Table 3.
Neuroimaging studies of apathy in PD
| Study | Subjects | Sex (M/F) | H and Y (Mean ± SD) | Duration of PD (years) | UPDRS‐III | Imaging modality | Imaging analytical method | Diagnosis/measurement | Key findings |
|---|---|---|---|---|---|---|---|---|---|
| Huang et al. (2013) 14 |
26 PDs 12 HCs |
16/10 7/5 |
1–2.5 | 5.5 ± 0.7 | No data | [18F]FDG‐PET, T1‐weighted |
ROI (PET) WB (T1) |
BDI, BAI, AES |
Positive correlation between apathy and bi. ACC and orbitofrontal lobes Inverse correlation between apathy and right inferior parietal and left superior temporal gyri No volumetric difference between HCs and PDs |
| Lawrence et al. (2011) 55 |
10 low aPDs 10 high aPDs |
No data |
2.35 ± 0.6 2.7 ± 0.8 |
No data |
25.6 ± 11.0 28.2 ± 11.4 |
H2 15O PET FMRI | ROI | AS | ↓ Activity in left amygdala and striatum, bi. vmPFC, and midbrain in high aPDs |
| Le Jeune et al. (2009) 56, a | 12 PDs | 8/4 |
1.6 ± 1.2 (off) 0.9 ± 1.0 (on) |
No data |
14.3 ± 0.9 (off) 5.5 ± 3.4 (on) |
[18F]FDG‐PET | WB | AES, MADRS, AMDP‐AT |
Positive correlation between apathy and metabolism in right, frontal and parietal regions and left fusiform gyrus Inverse correlation between apathy and metabolism in bi. cingulate and left middle frontal gyri |
| Remy et al. (2005) 17 |
8 dPDs 12 PDs 7 HCs |
5/3 9/3 |
1–3.5 1–3.5 |
3.1 ± 1.8 4.9 ± 2.6 |
24.3 ± 11.2 23.3 ± 6.7 |
[11C]RTI‐32 PET | ROI | BDI, AES, STAS | Inverse correlation between apathy and binding value in bi. ventral striatum |
| Robert et al. (2012) 57 | 45 PDs (no depression) | No data | No data | 11.3 ± 4.1 |
8.4 ± 5.9 (ON) 29.9 ± 12.2 (OFF) |
[18F]FDG ‐PET | WB | AES, MADRS |
Positive correlations between apathy and cerebral metabolism in right inferior frontal gyrus, middle frontal gyrus, cuneus and insula Inverse correlations between apathy and cerebellar metabolism in bi. posterior cerebellums |
| Robert et al. (2014) 58 | 36 PDs (no depression) | No data | No data | No data | 7.9 ± 5.4 | [18F]FDG ‐PET | WB | AES, MADRS | Positive correlation between apathy and increased metabolism in left PCC |
| Robert et al. (2014) 59 | 44 PDs (no depression) | No data | No data | 11.4 ± 4.1 |
7.5 ± 5.2 (ON)b
32.6 ± 12.8 (OFF) |
[18F]FDG ‐PET | ROI | AES, MADRS, AMDP‐AT | Inverse correlation between metabolism in right ventral striatum and postoperative increased AES scores |
| Thobois et al. (2010) 60 |
12 aPDs 13 PDs |
6/6 10/3 |
No data |
10.3 ± 2.2 10.5 ± 3.0 |
14.5 ± 9.9 10.3 ± 5.9 |
[11C]‐raclopride PET | WB, ROI | BDI, BAI, SAS | aPDs > PDs: Binding value in bi. orbitofrontal and temporal cortices, and PCC; left dorsolateral prefrontal cortex, striatum and thalamus; right amygdala |
| Santangelo et al. (2015) 61 |
14 aPDs 14 PDs |
4/10 4/10 |
No data |
13.5 ± 6.1 12.8 ± 5.8 |
14.27 ± 7.4 14.1 ± 8.9 |
[123I]‐FP‐CIT SPECT | ROI | AES |
PDs > aPDs: dopamine in right caudate Inverse correlation between dopamine density in right caudate and apathy |
| Isella et al. (2002) 62 |
33 PDs 25 HCs |
18/15 12/13 |
No data | 4.9 ± 3.86 | 31.9 ± 15.69 | T1‐weighted | ROI | AES, GDS | PDs: Apathy was positively correlated with bi. temporal atrophy but inversely correlated with thickness of the right mesial temporal lobe |
| Reijnders et al. (2010) 63 | 60 PDs | No data | 1.5–3 | 6.6 ± 4.3 | 17.3 ± 4.9 | T1‐weighted | WB | AES, LARS, HAM‐D, NPI | Inverse correlation between apathy and grey matter density in bi. precentral gyri, inferior frontal and parietal gyri, and insula, right precuneus and PCC |
| Baggio et al. (2015) 64 |
25 aPDs 37 PDs 31 HCs |
20/5 17/20 15/16 |
1.84 ± 0.69 1.70 ± 0.57 |
7.24 ± 4.13 7.54 ± 5.52 |
15.56 ± 7.94 15.37 ± 8.48 |
RS‐FMRI T1‐weighted |
ROI | AS, BDI |
HCs and PDs > aPDs: Functional connectivity in left limbic striatal and frontal networks PDs + aPDs: Apathy was inversely correlated with connectivities between left limbic striatal and left frontal areas and between left frontal subdivisions No group differences or correlations with apathy or GM volume or subcortical volume/ shape |
| Skidmore et al. (2013) 40 | 15 PDs | 12/3 | No data | No data | 37 ± 13 | RS‐FMRI | WB | HAM‐D, LARS |
Apathy was positively correlated with regional cerebral functional signal in right middle orbital gyrus and bi. subgenual cingulate, but inversely correlated with left SMA, IPL, fusiform gyrus, and bi. cerebellums Apathy was predicted by regional cerebral functional signal in left SMA |
| Carriere et al. (2014) 65 |
10 HCs 10 aPDs 10 PDs |
4/6 6/4 6/4 |
No data |
11.9 ± 6.5 11.9 ± 3.2 |
28.1 ± 10.8 11.9 ± 3.2 |
T1‐weighted DTI |
T1: ROI DTI: WB |
LARS |
PDs + HCs > aPDs: Left nucleus accumbens HCs > aPDs: Bi. nucleus accumbens PDs > aPDs: Dorsolateral part of left caudate Positive correlation between apathy and atrophy in left nucleus accumbens No difference in FA |
ACC, anterior cingulated cortex; AES, Apathy Evaluation Scale; ALFF, amplitude of low frequency function; AMDP‐AT, Association for Methodology and Documentation in Psychiatry − Anxiety; aPDs, PD patients with apathy; AS, Apathy Scale; BAI, Beck Anxiety Inventory; BDI, Beck Depression Inventory; bi., bilateral; dPDs, PD patients with depression; DTI, diffusion tensor imaging; FA, fractional anisotropy; GDS, Geriatric Depression Scale; GM, grey matter; HAM‐D, Hamilton Depression Scale; HCs, healthy controls; IPL, inferior parietal lobule; LARS, Lille Apathy Rating Scale; MADRS, Montgomery Asberg Depression Rating Scale; NPI, Neuropsychiatric Inventory; PCC, posterior cingulate cortex; PDs, patients with PD alone; PET, positron emission tomography; ROI, region of interest; RS‐FMRI, resting state functional magnetic resonance imaging; SAS, Starkstein Apathy Scale; SMA, supplementary motor area; SPECT, single‐photon emission computed tomography; STAS, State‐Trait Anxiety Scale; UPDRS‐III, Unified Parkinson's Disease Rating Scale III; vmPFC, ventromedial prefrontal cortex; WB, whole brain.
Only the postoperative AES scores are used here as apathy significantly increased after subthalamic nucleus deep brain stimulation;
Only pre‐operative UPDRS‐III scores are shown here.