Declínio da memória episódica relacionado à idade e o papel da beta-amiloide: uma revisão sistemática

Souto, Jandirlly Julianna; Silva, Gabriella Medeiros; Almeida, Natalia Leandro; Shoshina, Irina Ivanovna; Santos, Natanael Antonio; Fernandes, Thiago Paiva

doi:10.1590/1980-57642021dn15-030002

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Original Article • Dement. neuropsychol. 15 (03) • Jul-Sep 2021 • https://doi.org/10.1590/1980-57642021dn15-030002 linkcopiar

Declínio da memória episódica relacionado à idade e o papel da beta-amiloide: uma revisão sistemática

Autoria SCIMAGO INSTITUTIONS RANKINGS

O envelhecimento tem sido associado a um declínio funcional da memória episódica (ME). Algo ainda sem resposta é se o declínio da ME ocorre mesmo no envelhecimento saudável e se esse declínio pode estar relacionado à deposição de Aβ no hipocampo.

Objetivo: Nosso objetivo principal foi investigar os dados sobre a relação entre a memória episódica e a deposição de Aβ no envelhecimento saudável.

Métodos: Nós buscamos nas bases de dados Cochrane, MEDLINE, Scopus, Web of Science e nas listas de referências dos estudos dos últimos 10 anos. A busca inicial nas bases de dados identificou 517 estudos. Após a triagem de título, resumos, palavras-chave e referências, 56 estudos atenderam aos critérios de inclusão.

Resultados: O resultado geral revelou que o aumento de Aβ estava relacionado ao menor volume do hipocampo e pior desempenho em testes de ME. Em resumo, os resultados da presente revisão sistemática revelaram que altos níveis de Aβ podem estar relacionados ao declínio de ME e conversão progressiva para a Doença de Alzheimer.

Conclusões: Aqui, discutimos os pontos fortes e as limitações dos testes e técnicas para investigar a deposição ME e Aβ, bem como questões metodológicas e direções futuras.

Palavra-chave:
memória; memória episódica; envelhecimento; envelhecimento saudável; peptídeos beta-amiloides; revisão sistemática

Authors	Sample	Aβ technique	Others techniques	Regions of interest	EM task	Main findings	PEDro	AXIS
Chételat et al.⁵⁸	93	PiB-PET	N/A	Gray matter, white matter, and CSF	CVLT-II And RCFT	EM involvement is related to Aβ deposition, especially in the temporal neocortex, and regardless of hippocampal atrophy	4	15
Lim et al.⁵⁹	141	PiB-PET	Blood exam	Cerebellum	CVLT-II and PAL	High Aβ showed significantly greater decline in verbal and visual EM at 18 months	5	15
Marchant et al.⁶⁰	54	PiB-PET	MRI and FLAIR	CSF, WMH, frontal, parietal, and temporal cortex, posterior cingulate, and precuneus	CVLT and MAS	Aβ did not explain changes in EM	5	16
Perrotin et al.⁶¹	48	PiB-PET	MRI	Medial PFC/ACC, precuneus/PCC/ICC, and temporal lobe	CVLT-II and WMS-R	High Aβ performed worse than low Aβ just on the EM measure test CVLT	5	15
Rodrigueet al.⁶²	137	F-florbetapir PET	Blood exam	–	HVLT and CANTAB	Aβ subgroup has no significant association with EM	5	16
Adamczuk et al.⁶³	64	F-flutemetamol PET	MRI	Frontal, parietal, anterior cingulate, precuneus/posterior cingulate, and lateral temporal	BNT, AVF, and RPM	Aβ and EM were negatively correlated only in the BDNF group of met +ve/APOE ε 4 +ve	5	14
Doré et al.⁶⁴	133	PiB-PET	MRI	Gray matter, white matter, CSF, and cerebellum	CVLT-II and LMT-II	No significant differences in EM between the Aβ- and Aβ+ groups. There was a significant reduction in the precuneus and hippocampus	5	13
Ellis et al. ⁶⁵	178	PiB-PET	Blood exam	Frontal, superior parietal, lateral temporal, lateral occipital, and anterior and posterior cingulate	CVLT-II, LMR, and RCFT	High Aβ showed greater decline in EM	5	14
Hedden et al.⁶⁶	168	PiB-PET	MRI and FLAIR	Frontal, lateral, parietal, temporal, and retrosplenial cortices	FNAME, STSRT, and MCT	Aβ burden and WMH had distinct cognitive profiles. Aβ was associated with a decline in EM	5	14
Lim et al.⁶⁷	234	PiB-PET	Blood exam	Cerebellar cortex, frontal, superior parietal, lateral temporal, lateral occipital, and anterior and posterior cingulate	CVLT-II and RCFT	No differences were observed between HC high and low Aβ groups	4	15
Sperling et al.⁶⁸	78	Florbetapir F 18 PET	MRI	Grey matter, frontal, temporal, parietal cortices, anterior cingulate, and posterior cingulate	WLM-I, WLM-D, and DSS	The highest SUVr correlated with the lowest immediate memory	8	16
Wirth et al.⁶⁹	38	PiB-PET	FDG-PET and MRI	Frontal, temporal, parietal, and anterior/posterior cingulate	LMR and VRT	PiB positivity was associated with nonmemory decline	3	14
Lim et al.⁷⁰	225	PiB-PET	Blood exam	Cerebellar cortex	CVLT-II	High Aβ HC and MCI groups showed moderate decline in EM	7	16
Lim et al.⁷¹	413	PiB-PET	Blood exam	Cerebellar cortex	LMR, CVLT-II, RCFT, and COCLT	Aβ+ showed greater decline on the verbal EM and visual EM	7	16
Ossenkoppele et al. ⁷²	81	PiB-PET	FDG-PET and MRI	Gray matter, posterior cingulate cortex, bilateral angular gyri, and bilateral inferior temporal gyri	CVLT and VRT	Aβ was associated with higher metabolic activity and lower visual episodic memory scores	5	15
Villeneuve et al.⁹	67	PiB-PET	MRI	Right frontal, parietal, temporal, occipital, and precuneus	MAS	High Aβ was associated with cortical thinning and lower performance of EM	5	16
Amariglio et al.⁷³	257	PiB-PET	FDG-PET and MRI	Hippocampal volume	FNAME, STSRT, and MCT	Aβ and ND biomarkers predict biggest changes in EM	8	16
Aschenbrenner et al.⁷⁴	238	PiB-PET	Cerebrospinal fluid assessment	Orbitofrontal, parietal, frontal, frontal, and temporal	SRT	EM was not correlated with levels of Aβ	5	16
Lim et al. ⁷⁵	227	PiB-PET	MRI	Gray matter, white matter, cerebrospinal fluid, and hippocampus	OCL	Aβ+ CN and MCI groups showed decline on the EM measures	6	15
Lim et al. ⁷⁶	333	PiB-PET	Blood exam	Cerebellar cortex	LMR, CVLT-II, RCFT, and COCLT	Aβ+ ɛ4+ individuals showed cognitive decline across all domains. Aβ+ ɛ4− individuals showed faster decline only in verbal EM	8	17
Mander et al.⁷⁷	26	PiB-PET	fMRI and EEG	Hippocampus and mPFC	TWPT	Aβ impairs sleep and has indirect implications for EM decline	8	18
Mattsson et al.⁵²	743	Florbetapir PET	FDG-PET and MRI	Gray matter	LMR and AVLT	Aβ+ was associated with lower EM scores	4	16
Pietrzak et al.⁷⁸	333	PiB-PET	–	–	CVLT and LMR	High Aβ was associated with a subtle decrease in EM	8	16
Racine et al.⁷⁹	175	Electrochemiluminescence	MRI and FLAIR		RAVLT and WMS-RLM	High levels of Aβ and higher rates of decline in EM tests	4	18
Wang et al.⁸⁰	188	CSF collection	MRI	Entorhinal cortex, fusiform gyrus, inferior, middle, and superior temporal gyri, superior and inferior parietal lobules, posterior cingulate gyrus, and precuneus	N/A	Reduced CSF Aβ42 was related to poorer performance on EM	3	16
Wang et al.⁸¹	263	PiB-PET	Blood exam	–	LMIRD and WLIRD	For asymptomatic carriers, Aβ burden was predictive of longitudinal decline in EM	8	15
Bischof et al.⁸²	147	Florbetapir PET	–	–	HVLT and CANTAB	Higher Aβ may have an influence on EM, especially between 30 and 55 years of age	7	16
Lim et al.⁸³	423	PiB-PET	Blood exam	Cerebellar cortex	CVLT, LMR, and RCFT	Significantly increased decline in EM in Aβ+ APOE ε4 carriers	7	17
Mielke et al.⁸⁴	465	PiB-PET	–	–	AVLT, WMS-RLM, WMS-RVR, and CogState	High Aβ was not associated with changes in EM	5	16
Song et al.⁸⁵	82	F18-AV-45-florbetapir PET	MRI and fMRI	–	HVLT and CANTAB	Aβ had no effects or interaction in EM	4	14
Ayton et al.⁸⁶	117	PiB-PET		Hippocampus	CVLT and RCFT	Aβ pathology and higher levels of quantitative susceptibility of the hippocampus predicted accelerated deterioration in EM	6	17
Boots et al.⁸⁷	140	PiB-PET	–	–	RAVLT	BDNF was associated with a decline in EM and was exacerbated by a greater Aβ load	6	17
Farrell et al.⁸⁸	174	F-florbetapir PET	–	–	–	Aβ+ and the increase in baseline SUVR predicted an increasing decline in EM	7	16
Lim et al.⁸⁹	989	PiB-PET	Blood exam and MRI	Hippocampus volume	CVLT-II, LMR, and RCFT	APOEɛ4 homozygotes (ɛ4/ɛ4) showed significantly worse EM and higher Aβ levels than heterozygous ɛ4	5	14
Lim et al.⁹⁰	446	PiB-PET	Blood exam	Hippocampus volume	LMR, CVLT-II, and RCFT	Aβ- Val and Aβ+ Val homozygotes showed a decline in EM	4	17
Pietrzak et al.⁹¹	416	PiB-PET	MRI	Plasmatic cortisol	CVLT-II, LMR, and RCFT	Older Aβ+ adults experienced a faster decline in EM	3	16
Vogel et al.⁹²	136	PiB-PET	–	–	N/A	Decline in EM was observed only when cognitive decline and Aβ were present	7	17
van Bergen et al.⁹³	116	Flutemetamol PET	MRI	–	MMSE and VLMT	Local correlation between iron and β-amyloid is related to levels of cognitive performance	5	18
Bilgel et al.⁹⁴	171	PiB-PET	MRI	Hippocampus	CVLT and BVRT	Amyloidosis or hippocampal atrophy had longitudinal declines in EM verbal and learning	3	17
Farrell et al.⁹⁵	126	Florbetapir PET	MRI	Hippocampal and cortical volume	HVLIR and CANTAB	Decline in EM and increase in Aβ accumulation	7	18
Jansen et al.⁹⁶	2,908	PiB-PET	–	–	VWLT	Aβ positivity was associated with low memory	6	17
Leal et al.⁹⁷	71	PiB-PET	–	–	WMS - II and CVLT	Higher levels of Aβ are associated with the decline of EM	5	16
Lim et al.⁹⁸	447	PiB-PET	MRI	–	RAVLT	Worsens in EM of Aβ+ than Aβ− and may exacerbate with age	5	18
Mecca et al.⁹⁹	45	PiB-PET	MRI	Gray matter	N/A	In middle-aged individuals, Aβ load does not affect EM performance	6	18
Ko et al.¹⁰⁰	762	PiB-PET	–	–	RAVLT and ADAS-Cog	EM was a predictor for Aβ positivity	6	17
Pothier et al.¹⁰¹	65	F-florbetapir PET	–	–	FCSRT	Significant difference for EM over time, with better performance in Aβ- compared with Aβ+.	8	19
Rabin et al.¹⁰²	253	PiB-PET	MRI	Fornix	WMS-RLM, FCSRT, and STSRT	Elevated Aβ load has been associated with a faster decline in EM over time	4	17
Rahayel et al.¹⁰³	104	PiB-PET	MRI	–	WMS - III and RAVLT	Higher Aβ had worse episodic memory	5	17
Yu et al.¹⁰⁴	148	SRM	–	–	–	Aβ is unrelated with decline in EM	8	19
Dupont et al.¹⁰⁵	104	PiB-PET	MRI	WMHs	LMT -II	Deposition Aβ predicts weaker EM performance	8	18
Joannette et al.¹⁰⁶	104	PiB-PET	MRI	–	RAVLT	EM performance is associated with Aβ load	6	18
Lim et al.¹⁰⁷	213	PiB-PET	Blood exam	–	CVLT and RAVLT	Aβ is related to the decline of EM	7	16
Lindbergh et al.²³	149	Florbetapir PET		Gray matter	RAVLT and RCFT	Women with high Aβ are more vulnerable to declining EM than men	6	18
Squarzoni et al.¹⁰⁸	108	PiB-PET			RAVLT	Aβ load and poorer memory performance were detected only in stages +	6	16
Busatto Filho et al.¹⁰⁹	124	PiB-PET	MRI and FDG-PET	Hippocampal subregions	AVLT and SCPT	Subicular volumes were inversely correlated with the degree of Aβ deposition. Verbal EM scores were significantly lower in both (N)+ groups	5	15
Han et al.¹¹⁰	154	PiB-PET	MRI	VL and WS	SENAS	Aβ influence retention in EM change	6	19

6-TSRT: 6-Trial Selective Reminding Test; Aβ: amyloid-β; AD: Alzheimer’s disease; ADAS-Cog: Alzheimer’s Disease Assessment Scale–Cognitive Subscale; APOE: apolipoprotein E; AVF: Animal Verbal Fluency Test; AVLT: Auditory Verbal Learning Test; BDNF: brain-derived neurotrophic factor; BNT: Boston Naming Test; BVRT: Benton Visual Retention Test; CAA: cerebral amyloid angiopathy; CANTAB: Cambridge Neuropsychological Test Automated Battery; CSF: cerebrospinal fluid; COBT: Cogstate One Back Task; COCLT: Cogstate One Card Learning task; CVLT-II: California Verbal Learning Test, second edition; DMST: Delayed Matching-to-Sample Task; DTI: diffusion tensor imaging; EEG: electroencephalogram; ELISA: enzyme-linked immunosorbent assay; EM: episodic memory; FCSRT: Free and Cued Selective Reminding Test; FDG: fluorodeoxyglucose; FLAIR: fluid attenuation inversion recovery; fMRI: functional magnetic resonance imaging; FNAME: Face–Name Associative Memory Exam; FNET: Face–Name Experimental Task; FSRT: Free and Selective Reminding Test; HVLIR: Hopkins Verbal Learning Immediate Recall; HVLT: Hopkins Verbal Leaning Task; PiB-PET: Pittsburgh compound B positron emission tomography; IA: immunosorbent assay; LMT-II: Logical Memory Test, second edition; LMR: Logical Memory Recall; LMIR: Logical Memory Immediate Recall and Delayed Recall; MAC-Q: Memory Complaint Questionnaire; MAS: Memory Assessment Scale; MBT: Memory Binding Test; MMSE: Mini Mental State Examination; MPRAGE: magnetization-prepared rapid gradient echo; MRI: magnetic resonance imaging; MCT: Memory Capacity Test; mPFC: medial prefrontal cortex; MR: magnetic resonance; MTL: medial temporal lobe; N/A: no data available; OCL: One Card Learning; PAL: paired-associate learning; P-tau: tau pathology; RAVLT: Rey Auditory Verbal Learning Test; RCFT: Rey Complex Figure Test; ROCF: Rey-Osterrieth complex figure; RPM: Raven’s Progressive Matrices; SCC: subjective cognitive concerns; SCPT: Short Cognitive Performance Test; SENAS: Spanish and English Neuropsychological Assessment Scale; SMD: subjective memory decline; SRM: selected reaction monitoring; SRT: Selective Reminding Test; STSRT: Six-Trial Selective Reminding Test; SUVR: neocortical standardized uptake value ratio; TMADA: TaqMan allelic discrimination assay; TWPT: the word-pairs task; VPATS: Visual Paired Associates Total Score; VL: vascular load; VRM: verbal recognition memory; VRT: Visual Reproduction test; VWLT: Verbal Word Learning Test; WAIS: Wechsler Adult Intelligence Scale; WLM-V: Wechsler Logical Memory–Delayed Recall; WM: working memory; WMS-RLM: Wechsler Memory Scale-Revised Logical Memory; WMS-RVR II: Wechsler Memory Scale-Revised Visual Reproductions II; WLIRD: Word List Immediate Recall and Delayed Recall; WLM-I: Wechsler Logical Memory I and II Story A Immediate; WMH: white matter hyperintensities.

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