The Relationship Of Musical Abilities With Cognition And Neurodegenerative Pathology In Older Adults With Mild Cognitive Impairment

Older adults with mild cognitive impairment (MCI) are at increased risk for dementia. Despite the presence of cognitive deficits in persons with MCI and dementia, older adults with dementia preserve their ability to engage in music throughout their disease. However, musical abilities have not previously been explored in individuals with MCI. The purpose of this dissertation was twofold: 1) to better understand the relationship between musical and cognitive abilities in persons with MCI (Chapter II) and how preserved musical abilities may contribute to enhanced cognitive abilities despite the underlying atrophy in the brain (Chapter III); and 2) to develop and submit a post-doctoral application to investigate the feasibility and acceptability of an individualized music intervention to reduce sleep disturbances in older adults with dementia (Chapter IV). We conducted a cross-sectional study at the University of Pennsylvania Alzheimer’s Disease Core Center (ADCC). We combined existing data from the ADCC and asked 60 older adults with MCI to complete two questionnaires, one screening for depression and the other gauging their musical abilities. We broadly operationalized musical abilities as musical skills, expertise, achievements and related behaviors and used hippocampal volume as a biomarker for the underlying atrophy in the brain. The participants, on average, scored lower on the index of musical abilities compared to published norms. Using Pearson’s correlations and linear regression analyses, we found that participants who scored lower on the index of musical abilities had lower scores on the measure of verbal naming. Additionally, musical abilities moderated the relationship between hippocampal volume and one of the cognitive abilities – executive function in 38 older adults for whom magnetic resonance imaging was available. Enhanced musical abilities emerged as a possible compensatory mechanism for persons with MCI who are struggling with cognitive deficits. Given the relationship between musical and cognitive abilities, music may be an effective intervention to maintain cognition and improve the well-being of older adults with cognitive impairment. This body of work, my passion for music, and a desire to garner skills in intervention research served as a platform for writing and submitting a post-doctoral application exploring how a music intervention may help alleviate one of the most distressing behavioral symptoms of dementia – sleep disturbances

Remote Monitor System for Alzheimer disease

Health Remote Monitoring Systems (HRMS) offer the ability to address health-care human resource concerns. In developing nations, where pervasive mobile networks and device access are linking people like never before, HRMS are of special relevance. A fundamental aim of this research work is the realization of technological-based solution to triage and follow-up people living with dementias so as to reduce pressure on busy staff while doing this from home so as to avoid all unnecessary visits to hospital facilities, increasingly perceived as dangerous due to COVID-19 but also raising nosocomial infections, raising alerts for abnormal values. Sensing approaches are complemented by advanced predictive models based on Machine Learning (ML) and Artificial Intelligence (AI), thus being able to explore novel ways of demonstrating patient-centered predictive measures. Low-cost IoT devices composing a network of sensors and actuators aggregated to create a digital experience that will be used and exposure to people to simultaneously conduct several tests and obtain health data that can allow screening of early onset dementia and to aid in the follow-up of selected cases. The best ML for predicting AD was logistic regression with an accuracy of 86.9%. This application as demonstrated to be essential for caregivers once they can monitor multiple patients in real-time and actuate when abnormal values occur.info:eu-repo/semantics/acceptedVersio

A Qualitative Multiple Case Study of Rural Spousal Caregivers’ Experience with Health Promotion

Rural spousal caregivers caring for a person living with moderate to severe dementia at home are at risk of serious health consequences because they are unable to attend to their own personal health needs. Insufficient evidence exits that informs how contextual components of the rural spousal caregiving situation prevent caregivers from practicing personal health promotion and wellness while caregiving during the later stages of dementia. The aims of this qualitative, descriptive, multiple case study were to: 1) describe transition points in the rural spousal caregiver’s role across the dementia disease trajectory, 2) describe the rural spousal caregiver’s experience with personal health promotion and physical activity across the dynamic context of care provision to a spouse in the moderate to severe stages of dementia, and 3) describe the rural spousal caregiver’s perceptions of feasible and desirable strategies and resource needs for promoting their own physical activity across the dementia caregiving trajectory. Four cases of spousal caregivers were enrolled from rural areas of Nebraska. Multiple sources of data informed analysis including environmental descriptive memos, serial in-person semi-structured interviews, life history timelines, archival and photo data, field and reflexive notes, rural community resources, and local community resource mapping. Thematic analysis was conducted within-case and across-case. Rigor was achieved with confirmability, dependability, credibility, and transferability. Themes related to caregivers’ emotional experience undergoing role transition periods, enduring unpredictable days, and struggling with balancing personal health promotion emerged. Rural spousal caregivers did everything for their livelihood themselves with little support. As the spouse’s dementia worsened, rural contextual nuances including the stress of maintaining upkeep of the farm, the immense physical labor of work on the farm, and scarcity of rural caregiving resources contributed to caregivers postponing their own health needs and health promotion activities. Knowledge gained from this research provides the groundwork for an intervention that includes unique rural specific supports and resources during the later stages of dementia so caregivers can focus on personal health promotion

The role of physical activity and bilingualism in the development of neurodegenerative disorders: Cross-sectional and neuroimaging evidence

Delaying Alzheimer’s disease (AD), the most common form of dementia, by five years could decrease the global prevalence of AD by 57% and halve the annual economic impact which is currently estimated to surpass US$2 trillion by 2030. Since no treatment or cure for dementia exist, identifying modifiable factors to reduce the incidence of dementia has become a public health priority. Increased physical activity (PA) has been associated with a lower risk of developing dementia in observational studies. Observational studies have also linked bilingualism (the ability to speak two languages) with a delayed onset of dementia but no risk-reduction in dementia in bilinguals relative to monolinguals. Differences in study outcomes in the fields of PA- and bilingualism- related research to methodological limitations including poor measurement of the exposure (PA and language profiles), small sample sizes, and recruitment of participants with different dementia etiologies. The purpose of this thesis was twofold: i) to explore the roles of PA and bilingualism in dementia risk and ii) to inform the development of a randomized controlled trial (RCT) to test whether studying a foreign language combined with increasing PA can improve cognitive performance in seniors who are at a higher risk of developing AD. The aim of Chapter two was to review the available evidence linking PA with the risk of developing dementia as well as to explore the effects of increasing PA on cognition in individuals with dementia. Results showed that aerobic, and high-intensity, habitual PA was associated with improved cognition-related biomarkers and lower dementia risk in epidemiological studies. Experimental evidence showed increasing PA improved cognition-related biomarkers and cognition in preclinical phases of dementia, but not in clinical phases. The findings showed that PA is linked with a lower risk of dementia in epidemiological studies, but experimental studies showed little to no improvements in cognition in participants with dementia following a structured PA program. There was evidence indicating that increasing PA levels in the preclinical phase of AD may result in greater translation impact than in participants at the more advanced clinical stage of AD. Most studies assessed PA with self-report measures questioning the accuracy and precision of exposure and recruited participants with dementia irrespective of aetiology, which makes it problematic to discern whether PA is differentially related to varying dementia aetiologies. The aim of Chapter three was to systematically review the association between bilingualism and the delay in the diagnosis of dementia and AD. Here, we retrieved a total of 20 studies, 15 of which were meta-analysed. Results showed that bilinguals were on average 3.2 (95% CI: 1.5, 4.9) years older than monolinguals at the time of dementia. Moreover, at the time of dementia diagnosis, bilinguals and monolinguals demonstrated a similar level of global cognitive impairment (Hedges’ g = 0.05 95% CI: -0.10, 0.21). Prediction intervals however showed a large dispersion of effect sizes in the meta-analysis comparing monolinguals to bilinguals on the age of dementia diagnosis. To explore possible reasons for the observed dispersion in effect sizes, we conducted subgroup analyses. In one subgroup meta-analysis comparing studies that had recruited participants with dementia to studies that had recruited participants with AD, bilinguals were 4.2 (95% CI: 2.0, 6.2) and 1.7 (95% CI: -1.4, 4.7) years older than monolinguals at dementia and AD diagnosis, respectively. Meta-analytic results combining prospective longitudinal studies showed no risk reduction in dementia among bilinguals compared to monolinguals (Odds Ratio: 0.85; 95% CI: 0.69-1.05). Risk of bias assessment revealed that most studies carried several methodological limitations including poor measurement of participants’ language profiles and small sample sizes. The aim of Chapter four was to explore the underlying mechanisms in the brain that may be responsible for the observed findings in the first systematic review (Chapter three). In this study, we observed that bilinguals compared to monolinguals had greater brain volume in the frontostriatal and frontoparietal circuits. Also, functional neuroimaging studies showed that bilinguals made use of relevant brain areas more efficiently than monolinguals when completing interference cognitive tasks. Results from the cross-sectional studies showed that higher levels of language acculturation were associated with significantly greater verbal and psychomotor speed performance than lower levels of language acculturation. The aim of the Chapter five was to explore the link between language acculturation and cognition in older individuals from ethnic minorities (Hispanic and Asian) living in the United States of America using an epidemiological dataset. In this cross-sectional epidemiological study, we analyzed data from the National Health and Nutrition Examination Survey using a larger sample size than previous studies. We found that higher levels of language acculturation (i.e. speaking the native language and that of the recipient’s country at home) was associated with greater psychomotor speed processing than lower levels of language acculturation (mostly speaking the native language at home) and some, but not all, measures of verbal fluency. Overall, the findings suggest that higher levels of language acculturation are associated with greater cognitive performance in older individuals from ethnic minorities. Overall, the evidence gathered in the previous chapters indicate that i) increasing PA in individuals who are at a higher risk of developing AD might be more useful in improving cognitive performance than in individuals who already have developed AD and ii) bilingualism might render the brain areas typically affected by AD such as the frontostriatal and frontoparietal brain circuits more resilient against neurodegeneration and in turn, delay the onset of AD symptoms and diagnosis. Therefore, because no randomized-controlled trial (RCT) testing the combined effects of increased PA with studying a foreign language currently exist, Chapter five presents a detailed study protocol for an RCT addressing this gap in the literature while addressing the limitations of previous studies in the fields of PA- and bilingualism-based research. The purpose of this thesis was to explore the roles of PA and bilingualism in dementia onset and risk and to inform the development of a randomized controlled trial (RCT) testing the effects of studying a foreign language with increased PA in individuals at a higher risk of dementia. Increasing PA levels are associated with greater cognition in individuals at the preclinical phase of AD rather than in participants with a diagnosis of dementia or AD. Bilingualism was also associated with later age of AD diagnosis on average by 4.7 years. This finding is clinically relevant because a five-year delay in the onset of AD could lower the number of individuals with AD worldwide by 57% and as a consequence, halving the associated economic costs. Moreover, we also showed that bilingualism may be responsible for rendering brain areas typically affected by AD more resilient against neuropathology. Moreover, this thesis revealed that studies in the field of exercise science and bilingualism research in dementia carry important methodological limitations that question the internal validity of these two lines of research. Consequently, the evidence gathered within this thesis led us to propose a novel RCT exploring the effects of increasing PA levels and studying a foreign language in monolingual individuals at a higher risk of AD while addressing the most important limitations of previous research

Interactive Effects of Physical Activity and APOE-ε4 On White Matter Tract Diffusivity in Healthy Elders

Older adult apolipoprotein-E epsilon 4 (APOE-ε4) allele carriers vary considerably in the expression of clinical symptoms of Alzheimer\u27s disease (AD), suggesting that lifestyle or other factors may offer protection from AD-related neurodegeneration. We recently reported that physically active APOE-ε4 allele carriers exhibit a stable cognitive trajectory and protection from hippocampal atrophy over 18 months compared to sedentary ε4 allele carriers. The aim of this study was to examine the interactions between genetic risk for AD and physical activity (PA) on white matter (WM) tract integrity, using diffusion tensor imaging (DTI) MRI, in this cohort of healthy older adults (ages of 65 to 89). Four groups were compared based on the presence or absence of an APOE-ε4 allele (High Risk; Low Risk) and self-reported frequency and intensity of leisure time physical activity (PA) (High PA; Low PA). As predicted, greater levels of PA were associated with greater fractional anisotropy (FA) and lower radial diffusivity in healthy older adults who did not possess the APOE-ε4 allele. However, the effects of PA were reversed in older adults who were at increased genetic risk for AD, resulting in significant interactions between PA and genetic risk in several WM tracts. In the High Risk-Low PA participants, who had exhibited episodic memory decline over the previous 18-months, radial diffusivity was lower and fractional anisotropy was higher, compared to the High Risk-High PA participants. In WM tracts that subserve learning and memory processes, radial diffusivity (DR) was negatively correlated with episodic memory performance in physically inactive APOE-ε4 carriers, whereas DR was positively correlated with episodic memory performance in physically active APOE-ε4 carriers and the two Low Risk groups. The common model of demyelination-induced increase in radial diffusivity cannot directly explain these results. Rather, we hypothesize that PA may protect APOE-ε4 allele carriers from selective neurodegeneration of individual fiber populations at locations of crossing fibers within projection and association WM fiber tracts

Cross-sectional analysis of FDG PET measured amygdala and parietal activity in patients with Alzheimer's disease and cognitive decline of unknown aetiology, for patients who may have limbic-predominant age-related TDP43 encephalopathy

Background: Limbic-predominant age-related TDP-43 encephalopathy (LATE) is a recently recognized cerebral proteinopathy that can lead to a clinical syndrome indistinguishable from Alzheimer’s disease (AD) in the antemortem setting. Objective: To assess the prevalence and degree of amygdala hypometabolism in elderly patients referred to a tertiary hospital for assessment of cognitive decline. Methods: Retrospective cross-sectional exploratory analysis (for the period of 2010 to 2022) of two cohorts (60 to70 years old [y.o] and 80y.o and above). All subjects’s data was retrieved from the Government of Western Australia Department of Health database, and the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. A total of 348 subjects were used for this study. We used standard uptake values ratios (SUVRs) to to quantify metabolic activity in the amygdala and parietal lobe region. The normal range of metabolic activity for the amygdala and parietal lobe regions was generated by taking the mean SUVRs ±2 standard deviations from our Normal group (cognitively assessed normal subjects for their age). Subjects below the normal range of metabolic activity with only amygdala but not parietal lobe reduction formed our suspected LATE cases. Subjects with only parietal lobe reduction formed AD cases, and subjects with the both amygdala and parietal reduction formed our suspected comorbid AD /LATE cases. Results: Suspected pure LATE, and comorbid AD/LATE in subjects with CDUA and AD is more common in age group 80 and over than in age group 60 to 70, with presence in respectively 7% and 6.3% of cases. Overall prevalence of amygdala reduction in AD subjects was approximately 18% in age group 80 and over, and 23.5% in age group 60 to 70, which is similar to what is suggested in the literature (approximately 20% LATE). Conclusion: Results support using measured amygdala activity as a technique to further categorise CDUA and AD patients to determine suspected LATE status

Does loneliness contribute to mild cognitive impairment and dementia? A systematic review and meta-analysis of longitudinal studies

There is growing evidence that loneliness is associated with mild cognitive impairment (MCI) and dementia. However, the extent of this association remains unclear. A systematic review and meta-analysis of longitudinal studies examining this association was conducted. Six electronic databases were searched from inception to November 15th 2018. A random-effects meta-analysis was performed to obtain pooled estimates and 95% CIs. Studies were also assessed for heterogeneity, methodological quality and publication bias. A total of 4270 hits were retrieved based on the initial search strategy and ten studies met the eligibility criteria involving 37339 individuals (mean age from 64.9 to 83.1 years). Variation between studies was present for the measurement of loneliness as well as for the case ascertainment of MCI and dementia. Loneliness was positively associated with increased risk of dementia (overall RR = 1.26; 95% CI = 1.14, 1.40; n = 8). Due to lack of sufficient data, we could not explore the association between loneliness and risk of MCI through a meta-analysis, but limited evidence suggests a potential effect of loneliness on MCI. A further understanding of the deleterious effects of loneliness on MCI and dementia may assist the design of environmental and psychological interventions to prevent or delay the onset of these neuropsychiatric condition