Table 2.

Cohort studies.

References	Objective	Intervention	Number of subjects	Main outcome measures	Findings
Lopez et al. (1999)	To examine the association of psychotropic medication use with cognitive, functional, and AD	1983–1988	179 patients with Alzheimer's disease age 82.2 mean 6.6	Cognitive impairment was evaluated using the Mini-Mental Status Evaluation (MMSE)	BZDs increase the risk of AD
Ellul et al. (2007)	To examine the effects of several drugs on the progression of disease in patients with Alzheimer's disease.	Not reported	257 patients with Alzheimer's disease age 82.2 mean 6.6 standard deviation	The diagnosis of Alzheimer's disease was made according to NINCDS-ADRDA criteria	Antipsychotics and BZDs were associated with a greater cognitive decline in patients treated with these drugs.
Rosenberg et al. (2012)	To examine the longitudinal association of psychotropic medication through the Persistency Index, which represents years of drug use divided by years of observation following AD diagnosis with cognitive, functional, and neuropsychiatric symptom among community-ascertained incident AD cases from the Cache County Dementia Progression Study	Not reported	335 participants were diagnosed with incident AD	Cognitive impairment was Mini-Mental State Evaluation (MMSE) and Clinical Dementia Rating	Psychotropic medication use was associated with more rapid cognitive and functional decline in AD
Hessmann et al. (2018)	To evaluate the continuity of BZDs prescriptions in patients with dementia insured in a German public sickness fund (Allgemeine Ortskrankenkasse AOK, 2018) in Lower Saxony, Germany	2014–2015	1,298 subjects with dementia.	Diagnosis of dementia in 2014, identified according to the International Classification of Diseases	The use of long acting BZD should be avoided in dementia patients.
Lee et al. (2018)	Association between sedative-hypnotic use and the risk of AD, in a Korean population through a retrospective cohort study from the National Health Insurance of Korea database	2002–2015 follow-up.	268,170 subjects. Age ≥ 50 The dosage of sedative-hypnotics was standardized by defined daily dose (DDD).	Comparison between the ever exposed, who were prescribed over 30 DDD of sedative-hypnotics and the non-exposed.	The risk of AD was higher in subjects exposed to sedative-hypnotics. (GABAA receptor agonists). Patients exposed to over 360 DDD of sedative-hypnotics showed a higher risk of dementia when compared to non-treated patients
Grande et al. (2019)	To investigate the effect of BDZs on first cognitive alterations in primary care patients suffering early cognitive alterations. Data comes from the REMIND—REteMilanese INtegrata per le Demenze— database.	Not reported	4,249 subjects (mean age 77.0 ± 8.2) enrolled by 353 General Practitioners (GPs) in the Milan metropolitan area.)	Evaluation of cognitive function by ad hoc trained GPs, using the Mini Mental State Examination (MMSE).	BZD use is not associated with an increased risk of poorer cognitive performance in primary care patients with first cognitive complaints.