Combination therapy with galantamine and memantine improves behavioral and psychological symptoms of dementia (BPSD) in patients with early-onset Alzheimer’s disease

To the Editor

I report herein the case of a 53-year-old female Alzheimer’s disease (AD) patient who showed improvements in behavioral and psychological symptoms of dementia (BPSD) following pharmacotherapy. Specifically, improvements were observed from using a combination of galantamine and memantine.

An initial symptom including memory impairment surfaced three years ago. Family members noticed that she could no longer properly clean her bathroom and kitchen two years ago. The patient’s sister took her to a memory clinic for a routine visit.

No neurological disorders were observed. The patient’s score on the Mini Mental State Examination (MMSE) was 18. As a result, she could recall only one out of three items. Additionally, she could not accurately copy a figure of intersecting pentagons. Atrophy in the parietal lobe was observed by computed tomography (CT), and hypo perfusion of the occipital lobe was observed by single photon emission computed tomography (SPECT). Consequently, the patient was diagnosed with early-onset Alzheimer’s disease (EOAD). A daily prescription of 5 mg of donepezil hydrochloride was started. However, no initial improvements in her symptoms were seen. Moreover, the patient was observed to be in a state of gloom, and repeatedly asked the same questions. She sometimes resorted to violence toward her caregivers. To suppress her excessive irritability, 5 mg of memantine hydrochloride was added to her existing medication of donepezil. After nine months of combination therapy, however, no improvements in her symptoms were observed. She would excessively raise her voice and broke her own cell phone. As a result, her prescription was switched from donepezil to galantamine hydrobromide. After four weeks on the new medication, improvements in her cognitive functioning were not observed (MMSE; 18→15). But, her symptoms of irritability and violence gradually decreased and disappeared.

The pharmacological action of memantine is one of the N-methyl-d-aspartate (NMDA) receptor antagonists known to adjust the synaptic concentration of glutamate. In contrast, galantamine is characterized by two mechanisms, an inhibition of acetylcholine esterase and an activation of the nicotinic acetylcholine receptor. There is the action of glutamic acid receptors (Jensen et al., 2005). In the previous study of the pharmacology of the two compounds, the close examination suggested that galantamine can augment memantine’s glutamatergic noise suppression while simultaneously enhancing the physiologic glutamatergic signal (Geerts and Grossberg, 2006). However, little is known regarding the effectiveness of pharmacotherapy for EOAD with BPSD. Combination therapy may be beneficial because the therapies do not involve competing mechanisms. The present case study confirmed improvements in AD symptoms using a combination of galantamine hydrobromide and memantine hydrochloride even though symptomatic improvements were not initially seen using a combination of donepezil hydrochloride and memantine hydrochloride. Although galantamine hydrobromide and donepezil hydrochloride have similar pharmacological mechanisms, they exhibited different effects on BPSD.