. 2022 Oct 26;39(11):863–874. doi: 10.1007/s40266-022-00980-9

Table 2.

An overview of cognitive tests and their frequency in the interventional studies included in this review and details on the interventions and assessments utilised in those studies

Number of cognitive tests	Number of studies (thereof pharmacological interventions)	Number of studies with positive outcome (thereof pharmacological interventions)	Intervention(s) and cognitive tests (underlined and in italics) used in the studies without impact (separated by a semicolon)	Intervention(s) and cognitive tests (underlined and in italics) used in the studies with positive outcome (separated by a semicolon)
1-2	3 (1)	0 (−)	A multi-component intervention including medication review and recommendations to primary care providers regarding discontinuing or reducing medications associated with delirium, using the American Geriatrics Society Beers guidelines, versus usual care [46] Minimum Data Set Cognitive Performance Scale (MDS-CPS), Brief Interview of Mental Status (BIMS); Educational intervention for nursing staff working in the intervention wards/two 4-h interactive training sessions based on constructive learning theory to recognise harmful medications and adverse drug events [47] Verbal fluency and clock drawing tests; One group was treated with antioxidant formula F at a dose of one ampule/day in the morning immediately before breakfast [48] MMSE II and a three-point scale for sleeping;	–
3 or more tests	10 (7)	5 (4)	In a parallel group design participants were randomised to receive 24 weeks of treatment with daily oral doses of 1000 mg cobalamin, a combination of 1000 mg cobalamin and 400 mg folic acid, or placebo [40] A neuropsychological test battery including MMSE; The intervention involved consultation and treatment by a psychiatrist and follow-up by a research nurse and the patient’s family physician [41] Hamilton Depression Rating Scale (HAMD), the Medical Outcomes 36-item Short Form (SF-36), the Diagnostic Interview Schedule (DIS), MMSE; Oral oestradiol 1mg daily and norethisterone 0.5 mg daily or placebo [45] Dementia Rating Scale, MMSE, Word List Memory, constructional praxis, Wechsler Adult Intelligence Scale–Digit Symbol-Coding, Trail Making Test, Part Al; Modified Consortium to Establish a Registry for AD (CERAD) Boston Naming Test; Single Multidisciplinary Multistep Medication Review (3MR) [50]. MMSE, Neuropsychiatric Inventory–Nursing Home Version (NPI-NH); Discontinuation of antihypertensive medications [51]. MMSE & overall cognition (compound score): computed if 5 of the following 6 tests were available: Stroop Colour Word Test and Trail Making Test for executive functioning, 15-Word Verbal Learning Test and Visual Association Test for (immediate and delayed) verbal and picture memory and Letter-Digit Substitution Test for psychomotor speed	Patients were withdrawn from their usual antiparkinsonian medications. On 3 consecutive days, they took 0.2 mg/kg oral methylphenidate or placebo followed 30 minutes later by a 1-h intravenous L-Dopa (2 mg/kg/h) or placebo infusion [39] Simple reaction time and choice reaction time Stroop test, covert orienting of spatial attention, and digit ordering. Self-assessed mood, anxiety, arousal or concentration; Four component intervention: exercise training, intake of high protein nutritional shakes, memory training, and medication review. Control group received standard care. Both groups were also given counselling regarding dietary habits, lifestyle recommendations, and domestic hazards [49] Neuropsychological performance as measured by Short and Medium-Term Verbal Memory, Animal Naming Test, evocation of words beginning with one explicit letter, designation of famous people’s names, Verbal designation of images and verbal abstraction of word pairs; Concurrent treatment with a AChEI and either folic acid (1 mg capsule) or placebo [42] Response according to the NICE criteria, MMSE, DSST, and IADL and Social Behaviour (SB) subscales of NOSGER; Treatment with Quetiapine (25–200 mg) or haloperidol (0.5– mg) in addition to cholinesterase inhibitors [43]. NPI, CERAD neuropsychological test battery (which included the following tests: verbal fluency, modified Boston Naming Test, MMSE, constructional praxis and recall, word-list memory, word-list recognition and recall), NOSGER; Oral tamoxifen 20 mg per day or oral raloxifene 60 mg per day [44] A cognitive test battery: Global cognition screening, verbal knowledge, verbal fluency, memory (figural and verbal), attention and working memory, spatial ability, fine motor speed

Number of cognitive tests

Number of studies (thereof pharmacological interventions)

Number of studies with positive outcome (thereof pharmacological interventions)

Intervention(s) and cognitive tests (underlined and in italics) used in the studies without impact (separated by a semicolon)

Intervention(s) and cognitive tests (underlined and in italics) used in the studies with positive outcome (separated by a semicolon)

1-2

(1)

(−)

A multi-component intervention including medication review and recommendations to primary care providers regarding discontinuing or reducing medications associated with delirium, using the American Geriatrics Society Beers guidelines, versus usual care [46]

Minimum Data Set Cognitive Performance Scale (MDS-CPS), Brief Interview of Mental Status (BIMS);

Educational intervention for nursing

staff working in the intervention wards/two 4-h

interactive training sessions based on constructive learning

theory to recognise harmful medications and adverse drug events [47]

Verbal fluency and clock drawing tests;

One group was treated with antioxidant formula F at a dose of

one ampule/day in the morning immediately before breakfast [48]

MMSE II and a three-point scale for sleeping;

–

3 or more tests

(7)

(4)

a parallel group design participants were randomised to receive 24 weeks of treatment with daily oral doses of 1000 mg cobalamin, a combination of 1000 mg cobalamin and 400 mg folic

acid, or placebo [40]

A neuropsychological test battery including MMSE;

The intervention involved consultation and

treatment by a psychiatrist and follow-up by a research nurse

and the patient’s family physician [41]

Hamilton Depression Rating Scale (HAMD), the Medical Outcomes 36-item

Short Form (SF-36), the Diagnostic Interview Schedule (DIS), MMSE;

Oral oestradiol 1mg daily and norethisterone 0.5 mg daily

or placebo [45]

Dementia Rating Scale, MMSE, Word List Memory, constructional praxis, Wechsler Adult Intelligence

Scale–Digit Symbol-Coding, Trail Making Test, Part Al; Modified Consortium to Establish a Registry for AD (CERAD) Boston Naming Test;

Single Multidisciplinary

Multistep Medication Review (3MR) [50].

MMSE, Neuropsychiatric Inventory–Nursing Home Version (NPI-NH);

Discontinuation of antihypertensive medications [51].

MMSE & overall cognition (compound score): computed if 5 of the following 6 tests were available: Stroop Colour Word Test and Trail Making Test for executive functioning, 15-Word Verbal Learning Test and

Visual Association Test for (immediate and delayed) verbal and picture memory and Letter-Digit Substitution Test for psychomotor speed

Patients were withdrawn from their usual antiparkinsonian medications. On 3 consecutive days, they took 0.2 mg/kg oral methylphenidate or placebo followed 30 minutes later by a 1-h intravenous L-Dopa (2 mg/kg/h) or placebo infusion [39]

Simple reaction time and choice reaction time

Stroop test, covert orienting of spatial

attention, and digit ordering. Self-assessed mood, anxiety, arousal or concentration;

Four component intervention: exercise training, intake of high protein

nutritional shakes, memory training, and medication review. Control group received standard care. Both groups were also

given counselling regarding dietary habits, lifestyle recommendations,

and domestic hazards [49]

Neuropsychological performance as measured by Short and Medium-Term Verbal Memory, Animal Naming Test, evocation of words beginning with one explicit letter, designation of famous people’s names, Verbal designation of images and verbal abstraction of word pairs;

Concurrent treatment with a AChEI and either folic acid (1 mg capsule) or placebo [42]

Response according to the NICE criteria, MMSE, DSST, and IADL and Social Behaviour (SB) subscales of NOSGER;

Treatment with Quetiapine (25–200 mg) or haloperidol (0.5– mg) in addition to cholinesterase inhibitors [43].

NPI, CERAD neuropsychological test battery (which included the following tests: verbal fluency, modified Boston Naming Test, MMSE, constructional praxis and recall, word-list memory, word-list recognition and recall), NOSGER;

Oral tamoxifen 20 mg per day or oral raloxifene 60 mg per day [44]

A cognitive test battery: Global cognition screening, verbal knowledge, verbal fluency, memory (figural and verbal), attention and working memory, spatial ability, fine motor speed

MMSE mini-mental state examination, DAT The human dopamine transporter, VNTR variable number of tandem repeats, AD Alzheimer’s Disease, AChEI Acetylcholinesterase Inhibitor, NICE National Institute for Health and Care Excellence, DSST Digit Symbol Substitution Test, IADL Instrumental Activities of Daily Living, NOSGER Nurses Observation Scale for Geriatric Patients, HDRS Hamilton Depression Rating Scale, WCST Wisconsin Card Sorting Test, CERAD Consortium to Establish a Registry for Alzheimer’s Disease. Pharmacological interventions: “single drug group interventions” such as those with withdrawal of antiepileptics or antipsychotics or trials involving at least two drug substances. Single drug interventions for drugs approved for treatment in the particular field (e.g., dementia, pain) were excluded