Table 1.
An overview of the literature regarding studies with significant microstructural changes of inferior longitudinal fasciculus in association with PD symptoms.
| Study | Groups studied | Number of participants (Males) | Mean age ± SD (years) | Disease duration (mean years ± SD) | Field strength (Tesla) | b-value (s/mm2) | Analysis method | Symptom or condition | ILF FA/QA comparison/correlation | ILF MD, AD or RD comparison/correlation | Methodological assessment |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Hattori et al. (39) | PD-NC PD-MCI PDD HC | 32 (12) 28 (16) 25 (13) 40 (18) |
75.9 ± 2 76.3 ± 6.4 80 ± 4.5 76.9 ± 4.9 |
5.8 ± 4.6 6.3 ± 4.3 7.8 ± 6.2 | 1.5 | 1,000 | TBSS | Cognitive decline | PDD, PD-MCI < HC PDD < PD-NC Positive correlation with MMSE scores in PD (Bilateral ILF) | Not investigated | MMSE, Clinical Dementia Rating |
| Melzer et al. (40) | PD-NC PD-MCI PDD HC | 63 (43) 28 (18) 18 (16) 32 (22) |
64.0 ± 9.2 71.0 ± 7.3 73.7 ± 6.5 70.1 ± 9.0 | 3.7 ± 3.2 5.8 ± 5.1 12.3 ± 8.6 | 3 | 1,000 | TBSS | Cognitive decline | PDD, PD-MCI < HC Positive correlation with attention, working memory, and processing speed score in posterior WM (Bilateral ILF) | PDD> PD-MCI > HC (MD, Bilateral ILF) | MDS Task Force criteria for diagnosis of dementia, Comprehensive neuropsychological testing |
| Chen et al. (41) | PD-NC PDD HC | 19 (9) 11 (5) 21 (10) |
59.47 ± 8.771 64.09 ± 11.35 61.10 ± 8.336 | 3.21 ± 1.960 3.64 ± 2.693 | 3 | Not specified | ROI | Cognitive decline | – | PDD > PD-NC Negative correlation with MoCA scores in PD (MD, Left ILF) | comprehensive neuropsychological testing, MDS Task Force criteria for dementia classification, MMSE, MoCA |
| Koshimori et al. (42) | PD HC | 26(13) 15 (4) |
70.5 ± 5.6 67.13 ± 5.1 | 6.7 ± 4.2 | 3 | 1,000 | TBSS | Cognitive decline | – | PD> HC Negative correlation with global composite z and executive composite z in PD (MD, Bilateral ILF) | extended neuropsychological test battery, MoCA |
| Duncan et al. (43) | PD HC | 125 (85) 50 (29) |
66.0 6 ± 10.5 65.86± 8.0 | 6.15 ± 4.66 months | 3 | 1,000 | TBSS | Cognitive decline | – | PD > HC PD-impaired semantic fluency> PD-NC, HC associated with performance on the semantic fluency and Tower of London tasks in PD (MD, Bilateral ILF) | Cognitive Drug Research battery, Neuropsychological Test Automated Battery, MoCA, MMSE |
| Gallagher et al. (44) | PD HC | 15 (12) 15 (9) |
62.7 ± 10 60.3 ± 6.5 |
5.6 ± 5 | 3 | Not specified | TBSS | Executive dysfunction | PD < HC Positive correlation with executive composite scores and Stroop interference scores in PD (Bilateral ILF) | PD > HC Negative correlation with Stroop interference scores in PD (MD, Bilateral ILF) | Neuropsychological test battery |
| Díez-Cirarda et al. (45) | PD HC | 37 (22) 15 (11) |
67.97 ± 6.17 65.07 ± 7.01 | 6.96 ± 5.61 | 3 | 1,000 | TBSS | Theory of mind deficit | – | Correlated with ToM deficit in PD (MD, RD, Left ILF) | Neuropsychological test battery |
| Lucas-Jimenez et al. (46) | PD HC | 37 (22) 16 (12) |
67.97 ± 6.18 65.13 ± 6.78 | 6.96 ± 5.61 | 3 | 1,000 | TBSS/ROI | Cognitive decline, DMN | PD < HC (Bilateral ILF) Positive correlation with DMN functional connectivity (Right ILF) | – | Neuropsychological test battery |
| Theilmann et al. (47) | PD HC | 25 (14) 26 (13) |
68.0 ± 8.9 65.9 ± 8.4 | 7.2 ± 4.8 | 1.5 | 1,000 | TBSS | Cognitive decline | PD < HC (Right ILF) No correlation with cognitive scores | PD > HC (MD, Right ILF; RD, Bilateral ILF) | MMSE, Judgment of Line Orientation Test (Visuospatial functioning), Digits Span Forward and Backward from the WAIS III (verbal working memory), Delis–Kaplan Executive Function System (verbal fluency), Trail Making Test (cognitive flexibility), Stroop Interference (inhibitory control) |
| Zheng et al. (48) | PD | 15 (11) | 62.2 ± 9.6 | 9.5 ± 6.0 | 3 | 1,000 | ROI | Cognitive decline | Negative correlation with language and attention (Left sagittal stratum including ILF) | Positive correlation with executive function and attention (MD, Left sagittal stratum including ILF), and language (MD, Bilateral sagittal stratum including ILF) | Comprehensive neuropsychological testing |
| Kamagata et al. (49) | PD PDD HC | 20 (8) 20 (10) 20 (10) |
71.6 ± 4.3 71.7 ± 5.3 72.7 ± 3.3 | 94.0 ± 53.4 months 146.6 ± 91.0 months | 3 | 1,000 | TBSS | Cognitive decline | PDD < HC (Bilateral ILF) No correlation with MMSE scores | PDD > HC (Bilateral ILF) | MMSE (Japanese version) |
| Sobhani et al. (50) | PD-Anosmia PD-Severe microsmia PD-Moderate microsmia PD-Mild microsmia PD-Normal olfaction HC | 18 (11) 26 (14) 17 (17) 12 (8) 12 (5) 36 (22) |
58.7 ± 7.5 59.3 ± 9 57.4 ± 9.9 54.7 ± 8.8 53.4 ± 7.8 60.1 ± 10.6 |
6.9 ± 9 6.6 ± 5.9 7.45 ± 7.8 4.45 ± 1.6 6.27 ± 4.6 |
3 | 1,000 | Connectometry | Olfactory dysfunction | PD-Anosmia < PD-Normal Olfaction PD-Severe microsmia < PD-Mild microsmia (QA, Left ILF) | Not investigated | Pennsylvania Smell Identification Test |
| Ford et al. (51) | PD-RBD PD-non-RBD | 46 (36) 78 (48) |
66.4 ± 9.9 65.8 ±10.9 | 6.5 ± 5.1 months 6.0 ± 4.4 months | 3 | 1,000 | TBSS | RBD | PD-RBD < PD-non-RBD (Bilateral ILF) (only significant in the uncorrected analysis) | PD-RBD > PD-non-RBD (Bilateral ILF) | question 1 on the Mayo Sleep Questionnaire |
| Huang et al. (52) | dPD ndPD | 15 (9) 15 (9) |
54.5 ± 12.2 54.8 ± 10.1 | 5.3 ± 4.8 4.2 ± 4.0 | 3 | 1,000 | TBSS | Depression | dPD < ndPD (Bilateral ILF) Left deep temporal cortex negatively correlated with severity of depression | – | HDRS |
| Wu et al. (53) | dPD ndPD | 31 (18) 37 (23) |
58.8 ± 8.67 59.1 ± 11.4 | 3.23 ± 3.04 2.40 ± 2.53 | 3 | 1,000 | ROI (PANDA) | Depression | dPD < ndPD (Left sagittal stratum, including ILF, no correlation with HDRS scores) | Not investigated | DSM IV criteria by an experienced psychiatrist, HDRS |
| Ghazi Sherbaf et al. (54) | dPD ndPD | 14 (11) 18 (11) |
58.28 ± 8.37 59.42 ± 11.3 | 7.5 ± 7.5 8.5 ± 7.5 | 3 | 1,000 | Connectometry | Depression | dPD < ndPD (QA, Left ILF) | Not investigated | Geriatric depression scale |
| Ansari et al. (55) | dPD ndPD | 40 (21) 19 (10) |
57.28 ± 7.9 57.5 ± 9.38 | Not specified (early drug-naïve) | 3 | 1,000 | Connectometry | Depression | dPD < ndPD (QA, Bilateral ILF) | Not investigated | Geriatric depression scale |
| Imperiale et al. (56) | PD-ICB PD-non-ICB HC | 35 (30) 50 (36) 50 (35) |
62.0 ± 10.4 61.5 ± 8.9 59.0 ± 12.4 | 9.5 ± 5.2 9.0 ± 6.1 | 1.5 | Not specified | probabilistic tractography | Impulsive compulsive behaviors | – | PD>HC (AD, Right ILF) | Diagnosis: current criteria based on comprehensive clinical interview by an expert neurologist and a trained neuropsychologist, QUIP Severity: QUIP rating scale |
| Mojtahed Zadeh et al. (57) | PD-ICD PD-non-ICD HC | 21 (14) 68 (44) 23 (12) |
57.7 ± 9.8 59.1 ± 9.5 58.3 ± 10.5 | 10.4 ± 10.5 5.8 ± 5.3 | 3 | 1,000 | Connectometry | Impulsive compulsive disorder | PD-ICD < HC (QA, Bilateral ILF) PD-non-ICD < HC (QA, Left ILF) | Not investigated | Questionnaire for Impulsive-Compulsive Disorders |
| Bertrand et al. (58) | PD HC | 26 (17) 7 (3) |
64.08 ± 8.57 70.43 ± 9.92 | 5.12 ± 3.24 | 3 | 700 | TBSS | Color discrimination deficit | – | Positive correlation with FM 100 performance (MD, small part of Right ILF) higher MD and RD in small part of Right ILF in PD with poor performance on the FM-100 | Farnsworth-Munsell 100 hue test |
| Baggio et al. (59) | PD HC | 39 (27) 23 (12) |
63.5 ± 11.4 61.0 ± 9.7 | 5.6 ± 3.8 | 3 | 1,000 | TBSS/ ROI | Facial emotion recognition | Negative correlation with sadness recognition in PD (Left ILF; no difference in between-group comparison) | Not investigated | Ekman 60 test (sadness sub-scores) |
| Li et al. (60) | PD HC | 31 (16) 22 (12) |
60.5 ± 9.3 59.7 ± 8.6 | Not specified (early stages) | 3 | 1,200 | TBSS | Motor severity in early PD | PD < HC (Left sagittal layer including ILF, no WM tract correlated with motor severity) | Not investigated | UPDRS (total, motor) |
| Pietracupa et al. (61) | PD-FOG PD-non-FOG HC | 21 (16) 16 (13) 19 |
66.3 ± 10.72 69,7 ± 11.1 66.74 ± 7.68 | 11 ± 6.3 9.5 ± 6.2 | 3 | 1,000 | TRACULA | Freezing of gate | – No correlation between DTI metrics in ILF and disease duration, H&Y, UPDRS III, MMSE, Frontal Assessment Battery, FOG-Q and Hamilton Depression Scale | PD-FOG > HC (MD, Right ILF) | Diagnosis: Timed get Up and Go test Severity: FOG Questionnaire |
| Wen et al. (62) | PD-TD PD-PIGD HC | 52 (32) 13 (10) 61 (41) |
60.46 ± 9.57 66.66 ± 10.17 60.19 ± 10.80 | 7.52 ± 8.00 months 6.54 ± 6.78 months | 3 | 1,000 | TBSS | Motor Subtypes (TD/PIGD) | TD > PIGD, HC Negative correlation with motor severity in PD-PIGD (Bilateral ILF) | TD < PIGD, HC (RD, Bilateral ILF) Positive correlation with motor severity in PD-PIGD (RD, AD, Bilateral ILF) No correlation with MoCA and GDS scores | tremor score/PIGD score based on UPDRS II and III |
| Luo et al. (63) | PD-TD PD-non-TD HC | 30 (16) 30 (15) 26 (13) |
53.42 ± 10.22 52.55 ± 7.33 54.46 ± 8.32 | 2.0 ± 1.71 2.35 ± 1.78 | 3 | 1,000 | TBSS | Tremor | – | PD-TD > PD-non-TD, HC Positive correlation with resting tremor score (MD, AD, Bilateral ILF) | UPDRS (motor) |
| Chiang et al. (64) | PD HC | 66 (23) 67 (29) |
58.1 ± 8.7 56.8 ± 9.8 | 3.856 ± 3.588 | 3 | 1,000 | ROI | Systemic inflammation | PD < HC (Bilateral ILF) Negative correlation with granulocyte LFA-1, granulocyte apoptosis (Left ILF) and lymphocyte apoptosis (Right ILF) | PD > HC (MD, Left ILF; RD, Right ILF) Positive correlation with granulocyte LFA-1, granulocyte apoptosis (RD, Left ILF) Positive correlation with P-selectin (MD, Left ILF) | Leukocyte apoptosis, adhesion molecules |
PD, Parkinson's disease; HC, healthy controls; FA, fractional anisotropy; MD, mean diffusivity; AD, axial diffusivity; RD, radial diffusivity; TBSS, tract-based spatial statistics; ROI, region of interest; VBA, voxel-based analysis; PANDA, pipeline for analyzing brain diffusion images; TRACULA, Tracts constrained by underlying anatomy; PDD, PD with dementia; PD-MCI, PD with mild cognitive impairment; PD-NC, PD with normal cognition; RBD, REM sleep behavior disorder; dPD, depressed PD; ndPD, non-depressed PD; ICB, impulsive compulsive behaviors; FOG, freezing of gait; TD, tremor dominant; PIGD, postural instability and gait difficulty; MMSE, mini-mental state examination; MoCA, Montreal cognitive assessment; ToM, theory of mind; HDRS, Hamilton depression rating scale; DSM-IV, diagnostic and statistical manual of mental disorders fourth edition; QUIP, questionnaire for impulsive–compulsive disorders in Parkinson's disease; UPDRS, unified Parkinson's disease rating scale; MDS, Movement Disorders Society; DMN, default mode network; LFA-1, lymphocyte function-associated antigen-1.