A AVALIAÇÃO DA MEMÓRIA DE TRABALHO USANDO A BATERIA AUTOMATIZADA DO CAMBRIDGE NEUROPSYCHOLOGICAL TEST PODE AJUDAR NO DIAGNÓSTICO DE COMPROMETIMENTO COGNITIVO LEVE: UMA REVISÃO SISTEMÁTICA E META-ANÁLISE

Sabahi, Zahra; Farhoudi, Mehdi; Naseri, Amirreza; Talebi, Mahnaz

doi:10.1590/1980-5764-dn-2022-0006

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Views & Reviews • Dement. neuropsychol. 16 (4) • Dez 2022 • https://doi.org/10.1590/1980-5764-dn-2022-0006 linkcopiar

A AVALIAÇÃO DA MEMÓRIA DE TRABALHO USANDO A BATERIA AUTOMATIZADA DO CAMBRIDGE NEUROPSYCHOLOGICAL TEST PODE AJUDAR NO DIAGNÓSTICO DE COMPROMETIMENTO COGNITIVO LEVE: UMA REVISÃO SISTEMÁTICA E META-ANÁLISE

Autoria SCIMAGO INSTITUTIONS RANKINGS

O comprometimento cognitivo leve (CCL) é um estado intersticial entre o envelhecimento normal e a demência.

Objetivo: Neste estudo, investigamos os perfis de memória de trabalho (MT) de pacientes com CCL usando a bateria automatizada de testes neuropsicológicos de Cambridge (Cambridge Neuropsychological Test Automated Battery – CANTAB). Também examinamos a acurácia diagnóstica e possíveis fatores associados como desfechos secundários do estudo.

Métodos: Foi realizada uma busca eletrônica nas bases de dados EMBASE, PubMed e ScienceDirect. Foram incluídos estudos com participantes com CCL e utilizando subtestes da bateria CANTAB para avaliação da MT. A meta-análise foi realizada usando o software CMA2.

Resultados: Dos 1.537 registros, esta revisão sistemática abordou 14 estudos, e 7 deles foram incluídos na meta-análise. Houve uma diferença significativa entre pacientes com CCL e controles saudáveis na memória de trabalho espacial (MTE) (DPM: 0,535; IC95% 11–96; valor p=0,014), spatial span (SSP) (SDM: 0,649; IC95% 0,297–0,100; valor p<0,01) e processamento rápido de informação visual (PRV) (DPM: 0,52; IC95% 0,386–0,654; valor p<0,01). A MT de pacientes com CCL foi associada com os níveis de proteína tau e beta-amiloide (Aβ) no líquido cefalorraquidiano (CSF).

Conclusões: A MT é um domínio cognitivo prejudicado no CCL. Os subtestes CANTAB WM, incluindo SSP, MTE e PRV, são precisos o suficiente para serem usados como uma ferramenta de avaliação adequada para o diagnóstico de CCL em ambientes clínicos. A proteína Tau e Aβ estão associadas a pontuações de MT mais baixas em pacientes com CCL; entretanto, sexo, idade, transtornos psiquiátricos, alelo da apolipoproteína 4 e escores de atividade funcional não podem afetar a MT.

Palavras-chave:
Disfunção Cognitiva; Memória de Curto Prazo; Testes Neuropsicológicos; Revisão Sistemática; Metanálise

Author (year)	Study design	Sample size	Mean age	Education	Male ratio (%)	MMSE score	Eligibility criteria MCI	Eligibility criteria-control	CANTAB subtests for WM	MCI			Control			Associated factors	Non-associated factors
Author (year)	Study design	Sample size	Mean age	Education	Male ratio (%)	MMSE score	Eligibility criteria MCI	Eligibility criteria-control	CANTAB subtests for WM	Mean	SD	n	Mean	SD	n
Nathan et al. 2017⁴⁰	Cross-sectional	145	68.2±7.37	46.9% above 10 years of education	42.8	26.6±1.9 (24 to 30)	Age 55–90 years; subjective memory complaint verified by a family relative; at least 1 standard deviation deficit in a measure of episodic memory; an MMSE score of 24–30; a CDR scale score of 0.5 (with a score of 0.5 for the memory subscale); a clinical diagnosis of amnestic MCI, but preservation of general cognitive and functional performance to no meet clinical criteria for AD; GDS scale score <6; and Hachinski Modified Ischemic Scale score ≤4		SWM between errors	27.7	8.3	145				Aβ42, total tau, p-tau, hippocampal volume	Age, GDS, NPIQ, FAQ, MMSE, education, sex, APOE4
									SWM strategy	19.9	2.4
									DMS % correct (all delays)	67.9	16.3
									RVP A’	0.8	0.1
Saunders and Summers et al. 2010⁴¹	Cross-sectional	131	Control: 69.32±5.83 S-MCI: 71.16±7.08 A-MCI: 71.18±7.02	Control: 13.56±3.14 S-MCI: 13.00±3.52 A-MCI:13.13±3.35	48.09	–	Memory problems, with a history of decline from a former level; preserved cognitive functioning; intact activities of daily living; no history of significant medical, neurological, or psychiatric condition; no history of major risk factors for vascular disease; and no history of alcohol abuse, sensory impairment, or impairment of hand mobility.	No cognitive complaints or medical history, participants with matched mean age and level of education	SWM total errors (S-MCI)	42.06	15.05	32	33.68	13.08	25	Age, WTAR (a-MCI), DRS II (a-MCI), BNT (a-MCI), RAVLT trial 5 recall (a-MCI), RAVLT delayed (a-MCI)	Education, sex, WTAR (S-MCI), WAIS-II FSIQ, GDS, PAL, DRS II (S-MCI), BNT (S-MCI), RAVLT trial 5 recall (S-MCI), RAVLT delayed (S-MCI)
									SWM total errors (A-MCI)	51.82	15.15	60	33.68	13.08
									SSP length (S-MCI)	5.20	0.69	32	5.80	0.76
									SSP length (A-MCI)	4.96	0.64	60	5.80	0.76
									RVP A’ (S-MCI)	0.86	0.05	32	0.93	0.04
									RVP A’ (A-MCI)	0.87	0.05	6	0.93	0.04
									RVP latency (S-MCI)	530.70	123.75	32	447.50	77.51
									RVP latency (A-MCI)	519.68	123.57	60	447.50	77.51
Egerházi, et al. 2017⁴²	Cross sectional	40	55±6	–	47.5	28±0.6	No neurological symptoms or other physical disorders, amnestic MCI diagnosis according to the criteria of Petersen, CDR= 0.5, mild short-term memory loss, with symptoms insufficient for the diagnosis of dementia according to the criteria of the DSM-IV, MMSE≥26, normal CT/MRI, No medication intake		SWM (Z-score)	-0.8871		25	–	–	–	–	–
									SSP (Z-score)	-0.755			–	–	–
									RVP (Z-score)	-2.101			–	–	–
Collie et al. 2002³⁹	cohort	46	Control: 65.94±5.37 MCI: 67.82±7.75	Control: 12.37 ±3.78 MCI: 11.64±3.86	45.65	28.12±1.42	Age >50 years, no psychiatric and neurological diagnosis. Exclusion criteria at this stage included a history of respiratory, circulatory, or endocrine disease, personal or family history of psychiatric illness, head injury or substance abuse. MCI based on CERAD neuropsychological battery		SWM Total errors	33.33	15.81	23	25.19	12.24	23	CERAD (word list recall and learning)	Age, sex, education, MMSE, depression, CERAD, APOE4, CFQ, WMS-R, state and trait anxiety test, and NART
									SWM Strategy score	17.04	3.24	23	15.15	2.57	23
									SSP task score	4.74	1.05	23	5.38	0.90	23
Facal et al. 2014⁴²	Cross sectional	145	MDA-MCI: 70.34±9.49 SDA-MCI: 67.62±9.40 Control: 67.36±9.09	MDA-MCI: 9.54±3.77 SDA-MCI: 9.23±4.10 CONTROL: 10.22±5.05	37.93	MDA-MCI: 22.86±1.65	MMSE >20, no history of clinical stroke, traumatic brain injury, motor sensory defects, alcohol, or drug abuse/dependence, not diagnosed with any significant medical or psychiatric illnesses, GDS <10.		SSP Correct items (MDA-MCI)	21.76	7.09	44	25.86	6.80	58	MMSE, WAIS vocabulary, memory complaints, CAMCOG (language, attention) CVLT	Age, education, occupational, complexity, vocabulary, frequency of reading, leisure and cultural activities, social participation
Facal et al. 2014⁴²	Cross sectional	145	MDA-MCI: 70.34±9.49 SDA-MCI: 67.62±9.40 Control: 67.36±9.09	MDA-MCI: 9.54±3.77 SDA-MCI: 9.23±4.10 CONTROL: 10.22±5.05	37.93	SDA-MCI: 27.00±1.81			SSP Correct items (SDA-MCI)	26.00	6.71	43	25.86	6.80	58
Juncos-Rabadán et al. 2014⁴⁴	Cross sectional	170	MDA-MCI: 71.06±8.36 SDA-MCI: 68.96±8.60 MDNA-MCI: 66.78±8.56 Healthy control: 68.16±8.75	MDA-MCI: 10.18±4.09 SDA-MCI: 9.52±4.08 MDNA-MCI: 7.96±3.77 Healthy control: 9.35±4.62	–	MDA-MCI: 23.40±1.58 SDA-MCI: 27.50±1.50 MDNA-MCI: 24.53±2.35	No prior diagnosis of dementia, psychiatric or neurological disorders, severe illness, deafness or blindness, not receiving chemotherapy, not consumers of substances or alcohol, informant-corroborated memory complaints, performance of 1.5 SDs below age norms on the Spanish version of (CVLT), no significant or minimal impact on activities of daily living assessed by the Lawton and Brody Index, not demented according the NINCDS-ADRDA and DMS-IV criteria. Normal or corrected-to-normal vision and hearing and visual acuity	Scored higher than the cutoff point in memory, general cognitive functioning, and specific cognitive tests, no history of clinical stroke, traumatic brain injury, motor-sensory defects, alcohol or drug abuse/dependence, and no diagnosis of any significant medical or psychiatric illnesses. Normal or corrected-to-normal vision and hearing and visual acuity	SSP length (MDA-MCI)	4.40	0.83	32	4.77	0.67	54	Memory complaints (informant), MMSE, CVLT Language, Attention, calculation, Praxis	Age, education, Visual acuity
									SSP length (SDA-MCI)	4.65	0.80	57
									SSP length (MDNA-MCI)	4.45	0.83	32
									SSP total errors (MDA-MCI)	11.93	3.97	32	11.68	3.97
									SSP total errors (SDA-MCI)	11.60	3.96	57
									SSP total errors (MDNA-MCI)	11.66	5.25	32
									SSP time to last response (MDA-MCI)	9063.22	4845.18	32	6429.49	1666.14
									SSP time to last response (SDA-MCI)	6698.75	2526.20	57
									SSP time to last response (MDNA-MCI)	7892.75	2674.63	32
Summers and Saunders et al. 2012³³	cohort	106	Control: 69.36±5.8 Stable MCI: 71.04±7.1 Progressed MCI:* 73.80±7.9	Control: 13.64±3.1 MCI: 12.55±3.0 Progressed: 14.60±3.5	46.25	–	Memory problems with a history of decline; preserved cognitive functioning; intact activities of daily living; no history of significant medical, neurological, or psychiatric condition; no history of major risk factors for vascular disease; and no history of alcohol abuse, sensory impairment, or impairment to hand mobility	No cognitive complaints or medical history of significance, control group was matched to the mean age level of education of the MCI groups.	SSP length (Stable MCI)	4.84	0.69	25	5.84	-0.75	25	WTAR	Age, education, FSIQ, DRS, sex, RAVLT, BNT
									SSP length (progressed)	4.70	0.82	10	5.84	-0.75
									SWM total errors (stable MCI)	50.24	18.46	25	32.92	12.95
									SWM total errors (progressed)	45.90	9.18	10	32.92	12.95
									RVP A’(stable MCI)	0.864	0.04	25	0.939	0.04
									RVP A’ (progressed)	0.820	0.05	10	0.939	0.04
Klekociuk and Summers et al. 2014⁴⁵	cohort	118	60–90	–	38.98	–	No previous medical, neurological, or psychological conditions, no evidence of dementia, AEMSS score ≥9, preserved activities of daily living, subclinical impairment as a performance 1.28 standard deviations or greater below age-appropriate normative references.	No previous medical, neurological, or psychological conditions, no evidence of dementia, AEMSS score ≥9, preserved activities of daily living. No evidence of subclinical impairment.	SSP length (a-MCI)	5.55	0.91	22	5.20	0.84	49	RAVLT, DRS-2, FSIQ, digit span, WAIS–III, LNS	Age, education, sex, HADS Depression
									SSP length (na-MCI)	4.72	0.74	25
									SSP length (a-MCI+)	4.68	0.72	22
									SWM total errors (a-MCI)	20.73	17.78	22	29.16	18.37
									SWM total errors (na-MCI)	30.52	17.31	25
									SWM total errors (a-MCI+)	38.18	17.08	22
									SWM strategy (a-MCI)	29.64	6.87	22	30.41	6.88
									SWM strategy (na-MCI)	33.52	5.85	25
									SWM strategy (a-MCI+)	33.23	6.02	22
									RVP latency (a-MCI)	407.08	90.50	22	469.34	9.30
									RVP latency (na-MCI)	542.48	109.6	25
									RVP latency (a-MCI +)	522.95	155.29	22
Cacciamani et al. 2018⁴⁶	cohort	25	MCI-AD: 68.58±6.65 MCI-ambiguous: 68.69±7.75	MCI-AD†: 10±3.94 MCI-ambiguous: 9±4.01	40	27.04±0.31	Age between 55 and 80 years, presence of subjective memory complaints, presence of memory impairment as documented by scoring at least 1 SD below cutoff point on the Logical Memory II subscale (delayed recall) from the WMS; Preserved or slightly impaired functional abilities on FAQ, not responding to diagnostic criteria for dementia, MMSE≥24, CDR score of 0.5, GDS <6, Hachinski Modified Ischemic scale ≤4, at least 5 years of formal education		SWM Strategy (overall MCI)	37.44	0.72	25	–			Total-tau, phospho-tau	Age, sex, education, FAQ score, Aβ42, CDR, MMSE, FAQ, GDS, Hachinski Modified Ischemic Scale, Logical Memory II, Mental Deterioration Battery, RAVLT
									SWM strategy (MCI-AD)	38.17	0.95	12
									SWM strategy (MCI-ambiguous)	36.77	1.06	13
									SWM errors (overall MCI)	53.96	4.25	25
									SWM errors (MCI-AD)	59.92	5.73	12
									SWM errors (MCI-ambiguous)	48.46	6.04	13
									RVP A’ (overall MCI)	0.81	0.02	25
									RVP A’ (MCI-AD)	0.81	0.03	12
									RVP A’ (MCI-ambiguous)	0.82	0.01	12
Reijs et al. 2017¹⁰	cohort	263	68.3±9.1	10.4±4.5	56	25.5±3.9	Memory clinic referral for the evaluation of cognitive complaints, age >60 years, a MMSE-score >19, one or more cognitive impairments on neuropsychological tests according to Petersen's criteria, and no clinical diagnosis of dementia.	Age >40, MMSE >the 10th percentile according to age- and education-adjusted local norms, no cognitive impairment on neuropsychological tests	SWM errors	29.6	8.8	73	19.2	10.0	46	Age, sex, education, MMSE, CDR, Aβ42, t-tau, wordlist learning and delayed recall and recognition, animal fluency	FAQ
Klekociuk and Summers et al. 2014⁴⁷	cohort	122	a-MCI: 70.61±7.99 na-MCI: 70.58±5.97 a-MCI+‡: 69.26±6.56 Control: 72.66±6.52	a-MCI: 14.43±3.16 na-MCI: 14.92±3.52 a-MCI+: 12.48±3.53 Control: 14.20±3.74	39.34	–	Presence of cognitive complaints (e.g., memory, attention); preserved general cognition (as assessed by the DRS-2; self-reported capacity to maintain independent daily functioning (confirmed by an informant); no history of major medical, neurological, or psychiatric illness); no history of major risk factors for vascular disease and no history of sensory impairment or impairment to hand mobility.		SWM total errors (a-MCI)	20.29	17.77	23	29.42	18.52	50	WTAR (FSIQ), DRS-2, Digit Span (forward and backward)	Hospital Anxiety and Depression Scale, LNS, Age, education, HADS, Letter-Number Sequencing total, Digit Symbol Coding
									SWM total errors (na-MCI)	32.04	18.83	26
									SWM total errors (a-MCI+)	36.63	18.96	23
									SSP length (a-MCI)	5.52	0.91	23	5.19	0.84
									SSP length (na-MCI)	4.73	0.71	26
									SSP length (a-MCI+)	4.74	0.71	23
									RVP latency (a-MCI)	482.92	112.31	23	468.04	89.73
									RVP latency (na-MCI)	545.36	108.20	26
									RVP latency (a-MCI+)	519.02	152.07	23
									RVP A’ (a-MCI)	0.90	0.047	23	0.902	0.042
									RVP A’ (na-MCI)	0.87	0.05	26
									RVP A’ (a-MCI+)	0.85	0.047	23
Saunders and Summers et al. 2011⁴⁸	cohort	106	Control: 69.19±5.75 na-MCI: 71.41±7.22 a-MCI: 70.96±6.85	Control: 13.50±3.09 na-MCI: 13.17±3.50 a-MCI: 13.04±3.39	–	–	Memory problems with a history of decline; preserved cognitive functioning; intact activities of daily living; no history of significant medical, neurological, or psychiatric condition; no history of major risk factors for vascular disease; no history of alcohol abuse, sensory impairment, or impairment to hand mobility		SWM strategy (a-MCI)	37.61	23.56	52	35.42	15.29	26	RAVLT trial 5, DRS-2 AEMSS, RAVLT, GDS, BNT	Age, education, WTAR, FSIQ
									SWM strategy (na-MCI)	38.23	10.71	29	35.42	15.29
									SWM errors (a-MCI)	50.50	14.56	52	33.39	12.84
									SWM total errors (na-MCI)	43.59	14.75	29	33.39	12.84
									SSP length (a-MCI)	4.90	0.57	52	5.82	0.76
									SSP length (na-MCI)	5.22	0.69	29	5.82	0.76
									RVP latency (a-MCI)	513.33	126.19	52	445	76.48
									RVP mean latency (na-MCI)	529.58	125.63	29	445	76.48
									RVP A’(a-MCI)	0.87	0.07	52	0.93	0.05
									RVP A’(na-MCI)	0.85	0.05	29	0.93	0.05
Stonsaovapak et al. 2020⁴⁹	cohort	45	MCI: 68.39±8.37 Control: 68.39±8.37	–	8.88	–	MCI diagnosis based on the criteria of the MCI Working Group of the European Consortium on Alzheimer's disease, age between 45 and 90 years, with a TMSE score of >23, (MoCA)-Thai score of <25		SWM between errors	53.48	13.10	23	51.45	14.81	22		age, sex, educational, TMSE score, MoCA
									SWM total errors	55.39	13.31		52.64	15.51
									RVP mean latency	2.77	0.12		2.72	0.11
									RVP total hits	10.61	5.23		13.68	4.57			Gender, education, CCI
Campos-Magdaleno et al. 2021⁵⁰	cohort	208	Control: 64.26±8.83 MCI-stable: 70.94±7.54 MCI-worsened: 75.44±7.14	Control: 10.28±4.71 MCI-stable: 9.15±3.40 MCI-worsened: 9.30±4.79	35.13	Control: 28.34±1.34 MCI-stable: 25.13±2.89 MCI-worsened: 24.04±2.53	No previous diagnosis of MCI or dementia, clinical stroke, traumatic brain injury, motor-sensory defects, alcohol or drug abuse/dependence, or any neurological or psychiatric disease. Self-reported, informant corroborated concerns about cognition, 1.5 SDs below age and education norms in one or more cognitive domains in CAMCOG-R except for memory, assessed by CVLT, no significant or minimal impact on activities of daily living	No previous diagnosis of neurologic disorders, normal adults in general functioning and specific domain tests, attending primary care health centers with self-reported cognitive concerns; confirmation of these concerns by the short Spanish version of the questionnaire for subjective memory complaints	SSP (MCI-stable)	4.5	2.82	32	5.00	3.84	149	age, Lawton-Brody, SCC, Praxis CAMCOG-R, MMSE, CVLT
Campos-Magdaleno et al. 2021⁵⁰	cohort	208			35.13				SSP (MCI-worsened)	3.9	3.27	27	5.00	3.84	149	age, Lawton-Brody, SCC, Praxis CAMCOG-R, MMSE, CVLT

Study	Q1	Q2	Q3	Q4	Q5	Q6	Q7	Q8
Nathan et al., 2017⁴⁰	Yes	No	NA	Yes	Yes	Yes	Yes	Yes
Saunders and Summers, 2010⁴¹	Yes	No	NA	No	Yes	No	Yes	Yes
Égerházi et al., 2007⁴²	No	No	NA	Yes	Yes	Yes	Yes	No
Collie et al., 2002³⁹	Yes	No	NA	Yes	Yes	Yes	Yes	Yes
Facal et al., 2014⁴³	Yes	No	NA	Yes	Yes	Yes	Yes	Yes
Juncos-Rabadán et al., 2014⁴⁴	Yes	Yes	NA	Yes	Yes	Yes	Yes	Yes
Summers and Saunders, 2012³³	Yes	No	NA	No	Yes	No	Yes	Yes
Klekociuk and Summers, 2014⁴⁵	Yes	Yes	NA	No	Yes	Yes	Yes	Yes
Cacciamani et al., 2017⁴⁶	Yes	No	NA	Yes	Yes	Yes	Yes	Yes
Reijs et al., 2017¹⁰	Yes	Yes	NA	Yes	Yes	Yes	Yes	Yes
Klekociuk and Summers, 2014⁴⁷	Yes	Yes	NA	No	Yes	Yes	Yes	Yes
Saunders and Summers, 2011⁴⁸	Yes	No	NA	No	Yes	Yes	Yes	Yes
Stonsaovapak et al. 2020⁴⁹	No	No	NA	No	Yes	Yes	Yes	Yes
Campos-Magdaleno et al., 2020⁵⁰	Yes	Yes	NA	Yes	Yes	Yes	Yes	Yes
Overall	85.7%	35.7%	NA	57.1%	100%	85.7%	100%	92.8%

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[TFN1] ^*
In this study, “Progressed” is used for the participants who were classified at baseline as a-MCI or na-MCI but were reclassified as a-MCI following the 20-month assessment

[TFN2] ^†
Subjects with mild cognitive impairment and Alzheimer's disease like CSF profiles

[TFN3] ^‡
MCI+ defined as multiple domains amnestic mild cognitive impairment in this study; CANTAB: Cambridge Neuropsychological Test Automated Battery; MMSE: Mini-Mental State Examination; WM: working memory; MCI: mild cognitive impairment; SWM: spatial working memory; SSP: spatial span; RVP: rapid visual information processing; DMS: delayed matching to sample; S-MCI: subjective MCI; A-MCI: amnestic MCI; NPIQ: Neuropsychiatric Inventory Questionnaire; FAQ: Functional Activities Questionnaire; APOE: apolipoprotein; Aβ: amyloid-beta; SDA-MCI: single-domain MCI; CFQ: Cognitive Failures Questionnaire; MDA-MCI: multiple-domain amnestic MCI; MNDA-MCI: multiple-domain non-amnestic MCI; GDS: Geriatric Depression Scale; BNT: Boston Naming Test; TMSE: Thai Mental State Examination; MoCA: Montreal Cognitive Assessment; CERAD: Consortium to Establish a Registry for Alzheimer's Disease; CAMCOG: Cambridge Cognitive Examination; CVLT: California Verbal Learning Test; DRS: dementia rating scale; RAVLT: Rey Auditory Verbal Learning Test; RCFT: Rey Complex Figure Test and Recognition Trial; FSIQ: Full Scale Intelligence Quotient; WTAR: Wechsler test of adult reading. CCI: Charlson Comorbidity Index; DSP: Digit Span; WAIS–III: Wechsler Adult Intelligence Scale, 3rd edition; LNS: Letter–Number Sequencing; MMSE: Mini Mental State Examination; CDR: Clinical dementia rating; FAQ: the Functional Assessment Questionnaire; WMS: Wechsler Memory Scale; SMCQ: subjective memory complaints questionnaire; SD: standard deviation, NINCDS-ADRDA: the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association; TMSE: Thai mental state examination; MOANS: Mayo Older American Normative; AEMSS: age- and education-corrected MOANS scaled scores (AEMSS) score.