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Cognitive rehabilitation in old age
Abstracts dysfunction is thought to be due to the secretion of neurotoxic substances from infected/activated macrophages and microglia. Feline immunodeficiency virus (FIV) infection of cats recapitulates all essential aspects of HIV infection in humans and has been used to perform detailed in vitro and in vivo studies of lentivirus-associated neuropathogenesis. In vitro studies have shown that a new class of non-peptide neurotrophin mimetics can reverse FIV- and HIV-associated neuronal dysfunction and damage. However, the translation of these findings to an in vivo model has been limited by the lack of behavioral assessment paradigms that track cognitive-motor disease progression with sensitivity and reliability. In an effort to develop tests of cognitive-motor function in cats, we initiated preliminary testing of FIV-infected cats using a prototype large animal T maze developed by CanCog Technologies. Infected cats compared to sham controls showed an increase in high hoop latencies and greater discrimination errors that correlated with FIV viral burden in cerebrospinal fluid. In addition, decreased habituation and increased vocalizations were observed in open field tests. Behavioral deficits were detected at 6-12 months post-infection reflecting the earliest (reversible) phases of neural disease progression. With further refinements in design, we anticipate that these tests will provide sensitive measures of neurological disease progression that can be used to investigate the cognitive effects of neurotrophin mimetics on FIV-infected cats. Key words: feline immunodeficiency virus; dementia; neurotrophin; therapy; behavior
GENE EXPRESSION CHANGES AS A FUNCTION OF AGE IN BEAGLES: PRELIMINARY RESULTS Elizabeth Head1,2,*, Amy L.S. Dowling1, Edward G. Barrett3, Eric M. Blalock2 1 Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, 40536 2 Department of Molecular and Biomedical Pharmacology, University of Kentucky, Lexington, KY, 40536 3 Lovelace Respiratory Research Institute, Albuquerque, NM, 87108 *Corresponding author: [email protected] During human aging, a number of brain changes contribute to impaired cognition, including oxidative damage, neuronal dysfunction, and b-amyloid (Ab) deposition. The canine (dog) model of aging is uniquely suited to aging research as they, like humans, spontaneously develop Ab plaques. Here, we examined gene expression changes in the parietal cortex of 15 beagles (5 young, 5 middle aged and 5 old) as a function of age. Total RNA was isolated and hybridized to Affymetrix GeneChip Canine Genome 2.0 Arrays (Affymetrix, Santa Clara, CA; one array per subject). Overall, 1,983 genes changed significantly across age (1-ANOVA; p % 0.05; False Discovery Rate 5 0.13). Post hoc pairwise contrasts revealed that the overwhelming majority of these changes
161 (64%; 537 upregulated, 724 downregulated) occurred between young and aged animals while mid-aged transcriptional profiles were relatively intermediate (74% similar to young, 66% similar to aged). Statistically significant genes with a linear trend to decrease (369 genes) or increase (292 genes) were subjected to DAVID analysis to identify biological processes. Upregulated genes were associated with transcription regulation, translation, RNA processing, DNA metabolic processes and ribonucleoprotein. In contrast, downregulated genes were associated with lipid binding, lipid biosynthesis, nervous system development and neurogenesis. In combination, the aged canine brain shows increased gene expression associated with possible compensatory responses and decreases in lipid and neurogenesis pathways that may be modifiable through targeted interventions. Funding provided by NIH/NIA AG032550 to EH. Key words: beagle; canine; gene expression
COGNITIVE REHABILITATION IN OLD AGE G. Winocur1,2,3,4,* 1 Rotman Research Institute, Baycrest Centre, Toronto, ON, M6A 2E1, Canada 2 Department of Psychology, Trent University, Peterborough, ON, K9J 7B8, Canada 3 Department of Psychology, University of Toronto, Toronto, ON, M5T 1R8, Canada 4 Department of Psychiatry, University of Toronto, Toronto, ON, M5T 1R8, Canada *Corresponding author: [email protected] Using a general model of strategic processing we developed an experimental evaluation of a new approach to cognitive rehabilitation in individuals with memory and memoryrelated problems. The program is based on the premise that older adults and younger adults with brain damage need assistance in selecting and implementing strategies that are appropriate to specific tasks. As participants become increasingly familiar with the application of various strategies in responding to cognitive demands, we predicted that this essential operation would be accomplished with reduced effort and incorporated into their daily lives. The result is a 12-week training protocol that divides into three components: (1) cognitive skills training, where the emphasis is on using internal and external aids to acquire, retain, and recover information; (2) goal-management training in which laboratory-based strategies, introduced during cognitive skills training, are transferred to ‘real-life’ situations; (3) psychosocial training, in which the aim is to enhance psychological well-being and establish the link between overall functional status and cognitive function. The protocol was tested on a sample of normal old people who complained of memory loss and other cognitive problems. The study is unique in several ways. It is one of a small number of trials to use a multiple baseline
162 control; it is comprehensive in assessing the relative importance of various factors that impact rehabilitation of cognitive performance; it spans a 12 month period and includes a follow-up assessment of long-term benefits several months after the termination of training; it provides a wide range of behavioural, neuropsychological, and psychosocial outcome measures. The results indicated significant benefits of rehabilitation on a broad range of cognitive and psychosocial measures. The experimental design allowed us to conclude that the
Journal of Veterinary Behavior, Vol 5, No 3, May/June 2010 changes were the direct result of rehabilitation, and not secondary to general participation or repeated assessments. We attribute the success of our program to a variety of factors, including the emphasis on strategic processes in lab-based and practical training, psychosocial factors that relate to cognitive function, the dynamics of the supportive group session, commitment to home assignments, as well as the identification and realization of individual goals. Key words: cognitive rehabilitation; strategic processing; older adults
GENE EXPRESSION CHANGES AS A FUNCTION OF AGE IN BEAGLES: PRELIMINARY RESULTS Elizabeth Head1,2,*, Amy L.S. Dowling1, Edward G. Barrett3, Eric M. Blalock2 1 Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, 40536 2 Department of Molecular and Biomedical Pharmacology, University of Kentucky, Lexington, KY, 40536 3 Lovelace Respiratory Research Institute, Albuquerque, NM, 87108 *Corresponding author: [email protected] During human aging, a number of brain changes contribute to impaired cognition, including oxidative damage, neuronal dysfunction, and b-amyloid (Ab) deposition. The canine (dog) model of aging is uniquely suited to aging research as they, like humans, spontaneously develop Ab plaques. Here, we examined gene expression changes in the parietal cortex of 15 beagles (5 young, 5 middle aged and 5 old) as a function of age. Total RNA was isolated and hybridized to Affymetrix GeneChip Canine Genome 2.0 Arrays (Affymetrix, Santa Clara, CA; one array per subject). Overall, 1,983 genes changed significantly across age (1-ANOVA; p % 0.05; False Discovery Rate 5 0.13). Post hoc pairwise contrasts revealed that the overwhelming majority of these changes
161 (64%; 537 upregulated, 724 downregulated) occurred between young and aged animals while mid-aged transcriptional profiles were relatively intermediate (74% similar to young, 66% similar to aged). Statistically significant genes with a linear trend to decrease (369 genes) or increase (292 genes) were subjected to DAVID analysis to identify biological processes. Upregulated genes were associated with transcription regulation, translation, RNA processing, DNA metabolic processes and ribonucleoprotein. In contrast, downregulated genes were associated with lipid binding, lipid biosynthesis, nervous system development and neurogenesis. In combination, the aged canine brain shows increased gene expression associated with possible compensatory responses and decreases in lipid and neurogenesis pathways that may be modifiable through targeted interventions. Funding provided by NIH/NIA AG032550 to EH. Key words: beagle; canine; gene expression
COGNITIVE REHABILITATION IN OLD AGE G. Winocur1,2,3,4,* 1 Rotman Research Institute, Baycrest Centre, Toronto, ON, M6A 2E1, Canada 2 Department of Psychology, Trent University, Peterborough, ON, K9J 7B8, Canada 3 Department of Psychology, University of Toronto, Toronto, ON, M5T 1R8, Canada 4 Department of Psychiatry, University of Toronto, Toronto, ON, M5T 1R8, Canada *Corresponding author: [email protected] Using a general model of strategic processing we developed an experimental evaluation of a new approach to cognitive rehabilitation in individuals with memory and memoryrelated problems. The program is based on the premise that older adults and younger adults with brain damage need assistance in selecting and implementing strategies that are appropriate to specific tasks. As participants become increasingly familiar with the application of various strategies in responding to cognitive demands, we predicted that this essential operation would be accomplished with reduced effort and incorporated into their daily lives. The result is a 12-week training protocol that divides into three components: (1) cognitive skills training, where the emphasis is on using internal and external aids to acquire, retain, and recover information; (2) goal-management training in which laboratory-based strategies, introduced during cognitive skills training, are transferred to ‘real-life’ situations; (3) psychosocial training, in which the aim is to enhance psychological well-being and establish the link between overall functional status and cognitive function. The protocol was tested on a sample of normal old people who complained of memory loss and other cognitive problems. The study is unique in several ways. It is one of a small number of trials to use a multiple baseline
162 control; it is comprehensive in assessing the relative importance of various factors that impact rehabilitation of cognitive performance; it spans a 12 month period and includes a follow-up assessment of long-term benefits several months after the termination of training; it provides a wide range of behavioural, neuropsychological, and psychosocial outcome measures. The results indicated significant benefits of rehabilitation on a broad range of cognitive and psychosocial measures. The experimental design allowed us to conclude that the
Journal of Veterinary Behavior, Vol 5, No 3, May/June 2010 changes were the direct result of rehabilitation, and not secondary to general participation or repeated assessments. We attribute the success of our program to a variety of factors, including the emphasis on strategic processes in lab-based and practical training, psychosocial factors that relate to cognitive function, the dynamics of the supportive group session, commitment to home assignments, as well as the identification and realization of individual goals. Key words: cognitive rehabilitation; strategic processing; older adults