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Cognitive Impairment Before Atrial Fibrillation-Related Ischemic Events: Neuroimaging and Prognostic Associations.

ABSTRACT: Background It is likely that a proportion of poststroke cognitive impairment is sometimes attributable to unidentified prestroke decline; prestroke cognitive function is also clinically relevant because it is associated with poor functional outcomes, including death. We investigated the radiological and prognostic associations of preexisting cognitive impairment in patients with ischemic stroke or transient ischemic attack associated with atrial fibrillation. Methods and Results We included 1102 patients from the prospective multicenter observational CROMIS-2 (Clinical Relevance of Microbleeds in Stroke 2) atrial fibrillation study. Preexisting cognitive impairment was identified using the 16-item Informant Questionnaire for Cognitive Decline in the Elderly. Functional outcome was measured using the modified Rankin scale. Preexisting cognitive impairment was common (n=271; 24.6%). The presence of lacunes (odds ratio [OR], 1.50; 95% CI, 1.03-1.05; P=0.034), increasing periventricular white matter hyperintensity grade (per grade increase, OR, 1.38; 95% CI, 1.17-1.63; P<0.0001), deep white matter hyperintensity grade (per grade increase, OR, 1.26; 95% CI, 1.05-1.51; P=0.011), and medial temporal atrophy grade (per grade increase, OR, 1.61; 95% CI, 1.34-1.95; P<0.0001) were independently associated with preexisting cognitive impairment. Preexisting cognitive impairment was associated with poorer functional outcome at 24 months (mRS >2; adjusted OR, 2.43; 95% CI, 1.42-4.20; P=0.001). Conclusions Preexisting cognitive impairment in patients with atrial fibrillation-associated ischemic stroke or transient ischemic attack is common, and associated with imaging markers of cerebral small vessel disease and neurodegeneration, as well as with longer-term functional outcome. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02513316.

SUBMITTER: Banerjee G

PROVIDER: S-EPMC6988157 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Cognitive Impairment Before Atrial Fibrillation-Related Ischemic Events: Neuroimaging and Prognostic Associations.

Banerjee Gargi G Chan Edgar E Ambler Gareth G Wilson Duncan D Cipolotti Lisa L Shakeshaft Clare C Cohen Hannah H Yousry Tarek T Al-Shahi Salman Rustam R Lip Gregory Y H GYH Muir Keith W KW Brown Martin M MM Jäger Hans Rolf HR Werring David J DJ

Journal of the American Heart Association 20200104 1

Background It is likely that a proportion of poststroke cognitive impairment is sometimes attributable to unidentified prestroke decline; prestroke cognitive function is also clinically relevant because it is associated with poor functional outcomes, including death. We investigated the radiological and prognostic associations of preexisting cognitive impairment in patients with ischemic stroke or transient ischemic attack associated with atrial fibrillation. Methods and Results We included 1102 ...[more]

PMID: 31902325

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Project description:Emerging evidence suggests that atrial fibrillation is associated with cognitive dysfunction independently of stroke, but the underlying mechanisms remain unclear. In this cross-sectional analysis from the Swiss-atrial fibrillation Study (NCT02105844), we investigated the association of serum neurofilament light protein, a neuronal injury biomarker, with (i) the CHA2DS2-VASc score (congestive heart failure, hypertension, age 65-74 or >75?years, diabetes mellitus, stroke or transient ischaemic attack, vascular disease, sex), clinical and neuroimaging parameters and (ii) cognitive measures in atrial fibrillation patients. We measured neurofilament light in serum using an ultrasensitive single-molecule array assay in a sample of 1379 atrial fibrillation patients (mean age, 72?years; female, 27%). Ischaemic infarcts, small vessel disease markers and normalized brain volume were assessed on brain MRI. Cognitive testing included the Montreal cognitive assessment, trail-making test, semantic verbal fluency and digit symbol substitution test, which were summarized using principal component analysis. Results were analysed using univariable and multivariable linear regression. Neurofilament light was associated with the CHA2DS2-VASc score, with an average 19.2% [95% confidence interval (17.2%, 21.3%)] higher neurofilament per unit CHA2DS2-VASc increase. This association persisted after adjustment for age and MRI characteristics. In multivariable analyses, clinical parameters associated with neurofilament light were higher age [32.5% (27.2%, 38%) neurofilament increase per 10?years], diabetes mellitus, heart failure and peripheral artery disease [26.8% (16.8%, 37.6%), 15.7% (8.1%, 23.9%) and 19.5% (6.8%, 33.7%) higher neurofilament, respectively]. Mean arterial pressure showed a curvilinear association with neurofilament, with evidence for both an inverse linear and a U-shaped association. MRI characteristics associated with neurofilament were white matter lesion volume and volume of large non-cortical or cortical infarcts [4.3% (1.8%, 6.8%) and 5.5% (2.5%, 8.7%) neurofilament increase per unit increase in log-volume of the respective lesion], as well as normalized brain volume [4.9% (1.7%, 8.1%) higher neurofilament per 100?cm3 smaller brain volume]. Neurofilament light was inversely associated with all cognitive measures in univariable analyses. The effect sizes diminished after adjusting for clinical and MRI variables, but the association with the first principal component was still evident. Our results suggest that in atrial fibrillation patients, neuronal loss measured by serum neurofilament light is associated with age, diabetes mellitus, heart failure, blood pressure and vascular brain lesions, and inversely correlates with normalized brain volume and cognitive function.

Project description:Background/objectivesOral anticoagulation (OAC) is challenging in older patients with nonvalvular atrial fibrillation (NVAF) who are often frail and have cognitive impairment. We examined the characteristics of older NVAF patients associated with higher odds of physical and cognitive impairments. We also examined if these high-risk patients have different OAC prescribing patterns and their satisfaction with treatment because it may impact optimal management of their NVAF.MethodsThe patients in the Systematic Assessment of Geriatric Elements in Atrial Fibrillation (SAGE-AF study cohort 2016-2018) had NVAF, were aged 65 and older, and eligible for the receipt of OAC. Measures included frailty (Fried Frailty scale), cognitive impairment (Montreal Cognitive Assessment Battery), OAC prescribing and type (direct oral anticoagulant [DOAC] or vitamin K antagonist [VKA]), depressive symptoms (Patient Health Questionnaire-9), bleeding, stroke risk, and treatment benefit (Anti-Clot Treatment Scale).ResultsPatients (n = 1,244) were 49% female, aged 76 (standard deviation = 7) years. A total of 14% were frail, and 42% had cognitive impairment. Frailty and cognitive impairment co-occurred in 9%. Odds of having both impairments versus none were higher with depression (odds ratio [OR] = 4.62; 95% confidence interval [CI] = 2.59-8.26), older age (OR = 1.56; 95% CI = 1.29-1.88), lower education (OR = 3.81; 95%CI = 2.13-6.81), race/ethnicity other than non-Hispanic White (OR = 7.94; 95% CI = 4.34-14.55), bleeding risk (OR = 1.43; 95% CI = 1.12-1.81), and stroke risk (OR = 1.35; 95% CI = 1.13-1.62). OAC prescribing was not associated with CI and frailty status. Among patients taking OACs (85%), those with both impairments were more likely to take DOAC than VKA (OR = 1.69; 95% CI = 1.01-2.80). Having both impairments (OR = 1.87; 95% CI = 1.08-3.27) or cognitive impairment (OR = 1.56; 95% CI = 1.09-2.24) was associated with higher odds of reporting lower treatment benefit.ConclusionIn a large cohort of older NVAF patients, half were frail or cognitively impaired, and 9% had both impairments. We highlight the characteristics of patients who may benefit from cognitive and physical function screenings to maximize treatment and enhance prognosis. Finally, the co-occurrence of impairment was associated with low perceived benefit of treatment that may impede optimal management.

Project description:ObjectivesEffective identification and management of subclinical left ventricular (LV) dysfunction (LVD) and subclinical atrial fibrillation (AF) by screening elderly populations might be compromised by mild cognitive impairment (MCI). We sought to characterise the prevalence and profile of MCI and evaluate associations with LV and left atrial (LA) dysfunction and AF, in a trial of screening for subclinical LVD and AF.DesignCross-sectional.SettingAustralian, community-based intervention trial.ParticipantsAdults aged ≥65 years with ≥1 LVD risk factors without ischaemic heart disease (n=337).Outcome measuresThe Montreal cognitive assessment (MoCA) was obtained. Subclinical LVD was defined as echocardiographic global longitudinal strain ≤16%, diastolic dysfunction or LV hypertrophy; abnormal LA reservoir strain (LARS) was defined as <24%. Subclinical AF was detected using a single-lead portable electrocardiographic device in those without pre-existing AF who gave consent (n=293).ResultsSubclinical LVD was found in 155 (46%), abnormal LARS in 9 (3.6%) and subclinical AF in 11 (3.8%). MoCA score consistent with MCI (<26) was found in 101 (30%); executive function (69%) and delayed recall (93%), were the most frequently abnormal domains. Compared with normal cognition, MCI was associated with non-adherence to AF screening (25% vs 40%, p=0.01). In multivariable logistic regression modelling, educational achievement, systolic blood pressure, body mass index and waist-to-hip ratio were independently associated with MCI. However, neither subclinical AF nor any measure of cardiac dysfunction, were associated with MCI.ConclusionsThe 30% prevalence of MCI among elderly subjects with risk factors for subclinical LVD and AF has important implications for screening strategies and management. However, MCI is not associated with subclinical myocardial dysfunction nor subclinical AF.Trial registration numberAustralian New Zealand Clinical Trials Registry (ACTRN12617000116325).

Dataset Information

Cognitive Impairment Before Atrial Fibrillation-Related Ischemic Events: Neuroimaging and Prognostic Associations.

Publications

Cognitive Impairment Before Atrial Fibrillation-Related Ischemic Events: Neuroimaging and Prognostic Associations.

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