Table 1 Characteristics of included studies.

From: Effect of Alzheimer’s disease medications on neurocognitive outcomes in children and adolescents with autism spectrum disorder and low IQ: a scoping review

Study

Country

Age range (years)

N enrolled/ N completers

Study design

Intervention

Dose

Estimate of cognitive ability

Neurocognitive measures by domains

Treatment duration (weeks)

Initial Dose (mg)

MD (mg/d)

Chez et al. [59]

USA

2 – 10

43/34

RCT, DBPC; OLE

Donepezil hydrochloride

2.5

2.5

Clinician-estimated intellectual impairment (IQ < 70)a

Language (ROWPVT [72]; EOWPVT [73])

6 (RCT) + 6 (OLE)

Handen et al. [61]

USA

8 – 17

34/31

RCT, DBPC; OLE

Donepezil

2.5

10

Treatment: 96.8 (73–142)e; Control: 96.7 (82–146)e

Executive Function (D-KEFS [76])

Language (EOWPVT [73])

Learning and Memory (CVLT [110], SR [111], PAL [112])

10 (RCT) + 10 (OLE)

Gabis et al. [60]

Israel

5 – 16

60/43

RCT, DBPC

Donepezil; Choline

2.5

5

Treatment: 61.64 (27.395)f; Control: 58.32 (23.132)f

Language (PLS-4 [71], WISC-IV [104])

General Cognitive Ability (K-BIT-2 [113])

12

Soorya et al. [62]

USA

6 – 12

23/14

RCT, DBPC

Memantine

3

6, 9, or 12h

Treatment: 80.17 (23.29)f; Control: 75.00 (21.58)f

Executive Function (ABC [75])

Language (NEPSY-II [78], EVT-2 [114])

Learning and Memory (NEPSY-II [78])

Perceptual-Motor Function (NEPSY-II [78], BOT-2 [115], Sensory Profile-II [116], Apraxia Profile [117])

General Cognitive Ability (WISC-IV [104], WASI-II [118])

24

Owley et al. [63]

USA

3 – 12

15/12

Pros-OL

Memantine

5

20

89.9 (22.3)g

Executive Function (ABC [75])

Language (EOWPVT [73], PPVT-III [119], DAS [105])

Learning and Memory (CMS [79])

General Cognitive Ability (RM [120], MSEL [107])

8

Erikson et al. [66]

USA

6 – 19

18/18

Ret-Obs

Memantine

2.5 or 5 g

20

Mild (40%), moderate (28%), or severe (1%) MRb; IQ within or above average range (31%)i

Executive Function (ABC [75])

1.5 – 56

Bouhadoun et al. [65]

Canada

5 – 16

8/5 l

Ret-Obs

Memantine

2.5 or 5g

10 or 20 g

Mild (20%), moderate (20%), and severe (20%) IDj,k; GDI (40%)k

Complex Attention (Caregiver report)

Executive Function (Neuropsychological Evaluation)

Language (Clinical evaluation, caregiver report)

Perceptual-Motor Function (Neuropsychological evaluation)

10 – 212

Hardan & Handen [64]

USA

7 – 19

8/8

Ret-OL

Donepezil

2.5

10

Mild (25%), moderate (25%), and severe (12.5%) MRb; Borderline IQ (12.5%)c; IQ within or above average range (25%)d

Executive Function (ABC [75])

8

Chez et al. [67]

USA

2 – 12

32/32

Ret-CS

Rivastigmine tartrate

0.8

0.8

Clinician-estimated intellectual impairment (IQ < 70)a

Complex Attention (CPRS [77])

Language (ROWPVT [72]; EOWPVT [73])

12

Chez et al. [68]

USA

2 – 26

151/151

Ret-CS

Memantine

5 – 10

2.5 – 30

Clinician-estimated intellectual impairment (IQ < 70)a

Language (CGI-I [121])

4 – 8

Nissenkorn et al. [69]

Israel

2 – 8

4/4

Ret-CS

Donepezil

2.5 or 5

 

Clinician-reported ID (100%)

Language (CDI [74])

Perceptual-Motor Function (CDI [74])

General Cognitive Ability (CDI [74]; ABAS-II [122])

52

Cosme-Cruz et al. [70]

USA

13

1/1

Case Report

Memantine

5

10

Clinician-reported ID

Language (Clinical evaluation, caregiver report)

Perceptual-Motor Function (Clinical evaluation, caregiver report)

48

  1. RCT, randomized controlled trial; DBPC, double-blind Placebo-Controlled; OLE, open-label extension; Pros-OL, prospective open-label trial; Ret-OL, retrospective open-label trial; Ret-CS, retrospective case series; Ret-Obs, retrospective observational study; MD, maintenance dose; MR, mental retardation; ID, intellectual disability; GDI, global developmental impairment; ABC, aberrant behavior checklist; D-KEFS, Delis-Kaplan executive function system; ROWPVT, receptive one word picture vocabulary test; EOWPVT, expressive one word picture vocabulary test; CVLT, California verbal learning test; SR, selective reminding; PAL, paired-associate learning test; K-BIT-2, Kaufman brief intelligence test-second edition; PLS-4, preschool language scale-fourth edition; WISC-IV, Wechsler intelligence scale for children-fourth edition; PPVT-III, peabody picture vocabulary test-third edition; CMS, children’s memory scale; EVT-2, Expressive Vocabulary Test-Second Edition; RM, Ravens matrices; MSEL, Mullen Scales of early learning; DAS, differential abilities scales; NEPSY-II, A Developmental Neuropsychological Assessment-Second Edition; BOT-2, Bruininks-Oseretsky Test of Motor Proficiency-Second Edition; WISC-IV, Wechsler Intelligence Scale for Children-Fourth Edition; WASI-II, Wechsler abbreviated scale of intelligence-second edition; CGI-I, clinical global impression improvement scale; CPRS, Conners’ parent rating scale; CDI, child development inventory; ABAS-II, adaptive behavior assessment system-II.
  2. aNo standardized cognitive testing was reported. However, based on diagnostic profile (e.g., profound autism) and author correspondence, most participants were likely intellectually impaired (IQ < 70).
  3. bMild, moderate, and severe MR is defined within the IQ range: 20 – 70 (American Psychiatric Association, 1994).
  4. cBorderline IQ is defined within the IQ range 71 – 84 (American Psychiatric Association, 1994).
  5. dNo estimate of cognitive ability was formally measured for this study, therefore cognitive ability was estimated based on comorbid diagnoses provided in Table 1 from Hardan & Handen (2002).
  6. eFSIQ (Mean, Range).
  7. fFSIQ (Mean ± SD).
  8. gNonverbal IQ (Mean ± SD).
  9. hDosage based upon weight.
  10. iNo estimate of cognitive ability was formally measured for this study; therefore, cognitive ability was estimated based on comorbid diagnoses provided in Table 1 from Erikson et al. (2007).
  11. jEssential features of ID are deficits in general mental abilities (IQ < 70) and adaptive functioning, in comparison to an individual’s age-, gender-, and sociocultural-matched peers (American Psychiatric Association, 2013).
  12. kNo estimate of cognitive ability was formally measured for this study, therefore cognitive ability was estimated based on comorbid diagnoses provided in Table 1 from Bouhadoun et al. [65].
  13. lN enrolled/completed reflects only the subset of participants from Bouhadoun et al. [65] who met this review’s inclusion criteria, not the total number enrolled or completing the original study.
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