Memantine in patients with behavioral variant frontotemporal dementia: An open-label pilot study

In comparison to Alzheimer's disease (AD), the rate of functional decline is greater in behavioral variant of frontotemporal dementia (bvFTD). Nevertheless, unlike AD, there are no US Food and Drug Administration approved therapies for bvFTD. We conducted the trial to investigate efficacy and safety of memantine in the treatment of patients with bvFTD. Between Jan 1, 2007 to Sep 1, 2013, seventy-six patients were recruited and treated with memantine (initiated at 5 mg/day and up-titrated with 5 mg weekly to a maintenance dosage of 10 mg twice daily) in this single-arm, open-label, 3-year study. The study visits were arranged at baseline, and month 1, 3, 6, 12, 18, 24, 30 and 36 after an 8-week screening period. The efficacy endpoints included changes from baseline in the scores of Mini Mental State Examination (MMSE), Addenbrooke's Cognitive Examination-revised (ACE-R), Frontal Assessment Battery (FAB), Frontal Behavior Inventory (FBI), Relevant Outcome Scale for Alzheimer's disease (ROSA), Clinical Dementia Rating (CDR), Geriatric Depression Scale (GDS), Unified Parkinson's Disease Rating Scale-motor (UPDRS), Cognitive-12 (Cog-12). Safety was monitored by the adverse events collected and physical and laboratory findings during the study. Mean changes in the scores of MMSE, ACE-R, Cog-12, FBI, ROSA, FAB and CDR showed a trend towards worsening at the final visit, reflecting a decline in cognitive and behavior performance, executive functions, severity of dementia. However, during one year after baseline, the measurement of cognitive and behavior performance, including MMSE, ACE-R, Cog-12, ROSA, demonstrated a transient improvement. While the mean changes of GDS and UPDRS, which showed mood and motor performance symptoms remained relatively stable. Memantine treatment was well tolerated and safe. Although memantine did not offer continued therapeutic benefit for up to 3 years in patients with bvFTD, it provided up to 6 months short-term benefits in cognitive and behavior performance. Memantine was well tolerated and future placebo-controlled trials of memantine should be conducted to evaluate the efficacy. Trial profile Longitudinal changes between the scores of every follow-up visit and baseline. ▲ indicates statistical significance between the scores of the follow-up visit and baseline • indicates no statistical significance between the scores of the follow-up visit and baseline (A) Mean ± SD change from baseline in Mini Mental State Examination (MMSE). (B) Mean ± SD change from baseline in Addenbrooke's Cognitive Examination-revised (ACE-R). (C) Mean ± SD change from baseline in Frontal Assessment Batten' (FAB). (D) Mean ± SD change from baseline in Frontal Behavior Inventory (FBI). (E) Mean ± SD change from baseline in Relevant Outcome Scale for Alzheimer's disease (ROSA). (F) Mean ± SD change from baseline in Clinical Dementia Rating (CDR). (G) Mean ± SD change from baseline in Geriatric Depression Scale (GDS). (H) Mean ± SD change from baseline in Unified Parkinson's Disease Rating Scale-motor (UPDRS). (I) Mean ± SD change from baseline in Cognitive-12 (Cog-12).