Orthostatic Hypotension and Cognitive Function in Individuals 85 Years of Age: A Longitudinal Cohort Study in Sweden

Orthostatic hypotension (OH) is more common in the elderly and associated with increased mortality. However, its implications for 85-year-olds are not known. In the prospective observational cohort study Elderly in Linköping Screening Assessment (ELSA 85), 496 individuals in Linköping, Sweden, were followed from age 85 years with cognitive assessments. Blood pressure (BP) was measured supine and after 1, 3, 5, and 10 minutes of standing. Participants with a BP fall of ≥20 mmHg systolic or ≥10 mmHg diastolic after 1 or 3 minutes were classified as classical continuous or classical transient OH depending on whether the BP fall was sustained or not, at subsequent measurements. Those with a BP fall of the same magnitude, but only after 5 or 10 minutes were classified as delayed OH. Of participants, 329 took part in BP measurements and were included. Of these, 156 (47.4%) had classical OH (113 [34.3%] continuous classical, 38 [11.6%] transient classical), and 15 (4.6%) had delayed OH. Cognitive assessments were not markedly different between groups. After 8.6 years, 195 (59.3%) of the participants had died, and delayed vs no OH was associated with twice the risk of all-cause mortality, HR 2.15 (95% CI 1.12-4.12). Transient classical OH was associated with reduced mortality, HR 0.58 (95% CI 0.33-0.99), but not after multiple adjustments, and continuous classical OH was not associated with mortality. OH may have different implications for morbidity and mortality in 85-year-olds compared with younger populations.

The EQ-5D questionnaire is comprised of 5 subitems of which 3 were used in this study: mobility, selfcare, and usual activities.The response options for mobility were "I have no problems in walking about", "I have some problems in walking about", and "I am confined to bed"; for self-care were "I have no problems with self-care", "I have some problems washing or dressing myself", and "I am unable to wash or dress myself"; and for usual activities were "I have no problems with performing my usual activities", "I have some problems with performing my usual activities", and "I am unable to perform my usual activities".
The Instrumental Activity Measure (IAM) questionnaire covered 8 activities: locomotion outdoors, preparing a simple meal, cooking, using public transport, small-scale shopping, large-scale shopping, cleaning, and laundry.The response options were "no difficulties", "some difficulties", "great difficulties, "too difficult", and "I have not tried/not applicable".The latter response option was treated as missing.
The Personal Activities of Daily Living (PADL) questionnaire covered 4 activities: bathing/showering, dressing and undressing, toileting, and eating.For each activity, participants were asked if they could manage it independently, and response options were "manages without help", "I need some help", and "I need much help".

Methods, statistical analyses
In multiple adjustments, Model 3, living in a nursing home was not included when analyzing living in a nursing home, presence of neurological disease or dementia was not included when analyzing presence of neurological disease or dementia, atrial fibrillation was not included when analyzing atrial fibrillation, supine BP was not included when analyzing elevated supine BP or abnormal pulse response, use of antidepressants were not included when analyzing use of antidepressants, use of sedatives were not included when analyzing use of sedatives, and polypharmacy was not included when analyzing polypharmacy.
Data missing completely at random or at a rate below 10% were managed by listwise deletion, data missing at random at a rate above 20% were managed by multivariate imputations by chained equations (R package "mice" version 3.16.0)with a setting of 20 imputations and 20 iterations [4].

Results, missingness
Standing BP measurements were not obtained from 3, 5, and 10 minutes and onwards for 3 (0.9%), 2 (0.6%), and 10 (3.0%) of the participants, respectively.Based on the preceding standing BP measurements, all of these were categorized as having classical OH, except for 5 of those with missing values at 10 minutes, which were classified as having no OH.Missing rate for all other variables at baseline was less than 10%, except for the Parallel Serial Mental Operations test for which the missing rate was 27.4%, and these were managed using listwise deletion.At follow-up, the missing rates amongst the 109 participants that had not been lost to follow-up were 20-30% for the Clock Drawing Task and Cube Copying Test, the Token Test short version, the Symbol Digit Modalities Test, the Rey-Complex Figure Test, the Victoria Stroop Tests, and the Trail Making Test A, and 43% for the Parallel Serial Mental Operations test.These were considered as missing at random and managed using multivariate imputations by chained equations.1. Blood pressure and pulse measurements in the supine position and after 1, 3, 5, and 10 minutes of standing up, respectively, in relation to orthostatic hypotension status at baseline, shown as the mean and 95% CI. 2 OH was categorized as isolated systolic OH if systolic standing BP dropped at least 20 mmHg at 1, 3, 5, and/or 10 minutes; isolated diastolic OH if diastolic standing BP dropped at least 10 mmHg at 1, 3, 5, and/or 10 minutes; and as combined systolic; and diastolic OH if both of these criteria were fulfilled (not necessarily at the same point in time).3 This was evaluated for each of 1, 3, 5, and 10 minutes of standing systolic BP, and if it dropped below 90 mmHg at any or several of these measurements, it was categorized as such.BP, blood pressure; OH, orthostatic hypotension.

Supplementary Table 2. The odds ratios, means and 95% CI for the baseline results in relation to orthostatic hypotension status after adjustments of sex (model 2).
No Includes 5 participants with classical OH that could not be classified as transient or continuous because of missing values at 5 and 10 minutes of standing up.