:
Dementia is an important issue in western societies, and in the following years, this problem
will also rise in the developing regions, such as Africa and Asia. The most common types of dementia
in adults are Alzheimer’s Disease (AD), Dementia with Lewy Bodies (DLB), Frontotemporal Dementia
(FTD) and Vascular Dementia (VaD), of which, AD accounts for more than half of the cases.
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The most prominent symptom of AD is cognitive impairment, currently treated with four drugs: Donepezil,
rivastigmine, and galantamine, enhancing cholinergic transmission; as well as memantine, protecting
neurons against glutamate excitotoxicity. Despite ongoing efforts, no new drugs in the treatment
of AD have been registered for the last ten years, thus multiple studies have been conducted on genetic
factors affecting the efficacy of antidementia pharmacotherapy. The researchers investigate the effects
of variants in multiple genes, such as ABCB1, ACE, CHAT, CHRNA7, CYP2C9, CYP2C19, CYP2D6,
CYP3A4, CYP3A5, CYP3A7, NR1I2, NR1I3, POR, PPAR, RXR, SLC22A1/2/5, SLC47A1, UGT1A6,
UGT1A9 and UGT2B7, associated with numerous pathways: the development of pathological proteins,
formation and metabolism of acetylcholine, transport, metabolism and excretion of antidementia drugs
and transcription factors regulating the expression of genes responsible for metabolism and transport of
drugs. The most promising results have been demonstrated for APOE E4, dementia risk variant,
BCHE-K, reduced butyrylcholinesterase activity variant, and CYP2D6 UM, ultrarapid hepatic metabolism.
Further studies investigate the possibilities of the development of emerging drugs or genetic editing
by CRISPR/Cas9 for causative treatment.
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In conclusion, the pharmacogenetic studies on dementia diseases may improve the efficacy of pharmacotherapy
in some patients with beneficial genetic variants, at the same time, identifying the carriers of
unfavorable alleles, the potential group of novel approaches to the treatment and prevention of dementia.
Chemotranscriptome analysis indicates the neurotrophic and neuromodulator effects of a citicoline molecule
