A systematic review and meta-analysis on the association between orthostatic hypotension and mild cognitive impairment and dementia in Parkinson’s disease

Loureiro, Débora; Bilbao, Rodrigo; Bordet, Sofía; Grasso, Lina; Otero‐Losada, Matilde; Capani, Francisco; Ponzo, Osvaldo; Pérez-Lloret, Santiago

doi:10.1007/s10072-022-06537-3

Cited by 9 publications

(5 citation statements)

References 51 publications

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“…Regarding motor dysfunction, our nOH sample had higher MDS-UPDRS III scores than those without OH but did not differ from those with non-nOH. This general finding has been reported many times, but it remains unclear whether this association reflects a more aggressive PD phenotype or a shared tendency toward inactivity/deconditioning, which can worsen OH and motor impairment 43–48 . Both nOH and non-nOH performed worse on cognitive testing than those without OH, though the average magnitude of score differences was not large.…”

Section: Discussionsupporting

confidence: 68%

Longitudinal prevalence of neurogenic orthostatic hypotension in the idiopathic Parkinson Progression Marker Initiative (PPMI) cohort

Beach,

McKay

2023

Preprint

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Background Reported orthostatic hypotension (OH) prevalence in Parkinson disease (PD) varies widely, with few studies evaluating specifically neurogenic-OH (nOH). The ratio of orthostatic heart rate (HR) to systolic blood pressure (SBP) change (Δ) is a valid screening method to stratify nOH/non-nOH but had minimal epidemiologic application. Objective To estimate the prevalence of nOH and non-nOH in the PPMI using the ΔHR/ΔSBP ratio and examine associations between nOH and various motor and non-motor measures. Methods Longitudinal orthostatic vitals and motor and non-motor measures were extracted (baseline-month 48). Patients were consensus criteria classified as OH+/-, with ΔHR/ΔSBP sub-classification to nOH (ΔHR/ΔSBP<0.5) or non-nOH (ratio≥0.5). Prevalence was determined across visits. Independent linear mixed models tested associations between nOH/non-nOH and clinical variables. Results Of N=907 PD with baseline orthostatic vitals, 3.9% and 1.8% exhibited nOH and non-nOH, respectively. Prevalence of nOH/non-nOH increased yearly (P=0.012, chi-square), though with modest magnitude (baseline: 5.6% [95% CI: 4.3-7.3%]; month 48: 8.6% [6.4-11.5%]). nOH patients were older than PD with no OH and nOH was associated with greater impairment of motor and independent functioning than non-nOH/OH- groups. Cognitive function and typical OH symptoms were worse in PD+OH, generally. Conclusions nOH prevalence was greater than non-nOH in the PPMI early PD cohort, with modest prevalence increase over time. Our findings are consistent with prior studies of larges cohorts that evaluated nOH, specifically. Early PD with nOH were likelier to be older and suffer from greater motor and functional impairment, but OH presence was generally associated with more cognitive impairment.

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Section: Discussionsupporting

confidence: 68%

Longitudinal prevalence of neurogenic orthostatic hypotension in the idiopathic Parkinson Progression Marker Initiative (PPMI) cohort

Beach,

McKay

2023

Preprint

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“…Finally, during the 5-year follow-up, results of all tests declined regardless of OH status. Several previous studies, including two meta-analyses, have found associations between classical OH and neurodegenerative disorders, including in individuals aged in their 70's and 80's [12,28,31,32]. Delayed OH was associated with neurodegenerative disease in a study of admitted patients [14].…”

Section: Cognitive Assessments and The Prevalence Of Neurodegenerativ...mentioning

confidence: 85%

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

Geijerstam,

Harris,

Johansson

et al. 2024

Aging and disease

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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.

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“…Orthostatic hypotension prevalence is correlated to severity of CI, particularly with a lower performance in executive functions (EFs) [ 92 ]. It is a significant risk factor for CI in PD, especially in women and persons not suffering from hypotension [ 93 ]. Early hypotension, but not its symptom severity, increased dementia risk in PD patients by 14% while not being associated with other clinical or neuropathological variables [ 94 ].…”

Section: Risk Factors Of CI In Pdmentioning

confidence: 99%

Pathobiology of Cognitive Impairment in Parkinson Disease: Challenges and Outlooks

Jellinger

2023

IJMS

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Cognitive impairment (CI) is a characteristic non-motor feature of Parkinson disease (PD) that poses a severe burden on the patients and caregivers, yet relatively little is known about its pathobiology. Cognitive deficits are evident throughout the course of PD, with around 25% of subtle cognitive decline and mild CI (MCI) at the time of diagnosis and up to 83% of patients developing dementia after 20 years. The heterogeneity of cognitive phenotypes suggests that a common neuropathological process, characterized by progressive degeneration of the dopaminergic striatonigral system and of many other neuronal systems, results not only in structural deficits but also extensive changes of functional neuronal network activities and neurotransmitter dysfunctions. Modern neuroimaging studies revealed multilocular cortical and subcortical atrophies and alterations in intrinsic neuronal connectivities. The decreased functional connectivity (FC) of the default mode network (DMN) in the bilateral prefrontal cortex is affected already before the development of clinical CI and in the absence of structural changes. Longitudinal cognitive decline is associated with frontostriatal and limbic affections, white matter microlesions and changes between multiple functional neuronal networks, including thalamo-insular, frontoparietal and attention networks, the cholinergic forebrain and the noradrenergic system. Superimposed Alzheimer-related (and other concomitant) pathologies due to interactions between α-synuclein, tau-protein and β-amyloid contribute to dementia pathogenesis in both PD and dementia with Lewy bodies (DLB). To further elucidate the interaction of the pathomechanisms responsible for CI in PD, well-designed longitudinal clinico-pathological studies are warranted that are supported by fluid and sophisticated imaging biomarkers as a basis for better early diagnosis and future disease-modifying therapies.

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A systematic review and meta-analysis on the association between orthostatic hypotension and mild cognitive impairment and dementia in Parkinson’s disease

Cited by 9 publications

References 51 publications

Longitudinal prevalence of neurogenic orthostatic hypotension in the idiopathic Parkinson Progression Marker Initiative (PPMI) cohort

Longitudinal prevalence of neurogenic orthostatic hypotension in the idiopathic Parkinson Progression Marker Initiative (PPMI) cohort

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

Pathobiology of Cognitive Impairment in Parkinson Disease: Challenges and Outlooks

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