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

Abstract

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.

Altered Amyloid-β and Tau Proteins in Neural-Derived Plasma Exosomes in Patients with Type 2 Diabetes and Orthostatic Hypotension

“…Moreover, compared with patients with DM with early OH, the exosomal concentrations of Aβ42, T-tau, and P-T181-tau in patients with DM with delayed and/or prolonged OH were higher. This is in line with previous ndings that patients with delayed and/or prolonged OH are at a greater risk of cognitive decline or incident dementia in initially non-demented individuals than are patients with early OH [3], as they are more likely to experience longer periods of cerebral hypoperfusion.…”

“…The Toronto Clinical Neuropathy Score (TCNS) was used to evaluate neuropathy. The exclusion criteria were as follows: (1) a concomitant neurological disorder that could potentially affect cognitive function or a family history of dementia; (2) a history of cardiovascular problems and stroke or other factors that may in uence cerebral blood ow; (3) an abnormal nding on routine transcranial Doppler (TCD), such as middle cerebral artery (MCA) stenosis or vasospasm; (4) a poor temporal window on conventional TCD; (5) patients who were unable to continue TCD monitoring with head-up tilting(HUT) due to severe symptoms associated with orthostasis, such as syncope/presyncope, headache, faintness, dizziness, or signi cant tachycardia (> 150 beats per minute); and (6) other serious heart, lung, liver, kidney, or brain diseases that affect quality of life.…”

“…Alzheimer's disease (AD) [2,3], as well as substantially accelerated progression from MCI to AD [4], suggesting that OH may promote AD pathogenesis. OH leads to cerebral hypoperfusion, which, if regularly occurring, may cause the accumulation of amyloid and tau hyperphosphorylation in the brain and thereafter cognitive decline or dementia [5,6].…”

Prevalence of postural hypotension in primary, community and institutional care: a systematic review and meta-analysis

“…All measurements were repeated three times, with intervals of 3 min on the left arm in a sitting position 18.0 Primary care Reported as consensus definition of PH Bouhanick 2014 [ 25 ] Male and females living in France with type 2 diabetes, aged over 70 years with relatively preserved autonomy (Activity of Daily Living Score > 3/6) 77.0 After 5 min of supine rest and at 1, 3 and 5 min after standing up, BP was measured. The BP device was not stated 27.0 Fleg 2016 [ 26 ] Male and female participants with type 2 diabetes and a glycohaemoglobin level ≥ 7.5%, aged 40–79 years with cardiovascular disease or aged 55–79 years with anatomic evidence of subclinical atherosclerosis, albuminuria, left ventricular hypertrophy or ≥ 2 additional risk factors for cardiovascular disease, attending 77 sites across the U.S.A and Canada 40.0–79.0 BP was measured three times, at 1 min intervals, after 5 min of seated rest and on standing, using an automated oscillometric device (Omron HEM-907; Omron Healthcare Co. Kyoto, Japan) 17.7 Hirai 2009 [ 27 ] Male and female participants with type 1 or 2 diabetes living in Wisconsin 45.4 BP was measured using a standard mercury sphygmomanometer during supine rest and repeated within 3 min after participants were asked to stand up 16.1 Klanbut 2018 [ 28 ] Male and female participants with Parkinson’s disease (Hoehn and Yahr stage I-IV), stable on drug therapy or not received any drug modifications for 4 weeks prior to enrolment, attending King Chulalongkorn, Thailand 65.5 After 10 min of seated or supine rest, and within 3 min of standing, BP was measured using an automated sphygmomanometer (Omron HEM-7200) 22.0 Kleipool 2019 [ 29 ] Male and female participants (from the Amsterdam Dementia cohort) with subjective cognitive decline, mild cognitive impairment or dementia attending a memory clinic. 63.9 After 5 min of supine rest, and at 1 and 3 min after standing, BP was measured.…”

Genetically Determined Blood Pressure, Antihypertensive Medications, and Risk of Alzheimer’s Disease: A Mendelian Randomization Study

“…Consistent with this, one study also showed a greater effect of decreased DBP on white matter hyperintensity volume (WMHV) burden, particularly among those who previously had a greater increase in SBP [27]. Hypotension in late life might aggravate cerebral small vessel disease and decrease brain volume in cognitively normal individuals, potentially via shifts in the auto-regulatory curve and resultant cerebral hypoperfusion [28,29]. Alternatively, this nding might be mediated by increased arterial stiffness, which is associated with decreased DBP, although we did not nd a direct association between PP, a proxy marker of arterial stiffness, and AD risk.…”