Table 6 Outcomes of dementia/Alzheimer’s disease
Lead author, year | Study design | Interventions and comparator (dose/route of administration) | Adverse effects | Main outcome measures | Key findings | Retention rate (%) |
|---|---|---|---|---|---|---|
Bodick (1997) [99] | 6-month, randomised, double-blind, placebo- controlled, parallel-group trial | Intervention: Xanomeline Tartrate 25 mg (TID) 50 mg (TID) 75 mg (TID) Oral, 24 weeks Control: placebo | Syncope, nausea, vomiting, increased salivation, increased diaphoresis, mild to moderate increase in hepatic and biliary transaminase enzyme | ADAS-Cog CIBIC+, ADSS, NOSGER | Xanomeline at highest dose of 75 mg significantly improved CIBIC+ (p = 0.01), NOSGER score (p = 0.03) In ADSS score, higher improvement (p < 0.002) was evident for vocal outbursts, suspiciousness, delusions, agitations and hallucinations No significant improvement was observed in ADAS-cog scale compared to placebo | <30 |
Bruno (1986) [101] | Double blind, placebo controlled, randomised | Intervention: RS-86 Started at 0.5 mg/day Titrated up to 5 mg/day Maximum mean dose/day=4.6 mg (4–5 mg) 4 times a day 8 days oral Control: placebo Washout: 5 days | Diaphoresis, hypersalivation | Neuropsychological tests Story recall for immediate memory Word learning Dichotic listening Visual form of discrimination test Pictorial memory Recurring figures Reaction time | No significant difference between RS-86 and placebo in any of the tasks | 100 |
Hollander (1987) [100] | Double blind, cross-over, randomised, placebo-controlled | Intervention: RS-86 Dose varies between patients till Maximum tolerated Dose range = 0.75–1.5 mg Oral, 2 weeks Control: placebo | Chills, excessive sweating, flushing, depressed mood, prolongation of P-R interval on EKG, tremor, hypersalivation, and confusion | Cognitive and noncognitive symptoms using ADAS | No statistical significance difference was observed in any of the ADAS symptomatic subscales | 80 3 patients dropped out due to severe adverse events (syncope, abdominal distress, seizure) |
Thal (2000) [102] | Multisite 6-month, randomised, double-blind, placebo-controlled, parallel group trial | Intervention: Lu 25-109 25 mg (TID) 50 mg (TID) 100 mg (TID) oral 24 weeks Control: placebo | Dizziness, nausea, diarrhoea, fatigue, sweating, anorexia, increased salivation, vomiting, loss of weight, and asthenia | ADAS-Cog ADCS-ADL BEHAVE-AD | No significant differences in any of the outcome measures compared with placebo | 61 Higher discontinuation rate in high dose group due to adverse effects |
Veroff (1998) [98] | Multisite 6-month, randomized, double-blind, placebo- controlled, parallel-group trial | Intervention: xanomeline tartrate 25 mg (TID) 50 mg (TID) 75 mg (TID) Oral, 24 weeks Control: placebo | Not reported | CNTB ADAS | Xanomeline significantly improved CNTB summary score (p < 0.05), but not ADAS | 61 |