Abstract
Introduction: The aim of this study is to investigate the impact of orthostatic hypotension (OH) on cognitive functions in patients with multiple system atrophy (MSA) followed over time.Methods: Thirty-two MSA patients were enrolled and underwent a comprehensive neuropsychological battery; at baseline (T0) 15 out of 32 patients presented OH, assessed by means of orthostatic standing test. All patients underwent a follow-up (T1) evaluation 12 months after baseline. Thirteen out of 32 patients also underwent a second follow-up (T2) evaluation at 24 months. Changes over time on different neuropsychological tasks were compared between patients with and without OH by means of Mann-Whitney's U-test. Moreover, clinical categories of normal cognition, mild cognitive impairment, and dementia were determined, and changes at T1 and T2 in global cognitive status were compared between patients with and without OH.Results: At T0, patients with OH had better performance on words/non-words repetition task (p = 0.02) compared to patients without OH. Compared to patients without OH, patients with OH performed worse on semantic association task (p < 0.01) at T1 and on Stroop test-error effect (p = 0.04) at T2. The percentage of patients with worsened cognitive status at T1 was higher among patients with OH than among patients without OH (93 vs. 59%, p = 0.03). OH (β = −4.67, p = 0.01), education (β = 0.45, p = 0.02), age (β = 0.19, p = 0.03), and Montreal Cognitive Assessment battery (MOCA) score at T0 (β = −0.26, p = 0.04) were significant predictors of global cognitive status worsening at T1.Discussion: We found that global cognitive status worsened at 1-year follow-up in 93% of patients with OH, and OH, along with age, education, and MOCA score, predicted cognitive worsening over time. To clarify the relationship between OH and cognitive dysfunction in MSA, we suggest the use of clinical categories of normal cognition, mild cognitive impairment, and dementia in further longitudinal studies on MSA patients with and without OH.
Highlights
The aim of this study is to investigate the impact of orthostatic hypotension (OH) on cognitive functions in patients with multiple system atrophy (MSA) followed over time
Significant differences are indicated in bold. aTests used to identify NC, MCI, and dementia [12, 13]. bMSA with OH vs. MSA without OH. 15-RAWLT, Rey’s auditory 15-word learning test; ADL, Basic Activities of Daily Life; AES, Apathy Evaluation Scale; Beck Depression Inventory-II (BDI-II), Beck Depression Inventory; Benton’s Judgment of Line Orientation test (BJLO), Benton’s Judgment of Line Orientation; CDT, Clock Drawing test; IADL, Instrumental Activities of Daily Life; IQR, interquartile range; LEDD, total L-dopa equivalent daily dose; M, male; MCI, mild cognitive impairment; MOCA, Montreal Cognitive Assessment battery; MSA, multiple system atrophy; OH, orthostatic hypotension; N, number; NC, normal cognition; p, p-value; Trail Making Test-part A (TMT-A), part A of Trail Making Test; T0, baseline; UMSARS, Unified Multiple System Atrophy Rating Scale
Logistic regression analysis showed that OH (β = −4.67, p < 0.01), education (β = 0.45, p = 0.02), age (β = 0.19, p = 0.03), and MOCA score at T0 (β = −0.26, p = 0.04) were significant predictors of global cognitive status worsening at follow up1 (T1), explaining 48% of the variance (R2 = 0.49), with OH accounting for 24% of variance
Summary
The aim of this study is to investigate the impact of orthostatic hypotension (OH) on cognitive functions in patients with multiple system atrophy (MSA) followed over time. Multiple system atrophy (MSA) is a sporadic, progressive α-synucleinopathy, clinically characterized by different combinations of rapidly progressive parkinsonism, cerebellar ataxia, autonomic failure, and corticospinal impairment. The diagnosis of MSA is mainly based on clinical features including significant autonomic dysfunction [3]. One of the most important autonomic features of MSA is orthostatic hypotension (OH), defined as a blood pressure (BP) drop of at least 20/10 mm Hg (systolic/diastolic) from supine to standing position [4]. OH results from cardiovascular dysfunction caused by a complex interplay between central and peripheral autonomic dysregulation, cardiac noradrenergic sympathetic denervation, peripheral norepinephrine deficiency, and arterial baroreflex failure, leading to impaired arterial vasoconstriction and reduced compensatory cardiac output in response to hypotension [4]. OH is usually associated with cognitive symptoms; confusion is often described by affected patients [7, 8], but there is poor evidence about the relationship between OH and cognitive deficits in MSA patients [10]
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