The relation of blood pressure to dementia in the elderly : a community-based longitudinal study

This doctoral thesis concerns a community-based, prospective study aimed at investigating the complex relationship between blood pressure (BP) and risk of dementia in a dementia-free cohort (n = 1301) aged >=75 years in Stockholm, Sweden. After baseline survey (1987-1989), the cohort was followed for over 6 years, during which 2 waves of clinical examinations (1991-1993 & 1994-1996) for dementia and Alzheimer's disease (AD) (DSM-III-R diagnostic criteria) were performed. Data were analyzed with Cox proportional hazards models. The major findings from the five research papers included in this thesis are summarized below.

In Study I, the relationship between BP and dementia was examined. Subjects with high systolic BP (>1 80 vs. 141-180 mm Hg) or low diastolic BP (<65 vs. 66-90 mm Hg) had an increased risk for AD and dementia. The association between low diastolic BP and high risk of dementia was particularly pronounced among the users of antihypertensive drugs. Systolic BP <140 mm Hg and diastolic BP >90 mm Hg were not associated with the risk of AD and dementia.

In Study II, we examined the relationship between pulse pressure and risk of dementia and AD. Compared with median tertile of pulse pressure (70-84 mm Hg), lower pulse pressure (<70 mm Hg) and higher pulse pressure (>=85 mm Hg) were both found to be significantly associated with an increased risk of AD and dementia. The U-shaped relationship between pulse pressure and risk of dementia was present mainly among women.

In Study III, the combined effects of APOE epsilon-4 allele, high systolic BP, low diastolic BP, and use of antihypertensive drugs on the risk of AD were assessed. APOE epsilon-4 in combination with either high systolic BP (>=140 mm Hg) or low diastolic BP (<70 mm Hg) greatly increased the risk of AD. Antihypertensive drug use significantly reduced AD risk regardless of APOE epsilon-4 status, and counteracted the combined risk effect of APOE epsilon-4 allele with high systolic BP on the risk of AD.

In Study IV, we found that systolic and diastolic levels greatly decreased over 3 years before a dementia diagnosis and continued to decline thereafter. Diastolic BP decline was not significantly predictive of dementia, whereas a greater decline in systolic BP (>=15 mm Hg vs. no decline) was statistically associated with an elevated risk for AD and dementia among persons with systolic pressure level <160 mm Hg or those with vascular disease at baseline.

Finally, Study V indicated that heart failure was associated with relative risks of 1.7 (95% CI, 1.22.4) for AD and 1.5 (95% CI, 1. 1-2.0) for dementia. Use of antihypertensive medications counteracted the risk effect of heart failure on AD and dementia. Heart failure and low diastolic BP (<70 mm Hg) showed an additive effect on the risk of AD and dementia.

In summary, low diastolic and high systolic pressure, and both low and high pulse pressure are determinants of AD and dementia in very old adults. BP levels were affected by the dementing process. Chronic heart failure may increase the risk of dementia. Use of antihypertensive drugs reduces the risk of AD and dementia, diminishes the risk effects exerted by APOE epsilon-4 allele and heart failure on AD and dementia, and modifies the joint effects of high systolic BP and the APOE epsilon-4 allele on the risk of AD. These findings indicate that the atherosclerotic process and cerebral hypoperfusion may be involved in the pathogenesis and clinical expression of AD and dementia.

List of scientific papers

I. Qiu C, von Strauss E, Fastbom J, Winblad B, Fratiglioni L (2003). "Low blood pressure and risk of dementia in the Kungsholmen project: a 6-year follow-up study. " Arch Neurol 60(2): 223-8
https://pubmed.ncbi.nlm.nih.gov/12580707

II. Qiu C, Winblad B, Viitanen M, Fratiglioni L (2003). "Pulse pressure and risk of Alzheimer disease in persons aged 75 years and older: a community-based, longitudinal study. " Stroke 34(3): 594-9. Epub 2003 Feb 27
https://pubmed.ncbi.nlm.nih.gov/12624277

III. Qiu C, Winblad B, Fastbom J, Fratiglioni L (2003). "Combined effects of APOE genotype, blood pressure, and antihypertensive drug use on incident AD. " Neurology 61(5): 655-60
https://pubmed.ncbi.nlm.nih.gov/12963757

IV. Qiu C, von Strauss E, Winblad B, Fratiglioni L (2004). "Decline in blood pressure over time and risk of dementia: a population-based longitudinal study." (Manuscript)

V. Qiu C, Winblad B, Marengoni A, Fastbom J, Fratiglioni L (2004). "Heart failure and risk of dementia in the Kungsholmen project: a six-year follow-up study." (Manuscript)