title: 1-H MRS changes in dorsolateral prefrontal cortex after donepezil treatment in patients with mild to moderate Alzheimer's disease.
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 (ml) 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.
authors.affiliation: University of Zagreb, Vrapce Psychiatric Hospital, Department of General and Forensic Psychiatry and Clinical Psychophysiology, Zagreb, Croatia.
authors.forename: Neven
authors.initials: N
authors.lastname: Henigsberg
authors.forename: Petra
authors.initials: P
authors.lastname: Kalember
authors.forename: Pero
authors.initials: P
authors.lastname: Hrabać
authors.forename: Marko
authors.initials: M
authors.lastname: Rados
authors.forename: Maja
authors.initials: M
authors.lastname: Bajs
authors.forename: Milan
authors.initials: M
authors.lastname: Rados
authors.forename: Zrinka
authors.initials: Z
authors.lastname: Kovavić
authors.forename: Mladen
authors.initials: M
authors.lastname: Loncar
authors.forename: Tomo
authors.initials: T
authors.lastname: Madzar
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000473:pathology*; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use*; D003071:Cognition; D015331:Cohort Studies; D000077265:Donepezil; D005260:Female; D006801:Humans; D007189:Indans / Q000627:therapeutic use*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009483:Neuropsychological Tests; D010880:Piperidines / Q000627:therapeutic use*; D017397:Prefrontal Cortex / Q000737:chemistry / Q000187:drug effects / Q000473:pathology*
chemical_list: D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D000077265:Donepezil