Alzheimer’s disease is a debilitating, progressive neurodegenerative disorder in the elderly, characterized by severe loss of memory and higher cognitive functions. In the hundred years since its discovery, Alzheimer’s disease (AD) has traversed from the status of a ‘rare neurological oddity’ to one of the greatest challenges faced by healthcare and medicine in this millennium. A reported 44 million people currently suffer from AD but only 1 in 4 people have been diagnosed. Although AD has been an area of intense research for almost 50 years now, most studies have focused on the end stage disease. Years of study on the pathological cause underlying AD; have conclusively shown that the accumulation of the sticky peptide, Aβ, is one of the major triggers of AD pathogenesis. However, after the initial Aβ trigger, multiple processes contribute to disease progression, so that by the time a patient is diagnosed on the basis of overt behavioral phenotypes, it is difficult to understand and differentiate between the causative mechanisms and the consequential effects of the disease. It is, perhaps, because of this, that we are still struggling to find therapies for AD which will stop or at the very least slow the course of the disease. In the 2015 report on AD, issued by the Alzheimer’s association, much emphasis has been placed on the early diagnosis of AD and the revision of the diagnostic criteria for AD. According to the new guidelines proposed in 2011, AD has been divided into three stages where the first stage occurs before the appearance of overt behavioral symptoms such as memory loss, whereas by the 1984 guidelines, cognitive disabilities must have already occurred for diagnoses of AD. This proposed preclinical stage of AD has been defined, reflecting the current belief that AD pathogenesis begins almost 20 years before the occurrence of behavioral dysfunction. However, no diagnostic criteria are currently available to establish this stage. Hence, there is a need to understand the early pathogenic mechanisms of AD, which will yield early therapeutic targets as well as early diagnostic markers of AD. One of the earliest documented events in AD pathogenesis is synaptic dysfunction, which is later manifested as loss of dendritic spines. Deficits in long term potentiation (LTP) has been demonstrated in Aβ exposed hippocampal slices as well as in mouse models of AD, much before the appearance of pathological hallmarks such as plaques and tangles as well as overt behavioral phenotypes. While these and other studies indicate clearly that elevated levels of soluble Aβ peptide leads to impairment of synaptic function, the underlying molecular mechanisms are yet to be elucidated. One of the purported mediators of Aβ induced dysfunction is oxidative stress. The Aβ peptide, especially the Aβ42, is a self aggregating peptide with a propensity to form peptidyl radicals. Interaction of the peptidyl radicals with biomolecules leads to the generation of more free radical species via cascading chain reactions. Additionally, Aβ peptide has also been demonstrated to have synaptotoxic effects via its effect on NMDA receptors and calcium influx leading to deregulated reactive oxygen species (ROS) production as well as excitotoxicity. Hence, with a view to understanding Aβ mediated early synaptic dysfunction in AD, we studied early signaling changes in the synaptosomes derived from the cortex of APP/PS1 mice model of AD at various ages. The APP/PS1 model contains a mouse/human chimeric APP gene bearing the KM670/671NL Swedish mutation and the human PS1 gene with an exon 9 deletion. These mice exhibit behavioral deficits from 7 months of age while plaque deposition and gliosis become apparent by 9 months of age. We chose to study both pre-symptomatic ages (1 and 3 months old) as well as post symptomatic (9 months old) mice. Post nuclear supernatant (PNS) as well as synaptosomes were isolated from the cortex of APP/PS1 and age matched control mice. We assayed the levels of reactive oxygen species (ROS) in the PNS and the synaptosomes of post symptomatic 9 months old APP/PS1 mice and age matched controls. In contrast to reports of enhanced oxidative stress markers in the brains of AD patients, we did not find any increase in the levels of ROS in the PNS of post symptomatic APP/PS1 mice compared to age matched controls. However, synaptosomes from the cortex of these animals exhibited a significant increase in ROS levels in APP/PS1 mice compared to controls. We further found that there was significant increase in the ROS levels in synaptosomes, but not PNS, of very young asymptomatic 1 and 3 months old APP/PS1 mice. This is a first demonstration of synapse specific increase in oxidative stress in AD mice, as young as 1 month of age, indicating that disease specific mechanisms operate at the synapse much before the appearance of any overt cellular or behavioral symptoms. The increase in synaptic ROS levels correlated with a small but significant increase in the levels of Aβ42 in the brains of APP/PS1 mice compared to controls. We also found a concurrent change in the redox status of the cytoskeletal protein, actin, at the synapse. As early as 1 month of age, there was a significant decrease in the protein level of reduced actin indicating that there is an increase in the level of oxidized actin at the synapse. This loss of reduced actin was specific to the fibrillar pool of actin while no significant change was observed in the redox status of the monomeric globular pool of actin. Oxidation of actin has been demonstrated to lead to its depolymerization. Concurrently, we found a significant loss of fibrillar actin in the synaptosomes of APP/PS1 mice. Actin is the major cytoskeletal protein at the synapse. Changes in the globular to fibrillar actin ratio at the synapse at early pre-symptomatic ages in APP/PS1 mice will likely lead to structural and consequent functional changes at the synapse. This could potentially be one of the triggers of synaptic dysfunction in AD. Furthermore, changes in the Akt-mTOR signaling pathway was also observed in the synaptosomes of 1 month old APP/PS1 mice, which is sustained at 9 months. There was a significant loss of the mTOR-pS6K-4EBP1 axis in the synaptosomes, but not PNS, of APP/PS1 mice. We found that loss of Akt signaling, as evinced by loss of Akt phosphorylation, Akt kinase activity as well as loss of phosphorylation of downstream effector GSK3β, potentially underlies the loss of mTOR signaling. Further, the loss of Akt signaling is mediated by synapse specific redox modification of Akt and consequent interaction with the protein phosphatase PP2a. Loss of the Akt-mTOR signaling at the synapse is indicative of deficits in local protein translation. Loss of this essential synaptic function, which plays critical roles in synapse maintenance as well as synaptic plasticity during learning and memory, at an early age, will have long ranging impact on synaptic function such as long term potentiation (LTP) in APP/PS1 mice. Our study is the first demonstration of oxidative stress and consequent signaling changes which occur specifically at the synapse of very young 1 month old APP/PS1 mice. These changes occur much before the appearance of overt phenotype such as plaque deposition and behavioral dysfunction but sustain till the appearance of classical pathological hallmarks. Hence, the study demonstrates that disease progression starts much before previously thought and provides us a critical time window during which therapeutic strategies designed to delay or stop these changes might change the course of AD.

Orientador: Benito Pereira Damasceno / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-24T09:20:46Z (GMT). No. of bitstreams: 1 Dainez_ElisangelaCordtsLongo_M.pdf: 10128952 bytes, checksum: 5fac09888d865514f18ba1aad9694863 (MD5) Previous issue date: 2013 / Resumo: O Comprometimento Cognitivo Leve amnésico (CCLa) é um déficit cognitivo de pequena intensidade enquadrado no estágio de transição entre o envelhecimento normal e fases iniciais da doença de Alzheimer (DA). Por sua ez, a DA leve caracteriza-se como uma morbidade neurodegenerativa progressiva, na qual há perda moderada da memória para eventos recentes, dificuldade nas orientações visuo-espaciais, comprometimento para resolução de problemas e no desempenho de atividades da vida diária (AVD¿s). Diante dessas morbidades, a intervenção clínica da pesquisa foi pautada na reabilitação neuropsicológica (RN) e na terapia cognitivo-comportamental (TCC). A finalidade da RN é reduzir do comprometimento cognitivo, como também capacitar o sujeito nas diversas áreas de sua vida. Por outro lado, o foco da TCC é direcionado para o tratamento de sintomas cognitivos, emocionais e comportamentais. O objetivo do projeto foi intervir cognitiva-afetiva-comportamentalmente em indivíduos que apresentam CCLa e Demência Leve devido a DA, de modo a aperfeiçoar a cognição do sujeito, ou reduzir, ou ainda estacionar as suas deficiências cognitivas, bem como melhorar seus estados emocionais e comportamentos. O estudo caracteriza-se como experimental (ensaio clínico) de abordagem quantitativa, com duração de 12 meses, 6 meses para RN e 6 meses para TCC. A população estudada refere-se aos pacientes do Ambulatório de Neurologia do Hospital das Clínicas UNICAMP. A amostragem classifica-se como aleatória simples, composta de 15 indivíduos distribuídos de forma randomizada em amostra experimental, composta de 10 sujeitos (grupo A = 6 e grupo B = 4), e amostra controle composta de 5 participantes. Os grupos A e B da amostra experimental passaram pelo processo de cross-over de abordagem (TCC e RN) após 6 meses de intervenção. Os sujeitos da pesquisa foram submetidos a uma bateriade testes neuropsicológicos e psicológicos antes da intervenção (pré-teste), após 6 meses (pós-teste 1) e após 12 meses (pós-teste 2) de intervenção. Os instrumentos selecionados foram para avaliação cognitiva, psicológica e funcional. Desse modo, obteve-se como resultados desempenhos positivos, estáveis, bem como houve evolução da doença, pórem ritmo mais lento do que o esperado da amostra experimental comparada com a amostra controle. Ademais, a pesquisa sugere iniciar a TCC com os indivíduos CCLa seguindo com aplicação da RN. Por sua vez, os pacientes DA o estudo propõe iniciar com a RN após esta intervir com a TCC / Abstract: The amnesic Mild Cognitive Impairment (aMCI) is a cognitive deficit of low intensity is framed in the boundaries of normal aging and early stage of Alzheimer disease (mild AD). On the other hand, mild AD characterizes as a progressive neurodegenerative illness, in which there is moderate loss of memory for recent events, difficult in visuospacial orientation, impairment to problems resolution and decreases of the performance in the activities of daily life (ADL¿s). Given these morbidities, the clinical intervention of the present research was based on neuropsychological rehabilitation (NR) and behavioral-cognitive therapy (BCT). The purpose of NR is decreasing the cognitive impairment, but also capacitating the subject in several areas of his life. Whereas the focus of BCT is directed to treatment of cognitive, emotion and behavioral symptoms. The objective of project was intervened behaviorally-affective-cognitive in individuals how show aMCI and mild AD in order to improve the cognition of the subject, or to decrease, or still to stop the cognitive disabilities, as also to better the emotion statusand behavior. The study is experimental (clinical analysis) of the quantitative approach, lasting 12 months, 6 months to 6 months NR and psychotherapy BCT 6 months to TCC and 6 months to NR. The sample of population was composed of the patients of Neurology Ambulatory of the UNICAMP Clinics Hospital. The sample is described how simple random made up of 15 subjects who were randomized in the experimental sample, which was composed for 10 individual (who were shared to group A = 6 subjects and group B = 4 subjects) and 5 individual were randomized to control sample. The groups A and B of the experimental sample were changed cross-over to approach (BCT and BCT) after 6 months. The subjects were submitted to neuropsychology and psychology tests batteries before the intervention (pre-test), after 6 months (post-test 1) and after 12 months (post-test 2) intervention. The instruments were selected to evaluate cognitive, psychology and functional evaluation. Thus, it obtained positive and stable performances as results, as well as evolution of the disease, but the disease¿s evolution of the experimental sample was slower than of the control sample. Furthermore, the research suggests starting the BCT with aMCI individual, after this to apply to the NR. On the other hand, first to apply the NR after this to follow to BCT for the mild AD patients / Mestrado / Ciencias Biomedicas / Mestra em Ciências Médicas

OBJECTIVE: To determine whether volumetric measures of the hippocampus or entorhinal cortex in combination with other cortical measures can differentiate between cognitively normal individuals and participants with amnestic mild cognitive impairment (MCI). METHODS: T1-weighted magnetic resonance imaging (MRI) data acquired from 46 cognitively normal participants and 50 participants with amnestic MCI as part of the Boston University Alzheimer's Disease Center research registry and the Alzheimer's Disease Neuroimaging Initiative were used in this cross-sectional study. Cortical and subcortical volumes, including hippocampal subfield volumes, were automatically generated from each participant’s structural MRI data using FreeSurfer v6.0. Nominal logistic regression models containing these variables were used to evaluate their ability to identify participants with MCI. RESULTS: A model containing 11 regions of interest (insula, superior parietal cortex, rostral middle frontal cortex, middle temporal cortex, pars opercularis, paracentral lobule, whole hippocampus, subiculum, superior temporal cortex, precentral cortex and caudal anterior cingulate cortex) fit the data best (R2 = 0.7710, whole model test chi square = 102.4794, p < 0.0001). CONCLUSIONS: Volumetric measures acquired from MRI were able to correctly identify most healthy control subjects and those with amnestic MCI using measures of selected medial temporal lobe structures in combination with those from other cortical areas yielding an overall classification of 95.83% for this dataset. These findings support the notion that while clinical features of amnestic MCI may reflect medial temporal atrophy, differences that can be used to distinguish between these two populations are present elsewhere in the brain. This finding further affirming that atrophy can be identified before clinical features are expressed. Additional studies are needed to assess how well other imaging modalities, such as resting state functional connectivity, diffusion imaging, and amyloid and tau position emission tomography (PET), perform in classifying participants who are cognitively normal versus those who are amnestic MCI.

Indiana University-Purdue University Indianapolis (IUPUI) / Over 5 million older adults have Alzheimer's disease (AD) in the US, and this number is projected to double by 2050. Clinical trials of potential pharmacological treatments for AD have largely shown that once cognitive decline has occurred, targeting AD pathology in the brain does not improve cognition. Therefore, it is likely that the most effective treatments for AD will need to be administered before cognitive symptoms occur, necessitating a biomarker for the early, preclinical stages of AD. Cerebral blood flow (CBF) is a promising early biomarker for AD. CBF is decreased in individuals with AD compared to their normally aging counterparts, and it has been shown that CBF is altered in mild cognitive impairment (MCI) and earlier stages and may occur prior to amyloid or tau aggregation. In addition, CBF can be measured using arterial spin labeled (ASL) MRI, a noninvasive imaging technique that can be safely repeated over time to track prognosis or treatment efficacy. The complex temporal and spatial patterns of altered CBF over the course of AD, as well as the relationships between CBF and AD-specific and -nonspecific factors, will be critical to elucidate in order for CBF to be an effective early biomarker of AD. Here, we begin to characterize the relationships between CBF and risk factors, pathologies, and symptoms of AD. Chapter 1 is a systematic review of published literature that compares CBF in individuals with AD and MCI to CBF in cognitively normal (CN) controls and assesses the relationship between CBF and cognitive function. Chapter 2 reports our original research assessing the relationships between CBF, hypertension, and race/ethnicity in older adults without dementia from the the Indiana Alzheimer’s Disease Research Center (IADRC) and Alzheimer’s Disease Neuroimaging Initiative (ADNI). Chapter 3 reports our original research assessing the relationships between CBF and amyloid beta and tau aggregation measured with PET, as well as whether hypertension or APOEε4 positivity affects these relationships, in older adults without dementia from the IADRC. Chapter 4 reports our original research assessing the relationship between the spatial distribution of tau and subjective memory concerns. / 2023-05-24

Background: Inflammation is proposed to play a role in the development of Alzheimer's disease, and may also be involved in the pathogenesis of mild cognitive impairment (MCI). This study examined the association of inflammatory markers in serum or plasma with prevalent MCI and MCI subtypes in a population-based sample. Methods: Olmsted County, MN, residents aged 70-89 years on October 1, 2004, were evaluated using the Clinical Dementia Rating Scale, a neurological evaluation, and neuropsychological testing. Information ascertained for each participant was reviewed by an expert panel of neuropsychologists, physicians, and nurses, and a diagnosis of normal cognition, MCI, or dementia was made by consensus. C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis alpha (TNFα), and adiponectin were measured at baseline. Results: Among 313 subjects with MCI and 1570 cognitively normal subjects, a CRP level in the upper quartile (>3.3 mg/L) was significantly associated with MCI (odds ratio [OR], 1.42; 95% confidence interval [CI], 1.00-2.01) and with nonamnestic MCI (OR, 2.05; 95% CI, 1.12-3.78) after adjusting for age, sex, and years of education. However, there was no association with amnestic MCI (OR, 1.21; 95% CI, 0.81-1.82). No association was observed with the other inflammatory markers. Conclusions: Plasma CRP is associated with prevalent MCI and with nonamnestic MCI in elderly, nondemented persons in a population-based setting. These findings suggest the involvement of inflammation in the pathogenesis of MCI.

Although cognitive rehabilitation is not a new field of intervention, as it dates back to the treatment of brain-injured soldiers during World War I, the use of cognitive rehabilitation intervention therapies for individuals with dementia and mild cognitive impairment has yet to draw definite conclusions about its effectiveness. Based on the conceptual framework of biopsychosocial theoretical model, this study explored to what extend cognitive rehabilitation intervention was effective in improving the memory and mood functioning of elderly adults with mild cognitive impairments. An archived data set of 216 elderly adults collected at a midwestern agency in the United States during the period of May 2012 through December 2013 was used. Wilcoxon matched pair tests were used to assess elders' changes in memory and mood functioning. Results indicated that there were no significant changes in memory skills or mood functioning found after the elderly individuals participated in the cognitive rehabilitation program within the 18-month period of continuous intervention training. Several limitations could explain these results including a small sample size of 88 participants that finished the 18-month program; the quality of the assessment process; and the lack of further information on the archived data such as demographics, patients' medication regimen, or type of family support. Health care professionals, families, and caretakers may use these results to understand the importance of closely monitoring the training and checking for positive results and adjusting the intervention as needed. Results of the study also highlighted the importance of focusing on promoting a take-charge collaborative approach to awareness and life satisfaction which is a salient implication for positive social change.

No description available.

Bakgrund: Antalet äldre i världen ökar ständigt. Åtta procent av Sveriges befolkning, som är 65 år och äldre, har någon form av kognitiv svikt. Med åldern ökar risken för mild kognitiv svikt, vilket påverkar alla områden i människans liv. Mild kognitiv svikt är ett tillstånd som kan leda till mer omfattande kognitiv nedsättning om det inte åtgärdas i ett tidigt skede. Det är därför viktigt att tidigt upptäcka och åtgärda de första symtomen på mild kognitiv svikt.  Syfte: Syftet med studien var att undersöka vilka interventioner som kan förbättra livskvaliteten hos äldre personer med mild kognitiv svikt. Metod: Systematisk blandad litteratur översikt (Systematic mixed studie review) med narrativ sammanfattning (narrativ summary) enligt Ryan (2013) valdes som studiedesign. Artiklar söktes systematiskt i databaserna Cinahl, PubMed och PsycINFO. Följande kategorier fastställdes vid analysen: fysisk aktivitet, kognitiv stimulans, kombinerade fysiska och kognitionsstimulerande interventioner och estetiska aktiviteter. Resultat: Studiens resultat baserades på en analys av elva kvantitativa och tre kvalitativa studier som omfattade äldre personer i ålder 65+ med MCI. Dessa artiklar publicerades mellan åren 2019 och 2023 och omfattade länderna Italien (1), Kanada (1), Kina (6), Mexiko (1), Nederländerna (1), Sverige (1), Tyskland (1) och USA (2). Interventioner som inkluderades i studien omfattade: fysiska aktiviteter som Tai Chi, måttlig aerob träning och squaredans; interventioner för kognitiv stimulans med hjälp av modern teknink; fysiska aktiviteter kombinerade med kognitiv träning; samt estetiska aktiviteter som stråkkonst, akvarell och akrylmålning. Interventionerna visade varierande grad av påverkan på livskvalitet för äldre personer med MCI, men samtliga visade positiv effekt på livskvaliteten. Slutsatser: Det finns evidens som tyder på att användandet av moderna teknologier kan förbättra äldre personernas med MCI livskvalitet. Interventioner som mindfulness, reminiscens, estetiska och fysiska aktiviteter kan också ge en positiv effekt på livskvalitet hos äldre personer med MCI. / Background: The number of elderly people in the world is constantly increasing. Eight percent of Sweden's population, who are 65 years and older, have some form of cognitive impairment. With age, the risk of mild cognitive impairment increases, which affects all areas of a person's life. Mild cognitive impairment is a condition that can lead to more extensive cognitive impairment if not addressed in its early stages. It is therefore important to detect and address the first symptoms of mild cognitive impairment at an early stage.  Aim: The aim of this study was to investigate which interventions can improve the quality of life in older people with mild cognitive impairment. Method: Systematic mixed study review with narrative summary according to Ryan (2013) was chosen as the study design. Articles were systematically searched in the databases Cinahl, PubMed and PsycINFO. The following categories were established in the analysis: physical activity, cognitive stimulation, combined physical and cognition-stimulating interventions, and aesthetic activities. Results: The results of the study were based on an analysis of eleven quantitative and three qualitative studies that included older people aged 65+ with MCI. These articles were published between the years 2019 and 2023 and covered the countries Italy (1), Canada (1), China (6), Mexico (1), the Netherlands (1), Sweden (1) Germany (1), and the United States (2). Interventions in the study included: physical activities such as Tai Chi, moderate aerobic, and square dancing; interventions for cognitive stimulation using modern technology; physical activities combined with cognitive training; as well as aesthetic activities such as string art, watercolor, and acrylic painting. The interventions showed varying degrees of impact on quality of life for older people with MCI, but all showed a positive effect on quality of life.  Conclusions: There is evidence to suggest that the use of modern technologies can improve the quality of life of older people with MCI. Interventions such as mindfulness, reminiscence, aesthetic and physical activities can also have a positive effect on quality of life in older people with MCI.

Alzheimer's disease (AD) is neurodegenerative disorder that causes memory loss and cognitive dysfunction. It affects one in five people over the age of 80 and is distressing for both sufferers and their families. A transitional stage between normal ageing and dementia including AD is termed a mild cognitive impairment (MCI). Recent studies have shown that people with MCI may convert to AD over time although not all MCI cases progress to AD. Much research is now focussing on early detection of AD and diagnosing an MCI that will progress to AD to allow prompt treatment and disease management before the neurons degenerate to a stage beyond repair. Hence, the ability to obtain a method of identifying MCI is of great importance. Virtual reality plays an important role in healthcare and offers opportunities for detection of MCI. There are various studies that have focused on detection of early AD using virtual environments, although results remain limited. One significant drawback of these studies has been their limited capacity to incorporate levels of difficulty to challenge users' capability. Furthermore, at best, these studies have only been able to discriminate between early AD and healthy elderly with about 80% of overall accuracy. As a result, a novel virtual simulation called Virtual Reality for Early Detection of Alzheimer's Disease (VREAD) was developed. VREAD is a quick, easy and friendly tool that aims to investigate cognitive functioning in a group of healthy elderly participants and those with MCI. It focuses on the task of following a route, since Topographical Disorientation (TD) is common in AD. An investigation was set up with two cohorts: non-elderly and elderly participants. The findings with regard to the non-elderly are important as they represent a first step towards implementation with elderly people. The results with elderly participants indicate that this simulation based assessment could provide a method for the detection of MCI since significant correlations between the virtual simulation and existing neuropsychological tests were found. In addition, the results proved that VREAD is comparable with well-known neuropsychological tests, such as Cambridge Neuropsychological Automated Test Battery, Paired Associate Learning (CANTAB PAL) and Graded Naming Test (GNT). Furthermore, analysis through the use of machine learning techniques with regard to the prediction of MCI also obtained encouraging results. This novel simulation was able to predict with about 90% overall accuracy using weighting function proposed to discriminate between MCI and healthy elderly. / Ministry of Higher Education, Malaysia and University Sultan Zainal Abidin, Malaysia (UNisZa)

OBJECTIVE: Everyday tasks, such as meal preparation and bill paying, require the coordination of multiple cognitive processes and are essential for independent living. In dementia, cognitive impairment disrupts the ability to perform everyday tasks, though subtle difficulties occur prior to the onset of a frank dementia and predict risk of further decline. Current clinical methods of assessing everyday functioning fail to elucidate the reasons people experience mild functional difficulties, but new sensitive and objective measures of mild functional difficulties may advance our understanding of the cognitive mechanisms associated with very early functional decline. In separate paradigms, prior work has identified two markers of mild functional difficulties that distinguish healthy older adults from younger adults: (1) micro errors, inefficient reaching movements (e.g., reaching for but not using a distractor object) and (2) inefficient eye movements during verbal description of common everyday activities (e.g., making coffee). The present study used a novel single, streamlined paradigm that integrates analysis of inefficient eye movements with inefficient reaching to increase sensitivity for early detection and advance our understanding of mild functional difficulties. METHODS: Thirty-four older adults with healthy cognition (n = 28) or mild cognitive impairment (n = 6) completed a novel, non-immersive virtual reality (VR) test involving two everyday tasks (Breakfast and Lunch) during which both eye movements and reaching movements were measured. Participants also completed clinical questionnaires and a performance-based test (with real objects) of everyday functioning as well as cognitive testing. Analyses examined whether eye movements are (1) associated with precision of reaching movements during the VR task (Aim 1); (2) associated with clinical measures of everyday function (Aim 2); and (3) show meaningful patterns across the VR tasks (beginning vs. end; between vs. within subtask) that are differentially associated with cognitive measures (Aim 3). RESULTS: Within the VR task, participants spent the highest proportion of time viewing objects necessary for completion of the current task step (target objects) compared to distractor objects or objects not needed at the current task step. Relations between efficiency of eye movements and reaching movements during the VR task were not statistically significant (Aim1). Time spent viewing non-target objects in the VR task was moderately correlated with errors on the performance-based test, but not with clinical questionnaires of everyday functioning (Aim 2). Participants spent a greater proportion of time viewing non-target objects at the beginning of the task sequence compared to later in the task sequence, as well as between sub-tasks compared to within sub-tasks, but correlation coefficients between these viewing patterns and cognitive tests failed to reach statistical significance (Aim 3). CONCLUSIONS: Results provide preliminary evidence that eye movements during execution of a VR task of everyday functioning involving reaching movements may be a reliable and sensitive measure of subtle, real-world functional difficulties. Eye movement patterns suggest premature decay of task goals and interference from competing task goals are mechanisms that may contribute to early functional decline in older adults. Further study is required to demonstrate the utility of eye movements in predicting cognitive and functional decline in older adults. / Psychology