Effects of an Adaptogenic Extract on Electrical Activity of the Brain in Elderly Subjects with Mild Cognitive Impairment: A Randomized, Double-Blind, Placebo-Controlled, Two-Armed Cross-Over Study

Abstract

Background: The current and potential uses of adaptogens are mainly related to treatment of stress-induced fatigue, impaired cognitive function, mental illness, and behavioral- and age-related disorders. However, clinical evidence regarding the efficacy of adaptogens is limited. The primary aim of this study is to determine whether a combination of adaptogenic plant extracts from Andrographis paniculata and Withania somnifera (Adaptra^® Forte) could be used as effective and safe treatment for impaired cognitive, memory, or learning ability functions and sleep disorders.

Methods: The changes in electroencephalogram (EEG) frequency ranges in 17 different brain regions, psychometric tests of cognitive performance, as well as standard questionnaires of assessment of mood and sleep were measured after single and repeated administration of Adaptra^® or placebo for four weeks and after a two-week treatment-free follow-up period within a randomized, double-blind, placebo-controlled two-armed cross-over study.

Results: Adaptra^® Forte significantly improved cognitive performance in the d2-Test for attention and the concentration performance test after four weeks' treatment, and was positively correlated with increases in δ and θ power in the quantitative EEG compared with placebo during cognitive challenges.

Conclusion: The results of this study suggest that Adaptra^® Forte exhibits a calming and anxiolytic effect without sedation, and is associated with overall stress-protective activity.

Keywords: Andrographis paniculata; Withania somnifera; adaptogens; cognition; discriminant analysis; elderly subjects; psychometry; quantitative EEG; sleep.

Figure 1

Effect of Adaptra^® Forte in comparison with placebo with regard to spectral changes in all brain regions and at all six frequency ranges (2 h after intake) regarding an average of all electrode positions during recording with either eyes open or eyes closed. Results from first experimental day (acute) on the left side, from the last day (repetitive) after 4 weeks of intake on the right side of the image. Baseline values were set as 100%. * p < 0.12; ** p < 0.05; ***p < 0.01.

Figure 2

Spectral power differences under the eyes open recording condition on the first experimental day (acute) and on the last experimental day (repetitive) with administration of placebo or Adaptra^® Forte in all brain regions as represented by the electrode positions. C = central, p = parietal, O = occipital, F = frontal, T = temporal. Even numbers indicate location in the right hemisphere while odd numbers indicate the left hemisphere. Frequencies: red = δ, orange = θ, yellow = α1, green = α2, turquoise = β1, and blue = β2. The spectral power (between 30% and 270% on the ordinate of the bar graph) was averaged over 6 min and plotted against the pre-drug value (values at 0 min set as 100%), thus reflecting the effect of placebo or Adaptra^® Forte. * p < 0.12; ** p < 0.05; *** = p < 0.01 (non-parametric sign test) between placebo and Adaptra^® Forte. The direction of change is marked by + or − underneath the relevant bar.

Figure 3

Spectral power differences under the eyes closed recording condition on the first experimental day (acute) and on the last experimental day (repetitive) with administration of placebo or Adaptra^® Forte in all brain regions as represented by the electrode positions. C = central, p = parietal, O = occipital, F = frontal, T = temporal. * p < 0.12; ** p < 0.05; *** p < 0.01.

Figure 4

Spectral power differences on d2-attention-test, Concentration Performance Test CPT, and memory tests as deviation from the eyes open recording condition, which was set as 100% on the last experimental day with the administration of placebo or Adaptra^® Forte in all brain regions represented by the electrode positions. C = central, p = parietal, O = occipital, F = frontal, and T = temporal. Even numbers are located in the right hemisphere, uneven numbers in the left. Frequencies: red = δ, orange = θ, yellow = α1, green = α2, turquoise = β1, and blue = β2. The spectral power (between 30% and 270% on the ordinate of the bar graph) was averaged over 5 min and plotted against the eyes open condition (set as 100%), thus reflecting the effect of the placebo or Adaptra^® Forte. Statistical significance (non-parametric sign test) between placebo and Adaptra^® Forte: * p < 0.12; ** p < 0.05; *** p < 0.01.

Figure 5

Data during eyes open and eyes closed conditions at baseline compared with follow-up (day FU) in comparison with day A (100%). Statistical significance between FU in comparison to day A is depicted for each brain region and each frequency range. Statistical difference in FU data is marked as: * p < 0.12; ** p < 0.05.

Figure 6

Result of discriminant analysis. Acute effect during eyes open recording condition: Adaptra Forte ac; repetitive effect during eyes open recording condition: Adaptra Forte re. Results from first 3 discriminant functions are displayed with respect to space (x, y, and z coordinates. Results from the next 3 discriminant functions are displayed as additive color mixture similarly to RGB mode on a TV. If preparations are projected in rather close proximity, they cannot well be discriminated from each other, which means they have a similar effect or can be used within a similar clinical indication.

Figure 7

Design and timeline of the study days A, B, C, D, and FU. Performance: eyes open (Eo), eyes closed (Ec) and different cognitive tests: attention test (d2-Test), memory test (ME-Test), and concentration performance test (CPT).