Combined effects of APOE genotype, blood pressure, and antihypertensive drug use on incident AD
Qiu C, Winblad B, Fastbom J and Fratoglioni L;
Commented by , 27 Oct 2003
Aim of the study
To study the hypothesis that APOE allele may interact with blood pressure and modify the incidence of Alzheimer’s disease (AD), and that antihypertensive treatment could modify this effect.
Method
A cohort of 966 cognitively normal persons aged 75 years and older, living in the community in Stockholm, was followed over time, as the Kungsholmen Project. AD was diagnosed using DSM-III-R criteria in a three-step diagnostic process during follow-up visits. Cox proportional hazard models were used with adjustment for several potential confounders such as age, gender, education, vascular disease and baseline MMSE scores.
Results
During a 6-year follow-up, AD was diagnosed in 204 persons. APOE4 allele, high systolic blood pressure (> 140 mm Hg) and low diastolic blood pressure (<70 mm Hg) were associated with an increased risk of AD, but antihypertensive therapy reduced AD risk regardless of APOE status, and thus counteracted the risk associated with APOE4 and high systolic blood pressure.
The limitation of these results is that the strength of the association between systolic hypertension, APOE4 and AD may be age dependent, and these findings cannot be applied directly to younger persons.
Discussion
The evidence provided in this study offers some reassurance to persons carrying one or two copies of the APOE4 allele: they can reduce their risk of AD by control of systolic hypertension. These data are consistent with randomized clinical trials such as Syst-Eur where a calcium channel blocker reduced the incidence of dementia by 50%.
The links between AD and vascular risk factors have been strengthened by epidemiological studies such as the one described in this publication, and the pathophysiology of the ‘vascular burden of the brain’ has been discussed in a meeting sponsored by the International Psychogeriatric Association that took place in Madrid in November 2001, summarized as proceedings in International Psychogeriatrics, vol 15, Suppl 1, 2003.
Furthermore the new VASCOG association has been created to foster interaction between investigators and clinicians interested in AD and vascular cognitive impairment, with its first meeting in Göteborg in August 2003, to be followed by Florence in 2005.