Evidence
This page contains a snapshot of featured content which highlights evidence addressing key clinical questions including areas of uncertainty. Please see the main topic reference list for details of all sources underpinning this topic.
BMJ Best Practice evidence tables
Evidence tables provide easily navigated layers of evidence in the context of specific clinical questions, using GRADE and a BMJ Best Practice Effectiveness rating. Follow the links at the bottom of the table, which go to the related evidence score in the main topic text, providing additional context for the clinical question. Find out more about our evidence tables.
This table is a summary of the analysis reported in a Cochrane Clinical Answer that focuses on the above important clinical question.
Confidence in the evidence is high or moderate to high where GRADE has been performed and the intervention is more effective/beneficial than the comparison for key outcomes.
Population: Adults with moderate to severe Alzheimer disease (mean age 65-79 years of age, 60-85% female, where specified) DSM III‐R/IV or NINCDS‐ADRDA criteria
Intervention: Memantine (duration 16 weeks to 1 year) ᵃ
Comparison: Placebo
| Outcome | Effectiveness (BMJ rating)? | Confidence in evidence (GRADE)? |
|---|---|---|
Clinical global rating (follow‐up: 6‐7 months) | Favors intervention | High |
Cognitive function (follow‐up: 6‐7 months) | Favors intervention | High |
Decline in Activities of Daily Living (ADL) (follow‐up: 6‐7 months) | Favors intervention | High |
Behavior and mood (follow‐up: 6‐7 months) | Favors intervention | High |
All-cause discontinuation (follow‐up: 6‐7 months) | No statistically significant difference | GRADE assessment not performed for this outcome |
Discontinuations due to adverse events (follow‐up: 6‐7 months) | No statistically significant difference | High |
Serious adverse events (follow‐up: 6‐7 months) | No statistically significant difference | GRADE assessment not performed for this outcome |
Quality of life | - | None of the studies identified by the review assessed this outcome |
Note ᵃ Three RCTs administered memantine alongside donepezil. The Cochrane review which underpins this Cochrane Clinical Answer (CCA) notes that the beneficial effect of memantine at 6 months is also evident in those taking cholinesterase inhibitors.
This evidence table is related to the following section/s:
This table is a summary of the analysis reported in a guideline (underpinned by a systematic review) that focuses on the above important clinical question.
Confidence in the evidence is very low or low where GRADE has been performed and the intervention may be more effective/beneficial than the comparison for key outcomes. However, this is uncertain and new evidence could change this in the future
Population: Older adults with mild cognitive impairment
Intervention: Cognitive training ᵃ
Comparison: Usual care or no intervention
| Outcome | Effectiveness (BMJ rating)? | Confidence in evidence (GRADE)? |
|---|---|---|
Cognitive function (assessed with MMSE, RBANS, ADAS-Cog, DRS-2, RBMT, RBMT–II CMMSE, MOCA, Cattell CFT, CAMCOG-R) | Favors intervention | Low |
Incidence of mild cognitive impairment | - | No data available for this outcome |
Incidence of dementia | See note ᵇ | Very Low |
Quality of life (QOL) (follow-up range: 2 weeks to 28 months; assessed with: WBS, QOL FACE scale, QOLQ, QOL-AD, KQOL-AD, RAND, ICQ) | No statistically significant difference | Low |
Functional level (activities of daily living) (follow-up range: 2 weeks to 2 years; assessed with: BADL, IADL, DAFS-R, E-Cog, RBMT, MMQ, CDAD, CDR, MFQ, CDR, ADLS, SAILS, LIADL, ADL-PI, MMA, FRSSD, EFPT) | Favors intervention | Low |
Adverse events | - | No data available for this outcome |
Drop-out rates | - | No data available for this outcome |
Recommendations as stated in the source guideline Cognitive training may be offered to older adults with normal cognition and with mild cognitive impairment to reduce the risk of cognitive decline and/or dementia. Strength of the recommendation: conditional.
Note ᵃ The guideline also evaluated cognitive stimulation versus usual care or no intervention. However, they did not identify any evidence for this intervention. ᵇ Results reported narratively. Two RCTs reported this outcome. One found that at 8 months, dementia developed in half of the control group compared with none of the intervention group. The other RCT reported no significant difference between groups at 2 years.
This evidence table is related to the following section/s:
This table is a summary of the analysis reported in a Cochrane Clinical Answer that focuses on the above important clinical question.
Confidence in the evidence is moderate or low to moderate where GRADE has been performed and the intervention may be more effective/beneficial than the comparison for key outcomes.
Population: People (where reported, age range 56‐103 years) with dementia and resident in nursing homes, residential homes, and hospital floor for older adults ᵃ
Intervention: Music-based therapy (duration 3-16 weeks)
Comparison: Usual care (where defined: other activities such as reading, cognitive stimulation, painting, cooking, handwork, playing shuffleboard, and puzzle games)
| Outcome | Effectiveness (BMJ rating)? | Confidence in evidence (GRADE)? |
|---|---|---|
Emotional well‐being including quality of life (end of treatment) ᵇ | Favors intervention | Low |
Depression (end of treatment) ᵇ | Favors intervention | Moderate |
Anxiety (end of treatment) ᵇ | Favors intervention | Low |
Agitation or aggression (end of treatment) ᵇ | No statistically significant difference | Moderate |
Any behavior problem (end of treatment) ᵇ | Favors intervention | Moderate |
Social behavior (end of treatment) ᵇ | Favors intervention | Very Low |
Cognition (end of treatment) ᵇ | No statistically significant difference | Low |
Note ᵃ Dementia was diagnosed, where reported, by DSM-IV, DSM-5, or ICD-10. All severities of dementia (mild to severe) as measured by the Mini Mental State Examination (MMSE) were included. However, dementia subtypes (e.g., frontotemporal dementia, Alzheimer disease, lewy body disease, etc) were not accounted for. ᵇ The CCA also reports results for 4 to 12 weeks after treatment. No statistically significant difference between treatment groups was reported for all outcomes in this table along with a low GRADE rating, apart from anxiety and social behavior which are very low. End of treatment was also reported in the Summary of Findings main comparison table of the Cochrane review underpinning this CCA.
This evidence table is related to the following section/s:
This table is a summary of the analysis reported in a Cochrane Clinical Answer that focuses on the above important clinical question.
Confidence in the evidence is moderate or low to moderate where GRADE has been performed and there may be no difference in effectiveness between the intervention and comparison for key outcomes.
Population: Adults with possible or probable Alzheimer disease or adults with mild cognitive impairment
Intervention: Vitamin E capsules (treatment for 6 months to 4 years in people with possible or probable Alzheimer disease or for 36 months in people with mild cognitive impairment) ᵃ
Comparison: Placebo
| Outcome | Effectiveness (BMJ rating)? | Confidence in evidence (GRADE)? |
|---|---|---|
Adults with possible or probable Alzheimer disease | ||
Cognitive function using the Alzheimer Disease Assessment Scale ‐ Cognitive subscale (ADAS‐Cog) (follow‐up: 6-48 months) | No statistically significant difference | Moderate |
Cognitive function using the Mini‐Mental State Examination (MMSE) (follow‐up: 6-48 months) | No statistically significant difference | Moderate |
Activities of daily living (follow‐up: 6-48 months) | Favors intervention | Moderate |
Mortality (follow‐up: 6-48 months) | No statistically significant difference | Moderate |
Number of participants reporting ≥ 1 serious adverse event at 6-48 months | No statistically significant difference | Moderate |
Number of participants reporting ≥ 1 adverse event at 6-48 months | No statistically significant difference | Moderate |
Behavioral disturbance at 6-48 months | No statistically significant difference | Moderate |
Carer burden; quality of life | - | None of the studies identified by the review assessed these outcomes |
Adults with mild cognitive impairment | ||
Number of people progressing to Alzheimer disease by 36 months | No statistically significant difference | Moderate |
Mortality over 36 months | No statistically significant difference | Moderate |
Adverse events | See note ᵇ | GRADE assessment not performed for this outcome |
Cognitive function; activities of daily living; behavioral disturbance; serious adverse events; caretaker burden; quality of life | See note ᶜ | GRADE assessment not performed for these outcomes |
Note ᵃ The Cochrane review which underpins this Cochrane Clinical Answer (CCA) notes that conclusions are based on the alpha‐tocopherol formulation of vitamin E only and no conclusions can be drawn on the effectiveness of other preparations. ᵇ Results reported narratively. One RCT (516 participants) reported that diarrhea and cataract extraction were “common” in the vitamin E group, but this was not statistically significant. Withdrawals (66/257 [26%] in vitamin E group and 72/259 [28%] in placebo group) were mostly due to withdrawal of consent or adverse events. ᶜ Results reported narratively. The CCA notes that one RCT (516 participants) reported no significant difference between treatment groups for cognitive function or activities of daily living. No studies were found that assessed the other outcomes.
This evidence table is related to the following section/s:
This table is a summary of the analysis reported in a Cochrane Clinical Answer that focuses on the above important clinical question.
Confidence in the evidence is high or moderate to high where GRADE has been performed and there is no difference in effectiveness between the intervention and comparison for key outcomes.
Population: Adults (mean age 75 years) with depression and dementia ᵃ
Intervention: Any antidepressant
Comparison: Placebo
| Outcome | Effectiveness (BMJ rating)? | Confidence in evidence (GRADE)? |
|---|---|---|
Depression endpoint mean scores at 6‐13 weeks | No statistically significant difference | High |
Number of responders at 6-12 weeks ᵃ | No statistically significant difference | Low |
Number of people with remission at 6-12 weeks ᵇ | Favors intervention | Moderate |
Cognitive function measured by Mini‐Mental State Scores (MMSE) endpoint mean scores at 6-12 weeks ᶜ | No statistically significant difference | Moderate |
Activities of daily living (ADLS), endpoint values at 6-13 weeks ᶜ | No statistically significant difference | High |
Withdrawals for any cause at 6-13 weeks ᶜ | Occurs more commonly with antidepressants compared with placebo (favors comparison) | Moderate |
Number of people experiencing at least one adverse event | Occurs more commonly with antidepressants compared with placebo (favors comparison) | Moderate |
Note The Cochrane review which underpins this Cochrane Clinical Answer (CCA) states that there was insufficient evidence to draw conclusions about individual antidepressant drugs or about subtypes of dementia or depression. ᵃ Defined as meeting NINCDS‐ADRDA criteria for probable Alzheimer disease or DSM criteria for dementia; and also DSM criteria for major or minor depression or a score of more than 8 on the Cornell Scale for Depression in Dementia and symptoms for 4 weeks or more. ᵇ No statistically significant difference between treatment groups was reported at 24 weeks but the reviewers did not perform a GRADE assessment for this time point. ᶜ No statistically significant difference between treatment groups was reported at 6 to 9 months but the reviewers did not perform a GRADE assessment for this time point.
This evidence table is related to the following section/s:
This table is a summary of the analysis reported in a systematic review that focuses on the above important clinical question.
Confidence in the evidence is high or moderate to high where GRADE has been performed and there is a trade off between benefits and harms of the intervention.
Population: People with Alzheimer dementia
Intervention: Cholinesterase inhibitors or atypical antipsychotics
Comparison: Placebo
| Outcome | Effectiveness (BMJ rating)? | Confidence in evidence (GRADE)? |
|---|---|---|
Cholinesterase inhibitors versus placebo | ||
Neuropsychiatric symptoms (NPI Scale): follow up 12-114 weeks | Favors intervention | Moderate |
Adverse events | Occurs more commonly with cholinesterase inhibitors compared with placebo (favors comparison) | GRADE assessment not performed for this outcome |
Dropouts due to adverse events | Occurs more commonly with cholinesterase inhibitors compared with placebo (favors comparison) | GRADE assessment not performed for this outcome |
Atypical antipsychotics versus placebo | ||
Neuropsychiatric symptoms (NPI Scale): follow up 6 weeks | Favors intervention | High |
Adverse events | Occurs more commonly with atypical antipsychotics compared with placebo (favors comparison) | GRADE assessment not performed for this outcome |
Dropouts due to adverse events | Occurs more commonly with atypical antipsychotics compared with placebo (favors comparison) | GRADE assessment not performed for this outcome |
Note This systematic review concludes that cholinesterase inhibitors and atypical antipsychotics significantly improved neuropsychiatric symptoms but with poor safety outcomes. Neuropsychiatric outcomes: include either Neuropsychiatric Inventory (NPI) (NPI-10 item, NPI-12 item, or NPI-NH); or the Behavioral Pathology in Alzheimer’s Disease (BEHAVE-AD) rating scale.
This evidence table is related to the following section/s:
Cochrane Clinical Answers
Cochrane Clinical Answers (CCAs) provide a readable, digestible, clinically focused entry point to rigorous research from Cochrane systematic reviews. They are designed to be actionable and to inform decision making at the point of care and have been added to relevant sections of the main Best Practice text.
- For cognitively healthy older adults, do aspirin and non‐steroidal anti‐inflammatory drugs (NSAIDs) help prevent dementia?
- What is the accuracy of Mini‐Cog for the diagnosis of dementia in secondary care settings?
- What are the benefits and harms of rivastigmine for Alzheimer's disease?
- How does memantine compare with placebo for treating adults with moderate to severe Alzheimer's disease?
- In people with dementia, does music‐based therapy improve outcomes?
- Do NSAIDs, aspirin, or corticosteroids improve outcomes in people with Alzheimer's disease?
- What are the benefits and harms of vitamin E in people with Alzheimer's dementia and in those with mild cognitive impairment?
- Can antidepressants improve outcomes for adults with dementia and comorbid depression?
- In dementia with agitation, is there randomized controlled trial evidence to support the use of haloperidol?
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