Table 1.
Randomized controlled trial of non-pharmacological interventions for apathy and depression.
| Authors | n | Recruitment | Participants | Dementia severity | Measures | Depression score at baseline Mean (SD) |
Apathy score at baseline Mean (SD) |
Interventions | Primary outcome | Main results | Evaluation |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Alves et al. (2014) | IG: n = 10 CG: n = 7 |
Day care and long-term older adult center | Patients with MCI and mild-to-moderate dementia | MCI and mild to moderate | Cognitive function: MMSE Depression: GDS (version unclear) Apathy: Not measured |
IG: 11.3 (5.33) CG: 9 (4.87) |
IG: Standard intervention group of CST (CA, SA) CG: Waiting list (No intervention except for the usual care) |
Cognitive function, IADL, and therapy experience | Changed score of pre-post intervention was not significant between both groups (p = 0.84). | Ineffective | |
| Bergamaschi et al. (2013) | IG: n = 16 CG: n = 16 |
Hospital | Patients with AD who have taken donepezil. | Mild to moderate | Cognitive function: MMSE Depression: CSDD Apathy: Not measured |
IG: 29.37 (4.47) CG: 27.19 (8.28) |
IG: Cognitive training (CA) CG: Multiple sessions of non-specific cognitive activities (SA) |
Not clearly described | CSDD score was not significant between both groups at pre-post evaluation (p = 0.84). | Ineffective | |
| Brooker et al. (2011) | IG: n = 144 CG: n = 149 |
Extra care housing | Residents with dementia | Moderate | Cognitive function: MMSE Depression: GDS-15 Apathy: Not measured |
IG: 6.3 (SE = 0.5) CG: 5.3 (SE = 0.4) |
IG: Enriched opportunities program (OA) CG: Project support worker coach (OA) |
Not clearly described | IG group showed significant improvement of GDS score at 6 (p < 0.001), 12 (p < 0.001), and 18 months (p < 0.001). | Effective | |
| Fernández-Calvo et al. (2015) | IG: n = 25 CG: n = 30 |
The Alzheimer’s Association of Salamanca | Patients with AD | Mild | Cognitive function: MMSE Depression: CSDD Apathy: Not measured |
IG: 8.32 (2.14) CG: 7.83 (1.98) |
IG: Multi-intervention Program (CA, SA) CG: Waiting list |
Unawareness | CSDD in IG group scored lower than CG at post-treatment assessment (p < 0.05), d = 0.23, CI (−0.30, 0.76). | Effective | |
| Gomez-Soria et al. (2020) | IG: n = 54 CG: n = 68 |
Hospital | People with MCI | MCI | Cognitive function: MMSE Depression: GDS-15 Apathy: Not measured |
IG: 2.93 (2.60) CG: 3.14 (2.89) |
IG: Cognitive stimulation (CA) CG: No intervention |
Cognitive function | GDS score did not show a significant difference between both groups at post-test (p = 0.600) and 6 months post-test (p = 0.600). | Ineffective | |
| Hattori et al. (2011) | IG: n = 20 CG: n = 19 |
Outpatient clinic at hospital | Patients with AD | Mild | Cognitive function: MMSE Depression: GDS-30 Apathy: SAS |
IG: 4.3 (2.8) CG: 2.3 (1.8) |
IG: 15.9 (7.1) CG: 13.0 (4.7) |
IG: Art therapy (SA) CG: Calculation drill (CA) |
Not clearly described | GDS score was not improved in both groups (IG, p = 0.294; CG, p = 0.466) at post-test. SAS score was improved only in IG (p = 0.014) at post-test (CG, p = 0.090). | Effective (Apathy) Ineffective (Depression) |
| Hsieh et al. (2010) | IG: n = 29 CG: n = 32 |
Nursing home | Residents with dementia | Mild | Cognitive function: CDR Depression: GDS-15, NPI Apathy: AES, NPI |
GDS IG: 7.79 (1.83) CG: 7.41 (1.76) NPI IG: 2.83 (4.06) CG: 1.97 (3.83) |
AES-C (Behavior, Emotion, Cognition) IG: 9.55 (1.57), 4.59 (1.05), 17.79 (2.38) CG: 8.94 (2.50), 4.00 (0.88), 16.19 (3.40) NPI IG: 3.28 (3.89) CG: 2.25 (3.07) |
IG: Reminiscence Group Therapy (EA) CG: not described |
Depressive symptoms and apathy | GDS and NPI depression subscale scores were significantly improved in IG (GDS, p = 0.003; NPI, p = 0.028). AES behavior subscale score was improved in IG (p = 0.002), but other subscale scores of AES and NPI apathy subscale score were not improved. | Effective (Apathy) Effective (Depression) |
| Huang et al. (2019). | IG: n = 36 CG: n = 38 |
Hospital and long-term care facilities | People with dementia | Mild | Cognitive function: MMSE Depression: GDS (version unclear) Apathy: Not measured |
IG: 4.83 (2.57) CG: 4.95 (1.93) |
IG: Tai Chi exercise (SA) CG: Only routine treatments and personalized daily care (OA) |
Not clearly described | GDS score in IG was significantly improved between baseline and 10 months (p < 0.05, d = 0.35), and GDS score in IG was lower than that in CG at 10 months (p < 0.05, d = 0.87) | Effective | |
| Lai et al. (2020) | IG: n = 50 CG: n = 50 |
Community | Older adults with dementia and caregivers | Mild to moderate | Cognitive function: MoCA Depression: RMBPC Apathy: Not measured |
IG: 20.877 (5.56) CG: 21.07 (5.64) |
IG: Dementia care education activity scheduling (OA) CG: Usual dementia care education (OA) |
Caring role | The between and within-group differences were significant between both groups (between, p < 0.05, d = 0.47; within, p < 0.05, d = 0.50). RMBPC score in IG was significantly improved. | Effective | |
| Larouche et al. (2019) | IG: n = 23 CG: n = 22 |
Community | Older adults with amnestic MCI | MCI | Cognitive function: MoCA Depression: GDS-30 Apathy: Not measured |
IG:8.2 (SE 1.2) CG: 7.7 (SE 1.2) |
IG: Mindfulness-based intervention (OA) CG: Psychoeducation-based intervention (OA) |
Depression | GDS score of both interventions was significantly improved (time effect, p = 0.033; condition effect, p = 0.652; interaction between time and condition, p = 0.864). | Effective | |
| Lin et al. (2019). | IG: n = 43 CG: n = 48 |
Long-term care facilities | Residents with dementia | Moderate | Cognitive function: MMSE Depression: CSDD Apathy: Not measured |
IG: 3.79 (2.57) CG: 5.04 (4.03) |
IG: Creative expression therapy (SA) CG: Standard cognitive training (CA) |
Not clearly described | CSDD score of IG was significantly improved at post-test (p = 0.001, d = 1.54), which was maintained at follow-up (p = 0.012, d = 0.93). | Effective | |
| Olsen et al. (2016) | IG: n = 23 CG: n = 25 |
Nursing home | Residents with dementia or cognitive deficit | Moderate to severe | Cognitive function: MMSE Depression: CSDD Apathy: Not measured |
IG: 8.35 (4.65) CG: 6.88 (4.70) |
IG: Animal-assisted activities (SA) CG: Usual care |
Depression, agitation, and QOL | CSDD score of IG was not significantly different at pre-post (T1-T0) assessment (p = 0.171), but significantly improved between baseline and follow-up (T2-T0, p = 0.037). | Effective | |
| Pérez-Ros et al. (2019) | IG: n = 47 CG: n = 72 |
Nursing home | Residents with dementia | Moderate | Cognitive function: MMSE Depression: GDS-15, CSDD Apathy: Not measured |
GDS IG: 8.31 (5.78) CG: 9.77 (6.98) CSDD IG: 5.00 (4.53) CG: 8.03 (5.89) |
IG: Preference for listening to music (SA) CG: Occupational therapy programs with no music-based intervention (SA) |
Functional, cognitive, and emotional dimensions | GDS score in IG was maintained, but, in CG, it was worsened at post-test (p < 0.01). CSDD score was not different in both groups at post-test. | Effective | |
| Pongan et al. (2017). | IG: n = 31 CG: n = 28 |
Memory clinic | Patients with AD | Mild | Cognitive function: MMSE Depression: GDS Apathy: Not measured |
IG: 8.81 (SE 5.99) CG: 8.79 (SE 6.23) |
IG: Singing intervention (SA) CG: Painting intervention (SA) |
Pain | GDS score of CG (painting intervention) was significantly improved (interaction time*group: p = 0.01). | Effective | |
| Reverté-Villarroya et al. (2020) | IG: n = 13 CG: n = 15 |
Hospital | Patients with dementia and their caregivers | Moderate | Cognitive function: MMSE Depression: GDS-30, NPI Apathy: NPI |
IG: 4.85 (0.68) CG: 5.07 (0.88) |
Not described | IG: Routine clinical practice and educational nursing education for the family caregivers (OA) CG: Routine clinical practice |
BPSD | GDS score of IG was worsened at post-test (p < 0.001). Although NPI was used to assess apathy, quantitative assessment was not conducted. | Ineffective |
| Schmitter-Edgecombe and Dyck (2014) | IG: n = 23 CG: n = 23 |
Community | Care-dyads | MCI and mild dementia | Cognitive function: TICS and CDR Depression: GDS-15 Apathy: Not measured |
IG: 3.27 (2.84) CG: 3.17 (2.72) |
IG: Cognitive rehabilitation techniques with multi-family group (CA) CG: Standard care |
Medication management ability assessment, bill paying subtest from the executive function performance, activities of daily living-prevention instrument, coping self-efficacy scale | GDS score of both groups of participants with MCI did not show a significant difference (p = 0.07). | Ineffective | |
| Treusch et al. (2015) | IG: n = 67 CG: n = 50 |
Nursing home | Dementia patients with apathy | Severe | Cognitive function: MMSE Depression: DMAS Apathy: AES, NPI |
IG: 17.41 (14.19) CG: 15.48 (12.10) |
AES IG: 50.01 (11.17) CG: 47.38 (8.87) |
IG: Occupational therapy in the form of a “biographically orientated mobilization” (SA) CG: No special intervention |
Apathy | AES score of IG was maintained at pre-post intervention, but CG was worsened (p = 0.01). DMAS and NPI were not used as the outcome of the intervention. | Effective |
| Valentí Soler et al. (2015) | Phase 1 Nursing home IG1: n = 30 IG2: n = 33 CG: n = 38 Day care center IG: n = 20 Phase 2 Nursing home: IG 1: n = 36 IG2: n = 42 CG: n = 32 Day care center: IG2: n = 17 | Nursing home and day care center | People with dementia | Mild to severe | Cognitive function: MMSE Depression: Not measured Apathy: NPI, APADEM-NH, AI |
Phase 1 Nursing home APADEM-NH IG1: 45.06 (20.69) IG2: 48.40 (19.12) CG: 43.21 (21.80) NPI IG1: 8.85 (2.55) IG2: 9.26 (2.28) CG: 8.73 (2.54) |
Phase 1 Nursing home IG1: NAO (Humanoid) (SA) IG2: PARO (Animal) (SA) CG: Conventional therapy Day care center IG: NAO (SA) Phase 2 Nursing home IG1: Dog (real animal) (SA) IG2: PARO (SA) CG: Conventional therapy Day care center IG2: PARO (SA) |
Apathy | APADEM-NH total scores in IG1 (p = 0.030) and IG2 (p = 0.049) and NPI apathy subscale score in IG1 (p = 0.047) showed a significant decrease at Phase 1 in nursing home. | Effective | |
| Van Bogaert et al. (2016) | IG: n = 29 CG: n = 31 |
Nursing home | Residents with dementia | Mild to moderate | Cognitive function: MMSE Depression: CSDD Apathy: Not measured |
IG: 5 (2 – 8) CG: 3 (1 – 5) Note. Median (Inter-Quartile Range) |
IG: Standardized individual reminiscence intervention based on SolCos model (EA) CG: usual care |
Depressive symptoms | Delta score of CSDD showed a significant difference between IG and CG (Δ = −4, p < 0.05), but linear regression analysis did not show the effect of the intervention (b = −2.37, 95% CI [−4.81, 0.06], p = 0.056). | Ineffective | |
| Wang et al. (2010) | IG: n = 16 CG: n = 13 |
Outpatient clinic at hospital | Patients with CVD | Mild | Cognitive function: MMSE Depression: GHQ Apathy: Not measured |
IG: 2.13 (2.17) CG 1.33 (1.72) |
IG: Tai Chi exercise (SA) CG: Rehabilitation (SA) |
P300, GHQ, sleep quality | GHQ severe depression subscale score was significantly improved in the IG (time*group interaction, F = 6.143, p = 0.02). | Effective |
AD, Alzheimer’s Disease; AES, Apathy Evaluation Scale; AI, Apathy Inventory; APADEM-NH, the Apathy Scale for Institutionalized Patients with Dementia-Nursing Home version; CDR, Clinical Dementia Rating; CA, Cognition-oriented Approaches; CG, Control Group; CSDD, Cornell Scale for Depression with Dementia; CST, Cognitive Stimulation Therapy; CVD, Cerebral Vascular Disorder; DMAS, Dementia Mood Assessment Scale; EA, Emotion-oriented Approaches; GDS, Geriatric Depression Scale; GHQ, General Health Questionnaire; IADL, Instrumental Activities of Daily Living; IG, Intervention Group; MCI, Mild Cognitive Impairment; MoCA, Montreal Cognitive Assessment; MMSE, Mini-Mental State Examination; NPI, Neuropsychiatric Inventory; OA, Other Approaches; QOL, Quality of Life; RMBPC, Revised Memory and Behavior Problem Checklist; SA, Stimulation-oriented Approaches; SD, Standard Deviation; SE, Standard error; and TICS, Telephone Interview of Cognitive Status.