Pharmacogenetic analyses of variations of measures of cardiovascular risk in Alzheimer's dementia

Oliveira, Fabricio Ferreira de; Berretta, Juliana Marília; Almeida, Guido Veiga de; Almeida, Sandro Soares de; Chen, Elizabeth; Smith, Marı́lia de Arruda Cardoso; Bertolucci, Paulo Henrique Ferreira

doi:10.4103/ijmr.ijmr_1209_17

Cited by 12 publications

(2 citation statements)

References 34 publications

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“…Lithium PGx is very complex. Caution and personalized dose adjustment is highly recommended in patients with the following genotypes: BCR (Asn796Ser), BDNF (C/G (rs988748) and G/A (Val66Met)), CACNG2 (rs2284017, rs2284018, and rs5750285), GSK3B The influence of PGx factors on the pharmacogenetics and pharmacodynamics of many antidepressants has been reasonably well documented [55,66,[235][236][237]; however, important aspects such as body weight gain, suicidality, cyclothymic reactions, cardiovascular risks, and potential neurotoxicity still remain obscure [55].…”

Section: Selective Serotonin and Norepinephrine Reuptake Inhibitors (mentioning

confidence: 99%

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: Selective Serotonin and Norepinephrine Reuptake Inhibitors (mentioning

confidence: 99%

Pharmacogenomics of Cognitive Dysfunction and Neuropsychiatric Disorders in Dementia

Cacabelos

2020

IJMS

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“…Angiotensin-converting enzyme (ACE) variants influence mood in AD [ 49 ]. The co-administration of ACE inhibitors and statins with antidepressants may affect therapeutic outcomes [ 70 ]. In our case, we did not observe any ADRs in the patients treated with small doses of enalapril, atorvastatin, and SSRIs.…”

Section: Discussionmentioning

confidence: 99%

Influence of Pathogenic and Metabolic Genes on the Pharmacogenetics of Mood Disorders in Alzheimer’s Disease

et al. 2021

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Background: Mood disorders represent a risk factor for dementia and are present in over 60% of cases with Alzheimer’s disease (AD). More than 80% variability in drug pharmacokinetics and pharmacodynamics is associated with pharmacogenetics. Methods: Anxiety and depression symptoms were assessed in 1006 patients with dementia (591 females, 415 males) and the influence of pathogenic (APOE) and metabolic (CYP2D6, CYP2C19, and CYP2C9) gene variants on the therapeutic outcome were analyzed after treatment with a multifactorial regime in a natural setting. Results and Conclusions: (i) Biochemical, hematological, and metabolic differences may contribute to changes in drug efficacy and safety; (ii) anxiety and depression are more frequent and severe in females than males; (iii) both females and males respond similarly to treatment, showing significant improvements in anxiety and depression; (iv) APOE-3 carriers are the best responders and APOE-4 carriers tend to be the worst responders to conventional treatments; and (v) among CYP2D6, CYP2C19, and CYP2C9 genophenotypes, normal metabolizers (NMs) and intermediate metabolizers (IMs) are significantly better responders than poor metabolizers (PMs) and ultra-rapid metabolizers (UMs) to therapeutic interventions that modify anxiety and depression phenotypes in dementia. APOE-4 carriers and CYP-related PMs and UMs deserve special attention for their vulnerability and poor response to current treatments.

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Basic Information Science Methods for Insight into Neurodegenerative Pathogenesis

2023

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Pharmacogenetic analyses of variations of measures of cardiovascular risk in Alzheimer's dementia

Cited by 12 publications

References 34 publications

Pharmacogenomics of Cognitive Dysfunction and Neuropsychiatric Disorders in Dementia

Pharmacogenomics of Cognitive Dysfunction and Neuropsychiatric Disorders in Dementia

Influence of Pathogenic and Metabolic Genes on the Pharmacogenetics of Mood Disorders in Alzheimer’s Disease

Basic Information Science Methods for Insight into Neurodegenerative Pathogenesis

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