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Objective: In this study, we evaluated the long- term effects of memantine on cognitive function, BPSD, and the care burden in patients with moderate to severe Alzheimer’s disease (AD) for 72 weeks. Further, we examined the association between the long-term effects of memantine and brain blood flow using near-infrared spectroscopy (NIRS).  Methods: We evaluated the effects of memantine administration from baseline using the Clinical Global Impression - Improvement scale (CGI-I) , Mini-Mental State Examination (MMSE), Clock Drawing Test (CDT), Neuropsychiatric Inventory (NPI), Japanese version of the Zarit Burden Interview (J-ZBI), and NIRS on two groups; a combined donepezil and memantine administration group (combination group, n=19), and donepezil only administration group (control group, n=18) were assessed at weeks 0, 4, 12, 24, 48 and 72.  Results: A significant difference was found between the combination group and the control group in the scores of CGI-I after 4 weeks, CDT after 24 weeks, and NPI and J-ZBI after 12 weeks. A significant correlation was observed between the irritability subscore of NPI and total score of J-ZBI. In the NIRS measurements, there was no significant interaction in total value of Oxy- Hb integral from of all channels at the 72nd week, although oxyhemoglobin suppression was observed in CH5, CH7, and CH8 at 12th and 24th week.  Conclusions: In this study, long-term administration of memantine to AD patients improved clinical symptoms overall, cognitive function, and BPSD, thereby reducing the burden of caregivers and inhibited transiently the reduction of cerebral blood flow in the prefrontal area.

Long-Term Effects Of Combined Treatment With Memantine And Donepezil On Alzheimer's Disease Patients: 72-Week Study