Mohammed T. Abou-Saleh

256 PRINCIPLES AND PRACTICE OF GERIATRIC PSYCHIATRYhave mixed pathologies 7,8 . Cerebrovascular diseases may increasethe possibility that individuals with AD lesions in their brains willexpress a dementia syndrome 9 , and ‘‘post-stroke dementia’’ isoften a mixture of the direct consequences of stroke, pre-existingAD pathology and the additive effects of these lesions andageing 10 . The coincidence of AD and VaD may even be the mostcommon form of dementia.REFERENCES1. Tatemichi TK, Desmond DW, Mayeux R et al. Dementia after stroke:baseline frequency, risks, and clinical features in a hospitalized cohort.Neurology 1992; 42: 1185–93.2. Fischer P, Gatterer G, Marterer A et al. Course characteristics in thedifferentiation of dementia of the Alzheimer type and multi-infarctdementia. Acta Psychiat Scand 1990; 81: 551–3.3. Skoog I. Guest editorial. Status of risk factors for vascular dementia.Neuroepidemiology 1998; 17: 2–9.4. Skoog I. Blood pressure and dementia. In Hansson L, BirkenhägerWH, eds, Handbook of Hypertension, vol 18: Assessment ofHypertensive Organ Damage. Elsevier Science: Amsterdam 1997:303–31.5. Román GC, Tatemichi TK, Erkinjuntti T et al. Vascular dementia:diagnostic criteria for research studies. Report of the NINDS–AIREN international workshop. Neurology 1993; 43: 250–60.6. De la Monte SM. Quantitation of cerebral atrophy in preclinical andend-stage Alzheimer’s disease. Annals of Neurology, 1989; 25: 450–9.7. Holmes C, Cairns N, Lantos P, Mann A. Validity of current clinicalcriteria for Alzheimer’s disease, vascular dementia and dementia withLewy bodies. Br J Psychiat 1999; 174: 45–508. Lim A, Tsuang D, Kukull W. Clinico-neuropathological correlationof Alzheimer’s disease in a community-based case series. J Am GeriatSoc, 1999; 47: 564–9.9. Snowdon DA, Greiner LH, Mortimer JA et al. Brain infarction andthe clinical expression of Alzheimer disease. The nun study. JAmMed Assoc, 1997; 277: 813–17.10. Pasquier F, Leys D. Why are stroke patients prone to developdementia? J Neurol, 1997; 244: 135–42.The Role of Blood Pressure in DementiaIngmar SkoogSahlgrenska University Hospital, Go¨teborg, SwedenThe association between hypertension and dementia/cognitiveimpairment has received increased interest recently. Both theHonolulu–Asia Aging Study 1 and the Framingham Study 2 reportthat low performance in psychometric tests in the population isrelated to a higher systolic blood pressure decades before themeasurement of cognitive function. We found that systolic anddiastolic blood pressure was increased 10–15 years before theonset of both Alzheimer’s disease (AD) and vascular dementia, aswell as in individuals with white matter lesions 3 . Furthermore,middle-aged non-demented hypertensive individuals have anincreased amount of senile plaques and neurofibrillary tangles,the histopathological hallmarks of AD, in their brains 4 . In crosssectionalstudies, blood pressure is generally negatively correlatedto cognitive performance before age 75, while there is a positivecorrelation above that age. Furthermore, elderly subjects withalready manifested AD and vascular dementia have lower bloodpressure than the non-demented 5 . Thus, although previously highblood pressure seems to be related to cognitive decline anddementia, low blood pressure is often related to alreadymanifested dementia.Several mechanisms may be involved in the association betweenhypertension and dementia/cognitive decline. First, the risk ofstroke increases with inceasing blood pressure, and stroke is astrong risk factor for dementia. It is thus reasonable to believethat high blood pressure is a risk factor for stroke-relateddementia. Hypertension is also a risk factor for ischaemicsubcortical white-matter lesions (WMLs) 6 , which are oftenfound in subjects with late-onset AD and multi-infarct dementia(MID). The main hypothesis regarding the cause of WMLs is thatlongstanding hypertension causes lipohyalinosis and thickening ofthe vessel walls, with narrowing of the lumen of the smallperforating arteries and arterioles that nourish the deep whitematter. Episodes of hypotension may lead to hypoperfusion andhypoxia–ischaemia, leading to loss of myelin in the white matter.It has been suggested that the arterial changes are due to exposureof vessel walls to increased pressure over time. The greater thepressure and/or lifespan, the more likely are these changes to bepresent.A third explanation is that chronic hypertension may lead to adysfunction of the the blood–brain barrier (BBB), with increasedpermeability of the endothelial cell layer and extravasation ofserum proteins 7 . The CSF:serum albumin ratio is a generallyaccepted method of assessing the BBB function in living subjects.We recently found that AD, MID and severe forms of WMLswere all associated with an increased CSF:serum albumin ratio ina population-based study of 85 year-olds 8 . A breakdown in theBBB may cause brain lesions by cerebral oedema, activation ofastrocytes, or destructive enzymes or other poisons that passthrough the damaged vessel walls. Fourth, the renin–angiotensinsystem is an example of a system that may be involved in thepathogenesis of both hypertension and dementia 9 . Its effectorpeptide, angiotensin II, has several blood pressure increasingeffects, promotes hyperplasia and hypertrophy in vascular smoothmuscle cells, and affects memory and behaviour. Fifth, psychologicalstress has been suggested to be a risk factor for bothhypertension and dementia 10 .The association between low blood pressure and dementia hasseveral explanations. First, systemic hypotension associated withreduced cerebral blood flow may give rise to a spectrum ofischaemic neuronal lesions in the brain and may also lead toischaemic loss of myelin in the white matter. Second, several of theblood pressure-regulating areas in the central nervous system areaffected in dementia disorders. Therefore, dementia disorders andtheir associated brain changes may per se influence the bloodpressure 5 . A correlation between the number of C-1 neurons in themedulla oblongata and blood pressure has been reported in AD 11 .Blood pressure decline during the course of AD, and low bloodpressure was related to cerebral atrophy in non-demented 85 yearolds5 . It thus seems likely that low blood pressure in dementedindividuals is secondary to the brain lesions. If cerebral disorder