Alteration of medial temporal lobe metabolism related to Alzheimer's disease and dementia with lewy bodies.

BACKGROUND: Association of medial temporal lobe (MTL) metabolism with Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) has not been evaluated considering their mixed disease (MD). METHODS: 131 patients with AD, 133 with DLB, 122 with MD, and 28 normal controls (NCs) underwent neuropsychological tests, assessments for parkinsonism, cognitive fluctuation (CF), and visual hallucinations (VH), and 18F-fluorodeoxyglucose PET to quantify MTL metabolism in the amygdala, hippocampus, and entorhinal cortex. The effects of AD and DLB on MTL metabolism were evaluated using general linear models (GLMs). Associations between MTL metabolism, cognition, and clinical features were evaluated using GLMs or logistic regression models separately performed for the AD spectrum (NC + AD + MD), DLB spectrum (NC + DLB + MD), and disease groups (AD + DLB + MD). Covariates included age, sex, and education. RESULTS: AD was associated with hippocampal/entorhinal hypometabolism, whereas DLB was associated with relative amygdalar/hippocampal hypermetabolism. Relative MTL hypermetabolism was associated with lower attention/visuospatial/executive scores and severe parkinsonism in both the AD and DLB spectra and disease groups. Left hippocampal/entorhinal hypometabolism was associated with lower verbal memory scores, whereas right hippocampal hypometabolism was associated with lower visual memory scores in both the AD spectrum and disease groups. Relative MTL hypermetabolism was associated with an increased risk of CF and VH in the disease group, and relative amygdalar hypermetabolism was associated with an increased risk of VH in the DLB spectrum. CONCLUSIONS: Entorhinal-hippocampal hypometabolism and relative amygdala-hippocampal hypermetabolism could be characteristics of AD- and DLB-related neurodegeneration, respectively.

Association of Family History and Polygenic Risk Score With Longitudinal Prognosis in Parkinson Disease.

Background and Objectives: Evidence suggests that either family history or polygenic risk score (PRS) is associated with developing Parkinson disease (PD). However, little is known about the longitudinal prognosis of PD according to family history and higher PRS. Methods: From the Parkinson's Progression Markers Initiative database, 395 patients with PD who followed up for more than 2 years were grouped into those with family history within first-degree, second-degree, and third-degree relatives (N = 127 [32.2%]) vs those without (N = 268 [67.8%]). The PRS of 386 patients was computed using whole-genome sequencing data. Longitudinal assessment of motor, cognition, and imaging based on dopaminergic degeneration was conducted during the regular follow-up period. Effects of family history, PRS, or both on longitudinal changes of cognition, motor severity, and nigrostriatal degeneration were tested using a linear mixed model. The risk of freezing of gait (FOG) according to family history was assessed using the Kaplan-Meier analysis and Cox regression models. Results: During a median follow-up of 9.1 years, PD with positive family history showed a slower decline of caudate dopamine transporter uptake (ß estimate of family history × time = 0.02, 95% CI = 0.002-0.036, p = 0.027). Family history of PD and higher PRS were independently associated with a slower decline of Montreal Cognitive Assessment (ß estimate of family history × time = 0.12, 95% CI = 0.02-0.22, p = 0.017; ß estimate of PRS × time = 0.09, 95% CI = 0.03-0.16, p = 0.006). In those 364 patients without FOG at baseline, PD with positive family history had a lower risk of FOG (hazard ratio of family history = 0.57, 95% CI = 0.38-0.84, p = 0.005). Discussion: Having a family history of PD predicts slower progression of cognitive decline and caudate dopaminergic degeneration, and less FOG compared with those without a family history independent of PRS. Taken together, information on family history could be used as a proxy for the clinical heterogeneity of PD. Trial Registration Information: The study was registered at clinicaltrials.gov (NCT01141023), and the enrollment began June 1, 2010.

Dopamine transporter positron emission tomography in patients with Alzheimer's disease with Lewy body disease features.

In 36 normal controls (NC), 37 patients with Alzheimer's disease (AD) without parkinsonism (ADP-), 31 AD with parkinsonism (ADP+), and 40 AD with dementia with Lewy bodies (ADDLB), dual-phase dopamine transporter (DAT) positron emission tomography (PET) were performed to evaluate the diagnostic performance of DAT and early-to-delayed uptake ratios (E/Ds) in the anterior caudate (AC), posterior caudate (PC), anterior putamen (AP), posterior putamen (PP), and substantia nigra (SN) to differentiate ADP+/ADDLB from NC, and their effects on parkinsonism and cognition. DAT-SN and E/D-PP showed higher accuracies to differentiate ADP+/ADDLB from NC than DAT-PP. Among AD patients, lower DAT in the putamen and PC and higher E/Ds in the striatum were associated with severe parkinsonism, while higher E/Ds in the putamen, PC, and SN were associated with executive dysfunction. Our results suggest that decreased DAT-SN and increased E/D-PP could be biomarkers differentiating ADP+/ADDLB from pure AD and controls. Meanwhile, increased E/Ds in the putamen could reflect the severity of DLB presenting with parkinsonism and executive dysfunction among AD patients.

Effects of amyloid beta and dopaminergic depletion on perfusion and clinical symptoms.

INTRODUCTION: Although mixed pathologies are common in Alzheimer's disease (AD) and dementia with Lewy bodies (DLB), the effects of amyloid beta and dopaminergic depletion on brain perfusion and clinical symptoms have not been elucidated. METHODS: In 99 cognitive impairment patients due to AD and/or DLB and 32 controls, 18F-florbetaben (FBB) and dual-phase dopamine transporter (DAT) positron emission tomography (PET) were performed to measure the FBB standardized uptake value ratio (SUVR), striatal DAT uptakes, and brain perfusion. RESULTS: Higher FBB-SUVR and lower ventral striatal DAT uptake were intercorrelated and, respectively, associated with left entorhinal/temporo-parietal-centered hypoperfusion and vermis/hippocampal-centered hyperperfusion, whereas regional perfusion mediated clinical symptoms and cognition. DISCUSSION: Amyloid beta deposition and striatal dopaminergic depletion contribute to regional perfusion changes, clinical symptoms, and cognition in the spectrum of normal aging and cognitive impairment due to AD and/or LBD. HIGHLIGHTS: Amyloid beta (Aß) deposition was associated with ventral striatal dopaminergic depletion. Aß deposition and dopaminergic depletion correlated with perfusion. Aß deposition correlated with hypoperfusion centered in the left entorhinal cortex. Dopaminergic depletion correlated with hyperperfusion centered in the vermis. Perfusion mediated the Aß deposition/dopaminergic depletion's effects on cognition.

Neuropsychological Comparison of Patients With Alzheimer's Disease and Dementia With Lewy Bodies.

BACKGROUND AND PURPOSE: This study aimed to determine the neuropsychological differences between patients with early-stage Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) with a Clinical Dementia Rating (CDR) score of ≤1. METHODS: We examined 168 patients with AD (126 with CDR score=0.5, 42 with CDR score=1) and 169 patients with DLB (104 with CDR score=0.5, 65 with CDR score=1) whose diagnoses were supported by 18F-flobetaben positron-emission tomography (PET) and 18F-N-(3-fluoropropyl)-2ß-carbon ethoxy-3ß-(4-iodophenyl) nortropane PET. Neuropsychological test scores were compared after controlling for age, sex, and education duration. Using a cutoff motor score on the Unified Parkinson's Disease Rating Scale of 20, patients with AD were further divided into AD with parkinsonism (ADP+, n=86) and AD without parkinsonism (ADP-, n=82). RESULTS: At CDR scores of both 0.5 and 1, the DLB group had lower scores on the attention (digit-span forward at CDR score=0.5 and backward at CDR score=1), visuospatial, and executive (color reading Stroop test at CDR score=0.5 and phonemic fluency test, Stroop tests, and digit symbol coding at CDR score=1) tests than the AD group, but higher scores on the memory tests. The ADP- and ADP+ subgroups had comparable scores on most neuropsychological tests, but the ADP+ subgroup had lower scores on the color reading Stroop test. CONCLUSIONS: Patients with DLB had worse attention, visuospatial, and executive functions but better memory function than patients with AD. Parkinsonism was not uncommon in the patients with AD and could be related to attention and executive dysfunction.

Association of Neuropsychiatric Symptom Profiles With Cognitive Decline in Patients With Parkinson Disease and Mild Cognitive Impairment.

BACKGROUND AND OBJECTIVES: Neuropsychiatric symptoms (NPS) are closely associated with cognitive decline in patients with Parkinson disease (PD). We investigated which profiles of NPS are associated with the risk of dementia in PD with mild cognitive impairment (PD-MCI). METHODS: We retrospectively assessed 338 patients with PD-MCI from a single tertiary hospital, who underwent neuropsychological tests and a neuropsychiatric inventory (NPI) questionnaire. We conducted a factor analysis of the dichotomized presence of 12 NPI symptoms, yielding 3 NPI factors: factor 1, mood symptoms; factor 2, hyperactivity-related symptoms; and factor 3, psychotic symptoms. Factor analysis of the severity of NPI symptoms also identified similar NPI factors. The neuropsychiatric correlates of NPI factors were evaluated using general linear models for cognitive tests. Subsequently, we evaluated the hazard ratio (HR) of NPI factors on conversion to dementia. RESULTS: A higher prevalence factor 1 score was associated with lower scores in the verbal memory (ß = -0.15; 95% CI -0.24 to -0.06; p = 0.001) and executive domains (ß = -0.16; 95% CI -0.28 to -0.04; p = 0.007), whereas higher severity factor 2 scores were associated with lower scores in the naming (ß = -0.16; 95% CI -0.28 to -0.03; p = 0.012), visuospatial (ß = -0.24; 95% CI -0.41 to -0.07; p = 0.005), and verbal memory domains (ß = -0.15; 95% CI -0.24 to -0.05; p = 0.005). A higher severity factor 3 score was associated with lower scores in the visuospatial domain (ß = -0.25; 95% CI -0.46 to -0.07; p = 0.007). Cox regression models demonstrated that the risk of dementia was increased in those with higher prevalence factor 1 (HR = 1.48, 95% CI 1.17-1.88, p = 0.001) and factor 2 scores (HR = 1.27, 95% CI 1.07-1.51, p = 0.007) and severity factor 3 score (HR = 1.52, 95% CI 1.29-1.80, p < 0.001) after adjusting for age, sex, education, disease duration, scores for cognition and parkinsonism, and levodopa equivalent dose. DISCUSSION: This study demonstrated that a higher burden of NPS is associated with dementia conversion in patients with PD-MCI.

Striatal dopamine transporter uptake, parkinsonism and cognition in Alzheimer's disease.

BACKGROUND AND PURPOSE: The correlates of motor parkinsonism in Alzheimer's disease (AD) remain controversial. The effects of nigrostriatal dopaminergic degeneration on parkinsonism and cognition in biomarker-validated patients with AD were evaluated. METHODS: This study recruited 116 patients with AD who underwent dual-phase 18 F-N-(3-fluoropropyl)-2ß-carbon ethoxy-3ß-(4-iodophenyl) nortropane positron emission tomography, 18 F-florbetaben positron emission tomography, 3 T brain magnetic resonance imaging, and Unified Parkinson's Disease Rating Scale (UPDRS) and neuropsychological tests. The mean cortical thickness in the frontal, temporal, parietal and occipital cortices, and the dopamine transporter (DAT) uptake in the caudate, anterior/posterior putamen and substantia nigra were quantified. The relationship between DAT uptake, mean lobar cortical thickness, UPDRS motor score and cognition was investigated using general linear models (GLMs) after controlling for age, sex, education, intracranial volume, and deep and periventricular white matter hyperintensities. A path analysis was performed for the UPDRS motor score with the same covariates. RESULTS: Path analysis and multivariable GLMs for UPDRS motor score showed that lower caudate DAT uptake was directly associated with a higher UPDRS motor score, whereas caudate DAT uptake confounded the association between mean frontal/parietal thickness and UPDRS motor score. Multivariable GLMs for cognitive scores showed that lower caudate DAT uptake was associated with visuospatial/executive dysfunction independent of mean frontal or parietal thickness. CONCLUSIONS: Nigrostriatal dopaminergic dysfunction is associated with parkinsonism and visuospatial/executive dysfunction in patients with AD.

Substantia nigral dopamine transporter uptake in dementia with Lewy bodies.

Nigrostriatal dopaminergic degeneration is a pathological hallmark of dementia with Lewy bodies (DLB). To identify the subregional dopamine transporter (DAT) uptake patterns that improve the diagnostic accuracy of DLB, we analyzed N-(3-[18F] fluoropropyl)-2ß-carbomethoxy-3ß-(4-iodophenyl)-nortropane (FP-CIT) PET in 51 patients with DLB, in 36 patients with mild cognitive impairment with Lewy body (MCI-LB), and in 40 healthy controls (HCs). In addition to a high affinity for DAT, FP-CIT show a modest affinity to serotonin or norepinephrine transporters. Specific binding ratios (SBRs) of the nigrostriatal subregions were transformed to age-adjusted z-scores (zSBR) based on HCs. The diagnostic accuracy of subregional zSBRs were tested using receiver operating characteristic (ROC) curve analyses separately for MCI-LB and DLB versus HCs. Then, the effect of subregional zSBRs on the presence of clinical features and gray matter (GM) density were evaluated in all patients with MCI-LB or DLB as a group. ROC curve analyses showed that the diagnostic accuracy of DLB based on the zSBR of substantia nigra (area under the curve [AUC], 0.90) or those for MCI-LB (AUC, 0.87) were significantly higher than that based on the zSBR of posterior putamen for DLB (AUC, 0.72) or MCI-LB (AUC, 0.65). Lower zSBRs in nigrostriatal regions were associated with visual hallucination, severe parkinsonism, and cognitive dysfunction, while lower zSBR of substantia nigra was associated with widespread GM atrophy in DLB and MCI-LB patients. Taken together, our results suggest that evaluation of nigral DAT uptake may increase the diagnostic accuracy of DLB and MCI-LB than other striatal regions.

Air pollution is associated with faster cognitive decline in Alzheimer's disease.

OBJECTIVE: Although chronic exposure to air pollution is associated with an increased risk of dementia in normal elderlies, the effect of chronic exposure to air pollution on the rates of cognitive decline in Alzheimer's disease (AD) has not been elucidated. METHODS: In this longitudinal study, a total of 269 patients with mild cognitive impairment or early dementia due to AD with the evidence of brain ß-amyloid deposition were followed-up for a mean period of 4 years. Five-year normalized hourly cumulative exposure value of each air pollutant, such as carbon monoxide (CO), nitrogen dioxide (NO2 ), sulfur dioxide (SO2 ), and particulate matter (PM2.5 and PM10 ), was computed based on nationwide air pollution database. The effects of chronic exposure to air pollution on longitudinal cognitive decline rate were evaluated using linear mixed models. RESULTS: Higher chronic exposure to SO2 was associated with a faster decline in memory score, whereas chronic exposure to CO, NO2 , and PM10 were not associated with the rate of cognitive decline. Higher chronic exposure to PM2.5 was associated with a faster decline in visuospatial score in apolipoprotein E ε4 carriers. These effects remained significant even after adjusting for potential confounders. INTERPRETATION: Our findings suggest that chronic exposure to SO2 and PM2.5 is associated with faster clinical progression in AD.

Comparison Between 18F-Florapronol and 18F-Florbetaben Imaging in Patients With Cognitive Impairment.

BACKGROUND AND PURPOSE: To determine the imaging characteristics and cutoff value of 18F-florapronol (FC119S) quantitative analysis for detecting ß-amyloid positivity and Alzheimer's disease (AD), we compared the findings of FC119S and 18F-florbetaben (FBB) positron-emission tomography (PET) in patients with cognitive impairment. METHODS: We prospectively enrolled 35 patients with cognitive impairment who underwent FBB-PET, FC119S-PET, and brain magnetic resonance imaging. We measured global and vertex-wise standardized uptake value ratios (SUVRs) using a surface-based method with the cerebellar gray matter as reference. Optimal global FC119S SUVR cutoffs were determined using receiver operating characteristic curves for ß-amyloid positivity based on the global FBB SUVR of 1.478 and presence of AD, respectively. We evaluated the global and vertex-wise SUVR correlations between the two tracers. In addition, we performed correlation analysis for global or vertex-wise SUVR of each tracer with the vertex-wise cortical thicknesses. RESULTS: The optimal global FC119S SUVR cutoff value was 1.385 both for detecting ß-amyloid positivity and for detecting AD. Based on the global SUVR cutoff value of each tracer, 32 (91.4%) patients had concordant ß-amyloid positivity. The SUVRs of FC119S and FBB had strong global (r=0.72) and vertex-wise (r>0.7) correlations in the overall cortices, except for the parietal and temporal cortices (0.4

Low skull bone density is associated with poor motor prognosis in women with Parkinson's disease.

Parkinson's disease (PD) and osteoporosis are degenerative diseases that have shared pathomechanisms. To investigate the associations of skull bone density with nigrostriatal dopaminergic degeneration and longitudinal motor prognosis in female patients with PD. We analyzed the data of 260 drug-naïve female PD patients aged ≥50 years old who were followed-up for ≥3 years after their first visit to the clinic with baseline dopamine transporter (DAT) imaging. We measured skull bone density as a surrogate marker for systemic bone loss by calculating the Hounsfield unit (HU) in computed tomography scans. A Cox proportional hazard model was built to compare the rates of levodopa-induced dyskinesia (LID) or wearing-off according to skull HU. Longitudinal changes in levodopa-equivalent dose (LED) during a 3-year follow-up were assessed using a linear mixed model. A lower skull HU was associated with lower baseline DAT availability in striatal subregions; however, this relationship was not significant after adjusting for age, disease duration, body mass index, and white matter hyperintensities. After adjusting for confounding factors, a lower skull HU was significantly associated with an increased risk of LID development (hazard ratio = 1.660 per 1 standard deviation decrease, p = 0.007) and wearing-off (hazard ratio = 1.613, p = 0.016) in younger (<67 years) but not in older patients. Furthermore, a lower skull HU was associated with a steeper increase in LED during follow-up in younger patients only (ß = -21.99, p < 0.001). This study suggests that baseline skull bone density would be closely linked to motor prognosis in drug naïve women with PD.

Effects of Alzheimer's genetic risk scores and CSF biomarkers in de novo Parkinson's Disease.

Coexisting Alzheimer's disease (AD) pathology is common in Parkinson's disease (PD). However, the implications of genetic risk scores (GRS) for AD have not been elucidated in PD. In 413 de novo PD and 195 healthy controls from the Parkinson's Progression Marker Initiative database, the effects of GRS for AD (GRS-AD) and PD (GRS-PD) on the risk of PD and longitudinal CSF biomarkers and clinical outcomes were explored. Higher GRS-PD and lower baseline CSF α-synuclein were associated with an increased risk of PD. In the PD group, GRS-AD was correlated positively with CSF p-tau/Aß and negatively with CSF α-synuclein. Higher GRS-PD was associated with faster CSF p-tau/Aß increase, and GRS-AD and GRS-PD were interactively associated with CSF α-synuclein. In the PD group, higher GRS-AD was associated with poor visuospatial function, and baseline CSF p-tau/Aß was associated with faster cognitive decline. Higher GRS-PD was associated with better semantic fluency and frontal-related cognition and motor function given the same levels of CSF biomarkers and dopamine transporter uptake. Taken together, our results suggest that higher GRS-AD and CSF p-tau/Aß, reflecting AD-related pathophysiology, may be associated with cognitive decline in PD patients.

Effects of Alzheimer and Lewy Body Disease Pathologies on Brain Metabolism.

OBJECTIVE: This study aimed to determine the pattern of 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) related to postmortem Lewy body disease (LBD) pathology in clinical Alzheimer disease (AD). METHODS: FDG-PET scans were analyzed in 62 autopsy-confirmed patients and 110 controls in the Alzheimer's Disease Neuroimaging Initiative. Based on neuropathologic evaluations on Braak stage for neurofibrillary tangle, Consortium to Establish a Registry for AD score for neuritic plaque, and Lewy-related pathology, subjects were classified into AD(-)/LBD(-), AD(-)/LBD(+), AD(+)/LBD(-), and AD(+)/LBD(+) groups. The association between postmortem LBD and AD pathologies and antemortem brain metabolism was evaluated. RESULTS: AD and LBD pathologies had significant interaction effects to decrease metabolism in the cerebellar vermis, bilateral caudate, putamen, basal frontal cortex, and anterior cingulate cortex in addition to the left side of the entorhinal cortex and amygdala, and significant interaction effects to increase metabolism in the bilateral parietal and occipital cortices. LBD pathology was associated with hypermetabolism in the cerebellar vermis, bilateral putamen, anterior cingulate cortex, and basal frontal cortex, corresponding to the Lewy body-related hypermetabolic patterns. AD pathology was associated with hypometabolism in the bilateral hippocampus, entorhinal cortex, and posterior cingulate cortex regardless of LBD pathology, whereas LBD pathology was associated with hypermetabolism in the bilateral putamen and anterior cingulate cortex regardless of AD pathology. INTERPRETATION: Postmortem LBD and AD pathologies had significant interaction effects on the antemortem brain metabolism in clinical AD patients. Specific metabolic patterns related to AD and LBD pathologies could be elucidated when simultaneously considering the two pathologies. ANN NEUROL 2022;91:853-863.

White matter connectivity networks predict levodopa-induced dyskinesia in Parkinson's disease.

BACKGROUND: Although levodopa-induced dyskinesia-relevant white matter change has been evaluated, it is uncertain whether these changes may reflect the underlying predisposing conditions leading to the development of levodopa-induced dyskinesia. OBJECTIVE: To elucidate the role of white matter connectivity networks in the development of levodopa-induced dyskinesia in drug-naïve Parkinson's disease. METHODS: We recruited 30 patients who developed levodopa-induced dyskinesia within 5 years from MRI acquisition (vulnerable-group), 47 patients who had not developed levodopa-induced dyskinesia within 5 years (resistant-group), and 28 controls. We performed comparative analyses of whole-brain white matter integrity and connectivity using tract-based spatial and network- and degree-based statistics. We evaluated the predictability of levodopa-induced dyskinesia development and relationship with its latency, using the average connectivity strength as a predictor in Cox- and linear-regression, respectively. RESULTS: Mean-diffusivity was lower mainly at the left frontal region in the vulnerable-group compared to the resistant-group. Network-based statistics identified a subnetwork consisting of the bilateral fronto-striato-pallido-thalamic and lateral parietal regions (subnetwork A) and degree-based statistics identified four subnetworks (hub-subnetwork) consisting of edges centered on the left superior frontal gyrus, left putamen, left insular, or left precentral gyrus, where the vulnerable-group had stronger connectivity compared to the resistant-group. Stronger connectivity within the subnetwork A and hub-subnetwork centered on the left superior frontal gyrus was a predictor of levodopa-induced dyskinesia development independent of known risk factors and had an inverse relationship with its latency. CONCLUSIONS: Our data suggest that white matter connectivity subnetworks within corticostriatal regions play a pivotal role in the development of levodopa-induced dyskinesia.

Erratum.

[This corrects the article DOI: 10.1002/dad2.12177.].

Implication of Small Vessel Disease MRI Markers in Alzheimer's Disease and Lewy Body Disease.

BACKGROUND: Small vessel disease (SVD) magnetic resonance imaging (MRI) markers including deep and periventricular white matter hyperintensities (PWMH), lacunes, and microbleeds are frequently observed in Alzheimer's disease (AD) and Lewy body disease (LBD), but their implication has not been clearly elucidated. OBJECTIVE: To investigate the implication of SVD MRI markers in cognitively impaired patients with AD and/or LBD. METHODS: We consecutively recruited 57 patients with pure AD-related cognitive impairment (ADCI), 49 with pure LBD-related cognitive impairment (LBCI), 45 with mixed ADCI/LBCI, and 34 controls. All participants underwent neuropsychological tests, brain MRI, and amyloid positron emission tomography. SVD MRI markers including the severity of deep and PWMH and the number of lacunes and microbleeds were visually rated. The relationships among vascular risk factors, SVD MRI markers, ADCI, LBCI, and cognitive scores were investigated after controlling for appropriate covariates. RESULTS: LBCI was associated with more severe PWMH, which was conversely associated with an increased risk of LBCI independently of vascular risk factors and ADCI. PWMH was associated with attention and visuospatial dysfunction independently of vascular risk factors, ADCI, and LBCI. Both ADCI and LBCI were associated with more lobar microbleeds, but not with deep microbleeds. CONCLUSION: Our findings suggest that PWMH could reflect degenerative process related with LBD, and both AD and LBD independently increase lobar microbleeds.

Implication of metabolic and dopamine transporter PET in dementia with Lewy bodies.

To evaluate the implication of 18F-fluorodeoxyglucose (FDG)- and dopamine transporter (DAT)-positron emission tomography (PET) in the diagnosis and clinical symptoms of dementia with Lewy bodies (DLB), 55 DLB patients and 49 controls underwent neuropsychological evaluation and FDG-, DAT-, and 18F-Florbetaben (FBB) PET. DAT- and FDG-uptake and FDG/DAT ratio were measured in the anterior and posterior striatum. The first principal component (PC1) of FDG subject residual profiles was identified for each subject. Receiver operating characteristic curve analyses for the diagnosis of DLB were performed using FDG- and DAT-PET biomarkers as predictors, and general linear models for motor severity and cognitive scores were performed adding FBB standardized uptake value ratio as a predictor. Increased metabolism in the bilateral putamen, vermis, and somato-motor cortices, which characterized PC1, was observed in the DLB group, compared to the control group. A combination of posterior putamen FDG/DAT ratio and PC1 showed the highest diagnostic accuracy (91.8% sensitivity and 96.4% specificity), which was significantly greater than that obtained by DAT uptake alone. Striatal DAT uptake and PC1 independently contributed to motor severity and language, memory, frontal/executive, and general cognitive dysfunction in DLB patients, while only PC1 contributed to attention and visuospatial dysfunction.

Effects of baseline serum uric acid and apolipoprotein E4 on longitudinal cognition and cerebral metabolism.

Serum uric acid, a natural antioxidant, may have a protective effect on the progression of Alzheimer's disease (AD). To investigate the effect of serum uric acid on longitudinal cognitive and brain metabolic changes, we utilized data on baseline serum uric acid levels, APOE genotyping, and longitudinal cognitive scores from the Alzheimer's Disease Neuroimaging Initiative for 1,343 participants with normal cognition (NC), mild cognitive impairment (MCI), or dementia. In 979 participants, brain metabolism was measured using 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) images. Higher serum uric acid levels exhibited a detrimental effect on NC, whereas a protective trend was observed in individuals with cognitive impairment. Interestingly, higher uric acid levels were associated with a slower decline in cognitive scores and brain metabolism in females with MCI, and this effect was found in APOE4 carriers, but not in non-carriers. Longitudinal AD-like patterns of brain metabolism on FDG-PET images also appeared to mediate the effects of baseline uric acid levels on longitudinal cognitive decline. In summary, higher serum uric acid may interact with APOE4 to alleviate longitudinal metabolic changes and cognitive decline in female MCI patients.