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| Study | Design study | Sample | COT | Cognitive domains trained | CCI | Intervention format | Outcome measures | fMRI protocol | Intervention fMRI results on MCI | MCI COT clinical results |
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| Rosen et al. [23] | RCT double-blind | 12 MCIs
6 COT MCI
Age/education: 70.7/16.7
6 CCI MCI
Age/education: 70.0/13.4 Petersen criteria | Computer-based auditory processing training by Posit Science Corporation | Auditory, accuracy, processing speed, immediate and working memory | Audio books, online newspaper Myst game. | Home-based computer-assisted for COT & CCI
24 sessions
5 times/week 90–100 min/session | Task-related hippocampal functional activity changes; performance at RBANs, and relationship with brain activity | Auditory verbal task with discrimination of concrete from abstract words | Increased activation on L hippocampus after COT and decreased activation in this area after CCI. L hippocampal activation was associated with immediate memory on RBANs. | COT MCI showed better gain in immediate memory performance on RBANs compared to CCI MCI. |
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| Belleville et al. [17] | CGT Single–blind | 15 COT HC Age/education: 70.0/13.4
15 COT MCI Age/education: 70.1/13.7
Petersen criteria | Visual imagery Method of loci
Face-name association
Hierarchical and semantic organization | Episodic memory and executive functions | No | Group sessions
6 sessions
1 times/week
120 min/session | Task-related whole-brain functional activity changes; performance at fMRI task, and off-scan word list recall | Verbal memory encoding and retrieval of a word list | MCI COT increased activation in R inferior parietal lobule, frontal gyrus, R cerebellum, and basal ganglia on encoding and increased activation in R/L superior temporal gyrus, L frontal, and parietal cortex on retrieval. Activation in R parietal lobule was associated with better performance on delayed word recall. | Improvement in performance on the retrieval scan task and on word list recall. Better performance on immediate recall compared with delayed recall |
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| Hampstead et al. [18] | Case series | 6 COT MCI Age/education: 73.5/15.7
Petersen criteria | Explicit memory strategy: visually identify a facial feature and then link it to a phonological cue to recall the associated name | Associative episodic memory | No | Individual sessions
5 sessions
2 weeks | Task-related whole-brain functional activity and connectivity; performance on face-name recognition off-scan task | Associative encoding of face name pairs | COT-specific activations in L temporoparietal junction, L frontal operculum, L temporal cortex, and R/L medial areas of frontal, parietal, and occipital cortices. Increased connectivity in lateral frontal and parietal regions | Improvement on memory performance for TS and US stimulus after COT. Better performance and fast reaction times in recognition of TS |
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| Hampstead et al. [20] | RCT single blind | 16 HC vs. 18 MCI 8 COT HC
Age/education: 72.1/15.8
8 CCI HC Age/education: 72.1/16.5
9 COT MCI Age/education: 71.7/17.4
9 CCI MCI Age/education: 70.8/16.8
Petersen criteria | Explicit memory strategy: identify a salient feature within the room near the object, use a verbally based “reason” that related the object to the specific feature, and then form a corresponding mental image | Associative episodic memory | Repeated exposition of stimuli | Individual sessions for COT & CCI
5 sessions
2 weeks | Task-related hippocampal functional activity; performance on-scan retrieval task | Associative encoding and retrieval of object location association task | COT aMCI showed increased activation in L hippocampal body on encoding of TS and US. Increased activation in R/L hippocampal body and tail on retrieval of TS and increased activation in R hippocampus for US | COT groups showed better performance on-scan retrieval task for TS compared to CCI groups. |
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| Balardin et al. [24] | CGT single blind | 18 COT HC Age/education: 68.25/11.19
17 COT MCI
Age/education: 69.5/9.2
17 COT MCI Age/education: 69.5/9.2
Petersen criteria | Semantic strategic training: organization of word lists into categories during encoding and retrieval according to their category | Episodic memory and executive functions | No | Individual session
1 session
30 min/session | Task-related whole-brain functional activity; performance at SR and UR word lists, recall, and relationship with brain activity | Verbal memory encoding of SR and UR word lists | COT MCI showed increased activation in frontoparietal network regions including L DLPFC and L VLPFC and decreased activations on the occipital cortex. Increased activation on R superior frontal gyrus and vmPFC cortex related to semantic strategy implementation. Better performance on strategic clustering was predictive of increased activation on OFC cortex. | Improvement on performance on word list recall and on semantic strategy implementation after COT. Better recall on the SR list compared to UR list. |
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| Lin et al. [15] | RCT single blind | 21 MCI
10 COT MCI Age/education: 1 72.9/1
11 CCI MCI Age/education: 73.1/5
Petersen criteria | Vision-based speed of processing training online program by Posit Science Corporation | Visual accuracy, processing speed attention, and working memory | Computer-based activities: online crosswords, sudoku, and solitaire games | 24 sessions
6 weeks
4 times/week 60 min/session
Home-based computer-assisted | Connectivity in DMN and CEN; performance at visual processing speed, working memory, verbal fluency, and IADL tasks | Resting state | Increased connectivity on CEN after COT. COT MCI showed increased connectivity on DMN compared to CCI MCI. | Improvement on performance on visual processing speed and attention test, and also on transfer domains tests related to working memory and IADLs after training |
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| De Marco et al. [16] | RCT single blind | 37 MCI
23 COT MCI Age/education: 73.74/8.7
14 CCI MCI Age/education: 73.74/10.5
Petersen criteria | Cognitive training package | Semantic processing, reasoning, executive functions, and episodic memory retrieval | Social interaction activities: volunteering, tour guiding, attending a club, or gardening | Home-based computer-assisted
20 sessions
5 times/week 60–90 min/session | Connectivity in DMN - performance at CCRI and relationship with brain activity | Resting State | Increased connectivity on Precuneus – Cuneus after COT. Enhances on CCRI were associated with increased connectivity on parietal DMN | No improvement verified on neuropsychological measures applied |
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