Table 1.
Overview of the above-mentioned studies investigating the relationship between BDNF and cognition.
| Study | Participants | Parameters | Results |
|---|---|---|---|
| Castrén et al. (84) | Animal study (rats) | Hippocampal mRNA expression of BDNF (among others) before and after induction of long-term potentiation (LTP) through stimulation of the perforant pathway. | Increase of BDNF mRNA in granular neurones of the dentate gyrus of both hemispheres by unilateral stimulation. |
| Cerasa et al. (91) | 29 patients with RRMS, 32 healthy controls (HC) | Effect of Val66Met polymorphism on brain activity during spatial working memory task measured by fMRI | Increased activation of the parieto-prefrontal network and decreased activation of the ventro-medial-prefrontal cortex and hippocampus in healthy controls, no effect in RRMS-patients. |
| Ehling et al. (95) | 19 patients with RRMS (12 treated with glatiramer acetate, 7 treatment-naïve) | Serum BDNF over 24 months | No difference between patients treated with glatiramer acetate and treatment-naïve patients and no change of BDNF serum levels over time |
| Engin et al. (87) | Animal study (mice) | Effect of α5-containing GABAa receptor knockout in dentate gyrus on cognition | Reduced tonic inhibition in knockout micee resulting in similar or better performance of memory tasks Impairment in cognitive tasks requiring formation of new/overwriting old circuits |
| Falkenberg et al. (85) | Animal study (rats) | Association of BDNF with motor activity, environment and cognition | Association of higher expression of BDNF mRNA in hippocampus with improved spatial memory and enriched environment |
| Fera et al. (92) | 26 RRMS patients without cognitive impairment, 25 healthy controls | Effect of Val66Met polymorphism on hippocampal function in fMRI during episodic memory task | Higher activity parahippocampal, in left posterior hippocampus and left posterior cingulate cortex during encoding and retrieval as well as higher connectivity between hippocampus and posterior cingulate cortex during retrieval in Val homozygote RRMS patients opposite effects in healthy controls |
| Giordano et al. (90) | 100 patients with progressive MS | Effects of BDNF and NTRK2 genes on motor recovery | In Val66Met carriers greater motor improvement after rehabilitation |
| Hakansson et al. (88) | 23 healthy participants (19 fully participated) | 35 min of aerobic exercice at moderate level, cognitive training through a computerized working memory training program or mindfulness practice using an app | Increase of serum BDNF levels after aerobic training, but not after cognitive training oder mindfulness practice Positive association of serum BDNF levels and working memory function |
| Hariri et al. (81) | 64 healthy participants | Association of Val66met genotype and hippocampal activity in fMRI during declarative memory task | Decreased hippocampal activity in Val66Met carriers compared to Val66Val during encoding and retrieval processes |
| Hulst et al. (78) | 34 patients with MS without cognitive impairment, 16 patients with MS with cognitive impairment, 30 healthy controls | fMRI during episodic memory task | Bilaterally increased brain activity parahippocampal and left anterior cingulate gyrus in patients without cognitive impairment during encoding, less brain activity para−/hippocampal and in the prefrontal cortex in cognitively impaired patients, but increased activity in posterior cingulate gyrus and left precuneus No structural differences between patients with and without cognitive impairment |
| Islam et al. (70) | Animal study (mice) | Effect of BDNF on multipotent neural stem cells | Modulation of neurogenesis by mainly mediated via TrkB, a.o. by regulating neural replacement, neural loss while |
| Loprinzi (73) | Metaanalysis | 52 studies—26 animal studies, 15 studies in humans | All animal studies showed improvement of memory, 97% increase of BDNF with 8 studies showing BDNF as mediator of the positive association of training and cognition. 44% of the studies in humans found an positive association of BDNF and cognitive improvement with 40% of these assuming BDNF as mediator |
| Liguori et al. (45) | 36 inactive patients with RRMS and 37 healthy controls | Effect of Val66Met polymorphism and BDNF levels on patients with RRMS over 24 months | Higher BDNF levels in patients with RRMS compared to healthy controls, regardless immunotherapy No correlation of Val66Met polymorphism with clinical or MRI characteristics |
| Linnarsson et al. (75) | Animal study (mice) | Effect of deletion of one copy of the BDNF gene | Significant cognitive impairment |
| Ninan et al. (83) | Animal study (mice) | Properties of hippocampal CA3-CA1 synapses of BDNF Met/Met mice and matched wild-type mice | Normal glutamatergic transmission, but decreased NMDA receptor-dependent transmission and long-term potentiation in BDNF met/met mice |
| Patanella et al. (77) | 30 patients with RRMS | PBMC production of BDNF, TNF-alpha, IL10 and IL6 | Association of low BDNF levels with worse performance in divided attention and visual scanning tasks Association of high IL-6 level with low mini mental state examination scores |
| Prokopova et al. (36) | 19 treatment naïve patients with MS, 19 healthy controls | BDNF plasma level, cognitive function as well as effect of mild stress (Stroop test) on neuroendocrine activation in early phase of multiple sclerosis | Association of cognitive impairment in male patients with MS with decreased BDNF plasma levels Higher anxiety, depression and poorer performance in Stroop test in patients with MS |
| Ramasamy et al. (60) | 188 patients with MS | Effect of Val66Met polymorphism on regional grey matter in MRI | Higher grey matter volume in the cingulate of patient with MS with Val66Met polymorphism compared to Val66Val patients |
| Vigers et al. (76) | Animal study (mice) | Quantification of dendritic spines in cortical neurons in late-onset forebrain-specific BDNF knockout mice | Smaller brain volume in knockout mice compared to wild-type mice with impairment in spatial learning and increased depression |
| Yalachkov et al. (86) | 36 patients with RRMS, PPMS, CIS | Effect of BDNF on disability and cognition after relapse | Association of disability improvement with higher serum BDNF levels and cognitive improvement with higher BDNF levels in CSF at baseline with a positive correlation between serum BDNF and EDSS improvement and CSF-BDNF with z-score change in cognitive tests |
| Zivadinov et al. (1) | 209 patients with MS (108 with cognitive testing) | Effect of Val66Met polymorphism on brain morphometry and functionality measured by MRI and cognitive testing | Positive association of Val66Met polymorphism with normalized grey matter volume and negative association with T2 lesion volume only trend towards a positive association |