Lower cognitive function in patients with age-related macular degeneration: a meta-analysis

Figures & data

Figure 1 Flow chart of the studies selection process.

Table 1 Baseline characteristic and quality of the included studies

Author	Year	Area	Design of study	Cases		Control selection	Sex (female %)		Age (years)		Education (years)		NOS score	Measure of cognitive
				AMD	CON		AMD	CON	AMD	CON	AMD	CON
Woo^Citation12	2012	Korea	Case-control	170	190	Community dwelling without AMD	47.1	41.6	72.5±7.6	76.8±6.1	12.0±7.3	9.8±5.2	7	MMSE, DST, TMT, WLT, etc
Rozzini^Citation21	2014	Italy	Case-control	51	24	Spouses, family member	53	83	73.7±7.2	71.7±6.2	8.4±4.3	7.5±2.8	8	MMSE, MOCA TMT, etc
Peiretti^Citation22	2014	Italy	Case-control	136	38	Normal individuals	44.9	55.3	76.5±9.7	75.3±5.5	N		7	MMSE
Mandas^Citation23	2014	Italy	Case-control	119	730	No vision problem	N		78.4±6.9	78.5±6.7	N		7	MMSE, ADL, CIRS
Al-Salem^Citation6	2014	US	Case-control	138	91	No retinal disease	52.2	54.9	76.6±8.6	75±8	N		5	Mini-Cog test
Demirci^Citation7	2015	Turk	Case-control	59	49	Healthy subjects	47	48	74.3±7.3	73.9±5.5	3.5±2.6	3.6±2.8	7	Mini-MMSE, animals, FAB, etc
Kelly^Citation24	2015	Irish	RCT	121	105	Low MP	66.9	50.5	65±9	47±12.1	P<0.00l		7	FAS, animals, PAL, etc

Abbreviations: NOS, Newcastle-Ottawa Scale; ADL, activities of daily living; AMD, age-related macular degeneration; CIRS, cumulative illness rating scale; CON, control; DST, digit span test; FAB, frontal assessment battery; FAS, a phonemic fluency score; MMSE, mini-mental state examination; MOCA, Montreal Cognitive Assessment; MP, macular pigment; N, information not provided in this study; PAL, paired associates learning; RCT, randomized controlled clinical trials; TMT, trail making test; WLT, word list memory test.

Table 2 Cognitive function test scores in each AMD subtype and control subject of the included studies

Study	AMD (total)				AMD (wet)				AMD (dry)				Control			Measure
	n	Mean	SD	P-value	n	Mean	SD	P-value	n	Mean	SD	P-value	n	Mean	SD
Woo^Citation12	170	24.97	3.30	<0.001	107	24.5	0.26	<0.001	17	23.42	0.62	<0.001	190	25.99	2.79	MMSE
Rozzini^Citation21	51	26.8	3.2	0.050	31	27.2	2.8	0.081	20	26.2	3.6	0.011	24	28.3	1.3	MMSE
Peiretti^Citation22	136	27.8	1.5	0.721									38	27.7	1.6	MMSE
Mandas^Citation23	119	20.9	6.3	0.008									730	22.5	6.0	MMSE
Al-Salem^Citation6	138	3.68	1.61	<0.001	56	3.95	1.65	0.001	82	3.5	1.59	<0.001	91	4.63	0.85	Mini-Cog test
Demirci^Citation7	59	24.3	3.88	0.002	45	25.46	2.80	0.071	14	20.71	4.71	<0.001	49	26.59	3.16	MMSE
Demirci^Citation7	59	13.7	5.50	0.21	45	14.84	5.20	0.845	14	10.14	5.03	0.005	49	15.06	5.66	Animal fluency
Kelly^Citation24	121	15.5	4.0	<0.001									105	21.6	5.8	Animal fluency
Woo^Citation12	170	83.49	78.10	0.001	107	96.34	5.35	<0.001	17	135.03	13.09	<0.001	190	64.83	37.61	TMT-A
Rozzini^Citation21	51	78.4	57.4	0.09	31	80.4	66.4	0.154	20	74.8	37.2	0.104	24	60	20.9	TMT-A
Woo^Citation12	170	201.22	86.09	0.002	107	222.59	7.39	<0.001	17	213.98	18.04	0.291	190	192.84	81.93	TMT-B
Rozzini^Citation21	51	131.9	72.5	0.92	31	130.9	88.4	0.856	20	133.7	32.9	0.600	24	127.3	44.9	TMT-B

Abbreviations: AMD, age-related macular degeneration; MMSE, mini-mental state examination; SD, standard deviation; TMT, trail making test.

Figure 2 Meta-analysis of the cognitive function in AMD patients and controls by MMSE, Animal fluency, Mini-Cog, TMT-A and -B.

Note: Weights are from random-effects analysis.
Abbreviations: AMD, age-related macular degeneration; CI, confidence interval; MMSE, mini-mental state examination; NA, not applicable; SMD, standard mean difference; TMT, trail making test.

Table 3 Stratified analyses according to AMD subtype and different tests

Subgroups	Number of studies	SMD (95% CI)	Meta-analyses		Heterogeneity
			Z	P-value	I^2 (%)	P-value
AMD (total)
MMSE	5	−0.32 (−0.51, −0.13)	3.28	0.001	50.7	0.087
Animal fluency	2	−0.75 (−1.73, 0.23)	1.51	0.132	94.1	<0.001
TMT-A	2	0.32 (0.13, 0.51)	3.27	0.001	0	0.807
TMT-B	2	0.10 (−0.10, 0.29)	0.98	0.326	0	0.914
Mini-Cog	1	−0.70 (−0.97, −0.43)	5.03	<0.001	0	1
AMD (wet)
MMSE	3	−0.58 (−0.77, −0.38)	5.80	<0.001	0	0.463
Animal fluency	1	−0.04 (−0.45, 0.36)	0.20	0.845	0	1
TMT-A	2	0.76 (0.13, 1.39)	2.38	0.017	78.1	0.033
TMT-B	2	0.32 (−0.04, 0.69)	1.73	0.084	45.3	0.176
Mini-Cog	1	−0.56 (−0.90, −0.22)	3.23	0.001	0	1
AMD (dry)
MMSE	3	−1.12 (−1.59, −0.64)	4.59	<0.001	48.6	0.143
Animal fluency	1	−0.89 (−1.50, −0.27)	2.84	0.005	0	1
TMT-A	2	1.23 (−0.18, 2.63)	1.71	0.087	91.8	<0.001
TMT-B	2	0.22 (−0.16, 0.61)	1.15	0.250	0	0.785
Mini-Cog	1	−0.90 (−1.21, −0.59)	5.63	<0.001	0	1

Abbreviations: AMD, age-related macular degeneration; CI, confidence interval; MMSE, mini-mental state examination; SMD, standard mean difference; TMT, trail making test.

Figure 3 Meta-analysis of the cognitive function in wet-AMD patients and controls by MMSE, Animal fluency, Mini-Cog, TMT-A and -B.

Note: Weights are from random-effects analysis.
Abbreviations: AMD, age-related macular degeneration; CI, confidence interval; MMSE, mini-mental state examination; NA, not applicable; SMD, standard mean difference; TMT, trail making test.

Figure 4 Meta-analysis of the cognitive function in dry-AMD patients and controls by MMSE, Animal fluency, Mini-Cog, TMT-A and -B.

Note: Weights are from random-effects analysis.
Abbreviations: AMD, age-related macular degeneration; CI, confidence interval; MMSE, mini-mental state examination; NA, not applicable; SMD, standard mean difference; TMT, trail making test.

Figure 5 Sensitivity analysis of the included studies for the cognitive function in patients with AMD.

Abbreviations: AMD, age-related macular degeneration; CI, confidence interval.

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