Katarzyna Jabbour, PharmD, BCPS

Evidence summary

Mixed results on exercise’s effect on neuropsychiatric symptoms

A 2020 systematic review and meta-analysis of 18 RCTs investigated the effect of home-based physical activity on several markers of behavioral and psychological symptoms of dementia (BPSD). These symptoms were measured using the caregiver-completed neuropsychiatric inventory (NPI), which in­cludes agitation. There was substantial heterogeneity between trials; however, 4 RCTs (472 patients) were included in a meta-­analysis of the NPI. These RCTs were nonblinded, given the nature of the intervention.¹

Interventions to enhance physical activity ranged from 12 weeks to 2 years in duration, with 2 to 8 contacts from the study team per week. The type of physical activity varied and included cardiorespiratory endurance, balance training, resistance training, and activities of daily living training.¹

Exercise was associated with significantly fewer symptoms on the NPI, although the effect size was small (standard mean difference [SMD] = –0.37; 95% CI, –0.57 to –0.17). Heterogeneity in the interventions and assessments were limitations to this meta-analysis.¹

A 2015 systematic review and meta-­analysis of 18 RCTs compared the effect of exercise interventions against a control group for the treatment of BPSD, utilizing 10 behavioral and 2 neurovegetative components of the NPI (each scored from 0 to 5) in patients with dementia. Studies were included if they used ≥ 1 exercise intervention compared to a control or usual care group without additional exercise recommendations. Thirteen studies had a multicomponent training intervention (≥ 2 exercise types grouped together in the same training session), 2 used tai chi, 4 used walking, and 1 used dance and movement therapy. These RCTs were conducted in a variety of settings, including community-dwelling and long-term care facilities (n = 6427 patients).²

Exercise did not reduce global BPSD (N = 4441 patients), with a weighted mean difference (WMD) of −3.9 (95% CI, −9.0 to 1.2; P = .13). Exploratory analysis did not show improvement in aberrant motor behavior with exercise (WMD = –0.55; 95% CI, –1.10 to 0.001; P = .05). Limitations of this review included the small number of studies, heterogeneity of the population, and limitations in data accessibility.²

A 2017 hospital-based RCT evaluated the effects of a short-term exercise program on neuropsychiatric signs and symptoms in patients with dementia in 3 specialized dementia care wards (N = 85). Patients had a diagnosis of dementia, minimum length of stay of 1 week, no delirium, and the ability to perform the Timed Up and Go Test. The intervention group included a 2-week exercise program of four 20-minute exercise sessions per day on 3 days per week, involving strengthening or endurance exercises, in addition to treatment as usual. The control group included a 2-week period of social-stimulation programs consisting of table games for 120 minutes per week, in addition to treatment as usual.³

Exercise remains a small tool to address a big problem.

Of 85 patients randomized, 15 (18%) were lost to follow-up (14 of whom were discharged early from the hospital). Among the 70 patients included in the final analysis, the mean age was 80 years; 47% were female and 53% male; and the mean Mini-Mental Status Examination score was 18.3 (≤ 23 indicates dementia). In both groups, most patients had moderate dementia, moderate neuropsychiatric signs and symptoms, and a low level of psychotic symptoms. Patients in the intervention group had a higher adherence rate compared with those in the control group.³

Continue to: The primary outcome...

The primary outcome was neuropsychiatric signs and symptoms as measured by the Alzheimer’s Disease Cooperative Study–­Clinical Global Impression of Change (ADCS-CGIC). Compared to the control group, the intervention group experienced greater improvement on the ADCS-CGIC dimensions of emotional agitation (SMD = –0.9; P < .001), lability (SMD = –1.1; P < .001), psychomotor agitation (SMD = –0.7; P = .01), and verbal aggression (SMD = –0.5; P = .04). However, there were no differences between groups in the physical aggression dimension. Trial limitations included potential impact of the drop-out rate and possible blinding issues, as nursing staff performing assessments could have seen to which group a patient was allocated.³

A 2016 factorial cluster RCT of 16 nursing homes (with at least 60% of the population having dementia) compared the use of ­person-centered care vs person-centered care plus at least 1 randomly assigned additional intervention (eg, antipsychotic medication use review, social interaction interventions, and exercise over a period of 9 months) (n = 277, with 193 analyzed per protocol). Exercise was implemented at 1 hour per week or at an increase of 20% above baseline and compared with a control group with no change in exercise.⁴

Exercise significantly improved neuropsychiatric symptoms. The baseline NPI score of 14.54 improved by –3.59 (95% CI, –7.08 to –0.09; P < .05). However, none of the study interventions significantly improved the agitation-specific scores. The primary limitation of this study was that antipsychotic prescribing was at the discretion of the provider and not according to a protocol. In addition, the authors noted that the trial was inadequately powered to correct for testing 3 primary outcomes.⁴

Editor’s takeaway

Dementia and dementia with agitation are challenging conditions to treat. Disappointingly, physical exercise had inconsistent and generally minimal effect on agitation in dementia. Nevertheless, exercise had other positive effects. So, considering the benefits that exercise does provide, its low cost, and its limited adverse effects, exercise remains a small tool to address a big problem.

Evidence summary

Mixed results on exercise’s effect on neuropsychiatric symptoms

A 2020 systematic review and meta-analysis of 18 RCTs investigated the effect of home-based physical activity on several markers of behavioral and psychological symptoms of dementia (BPSD). These symptoms were measured using the caregiver-completed neuropsychiatric inventory (NPI), which in­cludes agitation. There was substantial heterogeneity between trials; however, 4 RCTs (472 patients) were included in a meta-­analysis of the NPI. These RCTs were nonblinded, given the nature of the intervention.¹

Interventions to enhance physical activity ranged from 12 weeks to 2 years in duration, with 2 to 8 contacts from the study team per week. The type of physical activity varied and included cardiorespiratory endurance, balance training, resistance training, and activities of daily living training.¹

Exercise was associated with significantly fewer symptoms on the NPI, although the effect size was small (standard mean difference [SMD] = –0.37; 95% CI, –0.57 to –0.17). Heterogeneity in the interventions and assessments were limitations to this meta-analysis.¹

A 2015 systematic review and meta-­analysis of 18 RCTs compared the effect of exercise interventions against a control group for the treatment of BPSD, utilizing 10 behavioral and 2 neurovegetative components of the NPI (each scored from 0 to 5) in patients with dementia. Studies were included if they used ≥ 1 exercise intervention compared to a control or usual care group without additional exercise recommendations. Thirteen studies had a multicomponent training intervention (≥ 2 exercise types grouped together in the same training session), 2 used tai chi, 4 used walking, and 1 used dance and movement therapy. These RCTs were conducted in a variety of settings, including community-dwelling and long-term care facilities (n = 6427 patients).²

Exercise did not reduce global BPSD (N = 4441 patients), with a weighted mean difference (WMD) of −3.9 (95% CI, −9.0 to 1.2; P = .13). Exploratory analysis did not show improvement in aberrant motor behavior with exercise (WMD = –0.55; 95% CI, –1.10 to 0.001; P = .05). Limitations of this review included the small number of studies, heterogeneity of the population, and limitations in data accessibility.²

A 2017 hospital-based RCT evaluated the effects of a short-term exercise program on neuropsychiatric signs and symptoms in patients with dementia in 3 specialized dementia care wards (N = 85). Patients had a diagnosis of dementia, minimum length of stay of 1 week, no delirium, and the ability to perform the Timed Up and Go Test. The intervention group included a 2-week exercise program of four 20-minute exercise sessions per day on 3 days per week, involving strengthening or endurance exercises, in addition to treatment as usual. The control group included a 2-week period of social-stimulation programs consisting of table games for 120 minutes per week, in addition to treatment as usual.³

Exercise remains a small tool to address a big problem.

Of 85 patients randomized, 15 (18%) were lost to follow-up (14 of whom were discharged early from the hospital). Among the 70 patients included in the final analysis, the mean age was 80 years; 47% were female and 53% male; and the mean Mini-Mental Status Examination score was 18.3 (≤ 23 indicates dementia). In both groups, most patients had moderate dementia, moderate neuropsychiatric signs and symptoms, and a low level of psychotic symptoms. Patients in the intervention group had a higher adherence rate compared with those in the control group.³

Continue to: The primary outcome...

The primary outcome was neuropsychiatric signs and symptoms as measured by the Alzheimer’s Disease Cooperative Study–­Clinical Global Impression of Change (ADCS-CGIC). Compared to the control group, the intervention group experienced greater improvement on the ADCS-CGIC dimensions of emotional agitation (SMD = –0.9; P < .001), lability (SMD = –1.1; P < .001), psychomotor agitation (SMD = –0.7; P = .01), and verbal aggression (SMD = –0.5; P = .04). However, there were no differences between groups in the physical aggression dimension. Trial limitations included potential impact of the drop-out rate and possible blinding issues, as nursing staff performing assessments could have seen to which group a patient was allocated.³

A 2016 factorial cluster RCT of 16 nursing homes (with at least 60% of the population having dementia) compared the use of ­person-centered care vs person-centered care plus at least 1 randomly assigned additional intervention (eg, antipsychotic medication use review, social interaction interventions, and exercise over a period of 9 months) (n = 277, with 193 analyzed per protocol). Exercise was implemented at 1 hour per week or at an increase of 20% above baseline and compared with a control group with no change in exercise.⁴

Exercise significantly improved neuropsychiatric symptoms. The baseline NPI score of 14.54 improved by –3.59 (95% CI, –7.08 to –0.09; P < .05). However, none of the study interventions significantly improved the agitation-specific scores. The primary limitation of this study was that antipsychotic prescribing was at the discretion of the provider and not according to a protocol. In addition, the authors noted that the trial was inadequately powered to correct for testing 3 primary outcomes.⁴

Editor’s takeaway

Dementia and dementia with agitation are challenging conditions to treat. Disappointingly, physical exercise had inconsistent and generally minimal effect on agitation in dementia. Nevertheless, exercise had other positive effects. So, considering the benefits that exercise does provide, its low cost, and its limited adverse effects, exercise remains a small tool to address a big problem.

Evidence summary

Mixed results on exercise’s effect on neuropsychiatric symptoms

A 2020 systematic review and meta-analysis of 18 RCTs investigated the effect of home-based physical activity on several markers of behavioral and psychological symptoms of dementia (BPSD). These symptoms were measured using the caregiver-completed neuropsychiatric inventory (NPI), which in­cludes agitation. There was substantial heterogeneity between trials; however, 4 RCTs (472 patients) were included in a meta-­analysis of the NPI. These RCTs were nonblinded, given the nature of the intervention.¹

Interventions to enhance physical activity ranged from 12 weeks to 2 years in duration, with 2 to 8 contacts from the study team per week. The type of physical activity varied and included cardiorespiratory endurance, balance training, resistance training, and activities of daily living training.¹

Exercise was associated with significantly fewer symptoms on the NPI, although the effect size was small (standard mean difference [SMD] = –0.37; 95% CI, –0.57 to –0.17). Heterogeneity in the interventions and assessments were limitations to this meta-analysis.¹

A 2015 systematic review and meta-­analysis of 18 RCTs compared the effect of exercise interventions against a control group for the treatment of BPSD, utilizing 10 behavioral and 2 neurovegetative components of the NPI (each scored from 0 to 5) in patients with dementia. Studies were included if they used ≥ 1 exercise intervention compared to a control or usual care group without additional exercise recommendations. Thirteen studies had a multicomponent training intervention (≥ 2 exercise types grouped together in the same training session), 2 used tai chi, 4 used walking, and 1 used dance and movement therapy. These RCTs were conducted in a variety of settings, including community-dwelling and long-term care facilities (n = 6427 patients).²

Exercise did not reduce global BPSD (N = 4441 patients), with a weighted mean difference (WMD) of −3.9 (95% CI, −9.0 to 1.2; P = .13). Exploratory analysis did not show improvement in aberrant motor behavior with exercise (WMD = –0.55; 95% CI, –1.10 to 0.001; P = .05). Limitations of this review included the small number of studies, heterogeneity of the population, and limitations in data accessibility.²

A 2017 hospital-based RCT evaluated the effects of a short-term exercise program on neuropsychiatric signs and symptoms in patients with dementia in 3 specialized dementia care wards (N = 85). Patients had a diagnosis of dementia, minimum length of stay of 1 week, no delirium, and the ability to perform the Timed Up and Go Test. The intervention group included a 2-week exercise program of four 20-minute exercise sessions per day on 3 days per week, involving strengthening or endurance exercises, in addition to treatment as usual. The control group included a 2-week period of social-stimulation programs consisting of table games for 120 minutes per week, in addition to treatment as usual.³

Exercise remains a small tool to address a big problem.

Of 85 patients randomized, 15 (18%) were lost to follow-up (14 of whom were discharged early from the hospital). Among the 70 patients included in the final analysis, the mean age was 80 years; 47% were female and 53% male; and the mean Mini-Mental Status Examination score was 18.3 (≤ 23 indicates dementia). In both groups, most patients had moderate dementia, moderate neuropsychiatric signs and symptoms, and a low level of psychotic symptoms. Patients in the intervention group had a higher adherence rate compared with those in the control group.³

Continue to: The primary outcome...

The primary outcome was neuropsychiatric signs and symptoms as measured by the Alzheimer’s Disease Cooperative Study–­Clinical Global Impression of Change (ADCS-CGIC). Compared to the control group, the intervention group experienced greater improvement on the ADCS-CGIC dimensions of emotional agitation (SMD = –0.9; P < .001), lability (SMD = –1.1; P < .001), psychomotor agitation (SMD = –0.7; P = .01), and verbal aggression (SMD = –0.5; P = .04). However, there were no differences between groups in the physical aggression dimension. Trial limitations included potential impact of the drop-out rate and possible blinding issues, as nursing staff performing assessments could have seen to which group a patient was allocated.³

A 2016 factorial cluster RCT of 16 nursing homes (with at least 60% of the population having dementia) compared the use of ­person-centered care vs person-centered care plus at least 1 randomly assigned additional intervention (eg, antipsychotic medication use review, social interaction interventions, and exercise over a period of 9 months) (n = 277, with 193 analyzed per protocol). Exercise was implemented at 1 hour per week or at an increase of 20% above baseline and compared with a control group with no change in exercise.⁴

Exercise significantly improved neuropsychiatric symptoms. The baseline NPI score of 14.54 improved by –3.59 (95% CI, –7.08 to –0.09; P < .05). However, none of the study interventions significantly improved the agitation-specific scores. The primary limitation of this study was that antipsychotic prescribing was at the discretion of the provider and not according to a protocol. In addition, the authors noted that the trial was inadequately powered to correct for testing 3 primary outcomes.⁴

Editor’s takeaway

Dementia and dementia with agitation are challenging conditions to treat. Disappointingly, physical exercise had inconsistent and generally minimal effect on agitation in dementia. Nevertheless, exercise had other positive effects. So, considering the benefits that exercise does provide, its low cost, and its limited adverse effects, exercise remains a small tool to address a big problem.

EVIDENCE SUMMARY

A 2013 systematic review of 10 randomized controlled trials (RCTs) with a total of 543 patients with type 2 diabetes evaluated the effect of cinnamon (120 mg/d to 6 g/d) on measures of glycemic control.¹ Study duration ranged from 4 to 18 weeks. Fasting glucose levels demonstrated small but statistically significant reductions (−24.6 mg/dL; 95% confidence interval [CI], −40.5 to −8.7 mg/dL), whereas hemoglobin A1C levels didn’t differ between treatment and control groups (−0.16%; 95% CI, −0.39% to 0.02%). Study limitations included heterogeneity of cinnamon dosing and formulation and concurrent use of oral hypoglycemic agents.

Studies of glycemic control produce mixed results

A 2012 systematic review of 10 RCTs comprising 577 patients with type 1 (72 patients) or type 2 (505 patients) diabetes evaluated the effects of cinnamon supplements (mean dose, 1.9 g/d) on glycemic control compared with placebo, active control, or no treatment.² Study duration ranged from 4.3 to 16 weeks (mean, 10.8 weeks). Studies evaluating hemoglobin A1C lasted at least 12 weeks.

Fasting glucose as measured in 8 studies (338 patients) and hemoglobin A1C as measured in 6 studies (405 patients) didn’t differ between treatment groups (mean fasting glucose difference = −0.91 mmol/L; 95% CI, −1.93 to 0.11; mean hemoglobin A1C difference = −0.06; 95% CI, −0.29 to 0.18). The risk for bias was assessed as high or unclear in 8 studies and moderate in 2 studies.

A 2012 systematic review and meta-­analysis of 6 RCTs including 435 patients with type 2 diabetes evaluated the impact of cinnamon supplements (1 to 6 g/d) on glycemic control.³ Participants consumed cinnamon for 40 to 160 days. Hemoglobin A1C decreased by 0.09% (95% CI, 0.04% to 0.14%) in 5 trials (375 patients), and fasting glucose decreased by 0.84 mmol/L (CI, 0.66 to 1.02) in 5 trials (326 patients). Study limitations included heterogeneity of cinnamon dosing and study population.

RECOMMENDATIONS

The American Diabetes Association finds insufficient evidence to support the use of herbs or spices, including cinnamon, in treating diabetes.⁴

Editor’s Takeaway

Meta-analyses of multiple small, lower-­quality studies yield uncertain conclusions. If cinnamon does improve glycemic control, the benefit is minimal—but so is therisk.

EVIDENCE SUMMARY

A 2013 systematic review of 10 randomized controlled trials (RCTs) with a total of 543 patients with type 2 diabetes evaluated the effect of cinnamon (120 mg/d to 6 g/d) on measures of glycemic control.¹ Study duration ranged from 4 to 18 weeks. Fasting glucose levels demonstrated small but statistically significant reductions (−24.6 mg/dL; 95% confidence interval [CI], −40.5 to −8.7 mg/dL), whereas hemoglobin A1C levels didn’t differ between treatment and control groups (−0.16%; 95% CI, −0.39% to 0.02%). Study limitations included heterogeneity of cinnamon dosing and formulation and concurrent use of oral hypoglycemic agents.

Studies of glycemic control produce mixed results

A 2012 systematic review of 10 RCTs comprising 577 patients with type 1 (72 patients) or type 2 (505 patients) diabetes evaluated the effects of cinnamon supplements (mean dose, 1.9 g/d) on glycemic control compared with placebo, active control, or no treatment.² Study duration ranged from 4.3 to 16 weeks (mean, 10.8 weeks). Studies evaluating hemoglobin A1C lasted at least 12 weeks.

Fasting glucose as measured in 8 studies (338 patients) and hemoglobin A1C as measured in 6 studies (405 patients) didn’t differ between treatment groups (mean fasting glucose difference = −0.91 mmol/L; 95% CI, −1.93 to 0.11; mean hemoglobin A1C difference = −0.06; 95% CI, −0.29 to 0.18). The risk for bias was assessed as high or unclear in 8 studies and moderate in 2 studies.

A 2012 systematic review and meta-­analysis of 6 RCTs including 435 patients with type 2 diabetes evaluated the impact of cinnamon supplements (1 to 6 g/d) on glycemic control.³ Participants consumed cinnamon for 40 to 160 days. Hemoglobin A1C decreased by 0.09% (95% CI, 0.04% to 0.14%) in 5 trials (375 patients), and fasting glucose decreased by 0.84 mmol/L (CI, 0.66 to 1.02) in 5 trials (326 patients). Study limitations included heterogeneity of cinnamon dosing and study population.

RECOMMENDATIONS

The American Diabetes Association finds insufficient evidence to support the use of herbs or spices, including cinnamon, in treating diabetes.⁴

Editor’s Takeaway

Meta-analyses of multiple small, lower-­quality studies yield uncertain conclusions. If cinnamon does improve glycemic control, the benefit is minimal—but so is therisk.

EVIDENCE SUMMARY

A 2013 systematic review of 10 randomized controlled trials (RCTs) with a total of 543 patients with type 2 diabetes evaluated the effect of cinnamon (120 mg/d to 6 g/d) on measures of glycemic control.¹ Study duration ranged from 4 to 18 weeks. Fasting glucose levels demonstrated small but statistically significant reductions (−24.6 mg/dL; 95% confidence interval [CI], −40.5 to −8.7 mg/dL), whereas hemoglobin A1C levels didn’t differ between treatment and control groups (−0.16%; 95% CI, −0.39% to 0.02%). Study limitations included heterogeneity of cinnamon dosing and formulation and concurrent use of oral hypoglycemic agents.

Studies of glycemic control produce mixed results

A 2012 systematic review of 10 RCTs comprising 577 patients with type 1 (72 patients) or type 2 (505 patients) diabetes evaluated the effects of cinnamon supplements (mean dose, 1.9 g/d) on glycemic control compared with placebo, active control, or no treatment.² Study duration ranged from 4.3 to 16 weeks (mean, 10.8 weeks). Studies evaluating hemoglobin A1C lasted at least 12 weeks.

Fasting glucose as measured in 8 studies (338 patients) and hemoglobin A1C as measured in 6 studies (405 patients) didn’t differ between treatment groups (mean fasting glucose difference = −0.91 mmol/L; 95% CI, −1.93 to 0.11; mean hemoglobin A1C difference = −0.06; 95% CI, −0.29 to 0.18). The risk for bias was assessed as high or unclear in 8 studies and moderate in 2 studies.

A 2012 systematic review and meta-­analysis of 6 RCTs including 435 patients with type 2 diabetes evaluated the impact of cinnamon supplements (1 to 6 g/d) on glycemic control.³ Participants consumed cinnamon for 40 to 160 days. Hemoglobin A1C decreased by 0.09% (95% CI, 0.04% to 0.14%) in 5 trials (375 patients), and fasting glucose decreased by 0.84 mmol/L (CI, 0.66 to 1.02) in 5 trials (326 patients). Study limitations included heterogeneity of cinnamon dosing and study population.

RECOMMENDATIONS

The American Diabetes Association finds insufficient evidence to support the use of herbs or spices, including cinnamon, in treating diabetes.⁴

Editor’s Takeaway

Meta-analyses of multiple small, lower-­quality studies yield uncertain conclusions. If cinnamon does improve glycemic control, the benefit is minimal—but so is therisk.