TABLE 1.
Neuroimaging research regarding the neurobiological aspects of neuropsychiatric symptoms (NPS) published since 2016.
| Year | First author | Subjects | Imaging modalities | Main finding(s) |
| 2016 | Bensamoun | 119 AD, 308 MCI, 230 CN (ADNI) | Amyloid PET (18F-florbetapir PET) | Anxiety and irritability were associated with greater amyloid deposition |
| 2016 | Makovac | 58 AD | T1WI, DTI | Specific patterns of brain atrophy and disconnection in association with each NPS in AD |
| 2017 | Huey | 57 AD (ADNI) | T1WI | Apathy showed the most robust associations in the PFC, PCG, and STS |
| 2017 | Kazui | 98 aMCI | T1WI, perfusion SPECT | Apathy was associated with right caudate atrophy and hypoperfusion in the cortices |
| 2017 | Ng | 33 preAD, 60 AR-AD, 22 CN (ADNI) | 18F-FDG PET | Greater NPS predicted subsequent hypometabolism in the PCG in preclinical AD |
| 2017 | Poulin | 181 AD | T1WI | Dorsolateral prefrontal atrophy was present in persistent NPS but not in fluctuating NPS |
| 2017 | Tu | 32 AD, 24 SIVD | DTI | WM integrity showed associations with multi-domains of NPS in the CC, as well as domain-specific associations in other tracts |
| 2018 | Ogama | 217 AD, 39 aMCI | T1WI | Periventricular WMH in the frontal lobe was associated with verbal aggressiveness |
| 2018 | Sellami | 167 genetic FTD (GENFI) | T1WI | Different neuroanatomical correlates of NPS across major forms of genetic FTD |
| 2019 | Garcia-Alberca | 46 AD | T1WI | Medial temporal atrophy was associated with apathy and disinhibition |
| 2020 | Boublay | 53 AD, 40 CN | T1WI | Frontal lobe volume was the most powerful predictor of the progression of the NPI score |
| 2020 | Chang | 159AD | rs-fMRI | Functional connectivity parameters were associated with affective or psychotic symptoms |
| 2020 | Kanemoto | 22 DLB | 18F-FDG PET | Sleep disturbance was associated with hypometabolism around the thalamus |
| 2020 | Misquitta | 121 AD, 315 MCI, 225 CN (ADNI) | T1WI, T2WI, FLAIR | WMH and GM atrophy both contributed to NPS subdomains |
| 2020 | Serra | 101 AD, 56 aMCI, 35 CN | rs-fMRI | Patients with NPS showed functional connectivity changes that were not seen in the patients without NPS or CN |
| 2020 | Tumati | 26 AD, 61 MCI, 18 CN | rs-fMRI | Global or local network alterations were observed in patients with the apathy symptom |
| 2021 | Anor | 138 AD, 114 MCI (NACC) | T1WI, FLAIR | WMH predicts increases in delusions, hallucinations, agitation, depression, and irritability |
| 2021 | Jaramillo-Jimenez | 55 AD, 34 DLB | T1WI | Larger amygdala volume predicts lower agitation/aggression but higher depression |
| 2021 | Matuskova | 79 MCI, 37 SCI | T1WI | Reduced entorhinal cortex was associated with behavioral impairment |
| 2021 | Mohamed Nour | 105 AD (ADNI) | T1WI | GM in the left insula and hippocampus was associated with depression, anxiety, and apathy |
| 2021 | Nowrangi | 72 MCI/dementia | T1WI | ACC was the region most commonly associated with agitation and delusions |
| 2021 | Siafarikas | 133 AD, 102 MCI | T1WI | Associations between NPS and mainly frontotemporal brain structures |
| 2021 | Tissot | 26 AD, 52 MCI, 143 CN (TRIAD) | tau PET (18F-MK6240 PET) | Correlations between NPS and tau deposition |
| 2022 | Ge | 151 MCI (ADNI) | tau PET (18F-AV-1451 PET) | Association between tau deposition and dyscognition was observed only in the subjects with MCI with behavior symptom(s) |
| 2023 | Cannizzaro | 175 AD, 367 MCI, 223 CN (ADNI) | T1WI | Affective and vegetative NPS were associated with prefrontal and temporal areas |
| 2023 | Fan | 80 AD | T1WI, FLAIR | Total or occipital WMH was associated with delusions |
| 2023 | Jiang | 153 AD | T1WI, ASL | Hyperperfusion in the right ATN was associated with NPS |
| 2023 | Nakase | 102 AD, 54 aMCI | T1WI, perfusion SPECT | Hyperactivity may be affected by the functional relationship between GM and WM lesions |
| 2023 | Ozzoude | 126 AD/MCI, 40 ALS, 52 FTD, 140 PD, 155 CVD | T1WI, proton density, T2WI, FLAIR | WMH and reduced CT may contribute to NPS |
| 2024 | El Haffaf | 216 AD, 564 MCI, 660 CN (ADNI) | T1WI | Different correlation patterns were observed between hyperactive NPS and brain regions across AD, MCI, and CN |
| 2024 | Guan | 345 MCI, 912 CN (NACC) | T1WI | MBI was associated with broader brain atrophy and more rapid cognitive decline |
| 2024 | Kameyama | 121 AD (J-BIRD) | T1WI | Aggressive behavior was associated with frontal lobe asymmetry |
| 2024 | Kashibayashi | 180 AD, 77 aMCI (J-BIRD) | Perfusion SPECT | Brain hypoperfusion was associated with care refusal in the right hippocampus and with violence in the right temporal pole |
| 2024 | Kim | 66 PD-D, 291 PD-MCI, 123 PD-SCI | T2WI, 18F-FP-CIT PET | Enlarged periventricular spaces in the temporal lobe were associated with greater NPS in the patients with PD |
| 2024 | Liampas | 3,165 MCI, 4,051 CN (NACC) | T1WI | Frontotemporal atrophy was associated with elation, aberrant motor behavior, appetite disorders, apathy, and disinhibition in MCI but not in CN |
| 2024 | Marin-Marin | 81 aMCI | T1WI | Lower volumes of the left temporal pole were observed in depression, and lower volumes of right middle occipital gyrus were observed in agitation |
| 2024 | Pajavand | 61 MCI, 35 CN | T1WI, DTI | WM connectivity loss around the limbic system was associated with NPS |
| 2024 | Rashidi-Ranjbar | 74 MCI, 143 CVD, 137 PD (ONDRI) | T1WI | Apathy was cross-sectionally and longitudinally associated with the frontal-executive circuit |
| 2024 | Tachibana | 52 MCI, 38 dementia | T1WI | Associations between apathy and the insular cortex and between eating disturbance and various brain regions were observed |
| 2024 | Zhao | 192 AD, 178 CN (OASIS, ADNI) | rs-fMRI | The behavioral syndrome was associated with default-mode and somatomotor networks, and anxiety syndrome was associated with the visual network |
| 2025 | Kanemoto | 281 AD, 68 DLB, 180 MCI (J-BIRD) | T1WI, perfusion SPECT | Psychosis, agitation, and affective disturbance were differently associated with GM or perfusion across AD, DLB, and MCI |
| 2025 | Khoury | 752 AD (NACC) | T1WI | APOE4 status can affect the CT and NPS in women and men with AD differently |
| 2025 | Lu | 40 AD, 40 MCI, 40 CN | T1WI, FLAIR | Patients with NPS showed greater hippocampal atrophy and higher AD Resemblance Atrophy Index values |
| 2025 | Michelutti | 16 AD, 17 MCI | T1WI | The structural covariance network was associated with affective dysregulation, impulse dyscontrol, and social inappropriateness |
| 2025 | Rashidi-Ranjbar | 73 MCI, 144 CVD, 132 PD (ONDRI) | rs-fMRI | Associations between NPS and functional connectivity within the DMN, ECN, and SN were observed |
| 2025 | Sone | 258 AD, 56 DLB, 185 aMCI (J-BIRD), 694 CN | T1WI | Apathy was associated with older age of the brain derived from MRI |
| 2025 | Wright | 28 MCI-LB, 29 PD-MCI | rs-fMRI | Altered networks were associated with mood symptoms in PD-MCI |
18F-FP-CIT PET, N-3-[18F]fluoropropyl-2β-carbomethoxy-3β-4-iodophenyl nortropane; ACC, anterior cingulate cortex; AD, Alzheimer’s disease; ADNI, Alzheimer’s disease neuroimaging initiative; ALS, amyotrophic lateral sclerosis; aMCI, amnestic mild cognitive impairment; ARAD, asymptomatic at risk for Alzheimer disease; ASL, arterial spin labeling; ATN, anterior thalamic nuclei; CC, corpus callosum; CN, cognitively normal; CT, cortical thickness; CVD, cardiovascular disease; DLB, dementia with Lewy bodies; DMN, default mode network; DTI, diffusion tensor imaging; ECN, executive control network; FLAIR, fluid-attenuated inversion recovery; FTD, fronto-temporal dementia; GENFI, genetic frontotemporal initiative; GM, gray matter; J-BIRD, a Japan multicenter study: behavioral and psychological symptoms integrated research in dementia; MBI, mild behavioral impairment; MCI, mild cognitive impairment; MCI-LB, mild cognitive impairment with Lewy bodies; MRI, magnetic resonance imaging; NACC, National Alzheimer’s Coordinating Center; NPI, neuropsychiatric inventory; ONDRI, Ontario Neurodegenerative Research Initiative; PCG, posterior cingulate gyrus; PD, Parkinson’s disease; PD-D, Parkinson’s disease with dementia; PD-MCI, Parkinson’s disease with mild cognitive impairment; PD-SCI, Parkinson’s disease with subjective cognitive impairment; PFC, prefrontal cortex; rs-fMRI, resting-state functional magnetic resonance imaging; SCI, subjective cognitive impairment; SIVD, subcortical ischemic vascular dementia; SN, salience network; SPECT, single-photon emission computed tomography; STS, superior temporal sulcus; TRIAD, translational biomarkers in aging and dementia; WM, white matter; WMH, white matter hyperintensity.