at a global scale, but that challenges do arise, including: defining an informative, yet feasible geographical structure for the elicitation; defining what constitutes expertise in a global setting; structuring international, multidisciplinary expert panels; and managing demands on experts' time in the elicitation. This article was written as part of a workshop, "Methods for Research Synthesis: A Cross-Disciplinary Approach" held at the Harvard Center for Risk Analysis on October 13, 2013. © 2016 Society for Risk Analysis.

"Lernen" and Learning Styles: A Comparative Analysis of the Learning Styles of German Adolescents by Age, Gender, and Academic Achievement Level

ERIC Educational Resources Information Center

Hlawaty, Heide

2009-01-01

Students in every nation of the world learn new and difficult material in ways that are often similar and, at the same time, different from the way other students of the same age, gender, race, religion, culture, and nationality prefer to learn. The purpose of this study was to identify and compare the preferred learning-style characteristics of…

Deep Learning for Prediction of Obstructive Disease From Fast Myocardial Perfusion SPECT: A Multicenter Study.

PubMed

Betancur, Julian; Commandeur, Frederic; Motlagh, Mahsaw; Sharir, Tali; Einstein, Andrew J; Bokhari, Sabahat; Fish, Mathews B; Ruddy, Terrence D; Kaufmann, Philipp; Sinusas, Albert J; Miller, Edward J; Bateman, Timothy M; Dorbala, Sharmila; Di Carli, Marcelo; Germano, Guido; Otaki, Yuka; Tamarappoo, Balaji K; Dey, Damini; Berman, Daniel S; Slomka, Piotr J

2018-03-12

The study evaluated the automatic prediction of obstructive disease from myocardial perfusion imaging (MPI) by deep learning as compared with total perfusion deficit (TPD). Deep convolutional neural networks trained with a large multicenter population may provide improved prediction of per-patient and per-vessel coronary artery disease from single-photon emission computed tomography MPI. A total of 1,638 patients (67% men) without known coronary artery disease, undergoing stress 99m Tc-sestamibi or tetrofosmin MPI with new generation solid-state scanners in 9 different sites, with invasive coronary angiography performed within 6 months of MPI, were studied. Obstructive disease was defined as ≥70% narrowing of coronary arteries (≥50% for left main artery). Left ventricular myocardium was segmented using clinical nuclear cardiology software and verified by an expert reader. Stress TPD was computed using sex- and camera-specific normal limits. Deep learning was trained using raw and quantitative polar maps and evaluated for prediction of obstructive stenosis in a stratified 10-fold cross-validation procedure. A total of 1,018 (62%) patients and 1,797 of 4,914 (37%) arteries had obstructive disease. Area under the receiver-operating characteristic curve for disease prediction by deep learning was higher than for TPD (per patient: 0.80 vs. 0.78; per vessel: 0.76 vs. 0.73: p < 0.01). With deep learning threshold set to the same specificity as TPD, per-patient sensitivity improved from 79.8% (TPD) to 82.3% (deep learning) (p < 0.05), and per-vessel sensitivity improved from 64.4% (TPD) to 69.8% (deep learning) (p < 0.01). Deep learning has the potential to improve automatic interpretation of MPI as compared with current clinical methods. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

A neurocomputational account of cognitive deficits in Parkinson’s disease

PubMed Central

Hélie, Sébastien; Paul, Erick J.; Ashby, F. Gregory

2014-01-01

Parkinson’s disease (PD) is caused by the accelerated death of dopamine (DA) producing neurons. Numerous studies documenting cognitive deficits of PD patients have revealed impairments in a variety of tasks related to memory, learning, visuospatial skills, and attention. While there have been several studies documenting cognitive deficits of PD patients, very few computational models have been proposed. In this article, we use the COVIS model of category learning to simulate DA depletion and show that the model suffers from cognitive symptoms similar to those of human participants affected by PD. Specifically, DA depletion in COVIS produced deficits in rule-based categorization, non-linear information-integration categorization, probabilistic classification, rule maintenance, and rule switching. These were observed by simulating results from younger controls, older controls, PD patients, and severe PD patients in five well-known tasks. Differential performance among the different age groups and clinical populations was modeled simply by changing the amount of DA available in the model. This suggests that COVIS may not only be an adequate model of the simulated tasks and phenomena but also more generally of the role of DA in these tasks and phenomena. PMID:22683450

Precision global health in the digital age.

PubMed

Flahault, Antoine; Geissbuhler, Antoine; Guessous, Idris; Guérin, Philippe; Bolon, Isabelle; Salathé, Marcel; Escher, Gérard

2017-04-19

Precision global health is an approach similar to precision medicine, which facilitates, through innovation and technology, better targeting of public health interventions on a global scale, for the purpose of maximising their effectiveness and relevance. Illustrative examples include: the use of remote sensing data to fight vector-borne diseases; large databases of genomic sequences of foodborne pathogens helping to identify origins of outbreaks; social networks and internet search engines for tracking communicable diseases; cell phone data in humanitarian actions; drones to deliver healthcare services in remote and secluded areas. Open science and data sharing platforms are proposed for fostering international research programmes under fair, ethical and respectful conditions. Innovative education, such as massive open online courses or serious games, can promote wider access to training in public health and improving health literacy. The world is moving towards learning healthcare systems. Professionals are equipped with data collection and decision support devices. They share information, which are complemented by external sources, and analysed in real time using machine learning techniques. They allow for the early detection of anomalies, and eventually guide appropriate public health interventions. This article shows how information-driven approaches, enabled by digital technologies, can help improving global health with greater equity.

[Research of anti-aging mechanism of ginsenoside Rg1 on brain].

PubMed

Li, Cheng-peng; Zhang, Meng-si; Liu, Jun; Geng, Shan; Li, Jing; Zhu, Jia-hong; Zhang, Yan-yan; Jia, Yan-yan; Wang, Lu; Wang, Shun-he; Wang, Ya-ping

2014-11-01

Neurodegenerative disease is common and frequently occurs in elderly patients. Previous studies have shown that ginsenoside Rg1 was able to inhibit senescent of brain, but the mechanism on the brain during the treatment remains elucidated. To study the mechanism of ginsenoside Rg1 in the process of anti-aging of brain, forty male SD rats were randomly divided into normal group, Rg1 normal group, brain aging model group and Rg1 brain aging model group, each group with 10 rats (brain aging model group: subcutaneous injection of D-galactose (120 mg kg(-1)), qd for 42 consecutive days; Rg1 brain aging model group: while copying the same test as that of brain aging model group, begin intraperitoneal injection of ginsenosides Rg1 (20 mg x kg(-1)) qd for 27 d from 16 d. Rg1 normal group: subcutaneous injection of the same amount of saline; begin intraperitoneal injection of ginsenosides Rg1 (20 mg x kg(-1)) qd for 27 d from 16 d. Normal: injected with an equal volume of saline within the same time. Perform the related experiment on the second day after finishing copying the model or the completion of the first two days of drug injections). Learning and memory abilities were measured by Morris water maze. The number of senescent cells was detected by SA-beta-Gal staining while the level of IL-1 and IL-6 proinflammatory cytokines in hippocampus were detected by ELISA. The activities of SOD, contents of GSH in hippo- campus were quantified by chromatometry. The change of telomerase activities and telomerase length were performed by TRAP-PCR and southern blotting assay, respectively. It is pointed that, in brain aging model group, the spatial learning and memory capacities were weaken, SA-beta-Gal positive granules increased in section of brain tissue, the activity of antioxidant enzyme SOD and the contents of GSH decreased in hippocampus, the level of IL-1 and IL-6 increased in hippocampus, while the length of telomere and the activity of telomerase decreased in hippocampus. Rats of Rg1 brain aging group had their spatial learning and memory capacities enhanced, SA-beta-Gal positive granules in section of brain tissue decreased, the activity of antioxidant enzyme SOD and the contents of GSH increased in hippocampus, the level of IL-1 and IL-6 in hippocampus decreased, the length contraction of telomere suppressed while the change of telomerase activity increased in hippocampus. Compared with that of normal group, the spatial learning and memory capacities were enhanced in Rg1 normal group, SA-beta-Gal positive granules in section of brain tissue decreased in Rg1 normal group, the level of IL-1 and IL-6 in hippocampus decreased in Rg1 normal group. The results indicated that improvement of antioxidant ability, regulating the level of proinflammatory cytokines and regulation of telomerase system may be the underlying anti-aging mechanism of Ginsenoside Rg1.

External validation of ADO, DOSE, COTE and CODEX at predicting death in primary care patients with COPD using standard and machine learning approaches.

PubMed

Morales, Daniel R; Flynn, Rob; Zhang, Jianguo; Trucco, Emmanuel; Quint, Jennifer K; Zutis, Kris

2018-05-01

Several models for predicting the risk of death in people with chronic obstructive pulmonary disease (COPD) exist but have not undergone large scale validation in primary care. The objective of this study was to externally validate these models using statistical and machine learning approaches. We used a primary care COPD cohort identified using data from the UK Clinical Practice Research Datalink. Age-standardised mortality rates were calculated for the population by gender and discrimination of ADO (age, dyspnoea, airflow obstruction), COTE (COPD-specific comorbidity test), DOSE (dyspnoea, airflow obstruction, smoking, exacerbations) and CODEX (comorbidity, dyspnoea, airflow obstruction, exacerbations) at predicting death over 1-3 years measured using logistic regression and a support vector machine learning (SVM) method of analysis. The age-standardised mortality rate was 32.8 (95%CI 32.5-33.1) and 25.2 (95%CI 25.4-25.7) per 1000 person years for men and women respectively. Complete data were available for 54879 patients to predict 1-year mortality. ADO performed the best (c-statistic of 0.730) compared with DOSE (c-statistic 0.645), COTE (c-statistic 0.655) and CODEX (c-statistic 0.649) at predicting 1-year mortality. Discrimination of ADO and DOSE improved at predicting 1-year mortality when combined with COTE comorbidities (c-statistic 0.780 ADO + COTE; c-statistic 0.727 DOSE + COTE). Discrimination did not change significantly over 1-3 years. Comparable results were observed using SVM. In primary care, ADO appears superior at predicting death in COPD. Performance of ADO and DOSE improved when combined with COTE comorbidities suggesting better models may be generated with additional data facilitated using novel approaches. Copyright © 2018. Published by Elsevier Ltd.

Individualized Instruction in Science, Earth Space Project, Learning Activities Package.

ERIC Educational Resources Information Center

Kuczma, R. M.

Learning Activity Packages (LAP) relating to the earth and space are presented for use in sampling a new type of learning for a whole year. Eighteen topics are incorporated into five units: (1) introduction to individualized learning, (2) observation versus interpretation, (3) chemistry in the space age, (4) the space age interdisciplines, and (5)…

Ageing, Loss, and Learning: Hong Kong and Australian Seniors

ERIC Educational Resources Information Center

Boulton-Lewis, Gillian M.; Pike, Lucinda; Tam, Maureen; Buys, Laurie

2017-01-01

In this article, the discussion of loss and its relationship to learning is based on the analysis of interview data from 39 older adults in Hong Kong and 40 in Australia. The focus of the research was on ageing and learning. The phenomenon of life changes, specifically losses, and their relationship to learning was frequently mentioned, and this…

Adult Learning in the Digital Age: Perspectives on Online Technologies and Outcomes

ERIC Educational Resources Information Center

Kidd, Terry T., Ed.; Keengwe, Jared, Ed.

2010-01-01

As instructors move further into the incorporation of 21st century technologies in adult education, a new paradigm of digitally-enriched mediated learning has emerged. This book provides a comprehensive framework of trends and issues related to adult learning for the facilitation of authentic learning in the age of digital technology. This…

Correlates of Individual, and Age-Related, Differences in Short-Term Learning

ERIC Educational Resources Information Center

Zhang, Zhiyong; Davis, Hasker P.; Salthouse, Timothy A.; Tucker-Drob, Elliot M.

2007-01-01

Latent growth models were applied to data on multitrial verbal and spatial learning tasks from two independent studies. Although significant individual differences in both initial level of performance and subsequent learning were found in both tasks, age differences were found only in mean initial level, and not in mean learning. In neither task…

Interindividual Differences in Learning Performance: The Effects of Age, Intelligence, and Strategic Task Approach

ERIC Educational Resources Information Center

Kliegel, Matthias; Altgassen, Mareike

2006-01-01

The present study investigated fluid and crystallized intelligence as well as strategic task approaches as potential sources of age-related differences in adult learning performance. Therefore, 45 young and 45 old adults were asked to learn pictured objects. Overall, young participants outperformed old participants in this learning test. However,…

Learn with the Classics: Using Music To Study Smart at Any Age.

ERIC Educational Resources Information Center

Andersen, Ole; Marsh, Marcy; Harvey, Arthur

This book, accompanied by a musical CD-ROM, provides information on how to enhance learning through music at any age. Sections include: (1) "Let Music Prime Your Brain For Learning," which teaches how important it is to prime the brain for learning through music; (2) "Study Smart," which demonstrates highly effective studying techniques devised by…

Learning to choose: Cognitive aging and strategy selection learning in decision making.

PubMed

Mata, Rui; von Helversen, Bettina; Rieskamp, Jörg

2010-06-01

Decision makers often have to learn from experience. In these situations, people must use the available feedback to select the appropriate decision strategy. How does the ability to select decision strategies on the basis of experience change with age? We examined younger and older adults' strategy selection learning in a probabilistic inference task using a computational model of strategy selection learning. Older adults showed poorer decision performance compared with younger adults. In particular, older adults performed poorly in an environment favoring the use of a more cognitively demanding strategy. The results suggest that the impact of cognitive aging on strategy selection learning depends on the structure of the decision environment. (c) 2010 APA, all rights reserved

Characterizing Rule-Based Category Learning Deficits in Patients with Parkinson's Disease

ERIC Educational Resources Information Center

Filoteo, J. Vincent; Maddox, W. Todd; Ing, A. David; Song, David D.

2007-01-01

Parkinson's disease (PD) patients and normal controls were tested in three category learning experiments to determine if previously observed rule-based category learning impairments in PD patients were due to deficits in selective attention or working memory. In Experiment 1, optimal categorization required participants to base their decision on a…

Evodiamine improves congnitive abilities in SAMP8 and APPswe/PS1ΔE9 transgenic mouse models of Alzheimer's disease

PubMed Central

Yuan, Shu-min; Gao, Kai; Wang, Dong-mei; Quan, Xiong-zhi; Liu, Jiang-ning; Ma, Chun-mei; Qin, Chuan; Zhang, Lian-feng

2011-01-01

Aim: To investigate the effect of evodiamine (a quinolone alkaloid from the fruit of Evodia rutaecarpa) on the progression of Alzheimer's disease in SAMP8 and APPswe/PS1ΔE9 transgenic mouse models. Methods: The mice at age of 5 months were randomized into the model group, two evodiamine (50 mg·kg−1·d−1 and 100 mg·kg−1·d−1) groups and an Aricept (2 mg·kg−1·d−1) group. The littermates of no-transgenic mice and senescence accelerated mouse/resistance 1 mice (SAMR1) were used as controls. After 4 weeks of treatment, learning abilities and memory were assessed using Morris water-maze test, and glucose uptake by the brain was detected using positron emission tomography/computed tomography (PET/CT). Expression levels of IL-1β, IL-6, and TNF-α in brain tissues were detected using ELISA. Expression of COX-2 protein was determined using Western blot. Results: In Morris water-maze test, evodiamine (100 mg·kg−1·d−1) significantly alleviated the impairments of learning ability and memory. Evodiamine (100 mg·kg−1·d−1) also reversed the inhibition of glucose uptake due to development of Alzheimer's disease traits in mice. Furthermore, the dose of evodiamine significantly decreased the expression of IL-1β, IL-6, TNF-α, and COX-2 that were involved in the inflammation due to Alzheimer's disease. Conclusion: The results indicate that evodiamine (100 mg·kg−1·d−1) improves cognitive abilities in the transgenic models of Alzheimer's disease. PMID:21278785

The many facets of motor learning and their relevance for Parkinson's disease.

PubMed

Marinelli, Lucio; Quartarone, Angelo; Hallett, Mark; Frazzitta, Giuseppe; Ghilardi, Maria Felice

2017-07-01

The final goal of motor learning, a complex process that includes both implicit and explicit (or declarative) components, is the optimization and automatization of motor skills. Motor learning involves different neural networks and neurotransmitters systems depending on the type of task and on the stage of learning. After the first phase of acquisition, a motor skill goes through consolidation (i.e., becoming resistant to interference) and retention, processes in which sleep and long-term potentiation seem to play important roles. The studies of motor learning in Parkinson's disease have yielded controversial results that likely stem from the use of different experimental paradigms. When a task's characteristics, instructions, context, learning phase and type of measures are taken into consideration, it is apparent that, in general, only learning that relies on attentional resources and cognitive strategies is affected by PD, in agreement with the finding of a fronto-striatal deficit in this disease. Levodopa administration does not seem to reverse the learning deficits in PD, while deep brain stimulation of either globus pallidus or subthalamic nucleus appears to be beneficial. Finally and most importantly, patients with PD often show a decrease in retention of newly learned skill, a problem that is present even in the early stages of the disease. A thorough dissection and understanding of the processes involved in motor learning is warranted to provide solid bases for effective medical, surgical and rehabilitative approaches in PD. Copyright © 2017 International Federation of Clinical Neurophysiology. All rights reserved.

Preferred strategies for workforce development: feedback from aged care workers.

PubMed

Choy, Sarojni; Henderson, Amanda

2016-11-01

Objective The aim of the present study was to investigate how aged care workers prefer to learn and be supported in continuing education and training activities. Methods Fifty-one workers in aged care facilities from metropolitan and rural settings across two states of Australia participated in a survey and interviews. Survey responses were analysed for frequencies and interview data provided explanations to the survey findings. Results The three most common ways workers were currently learning and prefer to continue to learn are: (1) everyday learning through work individually; (2) everyday learning through work individually assisted by other workers; and (3) everyday learning plus group training courses at work from the employer. The three most common types of provisions that supported workers in their learning were: (1) working and sharing with another person on the job; (2) direct teaching in a group (e.g. a trainer in a classroom at work); and (3) direct teaching by a workplace expert. Conclusions A wholly practice-based continuing education and training model is best suited for aged care workers. Two variations of this model could be considered: (1) a wholly practice-based model for individual learning; and (2) a wholly practice-based model with guidance from coworkers or other experts. Although the model is preferred by workers and convenient for employers, it needs to be well resourced. What is known about the topic? Learning needs for aged care workers are increasing significantly because of an aging population that demands more care workers. Workforce development is largely 'episodic', based on organisational requirements rather than systematic life-long learning. This study is part of a larger 3-year Australian research to investigate models of continuing education training. What does this paper add? Based on an analysis of survey and interview data from 51 workers, the present study suggests effective models of workforce development for aged care workers. What are the implications for practitioners? The effectiveness of the suggested models necessitates a culture where aged care workers' advancement in the workplace is valued and supported. Those responsible for the development of these workers need to be adequately prepared for mentoring and coaching in the workplace.

Is the Alzheimer's disease cortical thickness signature a biological marker for memory?

PubMed

Busovaca, Edgar; Zimmerman, Molly E; Meier, Irene B; Griffith, Erica Y; Grieve, Stuart M; Korgaonkar, Mayuresh S; Williams, Leanne M; Brickman, Adam M

2016-06-01

Recent work suggests that analysis of the cortical thickness in key brain regions can be used to identify individuals at greatest risk for development of Alzheimer's disease (AD). It is unclear to what extent this "signature" is a biological marker of normal memory function - the primary cognitive domain affected by AD. We examined the relationship between the AD signature biomarker and memory functioning in a group of neurologically healthy young and older adults. Cortical thickness measurements and neuropsychological evaluations were obtained in 110 adults (age range 21-78, mean = 46) drawn from the Brain Resource International Database. The cohort was divided into young adult (n = 64, age 21-50) and older adult (n = 46, age 51-78) groups. Cortical thickness analysis was performed with FreeSurfer, and the average cortical thickness extracted from the eight regions that comprise the AD signature. Mean AD-signature cortical thickness was positively associated with performance on the delayed free recall trial of a list learning task and this relationship did not differ between younger and older adults. Mean AD-signature cortical thickness was not associated with performance on a test of psychomotor speed, as a control task, in either group. The results suggest that the AD signature cortical thickness is a marker for memory functioning across the adult lifespan.

Dissociation between Active and Observational Learning from Positive and Negative Feedback in Parkinsonism

PubMed Central

Kobza, Stefan; Ferrea, Stefano; Schnitzler, Alfons; Pollok, Bettina

2012-01-01

Feedback to both actively performed and observed behaviour allows adaptation of future actions. Positive feedback leads to increased activity of dopamine neurons in the substantia nigra, whereas dopamine neuron activity is decreased following negative feedback. Dopamine level reduction in unmedicated Parkinson’s Disease patients has been shown to lead to a negative learning bias, i.e. enhanced learning from negative feedback. Recent findings suggest that the neural mechanisms of active and observational learning from feedback might differ, with the striatum playing a less prominent role in observational learning. Therefore, it was hypothesized that unmedicated Parkinson’s Disease patients would show a negative learning bias only in active but not in observational learning. In a between-group design, 19 Parkinson’s Disease patients and 40 healthy controls engaged in either an active or an observational probabilistic feedback-learning task. For both tasks, transfer phases aimed to assess the bias to learn better from positive or negative feedback. As expected, actively learning patients showed a negative learning bias, whereas controls learned better from positive feedback. In contrast, no difference between patients and controls emerged for observational learning, with both groups showing better learning from positive feedback. These findings add to neural models of reinforcement-learning by suggesting that dopamine-modulated input to the striatum plays a minor role in observational learning from feedback. Future research will have to elucidate the specific neural underpinnings of observational learning. PMID:23185586

Third Age Learning: Adapting the Idea to a Thailand Context of Lifelong Learning

ERIC Educational Resources Information Center

Ratana-Ubol, Archanya; Richards, Cameron

2016-01-01

The concept of the university of the third age (U3A) is well established overseas and a key international focus for emerging global networks of senior citizen (i.e. seniors) lifelong learning. However it is yet to become so in Thailand although it too is in the process of becoming an ageing society. Moreover, this is despite the extent to which…

Age-related changes in rostral basal forebrain cholinergic and GABAergic projection neurons: Relationship with spatial impairment

PubMed Central

Bañuelos, C.; LaSarge, C. L.; McQuail, J. A.; Hartman, J. J.; Gilbert, R. J.; Ormerod, B. K.; Bizon, J. L.

2013-01-01

Both cholinergic and GABAergic projections from the rostral basal forebrain have been implicated in hippocampal function and mnemonic abilities. While dysfunction of cholinergic neurons has been heavily implicated in age-related memory decline, significantly less is known regarding how age-related changes in co-distributed GABAergic projection neurons contribute to a decline in hippocampal-dependent spatial learning. In the current study, confocal stereology was used to quantify cholinergic (choline acetyltransferase (ChAT) immunopositive) neurons, GABAergic projection (glutamic decarboxylase 67 (GAD67) immunopositive) neurons, and total (NeuN immunopositive) neurons in the rostral basal forebrain of young and aged rats that were first characterized on a spatial learning task. ChAT immunopositive neurons were significantly but modestly reduced in aged rats. Although ChAT immunopositive neuron number was strongly correlated with spatial learning abilities among young rats, the reduction of ChAT immunopositive neurons was not associated with impaired spatial learning in aged rats. In contrast, the number of GAD67 immunopositive neurons was robustly and selectively elevated in aged rats that exhibited impaired spatial learning. Interestingly, the total number of rostral basal forebrain neurons was comparable in young and aged rats, regardless of their cognitive status. These data demonstrate differential effects of age on phenotypically distinct rostral basal forebrain projection neurons, and implicate dysregulated cholinergic and GABAergic septohippocampal circuitry in age-related mnemonic decline. PMID:22817834

Patient perspectives on peer mentoring: type 1 diabetes management in adolescents and young adults.

PubMed

Lu, Yang; Pyatak, Elizabeth A; Peters, Anne L; Wood, Jamie R; Kipke, Michele; Cohen, Marisa; Sequeira, Paola A

2015-02-01

The purpose of the study was to identify attitudes and topics relevant to peer mentoring as an adherence-promoting intervention for adolescents and young adults (YAs) with type 1 diabetes (T1D). Self-administered survey data were collected in 2 diabetes clinics from a convenience sample of adolescents as prospective mentees (ages 13-18) and YAs as prospective mentors (ages 19-25) with T1D. Survey topics included demographics, disease history, glycemic control, adherence, depression, barriers to disease management, social support, and interest in peer mentoring. Descriptive statistical analyses, thematic coding, and stepwise multivariate logistic regression were performed. A majority of the 54 adolescents and 46 YAs expressed interest in a peer mentoring program. Having supportive friends and living in a large household positively predicted adolescent interest in having a peer mentor. Approximately one-third of all participants experienced social barriers to diabetes management. For adolescents, barriers included inflexible schedules, unfamiliar foods, and the embarrassment of checking blood glucose in front of others. Young adults reported barriers in tracking food consumption and remembering to check blood glucose. Various diabetes management skills were in high demand by adolescents, who especially desired to learn about managing T1D on their own and in college. Participants were open to multiple communication modes, including in-person meetings, phone, text messaging, and social media. Many adolescents and young adults with T1D are interested in peer mentoring as a way to facilitate learning and sharing essential diabetes management skills and experiences. © 2014 The Author(s).

Patient Perspectives on Peer Mentoring: Type 1 Diabetes Management in Adolescents and Young Adults

PubMed Central

Lu, Yang; Pyatak, Elizabeth A.; Peters, Anne L.; Wood, Jamie R.; Kipke, Michele; Cohen, Marisa; Sequeira, Paola A.

2014-01-01

Purpose The purpose of the study was to identify attitudes and topics relevant to peer mentoring as an adherence-promoting intervention for adolescents and young adults (YAs) with type 1 diabetes (T1D). Methods Self-administered survey data were collected in two diabetes clinics from a convenience sample of adolescents as prospective mentees (ages 13–18) and YAs as prospective mentors (ages 19–25) with T1D. Survey topics included demographics, disease history, glycemic control, adherence, depression, barriers to disease management, social support, and interest in peer mentoring. Descriptive statistical analyses, thematic coding, and stepwise multivariate logistic regression were performed. Results A majority of the 54 adolescents and 46 YAs expressed interest in a peer mentoring program. Having supportive friends and living in a large household positively predicted adolescent interest in having a peer mentor. Approximately one third of all participants experienced social barriers to diabetes management. For adolescents, barriers included inflexible schedules, unfamiliar foods, and the embarrassment of checking blood glucose in front of others. Young adults reported barriers in tracking food consumption and remembering to check blood glucose. Various diabetes management skills were in high demand by adolescents, who especially desired to learn about managing T1D on their own and in college. Participants were open to multiple communication modes, including in-person meetings, phone, text messaging, and social media. Conclusions Many adolescents and young adults with T1D are interested in peer mentoring as a way to facilitate learning and sharing essential diabetes management skills and experiences. PMID:25394732

Genetic Risk for Age-Related Cognitive Impairment Does Not Predict Cognitive Performance in Middle Age.

PubMed

Korthauer, Laura E; Awe, Elizabeth; Frahmand, Marijam; Driscoll, Ira

2018-05-26

Alzheimer's disease (AD) is characterized by memory loss and executive dysfunction, which correspond to structural changes to the medial temporal lobes (MTL) and prefrontal cortex (PFC), respectively. Given the overlap in cognitive deficits between healthy aging and the earliest stages of AD, early detection of AD remains a challenge. The goal of the present study was to study MTL- and PFC-dependent cognitive functioning in middle-aged individuals at genetic risk for AD or cognitive impairment who do not currently manifest any clinical symptoms. Participants (N = 150; aged 40-60 years) underwent genotyping of 47 single nucleotide polymorphisms (SNPs) in six genes previously associated with memory or executive functioning: APOE, SORL1, BDNF, TOMM40, KIBRA, and COMT. They completed two MTL-dependent tasks, the virtual Morris Water Task (vMWT) and transverse patterning discriminations task (TPDT), and the PFC-dependent reversal learning task. Although age was associated with poorer performance on the vMWT and TPDT within this middle-aged sample, there were no genotype-associated differences in cognitive performance. Although the vMWT and TPDT may be sensitive to age-related changes in cognition, carriers of APOE, SORL1, BDNF, TOMM40, KIBRA, and COMT risk alleles do not exhibit alteration in MTL- and PFC-dependent functioning in middle age compared to non-carriers.

Insufficient DNA methylation affects healthy aging and promotes age-related health problems.

PubMed

Liu, Liang; van Groen, Thomas; Kadish, Inga; Li, Yuanyuan; Wang, Deli; James, Smitha R; Karpf, Adam R; Tollefsbol, Trygve O

2011-08-01

DNA methylation plays an integral role in development and aging through epigenetic regulation of genome function. DNA methyltransferase 1 (Dnmt1) is the most prevalent DNA methyltransferase that maintains genomic methylation stability. To further elucidate the function of Dnmt1 in aging and age-related diseases, we exploited the Dnmt1+/- mouse model to investigate how Dnmt1 haploinsufficiency impacts the aging process by assessing the changes of several major aging phenotypes. We confirmed that Dnmt1 haploinsufficiency indeed decreases DNA methylation as a result of reduced Dnmt1 expression. To assess the effect of Dnmt1 haploinsufficiency on general body composition, we performed dual-energy X-ray absorptiometry analysis and showed that reduced Dnmt1 activity decreased bone mineral density and body weight, but with no significant impact on mortality or body fat content. Using behavioral tests, we demonstrated that Dnmt1 haploinsufficiency impairs learning and memory functions in an age-dependent manner. Taken together, our findings point to the interesting likelihood that reduced genomic methylation activity adversely affects the healthy aging process without altering survival and mortality. Our studies demonstrated that cognitive functions of the central nervous system are modulated by Dnmt1 activity and genomic methylation, highlighting the significance of the original epigenetic hypothesis underlying memory coding and function.

Age-related impairments in active learning and strategic visual exploration.

PubMed

Brandstatt, Kelly L; Voss, Joel L

2014-01-01

Old age could impair memory by disrupting learning strategies used by younger individuals. We tested this possibility by manipulating the ability to use visual-exploration strategies during learning. Subjects controlled visual exploration during active learning, thus permitting the use of strategies, whereas strategies were limited during passive learning via predetermined exploration patterns. Performance on tests of object recognition and object-location recall was matched for younger and older subjects for objects studied passively, when learning strategies were restricted. Active learning improved object recognition similarly for younger and older subjects. However, active learning improved object-location recall for younger subjects, but not older subjects. Exploration patterns were used to identify a learning strategy involving repeat viewing. Older subjects used this strategy less frequently and it provided less memory benefit compared to younger subjects. In previous experiments, we linked hippocampal-prefrontal co-activation to improvements in object-location recall from active learning and to the exploration strategy. Collectively, these findings suggest that age-related memory problems result partly from impaired strategies during learning, potentially due to reduced hippocampal-prefrontal co-engagement.

Ageing and Learning in Australia: Arguing an Evidence Base for Informed and Equitable Policy.

PubMed

Cuthill, Michael; Buys, Laurie; Wilson, Bruce; Kimberley, Helen; Reghenzani, Denise; Kearns, Peter; Thompson, Sally; Golding, Barry; Root, Jo; Weston, Rhonda

2016-01-01

Given Australia's population ageing and predicted impacts related to health, productivity, equity and enhancing quality of life outcomes for senior Australians, lifelong learning has been identified as a pathway for addressing the risks associated with an ageing population. To date Australian governments have paid little attention to addressing these needs and thus, there is an urgent need for policy development for lifelong learning as a national priority. The purpose of this article is to explore the current lifelong learning context in Australia and to propose a set of factors that are most likely to impact learning in later years. Evidence based policy that understands and incorporates learning opportunities for all citizens is required to meet emerging global challenges. Providing appropriate learning opportunities to seniors is one clear pathway for achieving diverse health, social and economic outcomes.

Memory Deficits Are Associated with Impaired Ability to Modulate Neuronal Excitability in Middle-Aged Mice

ERIC Educational Resources Information Center

Kaczorowski, Catherine C.; Disterhoft, John F.

2009-01-01

Normal aging disrupts hippocampal neuroplasticity and learning and memory. Aging deficits were exposed in a subset (30%) of middle-aged mice that performed below criterion on a hippocampal-dependent contextual fear conditioning task. Basal neuronal excitability was comparable in middle-aged and young mice, but learning-related modulation of the…

The Status of Rapid Response Learning in Aging

PubMed Central

Dew, Ilana T. Z.; Giovanello, Kelly S.

2010-01-01

Strong evidence exists for an age-related impairment in associative processing under intentional encoding and retrieval conditions, but the status of incidental associative processing has been less clear. Two experiments examined the effects of age on rapid response learning – the incidentally learned stimulus-response association that results in a reduction in priming when a learned response becomes inappropriate for a new task. Specifically, we tested whether priming was equivalently sensitive in both age groups to reversing the task-specific decision cue. Experiment 1 showed that cue inversion reduced priming in both age groups using a speeded inside/outside classification task, and in Experiment 2 cue inversion eliminated priming on an associative version of this task. Thus, the ability to encode an association between a stimulus and its initial task-specific response appears to be preserved in aging. These findings provide an important example of a form of associative processing that is unimpaired in older adults. PMID:20853961

Age differences in risky choice: a meta-analysis

PubMed Central

Mata, Rui; Josef, Anika K.; Samanez-Larkin, Gregory R.; Hertwig, Ralph

2012-01-01

Does risk taking change as a function of age? We conducted a systematic literature search and found 29 comparisons between younger and older adults on behavioral tasks thought to measure risk taking (N =4,093). The reports relied on various tasks differing in several respects, such as the amount of learning required or the choice framing (gains vs. losses). The results suggest that age-related differences vary considerably as a function of task characteristics, in particular the learning requirements of the task. In decisions from experience, age-related differences in risk taking were a function of decreased learning performance: older adults were more risk seeking compared to younger adults when learning led to risk-avoidant behavior, but were more risk averse when learning led to risk-seeking behavior. In decisions from description, younger adults and older adults showed similar risk-taking behavior for the majority of the tasks, and there were no clear age-related differences as a function of gain/loss framing. We discuss limitations and strengths of past research and provide suggestions for future work on age-related differences in risk taking. PMID:22023565

Neural correlates of the age-related changes in motor sequence learning and motor adaptation in older adults

PubMed Central

King, Bradley R.; Fogel, Stuart M.; Albouy, Geneviève; Doyon, Julien

2013-01-01

As the world's population ages, a deeper understanding of the relationship between aging and motor learning will become increasingly relevant in basic research and applied settings. In this context, this review aims to address the effects of age on motor sequence learning (MSL) and motor adaptation (MA) with respect to behavioral, neurological, and neuroimaging findings. Previous behavioral research investigating the influence of aging on motor learning has consistently reported the following results. First, the initial acquisition of motor sequences is not altered, except under conditions of increased task complexity. Second, older adults demonstrate deficits in motor sequence memory consolidation. And, third, although older adults demonstrate deficits during the exposure phase of MA paradigms, the aftereffects following removal of the sensorimotor perturbation are similar to young adults, suggesting that the adaptive ability of older adults is relatively intact. This paper will review the potential neural underpinnings of these behavioral results, with a particular emphasis on the influence of age-related dysfunctions in the cortico-striatal system on motor learning. PMID:23616757

Age and Second Language Acquisition.

ERIC Educational Resources Information Center

Singleton, David

2001-01-01

Reviews the age factor in second language learning. Sketches some of the relevant research findings that have emerged in the last three decades and hones in on the results recently published on age-related research. Concludes with a discussion of whether there is an age factor in second language learning. (Author/VWL)

The effect of presentation rate on implicit sequence learning in aging.

PubMed

Foster, Chris M; Giovanello, Kelly S

2017-02-01

Implicit sequence learning is thought to be preserved in aging when the to-be learned associations are first-order; however, when associations are second-order, older adults (OAs) tend to experience deficits as compared to young adults (YAs). Two experiments were conducted using a first (Experiment 1) and second-order (Experiment 2) serial-reaction time task. Stimuli were presented at a constant rate of either 800 milliseconds (fast) or 1200 milliseconds (slow). Results indicate that both age groups learned first-order dependencies equally in both conditions. OAs and YAs also learned second-order dependencies, but the learning of lag-2 information was significantly impacted by the rate of presentation for both groups. OAs showed significant lag-2 learning in slow condition while YAs showed significant lag-2 learning in the fast condition. The sensitivity of implicit sequence learning to the rate of presentation supports the idea that OAs and YAs different processing speeds impact the ability to build complex associations across time and intervening events.

Relationship between perceptual learning in speech and statistical learning in younger and older adults

PubMed Central

Neger, Thordis M.; Rietveld, Toni; Janse, Esther

2014-01-01

Within a few sentences, listeners learn to understand severely degraded speech such as noise-vocoded speech. However, individuals vary in the amount of such perceptual learning and it is unclear what underlies these differences. The present study investigates whether perceptual learning in speech relates to statistical learning, as sensitivity to probabilistic information may aid identification of relevant cues in novel speech input. If statistical learning and perceptual learning (partly) draw on the same general mechanisms, then statistical learning in a non-auditory modality using non-linguistic sequences should predict adaptation to degraded speech. In the present study, 73 older adults (aged over 60 years) and 60 younger adults (aged between 18 and 30 years) performed a visual artificial grammar learning task and were presented with 60 meaningful noise-vocoded sentences in an auditory recall task. Within age groups, sentence recognition performance over exposure was analyzed as a function of statistical learning performance, and other variables that may predict learning (i.e., hearing, vocabulary, attention switching control, working memory, and processing speed). Younger and older adults showed similar amounts of perceptual learning, but only younger adults showed significant statistical learning. In older adults, improvement in understanding noise-vocoded speech was constrained by age. In younger adults, amount of adaptation was associated with lexical knowledge and with statistical learning ability. Thus, individual differences in general cognitive abilities explain listeners' variability in adapting to noise-vocoded speech. Results suggest that perceptual and statistical learning share mechanisms of implicit regularity detection, but that the ability to detect statistical regularities is impaired in older adults if visual sequences are presented quickly. PMID:25225475

Relationship between perceptual learning in speech and statistical learning in younger and older adults.

PubMed

Neger, Thordis M; Rietveld, Toni; Janse, Esther

2014-01-01

Within a few sentences, listeners learn to understand severely degraded speech such as noise-vocoded speech. However, individuals vary in the amount of such perceptual learning and it is unclear what underlies these differences. The present study investigates whether perceptual learning in speech relates to statistical learning, as sensitivity to probabilistic information may aid identification of relevant cues in novel speech input. If statistical learning and perceptual learning (partly) draw on the same general mechanisms, then statistical learning in a non-auditory modality using non-linguistic sequences should predict adaptation to degraded speech. In the present study, 73 older adults (aged over 60 years) and 60 younger adults (aged between 18 and 30 years) performed a visual artificial grammar learning task and were presented with 60 meaningful noise-vocoded sentences in an auditory recall task. Within age groups, sentence recognition performance over exposure was analyzed as a function of statistical learning performance, and other variables that may predict learning (i.e., hearing, vocabulary, attention switching control, working memory, and processing speed). Younger and older adults showed similar amounts of perceptual learning, but only younger adults showed significant statistical learning. In older adults, improvement in understanding noise-vocoded speech was constrained by age. In younger adults, amount of adaptation was associated with lexical knowledge and with statistical learning ability. Thus, individual differences in general cognitive abilities explain listeners' variability in adapting to noise-vocoded speech. Results suggest that perceptual and statistical learning share mechanisms of implicit regularity detection, but that the ability to detect statistical regularities is impaired in older adults if visual sequences are presented quickly.

Relearning in the Elderly: Age-Related Effects on the Size of Savings

ERIC Educational Resources Information Center

van der Hoeven, Nienke; de Bot, Kees

2012-01-01

This article reports on a study on learning new and relearning forgotten words of French as a foreign language in young (mean age 22.4), middle-aged (mean age 50.3), and elderly speakers (mean age 76.0). The three age groups performed similarly on relearning old words, but the younger learners were significantly better at learning new words. Data…

The influence of demographics and work related goals on adaptive development for work related learning amongst private hospital employees.

PubMed

Tones, Megan; Pillay, Hitendra; Fraser, Jennifer

2010-01-01

Contemporary lifespan development models of adaptive development have been applied to the workforce to examine characteristics of the ageing employee. Few studies have examined adaptive development in terms of worker perceptions of workplace, or their learning and development issues. This study used the recently developed Revised Learning and Development Survey to investigate employee selection and engagement of learning and development goals, opportunities for learning and development at work, and constraints to learning and development at work. Demographic and career goal variables were tested amongst a sample of private hospital employees, almost all of whom were nurses. Workers under 45 years of age perceived greater opportunities for training and development than more mature aged workers. Age and physical demands interacted such that physical demands of work were associated with lower engagement in learning and development goals in mature aged workers. The opposite was observed amongst younger workers. Engagement in learning and development goals at work predicted goals associated with an intention to decrease work hours or change jobs to a different industry when opportunities to learn via work tasks were limited. At the same time limited opportunities for training and development and perceptions of constraints to development at work predicted the intention to change jobs. Results indicate consideration must be paid to employee perceptions in the workplace in relation to goals. They may be important factors in designing strategies to retain workers.

The effects of aging on the interaction between reinforcement learning and attention.

PubMed

Radulescu, Angela; Daniel, Reka; Niv, Yael

2016-11-01

Reinforcement learning (RL) in complex environments relies on selective attention to uncover those aspects of the environment that are most predictive of reward. Whereas previous work has focused on age-related changes in RL, it is not known whether older adults learn differently from younger adults when selective attention is required. In 2 experiments, we examined how aging affects the interaction between RL and selective attention. Younger and older adults performed a learning task in which only 1 stimulus dimension was relevant to predicting reward, and within it, 1 "target" feature was the most rewarding. Participants had to discover this target feature through trial and error. In Experiment 1, stimuli varied on 1 or 3 dimensions and participants received hints that revealed the target feature, the relevant dimension, or gave no information. Group-related differences in accuracy and RTs differed systematically as a function of the number of dimensions and the type of hint available. In Experiment 2 we used trial-by-trial computational modeling of the learning process to test for age-related differences in learning strategies. Behavior of both young and older adults was explained well by a reinforcement-learning model that uses selective attention to constrain learning. However, the model suggested that older adults restricted their learning to fewer features, employing more focused attention than younger adults. Furthermore, this difference in strategy predicted age-related deficits in accuracy. We discuss these results suggesting that a narrower filter of attention may reflect an adaptation to the reduced capabilities of the reinforcement learning system. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Procedural learning in Parkinson's disease, specific language impairment, dyslexia, schizophrenia, developmental coordination disorder, and autism spectrum disorders: A second-order meta-analysis.

PubMed

Clark, Gillian M; Lum, Jarrad A G

2017-10-01

The serial reaction time task (SRTT) has been used to study procedural learning in clinical populations. In this report, second-order meta-analysis was used to investigate whether disorder type moderates performance on the SRTT. Using this approach to quantitatively summarise past research, it was tested whether autism spectrum disorder, developmental coordination disorder, dyslexia, Parkinson's disease, schizophrenia, and specific language impairment differentially affect procedural learning on the SRTT. The main analysis revealed disorder type moderated SRTT performance (p=0.010). This report demonstrates comparable levels of procedural learning impairment in developmental coordination disorder, dyslexia, Parkinson's disease, schizophrenia, and specific language impairment. However, in autism, procedural learning is spared. Copyright © 2017 Elsevier Inc. All rights reserved.

Exploring educational needs and design aspects of internet-enabled patient education for persons with diabetes: a qualitative interview study.

PubMed

Jafari, Javad; Karimi Moonaghi, Hosein; Zary, Nabil; Masiello, Italo

2016-10-31

The objective of this article is to explore the educational needs and design aspects of personalised internet-enabled education for patients with diabetes in Iran. Data were collected using semistructured interviews and then qualitatively analysed using inductive content analysis. 9 patients with type 2 diabetes were included. Inclusion criteria were access to and knowledge on how to use the internet. The selection ensured representation based on gender, age, occupation and educational background. The sample population was patients with diabetes who were admitted to an outpatient diabetes clinic in Mashhad, a large city of Iran with about 3 million inhabitants. 4 core categories emerged from the data: (1) seeking knowledge about diabetes, including specific knowledge acquisition, patient's interactions and learning requirements; (2) teaching and learning, including using different teaching methods and different ways to learn about the disease; (3) facilitators, including internet and mobile phone use to learn about the disease; and (4) barriers, including lack of internet access, uncertainty of access to the internet and lack of website in the local language and also perceived cultural barriers, such as patients' fears of the internet, lack of time and awareness. This study provides a better understanding of the patient's educational expectations and technical needs in relation to internet-enabled education. This knowledge will inform the development of functional mock-ups in the next research phase using a design-based research approach in order to design internet-enabled patient education for self-management of diabetes. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Reliability of the five-repetition sit-to-stand test in patients with chronic obstructive pulmonary disease on domiciliary oxygen therapy.

PubMed

Cani, Katerine Cristhine; Silva, Isabela Julia Cristiana Santos; Karloh, Manuela; Gulart, Aline Almeida; Matte, Darlan Laurício; Mayer, Anamaria Fleig

2018-06-01

To evaluate the reliability and learning effect of the five-repetition sit-to-stand test (5STSt) in severe and very severe chronic obstructive pulmonary disease (COPD) patients on domiciliary oxygen therapy compare the results with those of COPD patients not on such therapy. Twenty-eight COPD patients were included in the domiciliary oxygen therapy group (DOTG) and 17 in the control group (CG). The participants of the groups were paired by age, sex, body mass index, and lung function. The groups performed two 5STSt (5STSt 1 and 5STSt 2 ). In total, 96% of the patients in the DOTG performed better on the second 5STSt (5STSt 2 ) (17.1 ± 4.63s), with an average reduction of 3.87 ± 3.50 s (p < 0.001) and a learning effect of 18.4%. In the CG, 82.3% of patients had better performance on the 5STSt 2 (15.06 ± 3.45 s), with an average reduction of 1.38 ± 2.51 s (p = 0.035) and a learning effect of 8.39%. The 5STSt had an ICC of 0.79 (95%CI: 0.02-0.93; p < 0.001) in the DOTG and of 0.89 (95%CI: 0.65-0.96; p < 0.001) in the CG. The 5STSt is reliable in patients with severe and very severe COPD on domiciliary oxygen therapy, with learning effect of nearly 18% in the DOTG. Thus, performing two tests is recommended to achieve the patient´s best performance in this population.

Lifestyle Habits among Adult Congenital Heart Disease Patients in Malta.

PubMed

Caruana, Maryanne; Grech, Victor

2016-07-01

Adult congenital heart disease patients are prone to health risk behaviors like their peers. Such behaviors can have serious implications, particularly in patients with complex congenital lesions. We investigated patterns in tobacco smoking, alcohol consumption, substance misuse, dental reviews, and physical activity in Maltese patients. A questionnaire modeled on the 2008 European Health Interview Survey was offered to consecutive adult congenital heart disease outpatients, aged 16 years and over, between May 2013 and May 2014. Foreigners and patients with learning difficulties or cognitive impairment were excluded. Data on these habits was compared with that from 372 age-matched and sex-matched 2008 survey responders (general population cohort). There were 125 patient responders (65 males; mean age 30.64, SD 12.80 years). Adult congenital heart disease patients smoked less (patients 18.4%, general 32.0% P = .004) and had more regular dental reviews (patients 60.9%, general 45.2% P = .003) but were less physically active than the general population cohort (patients 30.6%, general 62.9% P < .001). The difference in smoking was only significant in patients born after the mid-1970s (younger) and females, while dental reviews were only better in younger and male patients. Male patients consumed alcohol more frequently (38.1%) than general population males (23.3%, P = .02). In the patient cohort, smoking was more likely with milder congenital lesions (OR 4.689, P = .007), substance misuse more likely in males (OR 5.703, P = .036) and with milder lesions (OR 5.405, P = .030) and alcohol consumption more likely in males (OR 11.697, P < .001). Although there is an overall lower uptake of some unhealthy habits by Maltese adult congenital heart disease patients, this is not consistent between sexes or age groups. Male and older patients and those with milder lesions might need more reinforcement of the advice given regarding lifestyle habits. All patients need targeted exercise prescription to ensure better physical activity levels. © 2016 Wiley Periodicals, Inc.