Associations Between Multimorbidity and Cerebrospinal Fluid Amyloid: A Cross-Sectional Analysis of the European Prevention of Alzheimer’s Dementia (EPAD) V500.0 Cohort

Article type: Research Article

Authors: Stirland, Lucy E.^{a; b; *} | Russ, Tom C.^{a; b; c; d} | Ritchie, Craig W.^{a; b} | Muniz-Terrera, Graciela^{a; b} | EPAD Consortium

Affiliations: [a] Edinburgh Dementia Prevention, Centre for Clinical Brain Sciences, University of Edinburgh, Kennedy Tower, Royal Edinburgh Hospital, Morningside Terrace, Edinburgh, UK | [b] Division of Psychiatry, Centre for Clinical Brain Sciences, University of Edinburgh, Kennedy Tower, Royal Edinburgh Hospital, Morningside Terrace, Edinburgh, UK | [c] Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, UK | [d] NHS Lothian, Royal Edinburgh Hospital, Morningside Terrace, Edinburgh, UK

Correspondence: [*] Correspondence to: Lucy E. Stirland, Edinburgh Dementia Prevention, Centre for Clinical Brain Sciences, University of Edinburgh, Kennedy Tower, Royal Edinburgh Hospital, Morningside Terrace, Edinburgh, EH10 5HF, UK. Tel.: +44 131 537 6508; E-mail: l.stirland@ed.ac.uk.

Abstract: Background:Multimorbidity (the co-occurrence of multiple chronic conditions) is increasingly common, especially among people with dementia. Few neuroimaging studies have explored amyloid biomarkers in people with multimorbidity. Objective:We aimed to conduct the first study of the association between multimorbidity and cerebrospinal fluid amyloid-β42 (CSF Aβ). Method:The European Prevention of Alzheimer’s Dementia (EPAD) Longitudinal Cohort Study V500.0 dataset includes volunteers aged ≥50 years from 12 sites. Participants undergo detailed phenotyping, including CSF measures and a self-reported medical history. Using logistic and linear regression analyses, we explored the association between multimorbidity and continuous chronic condition count with CSF Aβ positivity (Aβ42 <1000pg/ml) and continuous CSF Aβ concentration. All models were adjusted for age, sex, APOE status, education, and family history of dementia. Results:Among 447 eligible participants without dementia, the mean (SD) age was 66.6 (6.6) years, 234 (52.3%) were women, and 157 (35.1%) were amyloid positive. With chronic conditions regarded as pseudo-continuous, each additional condition carried a decreased likelihood of amyloid positivity (OR = 0.82, 95% CI: 0.68–0.97; p = 0.026). With CSF Aβ as a continuous variable, each additional condition was associated with an increase of 54.2 pg/ml (95% CI: 9.9–98.5, p = 0.017). Having ≥2 conditions was inversely associated with amyloid positivity (OR 0.59, 95% CI: 0.37–0.95, p = 0.030) compared to one or none. Conclusion:Our findings suggest that the established association between multimorbidity and dementia may be due to a pathway other than amyloid. However, this cross-sectional study does not allow us to make causal inferences. Longitudinal work is required to confirm the inverse association found.

Keywords: Alzheimer’s disease, amyloid, dementia, multimorbidity

DOI: 10.3233/JAD-190222

Journal: Journal of Alzheimer's Disease, vol. 71, no. 2, pp. 703-711, 2019