1-H MRS changes in dorsolateral prefrontal cortex after donepezil treatment in patients with mild to moderate Alzheimer’s disease [1-H MRS promjene u dorzolateralnom prefrontalnom korteksu nakon primjene donepezila u pacijenata s blagim i umjerenim oblicima Alzhemierove bolesti]

Henigsberg, Neven and Kalember, Petra and Hrabač, Pero and Radoš, Marko and Bajs, Maja and Radoš, Milan and Kovačić, Zrinka and Lončar, Mladen and Madžar, Tomo (2011) 1-H MRS changes in dorsolateral prefrontal cortex after donepezil treatment in patients with mild to moderate Alzheimer’s disease [1-H MRS promjene u dorzolateralnom prefrontalnom korteksu nakon primjene donepezila u pacijenata s blagim i umjerenim oblicima Alzhemierove bolesti]. Collegium Antropologicum, 35 (S. 1). pp. 159-162. ISSN 0350-6134

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Abstract

Magnetic resonance spectroscopy (MRS) noninvasively provides information on the concentration of some cerebral metabolites in vivo. Among those measurable by proton magnetic resonance spectroscopy (1H-MRS), N-acetyl-aspartate (NAA) is decreased, and myo-inositol (mI) and choline (Cho) levels are increased in patients with Alzheimer’s disease (AD). Donepezil, an acetylcholinesteraze inhibitor, has proven effect on cognitive symptoms in patients with AD. In previous studies, treatment response was associated with an increase of NAA and NAA/Cr in the parietal lobe and hippocampi. Correlation of longitudinal changes of 1H-MRS detectable metabolites in dorsolateral prefrontal cortex (DLPFC) with clinically observable changes is a poorly researched topic. The objective of this non-interventional study is to assess whether changes in 1H-MRS measurable metabolites correlate with clinical outcome after donepezil treatment. Twelve patients with mild to moderate AD were evaluated during 26 weeks of donepezil treatment. 1H-MRS parameters in DLPFC were assessed before and after 26 weeks of donepezil treatment. Cognition was assessed with Alzheimer’s Disease Assessment Scale cognitive subscale (ADAS-Cog). A significant increase in NAA/Cr ratio and significantly lower decrease in mI/Cr ratio were found in AD patients with positive treatment response. The results of this study indicate possible modest donepezil effect on prevention of neuronal functional deterioration in DLPFC which correlates with clinical outcome and point the use of 1HMRS as technique of help in assessment of drug effect.

Abstract in Croatian

Magnentno rezonantna spektroskopija (MRS) metoda je koja neinvazivno pruža informacije o in-vivo koncetraciji određenih metabolita u mozgu. Među metabolitima koji se mogu mjeriti protonskom magnentno rezonantnom spektroskopijom (1H-MRS) u bolesnika s Alzheimerovom bolešću (AD) snižene su razine N-acetil-aspartata (NAA), dok su razine mio-inozitola (mI) i kolina (Cho) povišene. Donepezil, inhibitor enzima acetilkolin esteraze, pokazao se učinkovitim u liječenju kognitivnih simptoma u bolesnika od AD. U prethodnim ispitivanjima, odgovor na liječenje bio je povezan s povišenim vrijednostima NAA i omjera NAA/Cr u parijetalnom režnju i hipokampusu. Ipak, povezanost promjene vrijednosti metabolita koji se mogu otkriti metodom 1H-MRS u području dorzolateralnog prefrontalnog korteksa (DLPFC) s klinički uočljivim promjenama slabo je istraženo područje. Cilj ovog neinterventnog ispitivanja je procijeniti da li promjene u metabolitima koji se mogu otkriti metodom 1H-MRS odgovara kliničkom rezultatu nakon liječenja donepezilom. Promatrano je 12 ispitanika s blagom do umjerenom AD tijekom 26 tjedana liječenja donepezilom. Parametri mjereni metodom 1H-MRS ispitani su prije i nakon 26-tjednog liječenja donepezilom. Korištena je i ljestvica »Alzheimer’s Disease Assessment Scale cognitive subscale« (ADAS-Cog) za procjenu mentalnog stanja ispitanika. Znatno povećanje omjera NAA/Cr i znatno manje sniženje omjera mI/Cr pronađeni su u bolesnika s pozitivnim odgovorom na liječenje. Rezultati ovog ispitivanja upućuju na moguće blago pozitivne učinke donepezila na usporavanje funkcionalnog propadanja neurona u području DLPFC. Također, metoda 1H-MRS pokazala se korisnom u procjeni učinaka lijeka.

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