Journal of Psychiatric Research
journal homepage: www.elsevier.com/locate/jpsychires
Mindfulness intervention for mild cognitive impairment led to attention-related improvements and neuroplastic changes: Results from a 9-month randomized control trial
Junhong Yu a, * , Iris Rawtaer b , Lei Feng a , Johnson Fam a , Alan Prem Kumar d , Irwin Kee-Mun Cheah e , William G. Honer f , Wayne Su f , Yuan Kun Lee g , Ene Choo Tan h, i , Ee Heok Kua a , Rathi Mahendran a, c, **
a Department of Psychological Medicine, Mind Science Centre, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
b Department of Psychiatry, Sengkang General Hospital, Singhealth Duke-Nus Academic Medical Centre, Singapore
c Academic Development Department, Duke-NUS Medical School, 8 College Road, Singapore
d Cancer Science Institute of Singapore, National University of Singapore, And Medical Science Cluster, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
e Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
f Department of Psychiatry, University of British Columbia, Vancouver, Canada
g Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University Hospital, Singapore
h KK Research Laboratory, KK Women’s and Children’s Hospital, Singapore
i SingHealth Duke-NUS Paediatrics Academic Clinical Program, Singapore
ARTICLE INFO
Keywords:
Mindfulness
Meditation
RCT
Cognitive enhancement
Attention
Cortical thickness
Neuroplasticity
Mild cognitive impairment
ABSTRACT
Mindfulness-based interventions can enhance cognitive abilities among older adults, thereby effectively delaying cognitive decline. These cognitive enhancements are theorized to accompany neuroplastic changes in the brain. However, this mindfulness-associated neuroplasticity has yet to be documented adequately. A randomized controlled trial was carried out among participants with mild cognitive impairment (MCI) to examine the effects of a mindfulness-based intervention on various cognitive outcomes and cortical thickness (CT) in the context of age-related cognitive impairment. Participants were assigned to a mindfulness awareness program (MAP)(n = 27) and an active control condition — health education program (n = 27). In both, they attended weekly sessions for three months and subsequently, monthly sessions for six months. Cognitive assessments and structural scans were carried out across three time-points. Whole brain analyses on CT were carried out and were supplemented with region of interest-based analyses. ROI values and cognitive outcomes were analyzed with mixed MANOVAs and followed up with univariate ANOVAs. Nine-month MAP-associated gains in working memory span and divided attention, along with an increased CT in the right frontal pole and decreased CT in the left anterior cingulate were observed. Three-month MAP-associated CT increase was observed in the left inferior temporal gyrus but did not sustain thereafter. MAP led to significant cognitive gains and various CT changes. Most of these neurobehavioral changes, may require sustained effort across nine months, albeit at a reduced intensity. MAP can remediate certain cognitive impairments and engender neuroplastic effects even among those with MCI.
1. Introduction
Early treatment in dementia is crucial to maximizing treatment
outcomes and functional independence (Gauthier, 2005). To this end, the mild cognitive impairment (MCI) diagnostic entity conceptualized two decades ago, has been positioned as the intermediate stage between
* Corresponding author. Department of Psychological Medicine Yong Loo Lin School of Medicine, National University of Singapore MD1 Research Dry Laboratories (North), #12-01, 12 Science Drive 2, 117549, Singapore.
** Corresponding author. Senior Consultant and Associate Professor, Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, NUHS Tower Block, Level 9, 1E Kent Ridge Road, 119228, Singapore.
E-mail addresses: pcmyj@nus.edu.sg (J. Yu), pcmrathi@nus.edu.sg (R. Mahendran).
https://doi.org/10.1016/j.jpsychires.2021.01.032
Received 21 February 2020; Received in revised form 23 December 2020; Accepted 16 January 2021
Availableonline21January2021 0022-3956/©2021ElsevierLtd.Allrightsreserved.
healthy aging and dementia, in which researchers are optimistic that interventions would alter the course of subsequent cognitive decline (Petersen et al., 2014).
Among the non-pharmacological interventions that have been carried out on the MCI population, there has been a growing interest in mindfulness-based interventions (Chan et al., 2019). Although such interventions traditionally target psychoaffective or behavioral issues (Baer, 2003), evidence suggests that they can bring about a strong cognitive enhancement effect (Chiesa et al., 2011) as well— which can be exploited to delay subsequent cognitive decline. This is due to the fact that meditation recruits several cognitive processes, which are trained upon repeated sessions.
Mindfulness meditation generally involves focused attention and/or open monitoring. In focused attention, the meditator has to direct and sustain attention on an internal or external stimulus for a period of time. In doing so, the meditator needs to constantly monitor his/her thoughts to detect mind wandering. Occasionally, the meditator disengages from
a distracting object (attention switching) and redirects attention to another stimulus (selective attention)(Lutz et al., 2008). During open monitoring, the meditator attends to the moment-by-moment experience in the ‘here and now’ in a nonjudgmental manner. In doing so, he/she has to inhibit automatic cognitive appraisals and divert attention away from distracting stimuli that would obscure attention to the moment-by-moment experience (Jha et al., 2019). Essentially, meditation can be thought of as a type of cognitive training for these different cognitive abilities.
Alongside these training-related improvements, repeated sessions of meditation may also trigger experience-dependent neuroplastic changes. In this regard, one randomized controlled trial (RCT) assigned healthy participants (i.e., self-reported to be psychologically and physically healthy, and not taking any medications) to a nine-session Mindfulness-Based Stress Reduction (MBSR n = 16) intervention or a wait-list control condition (n = 17) and compared the gray matter (GM) changes between both groups. It was observed that the GM volumes in
Fig. 1. Consort flow diagram. MCI = mild cognitive impairment; MRI = magnetic resonance imaging; MAP = Mindfulness Awareness Program; HEP = Health Education Program; AX = assessment.
Table 1
Characteristics of participants assigned to both treatment conditions.
2. Material and methods
2.1.
Design
Female 19 21
Mean
Mean sessions attendeda (SD) First 3 months (12 sessions)
Subsequent 6 months (6 sessions)
Note. MAP = Mindfulness awareness program; HEP = Health education program; SD = standard deviation; MMSE = Mini-Mental State Examination. aAmong the analyzed longitudinal sample.
Table 2
Cognitive outcomes assessed.
Test
Semantic fluency test
Outcomes Cognitive functions assessed
Number of unique animals Verbal fluency
Color trails test Interference effect Divided attention and setswitching
Digit span subtests (WAISIII)
Rey Auditory Verbal Learning Test
Block design test (WAISIII)
Digits forward total score Working memory span
Digits backward total score Working memory manipulation
Immediate recall Immediate memory
Delayed recall Delayed memory
Delayed recognition Recognition memory
Total raw score Visuospatial processing
Note. WAIS-III = Wechsler Adult Intelligence Scale III.
left posterior cingulate cortex, left temporo-parietal junction, hippocampus and bilateral regions in the cerebellum had increased in the MBSR group as compared to the wait-list controls (Holzel et al., 2011).
Another RCT (Pickut et al., 2013) compared 14 patients with Parkinson’s disease assigned to an eight-week mindfulness-based intervention and 13 patients on usual care, and found increased GM volume in the bilateral caudate nucleus, left occipital lobe, left thalamus and bilateral temporo-parietal junction in the former group. A third RCT compared 12 college students assigned to a 4-week Sahaja Yoga meditation training with 30 wait-list controls and found meditation-associated GM increase in the right inferior frontal gyrus (Dodich et al., 2019). Additionally, two other RCTs (Tang et al., 2010; Wells et al., 2013) did not observe significant meditation-associated GM changes. In general, the evidence on the neuroplastic GM changes associated with meditation has been limited and inconclusive.
In addition to replicating the previously documented meditationassociated cognitive gains, we sought to make a meaningful contribution to the limited pool of evidence relating to the meditation-associated neuroplasticity. The current study evaluates the effect of a mindfulnessbased intervention on various cognitive outcomes and GM cortical thickness (CT) across a 9-month intervention period. We hypothesized that such intervention would engender significant cognitive gains, especially in the attentional domains, as well as increase CT in various cortical GM regions which were found to differ between experienced meditators and meditation-naïve controls.
The study was carried out as an open-label RCT. Randomization was stratified by gender and carried out in blocks of four using the Random Allocation Software 2.0 by an independent researcher. The intervention consisted of two arms— mindfulness awareness program (MAP) and health education program (HEP). The latter was used as an active control condition for the former, to control for possible effects due to social interaction. The intervention spans across nine months and consisted of two phases in both arms. During the first 3-month phase, sessions were held once per week for 12 sessions. Thereafter, these sessions took place once per month in the subsequent 6-month phase. The rationale for dividing the intervention into two different phases of different treatment intensities was to assess if the treatment gains from the first phase can be sustained with much less time commitment from the participants in the second phase. Each session would last for 45 min. The CONSORT flow diagram of the study is shown in Fig. 1. Ethical approval for the current study was granted by a university’s institutional research board.
2.2.
Participants
Participants of the current study were recruited from the community, as part of the larger Aging in a Community Environment Study cohort (Feng, 2015). Details regarding the recruitment, which was carried out from 2011 to 2016 have been described elsewhere (Yu et al., 2016). Subsequently, participants from this cohort were invited to participate in the current intervention study. The inclusion criteria were 1) aged between 60 and 85 (inclusive), 2) met the criteria for mild cognitive impairment (MCI), 3) able to travel to the intervention venue independently, 4) not presenting with any current psychiatric or neurological conditions, 5) not suffering from any terminal illness, 6) not participating in another interventional study and 7) for those undergoing magnetic resonance imaging (MRI) scans, not having any metallic body implants (e.g., pacemaker), with the exception of dental implants.
The Petersen’s (2004) criteria were used for the MCI diagnosis. These include subjective cognitive complaints as corroborated by a reliable informant, presence of objective cognitive impairment and largely preserved functional independence. In particular, the objective cognitive impairment criterion was operationalized as scoring 1.5 standard deviations (SD) below the age and education appropriate norms in any of six cognitive domains, as assessed via the digit span backward and block design tests from Wechsler Adult Intelligence Scale (WAIS-III), delayed recall and recognition tests from the Rey Auditory Verbal Learning Test (RAVLT), Color Trails Test (CTT), and semantic fluency test. The MCI diagnoses were made via a consensus from a panel of psychiatrists and psychologists.
Fifty-four participants were randomized into the two treatment conditions. Information regarding their demographic characteristics, general cognitive status and attendance are presented in Table 1 Independent samples t-tests suggest that both intervention groups were not significantly different in terms of attendance in the two phases (ps ≥ .77). Written informed consent was obtained from these participants prior to their participation. Among them, 51 had at least completed the first 3-month phase and 39 completed both phases. For the first three months, our calculations using G*Power indicated that the valid sample size would provide a power of 0.80 (assuming an alpha level of 0.05 and a 0.5 correlation between repeated measures) to detect a significant Time * Group interaction if the true effect was at least 0.40 SD. Across the entire 9-month intervention period, our calculations using the same parameters suggest that we can detect a true effect of at least 0.46 SD. Considering that a recent meta-analysis (Chan et al., 2019) revealed a much larger effect of meditation on global cognition among older adults (SMD = 0.56), our sample sizes are more than adequate to detect the hypothesized interaction effect on cognitive outcomes.
Table 3
Results of the mixed ANOVA on cognitive outcomes from baseline to ninth month.
Note. CTT = Color trails test; q = p values adjusted for false discovery rate.
2.3. Measures
Eight cognitive outcomes, indexing working memory span and manipulation, divided attention, immediate, delayed and recognition memory, verbal fluency and visuospatial processing from various tests were administered (see Table 2). The procedures for these tests are described in detail in the supplementary materials. For these measures, higher scores correspond to better performance, with the exception of the CTT interference, in which smaller interference scores relate to better performance.
2.4.
Intervention protocol
The MAP was modeled on similar group-based mindfulness meditation for older adults (McBee, 2008) and was led by an experienced instructor. Participants were taught 1) mindfulness of the senses practice— to attend to the different senses (i.e., vision, hearing, touch) to cultivate focused attention; 2) body scan practice— to develop kinesthesia by focusing their attention on various parts of their body as a relaxation technique, while in a sitting and/or supine position; 3) walking meditation practice— to cultivate calmness and momentary concentration by walking slowly with mindfulness; 4) ‘movement nature meant’ practice— to move with awareness for flexibility, strength and confidence; and 5) visuomotor limb tasks that train one’s mind-body coordination.
The weekly HEP didactic sessions were taught by an experienced instructor, and covered topics such as chronic medical conditions (e.g., hypertension, diabetes, arthritis), medication compliance, and healthy lifestyles (e.g., diet, nutrition, exercise, and relaxation). In the subsequent monthly discussion sessions, participants shared how they had applied what they learned to their daily lives. Both programs were separately carried out in a quiet room in a community location.
2.5. MRI acquisition
Participants were scanned in a 3-T Siemens Tim Trio scanner at the Clinical Imaging Research Center, Singapore. T1-weighted images were acquired using an MPRAGE protocol (TE = 1.90s; TR = 2.30s; TI = 900 ms; 256 × 256 matrix; 192 sagittal slices; in-plane resolution = 1 mm; slice thickness = 1 mm).
2.6. Image preprocessing
T1-weighted images were preprocessed longitudinally using the CAT12 (version r1450) as implemented in SPM12 (version 6225) within MATLAB (R2019a). Baseline and follow-up images were rigidly realigned within-subject to correct for differences in head position and a subject-specific average template was computed and used as reference in a subsequent realignment of the baseline and follow-up images. The realigned images were segmented into GM, white matter (WM) and cerebrospinal fluid, as well as corrected for signal inhomogeneities with reference to the subject average template. These GM and WM images
were used to estimate spatial normalization deformation fields using the high dimensional Diffeomorphic Anatomic Registration Through Exponentiated Lie Algebra (DARTEL) warping algorithm (Ashburner, 2007) which were applied to segmented images and subsequently modulated. These modulated images were then visually inspected.
Estimation of CT and the central surface was carried out using the projection-based thickness method (Dahnke et al., 2013), which consisted of topology correction (Yotter et al., 2011), spherical mapping, and spherical registration (Yotter et al., 2011). After obtaining the segmented images, WM distance was estimated and the local maxima were projected to other GM voxels using a neighbor relationship described by the WM distance (Dahnke et al., 2013). The ‘surface thickness and thickness estimation for ROI’ writing option was used to extract region-of-interest (ROI) values from the Desikan-Killiany atlas (Desikan et al., 2006).
2.7. Statistical analyses
We were primarily interested in the treatment gains at the two possible ‘exit points’ third and ninth month, hence for the following analyses we compared the outcomes between baseline and third month, as well as between baseline and ninth month timepoints.
First, we carried out whole brain analysis on the preprocessed surfaced images. Two subjects (one from each treatment group) were excluded from these analyses due to significant lesions. Then, treatment effects were assessed using a flexible factorial GLM, modeling the three factors of Subject, Group and Time, in which we examined the T contrasts for the Group * Time interaction (i.e., Timepost > Timepre & MAP > HEP and Timepost > Timepre & MAP < HEP). The results were thresholded using p < 0.05, family-wise error (FWE) correction against a null-distribution generated by 5000 nonparametric permutations using the TFCE toolbox, with a cluster extent threshold of k > 20. Significant clusters are labeled using the Desikan-Killiany atlas.
Given the relatively small number of scanned participants, a whole brain analysis was unlikely to yield multiple clusters that would survive the stringent FWE corrections. Hence, we supplemented the whole brain analyses with ROI-based analyses. Specifically, we selected on an a priori basis, ROIs that corresponded to the significant cortical GM clusters identified in a meta-analysis that compared between experienced meditators and meditation naïve controls (Fox et al., 2014). These included the bilateral regions of the anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), frontal pole (FP) and insula. Apart from the first two, these ROIs were extracted as they were parcellated in the atlas. The ACC ROI was created by summing the caudal and rostral anterior cingulate ROIs, and the OFC ROI was created by summing the lateral and medial orbitofrontal ROIs. These ROIs were entered into subsequent analyses together with the cognitive outcomes.
For the analyses of the cognitive outcomes and CT ROIs, in order to minimize the false positive results associated with multiple testing, multivariate analyses of variance (MANOVA) were carried out separately on the cognitive outcomes and CT ROIs, with time and group as the within- and between-subject factors, respectively, to determine the
J.
overall effect on the assessed outcomes. In line with our general analytical framework, the MANOVAs compared between baseline and third month, as well as between baseline and ninth month timepoints. If significant group*time interaction effects were obtained in any of these MANOVAs, post hoc univariate analyses of variance (ANOVA) were carried out individually on each outcome between the respective timepoints. Although it is possible to analyze all three timepoints in a single MANOVA and proceed with post hoc analyses, we did not do so. This is because the valid sample size at the ninth month timepoint is much smaller, given that the three-timepoint MANOVA can only be carried out
on participants with valid data on all three timepoints, such analyses would discard several participants with incomplete ninth month data, ultimately reducing statistical power. Effect sizes for the significant statistics relating to the time * group interactions were quantified using partial eta square (ηpartial 2 ), where ηpartial 2 of 0.06 and 0.13 indicates medium and large effect sizes, respectively. Statistical significance was set at p < .05. For the post-hoc ANOVAs, we have additionally computed p-values adjusted for false discovery rate (FDR). Nevertheless, we do not expect the significant results of these ANOVAs to survive such corrections, as this would require very large treatment effects and sample sizes
Fig. 2. Trajectories of cognitive outcomes in each group across time. The thick colored lines represent the mean trajectory of each group, which are enclosed within their respective 95% confidence intervals. *p < .05; **p < .01.
Table 4
Results of the mixed ANOVA on the regions-of-interest from baseline to ninth month.
Note. L = Left; R = Right; q = p values adjusted for false discovery rate.
that are beyond what is expected or practical for this study. These analyses were carried out R 4.0.2. The R code for executing these analyses and generating the figures are available at https://osf.io/ykz2c/files/.
3. Results
3.1. Effect of MAP on cognitive outcomes
The MANOVAs revealed a significant Time * Group effect on cognitive outcomes between the baseline and ninth month (F(8, 28) = 1.92; p = .022; ηpartial 2 = 0.44),but not between baseline and third month (F(8, 39) = 1.92; p = .106; ηpartial 2 = 0.27). Thus, univariate ANOVAs were carried out to follow up on the significant effects between the baseline and ninth month. The detailed results of all modeled effects in these ANOVAs are presented in Table 3 In these post hoc analyses, significant Time*Group interactions emerged for digit span forward and CTT interference. Fig. 2 showed that the digit span forward score and CTT interference among MAP participants had increased and decreased, respectively over time, relative to their HEP counterparts. As expected, none of these significant post-hoc results survived the FDR correction.
3.2. Effect of MAP on cortical thickness
The MANOVAs on the CT revealed a significant Time * Group effect between baseline and ninth month (F(8, 12) = 3.03; p = .041; ηpartial 2 = 0.67), but not between baseline and third month (F(8, 29) = 2.01; p = .080; ηpartial 2 = 0.36). Univariate ANOVAs were carried out to follow up on the significant effects between baseline and ninth month. The detailed results of all modeled effects in these ANOVAs are presented in Table 4.These ANOVAs revealed a significant Time * Group on the right FP (F(1, 19) = 5.19; p = .035; ηpartial 2 = 0.21) and left ACC (F(1, 19) = 5.18; p = .035; ηpartial 2 = 0.21). Fig. 3 showed that, relative to HEP participants, the CT in the right FP and left ACC among MAP participants had increased and decreased, respectively, across this period. None of these significant post-hoc results survived the FDR correction. Additionally, none of the CT changes in any ROIs were significantly correlated with any of the changes in cognitive outcomes. The descriptive statistics of the ROI CT values across the three time-points are reported in the supplementary materials (see table S2).
Next, CT was analyzed at the whole brain level. Across the first three months, whole brain analyses within the contrast of Time3-month > Timebaseline & MAP > HEP revealed a significant cluster in the left inferior temporal gyrus (ITG)(k = 28, peak level FWE-corrected p = .009; MNI = 55, 33, 24; see Fig. 4a). No significant clusters emerged in the reverse contrast (i.e., Time3-month > Timebaseline & MAP < HEP). Across the entire 9-month intervention period, no significant clusters were observed in any of the interaction contrasts. The uncorrected statistical maps of these contrasts are presented in the supplementary materials (see figures S1 and S2). Given these results, there is a possibility that the significant cluster obtained from the first 3-month period did not appear in the subsequent 6-month period, merely due to the reduced sample size. Hence, we investigated this further by
extracting the significant cluster as an ROI and entering these ROI values into a mixed ANOVA. The Time * Group effect across the entire 9-month intervention period was not significant (F(1, 36) = 0.21; p = .649; ηpartial 2 = 0.01 see Fig. 4b), in contrast to the significant interaction across the first three months (F(1, 19) = 23.27; p < .001; ηpartial 2 = 0.39).
4. Discussion
The current study examined the effects of a mindfulness-based intervention on cognitive outcomes and CT. In the cognitive domain, we observed a gradual improvement in working memory span and divided attention among MAP participants relative to their HEP counterparts, culminating in medium to large effect sizes across the entire 9month intervention period. As for CT, MAP participants, relative to their HEP counterparts had significantly increased CT, as quantified by a large effect size, in the right FP across the entire 9-month intervention period. At the end of the first 3-month phase, the CT in MAP participants had significantly increased in a left ITG cluster, as quantified by a large effect size, relative to HEP participants. However, these 3-month MAPassociated CT changes in the left ITG did not sustain until the ninth month. Overall, these results suggest that the MAP intervention led to significant cognitive gains and neuroplastic changes across the 9-month intervention period.
With repeated sessions of meditation, our MAP participants trained their abilities to engage and disengage their attention on various stimuli. Naturally, the effect of such attentional training would transfer to our measure of divided attention, where participants had to repeatedly engage and disengage between two sets of stimuli (i.e., pink and yellow circles in the CTT). Furthermore, we observed MAP-associated working memory improvements as measured by the digit span forward. Generally, working memory span benefits from an improved attention. A larger working memory span can be the result of a greater ability to control attention to avoid distraction and thereby maintain more stored items (Engle, 2002). Such controlled attention was practiced in our MAP as participants focused and sustained their attention on various external and interoceptive stimuli. However, we did not observe a similar MAP-associated improvement for working memory manipulation as measured by the digit span backward. Although meditation typically involves the manipulation information in the working memory, such manipulation is largely restricted to the engagement and disengagement of information in the present moment without judgment or elaboration (Jha et al., 2019). Arguably, this involves a relatively low cognitive load. Our measure of working memory manipulation requires elaborate processing of information— to reverse the order of the digits while holding these digits in the working memory. Essentially, for the digit span backward, working memory is being tested while being weighed down by an additional cognitive load. This is not something our MAP participants would have had more practice with than their HEP counterparts.
In terms of MAP-associated neuroplasticity, we observed some CT changes which are consistent with previous findings. First, there was a significant MAP-associated increase in the CT of the left ITG (at least within the first three months) and right FP. A meta-analysis (Fox et al.,
Fig. 3. Trajectories of cortical thickness values in each group across time. The thick colored lines represent the mean trajectory of each group, which are enclosed within their respective 95% confidence intervals. *p < .05.
2014) that compared between experienced meditators and meditation-naïve controls had observed similar clusters of GM volume increase in the right frontopolar cortex (including the FP) and left ITG. Relatedly, task-based functional MRI studies have shown that activations in the frontopolar cortex (Molenberghs et al., 2016) and the left ITG (Hasenkamp et al., 2012) were linked to meditation-associated meta-cognitive processes, such as meta-cognitive judgments and awareness of mind wandering. Given this, the MAP-associated CT increases in these regions could speculatively be linked to the enhanced meta-cognitive abilities typically brought about via repeated sessions of
meditation. As our intervention transitioned from weekly to monthly sessions, it was observed that the increased CT in the left ITG, were no longer sustained at the ninth month. Perhaps, this suggests that the monthly meditation sessions were not adequate to maintain such gains. It is plausible that if our intervention had continued its weekly sessions, greater neuroplastic changes and perhaps cognitive gains would be observed. Indeed, a meta-analysis on mind-body exercises observed that interventions with more frequent sessions were more likely to result in greater cognitive gains than those of less frequent sessions (Chan et al., 2019).
Fig. 4. a) Significant cluster (FWE-corrected p < 0.05) in left inferior temporal gyrus within the contrast of Time3-month > Timebaseline & MAP > HEP. b) trajectories of cortical thickness values of extracted cluster in each group across time. The thick colored lines represent the mean trajectory of each group, which are enclosed within their respective 95% confidence intervals. ***p < .001.
In contrast to previous cross-sectional studies that found increased ACC GM volume among experienced meditators (Fox et al., 2014), we observed a MAP-associated CT decrease in the ACC. Notwithstanding, the problems of comparing the current intervention results to cross-sectional findings, this decrease in ACC CT or volume should not always be viewed negatively, especially since the ACC is involved in several functions. One such function includes emotional processing (García-Cabezas and Barbas, 2016). In relation to this, a lesion study (Tolomeo et al., 2016) suggests that the removal of the anterior cingulate may be therapeutic for patients with intractable mood, anxiety and pain syndromes, specifically in terms of reducing negative affect. Relatedly, we speculate that the reduced ACC CT among MAP participants may reflect the neuroplastic changes corresponding to the MAP-associated attenuations in emotional reactivity to negative affect (Britton et al., 2012).
These findings present important implications in the clinical context. We have shown that a relatively low intensity (i.e., weekly or monthly sessions) non-pharmacological intervention can result in significant cognitive gains and neuroplastic changes in the context of age-related cognitive impairment. In essence, our intervention would be instrumental in delaying further cognitive decline or even enhancing one’s functional status, without the side-effects of medications (Smith, 2016) or exhaustion associated with intensive cognitive training (Vranic, 2017). Additionally, the MAP-associated cognitive gains were mostly observed within the domains of executive-attention. This would suggest that such mindfulness-based interventions would be more appropriate for older adults with executive-attentional impairments, such as those with nonamnestic MCI or at risk for frontotemporal dementia, than those with amnestic MCI or at risk for Alzheimer’s disease. It should also be noted that while the targeted cognitive gains are most relevant to this group of older adults, their executive functions deficits may bring about some difficulties during meditation, especially when they are required to sustain and focus their attention for a period of time.
The current study is subjected to a few limitations. First, this was an open-label study, in which both participants and the experimenters were aware of which treatment group the former was assigned to. There is a small possibility that the results may be confounded by observerexpectancy effects among experimenters and the differences in participants’ treatment expectancies between both groups. Second, the attrition rate for MRI data was quite significant; by the ninth month, the number of acquired scans was less than half of that at baseline. This limits the study’s ability to detect significant treatment effects on CT during the subsequent 6-month phase. Given that this attrition was largely due to various physical and psychological discomforts during the scans, future studies should attempt to alleviate some of these
discomforts in order to retain as many MRI-eligible participants as possible, especially among the older adult population.
CRediT authorship contribution statement
Junhong Yu: Writing - original draft, Formal analysis, Software, Visualization. Iris Rawtaer: Writing - original draft. Lei Feng: Writingreview & editing. Johnson Fam: Writing - review & editing. Alan Prem Kumar: Formal analysis, Writing - review & editing. Irwin Kee-Mun Cheah: Writing - review & editing. William G. Honer: Writing - review & editing. Wayne Su: Software, Formal analysis, Writing - review & editing. Yuan Kun Lee: Writing - review & editing. Ene Choo Tan: Writing - review & editing. Ee Heok Kua: Writing - review & editing, Funding acquisition. Rathi Mahendran: Writing - review & editing, Funding acquisition, Project administration, Supervision.
Declaration of competing interest
None.
Acknowledgement
We acknowledge the contributions of the following: the Late Mr Wee Sin Tho for developing and structuring the Mindfulness Program for this study and Dr Goh Lee Gan for developing and delivering the Health Education Talks
Appendix A. Supplementary data
Supplementary data to this article can be found online at https://doi. org/10.1016/j.jpsychires.2021.01.032
Financial support
This work was supported by Research Donations from Kwan Im Thong Hood Cho Temple and Lee Kim Tah Holdings Pte Ltd under the Mind Science Center, Department of Psychological Medicine, National University of Singapore.
References
Ashburner, J., 2007. A fast diffeomorphic image registration algorithm. Neuroimage 38, 95–113
Baer, R.A., 2003. Mindfulness training as a clinical intervention: a conceptual and empirical review. Clin. Psychol. Sci. Pract. 10, 125–143. https://doi.org/10.1093/ clipsy.bpg015
Britton, W.B., Shahar, B., Szepsenwol, O., Jacobs, W.J., 2012. Mindfulness-based cognitive therapy improves emotional reactivity to social stress: results from a randomized controlled trial. Behav. Ther. 43, 365–380. https://doi.org/10.1016/j. beth.2011.08.006
Chan, J.S.Y., Deng, K., Wu, J., Yan, J.H., 2019. Effects of meditation and mind–body exercises on older adults’ cognitive performance: a meta-analysis. Gerontol. https:// doi.org/10.1093/geront/gnz022
Chiesa, A., Calati, R., Serretti, A., 2011. Does mindfulness training improve cognitive abilities? A systematic review of neuropsychological findings. Clin. Psychol. Rev. 31, 449–464. https://doi.org/10.1016/j.cpr.2010.11.003
Dahnke, R., Yotter, R.A., Gaser, C., 2013. Cortical thickness and central surface estimation. Neuroimage 65, 336–348
Desikan, R.S., S´ egonne, F., Fischl, B., Quinn, B.T., Dickerson, B.C., Blacker, D., Buckner, R.L., Dale, A.M., Maguire, R.P., Hyman, B.T., 2006. An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest. Neuroimage 31, 968–980
Dodich, A., Zollo, M., Crespi, C., Cappa, S.F., Laureiro Martinez, D., Falini, A., Canessa, N., 2019. Short-term Sahaja Yoga meditation training modulates brain structure and spontaneous activity in the executive control network. Brain Behav 9. https://doi.org/10.1002/brb3.1159 e01159.
Engle, R.W., 2002. Working memory capacity as executive attention. Curr. Dir. Psychol. Sci. 11, 19–23. https://doi.org/10.1111/1467-8721.00160
Feng, L., 2015. Ageing in a community environment study (ACES) cohort. In: Pachana, N. A. (Ed.), Encyclopedia of Geropsychology 1–6. https://doi.org/10.1007/978-981287-080-3_360-1 Springer Singapore, Singapore.
Fox, K.C.R., Nijeboer, S., Dixon, M.L., Floman, J.L., Ellamil, M., Rumak, S.P., Sedlmeier, P., Christoff, K., 2014. Is meditation associated with altered brain structure? A systematic review and meta-analysis of morphometric neuroimaging in meditation practitioners. Neurosci. Biobehav. Rev. 43, 48–73. https://doi.org/ 10.1016/j.neubiorev.2014.03.016
García-Cabezas, M.A., Barbas, H., 2016. Anterior cingulate pathways may affect emotions through orbitofrontal cortex. Cerebr. Cortex 27, 4891–4910. https://doi. org/10.1093/cercor/bhw284
Gauthier, S.G., 2005. Alzheimer’s disease: the benefits of early treatment. Eur. J. Neurol. 12, 11–16. https://doi.org/10.1111/j.1468-1331.2005.01322.x
Hasenkamp, W., Wilson-Mendenhall, C.D., Duncan, E., Barsalou, L.W., 2012. Mind wandering and attention during focused meditation: a fine-grained temporal analysis of fluctuating cognitive states. Neuroimage 59, 750–760. https://doi.org/10.1016/j. neuroimage.2011.07.008.
Holzel, B.K., Carmody, J., Vangel, M., Congleton, C., Yerramsetti, S.M., Gard, T., Lazar, S. W., 2011. Mindfulness practice leads to increases in regional brain gray matter density. Psychiatry Res. Neuroimaging. 191, 36–43. https://doi.org/10.1016/j. pscychresns.2010.08.006
Jha, A.P., Denkova, E., Zanesco, A.P., Witkin, J.E., Rooks, J., Rogers, S.L., 2019. Does mindfulness training help working memory ‘work’ better? Curr. Opin. Psychol. 28, 273–278. https://doi.org/10.1016/j.copsyc.2019.02.012
Lutz, A., Slagter, H.A., Dunne, J.D., Davidson, R.J., 2008. Attention regulation and monitoring in meditation. Trends Cognit. Sci. 12, 163–169
McBee, L., 2008. Mindfulness-based Elder Care: A CAM Model for Frail Elders and Their Caregivers. Springer Publishing Co
Molenberghs, P., Trautwein, F.-M., Bockler, A., Singer, T., Kanske, P., 2016. Neural correlates of metacognitive ability and of feeling confident: a large-scale fMRI study. Soc. Cognit. Affect Neurosci. 11, 1942–1951. https://doi.org/10.1093/scan/ nsw093
Petersen, R.C., 2004. Mild cognitive impairment as a diagnostic entity. J. Intern. Med. 256, 183–194. https://doi.org/10.1111/j.1365-2796.2004.01388.x
Petersen, R.C., Caracciolo, B., Brayne, C., Gauthier, S., Jelic, V., Fratiglioni, L., 2014. Mild cognitive impairment: a concept in evolution. J. Intern. Med. 275, 214–228. https://doi.org/10.1111/joim.12190
Pickut, B.A., Van Hecke, W., Kerckhofs, E., Marien, P., Vanneste, S., Cras, P., Parizel, P. M., 2013. Mindfulness based intervention in Parkinson’s disease leads to structural brain changes on MRI: a randomized controlled longitudinal trial. Clin. Neurol. Neurosurg. 115, 2419–2425. https://doi.org/10.1016/j.clineuro.2013.10.002
Smith, G.E., 2016. Healthy cognitive aging and dementia prevention. Am. Psychol. 71, 268–275. https://doi.org/10.1037/a0040250
Tang, Y.-Y., Lu, Q., Geng, X., Stein, E.A., Yang, Y., Posner, M.I., 2010. Short-term meditation induces white matter changes in the anterior cingulate. Proc. Natl. Acad. Sci. Unit. States Am. 107, 15649–15652
Tolomeo, S., Christmas, D., Jentzsch, I., Johnston, B., Sprengelmeyer, R., Matthews, K., Douglas Steele, J., 2016. A causal role for the anterior mid-cingulate cortex in negative affect and cognitive control. Brain 139, 1844–1854. https://doi.org/ 10.1093/brain/aww069
Vranic, A., 2017. Leisure Time Activities as Cognitive Training: Can Cognitive Fitness Improve Well-Being of Older Adults?, in: Well-Being and Quality of Life-Medical Perspective. IntechOpen
Wells, R.E., Yeh, G.Y., Kerr, C.E., Wolkin, J., Davis, R.B., Tan, Y., Spaeth, R., Wall, R.B., Walsh, J., Kaptchuk, T.J., Press, D., Phillips, R.S., Kong, J., 2013. Meditation’s impact on default mode network and hippocampus in mild cognitive impairment: a pilot study. Neurosci. Lett. 556, 15–19. https://doi.org/10.1016/j. neulet.2013.10.001
Yotter, Rachel Aine, Dahnke, R., Thompson, P.M., Gaser, C., 2011. Topological correction of brain surface meshes using spherical harmonics. Hum. Brain Mapp. 32, 1109–1124
Yotter, Rachel A., Thompson, P.M., Gaser, C., 2011a. Algorithms to improve the reparameterization of spherical mappings of brain surface meshes. J. Neuroimaging 21, e134–e147
Yu, J., Rawtaer, I., Fam, J., Jiang, M.-J., Feng, L., Kua, E.H., Mahendran, R., 2016. Sleep correlates of depression and anxiety in an asian elderly population. Psychogeriatrics 16, 191–195. https://doi.org/10.1111/psyg.12138
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—Justo, justo! apoiou Meyer, então todo empenhado em picar um formoso coleoptero.
—Assim tambem é que eu entendo disse o mineiro.
—Mas, o que é jarracatiá, Sr. Pereira? insistiu o allemão.
Voltou-se o interpellado com impaciencia:
—É uma arvore, Sr. Meyer, arvore grande de folhas cortadas, que dá umas especies de mamõesinhos. Deitam leite muito grosso e queimão os beiços quando a gente não tem cuidado. É uma arvore ouviu? Uma arvore[97]!
—Ah! exclamou o allemão concertando a garganta.
Nesta occasião sacou Cyrino da canastra outros remedios e passou-os a Coelho, dando-lhe minuciosas informações sobre o modo por que havia de usar delles.
—Tem muito enjoo, quando come? perguntou o curandeiro.
—Muito Sr. doutor.
—Assim é, mas deixe estar; depois do leite de jaracatiá, volta-lhe a appetencia. Nos primeiros tempos, o senhor só hade beber claras de ovos bem batidas. Depois, irá a pouco e pouco tomando mais alimento.
—Deus o ouça...
Levantou-se Pereira e, chegando-se á porta, annunciou:
—Ahi vem gente... Estou ouvindo passos de animal montado... Sem duvida é algum pobre engorovinhado de doença. Isto de molestias, não faltam no mundo. Tambem ha tanta maldade, que não poderá ser por menos.
Depois de ligeira pausa, acrescentou em tom de surpresa e aborrecimento.
—Hi! meu Deus!... Nossa Senhora nos soccorra... Sabem quem vem chegando?... É o Garcia; está com o mal[98]?! ha mais de dois annos e não quer crer na desgraça... Pobre coitado, sem duvida vem comprar o desengano... Tenho muita pena dessa gente ... mas,
devéras, não a quero ver em minha casa... Vamos, Sr. doutor, despache o Garcia depressa Com lazaros não se brinca. A Senhora Sant'Anna de tal nos livre! Nem olhar é bom.
E, Pereira, voltando-se para dentro, pediu apressadamente:
—Não deixe o homem desapear, doutor: ficava-me depois o desgosto de ter que lhe fazer alguma mácreação. Pelo amor de Deus, vá lá fóra... Veja o que elle quer ... e dê-lhe boas tardes da nossa parte... Olhe, está chamando... Saia, doutor saia!
Ouvia-se, com effeito, uma voz perguntar se estava em casa o Sr. Pereira.
Este vendo que Cyrino não se apressava á medida dos seus desejos, ou temendo que o recem-chegado lhe entrasse na sala, sem demora appareceu á soleira da porta e, com manifesta sequidão, respondeu ao humilde comprimento de chapéu e á meiga saudação que lhe era dirigida.
[91]Emprestar de alguem, por tomar emprestado ou pedir emprestado, é locução muito corrente em todo o sertão de S. Paulo, Minas Geraes e Matto Grosso É legitimo gallicismo, que corresponde exactamente ao verbo emprunter.
Recordo-me da admiração com que ouvi uma pessoa da villa de Miranda, aliás de alguma leitura, dizer-me Venho ter com o Sr para lhe emprestar 20$000. Mas não preciso, retorqui-lhe. Não; quem precisa sou eu Eu empresto do Sr Ah! o Sr vem pedir-me 20$000, não é?—Pois foi o que eu lhe disse desde o principio.— Não querendo encetar uma discussão philologica, saquei do bolso o dinheiro pedido, o qual, para fazer justiça a quem emprestava, foi pontualmente pago no prazo promettido.
[92]Emprega-se, ás vezes, no sertão em lugar de a fio.
[93]Como já dissemos, talento é empregado como synonimo de força physica, robustez
[94]É o preço por que um curandeiro queria curar um empalamado, por cuja fazendola passámos em Julho de 1867, nesse mesmo sertão de Sant'Anna
[95]Corresponde ao dito popular no Rio Grande do Sul: Que é um boi para quem tem uma estancia?
[96]Differente
[97]A receita do leite de jaracatiá para a cura de hypoemia intertropical é veridico e causou-nos grande admiração, quando a ouvimos aconselhada por um medico do sertão.
Pareceu-nos tão absurda e violenta, que dissuadimos a pessoa que devia, conforme a sua resolução, pol-a em pratica dahi a dias. Entretanto, um profissional abalisado a quem contamos o caso, declarou-nos que fôra de proveitosa applicação naquella molestia
[98]Mal de S Lazaro; lepra
CAPITULO XVII
O MORPHETICO
O leproso.—Interesse?! Ah! nunca inspirei senão compaixão....
O militar.—Quão feliz fora eu, se pudesse dar-vos algum consolo!....
XAVIER DE MAISTRE.—O leproso de Aosta.
Não devo ter sociedade senão commigo mesmo; nenhum amigo, senão Deus. Generoso estrangeiro, adeus, sê feliz.
Adeus para sempre!....
IDEM.
A pessoa que chegára, bem que tivesse descavalgado, não se adeantou ao encontro do dono da casa. Pelo contrario como que recuou, conservando-se depois immovel, encostado a um burrinho, cujas redeas segurava.
De seu lugar perguntou-lhe Pereira com expressão não muito prazenteira:
—Então, como vae, Sr. Garcia?
—Como hei de ir, respondeu o interpellado. Mal ... ou, melhor, como sempre.
—Pois esteja na certeza de que muito sinto.
—Está ahi o cirurgião? indagou Garcia.
—Não tarda a vir vel-o ahi fóra... Olhe, é um instantesinho.
Palavras tão crueis não pareceram fazer mossa no desgraçado.
—Esperal-o-hei com toda a paciencia, replicou melancolico.
—Já sei que volta hoje para casa, affirmou Pereira.
—Volto. Se a noite me pegar em caminho, ficarei no pouso das Perdizes.
—É verdade: lá ha uma tapera. Mas o Sr. não tem medo de almas do outro mundo? Dizem que o tal rancho velho é mal assombrado.
—Eu?! exclamou o infeliz. Só tenho medo de mim mesmo. Quizesse um defunto vir gracejar um pouco commigo, e de agradecido lhe beijava os dedos roidos dos bichos. Olhe, Sr Pereira, continuou com voz um tanto alta e agoniada, não levo a mal o senhor não me convidar para entrar em sua casa; não, no seu caso, havia de fazer o mesmo.
—Oh! Sr. Garcia! quiz protestar Pereira.
—Nada;... digo-lhe isto do coração... Na minha familia, sempre tivemos nojo de lazaros... Sou o primeiro... O Sr. nem imagina... Vivi muitos annos meio desconfiado... A ninguem contei o caso... De repente, arrebentou o mal fóra. Já não era mais possivel enganar nem a um cégo... Ah! meu Deus, quanto tenho soffrido!...
—Permitta Elle, interrompeu Pereira em tom compassivo, que este doutor tenha algum remedio... Bem vê ... ás vezes...
—Curar a morphéa?! replicou Garcia com sorriso pungente de sarcasmo. Não ha esse pintado ... que em tal pense...
—Então para que quer ver o medico?
—Só para uma coisa... Saber pelos livros que elle tem lido e pelo conhecimento das molestias, se isto pega... É só o que quero... Porque então fujo de minha casa... Desappareço desta terra ... e voume arrastando até tombar nalgum canto por ahi... Dizem uns que pega ... outros que não ... que é só do sangue... Eu não sei.
E, abanando tristemente a cabeça, apoiou-se ao tosco sellim.
Depois, ergueu os olhos para os céus, e exclamou:
—Cumpra-se tudo quanto Deus Nosso Senhor Jesus-Christo houver determinado!... Se o medico me desenganar, não quero que a minha gente fique toda ... marcada... Irei para S. Paulo...
Pereira cortou este doloroso dialogo:
—Está bem, patricio Garcia, disse, vou já mandar-lhe o homem ... espere um pouco...
E, entrando, reiterou o pedido a Cyrino, que se demorara a receitar a Coelho umas beberagens de velame e pés de perdiz, plantas muito abundantes naquellas paragens, de grandes virtudes diureticas e que deveriam ser empregadas um mez depois da applicação do leite de jaracatiá.
—Ande, doutor, instou Pereira, vá lá fóra ver o coitado do outro e despache-me depressa. Estou todo enfernizado por vel-o no meu terreiro.
Cyrino sahiu então e, caminhando com lentidão, parou a alguns passos do malaventurado Garcia, cujo rosto repentinamente se contrahiu emquanto tirava o chapéo com submissão e receio.
Vinha então a tarde descendo, e a luz do crepusculo irradiava por toda a parte, tão melancolica e suave que, sem saber por que, a alma de Cyrino de repente se confrangeu.
Com assombro o encarava o lazaro. Deante delle se erguera quem lhe ia apontar o caminho da eterna proscripção. Dos seus labios ia cahir a sentença ultima, irremediavel, fatal!
Quanta angustia no olhar daquelle homem! Que pensamentos sinistros! Quanta dor!
Tambem ficara alli attonito, boquiaberto, á espera que a palavra de Cyrino lhe quebrasse o horroroso enleio.
—Então, disse este depois de breve pausa, que me quer o senhor?
—Doutor, balbuciou Garcia ... primeiro que tudo quero ... pagarlhe; ... trouxe algum ... dinheiro ... mas, talvez ... seja ... pouco.
Interrompeu-o Cyrino:
—Não recebo dinheiro para tratar ... da sua molestia.
—Quer isto dizer, replicou com acabrunhamento Garcia, que ella não tem cura... Eu bem sabia, mas ... é tão duro ouvir sempre isso!... Olhe, o meu mal é de pouco ... está em principio. Quem sabe ... se o Sr. não conhecerá alguma herva?...
—Infelizmente, respondeu Cyrino, nem eu, nem ninguem conhece essa planta...
—Emfim!
E Garcia, fechando os olhos como que para concentrar as forças, continuou:
—Ah! doutor, eu sou um pobre homem ... velho já cansado...
Porque não me veio a morte em lugar desta podridão que me está comendo as carnes?... Muito tempo a senti dentro de mim... Disfarcei, disfarcei, até ao dia em que minha neta ... a filha do meu coração ... a Jacyntha ella mesma, mostrou certo receio de me abraçar Ah! senhor, quanto se soffre nesta vida!
E Garcia parou offegante, empallidecendo muito.
—Dê-me agua, exclamou elle, agua ... pelo amor de Deus!... Pudesse agora ser o meu dia. A minha garganta está que nem fogo!...
E agarrou-se aos arreios para não cahir no chão.
Cyrino correu a buscar agua.
—Onde hade ser? perguntou Pereira.
—Onde queira, respondeu o outro com pressa, veja que aquelle christão está soffrendo...
—Ah! leve a caneca de louça... Depois a quebraremos...
Com sofreguidão tomou o lazaro o vaso, bebeu de um trago e pareceu melhorar.
—Foi um vágado, disse reassumindo aos poucos a calma. Mas, como lhe contava, certeza tinha eu do mal. Agora, só quero saber uma coisa e vou-me de partida. Este mal ... pega, doutor?
—Pega, affirmou Cyrino com tristeza.
—E que me resta fazer?
—Pedir á Senhora Sant'Anna paciencia e a Nosso Senhor JesusChristo...
Garcia abanava a cabeça acabrunhado.
... que o proteja na sua vida de desgraças.
—Meu Deus, balbuciou o morphetico a meia voz, dae-me forças coragem para que eu faça o que devo fazer.
E, com subita resolução:
—Cumpra-se a vontade do Altissimo! exclamou emfim. Doutor, obrigado! O pobre lazaro hade pedir ao Todo Poderoso que neste mundo e no outro lhe pague as suas palavras de homem de letras... Adeus! Eu me vou para as terras de S. Paulo ... talvez me junte á gente da minha especie. Adeus...
E, a custo montando a cavallo, voltou-se para as pessoas que tinham de longe vindo assistir á consulta.
—Adeus, disse elle acenando com o chapéu, gente e patricios. Senhor Pereira, Sr. Coelho, mais senhores, adeus! Eu me bóto de uma feita para lá das Parnahybas[99] ... Este sertão não me vê mais nunca!...
Acolheu o silencio essas palavras de eterna despedida.
Garcia então, esporeando com o calcanhar o ventre da cavalgadura, a passo tomou rumo da estrada geral e sumiu-se numa das voltas do caminho, quando ja vinha a noite estendendo o seu lugubre manto.
[99]Isto é, para lá do rio Paranahyba: Para cá ou para lá das Parnahybas é phrase muito usada no sertão em que corre aquelle grande rio.
IDYLLIO
Mas, que luz é essa que alli apparece, naquella janella? A janella é o oriente, e Julieta o sol. Sobe, bello astro, sobe e mata de inveja a pallida lua.
SHAKESPEARE.—Romeu e Julieta, Acto II.
Entretanto, desde algum tempo, sentia-se Virginia agitada de mal desconhecido... Em sua fronte, não pousava mais a serenidade, nem o sorriso lhe pairava nos labios... Pensa ella na noite, na solidão, e fogo devorador a abraza toda.
B. DE SAINT-PIERRE.—Paulo e Virginia.
Decorreram sem novidade dias e dias uns após outros; Cyrino diagnosticando e curando ou melhor, receitando; Meyer augmentando cada vez mais a sua bella collecção entomologica, sempre feitorisado por Pereira, que cautelosamente tratava de mantel-o no suspeitoso circulo da sua apertada vigilancia.
CAPITULO XVIII
Confidente de todos os infundados e mal empregados receios era Cyrino.
O allamão, dizia o mineiro, não me deixa pôr pé em ramo verde, mas também trago-o vigiado que é um gosto... Se desconfiasse, teria medo até da sua sombra... Estou em brazas... Não sei porque não chega o Manecão Dóca... Quero arriar a carga no chão... Agora, mais do que nunca, devo casar Nocencia... Estas mulheres botam sal na moleira de um homem. Salta! E ainda isto tudo não é nada.
—Então espera muito breve o Manecão? perguntou o outro com anciedade.
—Não pode tardar ... por estes dois ou tres dias quando muito... Vem de Uberaba e sem duvida por lá arranjou todos os papeis... Dei a certidão do meu casamento ... a do baptismo da pequena ... e adeantei dinheiro para as despezas ... bem que elle refugasse meio vexado.
—Então está tudo decidido? perguntou Cyrino com vivacidade.
—Boa duvida!... Já lhe tenho dito mais de uma vez. Hoje é coisa de pedra e cal... Se até trato o Manecão de filho... A honra desta casa é tambem honra delle.
—Mas sua filha?
—Que tem?
—Gosta delle?
—Ora se!... Um homemzarrão ... desempenado. E, quando não gostasse é vontade minha, e está acabado. Para felicidade della e, como boa filha que é, não tem que piar Estou, porem, certissimo de que o noivo lhe faz bater o coração ... tomara ver o cujo chegado!
Já nesse tempo, como dissemos, Innocencia de todo se restabelecera, ainda que Cyrino tivesse feito quanto possivel render a enfermidade. Mas, quando o rubor da saúde voltou á assetinada cutis da sertaneja e o vigor ao esbelto corpo, não houve pretexto a que se apegar, e as entrevistas curtas e graves de medico foram cortadas, até mesmo para não desviar a attenção de Pereira da pessoa de Meyer.
Com o coração, pois, partido de dor, declarou que os seus cuidados e presença se tornavam completamente desnecessario.
Seguiram-se então semanas inteiras, sem que pudesse pôr os anciosos olhos na formosa namorada, e por tal modo se exacerbou a sua paixão que, para encobril-a e disfarçar a excitação nervosa, a falta de appetite e pallidez extrema, teve que recorrer a desculpas de molestia; cahiu realmente doente.
A incerteza em que se via, sem, pelo menos, saber se o seu affecto era ou não correspondido, dava-lhe accessos de violenta angustia, que a deshoras tocava ás raias da exasperação.
Uma noite, em que havia luar embaciado por ligeira bruma, tomou a sua afflicção tal violencia que elle decidiu fugir daquelle local de soffrimentos e incertezas, logo na manhã seguinte.
Assente uma vez nesta resolução, ergueu-se do leito em que jazia prostrado pelo mais cruel desalento e, com algum custo, sahiu para o terreiro, abrindo cautelosamente a porta da casa, afim de não acordar os companheiros de quarto. Uma vez fóra, sentou-se num tronco de madeiro o alli ao ar fresco e acariciador da madrugada, entrou com mais tranquillidade a pensar no caso.
Seria uma hora depois de meia noite.
Estavam os espaços como que illuminados por essa luz serena e fixa que irradia de um globo despolido; luz fosca, branda, sem intermittencias no brilho, sem scintillações, e diffundida igualmente por toda a atmosphera.
Haviam já os gallos cantado uma vez, e, ao longe, muito ao longe, de vez em quando, se ouvia o clamor das anhumas pócas.
Levantou-se de repente Cyrino.
Depois de alguma vacillação, deu uma volta por toda a habitação, pulando os cercados, e tomou o rumo do frondoso laranjal, a cuja espessa sombra se abrigou por algum tempo.
Achegou-se, em seguida, á cerca dos fundos da casa o parou no meio do pateo, olhando com assombro para uma janella aberta.
Um vulto alli estava!... Era o della; Innocencia... Não havia duvidar.
A principio, nenhum movimento fez; mas, depois, lentamente se foi retirando e aos poucos fechou o postigo.
Cyrino deu um só pulo e de leve, muito de leve, bateu apressadas pancadas na taboa da janella.
Innocencia! Innocencia! chamou com voz sumida
—Innocencia!... Innocencia!... chamou com voz sumida, mas ardente e cheia de supplica.
Ninguem lhe respondeu.
—Innocencia, implorou o moço, olhe ... abra ... tenha pena de mim... Eu morro por sua causa...
Depois de breve tempo, que para Cyrino pareceu um seculo, descerrou-se a medo a janella, e appareceu a moça toda assustada, sem saber por que razão alli estava nem explicar tudo aquillo.
Parecia-lhe um sonho.
Quiz, entretanto, dar qualquer desculpa á situação e, fingindo-se admirada, perguntou muito baixinho e a balbuciar:
—Que vem ... mecê ... fazer aqui? ... já ... estou boa.
Da parte de fóra, agarrou-lhe Cyrino nas mãos.
—Oh! disse elle com fogo, doente estou eu agora... Sou eu que vou morrer ... porque você me enfeitiçou, e não acho remedio para o meu mal.
—Eu ... não, protestou Innocencia.
—Sim ... você que é uma mulher como nunca vi... Seus olhos me queimaram... Sinto fogo dentro de mim... Já não vivo ... o que só quero é vel-a ... é amal-a ... não conheço mais o que seja somno e, nesta semana, fiquei mais velho do que em muitos annos havia de ficar... E tudo, porque, Innocencia?
—Eu não sei, não, respondeu a pobresinha com ingenuidade.
—Porque eu amo amo-a, e soffro como um louco como um perdido...
—Ué, exclamou ella, pois amor é soffrimento?
—Amor é soffrimento, quando a gente não sabe se a paixão é acceita, quando se não vê quem se adora: amor é céu, quando se está como eu agora estou.
—E quando a gente está longe, perguntou ella, que se sente?...
—Sente-se uma dôr, cá dentro, que parece que se vae morrer...
Tudo causa desgosto: só se pensa na pessoa a quem se quer, a todas as horas do dia e da noite no somno, na reza, quando se ora a NossaSenhora, sempre ella, ella, ella! ... o bem amado ... e...
—Oh! interrompeu a sertaneja com singeleza, então eu amo....
—Você? indagou Cyrino sofregamente.
—Se é como ... mecê diz...
—É ... é ... eu lhe juro!...
—Então ... eu amo, confirmou Innocencia.
—E a quem?... Diga: a quem?
Houve uma pausa, e a custo retrucou ella, ladeando a questão:
—A quem me ama.
—Ah! exclamou o joven, então é a mim ... é a mim, com certeza, porque ninguem neste mundo, ninguem, ouviu? é capaz de amal-a como eu... Nem seu pae ... nem sua mãe, se viva fosse... Deixe falar seu coração... Se quer ver-me fóra deste mundo ... diga que não sou eu, diga!...
—E como ia mecê morrer? atalhou ella com receio.
—Não falta pau para me enforcar, nem agua para me afogar.
—Deus nos livre! não fale nisso... Mas, porque é que mecê gosta tanto de mim? Mecê não é meu parente, nem primo, longe que seja, nem conhecido sequer Eu lhe vi apenas pouco tempo e tanto se agradou de mim?
—E com você ... não succede o mesmo? perguntou Cyrino.
—Commigo?
—Sim, com você... Porque é que está acordada a estas horas? Porque é que não pode dormir? ... que a cama lhe parece um brazeiro, como a mim tambem parece?... Porque pensa em alguem a todo o instante? Entretanto, esse alguem não é primo seu, longe que seja, nem conhecido sequer?...
—É verdade, confessou Innocencia com doce candura.
Depois quiz emendar a mão:
—Mas, quem lhe disse que vivo pensando em mecê?
—Innocencia, implorou o moço, não queira negar; vejo que sou amado...
—Sempre amar! observou ella, mais para si do que para quem a ouvia. No anno que já passou e por occasião da Sra Sant'Anna[100] , aqui vieram umas parentas minhas e caçoaram commigo, porque eu não as entendia: tanto assim que uma dellas, a Nhã Tuca, me disse: «Deveras, mecê ainda não gostou de nenhum moço? E eu respondi: Não assumpto[101] o que mecê estão a prosear.» Aquillo era certo, e tão verdade como estar nosso Deus no paraiso... Hoje...
—E hoje?
—Hoje? repetiu a moça. Quem sabe se não era bem melhor não ter nunca gostado de ninguem?
—Isso não está na gente... É ordem lá de cima...
—Emfim, se for destino, que se cumpra.
Conservava-se Innocencia ainda um pouco arredada da janella, de modo que Cyrino, para lhe falar baixinho, tinha o corpo inclinado do lado de dentro. Segurava as mãos da namorada e puxava com doce violencia, quando mostrava querer afastar-se.
Era o ardente colloquio dos dois cortado de frequentes pausas, durante as quaes se embebiam reciprocos os olhares carregados de paixão.
—Deixa-me ver bem o teu rosto, dizia Cyrino a Innocencia. Para mim, e muito mais bello que a lua e tem mais brilho que o sol.
E, apezar de alguma resistencia, fraca embora, mas conscienciosa, que lhe foi opposta, conseguiu que a formosa rapariga se recostasse ao peitoril da janella.
—Amar, observou ella, deve ser coisa bem feia.
—Porque?
—Porque estou aqui e sinto tanto fogo no rosto!... Cá dentro me diz um palpite que é peccado mortal que faço ..
—Você tão pura! contestou Cyrino.
—Se alguem viesse agora e nos visse, eu morria de vergonha. Sr. Cyrino deixe-me ... vá-se embora! ... o Sr. me atirou algum quebranto ... aquella sua mézinha tinha alguma herva para mim tomar ... e me virar o juizo...
—Não, atalhou o mancebo com força, eu lhe juro! Pela alma de minha mãe ... o remedio não tinha nada!
—Então porque fiquei ... ansim, que me não conheço mais?... Se papae apparecesse ... não tinha o direito de me matar?...
Foi-se-lhe a voz tornando cada vez mais baixa e sumiu-se num golfão de lagrimas.
Atirou-se Cyrino de joelhos diante della.
—Innocencia, exclamou, pela salvação de minha alma lhe dou juramento: nada de mau fiz para prender o seu coração... Se você me ama, é porque Deus assim mandou... Sou um rapaz de bons costumes... Até hoje nunca tinha amado mulher alguma ... mas não sei como deixar de amar uma moça como você... Perdoe-me; se você soffre ... eu tambem padeço muito... Perdoe-me...
Alçara o mancebo um pouco a voz.
De repente Innocencia estremeceu.
—Não ouviu ruido? perguntou ella com terror.
—Não, respondeu Cyrino.
—Alguem acordou lá dentro...
—Pois então vá ver o que é e se não for nada, volte... Aqui a espero, escondido á sombra da parede...
Minutos depois, reappareceu a moça.
—Não vi nada, disse.
—Então foi abusão.
—É melhor que o Sr. se vá embora.
—Não, Innocencia, tenha pena de mim... Eu não poderei vel-a tão cedo e ... preciso conversar ... mesmo para arranjo da nossa vida... O
