Blood Pressure Circadian Variation, Cognition and Brain Imaging in 90+ Year-Olds

Natalie Bryant2, Maria M. Corrada1,2,3, Dana E. Greenia2, Evan Fletcher4, Baljeet Singh4, Claudia H. Kawas1,2,6 and Mark J. Fisher1
1Department of Neurology, School of Medicine, University of California, Irvine, Irvine, CA, United States
2Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, United States
3Department of Epidemiology, School of Medicine, University of California, Irvine, Irvine, CA, United States
4Department of Neurology, Center for Neuroscience, University of California, Davis, Davis, CA, United States
5Department of Radiological Sciences, School of Medicince, University of California, Irvine, Irvine, CA, United States
6Department of Neurobiology & Behavior, School of Biological Sciences, University of California, Irvine, Irvine, CA, United States
Purpose: To analyze the relationship between blood pressure (BP) variables, including circadian pattern, and cognition in 90+ year-olds.
Methods: Twenty-four hour ambulatory BP monitoring was completed on 121 participants drawn from a longitudinal study of aging and dementia in the oldest-old. Various measures of BP and its variability, including nocturnal dipping, were calculated. Each person was given both a neuropsychological test battery covering different cognitive domains and a neurological examination to determine cognitive status. Seventy-one participants had a brain magnetic resonance imaging (MRI) scan.
Results: Participants ranged in age from 90 to 102 years (mean = 93), about two-thirds were female, and nearly 80% had at least some college education. Mean nocturnal dips differed significantly between cognitively normal (n = 97) and impaired individuals (n = 24), with cognitively normal participants having on average greater nocturnal dips [6.6% vs. 1.3%, p = 0.006 for systolic BP (SBP); 11% vs. 4.4%, p = 0.002 for diastolic BP (DBP)]. Nocturnal dips were also related to performance on select cognitive test scores (especially those related to language, recent memory and visual-spatial ability), with individuals who performed below previously established median norms having significantly smaller nocturnal dips (both SBP and DBP) than those above the median. DBP reverse dippers had larger mean white matter hyperintensities (WMH as percent of total brain volume; 1.7% vs. 1.2%, 1.1% and 1.0% in extreme dippers, dippers, non-dippers) and a greater proportion had lobar cerebral microbleeds (CMBs; 44% vs. 0%, 7%, 16%, p < 0.05). Impaired participants had higher mean WMH than those with normal cognition (1.6% vs. 1.0% p = 0.03) and more tended to have CMB (31% vs. 20%, p = n.s.).Conclusion: These findings suggest that cognitive dysfunction is associated with dysregulation in the normal circadian BP pattern. Further study is warranted of the potential role of WHM and CMB as mediators of this association.IntroductionSeveral studies have found that blood pressure (BP) levels and other BP-related features such as variability, daytime and nighttime measures, and nocturnal dipping are associated with mortality, cardiovascular events, cerebrovascular disease, and subclinical damage to the heart, kidney and vessels (Boggia et al., 2007; Sörös et al., 2013; Diaz et al., 2014; Douma and Gumz, 2018). Although studies show that high BP in middle-age and late-life is associated with increased risk of cognitive decline and dementia (Launer et al., 2000; Kivipelto et al., 2001; Yamada et al., 2003; Whitmer et al., 2005; Arvanitakis et al., 2018), other work suggests that developing hypertension at older ages may protect against dementia (Corrada et al., 2017).Twenty-four hour ambulatory BP monitoring (ABPM) offers greater precision in estimating average BP than one-time readings and provides information on variability and circadian pattern of BP (O’Brien et al., 2013). While several studies have analyzed the association of BP variability and cognition in the elderly (van Boxtel et al., 1998, 2006; Kanemaru et al., 2001; Axelsson et al., 2008; Nagai et al., 2008; Guo et al., 2010; Conway et al., 2015), none, to our knowledge, have investigated this in the oldest-old (aged 90+ years). Considering the aging of the population with an increasing proportion of those aged 90+ (United Nations Department of Economic and Social Affairs Population Division, 2017) and the increasing risk of cognitive decline and dementia with age (Corrada et al., 2010), elucidating associations with cognitive function, especially of variables which are modifiable, remains vital. Therefore, using data from 24-h ABPM of 90+ year-olds, we analyzed the relationships between various BP measurements, their variability, and circadian pattern of BP and cognition with the aim of finding the variable most closely associated with cognitive function, hypothesizing that BP circadian variation impacts cognitive function.Materials and MethodsParticipantsStudy subjects were participants in The 90+ Study, a study of aging and dementia in individuals aged 90 years and older from the Laguna Woods Village (California) retirement community and its surroundings (Paganini-Hill et al., 2016). Subjects are seen in-person and longitudinally followed every 6 months. At each visit, their medical history is updated and they are given a neuropsychological test battery and a neurological examination as previously described (Whittle et al., 2007). Data from the visit closest in date to the date of ABPM were selected. The study was approved by the Institutional Review Board of the University of California Irvine and 149 participants agreed to and gave written informed consent for 24-h ABPM.Ambulatory Blood Pressure MonitoringSubjects underwent ABPM with a fully automatic device (Sun Tech—Oscar 2 with AccuWi n 3.4.4.0 software). The instrument was worn 24-h (during daytime and sleep) with sampling every 1 h. Systolic BP (SBP) readings greater than 260 mmHg or lower than 70 mmHg as well as diastolic BP (DBP) readings greater than 150 mmHg or lower than 40 mmHg were discarded. Participants were told to follow their normal daily activities during measurements. Daytime measures were considered those between 07:00 and 21:59 and nighttime as those between 22:00 and 06:59.We represented BP by several indices. Separately for 24-h, daytime and nighttime and for SBP and DBP, we calculated mean, minimum, maximum, standard deviation (SD), coefficient of variation (CV), average real variability (ARV), proportion of high values (SBP ≥140 mmHg, DBP ≥90 mmHg), and proportion of low values (SBP

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