Atypical brain FDG-PET patterns increase the risk of long-term cognitive and motor progression in Parkinson's disease.

peer reviewed[en] INTRODUCTION: Brain hypometabolism patterns have been previously associated with cognitive decline in Parkinson's disease (PD). Our aim is to evaluate the impact of single-subject fluorodeoxyglucose (FDG)-PET brain hypometabolism on long-term cognitive and motor outcomes in PD. METHODS: Forty-nine non-demented PD patients with baseline brain FDG-PET data underwent an extensive clinical follow-up for 8 years. The ability of FDG-PET to predict long-term cognitive and motor progression was evaluated using Cox regression and mixed ANCOVA models. RESULTS: Participants were classified according to FDG-PET pattern in PD with typical (n = 26) and atypical cortical metabolism (n = 23). Patients with atypical brain hypometabolic patterns showed higher incidence of dementia (60% vs 3%; HR = 18.3), hallucinations (56% vs 7%, HR = 7.3) and faster motor decline compared to typical pattern group. CONCLUSION: This study argues for specific patterns of FDG-PET cortical hypometabolism in PD as a prognostic marker for long term cognitive and motor outcomes at single-subject level

The emerging role of PET imaging in dementia [version 1; referees: 3 approved]

A compelling need in the field of neurodegenerative diseases is the development and validation of biomarkers for early identification and differential diagnosis. The availability of positron emission tomography (PET) neuroimaging tools for the assessment of molecular biology and neuropathology has opened new venues in the diagnostic design and the conduction of new clinical trials. PET techniques, allowing the in vivo assessment of brain function and pathology changes, are increasingly showing great potential in supporting clinical diagnosis also in the early and even preclinical phases of dementia. This review will summarize the most recent evidence on fluorine-18 fluorodeoxyglucose-, amyloid -, tau -, and neuroinflammation - PET tools, highlighting strengths and limitations and possible new perspectives in research and clinical applications. Appropriate use of PET tools is crucial for a prompt diagnosis and target evaluation of new developed drugs aimed at slowing or preventing dementia

Lifestyle modulators of neuroplasticity in Parkinson's disease: evidence in human neuroimaging studies

Parkinson's disease is a neurodegenerative disease characterized by both motor and non-motor symptoms. A progressive neuronal loss and the consequent clinical impairment lead to deleterious effects on daily living and quality of life. Despite effective symptomatic therapeutic approaches, no disease-modifying therapies are currently available. Emerging evidence suggests that adopting a healthy lifestyle can improve the quality of life of Parkinson's disease patients. In addition, modulating lifestyle factors can positively affect the microstructural and macrostructural brain levels, corresponding to clinical improvement. Neuroimaging studies may help to identify the mechanisms through which physical exercise, dietary changes, cognitive enrichment, and exposure to substances modulate neuroprotection. All these factors have been associated with a modified risk of developing PD, with attenuation or exacerbation of motor and non-motor symptomatology, and possibly with structural and molecular changes. In the present work, we review the current knowledge on how lifestyle factors influence Parkinson's disease development and progression and the neuroimaging evidence for the brain structural, functional, and molecular changes induced by the adoption of positive or negative lifestyle behaviours

In vivo MRI Structural and PET Metabolic Connectivity Study of Dopamine Pathways in Alzheimer's Disease.

peer reviewedBACKGROUND: Alzheimer's disease (AD) is characterized by an involvement of brain dopamine (DA) circuitry, the presence of which has been associated with emergence of both neuropsychiatric symptoms and cognitive deficits. OBJECTIVE: In order to investigate whether and how the DA pathways are involved in the pathophysiology of AD, we assessed by in vivo neuroimaging the structural and metabolic alterations of subcortical and cortical DA pathways and targets. METHODS: We included 54 healthy control participants, 53 amyloid-positive subjects with mild cognitive impairment due to AD (MCI-AD), and 60 amyloid-positive patients with probable dementia due to AD (ADD), all with structural 3T MRI and 18F-FDG-PET scans. We assessed MRI-based gray matter reductions in the MCI-AD and ADD groups within an anatomical a priori-defined Nigrostriatal and Mesocorticolimbic DA pathways, followed by 18F-FDG-PET metabolic connectivity analyses to evaluate network-level metabolic connectivity changes. RESULTS: We found significant tissue loss in the Mesocorticolimbic over the Nigrostriatal pathway. Atrophy was evident in the ventral striatum, orbitofrontal cortex, and medial temporal lobe structures, and already plateaued in the MCI-AD stage. Degree of atrophy in Mesocorticolimbic regions positively correlated with the severity of depression, anxiety, and apathy in MCI-AD and ADD subgroups. Additionally, we observed significant alterations of metabolic connectivity between the ventral striatum and fronto-cingulate regions in ADD, but not in MCI-AD. There were no metabolic connectivity changes within the Nigrostriatal pathway. CONCLUSION: Our cross-sectional data support a clinically-meaningful, yet stage-dependent, involvement of the Mesocorticolimbic system in AD. Longitudinal and clinical correlation studies are needed to further establish the relevance of DA system involvement in AD

Editorial: Imaging brain molecular connectivity in health and disease.

peer reviewe

Validation of 18F-FDG-PET Single-Subject Optimized SPM Procedure with Different PET Scanners.

18F-fluoro-deoxy-glucose Positron Emission Tomography (FDG-PET) allows early identification of neurodegeneration in dementia. The use of an optimized method based on the SPM software package highly improves diagnostic accuracy. However, the impact of different scanners for data acquisition on the SPM results and the effects of different pools of healthy subjects on the statistical comparison have not been investigated yet. Images from 144 AD patients acquired using six different PET scanners were analysed with an optimized single-subject SPM procedure to identify the typical AD hypometabolism pattern at single subject level. We compared between-scanners differences on the SPM outcomes in a factorial design. Single-subject SPM comparison analyses were also performed against a different group of healthy controls from the ADNI initiative. The concordance between the two analyses (112 vs. 157 control subjects) was tested using Dice scores. In addition, we applied the optimized single-subject SPM procedure to the FDG-PET data acquired with 3 different scanners in 57 MCI subjects, in order to assess for tomograph influence in early disease phase. All the patients showed comparable AD-like hypometabolic patterns, also in the prodromal phase, in spite of being acquired with different PET scanners. SPM statistical comparisons performed with the two different healthy control databases showed a high degree of concordance (76% average pattern volume overlap and 90% voxel-wise agreement in AD-related brain structures). The validated optimized SPM-based single-subject procedure is influenced neither by the scanners used for image acquisition, nor by differences in healthy control groups, thus implying a great reliability of this method for longitudinal and multicentre studies

Sex differences in dementia with Lewy bodies: an imaging study of neurotransmission pathways

Purpose: Dementia with Lewy bodies (DLB) is characterized by a wide clinical and biological heterogeneity, with sex differences reported in both clinical and pathologically confirmed DLB cohorts. No research evidence is available on sex differences regarding molecular neurotransmission. This study aimed to assess whether sex can influence neurotransmitter systems in patients with probable DLB (pDLB). Methods: We included 123 pDLB patients (male/female: 77/46) and 78 control subjects (male/female: 34/44) for comparison, who underwent 123I-FP-CIT SPECT imaging. We assessed sex differences in the dopaminergic activity of the nigrostriatal and mesolimbic systems using regional-based and voxel-wise analyses of 123I-FP-CIT binding. We tested whether sex-specific binding alterations would also pertain to the serotoninergic and noradrenergic systems by applying spatial correlation analyses. We applied molecular connectivity analyses to assess potential sex differences in the dopaminergic pathways. Results: We found comparable 123I-FP-CIT binding decreases in the striatum for pDLB males and females compared to controls. However, pDLB females showed lower binding in the extrastriatal projections of the nigrostriatal and mesolimbic dopaminergic systems compared to pDLB males. According to the spatial correlation analysis, sex-specific molecular alterations were also associated with serotonergic and noradrenergic systems. Nigrostriatal and mesolimbic systems' connectivity was impaired in both groups, with males showing local alterations and females presenting long-distance disconnections between subcortical and cortical regions. Conclusions: Sex-specific differences in 123I-FP-CIT binding were found in our cohort, namely, a trend for lower 123I-FP-CIT binding in females, significant in the presence of a pDLB diagnosis. pDLB females showed also different patterns of connectivity compared to males, mostly involving extrastriatal regions. The results suggest the presence of a sex-related regional vulnerability to alpha-synuclein pathology, possibly complicated also by the higher prevalence of Alzheimer's disease co-pathology in females, as previously reported in pDLB populations.</p

The brain metabolic signature of visual hallucinations in dementia with Lewy bodies.

peer reviewedVisual hallucinations (VH) are a core clinical feature of dementia with Lewy bodies (DLB), but their specific neural substrate remains elusive. We used (18)F-FDG-PET to study the neural dysfunctional signature of VH in a group of 38 DLB patients (mean age±SD 72.9 ± 7.5) with available anamnestic records, cognitive and neurological examination and NeuroPsychiatric Inventory assessing VH. We tested the voxel-wise correlation between (18)F-FDG-PET hypometabolism and VH NPI scores at the whole-group level, then adopting inter-regional correlation analysis to explore the resting-state networks (RSNs) metabolic connectivity in DLB patients with and without visual hallucinations, as compared to N = 38 age-matched healthy controls (HCs) (mean age±SD 71.5 ± 6.9). At the whole-group level, we found a negative correlation between VH NPI scores and (18)F-FDG-PET hypometabolism in the right occipito-temporal cortex (p < .001 uncorrected, p < .05 Family-Wise Error cluster-corrected). Then, splitting the group according to VH presence, we found that DLB non-hallucinators presented a pattern of connectivity seeding from this occipito-temporal cluster and extending to the ventral visual stream. At difference, the DLB hallucinators showed a metabolic connectivity pattern limited to the occipital-dorsal parietal regions. As for RSNs, both the DLB subgroups showed a markedly reduced extent of attention and visual networks compared to HCs, with a variable alteration in the topography. DLB-VH patients showed a more pronounced shrinkage of the primary visual network, which was disconnected from the higher visual hubs, at difference with both HC and DLB non-hallucinators. These findings suggest that an altered brain metabolic connectivity within and beyond visual systems may promote VH in DLB. These results support the most recent neurocognitive models interpreting VH as the result of an inefficient recruitment of the ventral visual stream and of a large-scale multi-network derangement