Annals of Internal Medicine: Dementia Topic Collection

Cognitive Impairment Associated With Atrial Fibrillation A Meta-analysis

Kalantarian S, Stern TA, Mansour M, et al. — Tue, 05 Mar 2013 00:00:00 GMT

Background:

Atrial fibrillation (AF) has been linked with an increased risk for cognitive impairment and dementia.

Purpose:

To complete a meta-analysis of studies examining the association between AF and cognitive impairment.

Data Sources:

Search of MEDLINE, PsycINFO, Cochrane Library, CINAHL, and EMBASE databases and hand search of article references.

Study Selection:

Prospective and nonprospective studies reporting adjusted risk estimates for the association between AF and cognitive impairment.

Data Extraction:

Two abstracters independently extracted data on study characteristics, risk estimates, methods of AF and outcome ascertainment, and methodological quality.

Data Synthesis:

Twenty-one studies were included in the meta-analysis. Atrial fibrillation was significantly associated with a higher risk for cognitive impairment in patients with first-ever or recurrent stroke (relative risk [RR], 2.70 [95% CI, 1.82 to 4.00]) and in a broader population including patients with or without a history of stroke (RR, 1.40 [CI, 1.19 to 1.64]). The association in the latter group remained significant independent proof of clinical stroke history (RR, 1.34 [CI, 1.13 to 1.58]). However, there was significant heterogeneity among studies of the broader population (I² = 69.4%). Limiting the analysis to prospective studies yielded similar results (RR, 1.36 [CI, 1.12 to 1.65]). Restricting the analysis to studies of dementia eliminated the significant heterogeneity (P = 0.137) but did not alter the pooled estimate substantially (RR, 1.38 [CI, 1.22 to 1.56]).

Limitations:

There is an inherent bias because of confounding variables in observational studies. There was significant heterogeneity among included studies.

Conclusion:

Evidence suggests that AF is associated with a higher risk for cognitive impairment and dementia, with or without a history of clinical stroke. Further studies are required to elucidate the association between AF and subtypes of dementia as well as the cause of cognitive impairment.

Primary Funding Source:

Deane Institute for Integrative Research in Atrial Fibrillation and Stroke at the Massachusetts General Hospital.

The Association Between Physical Fitness and Dementia

Tue, 05 Feb 2013 00:00:00 GMT

Never Too Fit for Body and Mind

Sano M. — Tue, 05 Feb 2013 00:00:00 GMT

Physical fitness is beneficial in several health areas. In this issue, DeFina and colleagues find that cardiorespiratory fitness levels in midlife were associated with lower risk for dementia later in life. The editorialist discusses the study's findings, concluding that physical activity does seem to be a reasonable prescription for dementia prevention.

The Association Between Midlife Cardiorespiratory Fitness Levels and Later-Life Dementia A Cohort Study

DeFina LF, Willis BL, Radford NB, et al. — Tue, 05 Feb 2013 00:00:00 GMT

Chinese translation

Background:

Primary prevention of Alzheimer disease and other types of dementia (all-cause dementia) is an important public health goal. Evidence to date is insufficient to recommend any lifestyle change to prevent or delay the onset of dementia.

Objective:

To assess the association between objectively measured midlife cardiorespiratory fitness (“fitness”) levels and development of all-cause dementia in advanced age.

Design:

Prospective, observational cohort study.

Setting:

Preventive medicine clinic.

Patients:

19 458 community-dwelling, nonelderly adults who had a baseline fitness examination.

Measurements:

Fitness levels, assessed using the modified Balke treadmill protocol between 1971 and 2009, and incident all-cause dementia using Medicare Parts A and B claims data from 1999 to 2009.

Results:

1659 cases of incident all-cause dementia occurred during 125 700 person-years of Medicare follow-up (median follow-up, 25 years [interquartile range, 19 to 30 years]). After multivariable adjustment, participants in the highest quintile of fitness level had lower hazard of all-cause dementia than those in the lowest quintile (hazard ratio, 0.64 [95% CI, 0.54 to 0.77]). Higher fitness levels were associated with lower hazard of all-cause dementia with previous stroke (hazard ratio, 0.74 [CI, 0.53 to 1.04]) or without previous stroke (hazard ratio, 0.74 [CI, 0.61 to 0.90]).

Limitations:

Dementia diagnoses were based on Medicare claims, and participants generally were non-Hispanic white, healthy, and well-educated and had access to preventive health care. This study evaluated fitness levels, so a specific exercise prescription cannot be generated from results and the findings may not be causal.

Conclusion:

Higher midlife fitness levels seem to be associated with lower hazards of developing all-cause dementia later in life. The magnitude and direction of the association were similar with or without previous stroke, suggesting that higher fitness levels earlier in life may lower risk for dementia later in life, independent of cerebrovascular disease.

Primary Funding Source:

The Cooper Institute; University of Texas Southwestern Medical Center; National Heart, Lung, and Blood Institute; and American Heart Association.

Review: Cholinesterase inhibitors do not reduce progression to dementia from mild cognitive impairment

Masoodi N. — Tue, 19 Feb 2013 00:00:00 GMT

Question

In adults with mild cognitive impairment, what are the efficacy and safety of cholinesterase inhibitors (ChEIs)?

Review scope

Included studies compared ChEIs (donepezil, rivastigmine, galantamine, or tacrine) with placebo for ≥ 1 month in adults with mild cognitive impairment (as defined by each study but including subjective memory complaint and relatively preserved daily functioning). Primary outcomes were progression to dementia, which included Alzheimer disease (National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer's Disease and Related Disorders Association criteria); vascular dementia (consensus criteria); and Lewy body dementia (consensus criteria) assessed at 12, 24, and 36 months; or dementia syndrome (Diagnostic and Statistical Manual of Mental Disorders, 4th edition, or World Health Organization International Statistical Classification of Diseases and Related Health Problems, 10th revision); and adverse events. Secondary outcomes included mortality.

Review methods

Cochrane Dementia and Cognitive Improvement Group Specialised Register (ALOIS), which includes search results from MEDLINE, EMBASE/Excerpta Medica, CINAHL, PsycINFO, LILACS, trial registers, Cochrane Central Register of Controlled Trials, and gray literature; and reference lists were searched for double-blind, randomized, controlled trials (RCTs). 9 RCTs (n = 5149, age range 45 to 90 y, follow-up range 16 wk to 3 y) met selection criteria. All RCTs had adequate randomization, blinding, and intention-to-treat analysis; 8 were funded by pharmaceutical manufacturers. Donepezil was studied in 3 RCTs, galantamine in 4, and rivastigmine in 2.

Main results

The main results are in the Table.

Conclusion

In adults with mild cognitive impairment, cholinesterase inhibitors do not differ from placebo for progression to dementia at 1 and 3 years but increase nonserious adverse events.Cholinesterase inhibitors (ChEIs) vs placebo in adults with mild cognitive impairment*OutcomesNumber of trials (n)Weighted event ratesAt 16 wk to 3 yChEIsPlaceboRRR (95% CI)NNT (CI)Dementia at 1 y3 (2560)7.6%12%31% (0 to 53)NSDementia at 2 y2 (2048)12%18%33% (17 to 45)17 (12 to 34)Dementia at 3 y2 (1530)20%24%16% (−2 to 30)NSSerious adverse events6 (4207)19%19%3% (−10 to 14)NSRRI (CI)NNH (CI)Any adverse event6 (4207)89%82%9% (2 to 16)15 (10 to 50)Diarrhea7 (4761)29%18%110% (30 to 239)10 (7 to 15)Nausea7 (4761)22%9.1%197% (157 to 242)8 (5 to 34)Mortality7 (4719)3.3%3.3%8% (−46 to 21)NS*NS = not significant; other abbreviations defined in Glossary. Weighted event rates, RRR, RRI, NNT, NNH, and CI calculated from control event rates and risk ratios in article using a random-effects model.

Review: Nonpharmacologic caregiver interventions improve dementia symptoms and caregiver reactions

Paolino N, O’Malley PG. — Tue, 19 Feb 2013 00:00:00 GMT

Question

Do nonpharmacologic interventions involving family caregivers of community-dwelling patients with dementia reduce neuropsychiatric symptoms and caregivers' adverse reactions to neuropsychiatric symptoms?

Review scope

Included studies compared nonpharmacologic interventions involving caregivers (live-in family member) of patients with dementia with control. Studies of respite care, drug therapy, or patients with schizophrenia or bipolar disorder were excluded. Outcomes were neuropsychiatric (behavioral and psychological) dementia symptoms in patients and caregivers' adverse reactions to patients' neuropsychiatric symptoms.

Review methods

MEDLINE, EMBASE/Excerpta Medica, PsycINFO, and Scopus (all 1985 to Jul 2010) were searched for experimental and clinical trials and single-case studies with > 5 patients published in English. 23 studies (n = 3279 patient–caregiver dyads) met the selection criteria: 16 were randomized controlled trials (RCTs), and 7 reported randomization but did not clearly meet the criteria to be classified as RCTs. 14 studies had ≥ 80 caregivers or dyads. Intervention types included skills training for caregivers (18 studies), education for caregivers (21 studies), activity planning and environmental redesign (5 studies), enhancing support for caregivers (5 studies), self-care techniques for caregivers (12 studies), and miscellaneous strategies (e.g., collaborative care with health professionals, exercise for patient) (3 studies), often given in combination; and were delivered individually to caregivers or dyads in 20 studies. Intervention duration ranged from 6 weeks to 24 months.

Main results

Meta-analyses showed that caregiver interventions reduced neuropsychiatric symptoms in patients and reduced related adverse reactions in caregivers (Table).

Conclusion

Nonpharmacologic interventions involving family caregivers reduce neuropsychiatric symptoms in community-dwelling persons with dementia and caregivers' adverse reactions to neuropsychiatric symptoms.Nonpharmacologic caregiver interventions vs control in patients with dementia and their live-in family caregivers*OutcomesNumber of studies† (comparisons)Mean effect size‡ at 6 wk to 24 mo (95% CI)P valueBehavioral and psychological symptoms of dementia17 (25)0.34 (0.20 to 0.48)< 0.01Caregiver adverse reactions to behavioral and psychological symptoms of dementia13 (16)0.15 (0.04 to 0.26)0.006*CI defined in Glossary. Number of comparisons exceeds number of studies because some studies had multiple comparisons.†7 of 23 studies were classified as pseudorandomized.‡Positive effect size indicates positive overall effect of caregiver interventions on outcomes. Effect sizes (difference between treatment and control groups or between pre-and posttreatment assessments) were standardized mean differences (Cohen d) calculated using a random-effects model.