Orthostatic Hypotension: An Important Risk Factor for Clinical Progression to Mild Cognitive Impairment or Dementia. The Amsterdam Dementia Cohort

Background: Orthostatic hypotension (OH) has been cross-sectionally and longitudinally related to dementia in the general population. Whether OH contributes to clinical progression to mild cognitive impairment (MCI) or dementia is less certain. Also, differences in risk of progression between patients with early OH (EOH) versus delayed and/or prolonged OH (DPOH) are unclear. Objective: Assess the prevalence of EOH and DPOH, investigate the longitudinal association between EOH and DPOH and either incident MCI or dementia. Methods: 1,882 patients from the Amsterdam Dementia Cohort [64 +/- 8 years; 43% female; n = 500 with subjective cognitive decline (SCD), n = 341 MCI, n = 758 Alzheimer's disease (AD), n = 49 vascular dementia (VaD), n = 146 frontotemporal dementia (FTD), n = 88 Lewy body dementia (DLB)]. Definition OH: systolic blood pressure (BP) drop >= 20 mmHg and/or a diastolic BP drop >= 10 mmHg at 1 and/or 3 minutes after standing. EOH: OH only at 1 minute, DPOH: OH at (1 and) 3 minutes. Results: Prevalence OH: 19% SCD, 28% MCI, 41% dementia. Compared to SCD, odds of having OH were highest in patients with VaD and DLB; ORs (95%CI) were 2.6 (1.4-4.7) and 5.1 (3.1-8.4), respectively. After a mean (SD) follow- up of 2.2 (1.4) years, 105 (22%) of SCD or MCI patients showed clinical progression. Compared to patients without OH, those with DPOH had an increased risk of progression; hazard ratio (95% CI) was 1.7 (1.1-2.7), and those with EOH did not; 0.8 (0.3-1.9). Conclusion: Compared to SCD, prevalence of OH was higher in MCI and highest in dementia, particularly in VaD and DLB. DPOH, more likely associated with autonomic dysfunction, is a risk factor for incident MCI or dementia.