Table 1.
Published results of clinical trials in mild to moderate Alzheimer’s disease where volumetric magnetic resonance imaging was used as an imaging endpoint
| Compound | Subject numbers | Follow-up duration (months) | Treatment effect | |
|---|---|---|---|---|
| Placebo arm | Treatment arm | |||
| AN-1792 [35] | 57 | 231a | 11 | Ventricles (⇑), whole brain atrophy (⇑, antibody responders only), hippocampus (⇔) |
| Atorvastatin and donepezil [38] | 64b | 18 | Whole brain (⇔), hippocampus (⇓) | |
| Bapineuzumab (phase II) [21] | 122 | 107 | 18 | Whole brain (⇓, in ε4 noncarriers)c, ventricles (⇑, in ε4 carriers)d |
| Bapineuzumab (phase III) ε4 carriers [22] | 238 | 352 | 18 | Whole brain (⇔) |
| Bapineuzumab (phase III) ε4 noncarriers [22] | 244 | 315e | 18 | Whole brain (⇔) |
| CAD106 [19] | 7/5 | 24/21f | 6, 12 | Whole brain (⇔)g, ventricles (⇔), hippocampus (⇓)h |
| Docosahexaenoic acid [33] | 49 | 53 | 18 | Whole brain (⇔), ventricles (⇔), hippocampus (⇔) |
| Intravenous immunoglobulin [32] | 7 | 21 | 3, 6 | Whole brain (⇔), hippocampus (⇔) |
| Memantine [40] | 40i | 12 | Whole brain (⇔), ventricles (⇔), hippocampus(⇓, right only) | |
| Memantine [41] | 118 | 110 | 12 | Whole brain (⇔), hippocampus (⇔) |
| Rosiglitazone [34] | 38 | 38 | 6, 12 | Whole brain (⇔) |
| Scyllo-inositol [31] | 83 | 259 | 18 | Whole brain (⇔), ventricles (⇑), hippocampi (⇔) |
| Semagacestat [30] | 208b | 18 | Whole brain (⇔), hippocampus (⇔) | |
| Solaneuzumab [29] | 370/400j | 370/406 | 18 | Whole brain (⇔), hippocampus (⇔) |
| Tramiprosate [45,46] | 109 | 203k | 18 | Hippocampus (⇓)l |
⇑, Treatment effect of increased atrophy (or ventricular enlargement); ⇓, treatment effect of decreased atrophy (or ventricular enlargement); ⇔, no treatment effect found. aOf these 231 subjects in the treatment arm, 45 were antibody responders. bThe number of subjects enrolled in the magnetic resonance imaging substudy does not identify a division between the placebo arm and the treatment arm, thus the number in the cell indicates the total number of subjects over both arms. cLess brain atrophy (10.7 ml over 71-week follow-up) in apolipoprotein E noncarriers receiving bapineuzumab. dMore ventricular enlargement (2.6 ml over 71 week follow-up) in apolipoprotein E carriers receiving bapineuzumab. eThe 315 subjects consisted of 169 at 0.5 mg/kg dose and 146 at 1.0 mg/kg dose. fThe CAD106 study had two cohorts, where the treatment arm dosage was different (Cohort I, 50 μg; Cohort II, 150 μg). gOne global measure of atrophy, left cerebral white matter, did show a treatment effect in Cohort I, but this did not survive correction for multiple comparisons. hIn Cohort I, the right hippocampus showed a treatment effect and left hippocampus showed a trend towards treatment effects, but these did not survive multiple comparisons. iSingle-group open-label study where subjects had a 24-week lead-in period, followed by 24 weeks treatment of memantine. jThe publication consisted of two phase III studies, neither of which showed any treatment effects. kTwo treatment arms: 103 subjects at 100 mg twice daily, 100 subjects at 150 mg twice daily. lOriginal model showed no treatment effects, but post-hoc analysis putting in site as a random effect and important covariates showed a treatment effect.