ObjectiveTo investigate in vivo whether synaptic loss and neurofibrillary tangle load spatially overlap and correlate with clinical symptoms in patients with amnestic mild cognitive impairment (aMCI).MethodsIn this cross-sectional study, 10 patients with aMCI and 10 healthy controls underwent triple PET-MRI with 11C-UCB-J (synaptic vesicle protein 2A), 18F-MK-6240 (tau deposition), and 11C-Pittsburgh compound B (β-amyloid) and neuropsychological assessment. Gray matter atrophy was assessed by voxel-based morphometry with T1-weighted MRIs. Voxel-wise and volume-of-interest analyses were conducted on PET data. The interrelationship of synaptic density and tau deposition was investigated. We also investigated correlations of 18F-MK-6240 and 11C-UCB-J binding with cognitive performance.ResultsCompared to controls, patients with aMCI showed a decreased 11C-UCB-J binding mainly in substructures of the medial temporal lobe (MTL; 48%–51%, pcluster = 0.02). Increased 18F-MK6240 binding in the same region was observed (42%–44%, pcluster = 0.0003), spreading to association cortices. In the MTL, higher 18F-MK-6240 binding inversely related to lower 11C-UCB-J binding (p = 0.02, r = −0.76). Decreased performance on cognitive tests was associated with both increased 18F-MK-6240 and decreased 11C-UCB-J binding in the hippocampus (p < 0.01, r > 0.7), although in a multivariate analysis only 18F-MK-6240 binding was significantly related to cognitive performance.ConclusionsPatients with aMCI have high tau deposition and synaptic density loss mainly in key regions known to be involved in early cognitive impairment, indicating that these are interrelated in the MTL, while tau binding had already spread toward association cortices. Longitudinal data are needed to provide further insight into the temporal aspects of this relationship.

Purpose: The endocannabinoid system plays a regulatory role in a number of physiological functions, including motor control but also mood, emotion and cognition. A number of preclinical studies in Parkinson´s disease (PD) models demonstrated that modulating the type 1 cannabinoid receptor (CB1R) may improve motor symptoms and components of cognitive processing. However, the relation between CB1R, cognitive decline and behavioral symptoms has not been investigated in PD patients so far. The aim of this study was to examine whether CB1R availability is associated with measures of cognitive and behavioral function in PD patients.Methods: Thirty-eight PD patients and ten age-and gender-matched controls underwent a [ 18 F]MK-9470 PET scan to assess CB1R availability, as well as volumetric MR imaging. Neuropsychological symptoms were evaluated using an extensive cognitive and behavioral battery covering the five cognitive domains, depression, anxiety, apathy and psychiatric complications, and were correlated to CB1R availability using vowel-wise regression analysis (P<0.05, corrected for familywise error).Results: PD patients with poorer performance in episodic memory, executive functioning, speed and mental flexibility (range P: 0.003-0.03) showed lower CB1R availability in predominantly the midcingulate cortex and middle to superior frontal gyrus (Tpeak-level>4.0). Also, PD patients with more severe visuospatial dysfunction showed decreased CB1R availability in the precuneus, midcingulate, supplementary motor cortex, inferior orbitofrontal gyrus and thalamus (Tpeak-level=5.5). These correlations were not related to cortical grey matter atrophy. No relationship was found between CB1R availability and mood or behavioral symptom scores.Conclusions: Decreased CB1R availability in the prefrontal and midcingulate cortex in PD patients is strongly correlated with disturbances in executive functioning, episodic memory and visuospatial functioning. Further investigation of regional CB1R expression in groups of PD patients with mild cognitive impairment or dementia is warranted in order to further investigate the role of CB1R expression in different levels of cognitive impairment in PD.

OBJECTIVE: MRI derived hippocampal volume (HV) and amyloid PET may be useful clinical biomarkers for differentiating between geriatric depression and Alzheimer's Disease (AD).Here we investigated the incremental value of HV and 18F-flutemetmol PET in tandem and sequentially to improve discrimination in unclassified participants. METHOD: Two approaches were compared in 41 participants with geriatric depression and 27 participants with probable AD: (1) amyloid and HV combined in one model and (2) HV first and then amyloid. RESULTS:(1) Both HV(χ 2 (1) = 6.46: p= 0.011) and amyloid (χ 2 (1) =11.03: p=0.0009) were significant diagnostic predictors of depression (sensitivity: 95%, specificity: 89%). (2) 51% of participants were correctly classified according to clinical diagnosis based on HV alone, increasing to 87% when adding amyloid data (sensitivity: 94%, specificity: 78%). CONCLUSION: Hippocampal volume may be a useful gatekeeper for identifying depressed individuals at risk for AD who would benefit from additional amyloid biomarkers when available. _________________________________________________________________________.

OBJECTIVE: MRI derived Hippocampal volume (HV) and amyloid PET may be useful clinical biomarkers for differentiating between geriatric depression and Alzheimer's Disease (AD). Here we investigated the incremental value of HV and 18F-flutemetmol PET in tandem and sequentially to improve discrimination in unclassified participants. METHOD: Two approaches were compared in 41 participants with geriatric depression and 27 participants with probable AD: (1) amyloid and HV combined in one model and (2) HV first and then amyloid. RESULTS: (1) Both HV(χ2(1) = 6.46: p= 0.011) and amyloid (χ2(1) =11.03: p=0.0009) were significant diagnostic predictors of depression (sensitivity: 95%, specificity: 89%). (2) 51% of participants were correctly classified according to clinical diagnosis based on HV alone, increasing to 87% when adding amyloid data (sensitivity: 94%, specificity: 78%). CONCLUSION: Hippocampal volume may be a useful gatekeeper for identifying depressed individuals at risk for AD who would benefit from additional amyloid biomarkers when available