Análise longitudinal da memória episódica verbal em pacientes com esclerose múltipla remitente-recorrente

Boa, Izadora Nogueira Fonte; Rimkus, Carolina de Medeiros; Campanholo, Kenia Repiso; Pereira, Samira Luisa Apóstolos; Junqueira, Thiago de Faria; Machado, Melissa de Almeida Rodrigues; Callegaro, Dagoberto; Otaduy, Maria Concepción García; Leite, Claudia da Costa; Miotto, Eliane Correa

doi:10.1590/0004-282X20180038

Izadora Nogueira Fonte Boa Correspondence: Izadora Nogueira Fonte Boa; Rua Piranhas, 48, apto 302; 30770-540 Belo Horizonte MG, Brasil; E-mail: izadoranogfb@hotmail.com

Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Departamento de Neurologia, São Paulo SP, Brasil

Carolina de Medeiros Rimkus

Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Departamento de Neurologia, São Paulo SP, Brasil

Kenia Repiso Campanholo

Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Departamento de Neurologia, São Paulo SP, Brasil

Samira Luisa Apóstolos Pereira

Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Departamento de Neurologia, São Paulo SP, Brasil

Thiago de Faria Junqueira

Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Departamento de Neurologia, São Paulo SP, Brasil

Melissa de Almeida Rodrigues Machado

Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Departamento de Neurologia, São Paulo SP, Brasil

Dagoberto Callegaro

Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Departamento de Neurologia, São Paulo SP, Brasil

Maria Concepción García Otaduy

Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Departamento de Neurologia, São Paulo SP, Brasil

Claudia da Costa Leite

Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Departamento de Neurologia, São Paulo SP, Brasil

Eliane Correa Miotto

Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, Departamento de Neurologia, São Paulo SP, Brasil

Correspondence: Izadora Nogueira Fonte Boa; Rua Piranhas, 48, apto 302; 30770-540 Belo Horizonte MG, Brasil; E-mail: izadoranogfb@hotmail.com

Conflict of interest: There is no conflict of interest to declare.

Cognitive domains assessed	Neuropsychological instruments used
Attention
Sustained	Trail Making Test A
Divided	Trail Making Test B
Selective	Stroop Test Victoria – part 3
Information Processing Speed	Symbol Digit Modalities Test
Short-term memory (verbal and visual-spatial)
Immediate	Digit Span - Forward (WAIS-III)
Immediate	Corsi Blocks - Forward (WMS)
Working	Digit Span - Backward (WAIS-III)
	Letter-Number Sequencing (WAIS-III)
	Corsi Blocks - Backward (WMS)
Episodic memory (verbal and visual-spatial)
Immediate Recall	HVLT, BVMT, Logical Memory (WMS)
Delayed Recall	HVLT, BVMT, Logical Memory (WMS), ROCF
Recognition	HVLT* and BVMT
Executive functions
Mental Flexibility	Modified Wisconsin Card Sorting Test
Verbal Fluency	Controlled Oral Word Association Test
Visual-spatial functions
Visual-construction	Rey-Osterrieth Complex Figure (ROCF)
Language
Naming	Boston Naming Test

Variable		Controls (n = 26)	Patients at baseline (n = 29)	P (controls vs patients at baseline)	Patients at follow-up (n = 29)
Age (years)				0.667
	Mean (SD)	30.62 (8.47)	29.62 (8.55)		34.34 (8.52)
	Median (min-max)	28.00 (20.00–53.00)	27.00 (18.00–48.00)		33.00 (23.00–52.00)
Education (years)				0.291
	Mean (SD)	15.46 (3.56)	14.55 (2.74)		15.62 (3.12)
	Median (min-max)	15.00 (11.00–24.00)	15.00 (10.00–19.00)		16.00 (10.00–22.00)
Gender (female/male)		17/09	19/10	0.992	19/10

Variable		Baseline		Follow-up
Variable		Median (min–max)	Mean (SD)	Median (min–max)	Mean (SD)
Disease duration (years)		2.16(0.25–7.05)	2.64(1.94)	6.68(3.62–12.69)	7.25(2.33)
Time since diagnosis (years)		0.30(0.00–5.01)	0.96(1.30)	5.26(3.32–10.66)	5.57(1.85)
Number of relapses		2.00(1.00–7.00)	2.66(1.77)	4.00(1.00–11.00)	4.10(2.63)
Time since last relapse (months)		7.70(0.40–41.96)	13.65(12.23)	28.90(2.70–107.03)	36.08(26.85)
EDSS		1.00(0.00–3.00)	1.21(0.94)	1.00(0.00–4.00)	1.14(1.21)
Disease modifying therapies (DMTs) (y/n)		-		25/04
	Interferon (Betaferon, Avonex, Rebif)	-		12
	Glatiramer acetate (Copaxone)	-		9
	Natalizumab (Tysabri)	-		1
	Rituximab (Mabthera)	-		1
	Fingolimod (Gilenya)	-		2
Antidepressants (y/n)		-		10/19
Poor adherence to DMTs (y/n)		-		13 / 16

Neuropsychological instruments	Patients at Baseline		Patients at Follow-up		p-value
Neuropsychological instruments	Median (min-max)	M (SD)	Median (min-max)	M (SD)	p-value
HVLT – Immediate recall	−0.80 (–2.20–1.00)	−0.97 (0.84)	−0.50 (–2.20–1.70)	−0.48 (0.94)	0.019^* * p < 0.05; HVLT: Hopkins verbal learning test; BVMT: Brief visuospatial memory test; WAIS: Wechsler adult intelligence scale; WMS: Wechsler memory scale; HVLT: Hopkins verbal learning test-revised; BVMT: brief visuospatial memory test-revised; COWA: controlled oral word association.
HVLT – Delayed recall	−0.80 (–2.20–1.30)	−0.81 (0.85)	−0.10 (–3.00–1.10)	−0.48 (1.08)	0.092
HVLT – Recognition	0.60 (–2.20–0.80)	0.18 (0.76)	0.70 (–3.00–1.00)	−0.06 (1.19)	0.829
BVMT – Immediate recall	0.90 (–2.20–1.50)	0.49 (1.35)	0.50 (–2.00–1.70)	0.36 (0.98)	0.681
BVMT – Delayed recall	1.00 (–2.20–1.50)	0.53 (0.95)	1.00 (–3.00–1.50)	0.53 (1.10)	0.497
BVMT – Recognition	0.00 (0.00–0.00)	0.00 (0.00)	0.00 (–1.90–0.00)	−0.18 (0.53)	0.102
Letter-number sequencing	0.40 (–1.00–2.00)	0.38 (0.78)	0.70 (–0.70–2.00)	0.62 (0.75)	0.190
Digit span (WAIS-III)	0.70 (–1.00–2.50)	0.58(0.80)	1.00 (–0.30–3.00)	1.13(0.98)	0.002^* * p < 0.05; HVLT: Hopkins verbal learning test; BVMT: Brief visuospatial memory test; WAIS: Wechsler adult intelligence scale; WMS: Wechsler memory scale; HVLT: Hopkins verbal learning test-revised; BVMT: brief visuospatial memory test-revised; COWA: controlled oral word association.
Corsi blocks (WMS-R)	−0.60 (–1.50–1.60)	−0.38 (0.67)	0.00 (–1.80–1.40)	−0.17(0.79)	0.175
Logical memory – immediate recall	−0.30 (–1.90–1.60)	−0.21 (0.86)	−0.10 (–1.80–3.50)	0.12(0.99)	0.178
Logical memory – delayed recall	−0.10 (–1.30–1.30)	−0.16 (0.66)	0.00 (–1.00–2.40)	0.22(0.87)	0.042^* * p < 0.05; HVLT: Hopkins verbal learning test; BVMT: Brief visuospatial memory test; WAIS: Wechsler adult intelligence scale; WMS: Wechsler memory scale; HVLT: Hopkins verbal learning test-revised; BVMT: brief visuospatial memory test-revised; COWA: controlled oral word association.
Stroop test Victoria - part 3	−0.50 (–2.20–1.50)	−0.46 (1.07)	−0.20 (–2.30–1.70)	−0.18(0.97)	0.234
Trail making test A	−0.10 (–2.20–0.70)	−0.33 (0.77)	0.00 (–2.90–1.40)	0.01(0.87)	0.028^* * p < 0.05; HVLT: Hopkins verbal learning test; BVMT: Brief visuospatial memory test; WAIS: Wechsler adult intelligence scale; WMS: Wechsler memory scale; HVLT: Hopkins verbal learning test-revised; BVMT: brief visuospatial memory test-revised; COWA: controlled oral word association.
Trail making test B	−0.10 (–2.20–0.90)	−0.44 (0.93)	0.00 (–3.00–1.00)	−0.52(1.20)	0.750
FAS form of the COWA test	−0.90 (–2.20–1.10)	−0.80 (0.78)	−0.80 (–2.60–0.70)	−0.90(0.84)	0.463
Animals	−0.60 (–1.70–1.10)	−0.56 (0.71)	0.00 (–1.40–2.20)	0.08(0.83)	<0.001^* * p < 0.05; HVLT: Hopkins verbal learning test; BVMT: Brief visuospatial memory test; WAIS: Wechsler adult intelligence scale; WMS: Wechsler memory scale; HVLT: Hopkins verbal learning test-revised; BVMT: brief visuospatial memory test-revised; COWA: controlled oral word association.
Symbol digit modalities test	−0.80 (–2.40–0.60)	−0.79 (0.88)	−0.70 (–2.00–1.00)	−0.71(0.82)	0.509
Modified Wisconsin card sorting test	0.70 (–2.20–0.70)	0.17 (0.89)	0.70 (–3.00–0.70)	0.16(0.88)	0.726
Boston naming test	−0.60 (–2.20–0.10)	−0.90 (0.76)	−0.20 (–2.60–1.10)	−0.40(0.94)	0.004^* * p < 0.05; HVLT: Hopkins verbal learning test; BVMT: Brief visuospatial memory test; WAIS: Wechsler adult intelligence scale; WMS: Wechsler memory scale; HVLT: Hopkins verbal learning test-revised; BVMT: brief visuospatial memory test-revised; COWA: controlled oral word association.

Neuropsychological instruments	Patients at Baseline		Control		p-value¹ 1 comparison between patient and control groups at baseline using the Mann Whitney test.
Neuropsychological instruments	Median (min–max)	M (SD)	Median (min–max)	M (SD)
HVLT – Immediate recall	−0.80 (–2.20–1.00)	−0.97 (0.84)	0.15 (–1.30–1.30)	−0.05 (0.82)	< 0.001^* * p < 0.05;
HVLT – Delayed recall	−0.80 (–2.20–1.30)	−0.81 (0.85)	0.00 (–1.70–1.00)	−0.08 (0.93)	0.006^* * p < 0.05;
HVLT– Recognition	0.60 (–2.20–0.80)	0.18 (0.76)	0.80 (–0.80–0.80)	0.29 (0.65)	0.495
BVMT – Immediate recall	0.90 (–2.20–1.50)	0.49 (1.35)	0.80 (–2.20–2.00)	0.69 (0.89)	0.826
BVMT – Delayed recall	1.00 (–2.20–1.50)	0.53 (0.95)	1.05 (–2.20–1.50)	0.78 (0.81)	0.314
BVMT – Recognition	0.00 (0.00–0.00)	0.00 (0.00)	0.00 (0.00–0.00)	0.00 (0.00)	> 0.999
Letter-number sequencing	0.40 (–1.00–2.00)	0.38 (0.78)	0.55 (–1.00–4.00)	0.81 (1.25)	0.300
Digit span (WAIS-III)	0.70 (–1.00–2.50)	0.58 (0.80)	0.70 (–1.00–4.00)	0.85 (1.11)	0.553
Corsi blocks (WMS-R)	−0.60 (–1.50–1.60)	−0.38 (0.67)	0.00 (–2.00–2.00)	−0.12 (0.98)	0.184
Logical memory – immediate recall	−0.30 (–1.90–1.60)	−0.21 (0.86)	0.35 (–1.00–1.90)	0.38 (0.81)	0.013^* * p < 0.05;
Logical memory – delayed recall	−0.10 (–1.30–1.30)	−0.16 (0.66)	0.50 (–1.30–2.40)	0.47 (0.81)	0.003^* * p < 0.05;
Stroop test Victoria – part 3	−0.50 (–2.20–1.50)	−0.46 (1.07)	0.55 (–2.10–2.50)	0.36 (0.89)	0.007^* * p < 0.05;
Trail making test A	−0.10 (–2.20–0.70)	−0.33 (0.77)	0.05 (–2.20–1.60)	−0.05 (0.95)	0.227
Trail making test B	−0.10 (–2.20–0.90)	−0.44 (0.93)	0.20 (–3.00–2.00)	0.12 (1.17)	0.023^* * p < 0.05;
FAS form of the COWA test	−0.90 (–2.20–1.10)	−0.80 (0.78)	−0.45 (–1.50–1.30)	−0.40 (0.75)	0.050
Animals form of the COWA test	−0.60 (–1.70–1.10)	−0.56 (0.71)	0.05 (–1.70–2.30)	0.08 (0.98)	0.009^* * p < 0.05;
Symbol digit modalities test	−0.80 (–2.40–0.60)	−0.79 (0.88)	−0.40 (–1.50–1.60)	−0.14 (0.90)	0.017^* * p < 0.05;
Modified Wisconsin card sorting test	0.70 (–2.20–0.70)	0.17 (0.89)	0.70 (–1.60–0.70)	0.30 (0.70)	0.731
Boston naming test	−0.60 (–2.20–0.10)	−0.90 (0.76)	−0.30 (–2.20–1.30)	−0.37 (0.88)	0.007^* * p < 0.05;

Variable	Working memory		Information processing speed	Executive function	p group
Variable	p Dígitos	p SNL	p SDMT	p MWCST	p group
HVLT - Immediate recall	0.112	0.016^* * p > 0.05.	0.948	0.310	0.001^* * p > 0.05.
HVLT - Delayed recall	0.911	0.060	0.596	0.028^* * p > 0.05.	0.028^* * p > 0.05.
Logic Memory - Immediate recall	0.084	0.094	0.568	0.068	0.068
Logic Memory - Delayed recall	0.715	0.172	0.698	0.017^* * p > 0.05.	0.017^* * p > 0.05.

Cognitive domain	Cognitive ability	Neuropsychological test	p/r	Measures of episodic verbal memory
Cognitive domain	Cognitive ability	Neuropsychological test	p/r	HVLT - Immediate recall	HVLT - Delayed recall	Logic memory - Immediate recall	Logic memory - Delayed recall
Attention	Selective	Stroop Test Victoria	r	0.027	0.062	−0.119	−0.074
	Selective	Stroop Test Victoria	p	0.888	0.749	0.538	0.702
	Sustained	TMT A	r	0.271	−0.024	0.130	0.094
	Sustained	TMT A	p	0.155	0.900	0.501	0.627
	Divided	TMT B	r	0.303	0.173	0.311	0.344
	Divided	TMT B	p	0.110	0.370	0.100	0.067
	Processing speed	SDMT	r	0.285	0.350	0.464^* * p < 0.05.	0.415^* * p < 0.05.
	Processing speed	SDMT	p	0.134	0.063	0.011	0.025
Executive function	Verbal fluency to letters	COWAT - F.A.S	r	0.088	0.072	0.174	0.298
	Verbal fluency to letters	COWAT - F.A.S	p	0.651	0.712	0.366	0.117
	Verbal fluency semantic	COWAT - animals	r	0.165	0.278	0.115	0.080
	Verbal fluency semantic	COWAT - animals	p	0.393	0.144	0.551	0.680
	Strategy training and mental flexibility	MWCST	r	0.560^* * p < 0.05.	0.229	0.391	0.423
	Strategy training and mental flexibility	MWCST	p	0.005	0.232	0.036	0.022
	Verbal working memory	SNL-WAIS	r	0.560^* * p < 0.05.	0.183	0.347	0.218
		SNL-WAIS	p	0.002	0.341	0.066	0.255
		Dígits-WAIS	r	0.401^* * p < 0.05.	0.260	0.063	−0.067
		Dígits-WAIS	p	0.031	0.174	0.747	0.730

[TFN1] WAIS: Wechsler adult intelligence scale; WMS: Wechsler memory scale; HVLT: Hopkins verbal learning test-revised; BVMT: brief visuospatial memory test-revised; ROCF: Rey-Osterrieth complex figure; *Measures assessing verbal episodic memory.

Análise longitudinal da memória episódica verbal em pacientes com esclerose múltipla remitente-recorrente

RESUMO