Table 3 Results for Imaging Outcome measures

Suo et al. [19] 2016

Combined cognitive training and progressive resistance training led to increased cortical thickness in posterior cingulate cortex. Cognitive training alone led to atrophy.

-

Cognitive training groups showed Group X Time interaction indicating decreased connectivity between the posterior cingulate and superior frontal lobe (F(67) = 31.7, p < 0.001) and between the posterior cingulate and the anterior cingulate cortex (F(67) = 13.9, p < 0.001)^a.

Cognitive training group (alone or combined with exercise) showed a Group X Time interaction indicating increased connectivity between hippocampus and the left superior frontal lobe compared with non-computerized cognitive training (p = 0.012)^a

Computerized cognitive training (alone and with resistance training):

Memory domain: Group X Time interaction (F(90) = 5.7, p < 0.02) showing no decline in cognitive training group compared to non-cognitive training groups^a

ADAS-Cog: No effect of cognitive training

Change in posterior cingulate grey matter correlated with improvement in the ADAS-Cog (r = 0.25, p = 0.030)^a.

Increased connectivity between hippocampus and superior frontal lobe was correlated with improved memory domain performance (r = 0.33, p = 0.005)^a

Rosen et al. [18] 2011

-

Significant increase of activation in left anterior hippocampus in experimental group compared with controls.

-

A non-significant but greater gain in memory performance in experimental group compared with control group (F(1,10) = 4.76, p = 0.054).

Change scores showed improved memory performance in intervention group compared with decrease in performance in the control group (t(10) = 2.61, p < .0027, Cohen’s d = 1.38)

Non-significant trend

showing changes in hippocampal activation correlated positively with changes in memory score on RBANS in all participants

(r = 0.49, p = 0.10, Cohen’s

d = 1.14)

Lampit et al. [16] 2015

Significant increase in grey matter density in right post-central gyrus in training group compared with a decrease in control.

Vertex-based analysis showed significant difference in rate of thickness change over time between training and control in both the left fusiform gyrus (T > 3.39) and the supramarginal and post-central gyri (T > 2.24).

-

Group x Time interaction showed functional connectivity decrease between posterior cingulate and right superior frontal gyrus in training group while functional connectivity increased in the control group (p = .006) at FU1.

Group x Time interaction showed functional connectivity increase between right hippocampus and left superior temporal gyrus in CCT, while decreased in control at first FU1 (p = .029).

No significant Group x Time interactions found for Magnetic Resonance Spectroscopy (MRS) and whole brain Diffusion Tensor Imaging (DTI)

Repeated-measured ANOVA showed improved global cognition in training group compared to control (Group X Time, F = 7.833, p = 0.003).

Effect size on Global Cognition (d = 0.94 baseline versus FU1 and d = 2.18 baseline versus FU2)

Significant positive correlation between change in grey matter density in right post-central gyrus at FU2 and change in global cognition at FU1(r = 0.647, p = .023) and FU2 (r = 0.584, p = 0.046) in both

training and control.

Inverse correlation between functional connectivity between posterior cingulate and right superior frontal gyrus at FU1 and change in global cognition at FU2 (r = −.771, p = .003).

Significant positive correlation in functional connectivity between the right hippocampus and left superior temporal gyrus at FU1 and change in global cognition at FU2 (r = 0.591, p = .043).

Belleville et al. [21] 2014

-

Single Repeated:

Alphanumeric single

task: Decreased post-

training activation in inferior and right middle frontal gyrus

(t = 5.91), left middle

frontal gyrus (t = 4.57) and left thalamus (t = 5.37).

Visual detection single

task: no change

Dual task: no change

Divided Fixed

Alphanumeric single task: no change

Visual detection single task: Decreased post-training activation in right cerebellum (t = 4.73) and right middle occipital gyrus (t = 4.68) when performing the visual detection task.

Dual task (50/50): Small increase in post-training activation in right and left middle frontal gyrus (areas 11, 47; t = 4.41 and t = 4.52 respectively).

Divided Variable

Alphanumeric single task: no change

Visual detection single task: no change

Dual task:

Significant increased activation in right middle frontal gyrus (area 10; for 20% attention allocation t = 5.35 and 50% attention allocation t = 4.78). No reduced post-training activation in 80% attention allocation.

-

Alphanumeric single task: All groups showed improved reaction time (RT; F(1,34) = 9.75, p < .001, η² = .22) and accuracy (AC; F(1,34) = 14.8, p = .001, η² = .30)

Visual detection single task: No change

Dual task (cost score) ^b:

Single repeated: No improvements in dual tasking

Divided Fixed: Reduced dual-task cost (F(1,34) = 6.97, p < .001, η² = .45)

Divided Variable: Reduced dual-task cost and were able to modify attentional priority (F(2,33) = 5.17, p < .001, η² = .34)

Single Repeated:

Alphanumeric single task: Significant positive correlation between right inferior and middle frontal gyrus activation and reaction time (r = .56, p < .05).

Divided Variable: Significant negative correlation (post training) between activation of right superior and middle frontal gyrus (Brodmann area 10) and attentional cost (r = −.55, p < .05)

Lin et al. [17] 2014

-

-

Training group: Significant increased functional connectivity in (all p’s < 0.005):

1.Left hippocampus-right inferior frontal gyrus

2.Left hippocampus-right middle frontal gyrus

3.Right hippocampus-left middle frontal gyrus

4.Right hippocampus-left inferior frontal gyrus

5.Right hippocampus-left superior frontal gyrus

6.Right hippocampus-left parietal lobe

Control group:

Significantly decreased functional connectivity (all p’s < 0.005):

1. Left hippocampus-right middle occipital gyrus

2. Right hippocampus-right posterior lobe or cerebellum

3. Right hippocampus-left superior temporal gyrus

Training group:

1. Significant improved scores on 5/7 subtests from Wechsler Memory Scale, namely: Mental control (p = 0.003), Logical memory (p < 0.001), Digits forward and backward (p = 0.014), Visual reproduction (p = 0.008), and Associated learning (p < 0.001).

2. Improved Memory quotient (p = 0.005)

3. Improved performance on Trail Making Test-A (p < 0.001)

Control group: no significant changes between baseline and 10-week scores

Training group: significant positive correlations between (all p’s < 0.001):

1. Memory quotient and functional connectivity of left hippocampus-right frontal lobe (r = 0.64)

2. Memory quotient and functional connectivity of right hippocampus-left frontal lobe (r = 0.85)

3. Memory quotient and functional connectivity of right hippocampus-left parietal lobe (r = 0.79)

4. Trail Making Test-A score and functional connectivity of left hippocampus-right frontal lobe (r = 0.94)

5. Trail Making Test-A and functional connectivity of right hippocampus-left frontal lobe (r = 0.68)

Control group: no significant correlations between cognition and functional connectivity^c

Strenziok et al. [24] 2014

-

-

Ventral Network:

Axial diffusivity (AD) in the right occipito-temporal white matter significantly increased after BF compared with a decrease after SF and RON (p < 0.05)

Dorsal Network:

Functional connectivity between right superior parietal cortex (SPC) and left posterior inferior temporal lobe (ITL) decreased in SF and increased in RON (p = 0.02).

Functional connectivity between right SPC and left anterior ITL decreased in BF and showed an increase in RON (p = 0.03)

Univariate ANOVA showed main effects of training group:

Reasoning on Everyday Problems Test:

Main effect of training group (F(2,39) = 5.34, p < 0.01, partial η² = 0.215).

BF and SF showed improved performance after training and RON showed no effect.

Spatial Working Memory:

Main effect of training group (F(2,39) = 5.03, p < 0.001, partial η² = 0.205).

SF improved performance after training, RON decreased performance, and BF showed no effect.

Matrix Reasoning:

Main effect of training group (F(2,39) = 3.40, p < 0.044, partial η² = 0.148).

Largest gains seen in BF and a smaller gain in RON. The SF group showed a decrease in reasoning after training

Cognition and White Matter Integrity

Positive correlation between change in thalamic AD and change in working memory performance in all participants (r = 0.44, p < 0.005).

Negative correlation between changes in occipito-temporal AD and everyday problem solving (r = −0.32, p < .05) and spatial working memory accuracy (r = −0.35, p < .05).

Negative correlation between changes in occipito-temporal-parietal AD and spatial working memory accuracy (r = −0.40, p < 0.05).

Cognition & Functional Connectivity

Positive correlation between changes in SPC-posterior ITL connectivity and changes in everyday problem solving time (r = −0.57, p < .001).

Lövden et al. [23] 2010

-

-

Mean Diffusivity (MD)

Group X Time interaction found for segment 1 (genu) of corpus callosum, showing a decrease in MD (t(11) = 2.39, p = .036). No changes in control group

Fractional Anisotropy (FA)

Group X Time interaction found for segment 1 of corpus callosum, showing an increase in FA (t(11) = 3.12, p = .010)

Unknown: analysis combined younger and older subsets

Unknown: analysis combined younger and older subsets

Antonenko et al. [20] 2016

Hippocampal volume: no difference pre to post training (p = 0.505)

Mean Diffusivity (MD): A significant decrease in fornix MD was found at post-training compared with pre-training (p = 0.036).

No difference in hippocampal MD from pre- to post-training (p = 0.669).

Fractional Anisotropy (FA): A non-significant increase in fornix FA was found between pre- and post-training (p = 0.114)

% Correct during training: Task performance significantly improved in a curvilinear convex manner over the 3 training days learning

- Higher increase in fornix FA from pre to post assessment was significantly related to better average recall performance on the object-location task during training, at 1-day post and follow-up (r = 0.431, p = 0.031)

- Change in fornix FA did not correlate with episodic memory performance on the control task (Rey Auditory Verbal Learning Test; p = 0.214)

- Change in fornix MD did not correlate with recall performance p = 0.728

- Change in hippocampal MD or volume did not correlate with recall performance (p = 0.688 and p = 0.758, respectively)

Heinzel et al. [22] 2014

No significant change in grey matter volume of working memory network post training (t(14)= 0.83, p = .421)

No significant 2(time)

×3(working memory

load) interaction (F = .24, p = .714, partial η² = .024).

Significant main effect of time (F = 12.68, p = .003, partial η² = .475) driven by BOLD decrease in 1-back (t = .99, p = .029).

A 2(time)×3(load) repeated measures ANOVA showed no changes in connectivity in working memory network (F(2,28) = 1.08, p = .355, partial η² = .071)

n-Back: paired t-tests showed improved performance on 1-Back (t(18) = 3.37, p = .003), 2-ack (t(18) = 7.47, p < .001), and 3-Back (t(18) = 4.86, p < .001)^d.

Repeated-measures MANOVA (factor time) showed improvements in neuropsychological measures after training. Post hoc paired t-tests showed improvements in Digit Span Fwd (t(18) = 2.97, p = 0.008), D2 test (t(18) = 6.48, p < 0.001), Digit Symbol (t(18) = 2.76, p = 0.013), Stroop Interference (t(18) = 3.28, p = 0.004), and Figural Relations (t(18) = 4.73, p < 0.001). No improvements after training were found in Digit Span Bwd, Verbal Fluency, and Raven’s SPM.^d

Non-significant trend between BOLD activation at baseline and relative improvement in Digit Span Fwd (r = .43, p = .067)