Epidemiology of multimorbidity and polypharmacy in ageing: a complementary analysis of mental and brain health in three datasets
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Date
27/06/2020Author
Stirland, Lucy Elizabeth
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Abstract
Multimorbidity, the co-existence of two or more chronic conditions, is common and
increasing in prevalence. It is associated with poor outcomes for patients and
increased costs for healthcare providers, so is attracting attention both from
policymakers and researchers. The use of multiple simultaneous medications
(polypharmacy) frequently co-occurs with multimorbidity. Multimorbidity including
physical and mental illnesses has been recognised as important and under-studied.
It not only poses challenges for patient management but also provides opportunities
for interventions which could prevent overall clinical decline.
This thesis separates physical and mental illnesses to explore associations between
multimorbidity and polypharmacy with mental health outcomes and brain health
biomarkers in ageing cohorts.
Although there are standard published definitions of multimorbidity, understanding the
concept is difficult due to the numerous ways to measure it. This thesis opens with a
systematic review of multimorbidity indices. Among 5 560 unique titles identified in a
literature search, 35 full-text papers were relevant, and are described and evaluated
in detail.
Data analysis took place in three datasets focused on ageing, with complementary
designs. These are the PREVENT Dementia and European Prevention of Alzheimer’s
Dementia (EPAD) study cohorts, and routinely collected data from the National Health
Service (NHS) Scotland’s Information Services Division (ISD).
In PREVENT Dementia, participants aged 40-59 years are deeply phenotyped,
allowing exploration of the epidemiological associations between increasing chronic
conditions and medication use with various clinical and biological outcomes. These
include self-reported depression, cognitive test results and markers of
neurodegeneration on magnetic resonance imaging (MRI). From regression analysis
of 210 participants’ data, each additional condition was associated with increased odds of self-reported depression (adjusted OR=1.41, 95% CI 1.11 to 1.80) and anxiety
disorder (OR=1.71, 95% CI 1.35 to 2.21). Increasing medication use was associated
with self-reported depression (adjusted OR per additional medication=1.36, 95% CI
1.07 to 1.73) but not anxiety disorder (OR=1.24, 95% CI 1.00 to 1.53). There were no
meaningful associations between multimorbidity or polypharmacy with MRI or
cognitive test outcomes.
The EPAD cohort permitted a more focused approach in people aged over 50 years,
specifically examining associations between increasing chronic conditions and
cerebrospinal fluid (CSF) amyloid-β. In 447 participants, each additional comorbid
condition carried a decreased likelihood of amyloid positivity (multiply-adjusted
OR=0.82, 95% CI 0.68 to 0.97). This informs the debate that amyloid may not play a
part in the pathway between multimorbidity and the development of dementia.
Analyses of NHS data used routinely collected information on prescriptions,
psychiatric hospital admissions and death certificate diagnoses from 1.23 million
people aged over 50 years in Scotland. Adjusted hazard ratios for each additional
drug were 1.03 (95% CI 1.03 to 1.04) for death with any psychiatric cause and 1.04
(95% CI 1.04 to 1.05) for admission to psychiatric hospital over 8.5 years of followup. In this and the analyses in PREVENT Dementia, the use of antidepressant or
psychotropic medication attenuated the associations.
The importance of patient and public involvement in research is also discussed,
including perspectives on this work from a Lay Contributor.
This thesis explores the measurement of multimorbidity in detail and provides further
evidence that physical multimorbidity and polypharmacy are associated with poor
mental health. However, the links with biological markers of brain disease such as
MRI findings and amyloid are less convincing. This leads to a discussion of possible
mechanisms, clinical implications, and proposed future work.