Table 3.
Study characteristics of functional imaging studies included in systematic review
| Author (year) | N of patients | MMSE (SD) | Anosognosia measure | Stimuli (meta-cognitive) | Type of scan | Threshold | Analysis | Peak coordinate (MNI/T88) |
Region [Brodmann area] | Correlation | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| x | y | z | ||||||||||
| Anosognosia | ||||||||||||
| Amanzio et al. (2011) | 28 AD | 22.4 (2.1) | Anosognosia Questionnaire Dementia Clinical Insight Rating Scale |
N/A | fMRI (activation) | Whole Brain | BOLD | −7 47 41 10 8 −42 −54 −57 22 −11 −3 26 |
54 −23 −71 36 23 10 3 13 4 2 −46 −53 |
5 49 25 3 26 −34 −31 −16 3 1 −36 29 |
Bilateral rostral prefrontal cortex [10] R postcentral gyrus [2] R middle temporal gyrus [39] R anterior cingulate [24] R anterior cingulate [24] L inferior temporal gyrus [21] L medial temporal gyrus [21] L superior temporal gyrus [38] R putamen L medial globus pallidus Bilateral cerebellum, posterior lobe R cerebellum, anterior lobe |
↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ |
| De Castro et al. (2007) | 21 AD | 18.2 (5.0) | Self-Consciousness Questionnaire Denial of Illness Scale |
N/A | HMPAO–SPECT (resting) | ROI | Cerebral perfusion | N/A | N/A | N/A | No significant regions | |
| Derouesne et al. (1999) | 88 AD | 22.5 (3.2) | Cognitive Difficulties Scale Clinical interview Psycho- behavioral questionnaire |
N/A | 123I-IMP SPECT (resting) | ROI | Cerebral perfusion | N/A | N/A | N/A | R frontal | ↓ |
| Guerrier et al. (2018) | 28 AD | 24 (3.8) | Cognitive Difficulties Scale | N/A | FGD-PET (resting) | Whole brain | 18F-FDG metabolism | −8 | 2 | 38 | L dorsal anterior cingulate [24] | ↓ |
| Hanyu et al. (2008) | 38 AD | Un-aware 25.8 (1.3) Aware 25.5 (1.1) |
Everyday Memory Checklist | N/A | 123I-IMP SPECT (resting) |
ROI | Cerebral perfusion | N/A | N/A | N/A | R/L subcallosal R/L anterior cingulate R cingulate gyrus L orbital gyrus |
↓ ↓ ↓ ↓ |
| Harwood et al. (2005) | 41 AD | 19.3 (6.7) | Neuro-behavioral rating scale (item score) | N/A | FDG-PET (resting) | ROI | 18F-FDG metabolism | N/A | N/A | N/A | R superior dorsolateral prefrontal cortex [6] R lateral frontal [8] R superior frontal pole [9] R caudal anterior cingulate [24] R lateral frontal [45] |
↓ ↓ ↓ ↓ ↓ |
| Jedidi et al. (2014) | 37 AD 25 HC |
N/A | Judgment of personality | N/A | FDG-PET (resting) | ROI | 18F-FDG metabolism | 12 −6 −8 −5✝ −5✝ −24✝ |
56 54 60 40✝ 54✝ 44✝ |
20 16 8 28✝ 14✝ 26✝ |
Dorsomedial PFC Dorsomedial PFC Ventromedial PFC Dorsomedial PFC Dorsomedial PFC Superior frontal sulcus |
↓ ↓ ↓ ↓ ↓ ↓ |
| Ott et al. (1996) | 40 AD | 18.5 (5.5) | Clinical Insight Rating Scale Instrumental Activities of Daily Living |
N/A | HMPAO-SPECT (resting) | ROI | Cerebral perfusion | N/A | N/A | N/A | R posterior temporal-occipital cortex L inferior frontal lobe |
↓ ↓ |
| Reed et al. (1993) | 57 AD | N/A | Anosognosia score | N/A | 123I-SPECT (resting) | ROI | Cerebral perfusion | N/A | N/A | N/A | R dorsolateral frontal cortex | ↓ |
| Ruby et al. (2009) | 14 AD 17 HC 17 YC |
N/A | Judgment of personality | N/A | fMRI (activation) | Whole brain | BOLD | −22 −26 40 |
−66 −50 −48 |
40 42 38 |
Intraparietal sulcus Intraparietal sulcus Intraparietal sulcus |
↓ ↓ ↓ |
| Salmon et al. (2006) | 206 AD | 21.0 (4.5) | Self-made anosognosia questionnaire | N/A | FDG-PET (Resting) | ROI | 18F-FDG metabolism | 22 −18 12 42 −18 40 |
−12 36 32 6 38 4 |
−30 −16 −16 0 44 20 |
R parahippocampal cortex L orbitofrontal cortex R gyrus rectus (inferior frontal gyrus) R insula L superior frontal sulcus R medial temporal lobe/cortex |
↓ ↓ ↓ ↓ ↓ ↓ |
| Sedaghat et al. (2010) | 42 AD | Un-aware 18.0 (4.0) Aware 21.0 (4) |
Clinical interview | N/A | HMPAO-SPECT (resting) | ROI | Cerebral perfusion | N/A | N/A | N/A | R prefrontal lobe R inferior parietal R/L medial temporal lobe/cortex |
↓ ↓ ↓ |
| Shibata et al. (2008) | 29 AD | 21.2 (2.9) | Anosognosia score | N/A | 123I-SPECT (resting) | ROI | Cerebral perfusion | −8 | 38 | 0 | L orbitofrontal cortex | ↓ |
| Starkstein et al. (1995) | 46 AD | Un-aware 19.1 (5.6) Aware 18.5 (4.7) |
Anosognosia Questionnaire Dementia | N/A | HMPAO-SPECT (resting) | ROI | Cerebral perfusion | N/A | N/A | N/A | R frontal inferior gyrus R frontal superior gyrus |
↓ ↓ |
| Sultzer et al. (2014) | 88 AD | N/A | Neuro-behavioral rating scale (insight item score) | N/A | FDG-PET (resting) | ROI | 18F-FDG metabolism | 4 | 54 | 6 | R frontal cortex [8, 9, 10, 24, 32] | ↓ |
| Tagai et al. (2018) | 37 AD 12 HC |
20.4 (4.6) | Anosognosia questionnaire dementia | N/A | 123I-SPECT (resting) | ROI | Cerebral perfusion | 56 −22 −18 −22 −38 20 46 22 16 |
36 −46 −50 −50 −22 −36 −82 −16 −98 |
−6 36 20 20 −22 46 30 50 22 |
R triangular inferior frontal gyrus L superior parietal lobe L precuneus L posterior cingulate cortex/gyrus L fusiform gyrus R precuneus R middle occipital gyrus R precentral gyrus R occipital lobe |
↓ ↑ ↑ ↑ ↑ ↑ ↑ ↑ ↑ ↑ |
| Vogel et al. (2005) | 36 AD 30 aMCI 33 HC |
24.0 (2.5) 26.1 (2.1) 29.3 (0.9) |
Anosognosia rating scale Memory questionnaire |
N/A | HMPAO-SPECT (resting) | ROI | Cerebral perfusion | N/A | N/A | N/A | R inferior frontal cortex | ↓ |
| Zamboni et al. (2013) | 17 AD 17 aMCI 17 HC |
22.2 (3.0) 26.8 (1.4) 29.9 (0.7) |
Anosognosia questionnaire dementia Patient/carer discrepancy score: Anderson trait list |
N/A | fMRI (activation) | Whole brain | BOLD | −4✝ −4✝ −19✝ −6✝ −10✝ −4✝ −42✝ −42✝ −62✝ −62✝ −62✝ −58✝ |
24✝ 8✝ 14✝ 38✝ −2✝ 24✝ −12✝ −16✝ −14✝ −14✝ −12✝ −4✝ |
36✝ 48✝ 48✝ 26✝ 48✝ 48✝ −14✝ −4✝ −20✝ −26✝ −12✝ −14✝ |
L paracingulate gyrus L paracingulate gyrus L paracingulate gyrus L anterior cingulate cortex/gyrus L anterior cingulate cortex/gyrus L superior frontal gyrus L superior temporal gyrus L superior temporal gyrus L middle temporal gyrus L middle temporal gyrus L superior temporal sulcus L superior temporal sulcus |
↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ |
| Metacognition | ||||||||||||
| Genon et al. (2014) | 21 AD 21 HC |
23.6 (2.0) | N/A | Adapted Remember/Know paradigm: Word recall Self-recognition task Self-recollection task |
fMRI (activation) | Whole brain | BOLD | N/A | N/A | N/A | No significant regions identified | |
| Mimura and Yano (2006) | 24 AD | 22.3 (3.8) | N/A | Judgment of Learning (JOLs): Auditory verbal learning test |
SPECT (resting) | ROI | Cerebral perfusion | 0 8 38 |
57 −48 25 |
−16 48 1 |
Medial frontal gyrus/lobe R precuneus Inferior frontal gyrus |
↓ ↓ ↓ |
| Rauchs et al. (2007) | 13 AD 10 HC |
24.8 (2.4) 29.4 (1) |
N/A | Remember/Know paradigm: Word recall |
FDG-PET (resting) | Whole brain | 18F-FDG metabolism | −32✝ 30✝ 14✝ −48✝ |
54✝ 54✝ 50✝ 46✝ |
2✝ 10✝ 44✝ −14✝ |
L middle frontal gyrus [10] R middle frontal gyrus [10] R median superior frontal gyrus [8] L frontal inferior orbital gyrus [47] |
↓ ↓ ↓ ↓ |
| Both Anosognosia and Metacognition | ||||||||||||
| Berlingeri et al. (2015) | 18 AD 15 HC |
Un-aware 24.1 (2.8) Aware 25.5 (3.4) 28.8 (1.2) |
Anosognosia Questionnaire Dementia | Judgment of Learning (JOLs): Episodic word recognition task Semantic Verbal Fluency Test |
fMRI (resting) | ROI | BOLD | −39✝ −39✝ |
−15✝ 12✝ |
−15✝ 3✝ |
L insular cortex L middle hippocampus (MTL) |
↓ ↓ |
| Perrotin et al. (2015) | 23 AD | 21.5 (4.6) | Cognitive Difficulties Scale Self-appraisal discrepancies |
Judgment of Learning (JOL): RL/RI-16 |
fMRI (Resting) FDG-PET |
ROI | BOLD 18F-FDG metabolism |
N/A | N/A | N/A | Medial temporal lobe Orbitofrontal Posterior cingulate cortex Orbitofrontal Posterior cingulate cortex |
↓ ↓ ↓ ↓ ↓ |
| Philippi et al. (2017) | 1 AD 7 AD 12 HC |
25 24.6 (1.0) 28.8 (1.0) |
Study specific anosognosia questionnaire | Remember/Know paradigm: Recognition memory test |
fMRI (resting) | ROI | BOLD | N/A | N/A | N/A | No fMRI results reported | |
All significant regions in studies reached threshold of FWE 0.05.
Key: AD, Alzheimer’s disease; aMCI, amnesic mild cognitive impairment; BOLD, Blood oxygen level–dependent imaging; FDG-PET, fluorodeoxyglucose-positron emission tomography; fMRI, functional magnetic resonance imaging; HMPAO, technetium-99m HMPAO isotope; HC, healthy older controls; L, left hemisphere; LPA, progressive aphasia; M, middle; MMSE, Mini-Mental State Examination; MNI, Montreal Neurological Institute; MRI, magnetic resonance imaging; MTL, medial temporal lobe; PNFA, primary nonfluent aphasia; R, right hemisphere; ROI, region of interest; T88, Talairach; SD, standard deviation; SPECT, single-photon emission computed tomography; YC, healthy young controls;123I, Iodine-123 isotope; 18F-FDG metabolism, Fludeoxyglucose metabolism.
Cerebral perfusion = regional cerebral function.
Resting state = evaluate function when no explicit task is performed.
Activation = evaluate function when explicit task is performed.
Bilateral = Both hemispheres.
↓ = negative correlation—decreased blood flow/glucose.
Metabolism associated with higher anosognosia score.
↑ = positive correlation—increased blood flow/glucose.
Metabolism associated with higher anosognosia score.
✝ = coordinates published but not AD only.