Ascertainment, prediction and implications of dementia diagnosis in a study of 'healthy' cognitive ageing: the Lothian Birth Cohort 1921

In the context of an ageing global population, dementia poses a significant public health challenge. While there is no cure, understanding the risks for dementia and how these may be minimised is key to reducing the impact of the disease. As life expectancy improves, increasing proportions of the population are expected to survive into advanced old age. As such, understanding the risks for dementia in the oldest-old and how these may differ from earlier old age is of increasing importance. The existing literature specific to the oldest-old is lower in volume and many of the findings are inconsistent. The first two chapters provide a background to the thesis such that the reader may understand the context for the subsequent studies. The first of these chapters provides an overview of dementia, focussing on the impact of the disease and the requirement for further research. The concept of the oldest-old age group is described, along with a discussion regarding the complexities associated with studying those in advanced old age. The potential impact of diverse and complex health and disease profiles in this sector of the population are introduced. The thesis objectives are introduced within the text and summarised at the close of the chapter. The second chapter introduces the study cohort on which all of the studies included in the thesis are based – the Lothian Birth Cohort 1921 (LBC1921). The present thesis had three primary objectives. The first was to determine incident cases of dementia in a study cohort of oldest-old participants: the LBC1921. Dementia cases in this cohort were ascertained using existing data primarily and the dementia ascertainment method was developed following a systematic review of such methodology within the literature. While no ‘gold standard’ method was found, the evidence on which the methodology for this thesis was developed is presented and discussed. Using this method, 22.5% of the n=489 eligible participants were found to have developed dementia during the follow-up period. Comparing these results with ‘expected’ dementia rates in the cohort, the ascertainment method was determined to be relatively effective. The second objective of this thesis was to investigate potential risk factors for dementia in oldest age, with a focus on those that would be considered modifiable. The first study of risk factors considered a range of potentially modifiable health and lifestyle factors including hypertension, diabetes, obesity, smoking, hypercholesterolaemia and physical activity. The most well documented genetic risk factor for Alzheimer’s disease – APOE ɛ4 – was also included in the analyses. Contrary to other studies of dementia in the oldest-old, the presented study found that carrying at least one APOE ɛ4 allele continued to be a statistically significant risk factor for dementia in those aged over 79 years (OR: 2.23; 95% CI: 1.29, 3.86). A history of hypertension was shown to decrease the risk for incident dementia after age 79 years (OR: 0.47, 95% CI: 0.23, 0.98). This is a similar pattern to that described within the literature on the oldest-old but differs in direction from the association observed in earlier old age. The results also indicated an increased risk for dementia with greater lifetime leisure-based physical activity (OR: 1.17, 95% CI: 1.04, 1.32). This finding was again contradictory to the findings of studies of dementia in earlier old age. A history of statin-use was also observed to increase risk for dementia (OR: 3.39, 95% CI: 1.04, 11.02), while increased height reduced the risk for dementia (OR: 0.72, 95% CI: 0.55, 0.95). Overall, the findings suggested that the risk factor profile for dementia in the oldest-old, as observed in the LBC1921, differs from the risk factor profile in earlier old age. The second study of risk factors examined the association between physical fitness and dementia. The published study presented within the chapter considered three specific measures of fitness in oldest age: grip strength, walking speed and lung function (FEV1). These analyses did not demonstrate an association between any of the fitness measures at age 79 years and subsequent dementia; FEV1 (HR per unit increase 1.30, p = 0.37), grip strength (HR 0.98, p = 0.35), walking speed (HR 0.99, p = 0.90). The findings were again different to those described in studies of younger participants and supported the possibility of a changed risk factor profile for dementia in oldest-age. The final study of risk factors considered whether DNA methylation-based measures of accelerated ageing may be associated with dementia risk. Such measures of accelerated ageing may be considered, in simplest terms, as whether someone’s ‘biological age’ is more advanced than their chronological age. The results did not demonstrate any consistent association between recognised age acceleration measures and dementia. The third objective of the thesis was to revisit previous studies of non-pathological cognitive ageing in the LBC1921 and determine whether previously unidentified cases of dementia had influenced the findings. The study looked at five previous studies, and four factors reported to be associated with poorer cognitive ageing: smoking, APOE ɛ4, reduced fitness and lower vitamin B12. After excluding those participants who had gone on to develop dementia, the analyses were repeated. The overall findings were unchanged from the original studies, with all four factors continuing to be associated with poorer cognitive ageing (p<0.05). The final chapter of the thesis provides an overview and summary of the findings from the included studies. The general limitations, with regard to methodology and the study cohort, are outlined. The chapter closes with suggestions for further research

Brain volumetric changes and cognitive ageing during the eighth decade of life

Later‐life changes in brain tissue volumes—decreases in the volume of healthy grey and white matter and increases in the volume of white matter hyperintensities (WMH)—are strong candidates to explain some of the variation in ageing‐related cognitive decline. We assessed fluid intelligence, memory, processing speed, and brain volumes (from structural MRI) at mean age 73 years, and at mean age 76 in a narrow‐age sample of older individuals (n = 657 with brain volumetric data at the initial wave, n = 465 at follow‐up). We used latent variable modeling to extract error‐free cognitive levels and slopes. Initial levels of cognitive ability were predictive of subsequent brain tissue volume changes. Initial brain volumes were not predictive of subsequent cognitive changes. Brain volume changes, especially increases in WMH, were associated with declines in each of the cognitive abilities. All statistically significant results were modest in size (absolute r‐values ranged from 0.114 to 0.334). These results build a comprehensive picture of macrostructural brain volume changes and declines in important cognitive faculties during the eighth decade of life

Physical fitness and dementia risk in the very old:A study of the Lothian Birth Cohort 1921

Abstract Background Previous studies have demonstrated that individual measures of fitness – such as reduced pulmonary function, slow walking speed and weak handgrip – are associated with an increased risk of dementia. Only a minority of participants included in these studies were aged over 80. The aim of this study was therefore to investigate the association between physical fitness and dementia in the oldest old. Methods Subjects (n = 488) were enrolled in the Lothian Birth Cohort 1921 and aged 79 at baseline. Dementia cases arising after enrolment were determined using data from death certificates, electronic patient records and clinical reviews. Fitness measures included grip strength, forced expiratory volume in 1 s (FEV1) and walking speed over 6 m, measured at 79 years. Dementia risk associated with each fitness variable was initially determined by logistic regression analysis, followed by Cox regression analysis, where death was considered as a competing risk. APOE ε4 status, age, sex, height, childhood IQ, smoking, history of cardiovascular or cerebrovascular disease, hypertension and diabetes were included as additional variables. Cumulative incidence graphs were calculated using Aalen-Johansen Estimator. Results Although initial results indicated that greater FEV1 was associated with an increased risk of dementia (OR (odds ratio per unit increase) 1.93, p = 0.03, n = 416), taking into account the competing risk of mortality, none of the fitness measures were found to be associated with dementia; FEV1 (HR (hazard ratio per unit increase) 1.30, p = 0.37, n = 416), grip strength (HR 0.98, p = 0.35, n = 416), walking speed (HR 0.99, p = 0.90, n = 416). The presence of an APOE ɛ4 allele was however an important predictor for dementia (HR 2.85, p < 0.001, n = 416). Cumulative incidence graphs supported these findings, with an increased risk of dementia for APOE ɛ4 carriers compared with non-carriers. While increased FEV1 was associated with reduced risk of death, there was no reduction in risk for dementia. Conclusions In contrast to previous studies, this study found that lower fitness beyond age 79 was not a risk factor for subsequent dementia. This finding is not explained by those with poorer physical fitness, who would have been more likely to develop dementia, having died before onset of dementia symptoms

Risk factors for dementia in the ninth decade of life and beyond:A study of the Lothian Birth Cohort 1921

Logistic Regression Analysis with Physical Activity Age Groups. (DOCX 13 kb

Brain structural differences between 73- and 92-year olds matched for childhood intelligence, social background, and intracranial volume

Fully characterizing age differences in the brain is a key task for combating aging-related cognitive decline. Using propensity score matching on 2 independent, narrow-age cohorts, we used data on childhood cognitive ability, socioeconomic background, and intracranial volume to match participants at mean age of 92 years (n = 42) to very similar participants at mean age of 73 years (n = 126). Examining a variety of global and regional structural neuroimaging variables, there were large differences in gray and white matter volumes, cortical surface area, cortical thickness, and white matter hyperintensity volume and spatial extent. In a mediation analysis, the total volume of white matter hyperintensities and total cortical surface area jointly mediated 24.9% of the relation between age and general cognitive ability (tissue volumes and cortical thickness were not significant mediators in this analysis). These findings provide an unusual and valuable perspective on neurostructural aging, in which brains from the 8th and 10th decades of life differ widely despite the same cognitive, socioeconomic, and brain-volumetric starting points

El Diario de Pontevedra : periódico liberal: Ano XXXIV Número 9911 - 1917 abril 30

Logistic Regression Analyses for Probable and Possible Dementia. (DOCX 14 kb

ENERGIATESTI™ JA PAREMPI VIRE –SOVELLUKSEN VAIKUTUKSET HENKILÖSTÖN ELINTAPAMUUTOKSIIN : CASE –TUTKIMUS, BAYER NORDIC SE

Opinnäytetyön aiheena oli elintapojen vaikutus työhyvinvointiin, työkykyyn ja vireyteen. Työhyvinvoinnin osalta keskityttiin terveyden ja työkyvyn alueisiin sekä erityisesti työnantajan ja työterveyshuollon rooliin elintapamuutosten tukemisessa. Teoriaosuudessa tutkittiin tämän päivän työelämän vaatimuksia ja miten niihin voidaan elintavoilla vaikuttaa. Myös erilaisten liikuntainterventioiden ja sovellusten roolia yksilöiden ja työyhteisöjen elintapahaasteissa tutkittiin. Empiriaosuudessa selvitettiin työnantajan teettämän kuntotestauksen aktivoivaa vaikutusta henkilöstön elintapamuutoksiin. Tapaustutkimuksen toimeksiantaja oli Bayer Nordic SE. Tutkimuksella haluttiin selvittää Energiatestin käyttäjäkokemuksia ja aktivoivaa vaikutusta henkilöstön elintapamuutoksiin sekä Parempi Vire –sovelluksen tukiroolia. Tutkimus toteutettiin kyselylomakkein ja haastatteluin. Tutkimuksen kohteena olevalle ryhmälle lähetettiin sähköinen lomakekysely seurantajakson alussa ja lopussa. Sen lisäksi kutsuttiin muutamia testaukseen osallistuneita tarkempaan haastatteluun. Myös työterveyshuollon työntekijöitä haastateltiin. Testiin osallistuneet arvioivat tes-tin toteutusta, luotettavuutta ja innostavuutta. Testin jälkeen tehtyjen elintapamuutos-suunnitelmien toteutumista seurattiin seurantajakson ajan. Testin käyttäjäkokemukset olivat pääosin positiivisia ja henkilöstön suhtautuminen yrityksen teettämään kuntotestaukseen myönteinen. Erityisen tärkeäksi osoittautui testin tuloksena saatavan raportin huolellinen läpikäynti työterveyshuollon kanssa. Henkilöt odottavat ammattitaitoista ja kannustavaa tukea elintapamuutosten käynnistämiseen ja ylläpitoon. Työterveyshuolto odottaa henkilöstöltä oma-aloitteisuutta ja motivaatiota testitulosten analysoinnissa ja jatkotoimenpiteiden suunnittelussa. Tutkimustulos osoitti, että Energiatesti kannattaa ottaa säännölliseen käyttöön toimeksiantajayrityksessä. Kuntotestauksesta ja siitä seuraavista toimenpiteistä pitää tehdä strategiatason suunnitelma, jotta siihen saadaan tarvittavat resurssit. Pitkäjänteinen satsaus henkilöstön hyvinvointiin heijastuu ennen pitkää positiivisesti myös yrityksen tulokseen.The topic of the thesis was the impact of life style on work well-being, work ability and vitality. With respect to work well-being, the focus was on health and work ability and specifically on the role of the employer and Occupational Health Care in sup-porting life style changes. The theory part looked at the requirements of work life today and how they can be influenced by life style. The role of various exercise interventions and applications in the life style challenges of individuals and working communities was explored. The empirical part investigated the activating effect of fitness testing organized by the employer on the life style changes of the personnel. The sponsor of the case study was Bayer Nordic SE. The study was used to find out user experiences related to the Energiatesti (energy test) and its activating effect on the life style changes of the personnel and the supportive role of the Parempi Vire (better vitality) application. The study was conducted with questionnaires and interviews. An electronic questionnaire was sent to the group targeted in the study at the start and end of the follow-up period. In addition, some of those who participated in the fitness testing were invited to a more detailed interview. Occupational Health Care employees were also interviewed. The test participants evaluated the implementation, reliability and the motivational character of the test. The realization of the plans made after the test for life style changes were monitored during the follow-up period. The test user experiences were mainly positive and the personnel had a positive attitude towards the fitness testing carried out by the company. A thorough review of the test result with the Occupational Health Care turned out to be particularly important. The employees are expecting to receive professional and encouraging support in initiating and maintaining life style changes. Occupational Health Care is expecting initiative and motivation from the personnel in initiating and maintaining life style changes. According to the study results, the energy test is worth taking into regular use in the sponsor company. A strategy level plan needs to be compiled for the fitness testing and measures that follow it to obtain the required resources for it. Long-term investment in the well-being of personnel will before long be positively reflected in the company results