Table 1.

Phase 2/3 trials with published results

Trial number	Source	Intervention	Control	N	Phase	Follow-up intervals	Cognitive measures	Cognitive result	Level of Evidence	GRADE
IMP-based interventions
NCT03100149	Pagano et al., 2022	Prasinezumab	Placebo	316	2	52 weeks	MoCA	No significant differences in MoCA at high or low dose	2
NCT03769896	Peball et al., 2020	Nabilone	Placebo	48	2	4 weeks	MoCA	No significant change in MoCA	2
NCT04403399	Albin et al., 2021	Varenicline	Placebo	34	2	2 × 3-week treatment & washout periods	MoCA, SAT	Significant improvement on SAT (without distractor, treatment difference 0.076, 95% CI 0.0073–0.14, p=.03; non-significant after correction for multiple comparisons); No significant change in other cognitive tests	2	Low
NCT02642393	Mestre et al., 2021	Inosine	Placebo	298	3	2 years	MoCA	No significant change in MoCA	2
NCT03305809	Biglan et al., 2022	Mevidalen	Placebo	344	2	12 weeks	ADAScog, MoCA, ADCS-CGIC	No significant change in ADAScog or MoCA; Dose-dependent significant improvement in ADCS-CGIC in intervention group (minimal or better improvement: 32.9% of subjects in placebo vs 58.0% for 30 mg, 58.2% for 75 mg [p<.001 for both]; moderate or better improvement: 6.8% of subjects in placebo vs 21.7% for 30 mg, 30.9% for 75 mg [30mg p<.05; 75mg p<.001])	2	Moderate
Device-based interventions
NCT03417271	Dayal et al., 2020	STN DBS	OFF	16	2	4 weeks	Verbal fluency	No significant difference in verbal fluency	2

Abbreviations: GRADE = Grades of Recommendation Assessment, Development and Evaluation, IMP = Investigational Medicinal Product, MoCA = Montreal Cognitive Assessment, ADAScog = Alzheimer’s Disease Assessment Scale–Cognitive Subscale, ADCS-CGlC = Alzheimer’s Disease Cooperative Study - Clinical Global Impression of Change, SAT = Sustained Attention Test, STN DBS= Subthalamic nucleus deep brain stimulation, CI = Confidence interval