Ascertainment, prediction and implications of dementia diagnosis in a study of 'healthy' cognitive ageing: the Lothian Birth Cohort 1921
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Date
31/07/2021Author
Sibbett, Ruth Anne
Metadata
Abstract
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.