- Link:
- http://hdl.handle.net/1765/14187
- Collection:
-
- Subjects
- cognition dementia population based cohort studies elderly people
- Creator:
- Euser, S.M.
- Contributors:
- Westendorp, Prof. Dr. R.G.J. Breteler, Prof. Dr. M.M.B.
- Publisher
- Erasmus University Rotterdam
- Description
- The devastating impact of the loss of cognitive
abilities that often accompanies the aging process is feared by
many. Despite an increasing number of studies, the precise etiology
of the disease is not known yet. There is accumulating evidence
that a variety of causes, rather than a single factor, result in
impaired cognitive function and the clinical symptoms of dementia.
Glucose metabolism, vascular pathology and inflammation have all
been suggested to play a role in the development of cognitive
impairment and dementia.
The main objective of the work described
in this thesis was the investigation of potentially modifiable risk
factors, including factors involved in glucose metabolism, vascular
pathology and inflammation in especially the early stages of the
disease process. Furthermore, there have been studies that
suggested that in general, possible risk factors that play a role
at younger ages may not be important anymore when people survive
until higher ages. Therefore, I additionally studied the
age-specific effects of these risk factors in several large
prospective studies including the Rotterdam Study, the Leiden
85-plus Study, and the PROSPER study, that were complementary with
respect to the age of the participants and consequently allowed me
to study the association between several potentially modifiable
risk factors and cognitive function and decline over a wide age
range in the general population. Finally, I investigated suggested
preclinical biomarkers of dementia that might be !
used to
identify people who are at increased risk of developing dementia.
I first explored the measurement of cognitive function, with
respect to the effect of selection by health and survival on the
estimation of cognitive function and decline in epidemiological
studies. Chapter 2 showed that selection for health and survival
resulted in better age-specific cognitive test scores and less
cognitive decline, and that this selection affects both
cross-sectional and longitudinal studies. Subsequently, statistical
methods handling multiple and missing data did not seem to fully
correct for this bias. These results indicated that assessments of
cognitive function in the elderly must take particular care in
considering possible biases from health selection.
In chapter 3,
the results from studies on the relation between glucose metabolism
and cognitive function were presented. First, I investigated the
influence of fasting glucose levels and insulin resistance on
cognitive function in non-diabetic elderly from two independent
prospective studies: the PROSPER study and the Rotterdam Study
(chapter 3.1). Elevated fasting glucose levels and insulin
resistance were not associated with worse cognitive function or a
higher rate of cognitive decline in elderly subjects without a
history of diabetes. These data suggest either a threshold for
effects of dysglycaemia on cognitive function, or that factors
other than hyperglycaemia-related pathways impair cognition in
individuals with frank diabetes. In chapter 3.2, I described the
relation between genetically reduced insulin/IGF-1 signaling (IIS)
and cognitive function and decline, in participants from the Leiden
85-plus Study, aged 85 years and over. In addition to old age
survival, gene!
tically reduced IIS seemed to be beneficial for
cognitive function in women.
Chapter 4 described the relation
between vascular and inflammatory factors and cognitive function
and decline. In chapter 4.1, I evaluated the age-specificity of the
relation between blood pressure and cognitive function by examining
the relationship between baseline blood pressure and cognitive
function later in life across age groups. The data showed that high
blood pressure increased the risk of cognitive impairment up to 75
years, but was associated with better cognitive function
thereafter. This could mean that age-specific guidelines for blood
pressure management are needed, as the current directive that
’lower is better’ may not apply to blood pressure levels in the
very old. In chapter 4.2, I investigated the relation between
inflammatory markers and cognitive impairment in the early stages
of the development of dementia, and found that systemic markers of
inflammation were only moderately associated with cognitive
function and decline. Chapter 4.3 described the !
relation between
serum uric acid, a cardiovascular risk factor as well as a major
natural antioxidant, and the risk of dementia and cognitive
impairment. The results showed that notwithstanding the associated
increased risk of cardiovascular disease, higher levels of uric
acid were associated with a decreased risk of dementia and better
cognitive function later in life.
Chapter 5 showed the
investigation of potential preclinical biomarkers of dementia. In
chapter 5.1, I described the relation between plasma Aβ1-42 and
Aβ1-40 levels and the risk of dementia and evaluated the influence
of time-to-event on this relation. Additionally, I studied the
relation between plasma Aβ1-42 and Aβ1-40 levels and the risk of
cognitive decline in those who remained free of dementia. It seemed
that the risk of dementia associated with a lower plasma Aβ1-42 /
Aβ1-40 ratio was particularly increased within the first years
after the biomarker assessment. There was no association between
the plasma Aβ1-42 / Aβ1-40 ratio and the risk of cognitive
decline in those who did not develop dementia. This indicates that
assessment of the plasma Aβ1-42 / Aβ1-40 ratio alone is not
sensitive enough to identify people at risk for cognitive decline
at large.
In chapter 6, I evaluated the several methodological
issues that were related to the work described in this thesis and
discussed some suggestions for further research.
- Source
- Euser, S.M. (2008), Doctoral Thesis, Erasmus University
Rotterdam
- Language
- nl
- Type
- Doctoral thesis
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