Effects of Antihypertensive Treatment and Anticholinergics on Cognition in People with Vascular Dementia, Mixed Dementia and Alzheimers Disease A longitudinal case register study

Background: Approximately 850,000 people live with dementia in the UK. Vascular dementia (VaD) accounts for over 20% of dementia cases and has no licensed treatment available. Hypertension is the most prevalent comorbidity in people with dementia and is associated with cognitive decline. Although, antihypertensives have been investigated as potential therapeutics for dementia the evidence remains inconclusive. Anticholinergic medications are prescribed for a range of conditions and have been associated with cognitive decline. Given the modifiable nature of hypertension and prescribing practices these may present as potential pathways for dementia treatment or disease management. Aims/Objectives: The primary aims of this study were to investigate the effects of antihypertensive treatment intensity and exposure to anticholinergic medication on cognitive decline in people with VaD. Methods: Two scoping reviews were conducted to examine literature reporting the effects of antihypertensive treatment and anticholinergic burden on cognition in older people. A longitudinal, retrospective study using anonymised case register data on 6,244 people with dementia; VaD, Mixed Dementia (MXD) and Alzheimer’s disease (AD). A multi-level mixed effects model was used to examine treatment effects on change in MMSE score over time. Results: Scoping review findings suggests that antihypertensive treatment is not detrimental to cognition and intensive blood pressure control may have a protective effect. In the current study participants with AD prescribed ≥2 antihypertensives had significantly slower rates of cognitive decline versus those with untreated hypertension (2 antihypertensives MMSE = 0.21 95%CI 0.10 to 0.33, ≥3 antihypertensives MMSE = 0.19, 95%CI 0.00 – 0.37, p=0.002). Anticholinergic use was associated with faster cognitive decline in people with AD (-0.23 95%CI -0.32 to -0.14, p=0.000) and MXD (-0.22 95%CI -0.37 to -0.07, p=0.004). Supporting review findings which indicate a significant association between negative cognitive outcomes and anticholinergic exposure. Conclusions: Study findings suggest that intensive hypertension treatment and the reduction or deprescribing of anticholinergics may hold therapeutic potential. In AD, higher hypertension treatment intensity had a protective effect and exposure to anticholinergic medication in AD and MXD had a detrimental effect on cognition. Findings support the cholinergic hypothesis of AD and suggest treatment effects may differ according to pathology. Further research to help define these effects could lead to the development of more tailored treatment regimes.