Biomedical subjects

Gordon Winocur

Publications and source records attributed to Gordon Winocur.

At least 19 recordsLinked to original sources

PubMed2007

Cognitive rehabilitation in the elderly: a randomized trial to evaluate a new protocol.

This study provides an introduction to, and overview of, several papers that resulted from a randomized control trial that evaluated a new cognitive rehabilitation protocol. The program was designed to improve general strategic abilities in ways that would be expressed in a broad range of functional domains. The trial, which was conducted on a sample of older adults who had experienced normal age-related cognitive decline, assessed performance in the following domains: memory, goal management, and psychosocial status. The general rationale for the trial, the overall experimental design, and the approach to statistical analyses that are relevant to each paper are described here. The results for each functional domain are reported in separate papers in this series.

Aged↗

PubMed2007

Cognitive rehabilitation in the elderly: effects on memory.

This study reports the effects of a 12-week multimodular cognitive rehabilitation training program on memory performance in two groups of older adults. In the Memory Training module, participants were instructed on the nature of memory and how to improve memory performance; internal and external strategies were described and practiced over the training sessions. Memory performance was assessed by four tests: Alpha Span, Brown-Peterson, Hopkins Verbal Learning Test - Revised (HVLT-R), and Logical Stories. One group received training on entry into the study (Early Training Group, ETG), the other after a 3-month delay (Late Training Group, LTG). The results showed no training-related improvement in working memory (Alpha Span), primary memory (Brown-Peterson, HVLT-R), or recognition memory (HVLT-R). While the most direct analyses of a training effect (analyses of covariance) rarely demonstrated significant effects, exploratory analyses provided some evidence for a training benefit in several measures of secondary memory (Logical Stories; HVLT-R) and strategic processing (Brown-Peterson; Logical Stories; HVLT-R). Positive results were largely restricted to the ETG, possibly because the LTG lost motivation as a consequence of their delayed training. The results need to be treated with caution, but are promising for the rehabilitation of memory functioning in older adults.

Aged↗

PubMed2007

Cognitive rehabilitation in the elderly: effects on strategic behavior in relation to goal management.

Executive functions are highly sensitive to the effects of aging and other conditions affecting frontal lobe function. Yet there are few validated interventions specifically designed to address executive functions, and, to our knowledge, none validated in a healthy aging sample. As part of a large-scale cognitive rehabilitation randomized trial in 49 healthy older adults, a modified Goal Management Training program was included to address the real-life deficits caused by executive dysfunction. This program emphasized periodic suspension of ongoing activity to establish goal hierarchies and monitor behavioral output. Tabletop simulated real-life tasks (SRLTs) were developed to measure the processes targeted by this intervention. Participants were randomized to two groups, one of which received the intervention immediately and the other of which was wait-listed prior to rehabilitation. Results indicated improvements in SRLT performance and self-rated executive deficits coinciding with the training in both groups. These gains were maintained at long-term follow-up. Future research will assess the specificity of these effects in patient groups.

Aged↗

PubMed2007

Cognitive rehabilitation in the elderly: an evaluation of psychosocial factors.

In this study, we report changes in psychosocial function in two groups of older adults that participated in the experimental trial of our cognitive rehabilitation program. The results, based on tests that measured a range of psychosocial attributes, showed that, following training, participants improved in terms of overall well-being, as well as in specific areas that included perceived happiness, coping strategies, and quality of life. An important finding was that improvements were also observed in long-term follow-up testing. Both groups benefited from training, but the effect was greater in the group that received training before undergoing a control procedure. The results, which show that the benefits of our rehabilitation program extend into the psychosocial domain, underscore the potentially important relationship between psychosocial factors and cognitive performance in older adults.

Adaptation, Psychological↗

PubMed2007

Cognitive rehabilitation in the elderly: overview and future directions.

This study provides an overview of the papers emanating from the experimental trial that evaluated a new cognitive rehabilitation program in older adults who were experiencing normal cognitive decline. The main features of the design are summarized, along with evidence that the training produced long-lasting improvement in memory performance, goal management, and psychosocial status. The benefits were attributed to several factors, including the program's emphasis on techniques that promoted efficient strategic processing. Limitations of the program and directions for future research are discussed.

Aged↗

PubMed2006

The effects of the anti-cancer drugs, methotrexate and 5-fluorouracil, on cognitive function in mice.

There is evidence that standard-dose chemotherapy may impact cognitive function in cancer patients. The present study evaluated the effects of a combination of two anti-cancer drugs, methotrexate (37.5 mg/kg) and 5-fluorouracil (5FU, 75 mg/kg) on cognitive function in a mouse model. Drug-induced deficits were observed in adult BALB/C mice on tests of spatial memory, non-matching-to-sample (NMTS) learning and in a delayed-NMTS test of non-spatial memory. There were no group differences on tests of cued memory or discrimination learning. Performance-related variables were ruled out as possible explanations of the observed impairments. The impaired performance of the drug group, which was consistent with cognitive deficits observed in human cancer patients treated with similar types of chemotherapy, was attributed to functional changes in specific brain regions, including the frontal lobes and hippocampus.

Animals↗

PubMed2006

The cognitive neuroscience of remote episodic, semantic and spatial memory.

The processes and mechanisms implicated in retention and retrieval of memories as they age is an enduring problem in cognitive neuroscience. Research from lesion and functional neuroimaging studies on remote episodic, semantic and spatial memory in humans is crucial for evaluating three theories of hippocampal and/or medial temporal lobe-neocortical interaction in memory retention and retrieval: cognitive map theory, standard consolidation theory and multiple trace theory. Each theory makes different predictions regarding first, the severity and extent of retrograde amnesia following lesions to some or all of the structures mentioned; second, the extent of activation of these structures to retrieval of memory across time; and third, the type of memory being retrieved. Each of these theories has strengths and weaknesses, and there are various unresolved issues. We propose a unified account based on multiple trace theory. This theory states that the hippocampus is needed for re-experiencing detailed episodic and spatial memories no matter how old they are, and that it contributes to the formation and assimilation of semantic memories and schematic spatial maps.

Amnesia, Retrograde↗

PubMed2006

Inhibition of neurogenesis interferes with hippocampus-dependent memory function.

Rats treated with low dose irradiation, to inhibit adult hippocampal neurogenesis, and control rats were administered a non-matching-to-sample (NMTS) task, which measured conditional rule learning and memory for specific events, and a test of fear conditioning in which a discrete CS was paired with an aversive US in a complex environment. Irradiated rats were impaired on the NMTS task when the intervals between sample and test trials were relatively long, and in associating the shock-induced fear with contextual cues in the fear conditioning task. Irradiated rats were not impaired in learning the basic NMTS rule or in performing that task when the intervals between the sample and test trials were short. Nor were there group differences in conditioning the fear response to the CS in the fear conditioning task. The results, which extend the range of hippocampus-dependent tasks that can be said to be vulnerable to the effects of neurogenesis suppression, support the hypothesis that new hippocampal cells generated in adulthood participate in a broad range of hippocampal functions.

Animals↗

PubMed2006

Hippocampal contributions to recollection in retrograde and anterograde amnesia.

Lesions restricted to the hippocampal formation and/or extended hippocampal system (hippocampal formation, fornix, mammillary bodies, and anterior thalamic nuclei) can disrupt conscious recollection in anterograde amnesia, while leaving familiarity-based memory relatively intact. Familiarity may be supported by extra-hippocampal medial temporal lobe (MTL) structures. Within-task dissociations in recognition memory best exemplify this distinction in anterograde amnesia. The authors report for the first time comparable dissociations within recognition memory in retrograde amnesia. An amnesic patient (A.D.) with bilateral fornix and septal nuclei lesions failed to recognize details pertaining to personal past events only when recollection was required, during recognition of episodic details. His intact recognition of generic and semantic details pertaining to the same events was ascribed to intact familiarity processes. Recollective processes in the controls were reflected by asymmetrical Receiver's Operating Characteristic curves, whereas the patient's Receiver's Operating Characteristic was symmetrical, suggesting that his inferior recognition performance on episodic details was reliant on familiarity processes. Anterograde and retrograde memories were equally affected, with no temporal gradient for retrograde memories. By comparison, another amnesic person (K.C.) with extensive MTL damage (involving extra-hippocampal MTL structures in addition to hippocampal and fornix lesions) had very poor recognition and no recollection of either episodic or generic/semantic details. These data suggest that the extended hippocampal system is required to support recollection for both anterograde and retrograde memories, regardless of their age.

Age Factors↗

PubMed2006

Anterograde and retrograde amnesia in a person with bilateral fornix lesions following removal of a colloid cyst.

AD, a 45-year-old man, presented with a severe and global anterograde amnesia following surgery for removal of a colloid cyst. Structural neuroimaging confirmed bilateral lesions to the fornix and a small lesion in the basal forebrain. Testing for remote episodic memory of autobiographical events, and for remote semantic memory of personal and public events, and of famous people, revealed that AD had a severe retrograde amnesia for autobiographical episodes that covered his entire lifetime, and a time-limited retrograde amnesia for semantic memory. Because the fornix and basal forebrain lesions disrupted major afferent and efferent pathways of the hippocampus, it was concluded that the integrity of the hippocampus and its projections are needed to retain and/or recover autobiographical memories no matter how old they are. By contrast, hippocampal contribution to semantic memory is time-limited. These findings were interpreted as consistent with Multiple Trace Theory, which holds that the hippocampal system is essential for recovering contextually rich memories no matter how old they are, but is not needed for recovering semantic memories.

Amnesia, Anterograde↗

PubMed2006

Age effects on social cognition: faces tell a different story.

The authors administered social cognition tasks to younger and older adults to investigate age-related differences in social and emotional processing. Although slower, older adults were as accurate as younger adults in identifying the emotional valence (i.e., positive, negative, or neutral) of facial expressions. However, the age difference in reaction time was largest for negative faces. Older adults were significantly less accurate at identifying specific facial expressions of fear and sadness. No age differences specific to social function were found on tasks of self-reference, identifying emotional words, or theory of mind. Performance on the social tasks in older adults was independent of performance on general cognitive tasks (e.g., working memory) but was related to personality traits and emotional awareness. Older adults also showed more intercorrelations among the social tasks than did the younger adults. These findings suggest that age differences in social cognition are limited to the processing of facial emotion. Nevertheless, with age there appears to be increasing reliance on a common resource to perform social tasks, but one that is not shared with other cognitive domains.

Adult↗

PubMed2006

Age-related changes in brain activity across the adult lifespan.

A number of theories have emerged to explain the well-studied changes in memory that occur with age. Many of these theories invoke mechanisms that have the potential to affect multiple cognitive domains, in addition to memory. Such mechanisms include alterations in attentional or inhibitory function, or dysfunction of specific brain areas, such as the frontal lobes. To gain insight into these mechanisms, we used functional magnetic resonance imaging to examine brain activity during encoding and recognition tasks in young, middle-aged, and older adults to identify correlations between age and brain activity across the various tasks. The goal was to see whether these correlations were task-specific or common across tasks, and to determine whether age differences emerged in a linear fashion over the adult years. Across all memory tasks, at both encoding and recognition, linear increases of activity with age were found in areas normally decreased during task performance (e.g., medial frontal and parietal regions), whereas activity in regions with task-related activation (e.g., dorsolateral prefrontal cortex) decreased with age. These results suggest that there is a gradual, age-related reduction in the ability to suspend non-task-related or "default-mode" activity and engage areas for carrying out memory tasks. Such an alteration in the balance between default-mode and task-related activity could account for increased vulnerability to distraction from irrelevant information, and thereby affect multiple cognitive domains.

Adult↗

PubMed2005

High-fat diets, insulin resistance and declining cognitive function.

Results from our work in rats and others findings from human epidemiologic studies demonstrate deficits in cognitive performance following chronic ingestion of high fat, high saturated fat, diets. Yet, the precise physiologic mechanism underlying these deficits is not well understood. We report that older adults with insulin resistance show remarkably similar deficits in cognitive function and respond to glucose ingestion in a comparable manner to rodents fed a high-fat diet, suggesting that insulin resistance is a probable mediator of these diet-induced deficits. As insulin resistance worsens to overt type 2 diabetes, profound deficits in cognitive functions, especially those dependent on the medial temporal lobes, are apparent in both obese Zucker rats and humans with type 2 diabetes. Unlike the older adult with insulin resistance, glucose ingestion further impairs medial temporal lobe function in adults with type 2 diabetes. Collectively, the human and rodent data point to a role of diet-induced endocrine abnormalities, including the development of insulin resistance, as mediating the cognitive deficits associated with high fat consumption.

Animals↗

PubMed2005

Studies of the effects of high fat diets on cognitive function in a rat model.

This research summarises a research program that is concerned with the effects of high fat diets on cognitive function in rats. The diets selected accurately represent current upper limits of human fat consumption in western societies. Rats fed with diets high in saturated or unsaturated fat for 3 months, were severely impaired on a range of learning and memory tasks. Related studies showed that these effects were modulated by concentration of fat, environmental influences, and treatment with glucose. More work is needed to identify the neurobiological mechanisms underlying this impairment but saturated fatty acid intake, as well as insulin resistance and glucose intolerance may be important factors. In demonstrating a clear relationship between obesity and cognitive impairment, this research has important implications for aging. Older adults are particularly vulnerable to the adverse effects of dietary fat and the present results underscore the importance of evidence that seniors with marginal levels of nutrient intake often perform poorly on tests of cognitive function, and are at increased risk for various forms of dementia.

Animals↗

PubMed2005

Retrograde amnesia in rats with lesions to the hippocampus on a test of spatial memory.

The present study examined remote spatial memory in a test that spans several months to determine whether remote memories are spared relative to more recent ones, as predicted by models of memory consolidation. At 3, 6 or 12 months of age, groups of rats received forced-choice training as to the location of food reward in a cross maze. At 12.5 months, rats received bilateral neurotoxic lesions to the hippocampus or a control surgical procedure and 2 weeks later their memory for the spatial location was tested. Their performance was compared to that of rats with hippocampal or control lesions with no prior training on several measures of savings. The hippocampal group with no pre-training, as expected, was severely impaired in learning the location of the food reward. Compared to this group, rats with hippocampal lesions that were pre-trained consistently performed better at the shortest training-surgery interval but not at the longer ones. That is, rats with hippocampal lesions exhibited retrograde amnesia at all training-surgery intervals and a forgetting curve that paralleled that of the control groups. The results were interpreted within a framework that distinguishes between relational and associative context, and as providing evidence that the hippocampus is necessary for the retention and retrieval of memories that are bound to relational context, regardless of the age of the memory.

Amnesia, Retrograde↗

PubMed2005

Preserved spatial memory after hippocampal lesions: effects of extensive experience in a complex environment.

Damage to the hippocampus typically impairs spatial learning and memory in animals, but humans with hippocampal lesions retain spatial memories of premorbidly familiar environments. We showed that, like humans, normal rats reared in a complex environment and then given hippocampal lesions retained allocentric spatial memory for that environment. These results, which ruled out dependency on single cues, landmarks or specific routes, suggest that extensive premorbid experience leads to spatial representations that are independent of the hippocampus.

Animals↗

PubMed2005

Memory impairment in obese Zucker rats: an investigation of cognitive function in an animal model of insulin resistance and obesity.

The genetically obese Zucker rat is a widely investigated model of pathological changes associated with type 2 diabetes. To assess cognitive function, obese and lean Zucker rats were tested on a variable-interval delayed alternation test of learning and memory. There were no group differences in learning the alternation rule or at short intervals, but obese rats were impaired at longer intervals where performance is hippocampus dependent. Plasma membrane association of the insulin sensitive glucose transporter, GLUT4, was reduced in the hippocampus of obese rats in the absence of changes in total GLUT4 and insulin receptor expression. These results parallel those of human studies in pointing to the susceptibility of the hippocampus and related structures to the adverse environment of diabetes mellitus.

Analysis of Variance↗

PubMed2005

The relation between brain activity during memory tasks and years of education in young and older adults.

Higher education is associated with less age-related decline in cognitive function, but the mechanism of this protective effect is unknown. The authors examined the effect of age on the relation between education and brain activity by correlating years of education with activity measured using functional MRI during memory tasks in young and older adults. In young adults, education was negatively correlated with frontal activity, whereas in older adults, education was positively correlated with frontal activity. Medial temporal activity was associated with more education in young adults but less education in older adults. This suggests that the frontal cortex is engaged by older adults, particularly by the highly educated, as an alternative network that may be engaged to aid cognitive function.

Adult↗