Relationships between alcohol use and dementia: protocol for an observational study in the UK Clinical Practice Research Datalink

Preprint

Introduction: Alcohol consumption is an increasingly recognised modifiable risk factor for dementia, yet whether it has differential impacts on dementia subtypes and its role in disease progression remains unclear. This study aims to: 1) quantify the association between alcohol intake and incidence of dementia subtypes, and 2) examine whether individuals who drink heavily and develop dementia referred to herein as 'alcohol-related' - have poorer post-diagnosis outcomes compared to other dementia cases. Clarifying these relationships will determine whether alcohol selectively increases risk for specific dementia phenotypes or broadly heightens neurodegenerative vulnerability, with implications for prevention, clinical counselling, and therapeutic targeting.

Methods and analysis: This population-based cohort study will use linked UK electronic health records from Clinical Practice Research Datalink (CPRD), Hospital Episode Statistics (HES), and Office for National Statistics (ONS). Alcohol exposure will be defined through selfreported recorded weekly alcohol units and diagnostic codes for harmful or dependent alcohol use. Primary outcomes including incident all-cause and subtype-specific dementia (e.g., Alzheimer's, vascular, Lewy body, Parkinson's, frontotemporal) as well as secondary outcomes (i.e., mortality, care-home entry, and neuropsychiatric symptoms). Key covariates encompassing sociodemographic factors, smoking, and relevant comorbidities will be adjusted for. Multivariable Cox proportional hazards and Fine–Gray competing risk models will estimate associations with dementia incidence. Post-diagnosis prognosis will be compared for dementia in individuals with a history of heavy alcohol use (‘alcohol-related') and dementia in individuals with minimal alcohol exposure ('non-alcohol-related') cases using survival and logistic regression models. Multiple testing correction will be applied across dementia subtype comparisons. Alcohol exposure will be modelled continuously and nonlinearly using restricted cubic splines and categorically using binary indicators of harmful/dependent use. Missing covariate data will be assessed and addressed using appropriate methods, including multiple imputation and complete-case analysis. Data extraction and analysis are scheduled from 10/2025 to 10/2026.

Ethics and dissemination: Use of deidentified routine data will proceed under existing Research Ethics Committee and data governance approvals. Findings will be disseminated via open-access peer reviewed journals, academic conferences, and summaries targeted at patient, public and policy audiences. The results of this study will be reported according to the STROBE and RECORD guidelines.

Authors: Fatih, N; Bhaskaran, K; Kwok, ACH; Ebmeier, KP; Nichols, TE

• Publication status: Published
• Preprint server: medRxiv
• Publication date: 2025-10-10
• DOI: 10.1101/2025.10.09.25337654
• Language: English
• Keywords: alcohol-related dementia; Dementia; Primary care; Epidemiology; CPRD; protocol; neuropsychiatric symptoms; SBTMR