Hypertension affects millions of people worldwide and has been reported in patients with Alzheimer's disease (AD) some decades before the onset of the disease. High blood pressure has also been related to pathological manifestations of AD (Skoog and Gustafson, Reference Skoog and Gustafson2006). The hippocampus is a highly vulnerable and plastic structure that gets damaged by stimuli, e.g. hypoxia. In order to establish whether hypertension could damage the hippocampus and play a role in its atrophy we undertook a study to examine the relationship between hypertension and hippocampal atrophy in patients with AD.
A total of 32 patients fulfilling Neurological and Communicative Diseases and Stroke Alzheimer's Disease and Related Disorders (NINCDS-ARDA) Diagnostic Criteria for AD (M/F = 27/5, age range = 61–84 years, mean = 74.28 ± 5.8), with Mini-mental State Examination scores of 12.44 ± 6.6 (Stage I = 4, II = 22, III = 10) were included in the study. Mean duration of AD onset was 4.66 ± 2.6 years. Secondary causes of dementia were excluded by appropriate investigations. Delineation of entire hippocampal formation was done using the National Institutes of Health Image program (available at http://rsb.info.nih.gov/nih-image/).
Hypertension (defined as blood pressure equal or greater than 140/90) was present in 24 out of the 32 patients (75%) and atrophy of hippocampus was seen in 15 (46.8%) out of the 32 patients. In all except one, atrophy was associated with hypertension. Family history and history of head injury was present in two cases each (12.5%), and nine cases were diabetic (28.1%). Six patients (18.75%) had a history of coronary artery disease, and 15 (46.8%) had behavioral and psychological symptoms of dementia. Twenty patients were graduates, six (18.75%) illiterate and another six (18.75%) were postgraduates. There was no history of trauma or epileptic fits in any of them.
Hipppcampal atrophy is an important milestone in AD. Studies indicate that atrophy of this region correlates well with cognitive decline in AD patients (den Heijer et al., Reference den Heijer2005). We have previously reported hippocampal atrophy as a seizure predictor (Dhikav and Anand, Reference Dhikav and Anand2007), and a large study of over 500 subjects with no dementia showed that blood pressure and indicators of small-vessel disease in the brain may be associated with the atrophy of structures affected by AD pathology (Yavuz et al., 2006).
The study by Wiseman et al. (Reference Wiseman, Saxby, Burton, Barber, Ford and O'Brien2004) involving 103 hypertensive patients showed an adverse influence of hypertension on brain structures. Although patients in the present study had more factors that could potentially contribute to hippocampal atrophy, hypertension is the main one. The mechanism by which hypertension could be contributing towards atrophy of hippocampus is unknown, but we assume that hypo-perfusion and hypoxia of the hippocampus may be involved. If this assumption is correct, it would be interesting to investigate the extent to which hypertension contributes to atrophy, increases the likelihood of conversion from mild cognitive impairment to full-blown AD, or complicates the course of established AD. In line with this assumption, it is important that some observational studies have reported that use of antihypertensives decreases the risk of AD (Skoog and Gustafson, Reference Skoog and Gustafson2006). If hypertension is proven to be a significant predictor of hippocampal atrophy, then both primary and secondary prevention of AD could be achieved with anti-hypertentive drugs. A large comparative study involving AD patients with hypertension and hippocampal atrophy and those with no atrophy needs to be undertaken to establish this association further.
