Kalbe E. J Neurol Neuromedicine (2018) 3(2): 14-18 Neuromedicine www.jneurology.com www.jneurology.com Journal of Neurology && NeuromedicineNeuromedicine

Commentary Open Access

Cognitive Stimulation in : Time to Go into Detail. A Commentary Elke Kalbe1*, Ann-Kristin Folkerts1 1Medical | Neuropsychology and Gender Studies & Center for Neuropsychological Diagnostics and Intervention (CeNDI), University Hospital Co- logne, Kerpenerstraße 62, 50937 Cologne, Germany

Article Info ABSTRACT

Article Notes While it is undeniable that cognitive stimulation (CS) is effective in patients with Received: March 22, 2018 dementia, there is still a lack of understanding of the underlying mechanisms of Accepted: April 11, 2018 the effects, and questions like “Who benefits?” or “Which factors determine the *Correspondence: benefits?” are not yet answered. Therefore, this commentary gives an overview Prof. Dr. Elke Kalbe, Medical Psychology | Neuropsychology of different aspects (e.g., sociodemographic factors, disease characteristics, living and Gender Studies & Center for Neuropsychological setting) that need to be considered while doing research on CS to understand their Diagnostics and Intervention (CeNDI), University Hospital impact on CS effects. It is also necessary to examine the effects of CS in real-life Cologne, Kerpenerstr. 62, 50937 Cologne, Germany; settings (e.g., geriatric hospitals) with mixed samples (e.g., patients with different Telephone: +49 221 478- 96244; Fax: +49 221 478-3420, severity of dementia). Additionally, important factors for future studies on CS in Email: [email protected] dementia (e.g., reporting according to the CONSORT guidelines, more health- © 2018 Kalbe E. This article is distributed under the terms of the economics studies) are outlined. Creative Commons Attribution 4.0 International License

Introduction Keywords Cognitive stimulation (CS) as a non-pharmacological intervention Dementia Alzheimer’s disease in patients with dementia has attracted great interest during the past Intervention Cognitive stimulation Cognition decade. CS is defined as conducting a range of activities (e.g., cognitive Prediction stimulating games, sensory exercises) and discussions (e.g., talking about past experiences), usually carried out in small groups of 3 to 6 patients, with1,2 the aim of a general enhancement of cognitive and social functioning . Meta-analyses have shown that demonstrated CS 2-5 has positive a positive effects on various cognitive and non-cognitive symptoms2 . For example, the Cochrane review by Woods and colleagues impact on the global cognitive state, on quality of life, and on well-being, as well as on communication and social interaction – with effects over and above those of any medication. However, although the benefits of CS are undeniable, it is true that, upon closer inspection, many open questions remain. One major concern that challenges the generalisability of the found effects is that the target group of “patients with dementia” in itself is so heterogeneous and that the samples in the published studies differ so substantially. Thus, to boost the predictive power of CS, the next step will be to ask: “Do all patients benefit?” (which is unlikely) or, more precisely, “Who benefits under which circumstances?” and “Which factors determine whether a patient with dementia profits?” or “Which PossibleCS intervention factors is withbest foran whichimpact patients?” on CS benefits Sociodemographic variables

Many variables have the potential to have an impact on the effects of CS in patients with dementia (Table 1). For example, sociodemographic

Page 14 of 18 Kalbe E. J Neurol Neuromedicine (2018) 3(2): 14-18 Journal of Neurology & Neuromedicine

variables may be relevant. Age is one of them. Notably, Therefore, it is imaginable that patients in a more advanced betterwhile some results studies that examined cognitive training effects stage of the disease need CS programs that are cognitively in healthy older6-8 adults showed that younger age yield less challenging. Regarding disease severity, randomised (a finding that fits the notion that ageing9,10 controlled trials (RCTs) demonstrated that patients with. is related to reduced cognitive11 or age and having neural no plasticity impact ),. a lower cognitive baseline level were able to benefit more13,14 with CS, conflicting results exist, with higher age being12-14 from CS than patients with higher baseline results predictive of better results Besides the interpretation that there is more “room for Gender effects may also play a role. Besides the fact that improvement” in patients with lower cognitive baseline cognitive profiles might differ in female and male patients and levels, it is also possible that the CS exercises were too easy with dementia (e.g., verbal memory is more affected15 for the fitter patients and demanded too little of them. In in female patients16 with Alzheimer´s dementia this context, also, the question of group selection needs to Parkinson´s disease ), gender effects on benefits of CS for11. be reflected upon: Are mixed groups better (so that patients patients with dementia have been reported, indicating that arewith more more homogeneous severe symptoms groups will better profit (sofrom that those all patientsthat are cognitive outcomes improve more in female participants fitter, and the fitter ones profit from helping the others)? Or withA stronger mild cognitive benefit impairment in verbal memory/working (MCI) attending cognitive memory trainingwas also17 demonstrated for female than for male patients are cognitively challenged according to their own level of been proposed carefunctioning)? units vs. traditional This issue careis still units under investigation when it , and 18 gender-specific cognitive plasticity has comes to nursing home structures22-24 (e.g., dementia special . An alternative explanation, which has ), and, to the authors’ been proposed but not yet investigated in the context of knowledge, has not yet been studied in the context of the toCS, be could involved be that in womentheir health have issuesa more than active men) attitude19 (i.e., conduct of CS interventions. Possibly, and according to the show more knowledge, positive emotion, and motivation authors´ own experiences in conducting CS on patients . Finally, participantswith dementia, can groups be implemented in which the much intervention easier in programa rather although to the authors’ knowledge, level of education has can be matched to the level of functioning and needs of the not been found (and rarely studied) to have an impact on CS benefits, it has been identified as a predictor of cognitive homogenous setting with patients of similar dementia training effects within the ACTIVE Trial with older people severity. without dementia20 (Mini Mental State Examination (MMSE) While there are studies that only include patients > 23 points) , indicating that more years of education yields with possible or probable Alzheimer´s2,3,25-28 disease, vascular a better training response. Thus, it might also be relevant . dementia, and/or mixed dementia , other etiologies for CS effects, even more so as education21 is regarded as a have not been studied separately. However, cognitive Diseasedriver of characteristicsneural and cognitive and plasticitygroup composition aphasiaand neuropsychiatric be able to participate symptoms in differ a CS betweenprogram typesdespite of dementia. For example, will a patient with progressive a cognitiveDisease characteristicsmotor rehabilitation may also program have anwith impact patients on his or her problems in understanding/communication? benefits of CS. For example, in an observational reported study that using the Are patients with frontotemporal dementia willing to 12 participate, and do they constitute a challenge in a group with MCI and dementia, Binetti et al. setting due to behavioural symptoms? Indeed, the profile of aberrantresponders motor had significantlybehaviours lessthan impairment the non-responders. in insight, non-cognitive symptoms in patients with dementia might larger functional ability and less delusions, euphoria, and have a substantial influence on the benefits of CS, and the Table 1: Factors that potentially influence effects of cognitive ourrelationships own group between symptoms might be complex and stimulation in patients with dementia. need more research.14 For example, in the RCT conducted by • Sociodemographic variables: age, gender, education low cognitive baseline which examinedscores predicted the effects better of CSoutcome versus • Disease characteristics: dementia type/etiology, disease usual care in patients with dementia in long-term care, duration, disease severity, cognitive profile, other symptoms (e.g., and behavioural and psychiatric symptoms, comorbidities), medication in cognition. However, this association was moderated by • Living setting: at home, day-care facility, hospital, nursing home depressive symptoms, indicating that patients with lower • Characteristics of the cognitive stimulation intervention: cognitive baseline scores only benefitted more if they were frequency, intensity, type of tasks/activities, number of not (or less) depressed. This leads to the presumption that participants therapy of depressive symptoms could be an important • Group composition: heterogeneous vs. homogeneous (e.g., precondition for success of CS. Thus, although the ultimate regarding type of dementia/symptomatology/severity of aim should be to make efficient interventions such as CS disease) available to all patients who might profit, work should be done on investigating possible differential effects Page 15 of 18 Kalbe E. J Neurol Neuromedicine (2018) 3(2): 14-18 Journal of Neurology & Neuromedicine

depending on the type of dementia to clarify which care or whether they are directly related to the content of variations of CS are most powerful in which etiology or the . Finally,35 a recent Cochrane review with which symptom complex. At the same time, it needs by Woods and colleagues on reminiscence therapy in to be considered that the CS groups in real-life settings will dementia calculated subgroup analyses for people living mostly be mixed regarding aspects like dementia types in the community and in nursing homes. They found that and severity, behavioural and psychological symptoms in only nursing home residents improved in cognition and dementia (BPSD), and comorbidities; and in some settings quality of life, whereas only the community sample showed such as long-term care (see below), qualified diagnoses benefits in communication. As a last but also important might not even be available. Thus, CS effects should also be aspect, future studies will have to clarify which intervention examined in these settings (e.g., mixed patients in nursing type of which duration and frequency is most effective for Livinghomes, orsetting geriatric/psychogeriatric hospital units). Conclusionwhich dementia type and severity.

in patients with dementia is undeniable and argues in Indeed, the impact of the living setting of the patients on In summary, while the main message that CS is effective CS effects is insufficiently investigated. It is well known that patients living at home differ from patients in long-term favour of implementation of this type of intervention into clinical practice, more research is necessary to understand care in several 29,30characteristics: those in long-term care are typically older and suffer from more severe cognitive underlying mechanisms of the effects, so that CS can be tailored as efficiently as possible to the patients. Important as well 29,30 as functional impairment, including reduced mobility , as a result of being in more advanced stages aspects for future research are listed in Table 2. Among other research questions, future studies should define of dementia.31 Furthermore, residents are highly affected by in more detail the impact of sociodemographic factors BPSD . They often suffer from several comorbidities32 and (age, education, sex), clinical parameters (severity of takenot largeoperationalised quantities andaccording varieties to of medicationguidelines , leading disease, cognitive and non-cognitive symptoms, etiology, to side effects, and specific dementia diagnoses33 are often centres or in long-term care or in hospital settings) on the . Finally, medication), and living setting (at home or in day-care community-dwelling patients typically have stronger social support, which might enhance patients’ motivation and effects of CS – and examine whether different forms of CS on in terms of intensity, frequency, and content help patients compliancecognitive interventions for attending in cognitive dementia interventions. have not considered 2,5,25,27However, several systematic reviews and meta-analyses with different characteristics. With more knowledge on these topics, this powerful non-pharmacological demonstrated that patients in long-term care intervention could enter the era of personalised medicine. this factor. But34 few reviews took this aspect into account. Not to forget, health-economics studies, which have been Huang et al. widely neglected in CS and other non-pharmacological benefited significantly more from reminiscence therapy interventions in dementia, will also be necessary to with regard to depressive 4symptoms than the community between setting (inpatient vs. outpatient) and cognitive convince policy makers of the benefit of this intervention, sample, while Huntley et al. examined a possible association as few studies on this important factor for integrating this therapy36-38 option in standard care have been published so benefits after attending cognitive intervention sessions far . Many of the questions raised will need large-scale with the help of a meta-regression, but did not find effects. multi-center RCTs, conducted39,40 and reported according to To also face this barely recognised aspect, we conducted CONSORT guidelines . Let´s face it. a systematic review and meta-analysis on cognitive Table 2: Important aspects for future study designs and study reporting. livinginterventions in long-term (including care CS, but also cognitive training and reminiscence therapy)26 exclusively in individuals • Study reporting according to CONSORT guidelines, considering , and showed that these therapies the extended version for non-pharmacological interventions (Boutron et al., 2008) which includes, among other aspects, yielded significant moderate effects on global cognition, o a detailed description of the intervention controlautobiographical groups. In memory, studies comparing and BPSD, CS as withwell activeas significant control small effects on quality of life when compared with passive o a detailed description of the sample and its characteristics • Intention-to-treat analysis and per protocol analysis groups, significant moderate effects were also found on • Well-defined study samples as well as examining real-life settings global cognition and depression. Thus, the good news was that CS also seems effective for this specific group • Follow-up examinations over months and years of patients. However, our systematic review also showed • Prediction analysis: who benefits? limitations of the current state of knowledge, as it seemsd • Health-economics analysis unclear whether the effects on BPSD and quality of life only reflect unspecific changes due to additional attention an Page 16 of 18 Kalbe E. J Neurol Neuromedicine (2018) 3(2): 14-18 Journal of Neurology & Neuromedicine

Acknowledgement

14. Middelstaedt J, Folkerts AK, Blawath S, et al. Cognitive StimulationJ Alzheimers for PeopleDis with Dementia in Long-Term Care Facilities: Baseline Cognitive This research did not receive any specific grant from Level Predicts Cognitive Gains, Moderated by Depression. . 2016; 54(1): 253-268. funding agencies in the public, commercial, or not-for- Conflictprofit sectors. of Interest statement 15. Pusswald G, Lehrner J, Hagmann M, et al. Gender-Specific DifferencesJ Alzheimersin Cognitive Dis. Profiles 2015 of Patients with Alzheimer’s Disease: Results of the Prospective Dementia Registry Austria (PRODEM-Austria). ; 46(3): 631-637.

EK received grants from the German Ministry of 16. correctedFengler S, normativeRoeske S, data.Heber Psychol I, et al. Med Verbal memory declines more in Education and Research, the German ParkinsonFonds, and female patients with Parkinson’s disease: the importance of gender- 17. the German Parkinson Society as well as honoraria from: . 2016; 46(11): 2275-2286. oticon GmbH, Hamburg, Germany; Lilly Pharma GmbH, Bad NeuropsycholRahe J, Liesk DevJ, Rosen Cogn JB,B Aging et al. NeuropsycholSex differences Cogn. in cognitive training Homburg, Germany; Bernafon AG, Bern, Switzerland; and effects of patients with amnestic mild cognitive impairment. 2015; 22(5): 620- Desitin GmbH, Hamburg, Germany. AKF received a grant 638. from the German Parkinson Society, and honoraria from J Neurol. References 18. Beinhoff U, Tumani H, Brettschneider J, et al. Gender-specificities in ProLog Wissen GmbH, Cologne, Germany. Alzheimer’s disease and mild cognitive impairment. 2008; 1. 19. 255: 117-122. Neuropsychol in the active attitude toward treatment and health among older ClarRehabile L, Woods RT. Cognitive training and cognitive rehabilitation for Chylińska J, Łazarewicz M, Rzadkiewicz M, et al. The role of gender people with early-stage Alzheimer’s disease: a review. BMC Geriatr. . 2004; 14: 385-401. patients in primary health care-self-assessed health status and Cochrane Database sociodemographic factors as moderators. 2017; 17(1): 2. WSystoods Rev. B, Aguirre E, Spector AE, et al. Cognitive stimulation to improve 284. cognitive functioning in people with dementia. J Gerontol B Psychol 2012; 2: CD005562 20. SciLang Socbaum Sci JB, Rebok GW, Bandeen-Roche K, et al. Predicting memory training response patterns: results from ACTIVE. 3. Fukushima RLM, do Carmo EG, Pedroso RDV,Dement et al.Neuropsychol Effects of. . 2009; 64(1): 14-23. cognitive stimulation on neuropsychiatric symptoms in elderly with Neural Alzheimer’s disease: A systematic review. 21. Plast.Mandolesi L, Gelfo F, Serra L, et al. Environmental Factors Promoting 2016; 10(3): 178-184. Neural Plasticity: Insights from Animal and Human Studies. 2017; 2017: 7219461. 4. BMJHuntle Openy JD, Gould RL, Liu K, et al. Do cognitive interventions improve compa general cognition in dementia? A meta-analysis and meta-regression. 22. Crespo M,Int Hornillos Psychogeriatr C, Gómez MM. Dementia special care units: a . 2015; 5: e005247. rison with standard units regarding residents’ profile and care features. . 2013; 25(12): 2023-2031. 5. Kurz A, Leucht S, Lautenschlager N. The clinicalInt significance Psychogeriat. of cognition-focused interventions for cognitively impaired older adults: 23. Kok JS, Berg IJ, Scherder EJ.Dement Special Geriatr care unitsCogn andDis traditionalExtra care in A systematic review of randomized controlled trials. dementia: relationship with behavior, cognition, functional status and 2011; 23: 1364-1375. quality of life - a review. . 2013; 3(1): 360-375. 6. pretraining.Brooks JO, FriedmanInt Psychogeriatr. L, Pearman AM, et al. Mnemonic training in older adults: effects of age, length of training, and type of cognitive 24. Weyerer S, Schäufele M, HendlmeierInt J Geriatr I. EvaluationPsychiatry of special and 7. 1999; 11(1): 75-84. traditional dementia care in nursing homes: results from a cross- J Aging Health. sectional study in Germany. . 2010; 25(11): Rebok GW, Langbaum JB, Jones RN, et al. Memory training in the 1159-1167. ACTIVE study: How much is needed and who benefits? 2013; 25(8 suppl): 21S-42S. 25. dementia.Bahar-Fuchs Cochrane A, Clare Database L, Woods Syst B. Rev. Cognitive training and cognitive rehabilitation for mild to moderate Alzheimer’s disease and vascular 8. VerhaeghenPsychol P,Aging. Marcoen A, Goossens L. Improving memory 2013; (6): CD003260. performance in the aged through mnemonic training: a meta-analytic 9. study. 1992; 7(2): 242. Nat Rev 26. Folkerts AK, Roheger M, FranklinArch Gerontol J, et al. Geriatr. Cognitive interventions in Neurosci. patients with dementia living in long-term care facilities: Systematic Burke SN, Barnes CA. Neural plasticity in the ageing brain. review and meta-analysis. 2017; 73: 204-221. 2006; 7(1): 30-40. Acta Psychiatr Scand Clin Interv Aging. 27. Sitzer DI, Twamley EW, Jeste DV. Cognitive training in Alzheimer’s 10. Fernández-Ballesteros R, Botella J, Zamarrón MD, et al. Cognitive disease: a meta-analysis of the literature. . 2006; plasticity in normal and pathological aging. 2012; 114(2): 75-90. 11. 7: 15-25. Int J Geriatr 28. interventions.Spector A, Orrell Dement M, Hall Geriatr L. Systematic Cogn Disord review of neuropsychological PsychiatryAguirre E, Hoare Z, Streater A, et al. Cognitive stimulation therapy outcomes in dementia from cognition-based psychological (CST) for people with dementia--who benefits most? . 2012; 34(3-4): 244-255. . 2013; 28(3): 284-290. nursing homes. West J Nurs Res. 29. Maas ML, Kelley LS, Park M, et al. Issues in conducting research in 12. ClinicalBinetti G,practice Moretti recommendations. DV, Scalvini C, et al.Int Predictors J Geriatr ofPsychiatry. comprehensive 2002; 24: 373-389. stimulation program efficacy in patients with cognitive impairment. intervention research. West J Nurs Res. 2013; 30. Mentes JC, Tripp-Reimer T. Barriers and facilitators in nursing home 28(1): 26-33. 2002; 24: 918-936.

13. Graessel E, Stemmer R, Eichenseer B, et al. Non-pharmacological,BMC Med 31. Snowden M, Sato K, Roy-Byrne P. Assessment andJ Am treatment Geriatr Soc of. multicomponent group therapy in patients with degenerative nursing home residents with depression or behavioral symptoms dementia: a 12-month randomized, controlled trial. . 2011; associated with dementia: A review of the literature. 9: 129. 2003; 51: 1305-1317.

Page 17 of 18 Kalbe E. J Neurol Neuromedicine (2018) 3(2): 14-18 Journal of Neurology & Neuromedicine

Am J Alzheimers Dis Other Demen Arch 32. GerontolAkner G. Geriatr Analysis of multimorbidity in individual elderly nursing experiential relevance. . 2014; 29(6): home residents. Development of a multimorbidity matrix. 503-12. . 2009; 49: 413-419. Br J Psychiatry. Z ärztl. Fortbild. Qual. 37. Knapp M, Thorgrimsen L, Patel A, et al. Cognitive stimulation therapy 33. Bruene-CohrsGesundh.wes. U, Juckel G, Schröder SG. [The Quality of the Diagnostic for people with dementia: cost-effectiveness analysis. Assessment of Dementia in Nursing Homes]. 2006; 188: 574-80. 2007; 12: 611-615. 38. Orgeta V, Leung P, Yates L, et al. Individual cognitiveHealth stimulation Technol 34. Huang HC, Chen YT, Chen PY, et al. Reminiscence Therapy Improves Assesstherapy for dementia: a clinical effectiveness and cost-effectiveness CognitiveJ Am Functions Med Dir Assoc and Reduces Depressive Symptoms in Elderly pragmatic, multicentre, randomised controlled trial. People With Dementia: A Meta-Analysis of Randomized Controlled . 2015; 19(64): 1-108. Trials. . 2015; 16(12): 1087-1094. dementia. Cochrane Database Syst Rev. 39. Boutron I, Moher D, AltmanAnn DG, Intern et al. Med. CONSORT group. Extending the 35. Woods B, O’Philbin L, Farrell EM, et al. Reminiscence therapy for CONSORT statement to randomized trials of nonpharmacologic treatment: 2018; 3: CD001120. Explanation and elaboration. 2008; 148: 295-309.

36. Alves J, Alves-Costa F, Magalhães R, et al. Cognitive stimulation for 40. Schulzrandomised KF, trials. Altman PLoS DG, Med. Moher D. CONSORT Group. CONSORT Portuguese older adults with cognitive impairment: a randomized 2010 statement: updated guidelines for reporting parallel group controlled trial of efficacy, comparative duration, feasibility, and 2010; 7(3): e1000251.

Page 18 of 18