Despite evidence for an association between atrial fibrillation (AF) and cognitive decline and dementia independent of stroke, pathways underlying this relationship remain unclear. Critically, elevated levels of inflammatory markers, common in AF, are associated with the breakdown of the blood-brain barrier (BBB) and may contribute to neuroinflammation and neurodegeneration. To investigate this potential contributing pathway, we estimated associations of inflammatory markers with cognitive decline and dementia in AF adults. We used data from two population-based cohorts and found that inflammatory markers were associated with cognitive decline but not dementia. Some associations were modified by sex and apolipoprotein E (APOE) genotype. These findings provide preliminary evidence for inflammatory-mediated BBB dysfunction as a potential contributing pathway linking AF to cognitive decline. Future work examining the role of BBB dysfunction in AF and cognition may benefit from the use of markers of central inflammation to increase sensitivity, while considering possible differences by sex, dementia subtype, and APOE genotype.

No description available.

The purpose of this study is to explore the relationship between physical activity and working memory decline among older adults with APOE4 status. The APOE4 allele is currently the strongest predictor of risk for Alzheimer's disease and other related dementias. The publicly available data from the Health and Retirement Study was used to complete this Retrospective Longitudinal study. Three hypotheses were explored. H₁: It is expected that the presence of the APOE4 allele will be associated with worse overall working memory performance and a steeper rate of decline in working memory over time. H₂: Meanwhile, it is expected that participants that partake in a higher physical activity level will have better overall working memory performance and less decline in working memory than participants that only perform low or no activity. H₃: A moderation effect of physical activity on the relationship between working memory and APOE4 status is expected. A two-way repeated measure ANOVA was performed. Results indicted main effects for physical activity and years of education on the digit span task. Additionally, it was found that vigorous activity mitigates ill-effects of APOE4 on working memory. A statistical significance was found for the interaction between APOE4 status and physical activity. Findings suggest that physical activity may be prioritized as a primary intervention method for older and middle-aged APOE4 carriers.

No description available.

In der vorliegenden Arbeit wurden Zusammenhänge zwischen Parametern des peripheren Cholesterolstoffwechsels mit Makrostruktur und Mikrostruktur des Hippocampus anhand multimodaler 7 Tesla Magnetresonanztomografie bei älteren, kognitiv gesunden Menschen untersucht. Dabei wurden Unterschiede zwischen den biologischen Geschlechtern der Teilnehmenden sowie Unterschiede zwischen Teilnehmenden mit und ohne subjektive kognitive Beeinträchtigungen betrachtet. Als zentrales Ergebnis zeigte sich ein Zusammenhang zwischen hohen HDL-Werten und niedrigem Hippocampusvolumen bei Frauen.:Inhaltsverzeichnis II Abkürzungsverzeichnis V Abbildungsverzeichnis VII Tabellenverzeichnis IX 1 Einführung 1 1.1 Hintergrund 1 1.2 Demenzielle Erkrankungen 2 1.3 Subjective Cognitive Decline (SCD) in präklinischer Alzheimer-Demenz 4 1.4 Ätiopathogenese der Alzheimer-Demenz 6 1.4.1 Cholesterolstoffwechsel 7 1.4.2 Rolle des Cholesterolstoffwechsels in der Pathogenese der Alzheimer-Demenz 9 1.5 Hippocampus 14 1.5.1 Struktur und Funktionen 14 1.5.2 Physiologische und pathologische Veränderungen des Hippocampus 16 1.6 Die Verbindung zwischen Hyperlipidämie, Hippocampusstruktur und Kognition 20 2 Aufgabenstellung 23 3 Materialien und Methoden 25 3.1 Studienpopulation 26 3.1.1 Ein- und Ausschlusskriterien 26 3.1.2 Rekrutierung 26 3.1.3 Einteilung in Gruppen 27 3.2 Untersuchungen 27 3.2.1 Medizinische körperliche Untersuchung 29 3.2.2 Neuropsychologische Tests und Fragebögen 30 III 3.2.3 Magnetresonanztomografie (MRT) 31 3.3 Statistische Analyse 33 4 Ergebnisse 34 4.1 Deskriptive Statistik 34 4.1.1 Demografie 34 4.1.2 Somatische Parameter 35 4.2 Periphere Parameter des Lipidstoffwechsels und Hippocampusstruktur 39 4.2.1 Gesamte Gruppe 39 4.2.2 Geschlechter 42 4.2.3 Kognitive Gruppen 45 5 Diskussion 49 5.1 Zentrale Ergebnisse 49 5.2 Cholesterol 50 5.2.1 Cholesterolstoffwechsel und Pathogenese der Alzheimer-Demenz 50 5.2.2 Der Mythos des HDL-Cholesterols 53 5.3 Hippocampus 55 5.3.1 Volumen 55 5.3.2 Subfieldvolumetrie 56 5.3.3 Mean Diffusivity (MD) 57 5.4 Unterschiede zwischen den Geschlechtern 59 5.5 Subjective Cognitive Decline (SCD) 60 5.6 Stärken und Limitationen der Studie 63 5.6.1 Studiendesign 63 5.6.2 Studienpopulation 65 5.7 Schlussfolgerungen und Ausblick 66 6 Zusammenfassung 69 7 Literatur 73 8 Erklärung über die eigenständige Abfassung der Arbeit 93 9 Lebenslauf 94 10 Publikation 95 11 Danksagung 96

Olfactory function plays an important role in health and well-being. Deficits have been associated with a greater risk of cognitive decline, dementia, and death, indicating that olfactory ability may be an early marker of cognitive impairment and indicator of brain integrity. In the progression of cognitive impairment related to dementia, intraindividual variability in cognition may precede cognitive decline as an early risk factor, indicating that individuals with more variability in their cognitive performance may have an increased risk of cognitive impairment. Despite a significant amount of literature examining the relationship between olfaction and cognitive decline, to the best of our knowledge, no study has yet examined whether olfaction is associated with the earlier marker of cognitive decline, intraindividual variability in cognition. Project 1. In data drawn from the Rush Memory and Aging Project (N=1501), multistate models were used to estimate the association of olfactory identification with transition patterns through cognitive states including non-impaired cognitive functioning, clinically diagnosed mild cognitive impairment and dementia, and death. Additionally, multinomial regression models were fit to estimate life expectancies for overall and cognitively unimpaired years of life, relative to olfactory identification scores. This dissertation aims to contribute to the current body of literature suggesting potential for the use of olfactory identification as a clinically administered marker for the early detection of cognitive decline and risk of dementia. Project 2. In data collected by our lab (N=65), multilevel models were used to examine whether olfactory identification scores were associated with the magnitude and rate of change of intraindividual variability (IIV) in cognitive functioning. This dissertation aims to address whether olfactory identification is associated with IIV in cognition using self-administered mobile cognitive testing in a 14-day micro-longitudinal study. / Graduate

Yes / Objective: We conducted a U.K.-wide survey to collect information on people's beliefs, fears, perceptions, and attitudes to cognitive aging. Methods: This community-based aging survey included 3,146 adults aged 40 years and over. Results: Respondents believed memory might be the earliest cognitive skill to decline (mean: 59.4 years), followed by speed of thinking (mean: 64.9). Those in their 40s were more pessimistic, because they estimated cognitive changes would start up to 15 years earlier than respondents aged over 70. Having a purpose in life, healthy eating, challenging the mind, sleep, and physical activity ranked higher in terms of perceived importance for maintaining or improving cognitive skills. However, less than 50% engaged in any of these activities. Although 91% believed there are things people can do to maintain or improve their cognitive skills, more than 40% were unsure or did not know how to do so. Respondents who strongly agreed that changes in cognitive skills might be a sign of something more serious were significantly more likely to do various activities to benefit their cognitive skills. Conclusion: Results suggest that people are less aware of the potential cognitive benefits of certain activities, such as exercise and diet. It is important to build awareness about the benefits of lifestyles and activities for cognitive health. / Velux Stiftung (Project No. 1034).

京都大学 / 新制・課程博士 / 博士(医学) / 甲第25532号 / 医博第5105号 / 京都大学大学院医学研究科医学専攻 / (主査)教授 渡邉 大, 教授 村井 俊哉, 教授 高橋 淳 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

An increasingly older population will most likely lead to greater demands on the health care system, as older age is associated with an increased risk of having acute and chronic conditions. The number of diseases or disabilities is not the only marker of the amount of health care utilized, as persons may seek hospitalization without a disease and/or illness that requires hospital healthcare. Hospitalization may pose a severe risk to older persons, as exposure to the hospital environment may lead to increased risks of iatrogenic disorders, confusion, falls and nosocomial infections, i.e., disorders that may involve unnecessary suffering and lead to serious consequences. Aims: The overall aim of this thesis was to describe and explore individual trajectories of cognitive development in relation to hospitalization and risk factors for hospitalization among older persons living in different accommodations in Sweden and to explore older persons' reasons for being transferred to a hospital. Methods: The study designs were longitudinal, prospective and descriptive, and both quantitative and qualitative methods were used. Specifically, latent growth curve modelling was used to assess the association of cognitive development with hospitalization. The Cox proportional hazards regression model was used to analyse factors associated with hospitalization risk overtime. In addition, an explorative descriptive design was used to explore how home health care patients experienced and perceived their decision to seek hospital care. Results: The most common reasons for hospitalization were cardiovascular diseases, which caused more than one-quarter of first hospitalizations among the persons living in ordinary housing and nursing home residents (NHRs). The persons who had been hospitalized had a lower mean level of cognitive performance in general cognition, verbal, spatial/fluid, memory and processing speed abilities compared to those who had not been hospitalized. Significantly steeper declines in general cognition, spatial/fluid and processing speed abilities were observed among the persons who had been hospitalized. Cox proportional hazards regression analysis showed that the number of diseases, number of drugs used, having experienced a fall and being assessed as malnourished according to the Mini Nutritional Assessment scale were related to an increased hospitalization risk among the NHRs. Among the older persons living in ordinary housing, the risk factors for hospitalization were related to marital status, i.e., unmarried persons and widows/widowers had a decreased hospitalization risk. In addition, among social factors, receipt of support from relatives was related to an increased hospitalization risk, while receipt of support from friends was related to a decreased risk. The number of illnesses was not associated with the hospitalization risk for older persons in any age group or for those of either sex, when controlling for other variables. The older persons who received home health care described different reasons for their decisions to seek hospital care. The underlying theme of the home health care patients’ perceptions of their transfer to a hospital involved trust in hospitals. This trust was shared by the home health care patients, their relatives and the home health care staff, according to the patients. Conclusions: This thesis revealed that middle-aged and older persons who had been hospitalized exhibited a steeper decline in cognition. Specifically, spatial/fluid, processing speed, and general cognitive abilities were affected. The steeper decline in cognition among those who had been hospitalized remained even after controlling for comorbidities. The most common causes of hospitalization among the older persons living in ordinary housing and in nursing homes were cardiovascular diseases, tumours and falls. Not only health-related factors, such as the number of diseases, number of drugs used, and being assessed as malnourished, but also social factors and marital status were related to the hospitalization risk among the older persons living in ordinary housing and in nursing homes. Some risk factors associated with hospitalization differed not only between the men and women but also among the different age groups. The information provided in this thesis could be applied in care settings by professionals who interact with older persons before they decide to seek hospital care. To meet the needs of an older population, health care systems need to offer the proper health care at the most appropriate level, and they need to increase integration and coordination among health care delivered by different care services.

This study explored longitudinal change in executive function (EF) and episodic memory (EM) related to multimorbidity, number of chronic conditions, change in chronic conditions overtime in a nationally representative sample of young, middle-aged,and older adults. Participants were from the second (2004-2006) and third (2013-2015) waves of the Survey of Midlife Development in the United States (MIDUS; N=2,532). Participants completed telephone interviews and questionnaires providing information on demographics and chronic conditions. The Brief Test of Adult Cognition by Telephone (BTACT) assessedcognitive function. The BTACT includes measures of EM (ex. word list recall) and EF (ex. digits backward, category fluency, etc.).Overall, only change in chronic conditions was associated with EF decline in the whole sample. In young adults multimorbidity and number of chronic conditions was significantly associated with both EF and EM decline, whereas only change in number of chronic conditions was significantly associated with EF decline in middle aged adults.Future research is needed to assess a broader range of chronic conditions to determine their overall burden on EF and EM over time.