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.

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.

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.

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.

There has been accumulating scientific evidence, over the last three decades, of the role of inflammatory processes in the development of Alzheimer's disease (AD). Population based studies suggest that plasma levels of inflammatory markers are raised in peripheral blood of people with AD. People on long term use of non-steroidal anti-inflammatory drugs have a lower prevalence of AD. Moreover, both animal and human histopathology studies have reported localization of inflammation in brain areas primarily affected by AD pathology. Areas of increased inflammation can be visualized in vivo by Positron Emission Tomography (PET) scans using the PK11195 ligand that binds with the benzodiazepine receptor sites of activated microglial cells. Cognitive decline in AD has been shown to correlate with levels of microglial activation using PK11195 PET scans. People with amnestic mild cognitive impairment (MCI) are known to be at high risk of developing AD.We aimed to investigate the association between peripheral and central markers of inflammation and cognitive decline in a group of people with amnestic MCI.MCI subjects (n=70) underwent cognitive testing, IL-6 and CRP in peripheral blood were measured and repeated after 1 year. A sub group (n=15) was followed up for another year and central brain microglial activation was measured by PET using PK11195 along with cognitive and peripheral inflammatory marker measurement. The mean CRP and IL-6 levels of the cohort increased over one year but the rise was only significant for CRP. No association was detected between inflammatory markers levels and cognition as measured by a battery of cognitive instruments. Group comparisons of the PET cohort with healthy controls (n=5) showed increased PK11195 binding (mean binding potential) in frontal lobe, temporal lobe, parietal lobe, putamen, occipital lobes and significantly increased binding in posterior cingulate gyrus. This study, to our knowledge, is unique in studying makers of inflammation in amnestic MCI participants both in peripheral blood and brain. The results of this study, in the light of current literature, add to the importance of recognition of inflammatory processes in people at risk of developing AD. The results suggest that CRP levels rise significantly over time and are detectable in peripheral blood by using practically simple laboratory techniques. The results also suggest that activated microglia in amnestic MCI patients can be visualized in vivo by using PK11195 PET scans and show higher levels of activation as compared to healthy controls. These finding could be useful in identifying people with malactivated (pro-inflammatory) microglia as potential targets for prevention/early treatment strategies. Further studies with larger samples sizes and long term follow-up are needed to investigate whether these peripheral and central inflammatory markers could shed light on the aetiology of AD and be useful in monitoring disease progression.

As Ontario faces a major shift in demographics, it is anticipated that the number of community-dwelling people living with cognitive impairment will increase significantly. Occupational therapists (OTs) may play a key role in ensuring timely diagnosis and/or informing a comprehensive plan of care for this population by assessing and reporting on functional abilities. The purpose of this study was to explore the impact of an OT home assessment on diagnosis and plan of care for persons with Mild Cognitive Impairment (MCI) in a primary care Memory Clinic setting using a before and after design. A toolkit of clinical measures was developed to assess self-perception of occupational performance, instrumental activities of daily living (IADLs), falls risk and home safety. Thirty-one participants who had been assessed by a Memory Clinic team completed a one-hour OT home assessment focused on these attributes. A change in the plan of care was proposed for 24 of 31 participants (i.e., 77%) after the assessment findings were reviewed by the lead physicians of three Memory Clinic teams. Clinical information from an OT home assessment was used by the Memory Clinic teams to change follow-up visit times, plan diagnosis and/or medication review and initiate additional community supports for persons with MCI. Women in this sample were more likely than men to experience changes to their plan of care and were also at a higher falls risk as indicated by scores on a screening tool of this attribute. Several time sensitive issues were identified during the OT home assessment including falls risk, home safety issues and participant concern with driving ability. The addition of an OT home visit to an existing Memory Clinic Model has the potential to change the overall plan of care and to identify issues that may impact overall health and wellness, and the ability to live well at home. While the context for this study was an existing Memory Clinic Model in primary care, the findings have implications for older adults in any health setting who are experiencing cognitive changes. / Thesis / Master of Science Rehabilitation Science (MSc)

Thesis advisor: Elizabeth A. Kensinger / Although healthy young and older adults remember emotional information better than neutral, emotion does not confer the same benefit upon memory for those experiencing memory impairments due to Alzheimer's disease (AD). It is poorly understood at what stage of processing these deficits occur--are they due to declines in memory storage and retrieval processes, or to a decline in earlier stages of attention allocation, which then impact memory storage and retrieval? It remains an open question how attention and memory processes may interact in aging and age-related disease. The goal of this research was to examine the effects of aging on the neural mechanisms underlying selective memory for emotional information in visual scenes, and to compare memory between healthy older adults and patients with very early AD pathophysiological changes. Experiment 1 examined young and older adults' encoding-related neural activation associated with selective memory for emotional items within visual scenes and with successful memory for emotional items and the scene background. There were few regions showing significant interactions between age and memory for positive and negative scenes. In contrast, Experiment 2 showed that aging significantly affected the neural networks underlying selective emotional item memory and successful memory for emotional items and backgrounds. The results indicate that older adults require greater connectivity among prefrontal regions than young adults to encode all elements of a scene, rather than just encoding the emotional item. Experiment 3 showed that despite poorer memory overall, patients showing very early AD pathophysiological changes have relatively well preserved memory, especially for positive information. Dividing older adults' attention during encoding did not significantly alter their pattern of selective emotional item memory, suggesting that encoding of emotional items may be an easier or relatively automatic task compared to encoding of the background. In conclusion, there are significant age-related changes in the underlying neural networks, but not activation patterns, for selective memory for positive and negative scenes. Patients with early AD pathophysiological changes have impaired memory overall, however they may be able to recruit a similar neural network of prefrontal regions as healthy older adults for encoding of scenes with positive information. / Thesis (PhD) — Boston College, 2011. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Psychology.

Depression is associated with higher severity of memory disorders and has been shown to predict lower levels of cognitive functioning in those diagnosed with Mild Cognitive Impairment (MCI) or dementia. Yet, little is known about this association cross-culturally, particularly between Hispanics and European Americans. This study demonstrates that although levels of depression differed significantly across diagnostic group, Hispanics and European Americans were similar in levels of depression at each diagnosis. However, only for the European American group did depression levels predict lower scores in confrontational naming and semantic memory. Additionally, exploratory analyses of the entire sample demonstrated that lower depression predicted less likelihood of MCI or dementia diagnoses. This could indicate that there is a need for intervention and treatment of depression, in particular for later stages of MCI and dementia, that should be culturally catered to individual ethnicities. / Includes bibliography. / Thesis (M.A.)--Florida Atlantic University, 2018. / FAU Electronic Theses and Dissertations Collection

The Saint Louis University Mental Status (SLUMS) Examination is a relatively new brief cognitive screening measure developed for use with veterans. To date, there has been a paucity of research on its psychometric properties. Using a sample of 148 male veterans referred to a VA Mild Cognitive Impairment (MCI) Clinic for evaluation, the SLUMS’ ability to discriminate between MCI versus other diagnoses or no diagnosis was compared to results from a more comprehensive neuropsychological battery. Approximately 51% of the sample was diagnosed with MCI, 16% with Major Depressive Disorder (MDD), 17% did not meet criteria for a diagnosis, and 16% were given some other DSM-IV-TR diagnosis. The SLUMS demonstrated poor internal consistency (Cronbach’s alpha = .57), but scores were significantly correlated with scores on every neuropsychological measure, except for Trails B. Diagnostic discriminability was comparable to that of the more time intensive neuropsychological battery for discriminating between MCI and no diagnosis, and MCI and MDD. In the current sample, a cutoff score of 25 was optimal for discriminating between MCI and no diagnosis, whereas a slightly lower cutoff score of 24 is recommended for discriminating between MCI and those with MDD. Diagnostic indicators were poor for the SLUMS and the battery when discriminating between MCI and a heterogeneous group of other disorders. Possible reasons for low reliability in such a screening measure in the context of convergent validity are discussed. It is concluded that the SLUMS may be a viable brief cognitive screening measure in such veteran populations, particularly when discriminating between MCI and MDD; however, additional studies should be completed to evaluate other forms of consistency, such as test-retest reliability.

Cognitive impairment in Parkinson’s disease (PD) can impact negatively on caregivers and is associated with carer distress and feelings of burden. To investigate this relationship we examined level of burden, coping strategies, depression, anxiety and potential positive aspects of caregiving in the caregivers of 104 PD patients. The PD patients were classified as either showing normal cognition (PD-N; n=57), with mild cognitive impairment (PD-MCI; n=31) or with dementia (PD-D; n=16). The key finding was that mean Zarit burden score increased between carers of PD-N (M=14.1, SD=12.0) through to PD-MCI (M=21.1, SD=9.86) and PD-D (M=27.8, SD=10.61); F (2,101) =9.96, p<0.001. Post hoc tests (Newman-Keuls) identified significantly higher Zarit burden scores in PD-D caregivers compared to both PD-N (p<.001) and PD-MCI patients (p<.05), but carers of PD-MCI patients also showed increased burden scores relative to those of PD-N patients (p<.05). The proportion of carers showing significant levels of burden (Zarit burden score ≥21) also increased as cognition declined (21% for PD-N; 58% for PD-MCI; and 81% for PD-D). Time spent providing care and problem-focused, emotion-focused and dysfunctional coping strategies also increased with worsening cognition. While caregiver use of problem-focused coping mediated the association between patient cognitive status and caregiver burden, we could not be confident about this relationship as the inverse model was also significant. Caregiver Zarit burden was independent of caregiver depression, anxiety and positive attributions of caregiving. The study highlights the impact of Parkinson’s disease on those providing care when the patients’ cognition is poor, including those with MCI. Caregiver well-being has important implications for nursing home placement and disease course.