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Journal of Alzheimer’s Disease xx (20xx) x–xx 1

DOI 10.3233/JAD-160867
IOS Press

1 Meditation and Music Improve Memory


2 and Cognitive Function in Adults
with Subjective Cognitive Decline:

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3

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4 A Pilot Randomized Controlled Trial

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5 Kim E. Innesa,b,∗ , Terry Kit Selfea,b , Dharma Singh Khalsac,d and Sahiti Kandatia
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a Department of Epidemiology, West Virginia University School of Public Health, Morgantown, WV, USA
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b Center for the Study of Complementary and Alternative Therapies, University of Virginia Health System,
8 Charlottesville, VA, USA
c Department of Internal Medicine and Integrative Medicine, University of New Mexico School of Medicine,

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9

10 Albuquerque, NM, USA


11
d Alzheimer’s Research and Prevention Foundation, Tucson, AZ, USA

12 Handling Associate Editor: J. Wesson Ashford


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Accepted 23 November 2016

13 Abstract.
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14 Background: While effective therapies for preventing or slowing cognitive decline in at-risk populations remain elusive,
15 evidence suggests mind-body interventions may hold promise.
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16 Objectives: In this study, we assessed the effects of Kirtan Kriya meditation (KK) and music listening (ML) on cognitive
17 outcomes in adults experiencing subjective cognitive decline (SCD), a strong predictor of Alzheimer’s disease.
18 Methods: Sixty participants with SCD were randomized to a KK or ML program and asked to practice 12 minutes/day for
19 3 months, then at their discretion for the ensuing 3 months. At baseline, 3 months, and 6 months we measured memory
20 and cognitive functioning [Memory Functioning Questionnaire (MFQ), Trail-making Test (TMT-A/B), and Digit-Symbol
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21 Substitution Test (DSST)].


22 Results: The 6-month study was completed by 53 participants (88%). Participants performed an average of 93% (91% KK,
23 94% ML) of sessions in the first 3 months, and 71% (68% KK, 74% ML) during the 3-month, practice-optional, follow-up
24 period. Both groups showed marked and significant improvements at 3 months in memory and cognitive performance (MFQ,
25 DSST, TMT-A/B; p’s ≤0.04). At 6 months, overall gains were maintained or improved (p’s ≤ 0.006), with effect sizes
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26 ranging from medium (DSST, ML group) to large (DSST, KK group; TMT-A/B, MFQ). Changes were unrelated to treatment
27 expectancies and did not differ by age, gender, baseline cognition scores, or other factors.
28 Conclusions: Findings of this preliminary randomized controlled trial suggest practice of meditation or ML can significantly
29 enhance both subjective memory function and objective cognitive performance in adults with SCD, and may offer promise
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30 for improving outcomes in this population.

31 Keywords: Alzheimer’s disease, cognitive impairment, early memory loss, memory

∗ Correspondenceto: Kim E. Innes, MSPH, PhD, Department Morgantown, WV 26506, USA. Tel.: +1 304 293 5206; Fax: +1
of Epidemiology, WVU School of Public Health, PO Box 9190, 304 293 2700; E-mail: KInnes@hsc.wvu.edu.

ISSN 1387-2877/16/$35.00 © 2016 – IOS Press and the authors. All rights reserved
2 K.E. Innes et al. / Meditation and Music Listening for SCD

32 INTRODUCTION predate incident SCD [3]. These findings suggest 83

that SCD may be a sensitive early clinical marker 84

33 Alzheimer’s disease (AD), a progressive neurode- for AD. 85

34 generative disorder resulting in a loss of reasoning, To date, there are no approved treatments for early 86

35 memory, language, and ultimately, basic self-care memory loss [29]. Nonetheless, this preclinical or 87

36 skills, is a leading cause of death in the US, affect- prodromal period, when the burden of neurodegen- 88

37 ing at least 5.3 million Americans at an estimated erative changes is still relatively low, may represent 89

38 annual cost of $226 billion for those over 65 [1]. a crucial therapeutic window for addressing cogni- 90

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39 The development of AD is generally insidious, with tive decline and associated neuropathogenic changes. 91

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40 onset of clinical signs preceded years earlier by There is mounting evidence that mind-body therapies 92

41 perceived and/or objective cognitive decline [2]. such as meditation and music-based interventions, 93

42 Longitudinal studies have linked subjective cogni- including simple, passive (receptive) music listening, 94

43 tive decline (SCD) to accelerated deterioration in may offer promising treatment options. A grow- 95

44 cognitive function [3], an up to 4.5-fold increased ing body of literature suggests that both meditation 96

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45 risk for progression to mild cognitive impairment practice and listening to familiar and/or relaxing 97

46 (MCI) [4, 5], and a 2- to 6.5-fold increased risk classical music can improve neurostructural and 98

47 for AD [6, 7] after adjustment for demographics, neurophysiologic profiles, and may enhance mem- 99

48 depression, APOE4 status, and other risk factors. ory and cognitive performance in both healthy and 100

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49 Recent prospective research has likewise shown clinical populations, including those with and at 101

50 SCD in clinically normal elders to remain strongly risk for cognitive impairment [30–38]. For exam- 102

51 associated with cognitive performance even after ple, recent prospective controlled studies in older 103

52 adjustment for AD biomarkers, including amyloid-␤ adults with and without dementia suggest medita- 104

53 [8]. The annual conversion rate from SCD to MCI tion may induce beneficial structural and functional 105
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54 or dementia in otherwise healthy individuals has changes, including increased grey matter volume, 106

55 been estimated to be 7–10% [9–11]. Notably, in one grey matter density, and functional connectivity [38, 107

56 longitudinal study of 2,415 German elders [6], pro- 39], as well as enhanced oxygenation and glucose 108

57 gression from SCD to MCI was shown to carry a utilization in brain regions involved in cognitive pro- 109

58 20- to 60-fold increased risk for the development of cessing, memory consolidation, and attention [38, 110

AD dementia, highlighting the importance of early 40]. Similarly, findings from preliminary randomized
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59 111

60 intervention. controlled trials (RCTs) in these populations suggest 112


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61 While cognitive function is in the normal range in that meditation may also improve certain domains 113

62 those with SCD [12], a number of population-based of cognition, including attention, executive function, 114

63 studies have shown significant decrements in cogni- memory, and processing speed[34–36, 40]. 115

64 tive performance in adults with SCD relative to those Likewise, exposure to music has been shown 116

65 without memory complaints [13, 14]. SCD has also in experimental models to promote positive effects 117
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66 been characterized by increased amyloid-␤ depo- on the brain, including increased neurogenesis, 118

67 sition and other pathological changes of the brain enhanced synaptic plasticity, and beneficial changes 119

68 associated with AD [15–19], elevated levels of cere- in neurotropin and neurotransmitter (e.g., dopamine) 120

69 brospinal fluid markers of AD [19, 20], reductions levels [41, 42]; findings from recent human studies 121
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70 in hippocampal and grey matter volume [14, 21, 22], suggest listening to classical and/or familiar music 122

71 and increased white matter lesions [23]; neuropatho- may also increase grey and white matter volume 123

72 logical changes consistent with AD have likewise in cortical and subcortical brain areas involved in 124

73 been associated with SCD at autopsy even in those cognitive processing, enhance functional connectiv- 125
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74 who were not diagnosed with cognitive impairment ity of these regions, and modulate activity in brain 126

75 [24, 25]. Moreover, longitudinal studies of cogni- structures implicated in emotional regulation and 127

76 tively normal older adults have demonstrated not reward, behavioral responses, and working memory 128

77 only that SCD is strongly associated with episodic and attention [30, 31, 43]. Findings from recent pilot 129

78 memory-related hippocampal atrophy, a hallmark of research [32], including a Finnish RCT of caregiver- 130

79 AD [26], but that these neurodegenerative changes dementia patient dyads [44] suggest a simple music 131

80 can precede the development of SCD by years [27, listening program may lead to improvements in 132

81 28] and may help explain the subtle decline in certain critical domains of memory and cognitive 133

82 objective cognitive performance recently shown to functioning as well.


K.E. Innes et al. / Meditation and Music Listening for SCD 3

134 MATERIALS AND METHODS treatment). Study buddies willing to attend all assess- 183

ment visits were required for those with MCI and 184

135 Participant eligibility criteria, trial design, and encouraged for those with SCD who were concerned 185

136 study procedures are described in detail elsewhere about their ability to fully understand the consent 186

137 [48] and are outlined briefly below. The study was process or complete the questionnaires. 187

138 approved by the West Virginia University Institu-


139 tional Review Board. Assessments 188

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140 Study participants After providing written informed consent, par- 189

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ticipants completed the baseline assessment; we 190

141 Independently living older adults with early mem- gathered information on medical history, cur- 191

142 ory loss were recruited for the study, using intranet rent medication and supplement use, lifestyle and 192

143 and email advertising as well as brochures and fly- anthropometric characteristics, and demographic fac- 193

144 ers placed in community, health care, and workplace tors. We evaluated memory and cognitive function 194

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145 settings. Major study inclusion criteria were as fol- using three well-established, validated instruments 195

146 lows: English-speaking adults at least 50 years of age including measures of memory function (Memory 196

147 with either a) physician confirmed diagnosis of MCI; Functioning Questionnaire (MFQ) [50]), executive 197

148 or b) SCD as defined by meeting six criteria con- function (Trail Making Test Parts A and B (TMT) 198

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149 sistent with expert reviews and prospective studies [51]), and psychomotor speed, attention, and work- 199

150 available at the time [6, 10, 12, 49]. These included: ing memory (the 90-second Wechsler Digit-Symbol 200

151 1) presence of subjective cognitive deficits within the Substitution Test (DSST) [52]). The MFQ is a 64- 201

152 past 6 months; 2) frequency of memory problems item self-report questionnaire scored on a 7-point 202

153 at least once/week; 3) able to give an example in Likert scale, with higher scores indicating better 203
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154 which memory/cognitive problems occur in every- memory functioning; the four subscales include: 204

155 day life; 4) belief that one’s cognitive capacities have General Frequency of Forgetting, Seriousness of For- 205

156 declined in comparison with 5 or 10 years previously; getting, Retrospective Functioning, and Mnemonics 206

157 5) absence of overt cognitive deficits or dementia Usage. MFQ scores have been inversely associated 207

158 diagnosis: and 6) expressed worry regarding mem- with brain amyloid burden in cognitively normal 208

ory problems, a factor shown to further increase risk older adults [15–17], and shown to differentiate non-
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159 209

160 of progression to MCI and AD [3, 10]. Excluded from cognitively impaired adults from those with SCD 210
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161 the study were those who: 1) practiced meditation or [53], suggesting that the MFQ may offer a useful 211

162 other relaxation technique within the past year; 2) measure for detecting preclinical AD. The TMT, a 212

163 recently (within the last 6 weeks) changed dosage of sensitive measure of cognitive functioning [54] is a 213

164 cholinesterase inhibitors [e.g., donepezil (Aricept), two-part paper-and-pencil test: the TMT-A, in which 214

165 galantamine (Razadyne), rivastigmine (Exelon)] or numbers (1–25) are connected in an ascending order 215
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166 psychotropic medication (e.g., tricyclics, SSRIs, (1–2–3;. . . ); and the TMT-B which requires con- 216

167 MAOIs, anti-panic or anti-anxiety agents); 3) had a necting numbers (1–13) and letters (A–L) alternately 217

168 history of psychotic or schizophrenic episodes, major (1-A-2-B. . . ). Scores reflect the number of seconds 218

169 neurologic diagnosis (Parkinson’s, stroke, brain required to complete each part. While both parts are 219
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170 injury, epilepsy) or other condition that might impair designed to measure attention and information pro- 220

171 cognition or confound assessments [e.g., cardiovas- cessing speed, the TMT-B also measures additional 221

172 cular event within the past 6 months (myocardial domains of executive function, including cognitive 222

173 infarction, unstable angina, hospitalization for con- flexibility and working memory [54]. In a recent lon- 223
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174 gestive heart failure, bypass surgery or angioplasty gitudinal study of memory clinic patients with SCD, 224

175 (coronary or carotid), transient ischemic attack)]; worse TMT-B scores independently predicted sub- 225

176 4) had received chemotherapy treatment within the sequent conversion to MCI or AD [55]; likewise, 226

177 past 10 years; or 5) recently (within the last 3 TMT-B was found to be the best single predictor 227

178 months) experienced serious physical trauma or for dementia in a prospective study of Swedish MCI 228

179 received a diagnosis of a serious chronic health con- patients [56]. Finally, the DSST is a timed test in 229

180 dition requiring medical treatment and monitoring which participants are asked to translate numbers into 230

181 (e.g., uncontrolled hypertension, serious endocrine symbols, following a key which is visible through- 231

182 or pulmonary disorder, renal disease, active cancer out the test. One point is scored for each correctly 232
4 K.E. Innes et al. / Meditation and Music Listening for SCD

233 drawn symbol completed within 90 seconds. These clarify any additional issues that arose in the course 281

234 assessments were repeated at 3 months, and again at of the intervention. During the 3-month, practice- 282

235 6 months (3 months post-intervention). optional post-intervention period, participants were 283

236 To assess expectation of benefit, participants likewise asked to record any practice on their daily 284

237 completed the 6-item Credibility/Expectancy Ques- log sheets. 285

238 tionnaire (CEQ) [57] following their first intervention


239 practice session. To allow tracking of adherence, par- Kirtan Kriya meditation program 286

240 ticipants completed daily home practice logs which

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241 were collected at the follow-up assessment visits. At KK is a multisensory practice that engages several 287

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242 each follow-up visit, participants also recorded any areas of the brain, yet is easy to learn and practice. The 288

243 changes in medication and/or supplement use and in meditation includes a Kirtan (repeated singing of the 289

244 exercise routines using a form specifically designed ‘Sa-Ta-Na-Ma’ mantra), a mudra or physical/motor 290

245 for this purpose. In addition, participants were also component (touching each fingertip to the thumb in 291

246 asked to complete a 3- and 6-month study evaluation sequence with the chant), and a visualization compo- 292

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247 questionnaire adapted from that used in our previous nent (imagining the sound energy entering the crown 293

248 studies [45, 58]. This survey included a single 5-point of the head and exiting between the eyebrows in an 294

249 Likert scale item to assess change in concerns regard- ‘L’). The meditation CD contained a user-friendly 295

250 ing memory. All participant assessments and entry introductory track with detailed instructions regard- 296

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251 of outcomes data were performed by research staff ing the KK practice and five 12-minute meditation 297

252 blinded to participant treatment assignment. tracks, including three guided sessions. 298

253 Randomization and treatment allocation Music listening program


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254 Eligible participants were randomized to one of The ML CD contained 12 minutes of relaxing 300

255 two treatment groups described below, in a 1 : 1 instrumental music from each of 6 classical com- 301

256 ratio using a randomly varying block randomization posers. Participants were instructed to sample each 302

257 method to ensure equal distribution between groups composer at least once during the 12 weeks, but were 303

258 [59]. Following baseline assessment, the consenting otherwise left to listen to whichever composer they 304

team member, who had no advance knowledge of chose on a daily basis.


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259 305

260 the statistician-prepared group allocation schedule,


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261 gave the next sequentially numbered, sealed opaque Analysis 306

262 envelope containing the treatment assignment to the


263 participant. Data analysis was performed using IBM SPSS, 307

Version 23. Baseline differences between the 308

264 Interventions intervention groups and between dropouts and 309


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non-dropouts were assessed using chi-square (for 310

265 Following randomization, participants received categorical variables), independent samples t-tests 311

266 one-on-one training in their assigned relaxation (for normally distributed continuous variables), or 312

267 practice (see below). The 30–45-minute onsite train- Mann-Whitney U tests (for ordinal or continuous 313
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268 ing was delivered by a trainer familiar with both variables with evidence of skewing); a p value of 314

269 study programs and experienced in teaching a range ≥0.1 was used for determining baseline differences. 315

270 of mind-body skills. In addition, each participant Potential differences between treatment groups were 316

271 received a program CD and a short reference guide, analyzed using chi-square for retention, and one- 317
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272 along with a portable CD player for home use. Par- way ANOVA treatment expectancies and adherence. 318

273 ticipants were instructed to engage in their assigned In preliminary assessments, within-group changes 319

274 practice while seated comfortably with eyes closed, over time at 3 and 6 months were assessed using 320

275 for 12 minutes daily for 12 weeks (84 practice ses- ANCOVA with age and baseline scores as covariates; 321

276 sions total) and to record every practice session daily age-adjusted between-group differences in treatment 322

277 on the home practice log, along with any comments. outcomes were assessed using Repeated Measures 323

278 The trainer called each participant within the first ANOVA. In our intention-to-treat (ITT) analyses, we 324

279 week of the intervention to provide additional instruc- used the SPSS multiple imputation function (10 iter- 325

280 tion as needed, and remained available thereafter to ations) to replace missing data [60]. Effect sizes were 326
K.E. Innes et al. / Meditation and Music Listening for SCD 5

327 calculated using Cohen’s d. As this was a pilot fea- factors, obesity, or number of metabolic or other 376

328 sibility study, alpha was set at 0.05. Bivariate and modifiable risk factors. Likewise, baseline scores did 377

329 age-adjusted correlations were performed using Pear- not differ by history of depression or anxiety, high 378

330 son’s r. Variables with a non-normal distribution were cholesterol, hypertension, cancer or other chronic 379

331 log-transformed prior to analysis. conditions, or by use of medications commonly 380

332 To evaluate the robustness of our findings, we linked to memory changes. Reported change in med- 381

333 performed additional analyses restricted to those ication at the follow-up assessment was also similar 382

334 most at risk for cognitive decline, including partic- between groups (p ≥ 0.4). At 3 months, a total of six 383

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335 ipants: age ≥60 years with SCD onset within the participants (3 KK, 3 ML), reported a change in med- 384

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336 last 5 years; those with at least 2 AD risk fac- ication, including antidepressant (n = 2), analgesic 385

337 tors; those with poorer baseline scores on the MFQ (n = 2), steroid (n = 1), and muscle relaxant (n = 1). At 386

338 (<75th centile) and the TMT-B (≥88 seconds, a cut- the 6-month assessment, four participants reported 387

339 off shown to predict subsequent cognitive decline a change in medication (1 KK, 3 ML), including 388

340 and dementia in a recent study of memory clinic antidepressant (n = 2), analgesic (n = 1), and statin 389

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341 patients with MCI) [56]. We also evaluated the poten- medication (n = 1). 390

342 tial modifying influence of age (≥60 versus <60 All participants received the intervention to which 391

343 years), history of depression/anxiety, use of medi- they were allocated. Attrition rates were low, with 392

344 cations linked to memory change, baseline cognition 92% of participants (27/30 KK, 28/30 ML) com- 393

scores (<50th versus ≥50th centile) and obesity. To

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345 pleting the 12-week program, and 88% (26/30 KK, 394

346 assess the potential influence of medication change, 27/30 ML) completing the full 6-month study. Com- 395

347 we conducted additional analyses, both adjusting for pleters were similar to non-completers in all baseline 396

348 this factor statistically and excluding those reporting characteristics (p’s ≥0.3). 397

349 change in medication. Program adherence was high; participants com- 398
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pleted an average of 93% (91% KK, 94% ML) 399

of sessions in the first 12 weeks, and 71% (68% 400

350 RESULTS KK, 74% ML) of sessions during the 3-month, 401

practice-optional follow-up period. There were no 402

351 A total of sixty eligible adults, all with SCD, between-group differences in either retention or 403

were enrolled in the study. Enrolled participants adherence at any time point (p’s ≥0.4), or in any
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352 404

353 ranged in age from 50–84 years old (mean (M) = 60.6, domain of treatment expectancy (all p’s ≥0.2). In 405
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354 SE = 1.0). The majority of participants were female addition, treatment expectancy scores were not cor- 406

355 (85%) and non-Hispanic white (93%) (Table 1). related, at any time point, with change over time in 407

356 Baseline MFQ scores averaged 246.1 ± 2.9, with any outcome measured (p’s ≥0.1). No adverse events 408

357 42% of participants scoring 88 or above in their were reported by any participant. 409

358 baseline TMT-B. Participants reported experiencing


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359 memory problems for an average of approximately 3 Change in measures of memory and cognition 410

360 years (M = 35.42 ± 4.2 months). Prevalence of addi- over time 411

361 tional modifiable AD risk factors was also high.


362 Ninety-four percent of participants reported at least At 3 months, participants in both the KK and ML 412
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363 one, and 66% reported 2 or more metabolic/vascular groups showed significant improvements relative to 413

364 risk factors for AD; overall, prevalence of measured baseline in measures of both memory and cogni- 414

365 AD risk factors averaged 2.8 ± 0.2 in this sample of tive functioning, including the MFQ total score (p’s 415

366 older adults (Table 1). ≤0.004), the DSST (p’s ≤0.04), and the TMT-A and 416
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367 With the exception of prevalence of obesity, which B (p’s ≤0.05), and; changes in the MFQ included 417

368 was marginally lower in the KK than in the ML improvements in three of the four subscales as well 418

369 group, the two groups were similar overall in demo- (Table 3). In addition, the percentage of participants 419

370 graphics, lifestyle factors, medical history, and in scoring in the at-risk range on the TMT-B declined 420

371 baseline measures of memory and cognitive function- significantly over time (p’s ≤0.02); of the 24 partic- 421

372 ing (Tables 1 and 2). Baseline scores on measures ipants with low TMT-B scores at baseline, only 7 (2 422

373 of cognition and memory were correlated with age KK, 5 ML) remained in the at-risk range at 6 months. 423

374 (r’s ≥0.3, p’s ≤0.02), but were not significantly As indicated in Table 3, overall effect sizes varied 424

375 related to other demographic characteristics, lifestyle from small (DSST) to large (MFQ, TMT-B). These 425
6 K.E. Innes et al. / Meditation and Music Listening for SCD

Table 1
Participant baseline characteristics: Pilot feasibility RCT of a 12-week Kirtan Kriya meditation (KK) versus a 12-week music listening (ML)
program in 60 adults with subjective cognitive decline
Overall (n = 60) KK (n = 30) ML (n = 30) p
n % n % n %
Demographic characteristics
Age (range 50–84 years)
Mean ± SE 60.58 ± 1.01 60.93 ± 1.56 60.23 ± 1.32 0.73
Female Gender 51 85.00% 26 86.67% 25 83.33% 0.71

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Race/Ethnicity: Non-Hispanic White 56 93.33% 27 90.00% 29 96.67% 0.25

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Education 0.17
12 years or less 10 16.67% 3 10.00% 7 23.33%
≥12 years 50 83.33% 27 90.00% 23 76.67%
Employment status 0.65
Employed full or part time 44 73.33% 23 76.67% 21 70.00%
Retired/Homemaker/Other 16 26.67% 7 23.33% 9 30.00%
Marital status 0.65

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Married/co-habiting 39 65.00% 19 63.33% 20 66.67%
Divorced/widowed/separated/single 21 35.00% 11 36.67% 10 33.33%
Lifestyle and health-related factors
Smoking status 0.78
Never smoked 38 63.33% 19 63.33% 19 63.33%

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Former smoker 19 31.67% 10 33.33% 9 30.00%
Current smoker 3 5.00% 1 3.33% 2 6.67%
Caffeinated beverage consumption
Mean oz consumed/day±SE 21.92 ± 4.15 22.34 ± 7.07 21.51 ± 3.19 0.85
Physical activity 0.95
None 15 25.00% 8 26.67% 7 23.33%
111.64 ± 14.61 107.89 ± 15.89 115.78 ± 24.82
Mean minutes/week±SE
Au 0.44
Body mass index (BMI)
Obese (BMI ≥30) 29 48.33% 11 36.67% 18 60.00% 0.07
Mean ± SE 29.94 ± 0.94 29.17 ± 1.16 31.33 ± 1.34 0.23
History of diagnosed:
Diabetes 9 15.00% 4 13.33% 5 16.67% 0.72
Hypertension 19 31.67% 8 26.67% 11 36.67% 0.41
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High cholesterol 35 58.33% 19 63.33% 16 53.33% 0.43


Depression 23 38.33% 13 43.33% 10 33.33% 0.43
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Anxiety 17 28.33% 9 30.00% 8 26.67% 0.77


Number of cardiometabolic AD 1.83 ± 0.16 1.77 ± 0.23 1.90 ± 0.22 0.68
risk factors∗ Mean ± SE
Total number of major modifiable risk 2.82 ± 0.19 2.70 ± 0.29 2.93 ± 0.24 0.54
factors for AD∗∗ Mean ± SE
Number of medications (regular use)−t 0.71
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None 32 53.33% 16 53.33% 16 53.33%


One 14 23.33% 6 20.00% 8 26.67%
Two or more 14 23.33% 8 26.67% 6 20.00%
History of hormone replacement therapy−t−t 19 37.25% 8 30.77% 11 44.00% 0.61
∗ Including diabetes, hypertension, high cholesterol, obesity (BMI ≥30), cardiovascular disease. ∗∗ lso including history of depression or
anxiety disorder, current smoking, and lack of physical activity. −t Including those commonly linked to memory changes: Statins, narcotic
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analgesics, steroids, benzodiazepines, beta blockers, antihistamines, anticonvulsants, tricyclic and other non-SSRI/SNRI antidepressants.
−t−t Percentages calculated in women only.
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426 improvements were maintained or further strength- cognition at either 3 or 6 months (p’s >0.1). Similarly, 435

427 ened at 3-months post-intervention, with participants the two groups did not differ in reported concerns 436

428 in both groups showing significant improvements regarding their memory at the completion of the 6- 437

429 relative to baseline in all measures of cognitive month study; 57% of participants assigned to the KK 438

430 performance (p’s ≤0.006), as well as overall mem- group versus 54% of those in the ML program indi- 439

431 ory functioning and two MFQ subscales (Frequency cated they were less or much less concerned about 440

432 of Forgetfulness and Retrospective Memory Func- their memory than when they started. 441

433 tioning) (p’s ≤0.006). There were no significant Repeated ITT analyses yielded similar results. 442

434 between-group differences in measures of memory or Findings were not modified by gender, age, obesity, 443
K.E. Innes et al. / Meditation and Music Listening for SCD 7

Table 2
Participant baseline scores on memory and cognitive function tests and average reported duration of memory concerns.
KK (N = 30) ML (N = 30) P
Mean (SE) Mean (SE)
Memory Functioning Questionnaire
Total (range 64–448) 241.83 (9.92) 253.43 (10.07) 0.31
Frequency of Forgetting (range 33–231) 138.50 (5.43) 146.77 (5.26) 0.28
Seriousness of Forgetting (range 18–126) 64.83 (3.83) 73.87 (4.30) 0.15
Retrospective Memory Functioning (range 5–35) 11.70 (0.63) 11.64 (0.62) 0.82

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Mnemonic Use (range 9–56) 21.92 (1.60) 21.48 (1.92) 0.35

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90 Second Digit Symbol Substitution Test 50.57 (1.74) 50.20 (1.83) 0.89
Trail-making Test (TMT)
TMT-A 33.76 (1.08) 34.63 (2.18) 0.73
TMT-B 85.54 (7.14) 90.59 (7.64) 0.53
TMT-B ≥88 seconds: N (%) 13 (43.33%) 12 (40.00%) 0.79
Months Experiencing Memory Problems 36.30 ± 7.08 34.18 ± 4.47 0.80
(range 5 to 180 months, median = 24 months)

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444 history of depression/anxiety, number of AD risk DISCUSSION 480

445 factors, or baseline performance on memory or


cognition tests. Neither excluding those who had In this RCT of adults with SCD, both the KK

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446 481

447 changed medications, nor adjusting for medica- and ML groups showed significant improvements in 482

448 tion change in the models appreciably altered the subjective measures of memory function and objec- 483

449 findings. Improvements in the DSST at 3-months tive measures of attention, processing speed, and 484

450 post-intervention were significantly related to prac- executive function at 3 months, with effect sizes pri- 485

tice adherence (r = 0.3, p < 0.03), an association that marily in the moderate to large range. These gains
451
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452 was more pronounced in the KK than the ML group were sustained or further strengthened at 3-months 487

453 (r = 0.5, p < 0.005 versus 0.1, p = 0.3, respectively). post-intervention, with participants in both groups 488

454 Adherence was not significantly associated with other showing significant improvements relative to base- 489

455 measures of memory or cognition, although associa- line in all measures of cognitive performance, as well 490

tions were in the expected direction. as in multiple domains of memory functioning. At


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456 491

457 Relationships between change over time in both study completion, over 55% of participants reported 492

subjective and performance-based measures are a reduction in memory concerns relative to baseline, a
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458 493

459 given in Table 4. Reduced memory concerns at 6 factor linked to significantly increased risk for accel- 494

460 months were strongly related to certain improve- erated cognitive decline and conversion to MCI and 495

461 ments in the MFQ at both time points, including AD [3, 10, 61]. 496

462 the Frequency of Forgetfulness at 3 months (r = 0.5, To our knowledge, this is the first RCT designed to 497
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463 p < 0.001), and, at 6 months, the MFQ total score examine the effects of mind-body practices on mem- 498

464 (r = 0.5, p < 0.001) and two subscales (Frequency of ory and cognitive functioning in adults with SCD, 499

465 Forgetfulness (r = 0.5 and Seriousness of Forgetting, and among the first to evaluate the possible bene- 500

466 r = 0.4, p’s < 0.01). Regarding the relation of the MFQ fits of any behavioral or lifestyle intervention in this 501

to cognitive performance measures, improvements population [62, 63]. Gains observed in this study are
co

467 502

468 in the MFQ were significantly related only to those similar to or greater than those reported with con- 503

469 in the DSST at 3 months (r = 0.3, p ≤ 0.05 for the ventional exercise [64, 65], tai chi [64, 66], cognitive 504

470 MFQ total at 3 months and 6 months). In contrast, training [67, 68], and multicomponent interventions 505
Un

471 reported memory concerns at study conclusion were [62, 69, 70] in older adults with and without cogni- 506

472 not related to scores on objective performance-based tive impairment, including trials of physical activity 507

473 measures at any time point (p’s >0.1). Beneficial and other programs of nine months or longer duration 508

474 changes in DSST scores at 6 months were signifi- [64, 65, 67–70]. While studies regarding the effects 509

475 cantly associated with improvement in TMTA scores of meditation or music listening on indices of cog- 510

476 at both 3 months and 6 months (r = 0.3, p = 0.02 and nition in populations with or at risk for cognitive 511

477 r = 0.4, p = 0.009, respectively). Additional adjust- impairment remain few [33, 36, 71], our findings are 512

478 ment for age and education did not appreciably alter broadly consistent with those of a recent RCT of med- 513

479 these findings. itation in Chinese elders with sleep impairment [72]; 514
8
Table 3
Change over time in memory and cognitive functioning in older adults with subjective cognitive decline randomized to a 12 week Kirtan Kriya meditation program or a 12-week music listening
program

Un Change from Baseline (KK Meditation) Change from Baseline (Music Listening)

K.E. Innes et al. / Meditation and Music Listening for SCD


Outcome Measures 3 months p ES 6 months p ES 3 months P ES 6 months p ES
(Mean ± SE) (Mean ± SE) (Mean ± SE) (Mean ± SE)
Perceived Memory Function
Memory Functioning Questionnaire
co
Total
Frequency of Forgetfulness
Seriousness of Forgetting
rre
29.35 (8.44)
22.62 (5.68)
6.81 (3.08)
0.002 0.8
0.001 0.8
0.04 0.4
29.84 (7.82)
25.24 (5.60)
3.42 (3.28)
0.0008
0.00003
0.31
0.7
1.0
0.2
25.71 (8.18)
14.07 (4.86)
9.32 (3.44)
0.004
0.007
0.01
0.5
0.5
0.4
31.67 (10.65)
17.59 (5.84)
7.26 (4.75)
0.006
0.006
0.14
0.7
0.6
0.3

cte
Retrospective Memory Functioning 1.92 (0.65) 0.006 0.6 3.42 (0.67) 0.00003 1.0 2.57 (1.02) 0.02 0.8 4.22 (0.87) 0.00005 1.2
Mnemonic Use –2.00 (0.14) 0.22 –0.2 –1.50 (1.07) 0.17 0.2 –0.25 (1.55) 0.87 0.0 2.59 (1.31) 0.06 0.3
Executive Function, Information Processing/

d
Psychomotor Speed, Attention, Working Memory
Digit Symbol Substitution Test 2.08 (0.97) 0.04 0.2 5.15 (0.92) 0.000008 0.6 3.07 (0.94) 0.003 0.3 4.48 (0.93) 0.00006 0.4
Trail-making Test−t
TMT-A
TMT-B
% Change in no. of participants with poor
–2.84 (1.78)
–13.62 (6.27)
–46.8%
0.05
0.04
0.005
0.3
0.7
Au
–6.32 (1.64)
–21.35 (6.05)
–82.3%
0.0008
0.00165
0.004
0.8 –5.00 (2.31)
1.0 –19.43 (6.06)
–46.4%
0.04 0.5 –5.93 (1.90)
0.003 0.9 –22.30 (5.93)
0.02 –53.7%
0.004
0.001
0.008
0.7
1.0

TMT-B scores−t
Memory Concerns at 6 Months (%)−t−t
More concerned tho
(%)
0.00%
(%)
7.69%

rP
Same amount of concern 43.48% 38.46%
Less/Much less concerned 56.52% 53.85%
∗ No significant between group differences at 3 or 6 months (p’s >0.05); −t Baseline score ≥88 seconds; −t−t Calculated from participant responses to the 5-point Likert scale question ‘How concerned

are you about your memory compared to when you began the study?’; ES, effect size; SE, Standard error.

roo
f
Table 4
Correlations between change over time in measures of subjective memory function (MFQ, reported memory concerns at 6 months) and performance based measures of cognition (TMT-A, TMT-B,
and DSST)
Change over time at 3 months Change over time at 6 months
Change from Baseline MFQ MFQ MFQ MFQ MFQ TMT-A TMT-B DSST MFQ MFQ MFQ MFQ MFQ TMTA TMTB DSST Mem-Ory

Un
Total Retro Forget Serious Mne Total Retro Forget Serious Mne concerns
Mem ness monic Mem nes s monic

K.E. Innes et al. / Meditation and Music Listening for SCD


At 3 months

co
MFQ
Total MFQ 0.48−t−t 0.72−t−t 0.78−t−t 0.37−t 0.27∗ 0.69−t−t 0.31∗∗ 0.72−t−t 0.42∗∗ 0.28∗
Retrospective Memory 0.48−t−t 0.31∗ 0.31∗ 0.36∗∗ 0.38∗∗ 0.31∗ 0.27∗
Freq Forgetfulness
Seriousness of
Forge−t−t ing
0.72−t−t

0.78−t−t
0.31∗

0.31∗
rre 0.46−t−t

0.46−t−t 0.25(∗ )
0.24(∗ ) 0.91−t−t

0.49−t −t
0.35∗

0.23(∗ )
1.00−t−t

0.45−t
0.56−t−t

0.42∗∗
0.50−t−t

cte
Mnemonic use 0.37−t 0.25(∗ ) 0.63−t−t
TMT-A –0.32∗
TMT-B 0.59−t−t
0.27∗ 0.24(∗ ) 0.33∗ 0.25(∗ ) 0.25 (∗ ) 0.31∗ 0.48−t−t

d
DSST
At 6 months
MFQ
Total MFQ
Retrospective Memory
Freq Forgetfulness
0.69−t−t
0.31∗∗
0.72−t−t
0.36∗∗
0.38∗∗
0.31∗
0.91−t−t 0.49−t−t
0.35∗ 0.23(∗ )
1.00−t−t 0.45−t Au
0.29∗
0.44−t−t
0.91−t−t
0.44−t−t

0.35∗∗
0.91−t−t
0.35∗∗
0.83−t−t
0.27 (∗ )
0.56−t−t
0.31∗ 0.47−t−t

0.51−t−t
Seriousness of
Forge−t−t ing
Mnemonic use
0.42∗∗
0.28∗
0.27∗ 0.56−t−t 0.42∗∗
0.63−t−t tho
0.22∗ 0.83−t−t
0.31∗
0.27 (∗ ) 0.56−t−t

–0.36∗∗
0.40∗∗

rP
TMT-A
TMT-B 0.59−t−t 0.23(∗ )
DSST –0.33∗ 0.48−t−t –0.36∗∗

roo
Memory concerns at 6
months 0.50−t−t 0.47−t −t 0.51−t−t 0.40∗∗
(∗ ) p < 0.1, ∗ P < 0.05, ∗∗ p < 0.01, −t p < 0.001, −t−t P < 0.0001. Abbreviations: DSST = Digit Symbol Substitution Test; Freq = frequency; MFQ = Memory Functioning Questionnaire; TMT = Trail-
making Test.

9
10 K.E. Innes et al. / Meditation and Music Listening for SCD

515 pilot studies of KK meditation in depressed dementia High practice adherence diminished our ability to 567

516 caregivers [47], adults with memory loss [46], and detect effects of practice frequency on improvements 568

517 caregiver-AD patient dyads [45]; and two RCTs of in memory and cognitive functioning. However, we 569

518 music-based interventions in Finnish and Taiwanese nonetheless noted significant correlations between 570

519 dementia patients [44, 73] including a study of adults mean practice frequency and improvement in the 571

520 with early dementia and their caregivers [44] that DSST, suggesting a possible dose-response rela- 572

521 incorporated music listening at home. In contrast, tionship between practice and improvement in this 573

522 other controlled trials of mindfulness meditation in objective measure of cognitive function. 574

f
523 generally healthy elders [74–76], MCI patients [77]

roo
524 dementia caregivers [78] and nursing home residents Possible mechanisms of action 575

525 [79], of therapist-delivered music programs in psy-


526 chiatric in-patients with cognitive impairment [80] While mechanisms underlying the observed cogni- 576

527 and Italian elders with memory loss [81], and of pas- tive improvements with KK and ML are not yet well 577

528 sive music listening in Taiwanese AD patients [82] understood, these practices likely strengthen cogni- 578

rP
529 showed little or no improvement in cognitive indices. tive functioning via multiple pathways, as discussed 579

530 Reasons for the more limited effects of mindfulness, in our companion paper regarding the effects of KK 580

531 relative to those observed with KK, remain unclear. and ML on the psychosocial outcomes of this RCT 581

532 The apparent disparities in findings could reflect [87]. For example, meditation and ML may improve 582

tho
533 several factors including differences in target popu- cognitive function by reducing the neuropsychiatric 583

534 lations [74, 75], as well as in participant compliance impairment that commonly accompanies SCD, and 584

535 [74, 75]. For example, in studies of cognitively and which has been strongly linked to increased risk 585

536 psychologically healthy populations [74, 75], ceil- for subsequent cognitive decline, neurodegenerative 586

537 ing effects may have hampered investigators’ ability changes, and progression to MCI and dementia [4, 5, 587
Au
538 to detect improvements. Reduced participant adher- 36, 88–90], a relationship that is likely bidirectional. 588

539 ence to practice, perhaps in part due to the higher As documented in our previous paper we observed 589

540 time demands of the intervention, may also have con- significant, sustained improvements in mood, stress, 590

541 tributed [45, 83], potentially helping to explain the sleep, well-being, and quality of life (mental health 591

542 attenuation of benefits over time observed in some component) that were particularly pronounced in 592

studies [75, 84]. In addition, the inconsistency in find- the KK group [87]. Positive changes in psychoso-
d

543 593

544 ings may in part relate to the more active, multimodal cial status were directly correlated with gains in 594
cte

545 nature of KK practice, which, as discussed briefly memory function, and, albeit more modestly, cog- 595

546 below, may further contribute to gains in cognitive nitive performance, suggesting a possible functional 596

547 functioning. connection [87]. That gains in cognition were compa- 597

548 We found significant, although modest associa- rable between groups despite greater improvements 598

549 tions between changes in the MFQ, a measure of in psychosocial status with KK suggests that ML 599
rre

550 subjective memory loss, and both concomitant and may improve cognitive function via other pathways, 600

551 prior improvement in the DSST, a performance-based including those delineated below. 601

552 measure of psychomotor speed, attention, and work- Meditation and ML may also improve cognition 602

553 ing memory. These findings support the validity of the by promoting beneficial functional and structural 603
co

554 MFQ, and suggest that reduction in memory concerns changes in brain structures associated with cognitive 604

555 may in part reflect objective improvements in cer- processing, attention, memory, emotional regulation, 605

556 tain domains of cognition. While studies examining and reward [31, 44, 91–94]. For example, emerging 606

557 the relation between change over time in subjective evidence suggests that both meditation and ML can 607
Un

558 and objective measures of cognition are sparse, our induce favorable changes in central nervous system 608

559 findings are consistent with those of some, but not dopaminergic and other neurochemical systems [95, 609

560 all cross-sectional studies [85]; the former include a 96] and enhance autonomic regulation, in part by 610

561 recent investigation in healthy elders, which reported modulating activation of the sympathoadrenal sys- 611

562 a significant correlation between the MFQ and DSST tem and HPA axis [30, 31, 36]. In addition, recent 612

563 [86]. Notably, associations have been stronger in controlled trials of ML and meditation, including 613

564 better educated and non-depressed adults, and with exploratory studies of KK[46, 97], suggest these 614

565 measures of cognitive domains most affected in early practices can modulate activity, increase grey mat- 615

566 stages of AD [85]. ter volume and/or density, and promote functional 616
K.E. Innes et al. / Meditation and Music Listening for SCD 11

617 connectivity in multiple brain areas compromised in potential placebo effects. In addition, both KK and 667

618 AD, including the hippocampus, prefrontal cortex, ML have been shown to have positive effects on a 668

619 insula, amygdala, orbitofrontal cortex, and anterior range of health and psychosocial outcomes strongly 669

620 cingulate gyrus [30, 31, 37, 38, 44, 46, 92, 94, related to cognitive functioning and predictive of 670

621 97–104]. cognitive decline [33, 36, 142, 143], and the two inter- 671

622 Recent cross-sectional [105] and prospective stud- ventions were well matched in terms of structure, 672

623 ies [47, 105, 106] also suggest that meditation delivery, and practice time, reducing potential bias 673

624 may protect against the deleterious effects of stress- related to differential dosing, staff attention, ease of 674

f
625 induced cellular senescence on immune and neuronal access, social interaction, or other factors. 675

roo
626 function by promoting telomere maintenance, a factor Our use of a questionnaire to ascertain presence 676

627 implicated in cognitive decline and the development of SCD that incorporated criteria based on prior 677

628 of MCI and dementia [107–109]. Similarly, recent expert reviews and longitudinal studies and including 678

629 pilot trials offer preliminary evidence that medita- worries regarding one’s memory problems, a factor 679

630 tion [110–116] and music interventions[117, 118], shown to strengthen the link of SCD to incident MCI 680

rP
631 including simple music listening [118] might also and AD [3, 6, 10, 61], aided in capturing those at 681

632 attenuate or reverse harmful alterations in specific risk for cognitive decline. Our participants were char- 682

633 gene expression pathways implicated in AD patho- acterized by high prevalence of established AD risk 683

634 genesis, including those regulating cellular aging, factors, as well as mean MFQ baseline scores that 684

tho
635 inflammation, oxidative stress, and other factors con- were similar to those of persons with amnestic MCI 685

636 tributing to neuropathological changes and cognitive [144], and considerably lower than values reported in 686

637 decline [119–125]. community-based samples [145]. In addition, in over 687

638 Meditation and ML may also influence cognitive 40% of participants, TMT-B scores at baseline were 688

639 function indirectly by promoting reductions in sys- in the range associated with a high risk for acceler- 689
Au
640 temic inflammation, thought to play an important ated cognitive decline and progression to MCI and 690

641 role in cognitive decline and AD pathogenesis [126]. dementia [55, 56]. 691

642 Elevated systemic inflammation has been linked to This preliminary trial has several limitations 692

643 both telomere degradation [127–129] and cerebral as well. Our study sample size was relatively 693

644 volume loss [126]. Similarly, longitudinal studies small, and our study population comprised relatively 694

have consistently shown high blood levels of proin- young, well-educated, motivated volunteers with
d

645 695

646 flammatory biomarkers, including interleukin, tumor SCD, potentially restricting generalizability to other 696
cte

647 necrosis factor-alpha, and high sensitivity C-reactive populations with preclinical memory loss. While we 697

648 protein, to predict cognitive decline [126]. Elevated assessed memory and cognitive function, we did not 698

649 inflammatory markers are also strongly associated, conduct diagnostic evaluation of cognitive status in 699

650 in a bidirectional manner, to chronic psychologi- our study sample; it is thus possible that participants 700

651 cal stress, mood disturbance, sleep loss, and other included some individuals with undiagnosed MCI. 701
rre

652 distressful states [130–136]. While studies remain In addition, we lacked information on brain or CSF 702

653 sparse, and trials in adults with memory loss are lack- biomarkers of AD, and were thus unable to assess the 703

654 ing, emerging evidence from healthy [137–139] and effects of KK or ML on these potential mechanisms 704

655 stressed adults[140], lonely older adults [110], and of action, to evaluate the modifying influence of these 705
co

656 cancer patients [141] suggests that meditation[140] factors, or to examine the relation of these biomarkers 706

657 and ML may reduce systemic inflammation. to memory and cognitive function. 707

Possible practice effects may have accounted for 708

658 Strengths and limitations some of the improvement, although the relatively 709
Un

long interval between assessments renders this possi- 710

659 Strengths of this investigation include the rigorous bility less likely. As noted above, several trials of both 711

660 study design and measurement of both subjective and meditation and other non-pharmacologic interven- 712

661 objective cognitive performance. Participants were tions, including RCTs in adults at risk for cognitive 713

662 recruited from the community, potentially enhanc- decline, noted little change in cognition. For example, 714

663 ing generalizability and applicability of our findings. several studies of conventional exercise[146–148], tai 715

664 Additional strengths include the excellent adherence chi [149], and meditation-based programs [47, 74, 716

665 and retention rates in both groups. Collection of data 75] in healthy seniors [74, 146], senior facility resi- 717

666 on treatment expectancy also allowed adjustment for dents [148], depressed dementia caregivers [47], and 718
12 K.E. Innes et al. / Meditation and Music Listening for SCD

719 elders with or at risk for memory loss [147, 149] risk for AD. Additional rigorous trials are needed to 769

720 showed little or no change over time in the TMT further evaluate the possible benefits of KK and ML 770

721 among participants in the control group, with some for adults with preclinical memory loss, to ascertain 771

722 noting worsening over time in this measure [75, 146, the long term effects of these practices on cognitive 772

723 147, 149]; several trials likewise reported minimal or health, and to explore potential mechanisms of action. 773

724 no change even among participants assigned to the


725 active intervention [74, 75, 147–149]. By contrast,
726 we observed marked and significant improvement in ACKNOWLEDGMENTS 774

f
727 multiple domains of memory and cognition, includ-

roo
728 ing the TMT. Nonetheless, given that we did not This work was supported by the National Insti- 775

729 include a standard care control group, the possibility tutes of Health [1-K01-AT004108 and NIGMS 776

730 of practice effects cannot be ruled out. In addition, U54GM104942 to K.E.I.]; the Alzheimer’s Research 777

731 blinded treatment administration was not possible in and Prevention Foundation (ARPF); and West 778

732 this study, potentially biasing expectations of partic- Virginia University (Faculty Incentive Award; WVU- 779

rP
733 ipants and raising the possibility of placebo effects. MU Health Partnership Grant). 780

734 However, the expectancy scores of the two groups Authors’ disclosures available online (http://j-alz. 781

735 were similar and, most importantly, were unrelated to com/manuscript-disclosures/16-0867r1) 782

736 either subjective memory function or objective cogni-

tho
737 tive performance, rendering expectations of treatment REFERENCES 783
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