Is Long-Term Benzodiazepine Use a Risk Factor for Cognitive Decline? Results of a Systematic Review

Table 3

Cognitive domains, follow-up evaluation times, and outcome measures.

Study	Cognitive domains follow-up times	Results of data analyses (95% CI)	Cognitive decline ()
Dealberto et al. [18]	GCF 6 years	Logistic regression: OR = 1.18 ()	No
Hanlon et al. [19]	GCF 3 years	Logistic regression: β = 0.09 (−0.07–0.24)	No
Paterniti et al. [20]	GCF, MC, PS, SP and VM 4 years	Logistic regression: OR: GCF = 1.9 (1.0–3.6); MC = 1.2 (0.5–2.6); PS = 2.5 (1.5–4.4); SP = 2.3 (1.3–4.1); VM = 1.9 (0.8–4.5)	Yes: For GCF, PS and SP
Allard et al. [21]	AC, VM, VR and VS 3 years	ND	No
Bierman et al. [10]	GCF, I, SP and VM 9 years	Multilevel analyses: effect size (F^2) : GCF = 0.012 (); VM (delayed recall) = 0.003 (); VM (retention) = 0.004 (); I = 0.007 (); SP = 0.005 ()	Yes: For GCF, I and VM
van Vliet et al. [22]	AC, GCF, SP and VM 5 years	Linear regression analyses: difference in scores: GCF: −0.28 (−1.24–0.69) ; AC: 3.00 (−2.78–8.77) ; SP: −0.90 (−2.36–0.56) ; VM (immediate recall): 0.14 (−0.81–1.10) ; VM: (delayed recall): 0.21 (−0.22–0.64)	No
Puustinen et al. [23]	GCF 7.6 years (mean)	ND	No
Boeuf-Cazou et al. [24]	AC, NVM, PS and VM 10 years	Multilevel analyses: β scores (±SD) : men: AC: −0.30 ± 0.20; NVM: −0.57 ± 0.34 PS: −0.32 ± 1.70; VM (immediate recall): −0.40 ± 0.25 VM (delayed recall): −0.80 ± 0.42 women: AC: 0.01 ± 0.21; NVM: −0.12 ± 0.26 PS: 4.48 ± 2.65; VM (immediate recall): 0.52 ± 0.28 VM (delayed recall): −2.13 ± 0.67 ()	Yes: For VM and only for women
Desplenter et al. [25]	GCF 3 years	Linear mixed model: GCF: overall difference: 0.31 (SE = 0.16)	No
Gallacher et al. [26]	GCF, I and SP 22 years	Logistic regression: OR for cognitive decline = 0.63 (0.27–1.48)	No
Mura et al. [7]	AC, GCF, NVM, SP and VR 7 years	Nonlinear multivariate mixed model: interaction BZDs x time: AC: −0.11 (); GCF: −0.06 (); NVM: 0.12 (); SP: 0.005 (); VR: 0.05 ()	No
Gray et al. [27]	GCF 7.3 years (mean)	Linear regression: Difference in the mean cognitive score: 0.002 (−0.05–0.06)	No
Chung et al. [28]	GCF, VM 2 years	Mixed-effect model: changes in the scores: GCF : F (1, 27.60) = 0.09, VM (immediate recall): F (1, 27.40) = 0.003, ; VM (% of forgetting): F (1, 27.63) = 0.15, ; VM (learning): F (1, 27.57) = 0.76, ; VM (forgetting): F (1, 27.63) = 0.15,	No
Zhang et al. [29]	GCF 4.8 (mean)	Logistic regression: Interaction BZDs x time = −0.06 () for MMSE; 0.002 () for CDR-SB	No

AC = attention/concentration; BZDs = benzodiazepines; β = beta coefficient; CDR-SB = clinical dementia rating sum of boxes; CI = confidence interval; GCF = global cognitive functioning; I = intelligence; MC = motor control/performance; MMSE = mini mental state examination; ND = not described; NVM = nonverbal memory; OR = odds ratio; PS = psychomotor speed; SD = standard deviation; SE = standard error; SP = speed of processing; VM = verbal memory; VR = verbal reasoning; VS = visuospatial. Follow-up time was not complete (less than 80% of participants were followed).