Effects of blood pressure on neuropsychological functioning in Alzheimer's disease

Archives of Clinical Neuropsychology 18 (2003) 19–32 Effects of blood pressure on neuropsychological functioning in Alzheimer’s disease Robert N. Davis a,∗ , Paul J. Massman a,b , Rachelle S. Doody b a b Department of Psychology, University of Houston, Houston, TX 77204-5022, USA Department of Neurology, Baylor College of Medicine, 6550 Fannin, Suite 1801, Houston, TX 77030, USA Accepted 14 August 2001 Abstract Blood pressure is often lower among patients with Alzheimer’s disease (AD) compared to nondemented older adults. Lower blood pressure in AD correlates with reduced cerebral blood flow and cortical atrophy, but its effect on neuropsychological functioning is unclear. We assessed the effects of blood pressure on tests of dementia severity, attention, memory, language, verbal and nonverbal reasoning, motor/psychomotor functioning, and activities of daily living (ADL) among probable AD patients (n = 609). As hypothesized, lower systolic blood pressure (SBP) predicted reduced attention (Digits Forward and Backward), memory (Visual Reproduction I), and ADLs. Unexpectedly, lower pulse pressure (SBP–DBP) predicted greater dementia severity (Mini-Mental State Examination, MMSE), attention (Digits Forward and Backward), memory (Logical Memory I and Visual Reproduction I), and ADLs. These findings may reflect a tendency for less severely demented patients to exhibit normal age-related changes in blood pressure, whereas abnormal patterns may develop with increased dementia severity. © 2002 National Academy of Neuropsychology. Published by Elsevier Science Ltd. All rights reserved. Keywords: Alzheimer’s disease; Dementia; Blood pressure; Activities of daily living; Memory; Attention 1. Introduction Patients with probable Alzheimer’s disease (AD) tend to have lower blood pressure than normal, nondemented older adults (Guo, Viitanen, Fratglioni, & Winblad, 1997). Typical blood pressure findings among normal older adults are as follows. In industrialized societies, mean systolic blood pressure (SBP) increases with age until approximately 75 years, then tends to ∗ Corresponding author. Tel.: +1-713-743-8500; fax: +1-713-743-8588. E-mail address: (R.N. Davis). 0887-6177/02/$ – see front matter © 2002 National Academy of Neuropsychology. PII: S 0 8 8 7 - 6 1 7 7 ( 0 1 ) 0 0 1 7 8 - 0 20 R.N. Davis et al. / Archives of Clinical Neuropsychology 18 (2003) 19–32 decrease, whereas mean diastolic blood pressure (DBP) increases with age until approximately 55–65 years, then decreases slightly (Byyny, 1995; Skoog, Andreasson, Landahl, & Lernfelt, 1998). In addition, hypertension, which epitomizes high blood pressure, is very common among normal older adults. Hypertension is defined as SBP of 140 mmHg or greater, or DBP of 90 mmHg or greater (Joint National Committee, 1997; WHO-ISH, 1999). The National Health and Nutrition Examination Survey (NHANES III) found that 60% of whites, 71% of African Americans, and 61% of Hispanic Americans aged 60 and older had current hypertension and/or were taking antihypertensive medication (Burt et al., 1995). 2. Blood pressure is reduced in AD Blood pressure among patients with probable AD deviates markedly from blood pressure among normal older adults. First, the prevalence of hypertension is significantly lower in AD than among normal older adults. In a sample of 967 probable AD patients, only 25% had a history of hypertension (Corey-Bloom, Galasko, Hofstetter, Jackson, & Thal, 1993). Another study found a hypertension prevalence rate of 27.3% in a sample of 165 AD patients, compared to 42.8% for nondemented controls (Thorpe, Widman, Wallin, Beiswanger, & Blumenthal, 1994). Second, when blood pressure levels are evaluated as continuous variables, numerous cross-sectional comparisons have consistently found lower blood pressure among AD patients compared to normal older adults (Elmstahl et al., 1992; Guo, Viitanen, Fratglioni, & Winblad, 1996; Landin, Blennow, Wallin, & Gottfries, 1993; Siennicki-Lantz, Lilja, Rosen, & Elmstahl, 1998; Skoog et al., 1998; Wang et al., 1994). Hypertension also appears to be less prevalent among AD patients compared to patients with other types of dementia. AD patients had a significantly lower prevalence of hypertension (24%) compared to patients with multi-infarct dementia (81%) and major depression (40%) (Tresch, Folstein, Rabins, & Hazzard, 1985). Patients with probable AD had a significantly lower prevalence of hypertension (25%) compared to patients with mixed dementia (49%) (Corey-Bloom et al., 1993). An epidemiological study of African American women found that AD patients had a significantly lower prevalence of hypertension compared to patients with multi-infarct dementia, despite the higher overall prevalence of hypertension among African Americans (Harris et al., 1995). Reduced blood pressure in AD may be important in light of the relationship between blood pressure and neuropsychological functioning, an issue to which we now turn. 3. Lower blood pressure predicts reduced neuropsychological functioning A longitudinal study of 304 initially nondemented older adults aged 75–96 years found that people with SBP ≤ 140 mmHg had a significantly higher risk of developing AD at follow-up compared to people with SBP between 141 and 179 mmHg (Guo, Viitanen, Winblad, & Fratglioni, 1999). In addition, significantly more people with SBP ≤ 140 mmHg had MiniMental State Examination (MMSE; Folstein, Folstein, & McHugh, 1975) scores <24 at baseline, compared to people with SBP between 141 and 179 mmHg. DBP was not associated R.N. Davis et al. / Archives of Clinical Neuropsychology 18 (2003) 19–32 21 with dementia in this sample. These results are consistent with other studies that have found relationships between low blood pressure and low MMSE scores (Guo, Fratglioni, Winblad, & Viitanen, 1997; Guo, Viitanen, & Winblad, 1997). For example, low SBP (130) and DBP (70) were related to MMSE scores <24, as well as reduced activities of daily living (ADL; Lawton & Brody, 1969) in a very old sample (mean age = 85 years) (Guo, Viitanen, & Winblad, 1997). Another study found that SBP and DBP were positively associated with follow-up MMSE scores, and individuals at highest risk for having MMSE scores <24 were those with SBP <130 mmHg, after controlling for age, sex, education, antihypertensive medication usage, heart disease, and strokes (Guo, Fratglioni, et al., 1997). These researchers concluded that a certain blood pressure level, SBP of at least 130 mmHg, appeared to be important for maintenance of cognitive functioning among very old adults. 4. Lower blood pressure is associated with AD Lower blood pressure appears to be associated not only with reduced neuropsychological functioning among normal older adults, but also the development of AD. In a recent longitudinal study, individuals who developed AD at age 79–85 exhibited a greater decrease in both SBP and DBP from age 70 to 79–85, compared to patients who were (...truncated)