Abstract
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.
Highlights
Over 50 million people suffer dementia and it is expected that 75 million people will be affected in 2030 and 145 million in 2050, at an increasing rate of 7.7 million new cases per year
Epigenetic aberrations, cerebrovascular damage, and environmental inducers are the major risk factors that precipitate pathogenic cascades leading to the clinical phenotype of dementia
Dementia is characterized by progressive cognitive deterioration, behavioral changes, functional decline, and classical neuropathological hallmarks represented by extracellular Aβ deposition in senile plaques, intracellular neurofibrillary tangles, aberrant dendritic morphology, and neuronal loss in critical regions of the central nervous system (CNS) [3,4,5,6,7]
Summary
Over 50 million people suffer dementia and it is expected that 75 million people will be affected in 2030 and 145 million in 2050, at an increasing rate of 7.7 million new cases per year. 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 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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