The influence of n-3 polyunsaturated fatty acids on cognitive function in individuals without dementia: a systematic review and dose–response meta-analysis

Suh, Seung Wan; Lim, Eunji; Burm, Suh-Yuhn; Lee, Hyungji; Bae, Jong Bin; Han, Ji Won; Kim, Ki Woong

doi:10.1186/s12916-024-03296-0

Table 1 Characteristics of included studies

From: The influence of n-3 polyunsaturated fatty acids on cognitive function in individuals without dementia: a systematic review and dose–response meta-analysis

Study (year)	Country	Group	Age Mean (SD)	Female (%)	N	Duration (month)	n-3 PUFA (mg/day)	Cognitive measures used	Corresponding domain	Notes	Summary RoB
Andrieu (2017) [53]	France	DHA, EPA	75.6 (4.7)	64	320	36	1025	MMSE, FCSRT, CNT, DSST, TMT-A	GLO, MEM, EF, PS, ATT		Low
Andrieu (2017) [53]	France	Placebo	75.1 (4.3)	66	325	36	1025	MMSE, FCSRT, CNT, DSST, TMT-A	GLO, MEM, EF, PS, ATT		Low
Arellanes (2020) [36]	USA	DHA	68.5 (58,90)^*	89	15	6	2152	MoCA, CVLT, TMT-B, TMT-A	GLO, MEM, EF, ATT	CN at baseline	Unclear
Arellanes (2020) [36]	USA	Placebo	69 (58,79)^*	73	14	6	2152	MoCA, CVLT, TMT-B, TMT-A	GLO, MEM, EF, ATT	CN at baseline	Unclear
Bischoff-Ferrari (2020) [54]	Europe	DHA, EPA	74.7 (4.3)	62.3	1073	12, 24, 36	990	MoCA	GLO		Low
Bischoff-Ferrari (2020) [54]	Europe	Placebo	75.2 (4.6)	61.2	1084	12, 24, 36	990	MoCA	GLO		Low
Bo (2017) [45]	China	DHA, EPA	71.8 (5.68)	40.9	44	6	1200	BCAT, RM, MAE, PCT, SIE	GLO, MEM, EF, PS, VSF	MCI at baseline	Unclear
Bo (2017) [45]	China	Placebo	70.5 (6.82)	40.5	42	6	1200	BCAT, RM, MAE, PCT, SIE	GLO, MEM, EF, PS, VSF	MCI at baseline	Unclear
Chew (2015) [51]	USA	DHA, EPA	72.7 (7.7)	58.8	1226	12	1000	TICS	GLO		Low
Chew (2015) [51]	USA	Placebo	72.7 (7.8)	56.2	1235	12	1000	TICS	GLO		Low
Dadova (2022) [55]	Czech Republic	DHA, EPA	70.8 (3.6)	100	27	4	230	POBAV	MEM	Only women	Unclear
Dadova (2022) [55]	Czech Republic	Placebo	71.2 (4.0)	100	25	4	230	POBAV	MEM	Only women	Unclear
Dangour (2010) [52]	UK	DHA, EPA	74.7 (2.5)	46.6	376	24	700	GCF, CVLT, VF, SLM, DSF	GLO, MEM, EF, PS, ATT		Low
Dangour (2010) [52]	UK	Placebo	74.6 (2.7)	43.4	372	24	700	GCF, CVLT, VF, SLM, DSF	GLO, MEM, EF, PS, ATT		Low
Geleijnse (2012) [56]	Netherlands	DHA, EPA	69.2 (5.4)	33	627	10	400	MMSE	GLO		Low
Geleijnse (2012) [56]	Netherlands	Placebo	68.9 (5.4)	20	638	10	400	MMSE	GLO		Low
Hashimoto (2016) [49]	Japan	DHA	87.6 (3.3)	88.4	39	6, 12	1720	MMSE	GLO		Unclear
Hashimoto (2016) [49]	Japan	Placebo	89.6 (5.1)	84.4	27	6, 12	1720	MMSE	GLO		Unclear
Hashimoto (2021) [37]	Japan	ALA	71 (65, 83)^*	54.8	35	12	4000	FAB	EF	CN at baseline	High
Hashimoto (2021) [37]	Japan	Placebo	71 (64, 84)^*	51.5	24	12	4000	FAB	EF	CN at baseline	High
Howe (2018) [57]	Australia	DHA, EPA	63.2 (1.6)	31.6	19	5	2000	Corresponding Z scores (See Table S2)	GLO, EF, PS	Borderline hypertensive adults	Low
Howe (2018) [57]	Australia	Placebo	64.1 (2.3)	31.6	19	5	2000	Corresponding Z scores (See Table S2)	GLO, EF, PS	Borderline hypertensive adults	Low
Ichinose (2021) [38]	Japan	DHA, EPA	69.1 (5.3)	53.8	26	12	434 (297, 137)	MMSE	GLO	CN at baseline	Low
Ichinose (2021) [38]	Japan	Placebo	69.1 (4.9)	55.6	27	12	434 (297, 137)	MMSE	GLO	CN at baseline	Low
Kuszewski (2020) [58]	Australia	DHA, EPA	65.8 (1.4)	53	26	4	2400	RAVLT, Cognitive flexibility	MEM, EF		Low
Kuszewski (2020) [58]	Australia	Placebo	65.8 (1.4)	56	26	4	2400	RAVLT, Cognitive flexibility	MEM, EF		Low
Lee (2013) [46]	Malaysia	DHA, EPA	66.4 (5.1)	82.4	17	6, 12	1750	Corresponding Z scores (see Table S2)	MEM, EF, PS, VSF	MCI at baseline	Low
Lee (2013) [46]	Malaysia	Placebo	63.5 (3.0)	72.2	18	6, 12	1750	Corresponding Z scores (see Table S2)	MEM, EF, PS, VSF	MCI at baseline	Low
Macpherson (2022) [59]	Australia	DHA, EPA	70.0 (6.3)	70	69	6	1500	MoCA, TMT-B, CPF-z, TMT-A	GLO, EF, PS, ATT	Intervened only 6 months. Next 6 months was without n-3 PUFA	Low
Macpherson (2022) [59]	Australia	Placebo	70.5 (5.9)	70	72	6	1500	MoCA, TMT-B, CPF-z, TMT-A	GLO, EF, PS, ATT		Low
Mengelberg (2022) [47]	New Zealand	DHA, EPA	72.3 (6.2)	53	30	12	1842	RTot, RDM, TMT-B, DSF, RVC	GLO, MEM, EF, ATT, VSF		Low
Mengelberg (2022) [47]	New Zealand	Placebo	734. (7.0)	63	30	12	1842	RTot, RDM, TMT-B, DSF, RVC	GLO, MEM, EF, ATT, VSF		Low
Ogawa (2023) [39]	Japan	ALA	71.9 (3.7)	46.7	30	3	2200	MMSE, WMSR-VM, LF, WAIS-PSI, WMSR-AC, WAIS-PRI	GLO, MEM, EF, PS, ATT, VSF		Low
Ogawa (2023) [39]	Japan	Placebo	72.1 (4.3)	53.3	30	3	2200	MMSE, WMSR-VM, LF, WAIS-PSI, WMSR-AC, WAIS-PRI	GLO, MEM, EF, PS, ATT, VSF		Low
Power (2022) [40]	Ireland	DHA, EPA	69.0 (4.4)	56.7	28	24	520	RTot, SWM, SRT,	GLO, EF, PS	CN at baseline	Low
Power (2022) [40]	Ireland	Placebo	69.8 (3.7)	70.0	22	24	520	RTot, SWM, SRT,	GLO, EF, PS	CN at baseline	Low
Sala-Vila (2020) [50]	USA	ALA	69.4 (3.8)	67.4	324	6	1206	RAVLT, SF, SDMT, TMT-A, block design	MEM, EF, PS, ATT, VSF	Constituents were determined by FoodData Central^** CN at baseline	High
Sala-Vila (2020) [50]	USA	Placebo	68.9 (3.5)	68.5	312	6	1206	RAVLT, SF, SDMT, TMT-A, block design	MEM, EF, PS, ATT, VSF		High
Sinn (2012) [48]	Australia	DHA	74.2 (7.0)	28	16	6	1950/1830	ILFC	EF	MCI at baseline	Unclear
		EPA	74.9 (5.1)	18	13
		Placebo	73.0 (4.0)	53	15
Tokuda (2020) [42]	Japan	DHA, EPA	67.8 (0.8)	66.7	27	6	400	WMS-verbal delayed, VF, TMT-A	MEM, EF, ATT	CN at baseline	Low
Tokuda (2020) [42]	Japan	Placebo	67.7 (1.1)	52.38	21	6	400	WMS-verbal delayed, VF, TMT-A	MEM, EF, ATT	CN at baseline	Low
Valls-Pedret (2015) [43]	Spain	ALA	66.7 (5.3)	48.2	112	36	402.225	MMSE, RAVLT, VF, DSF	GLO, MEM, EF, ATT	Constituents were determined by FoodData Central^** CN at baseline	Unclear
Valls-Pedret (2015) [43]	Spain	Placebo	67.9 (5.4)	52.8	127	36	402.225	MMSE, RAVLT, VF, DSF	GLO, MEM, EF, ATT		Unclear
van de Rest (2008) [60]	Netherlands	DHA, EPA	69.9 (3.4)	45	96	3.25, 6.5	400, 1800	Corresponding Z scores (see Table S2)	MEM, EF, ATT		Low
van de Rest (2008) [60]	Netherlands	Placebo	70.1 (3.7)	44	103	3.25, 6.5	400, 1800	Corresponding Z scores (see Table S2)	MEM, EF, ATT		Low
Yurko-Mauro (2010) [44]	USA	DHA	70 (9.3)	23.14	219	6	300	MMSE, VRM, SOC	GLO, MEM, EF	CN at baseline	Unclear
Yurko-Mauro (2010) [44]	USA	Placebo	70 (8.7)	24.69	218	6	300	MMSE, VRM, SOC	GLO, MEM, EF	CN at baseline	Unclear

ATT attention, ALA alpha-linolenic acid, BCAT Basic Cognitive Aptitude Test, CN cognitively normal, CNT Category Naming Test, CPF-z Z score of Cogstate psychomotor function, CVLT California Verbal Learning Test, DHA docosahexaenoic acid, DSB Digit Span Backward, DSF Digit Span Forward, DSST Digit Symbol Substitution Test, EF executive function, EPA eicosapentaenoic acid, FAB frontal assessment battery, FCSRT Free and Cued Selective Reminding Test, GLO global cognition, GCF Global Cognition Function, ILFC Initial Letter Fluency Change, LM lexical fluency, MAE Mental Arithmetic Efficiency, MCI mild cognitive impairment, MEM episodic memory, MMSE Mini-Mental State Examination, MoCA Montreal Cognitive Assessment, PCT Perceptual Speed, POBAV Pojmenování OBrázků A jejich Vybavení (Picture naming and their recall), PS Processing Speed, RAVLT Rey Auditory Verbal Learning Test, RBANS Repeatable Battery for the Assessment of Neuropsychological Status, RDM delayed memory of RBANS, RM recognition memory, RVC visuospatial/constructional of RBANS, SDMT Symbol Digit Modalities Test, SF semantic fluency, SIE Space Imagery Efficiency, SLM Symbol Letter Modality, SOC Stockings of Cambridge, SRT simple reaction time, SWM spatial working memory, RTot total score of RBANS, TICS Telephone Interview for Cognitive Status, TMT-A Trail Making Test-A, TMT-B Trail Making Test-B, VF verbal fluency, VRM Verbal Recognition Memory, WAIS-PRI Wechsler Adult Intelligence Scale-perceptual reasoning index, WAIS-PSI Wechsler Adult Intelligence Scale-processing speed index, WMS Wechsler memory scale, WMSR-AC Wechsler memory scale revised-attention/concentration, WMSR-VM Wechsler memory scale revised-verbal memory
^*median (min, max); ^**From U.S. Department of Agriculture (https://fdc.nal.usda.gov/)

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