Randomized Controlled Trial of Multi-Component Cognitive Stimulation Therapy (SADEM) in Community-Dwelling Demented Adults

Abstract

Background:

Dementia is a persistent, progressive state of cognitive decline against which pharmacological intervention has a modest efficacy, reducing behavioral but not cognitive symptoms. Therefore, different non-pharmacological therapies have been developed; the most scientifically recognized are cognitive therapies that have improved cognitive function and daily life activities.

Objective:

To evaluate the effectiveness of a multicomponent cognitive stimulation therapy (SADEM) on cognitive and behavioral function and daily life activities in patients with mild stage dementia.

Methods:

Controlled clinical trial with pre- and post-intervention (12 months) and follow-up (24 months after) evaluations. Participants (67) diagnosed with mild dementia were randomly assigned to intervention group (n = 39) or control group (n = 28). The intervention took place throughout one year and consisted of two weekly 90-minute sessions and one more a year after a monthly follow-up. Instruments were used to evaluate outcomes in cognitive, behavioral, and affective domains.

Results:

The results showed statistically significant differences, with improvement in the cognitive outcomes and the Dementia Index post-intervention (p = 0.01). No progression of the disease was observed at the end of the study.

Conclusion:

The multicomponent intervention tested had positive effects on cognitive and behavioral functions and daily life activities in people with mild stage dementia, delaying progression for at least two years.

Keywords

Cognitive stimulation therapy dementia functional cognition multicomponent intervention music therapy SADEM

INTRODUCTION

Dementia is a neurodegenerative disorder that usually starts with the loss of memory, associated to alterations in other brain functions. It progressively affects the patient’s daily activities, leading to a state of dependency [1].

In 2015, 47 million people were living with dementia worldwide, and this figure is estimated to double every 20 years, reaching 115.4 million by 2050 [2]. In 2010, the global cost of care for persons with dementia (PWD) was 604 billion dollars, 1% of the GDP worldwide, and it is estimated to increase by 1.2 billion dollars in 2030 [2]. In 2012, the prevalence of dementia in Mexico was reported to be 7.9%; that is 800,000 people. It is reported to reach over 3 million Mexicans in 2050, representing a total expense of 3.8 billion dollars [3].

Cognitive impairment in dementia evolves individually in three stages: mild, moderate, and severe. These were established according to the cut-off points used on cognitive scales such as the Mini-Mental State Exam (MMSE) and the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) as well as clinical manifestations described in functional scales, such as the clinical dementia rating (CDR) scale and the global dementia scale (GDS) [4 –6]

There currently is no cure for dementia, but the pharmacological and non-pharmacological treatments developed seek to control mood and behavior manifestations. Most of the approved medications for treating dementia are acetylcholinesterase inhibitors and NMDA receptor antagonists [7].

In addition to pharmacological interventions, a multi-dimensional therapeutic approach is required. It must include non-pharmacological strategies aimed at optimizing the cognition and functionality of PWD while also attending to the needs of caregivers [6 , 9].

For this reason, a series of therapeutic interventions have been implemented, including cognition [10], motor stimulation [11], and music therapy [12]. The mechanisms involved in the response to music therapy in dementia are related to learned cognitive responses, activation of neural circuits, and stimulated neural coherence, as well as cellular and genetic changes to specific frequencies [13]. They show the strongest impact in patients with mild and moderate dementia [14]. Additionally, it has been pointed out that music therapy can improve depression, anxiety, and quality of life in PWD, helping to maintain their well-being for a longer time [15, 16].

On the other hand, the scientific basis of cognitive stimulation in aging in general, and dementias in particular, is centered on the neuroplasticity of the brain, brain potential and reserve, and the principles of neuropsychological rehabilitation. Neuroplasticity is understood as the ability of the brain to adapt to demands and re-establish equilibrium secondary to brain dysfunction [17, 18]. Neuroimaging studies indicate that cognitive interactions cause alterations in brain activation patterns. A reduced brain activity is related to a greater efficiency in healthy aging, while in pathological aging, the cognitive reserve demands the reactivation of specific neuronal networks of the frontal regions, the hippocampus, and the precentral gyrus [17].

Non-pharmacological therapies have a theoretical basis, are potentially replicable, and aim to help the patient, the caregiver, or both [19]. They attempt to delay deterioration, recover or preserve functionality, improve the control of behavioral symptoms and quality of life, and delay patient institutionalization [19 –21]. These therapies are based the principle that learning and attention should always be centered on the person and adapted to the deficits in each patient [22]. They should be directed by professionals experienced in the field of psychology [19, 23].

Some studies indicate that cognitive stimulation improves cognition and quality of life [24], and its benefit is comparable to that of cholinesterase-inhibiting medications [20, 25]. Later studies have also observed cognitive benefits in this kind of therapy [26, 27]; however, its alteration mechanisms remain unclear [28]. Therefore, it is necessary to perform controlled randomized trials that evaluate the long-term efficacy of these type of therapies in real life [29], including social and family environments [30].

Considering the above, a randomized triple-blind clinical trial was performed with elderly Mexicans with dementia and their caregivers as participants. The trial evaluated the efficacy and potential long-term effects of a multi-component cognitive stimulation program (SADEM program) for rehabilitation by stimulating preserved or relatively preserved cognitive regions.

MATERIALS AND METHODS

Study population

The study population was selected from a study on aging and dementia in Mexico (SADEM) conducted with 3,105 individuals aged 60 or older. The participants (aged 60 and older) were beneficiaries (users and non-users) attached to any of the 24 family medicine clinics of IMSS (Instituto Mexicano del Seguro Social) in Mexico City, chosen through random sampling. In the original study, the diagnosis of dementia was made according to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) and the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association (NINCDS-ADRDA). Under these criteria, only 67 patients with mild dementia were diagnosed as previously described [31, 32].

The inclusion criteria for this intervention study were age 60 or older, living in community, diagnosis of dementia in the previous 6 months, score on the CDR of 1 (mild dementia), score on the MMSE of 19–24 (mild dementia), sustained ability to communicate and understand communication, and having a main caregiver willing to participate in the study Fig. 1. We excluded those patients with physical or behavioral alterations (secondary to delirium or aggression), psychiatric disorders, visual, hearing, or physical disabilities. Patients suffering from other diseases that could interfere with learning and those whose caregiver had a disease or disability that prevented them from accompanying the patient to the sessions were excluded as well.

Fig. 1

Distribution of the study groups in Mexico City.

Before starting the study, both the patient and the caregiver received detailed information on the intervention and signed an informed consent letter in the presence of a witness, usually a member of the health care team. All patients were evaluated by a team consisting of a geriatrician, a nurse, and a neuropsychologist who interviewed the patient. The questionnaire applied included socio-economic data, clinical, neurological, physical, and memory alteration evaluations, current medications, and background data of all risk factors for dementia.

Methods

In order to include all elderly adults diagnosed with mild dementia in the SADEM (n = 67), the intervention group consisted of 39 patient-caregiver dyads, distributed in three groups of 13 dyads each while the controls (28 dyads) were also distributed into three groups, one with 10 and two with 9 dyads. The groups were distributed according to the score obtained in the MMSE and the medication received as treatment for dementia. The study was conducted using SPSS 25 and always sought homogeneity between the intervention and control groups. A research technician, independent from the research group, performed the randomization. The patients’ assignment codes were placed in an envelope to blind the researchers and evaluators who applied the follow-up interviews, and no evaluator interviewed the same dyad more than once.

In this randomized triple-blind clinical trial, the researcher, patient, caregiver, and interviewer did not know the assignment throughout the treatment.

A sample size was estimated for each group of 30 individuals to reach a power of 80%. The minimum effect size was based on the variation in the mean scores for MMSE and ADAS-Cog.

The intervention was performed over 12 months (two 90-min weekly sessions) and a year of monthly follow-up. Three measurements were made: before the study, after the intervention (12 months), and after the follow-up (24 months). A procedure guide was designed for all the steps to be followed across the intervention.

The research protocol was approved by the National Commission of Scientific Research and the IMSS Ethics Committee (registration number 2008-785-019).

Intervention

This is the first intervention designed for the Mexican population considering the level of recommendation (degree A). This is in accordance with the criteria of the medical center based on evidence and the differences reported on this multicomponent (patient-caregiver) intervention in other populations. The study design covers the stimulation of various cognitive functions as well as behavioral and neuropsychological activities to slow the progression of cognitive impairment. In addition, it establishes the functional state and reduces the appearance of behavioral symptoms in the participants. On the other hand, this study was longer than others, covering 48 weeks with two weekly 90-min sessions. The post-follow-up phase lasted 12 months and included monthly supervision. Furthermore, the results were evaluated by specific quantitative scales that not only focus on global cognitive function but also evaluate daily life activities, affective-behavioral alterations, mood and behavior alterations, and associated vascular risk factors.

The manual of the SADEM deals with a series of practice proposals, neuropsychological exercises, and specific material especially designed for people with cognitive disorders. It includes tasks for different cognitive domains, and the activities are scored according to the level of impairment, based on the global deterioration scale [33].

Each exercise is organized and structured into tasks according to the different components of cognitive function considered. The latter include Language, Orientation, Sensory activities, Attention and concentration, Body scheme, Memory, Gestures (praxis), and Reading and Writing.

Task description

The main objective of the activity to be performed covers three aspects: cognitive (i.e., working lexicon, paying attention, and maintaining orientation, among others), behavioral (i.e., promoting personal interaction), and psychological (i.e., increasing self-esteem and personal security).

The basic structure of the task includes a careful explanation of the components of the planned activity, mainly verbal expression, stimulus and response, conversation, and supervised execution, among others.

The general materials used in the task (objects of daily life, slides or specific images, paper and pencil, and paint, among others) are described.

The functional architecture describes the neuropsychological components of each area or task. Among the components are the afferences or type of stimulus (visual, auditory, verbal, tactile) and the means and components for processing in semantic levels. There are also the afferences requested (verbal, gesture), their components, and levels of processing.

The state of deterioration (GDS) is the phase in which the exercise can be applied (GDS 3 or 4), considering the abilities maintained and/or altered, according to clinical manifestations.

The daily life tasks describe the relationship between cognitive tasks and daily life activities that can be carried out naturally. This includes the stimulation the olfactory senso-perception (smelling bath soaps, perfumes, or lotions used daily).

The individual or group activity suggests how to perform the exercise; group tasks or exercises stimulate the social dimension and more if performed as games.

Intervention development

The intervention was developed in two stages, with the aim to facilitate the conserved residual cognitive execution. Techniques were used, such as: spatial memory, fading clues and error anticipation-avoidance. Environment was structured to offer external cognitive support that facilitates the information required (for example, visible calendars and clocks for time orientation).

a) Intensive phase

The first stage of the intervention lasted 48 weeks. The dyads in the three groups attended 90-min sessions, twice a week, at Centro Medico Nacional Siglo XXI, IMSS. They were given appointments at different times on the days scheduled for the intervention. Each group was managed by the same neuropsychologist and two assistant psychologists previously trained for such tasks.

Each session covered activities that included questions to locate time (date: day, month, year), attention exercises, memory and language, and directed daily life activities. The patients were urged to share experiences or personal memories.

The selection of activities for each 90-min session was distributed as follows:

Orientation to reality: (20 min)

Cognitive stimulation: attention, memory, and language exercises (30 min)

Memory techniques: sharing personal experiences (30 min)

Daily activities carried out at home (10 min of explanation)

During each session of this stage, the caregivers were trained so that they could carry out these tasks with the patient at home during the follow-up period.

In addition, caregiver support was provided during the follow-up once a month throughout the 12 months that the patients attended the cognitive stimulation program. In these sessions, a neuropsychologist listened to and oriented caregivers on their frustrations and uncertainties associated to the diagnosis and patient handling. Caregivers were offered information and general orientation, and they were provided contact with existing support programs.

In this phase, the participants in the control group and their caregivers followed the conventional treatment offered by IMSS to treat dementia (drug treatment). They were given appointments, just as their counterparts, at Centro Médico Nacional Siglo XXI, IMSS, to perform the corresponding evaluations.

b) Follow-up phase

The follow-up phase started after the 48 weeks of intervention. Patients and caregivers attended sessions once a month where they were given cognitive tasks to carry out at home; the aim was to provide continuity to the intervention. They only attended supervision and assignment sessions for the twelve months of this phase.

The participants in the control group continued with the treatment offered by IMSS during the 12 months of follow-up. As the participants in the intervention group, they were given appointments at the Centro Médico Nacional Siglo XXI, IMSS, at the end of the phase for the corresponding evaluations.

Outcome assessment

The cognitive function was evaluated using the MMSE [34]. While a score between 24 and 30 showed a cognitive function within the normal limits, a score of 18–23 represented mild to mild-moderate cognitive impairment, and one between 0 and 17 was interpreted as moderate-severe to severe cognitive decline [35, 36].

Verbal memory, language (spontaneous, denomination, and comprehension), and time and space orientation were measured using ADAS-Cog, including a battery of 11 tests [37]. The tests can be applied in a relatively short period of time. The range of the total score varies from 0 to 70, where a higher score indicates a greater cognitive deterioration [36].

The Syndrom-Kurztest (SKT) developed in 1989 documents the course of dementia and evaluates therapeutic aspects.

The pro-positive tests of verbal fluency evaluated the ability to evoke words in a specific period of time (1 min). The combination of tests evaluating semantic and phonological verbal fluency allows for a clear differentiation between cortical and subcortical dementias [38].

The Blessed Dementia Rating Scale (BDRS), evaluating difficulties in basic activities and those key to daily life, as well as emotional and behavioral disorders, was used to assess functionality in daily life activities. The total score, adjusted for age, ranges between 0 and 27 points, a higher score indicating greater cognitive impairment [22, 39].

To evaluate behavioral and affective symptoms, we used the Neuropsychiatric Inventory [40]. The questionnaire addresses the main caregiver’s neuropsychiatric symptoms in the previous month. Scores are obtained for 12 symptoms (delirium ideas, hallucinations, agitation/aggression, depression/dysphoria, anxiety, joy/euphoria, apathy/indifference, inhibition, irritability/lability, aberrant motor behavior, sleep, appetite/eating disorders) with scores on frequency according to acuteness and the caregiver’s stress [41].

In addition, we evaluated some vascular risk factors (diabetes, hypertension, dyslipidemia, cardio-ischemia, obesity, smoking, and alcoholism) associated with cognitive impairment and likely to influence the results.

The Beck Depression Inventory (BDI) was used to assess the effect of the intervention on the caregivers. It considers depression, anxiety, and caregiver burden during the period of the study in 21 questions, where 5–9 is considered normal, 10–18 represents mild to moderate depression, 19–29 describes moderate depression, and >30 indicates severe depression [42]. The Beck Anxiety Inventory (BAI) [43], which consists of 21 questions, was also used in the assessment. A score <21 represents low anxiety, 22–35 is moderate anxiety, and >36, severe anxiety. Finally, the Zarit Burden Interview (ZBI) [44], was also applied to the caregivers. It contains 22 items with scaled results (1–5), where <46 shows no overload, 47–55 indicates mild overload, and >55 suggests an intense overload.

Statistical analysis

The continuous variables were analyzed using either a t-test or a Mann-Whitney U test while the categoric variables were assessed with Fisher’s exact test. Changes in the line at 12 and 24 months were evaluated using the Mann-Whitney U test, calculating Cohen’s d (small: 0.2 to <0.50, medium: 0.50 to <0.80, and large 0.80). Linear mixed-effects models (LMMs) were developed using all the available data to evaluate the effect of the intervention at each point of the study (baseline, 12 months, and 24 months), adjusted by sex. The data that were not statistically significant were eliminated from the final model.

All the analyses were performed with intention-to-treat (ITT) analysis while multiple imputation was used for missing data at the two points of the study (12 and 24 months). The imputations were adjusted by sex, age, and education at each evaluation moment, and p < 0.05 was considered significant. A minimal clinically important improvement was defined as an improvement of 2 points in the general score on MMSE and ADAS-Cog. The analysis was performed using STATA version 15.

RESULTS

Subject characteristics

Out of the 256 eligible community-dwelling patients diagnosed with dementia (Fig. 1), only 67 were diagnosed with mild dementia, and they were randomized into 39 for the intervention arm and 28 for control. The caregivers mean age was 60.2 in the intervention group and 56.5 in controls.

The socio-demographical and clinical characteristics of the study groups are shown in Table 1. A statistically significant difference was only observed in gender (p = 0.04) due to the different proportion of men in the groups (5 in the control group and 16 in the intervention group). There were no statistically significant differences in the other factors studied (age, academic level, diabetes, hypertension, dyslipidemia, cardio-ischemia, obesity, smoking, and alcoholism). These results were the same after adjusting for gender.

Table 1

Demographic characteristics and vascular risk factors of participants at baseline evaluation

Characteristics	Intervention Group	Control Group	p ^**
	n = 39	n = 28
Age, y (mean, SD)	77.7 (7)	77.7 (9.3)	0.995^a
Gender:
Male (n %)	16 (41)	5 (18)	0.044^b
Female (n %)	23 (59)	23 (82)
Life status: live alone (n %)	13 (33)	7 (25)	0.242^b
Years of Academic Education (mean, SD)	6.5 (5)	5.4 (3.9)	0.33^a
None (n %)	6 (15)	4 (14)	0.982^b
<3 y (n %)	9 (23)	7 (25)
>3 y (n %)	24 (62)	17 (61)
Vascular risk	(n, %)	(n, %)	p ^*
Hypertension	26 (67)	22 (81)	0.263^b
Diabetes	18 (46)	8 (30)	0.208^b
Dyslipidemia	10 (26)	9 (33)	0.588^b
Cardio-ischemia	3 (7.8)	3 (11)	0.682^b
Obesity	4 (10)	2 (7)	1.00^b
Smoking	15 (38)	15 (55)	0.213^b
Alcoholism	18 (46)	15 (55)	0.617^b
Tests	Mean±SD	Mean±SD	p ^*
Global cognition (MMSE)	22.4 (0.8)	22.9 (1)	0.693
Global cognition (ADAS-Cog)	17.7 (1.8)	19.8 (2)	0.438
Global cognition (SKT)	10.4 (1.1)	9.1 (1.4)	0.509
Semantic verbal fluency	11.1 (0.9)	11.5 (1.1)	0.790
Phonological verbal fluency	6.4 (0.7)	6.4 (0.8)	0.985
Dementia index (BDRS)	5.9 (0.7)	5.7 (0.9)	0.864
Functional disability (RDRS)	26.2 (1.2)	26.7(1.4)	0.783
Depression (CESD-R)	36.7 (2.6)	36.9 (3.2)	0.856
Neuropsy symptom Frc (NPI)	2.7 (0.5)	2.7 (0.6)	0.911
Neuropsy symptom Grav (NPI)	12.6 (3.5)	10.8 (4.3)	0.746

MMSE, Mini-Mental State Exam; ADAS-Cog, Alzheimer’s Disease Assessment Scale-Cognitive Subscale; SKT, Syndrom-Kurztest; Frc, frequency; Grav, gravity; BDRS, Blessed Dementia Rating Scale; NPI, Neuropsychiatric Inventory; CESD-R, Center for Epidemiologic Studies Depression Scale-Revised; RDRS, Rapid Disability Rating Scale; SD, standard deviation. ^*Value of p calculated from coefficient of lineal regression model. ^**Significant difference with p < 0.05.

The caregivers’ mean age in the intervention group was higher (60.2±13.1) when compared against that of the caregivers in the control group (56.5±6.1). Most of the subjects in both groups were female, reaching 20 (72%) and 19 (70%) in the intervention and control groups, respectively. Still, there was no statistically significant difference.

Drop-outs

In the first stage of the study, at 12 months of follow-up, a total of 36 (92.3%) subjects in the intervention group and 24 (85.7%) in the control group completed the follow-up evaluation. The drop-outs in the intervention group were as follows: 1 died, 1 was gravely ill, and 1 left because of caregiver responsibility. In the control group, 2 died and 2 were gravely ill, as shown in Fig. 2.

Fig. 2

Diagram of distribution of the sample at end of the study.

At 24 months of follow-up, 32 patients in the intervention group completed the second phase versus 18 in the control group. Only 1 patient from the intervention group and 2 from the control group died and did not complete the phase (Hazard ratio = 1.764; 95% CI 0.538–5.781, p = 0.349). Other subjects in the intervention group dropped out due to change of address (1), serious illness (1), disability (1), and caregiver’s lack of disposition (1). In the control group, 2 persons died, 1 changed address, and 3 were gravely ill.

Upon comparing the socio-demographic, cognitive, behavioral, and affective variables in the group of patients who were lost to the study against those in the group who completed it, no significant differences were found in the post-intervention evaluations (12 and 24 months). Losses to follow-up were found in older patients and those with a lower academic level. After analyzing the losses to post-intervention and follow-up, vascular risk factors did not influence the results (data not shown).

Effect of the intervention (SADEM)

In the post-intervention stage, after finishing the multicomponent cognitive stimulation program (12 months), the cognitive and affective-behavioral variables were compared between the intervention and control groups. Significant differences were found mainly in the cognitive variables and the dementia index: MMSE, ADAS-Cog, SKT, semantic verbal fluency, and phonological verbal fluency (p < 0.05), as shown in Table 2.

Table 2

Change in the measures cognitive and affect-behavioral between groups at 12 and 24 months

	Intervention			Control			Intervention			Control
	12 months						24 months
	(n = 36)			(n = 24)			(n = 32)			(n = 18)
	Mean±SD	p ^*	Effect Size	Mean±SD	p ^*	Effect Size	p ^**	Mean±SD	p ^*	Effect Size	Mean±SD	p ^*	Effect Size	p ^**
Global cognition (MMSE)	−2.05±4.41	0.008	0.46	3.12±4.29	0–002	0.72	0.001	1.17±3.93	0.167	0.35	3.00±3.61	0.005	0.83	0.427
Global cognition ADAS-Cog	5.30±8.94	0.001	0.59	−3.87±8.48	0.035	0.45	<0.000	−2.47±9.45	0.222	0.26	−6.68±11.0	0.028	0.60	0.003
Global cognition (SKT)	6.9±6.25	<0.001	1.0	−4.81±5–73	0.001	0–84	<0.000	−0.90±4.57	0.362	0.19	−6.68±6.08	0.001	1.0	0.003
Semantic verbal fluency	0.88±4.29	0.231	0.20	3.83±4.26	<0.001	0.89	0.008	3.95±4.50	0.000	0.87	4.14±4.14	0.001	0.91	0.714
Phonological verbal fluency	−2.03±4.57	0.019	0.45	2.31±2.91	0.001	0.79	<0.000	−0.26±4.17	0.787	0.06	1.60±3.69	0.116	0.43	0.265
Dementia index (BDRS)	−0.52±5.12	0.541	0.10	−3.77±7.84	0.027	0.34	0.036	−0.84±6.35	0.529	0.13	−4.56±5.96	0.008	0.76	0.006
Functional handicap (RDRS)	−0.50±5.31	0.576	0.18	−2.66±7.71	0.102	0.26	0.299	−2.21±7.30	0.160	0.30	−5.81±8.16	0.012	0.71	0.101
Depression CESD-R	−5.08±16.8	0.080	0.35	−1.45±17.0	0.678	0.23	0.569	12.9±20.1	0.005	0.64	6.31±14.1	0.095	0.44	0.265
Frequency of neuropsy. symptoms (NPIfrec)	−1.16±2.31	0.668	0.07	−0.62±2.69	0.278	0.22	0.948	1.17±2.44	0.310	0.48	0.56±2.12	0.307	0.26	0.051
Gravity of neuropsy. symptoms (NPIgrav)	−1.63±14.4	0.501	0.11	−4.41±13.8	0.132	0.31	0.736	2.04±10.5	0.361	0.20	−5.56±15.8	0.182	0.35	0.006

MMSE, Mini-Mental State Exam; ADAS-Cog, Alzheimer’s Disease Assessment Scale-Cognitive Subscale; SKT, Syndrom-Kurztest; BDRS, Blessed Dementia Rating Scale; NPI, Neuropsychiatric Inventory; CESD-R, Center for Epidemiologic Studies Depression Scale-Revised; RDRS, Rapid Disability Rating Scale; SD, standard deviation. p^*, Difference between baseline measurement and follow-up period with significance, p < 0.05. p^**, Difference between measurement of control and intervention groups at end of follow-up period with significance, p < 0.05. The values statistically significant are indicate in bold.

The comparison of cognitive and affective-behavioral variables in the two groups at follow-up (24 months post-intervention) are also shown in Table 2. Significant differences were observed in the cognitive and behavioral variables [dementia index (BDRS) and functional handicap (Rapid Disability Rating Scale)] of the control group.

The effect sizes of global cognition (ADAS-Cog and SKT) and phonological verbal fluency were large (Cohen’s d ≤ 0.50). In contrast, those of MMSE and phonological verbal fluency (Cohen’s d ≤0.50), semantic verbal fluency, dementia index, and functional handicap (Cohen’s d = 0.20, 10, and 0.18, respectively) were moderate.

As shown in Table 3, the ITT analysis before imputation demonstrated a significant improvement (3 points approximately) in the cognitive function (p < 0.001) of the intervention group, while the control group lost 1–2 points. In the ADAS-Cog, the intervention group showed a reduction of 3.7 points in comparison with the control group, which increased by 1.7 points. In the SKT test, a reduction of 7.0 points was also observed in the intervention group versus a loss of 2.2 points in the control group. After the semantic verbal fluency test, the intervention group showed a slight loss of 2 points, while the control group lost 0.3 points. The phonological verbal fluency test showed a gain of 4 points in the intervention group against the loss of 1.1 points in the control group.

Table 3

Intention-to-Treat Analysis with and without Imputation^‡

	Change in the Baseline Score
	12 months				24 months
	Without Imputation		With Imputation		Without Imputation		With Imputation
Outcome	Mean±SE Points	p	Mean±SE Points	p	Mean±SE Points	p	Mean±SE Points	p
Global cognition (MMSE)	3.6±1.36	0.001	4.6±1.28	<0.000	0.80±1.63	0.427	1.65±5.29	0.103
Global cognition ADAS-Cog	−3.7±3.16	<0.000	−4.21±2.87	<0.000	−1.72±3.96	0.093	−2.24±12.11	0.028
Global cognition (SKT)	−7.04±1.54	<0.000	7.14±1.47	<0.000	−2.104±2.28	0.043	−0.45±6.68	0.652
Semantic verbal fluency	2.73±1.06	0.008	3.24±1.09	0.002	−0.37±1.28	0.714	1.43±3.65	0.155
Phonological verbal fluency	4.13±1.01	<0.000	5.30±1.02	<0.000	1.17±1.42	0.250	3.15±2.25	0.002
Dementia index (BDRS)	−2.14±1.57	0.036	−2.16±1.50	0.034	−2.36±1.84	0.024	−1.79±3.15	0.077
Functional handicap (RDRS)	−1.04±2.34	0.299	−1.80±2.39	0.076	−1.68±3.09	0.101	−1.49±8.28	0.140
Depression CESD-R	0.57±5.08	0.573	0.64±4.77	0.521	0.56±5.53	0.575	−1.35±18.50	0.181
Frequency of neuropsy. symptoms (NPIfrec)	−0.66±0.84	0.948	−0.54±0.84	0.589	−1.56±0.56	0.126	1.52±1.82	0.132
Gravity of neuropsy. symptoms (NPIgrav)	0.32±5.97	0.748	−0–17±5.81	0.865	−190±4.72	0.064	−0–173±9.70	0.863

SE, standard error; MMSE, Mini-Mental State Exam; ADAS-Cog, Alzheimer’s Disease Assessment Scale-Cognitive Subscale; SKT, Syndrom-Kurztest; BDRS, Blessed Dementia Rating Scale; NPI, Neuropsychiatric Inventory; CESD-R, Center for Epidemiologic Studies Depression Scale-Revised; RDRS, Rapid Disability Rating Scale. ^‡Linear Mixed-Effects Models adjusted for time, group, sex, baseline age, education. The values statistically significant are indicate in bold.

Once the affective-behavioral variables were compared, there were differences only in the BDRS test (dementia index), which showed a gain of 2.1 points in the intervention group against a loss of 2.3 points in the control group (p = 0.001).

The analysis of imputations showed a slightly greater improvement of the scores in MMSE, ADAS-Cog, SKT, semantic verbal fluency, and phonological verbal fluency.

On the other hand, as seen in Fig. 3, after the in-crease in post-intervention scores, the intervention group tended to return to baseline levels in all the clinical variables (cognitive and affective-behavioral). However, the control group showed a slight tendency toward the progression of cognitive impairment in both cognitive and affective-behavioral variables.

Fig. 3

Differences between groups from baseline through follow-up

Gender was the only variable not to show homo-geneity between groups from baseline. Then, differences between the three main measurements of global cognitive evaluation (MMSE, ADAS-Cog, and SKT) can be observed, once adjusted for the gender variable, across the three evaluation stages in intervention and control groups.

DISCUSSION

The scientific evidence indicates that the intervention with cognitive stimulation improves cognitive function, adaptive behavior, and the general wellbeing of patients with dementia [25, 42]. One of the main objectives of this study was to evaluate the effectiveness of a multicomponent program of cognitive stimulation, SADEM, in slowing the progress of cognitive impairment. The program seeks to stabilize the functional state of patients and reduce the appearance of behavioral symptoms in patients with dementia to offer this treatment as an alternative for the Mexican population.

We found favorable changes, indicating the im-provement in the cognitive function in the patients that participated in the program. Other studies [39] found no favorable changes, probably due to the high baseline scores in MMSE and ADAS-Cog. In our study, the baseline scores were low and increased significantly at the end of the intervention. Both MMSE and ADAS-Cog have shown sensitivity in detecting favorable effects of cognitive intervention in patients with dementia [24 , 45–47]. Spector et al. [28], Olanzarán et al. [42, 48], and Graff et al. [45] reported increases in MMSE scores (1 point) and reductions in ADAS-Cog (−1.5 to −1.7) to demonstrate the positive effect of the intervention in patients with dementia. As reported in those studies, we found greater differences pre- and post-intervention in both instruments. This increase was confirmed with the additional evaluation using other neuropsychological tests, particularly those of attention and memory (SKT) and pro-positive semantic and phonological verbal fluency, all standardized and validated in the Mexican population.

It has been reported that the MMSE and ADAS-Cog are the most frequently used tests to follow the progress of cognitive impairment. According to estimations, MMSE reports a loss of 1.8–4.2 points per year and ADAS-Cog, one of 8.3–9.3 in the same period [5]. In our study, no loss was observed in either instrument. Although MMSE increased by 2 points once the intervention was completed, the intervention group had returned to the original score after the completion of the follow-up. The same occurred with ADA-Cog, which was increased by 5.3 points. One year after the intervention, the experimental group showed scores not lower than baseline even though it did not maintain the level reached at the end of the program. This demonstrates that our multicomponent cognitive intervention was able to delay cognitive impairment for at least two years.

Most of the studies report brief cognitive intervention sessions (30–40 min) held weekly over 3 months [20, 25]. Nevertheless, and unlike Cove et al. [49], who used a brief cognitive stimulation based on evidence, our study proposed a longer intervention of weekly 90-min sessions throughout a year. In previous studies [25, 43], the benefit of the intervention was documented with a follow-up of only 1–3 months. In contrast, our study showed the efficacy of the intervention at one year and a stabilized decline two years after the follow-up.

Long-term therapies have been proven to have more lasting effects. They seem to favor learning consolidation and the stabilization of stimulated cognitive abilities.

In agreement with previous research, our study demonstrates that patients in the intervention group maintained cognitive and social stimulation post-intervention and in follow-up. Although they continued to show improved execution in cognitive evaluations, the patients had a relapse in cognitive levels, evidenced by the lack of continuity.

All of this suggests that cognitive stimulation should be permanent and continuous in order to maintain brain activation.

These results appear to suggest that a continued intervention for over a year may be more effective and have stabilized long-term effects. It has been documented that non-pharmacological cognitive interventions performed in groups, and not individually, also favorably influence the mood and behavior of patients with dementia [20, 28]. In our study, we found no evidence of these effects, which is likely due to the lack of sensitivity in the instruments used [48].

Limitations

This work only presents the global results from instruments used to measure alterations. It is important to determine the cognitive areas that showed a greater change after the intervention. This would allow for studies to improve, focusing on the functions that should be preserved in patients with dementia, namely a better quality of life and a functional state for a longer period of time. This would reduce the patient’s dependence as well as the social and institutional cost of mild stage dementia.

It is necessary to carefully examine the effect of a combined cognitive intervention on specific cognitive domains, such as memory, language, thought, and executive function. Cognitive functions must also be analyzed to establish the level of cognition where this intervention is the most effective. Given that this is a long-term intervention and the adherence to treatment was not measured, it is impossible to specify whether the same effect could be obtained in a shorter period. Furthermore, the logistics of participation were very demanding for the intervention group. Attending all the sessions may have been difficult for some patients, especially those whose caregivers were busy or who lived far from IMSS facilities or suffered from functional decline.

Conclusions

The results of our study show that the non-phar-macological intervention with a multicomponent program of cognitive stimulation improves cognitive function and delays the progression of impairment in people diagnosed with mild dementia by at least two years. In addition, this intervention is a good alternative for the care of the geriatric population in public health services. The multicomponent intervention of cognitive stimulation, called SADEM, is an original study and there are no similar works reported in Mexico. Given that the participants were selected from a population study, the results should be representative of patients with dementia.

The results and conclusions drawn from this research could be the basis of future cognitive stimulation therapies in hospitals and community care facilities, and the implementation of these treatments will be affordable for the population.

Footnotes

ACKNOWLEDGMENTS

This project was supported by grants from SSA/IMSS/ISSSTE-CONACYT (México) Salud-2007-01-69842 and the Fund for the Promotion of Health Research, Mexican Institute of Social Security, FIS/IMSS/PROT/G09/772.

Authors’ disclosures available online ().

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