Mid-life hypertension and Alzheimer’s dementia: A systematic review and meta-analysis
Matthew J. Lennon1,2, Steve R. Makkar 1,2, John D. Crawford1,2, Perminder S. Sachdev1,2,3
1. School of Medicine, University of New South Wales, NSW
2. Centre for Healthy Brain Ageing, University of New South Wales, NSW
3. Department of Neuropsychiatry, Prince of Wales Hospital, NSW
Background
The lack of any current effective treatment means that efforts need to be focused on disease prevention, that is targeting these modifiable risk factors in the pre-disease stages. Hypertension is an established risk factor for stroke and vascular dementia but recent meta-analyses looking at the association between Alzheimer's disease (AD) and hypertension have found no significant association. These meta-analyses included a number of short term studies starting in late life which very likely obscured the real effect of mid-life hypertension. We examined the association of AD with mid-life hypertension, by including only studies with a sufficiently long follow up duration and by clearly defining the type of hypertension.
Methods
Relevant studies were found by searches of MEDLINE, EMBASE and PubMed. Study outcomes were grouped by measures of blood pressure and definition of hypertension (e.g. Systolic hypertension >140 mmHg or >160 mmHg, diastolic hypertension or blood pressure measured in 10 mm Hg increments). We assessed pooled effect size estimates using a random effects model and heterogeneity of pooled estimates was assessed by examining significance of the I2 statistic.
Results
Literature search found 3426 unique publications of which only 7 were eligible studies. There was a significant association between systolic hypertension (>160 mm Hg) and AD (HR 1.25, 95CI 1.06 – 1.47, p=0.0065). Similarly, for systolic hypertension >140 mm Hg there was a smaller but still significant association (HR 1.18, 95CI 1.02 – 1.35, p=0.021). For diastolic hypertension, all four studies found no significant associations between diastolic hypertension and AD, and these data could not be pooled due to heterogeneity in reporting.
Conclusions
Our study found that midlife stage 1 and stage 2 systolic hypertension is associated with increased risk of AD by 18 and 25 percent respectively, although no association was found for diastolic hypertension. If we are to address the growing epidemiological challenge posed to us by AD there needs to be an assertive control of systolic hypertension.