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Visual short-term memory (VSTM) is a vital cognitive ability, allowing us to hold online the contents of visual awareness. Healthy older adults have reduced VSTM capacity compared to young adults; however recent evidence suggests that their performance may be improved by the use of a retroactive cue (“retro-cue”). The retro-cue reduces interference from irrelevant items within VSTM. Mild cognitive impairment (MCI) patients have reduced VSTM performance, compared to healthy older adults. Here, we examined whether the use of a retro-cue would increase VSTM capacity in MCI patients. By presenting a retro-cue after a to-be remembered array, we direct attention to the to-be probed location, which reduces interference from other items that are no longer relevant. The present findings suggest that VSTM capacity per se is not compromised in MCI patients, but these patients may be more susceptible to the effects of interference.

The recommendations for stroke best practice suggest that mild stroke patients could receive their therapy within an ambulatory environment. However, a significant number of mild stroke patients continue to be admitted to inpatient rehabilitation. A retrospective chart audit was conducted for acute stroke discharges from two centres in Ontario. Stroke cases with a Projected Full FIM® > 80, we're stratified into two groups: discharged home - discharged to inpatient rehabilitation. There were 813 patients eligible for inclusion. Overall, 33% of mild stroke patients were admitted to inpatient rehabilitation. The results did not explain why so many mild stroke patients are admitted to inpatient rehabilitation. The two groups did not differ in rates of recurrent stroke or re-admission to hospital at follow-up. According to the results, milder stroke patients may effectively be managed in the community where rehabilitation services are available.

Visual short-term memory (VSTM) is a vital cognitive ability, allowing us to hold online the contents of visual awareness. Healthy older adults have reduced VSTM capacity compared to young adults; however recent evidence suggests that their performance may be improved by the use of a retroactive cue (“retro-cue”). The retro-cue reduces interference from irrelevant items within VSTM. Mild cognitive impairment (MCI) patients have reduced VSTM performance, compared to healthy older adults. Here, we examined whether the use of a retro-cue would increase VSTM capacity in MCI patients. By presenting a retro-cue after a to-be remembered array, we direct attention to the to-be probed location, which reduces interference from other items that are no longer relevant. The present findings suggest that VSTM capacity per se is not compromised in MCI patients, but these patients may be more susceptible to the effects of interference.

The recommendations for stroke best practice suggest that mild stroke patients could receive their therapy within an ambulatory environment. However, a significant number of mild stroke patients continue to be admitted to inpatient rehabilitation. A retrospective chart audit was conducted for acute stroke discharges from two centres in Ontario. Stroke cases with a Projected Full FIM® > 80, we're stratified into two groups: discharged home - discharged to inpatient rehabilitation. There were 813 patients eligible for inclusion. Overall, 33% of mild stroke patients were admitted to inpatient rehabilitation. The results did not explain why so many mild stroke patients are admitted to inpatient rehabilitation. The two groups did not differ in rates of recurrent stroke or re-admission to hospital at follow-up. According to the results, milder stroke patients may effectively be managed in the community where rehabilitation services are available.

Mild Cognitive Impairment is characterized by age-related decline in a variety of cognitive domains, including reference and working memory and olfactory function. Importantly, declining age-related mnemonic abilities is not inevitable; learning and memory deficits emerge in some people by middle-age while others remain largely cognitively-intact even at advanced chronological ages. The goal of this thesis is to establish a Fischer 344 (F344) rat model with some features of human cognitive aging which can then be utilized to undercover the neurobiological underpinnings of age-related cognitive deficits. Young (6 mo), middle-aged (11 mo), and aged (22 mo) F344 rats were behaviorally characterized in a well-established reference memory version of the Morris water maze task. Indeed, age-related impairments did occur across the lifespan. Moreover, the reference memory protocol used here was sufficiently sensitive to detect a difference in individual abilities among aged F344 rats such that approximately half of the rats performed on par with young while the other half performed outside this range, demonstrating impairment. These data mimic individual differences in declarative memory among aged humans. Subsequently, subsets of rats initially characterized on the reference memory version of the water maze were tested on either a spatial working memory water maze task or an olfactory discrimination task. Despite detecting an age-related delay-dependent decline in spatial working memory, this impairment was not correlated with spatial reference memory. In contrast, a strong and significant relationship was observed among aged rats in the odor discrimination task such that aged rats with the worst spatial reference memory were also the most impaired in their ability to discriminate odors for a food reward. Importantly, this subset of cognitively-impaired rats was not impaired on digging media discrimination problems with identical task demands, nor were they anosmic. These data are among the first to demonstrate a cross-domain cognitive deficit in a rodent model of human aging. Together, the current study both confirms the use of the naturalistic F344 rat model for the study of cognitive deficits within the context of aging and provides the most comprehensive cognitive profile of this rat population to date.

Following a mild head injury (MHI), a person may report a variety of symptoms such as headache, memory disturbance, dizziness, and concentration difficulties. For most persons the symptoms are transient, but some suffer persistent symptoms that can have a major impact on everyday life. It remains poorly understood why some but not others have full recovery after MHI. The aim of this thesis was to investigate outcomes after MHI, with particular focus on neuropsychological functioning, fatigue, and risk of dementia. A related objective was to examine the potential association of a genetic factor, Apolipoprotein (APOE), with MHI outcome. The APOE є4 allele has been associated with unfavorable outcomes after moderate or severe head injury, but little is known about its influence on outcome after MHI. In Study I and II, data from a population-based longitudinal study were used to compare neuropsychological functioning and fatigue before and after MHI. The results from Study I showed a post-injury decline in neuropsychological performance for є4-carriers, whereas the performance remained unchanged for non-carriers. Study II showed an increase in self-reported fatigue after MHI for both є4-carriers and non-carriers, with a more pronounced increase for є4-carriers. In Study III, a case-control study was conducted to examine whether a history of MHI increased the risk of developing dementia later in life. It was found that MHI alone did not increase the risk, but the combination of MHI and APOE є4 was associated with increased risk of dementia. Taken together, the studies generally indicate a positive outcome after MHI, but in combination with APOE є4 even mild head injury may lead to long-lasting negative outcomes. Consideration of pre-injury level of functioning and genetic factors seems critical for a complete understanding of the impact of MHI.

Background: Elderly people who demonstrate memory impairment that falls short of dementia, are referred to as having amnestic Mild Cognitive Impairment (aMCI). AMCI patients have an elevated risk of developing dementia, although not all will do so. Clinical criteria for Alzheimer's Disease (AD) and aMCI do not specify how impairment of a cognitive nature should be defined. The process of differentially diagnosing these conditions can be improved, if knowledge of neuropsychological measures that best discriminate between neurodegenerative and non-neurodegenerative cognitive impairment is used to implement diagnostic criteria for aMCI and AD. Aims: We sought to 1) determine the frequency of aMCI referrals to our specialist memory clinic, 2) characterise the detailed neuropsychology of a group of patients with aMCI, 3) determine the utility in differential diagnosis and test-retest reliability of these neuropsychological measures, and 4) establish a subset of neuropsychological measures that were of prognostic utility in aMCI. Methods: The case notes of 187 consecutive referrals received by our Royal Edinburgh Hospital memory assessment service across an 18-month period were reviewed retrospectively and numbers of patients fulfilling aMCI criteria were recorded. The baseline neuropsychological performances of 46 patients with aMCI, 20 patients with very early stage AD, 20 elderly patients with depressive symptoms and 24 healthy elderly participants were compared in order to determine their usefulness in differential diagnosis. AMCI participants were followed-up across an average of 4 years. Baseline neuropsychological performances of the aMCI dementia converters and aMCI non-converters were compared. Logistic regression analysis was applied to ascertain the predictive accuracy of a combination of these. Results: One quarter of referrals received by our memory assessment service met criteria for aMCI, most of whom displayed additional neuropsychological impairments of a non-memory nature, all the while performing above the highest cut off points on even the most comprehensive dementia screening measures. A number of neuropsychological measures were highly sensitive and specific to early AD however, similar combinations of both high sensitivity and specificity to aMCI were not achieved. Forty one percent of patients presenting to our service who fulfilled criteria for aMCI, received a clinical diagnosis of dementia across an average 4-year period. Performances on a comprehensive cognitive screening measure and a measure of delayed word recognition accuracy at baseline, classified 74% of aMCI patients comprising our clinic sample in accordance with their prognostic fate. Conclusion: A significant proportion of patients presenting to specialist memory clinics display episodic and semantic memory or executive impairment that falls short of dementia and that is not detectable using traditional bedside screening measures. The vast majority of such patients (i.e. 72%) experience persisting or progressive cognitive impairment, and a significant proportion (41%) go on to receive a clinical diagnosis of dementia. The baseline neuropsychological performance of aMCI patients who do and do not develop dementia differs, and contributes over and above clinical information to the prediction of long-term diagnostic outcome. The high frequency with which aMCI is encountered in clinical practice, coupled with the minority of aMCI patients who experience resolution of their cognitive impairment, and the sensitivity and prognostic utility of several neuropsychological tasks, has implications for the clinical management of patients with aMCI.