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. Author manuscript; available in PMC: 2022 Jul 1.
Published in final edited form as: Ann Neurol. 2021 May 26;90(1):130–142. doi: 10.1002/ana.26102

TABLE 5.

Crossover Study Cognitive and Behavioral Outcomes: Intent-to-Treat Population (N = 34) for All Measures except SAT/dSAT (n = 21)

Varenicline LS, Mean (SE) Placebo LS, Mean (SE) Treatment Difference (95% CI) p
Cognitive measures reflecting cholinergic signaling
 SATa 0.73 (0.06) 0.66 (0.06) 0.076 (0.0073, 0.14) 0.03b
 dSATa 0.49 (0.06) 0.43 (0.06) 0.058 (−0.03, 0.15) 0.18
Conventional cognitive measures
 MoCA 26.83 (0.29) 27.23 (0.29) −0.40 (−1.22, 0.43) 0.34
 WAIS-III digit symbol 62.38 (1.29) 62.34 (1.28) 0.04 (−1.92, 2.00) 0.97
 CVLT STM 12.03 (0.32) 12.36 (0.32) −0.33 (−1.14, 0.48) 0.41
 CVLT LTM 12.44 (0.30) 12.80 (0.30) −0.36 (−0.77, 0.04) 0.07
 CVLT recognition 15.56 (0.13) 15.47 (0.13) 0.09 (−0.11, 0.30) 0.36
 D-KEFS Stroop III, interference 112.52 (3.42) 115.31 (3.37) −2.79 (−12.06, 6.47) 0.54
 JOLO 25.84 (0.48) 24.48 (0.48) 0.36 (−0.79, 1.52) 0.53
 D-KEFS sorting total 84.55 (1.57) 85.63 (1.55) −1.08 (−4.66, 2.49) 0.54
 D-KEFS verbal fluency–letters total 43.53 (1.05) 41.69 (1.04) 1.83 (−0.61, 4.27) 0.14
 D-KEFS verbal fluency–animal 18.19 (0.72) 18.07 (0.71) 0.12 (−1.33, 1.56) 0.87
 Trail Making Test 4 103.19 (8.12) 103.38 (8.03) −0.19 (−16.37, 15.98) 0.98
Behavioral
 GDS 3.56 (0.28) 3.31 (0.27) 0.25 (−0.33, 0.84) 0.38

Estimates (least squares or adjusted means and standard errors) and p values were obtained from a linear mixed model containing treatment sequence, treatment period, treatment group, and dependent-variable baseline value, with participant within treatment sequence as a random effect.

a

Estimates (least squares or adjusted means and standard errors) and p values were obtained from a linear mixed model containing treatment sequence, treatment period, and treatment group, with participant within treatment sequence as a random effect.

b

Statistically significant.

CI = confidence interval; CVLT = California Verbal Learning Test; D-KEFS = Delis–Kaplan Executive Function System; dSAT = SAT with a distractor; GDS = Geriatric Depression Scale; JOLO = Judgment of Line Orientation; LS = least squares; LTM = long-term memory; MoCA = Montreal cognitive assessment; SAT = Sustained Attention Test; SE = standard error; STM = short-term memory; WAIS-III = Wechsler Adult Intelligence Scale, 3rd edition.