QTc Prolongation in Patients with Dementia and Mild Cognitive Impairment: Neuropsychological and Brain Imaging Correlations

Danese, Alessandra; Federico, Angela; Martini, Alice; Mantovani, Elisa; Zucchella, Chiara; Tagliapietra, Matteo; Tamburin, Stefano; Cavallaro, Tiziana; Marafioti, Vincenzo; Monaco, Salvatore; Turri, Giulia

doi:10.3233/jad-190632

Cited by 5 publications

(32 citation statements)

References 34 publications

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“…A pharmacogenetic risk score has been proposed with top-scoring SNPs (rs12248560, rs878567, and rs17710780). The HTR1A rs878567 and CYP2C19 rs12248560 variants showed association with depression severity [233]. ACE variants influence mood in AD [111].…”

Section: Depressive Disordersmentioning

confidence: 96%

Pharmacogenomics of Cognitive Dysfunction and Neuropsychiatric Disorders in Dementia

Cacabelos

2020

IJMS

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Symptomatic interventions for patients with dementia involve anti-dementia drugs to improve cognition, psychotropic drugs for the treatment of behavioral disorders (BDs), and different categories of drugs for concomitant disorders. Demented patients may take >6–10 drugs/day with the consequent risk for drug–drug interactions and adverse drug reactions (ADRs >80%) which accelerate cognitive decline. The pharmacoepigenetic machinery is integrated by pathogenic, mechanistic, metabolic, transporter, and pleiotropic genes redundantly and promiscuously regulated by epigenetic mechanisms. CYP2D6, CYP2C9, CYP2C19, and CYP3A4/5 geno-phenotypes are involved in the metabolism of over 90% of drugs currently used in patients with dementia, and only 20% of the population is an extensive metabolizer for this tetragenic cluster. ADRs associated with anti-dementia drugs, antipsychotics, antidepressants, anxiolytics, hypnotics, sedatives, and antiepileptic drugs can be minimized by means of pharmacogenetic screening prior to treatment. These drugs are substrates, inhibitors, or inducers of 58, 37, and 42 enzyme/protein gene products, respectively, and are transported by 40 different protein transporters. APOE is the reference gene in most pharmacogenetic studies. APOE-3 carriers are the best responders and APOE-4 carriers are the worst responders; likewise, CYP2D6-normal metabolizers are the best responders and CYP2D6-poor metabolizers are the worst responders. The incorporation of pharmacogenomic strategies for a personalized treatment in dementia is an effective option to optimize limited therapeutic resources and to reduce unwanted side-effects.

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Section: Depressive Disordersmentioning

confidence: 96%

Pharmacogenomics of Cognitive Dysfunction and Neuropsychiatric Disorders in Dementia

Cacabelos

2020

IJMS

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“…This association has not been reported previously. However, other studies investigating prolongation of ventricular de/repolarization and brain imaging correlations did find an association between prolonged QTc and global and temporal atrophy, indicated by the bicaudate ratio [33]. A possible explanation could be that patients with a higher degenerative damage have a greater impairment of the cerebral autonomic network, which is then reflected by the prolongation of QTc.…”

Section: Discussionmentioning

confidence: 92%

Ventricular Repolarization is Associated with Cognitive Function, but Not with Cognitive Decline and Brain Magnetic Resonance Imaging (MRI) Measurements in Older Adults

Zonneveld

Noordam

Sabayan

et al. 2020

JCM

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We aimed to investigate the cross-sectional and longitudinal associations of electrocardiogram (ECG)-based QT, QTc, JT, JTc, and QRS intervals with cognitive function and brain magnetic resonance imaging (MRI) measurements in a cohort of older individuals at increased risk for cardiovascular disease, but free of known arrhythmias. We studied 4627 participants (54% female, mean age 75 years) enrolled in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER). Ten-second ECGs were conducted at baseline. Cognitive function was tested at baseline and repeated during a mean follow-up time of 3.2 years. Structural MRIs were conducted in a subgroup of 535 participants. Analyses were performed with multivariable (repeated) linear regression models and adjusted for cardiovascular risk-factors, co-morbidities, and cardiovascular drug use. At baseline, longer QT, JT, JTc—but not QTc and QRS intervals—were associated with a worse cognitive performance. Most notably, on the Stroop Test, participants performed 3.02 (95% CI 0.31; 5.73) seconds worse per standard deviation higher QT interval, independent of cardiovascular risk factors and medication use. There was no association between longer ventricular de- or repolarization and structural brain measurements. Therefore, specifically ventricular repolarization was associated with worse cognitive performance in older individuals at baseline but not during follow-up.

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“…A long QT interval was found to be associated with severe white matter hyperintensity. A recent study included patients from the outpatient Cognitive Impairment and Dementia Center of a hospital and reported that a prolonged QT interval was prevalent in patients with dementia and in patients with higher leukoaraiosis scale scores (Danese et al., 2019). Although the community population in our study was different from that of the other study, our results confirmed the results of the latter with larger sample size.…”

Section: Discussionmentioning

confidence: 99%

“…Although the community population in our study was different from that of the other study, our results confirmed the results of the latter with larger sample size. A previous study suggested that cerebral vascular load is associated with prolonged QTc (Danese et al, 2019). Patients with lesions in autonomic cardiac centers might have a change in the vascular origin, which causes unstable blood pressure with subsequent dysfunction of cerebral perfusion and alteration of the white matter (Dias et al, 2013).…”

Section: White Matter Grade 3-9mentioning

confidence: 99%

“…Investigators have increasingly focused on studying the effects of cardiovascular physiology on brain infarctions (Lee et al., 2018; Leung et al., 2017; Yaghi et al., 2018). A recent study has reported that electrocardiogram (ECG) abnormalities are associated with cerebrovascular diseases (Danese et al., 2019; Sawano et al., 2020), while the relationship between ECG parameters and silent vascular brain injury has not been assessed. Understanding the relationship between ECG and silent vascular brain injury may contribute to the improvement of subsequent stroke prevention strategies and provide evidence supporting the notion that cardiac structural or functional abnormalities may predispose patients to silent brain vascular injury (Yaghi et al., 2018).…”

Section: Introductionmentioning

confidence: 99%

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Electrocardiogram properties and risk of covert brain infarction and other magnetic resonance imaging abnormalities in a stroke‐free population

et al. 2023

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Objectives: This study aimed to investigate the association between electrocardiogram (ECG) abnormalities and silent vascular brain injury as defined by cerebral magnetic resonance imaging (MRI) in a stroke-free community-based population.Methods: A total of 5888 participants were studied from the Cardiovascular Health Study (CHS), a prospective cohort of community-living older adults. Standard 12-lead ECGs measured prior to MRI scan were used. MRI scans were conducted at years 4-6 and 10-11. The primary outcome was presence of incident covert brain infarcts (CBIs) on the 2nd MRI examination, excluding previous CBIs and stroke occurrence. Secondary outcomes included white matter, ventricular, and sulcal atrophy on the 1st MRI.Logistic and multiple linear regression models were used to assess the relationship between ECG findings and silent vascular brain injury.Results: Left axis deviation before MRI scan was related to presence of incident CBIs (odds ratio [OR]: 1.45; 95% CI: 1.01-2.08, p = .047). A long QT interval was associated with severe white matter hyperintensity (OR: 1.36; 95% CI: 1.04-1.77, p = .024). Minor Q and QS waves with ST-T abnormalities were positively related to sulcal atrophy (β: 0.43, 95% CI: 0.06-0.81, p = .023). Conclusions:Our study found that ECG abnormalities were related to presence of CBIs, white matter hyperintensity, and sulcal atrophy on MRI in a stroke-free relderly population. Specifically, those with left axis deviation had an increased risk of presence of CBIs.

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QTc Prolongation in Patients with Dementia and Mild Cognitive Impairment: Neuropsychological and Brain Imaging Correlations

Cited by 5 publications

References 34 publications

Pharmacogenomics of Cognitive Dysfunction and Neuropsychiatric Disorders in Dementia

Pharmacogenomics of Cognitive Dysfunction and Neuropsychiatric Disorders in Dementia

Ventricular Repolarization is Associated with Cognitive Function, but Not with Cognitive Decline and Brain Magnetic Resonance Imaging (MRI) Measurements in Older Adults

Electrocardiogram properties and risk of covert brain infarction and other magnetic resonance imaging abnormalities in a stroke‐free population

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