|
| Study | Participants
(mean age ± SD, years)—M/F | VCI subtype | Diagnostic criteria | MRI correlates | CNS active
drugs | TMS technique/type of coil/muscle(s) | Main TMS findings | Translational value |
|
Alagona
et al. [80] | 20 VCI patients (71.80 ± 9.37)—8/12
20 AD patients (72.20 ± 7.53)—7/13
20 controls (68.55 ± 7.96)—8/12 | Subcortical ischemic VaD | NINDS-AIREN
NINDS-ADRDA | Subcortical lacunes and/or multiple involvement of the inner white matter | NR | Single-pulse TMS/circular coil/first dorsal interosseus | ↓ rMT in VCI (++) and AD (+)
= MEP/CMAP
= CSP | Increased cortical excitability in both subcortical ischemic VaD and AD compared to healthy controls (especially VaD versus controls). |
|
Di Lazzaro
et al. [81] | 12 VCI patients (70.9 ± 9.6)—8/4
12 AD patients (69.3 ± 7.3)—NR
12 controls (73.1 ± 5.4)—NR | Subcortical ischemic VaD | NINDS-AIREN
NINDS-ADRDA | Small-vessel
disease with
multiple lacunar infarcts (<2 cm in size) | No | Single-pulse TMS + SAI protocol/
figure-of-eight coil/first dorsal interosseous | = rMT, aMT
= SAI in VaD
↓ SAI in AD (abnormal SAI in 75% of AD and in 25% of VaD patients) | Normal central
cholinergic circuit
functioning in most of the patients with subcortical ischemic VaD in contrast with those with AD. |
|
Nardone
et al. [82] | 20 patients (70.9 ± 4.4)—12/8
25 controls (71.8 ± 5.6)—14/11 | Subcortical ischemic VaD | NINDS-AIREN | 9 with
predominant lacunar
infarctions,
11 with predominant WMLs | No | Single-pulse and paired-pulse
TMS + SAI
protocol/
figure-of-eight coil/first dorsal interosseous | ↓ SAI in VaD
= rMT, aMT
= CMCT
= CSP
= SICI, ICF | Mean cholinergic activity significantly reduced in patients, although
individual data varied widely (from normal to markedly reduced). |
|
Manganelli
et al. [83] | 10 patients (70.9 ± 4.4)—5/5
10 controls (71.8 ± 5.6)—5/5 | CADASIL | Mutation in the exon 19 Notch3 gene | Bilateral WMLs with involvement of the external capsule | NR | Single-pulse TMS + SAI protocol/
figure-of-eight coil/first dorsal interosseous | ↓ rMT
↓ SAI | Impairment of
cholinergic activity in patients compared
to controls. |
|
Pennisi
et al. [84] | 20 VaD patients (71.8 ± 9.4)—8/12
20 VCI-ND patients (65.9 ± 10.6)—8/12
20 controls (68.5 ± 7.9)—8/12 | Subcortical ischemic VaD
VCI-ND | NINDS-AIREN | Lacunar state and/or WMLs | No | Single-pulse TMS/circular coil/first dorsal interosseus | ↓ rMT in VaD (++) and VCI-ND (+)
↑ MEP amplitude in VaD | Enhanced motor cortex excitability only in patients with dementia and not
in those without dementia and controls. |
|
Nardone
et al. [85] | 28 patients
(69.5, range 57–79)—17/11
20 controls
(69.2, range 55–79)—13/7 | Subcortical ischemic VaD | Research criteria for subcortical VaD | Cerebral
microbleeds, WMLs, lacunar infarction | No | Single-pulse and paired-pulse TMS + SAI protocol/
figure-of-eight coil/first dorsal interosseous | = rMT
= CMCT
= SICI, ICF
↓ SAI in patients with microbleeds
=rMT after
donepezil
↑ SAI after donepezil | The impact of
microbleeds on central cholinergic function was independent
of the extent of
associated white matter changes and ischemic stroke. |
|
Bella
et al. [86] | 15 VCI-depressed patients
(70.5 ± 6.6)—7/8
10 VCI-nondepressed patients
(70.8 ± 6.3)—6/4
10 controls (67.7 ± 3.9)—5/5 | VCI-ND | DSM-IV-TR for dementia and MDD
Research criteria for subcortical VaD | Subcortical vascular disease with predominant WMLs | No | Single-pulse and paired-pulse TMS/figure-of-eight coil/first dorsal interosseous | = rMT
= CSP
= CMCT
= SICI
↑ ICF | The neurophysiological mechanisms underlying vascular depression differ from those reported in major depressive disorder and seem to be similar to those of the patients with subcortical ischemic vascular disease. |
|
Bella
et al. [87] | 10 patients (70.8 ± 6.32)—6/4
10 controls (67.7 ± 3.92)—5/5 | VCI-ND | DSM-IV-TR for dementia
Research criteria for subcortical VaD | Subcortical vascular disease with predominant WMLs | No | Single-pulse and paired-pulse TMS/
figure-of-eight coil/first dorsal interosseous | = rMT
= CSP
= CMCT
= SICI, ICF | Evidence of functional changes in intracortical excitatory neuronal circuits in patients compared to controls. |
|
Bella
et al. [88] | 9 patients
(median 70, range 66–84)—NR
9 controls
(median 67, range 65–88)—NR | VCI-ND | DSM-IV-TR
for dementia
Research criteria for subcortical VaD | Subcortical vascular disease with predominant WMLs | No | Single-pulse and paired-pulse TMS/figure-of-eight coil/first dorsal interosseous | ↓ rMT at follow-up
No significant difference for the other electrophysiological measures at follow-up | Increased cortical excitability in patients during the progression of cognitive impairment,
suggesting plasticity as a compensatory mechanism. |
|
Lanza
et al. [89] | 15 patients (71.40 ± 5.53)—9/6
15 controls (68.67 ± 3.62)—9/6 | VCI-ND | DSM-IV-TR for dementia
Research criteria for subcortical VaD | Subcortical vascular disease with predominant WMLs | No | Single-pulse TMS/figure-of-eight coil/first dorsal interosseous | = rMT
= CSP, iSP
= MEP
= CMCT | Unlike mild cognitive impairment and degenerative
dementia,
transcallosal
inhibitory
functioning was preserved in
VCI-ND. |
|
List
et al. [90] | 20 patients
(72, range 63–78)—9/11
20 controls
(71, range 60–77)—10/10 | VCI-ND | Research criteria for subcortical VaD | Severe ischemic subcortical vascular disease | No | Single-pulse TMS + PAS protocol/figure-of-eight coil/abductor digiti minimi | = rMT
= MEP at baseline
↑ MEP amplitude to PAS in 80% of controls and 50%
of patients | Enhanced cortical plasticity as compensatory mechanism to counteract memory decline in severe subcortical small vessel disease. |
|
Palomar
et al. [91] | 10 patients
(56.9 ± 9.8, range 36–70)—5/5
10 controls
(57.0 ± 10.3, range 39–71)—4/6 | CADASIL | Mutation in the exon 19 Notch3 gene | Leukoaraiosis, external capsule and anterior temporal pole T2-hyperintensities, lacunar infarcts | No | Single-pulse and paired-pulse TMS + SAI and PAS protocols/figure-of-eight coil/first dorsal interosseous and abductor pollicis brevis | = rMT
= CSP
= SICI, LICI
↓ ICF
↓ SAI
↓ MEP facilitation after PAS | Acetylcholine and glutamate might
be involved in CADASIL; abnormal sensory-motor plasticity correlated with the neuropsychological profile. |
|
Concerto
et al. [76] | 11 VCI-depressed patients
(57.72 ± 3.20)—6/5
11 MDD patients (57.18 ± 7.10)—5/6
11 controls (67.36 ± 3.70)—6/5 | VCI-ND | DSM-IV-TR for dementia and MDD
Research criteria for subcortical VaD | Periventricular and deep WMLs or multiple lacunes in deep grey matter, and at least moderate WMLs | None in
VCI group;
all in MDD
group | Single-pulse and paired-pulse TMS/figure-of-eight coil/first dorsal interosseous | ↑ rMT (>left hemisphere) in MDD
↑ CSP (>left hemisphere) in MDD
= MEP
= CMCT
= SICI, ICF | Distinctive patterns of motor cortex excitability between late-onset depression with subcortical vascular disease and early-onset recurrent MDD without vascular lesions. |
|
Nardone
et al. [92] | 8 VCI patients (72.5 ± 6.1)—NR
8 AD patients (72.5 ± 6.1)—NR
8 controls (72.5 ± 6.1)—NR | CADASIL | Mutation in the exon 19 Notch3 gene
NINDS-ADRDA | NR | No | Single-pulse and paired-pulse TMS + SAI protocol/figure-of
-eight coil/first dorsal interosseous | = rMT
= SICI, ICF
↓ SAI in all patients
↑ SAI after L-Dopa
in AD patients only | Significantly reduced cholinergic circuit functioning in all patients, with restoration by
L-Dopa in AD subjects only. |
|
List
et al. [93] | 12 patients
(62.0 ± 14.0, range 30–74)—9/3
10 controls (66.8 ± 5.9)—NR | 3 patients with poststroke VCI-ND | ECST criteria for unilateral internal carotid artery high-grade stenosis or occlusion | Left anterior cerebral artery infarction; right internal capsule infarction; left anterior cerebral artery infarction; NR in the other patients | No | Single-pulse and paired-pulse TMS + PAS protocol/figure-of-eight coil/abductor pollicis brevis | In the affected hemisphere:
↑ rMT
↓ CSP
↓ LTP-like plasticity
= motor learning between hemispheres | Despite decreased LTP-like plasticity in the affected hemisphere, motor learning was comparable between hemispheres, possibly due to GABA-B-mediated cortical motor excitability changes within the affected side. |
|
Guerra
et al. [94] | 7 VCI patients (78.1 ± 4.3)—2/5
9 AD patients (74.3 ± 7.7)—0/9
9 controls (75.0 ± 15.5)—3/6 | Subcortical ischemic VaD | NINDS-AIREN
NINDS-ADRDA | High degree of white matter hyperintensities | No | Single-pulse TMS + mapping study/figure-of-eight/extensor digitorum communis and abductor digiti minimi | ↓ rMT in AD (++) and VaD (+)
↑ area and volume of muscular areas in AD (++) and VaD (+)
Medial-frontal shift of the center of gravity map in all patients. | Similarly enhanced cortical excitability and plasticity in AD and VaD; the hyperexcitability can promote cortical plasticity, likely playing a compensatory function. |
|
| Bella et al. [95] | 25 patients (67.50 ± 6.72)—10/15
20 controls (64.60 ± 7.67)—9/11 | VCI-ND | DSM-IV-TR for dementia
Research criteria for subcortical VaD | Subcortical vascular disease with predominant WMLs | No | Single-pulse TMS + SAI protocol/figure-of-eight coil/first dorsal interosseous muscle | = rMT
= CSP
= MEP
= CMCT
↓ SAI, but not after Bonferroni correction | Unlike degenerative dementia, central cholinergic pathway was not clearly involved in patients with leukoaraiosis compared to controls. |
|
| Pennisi et al. [96] | 16 depressed patients
(68.1 ± 8.6)—NR
11 VCI-nondepressed patients
(70.0 ± 7.0)—NR
15 controls (63.8 ± 7.2)—NR | VCI-ND | DSM-IV-TR for dementia and MDD
Research criteria for subcortical VaD | Subcortical vascular disease with predominant WMLs | No | Single-pulse and paired-pulse TMS/figure-of-eight coil/first dorsal interosseous | ↑ ICF in nondepressed at baseline
↓ rMT in all patients at follow-up
↑ CSP only in controls at follow-up
= ICF in all subjects at follow-up | The mechanisms enhancing the risk of dementia in patients with vascular depression might be related either to subcortical vascular lesions or to the lack of compensatory functional cortical changes. |
|
