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.

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.

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.

Distinct influence of parental occupation on cortical thickness and surface area in children and adolescents: Relation to self-esteem.

Studies of socioeconomic disparities have largely focused on correlating brain measures with either composite measure of socioeconomic status (SES), or its components-family income or parental education, giving little attention to the component of parental occupation. Emerging evidence suggests that parental occupation may be an important and neglected indicator of childhood and adolescent SES compared to absolute measures of material resources or academic attainment because, while related, it may more precisely capture position in social hierarchy and related health outcomes. On the other hand, although cortical thickness and surface area are brain measures with distinct genetic and developmental origins, large-scale neuroimaging studies investigating regional differences in interaction of the composite measure of SES or its components with cortical thickness and surface area are missing. We set out to fill this gap, focusing specifically on the role of parental occupation on cortical thickness and surface area by analyzing magnetic resonance imaging scans from 704 healthy individuals (age = 3-21 years). We observed spatially distributed patterns of (parental occupation × age2 ) interaction with cortical thickness (localized at the left caudal middle frontal, the left inferior parietal and the right superior parietal) and surface area (localized at the left orbitofrontal cortex), indicating independent sources of variability. Further, with decreased cortical thickness, children from families with lower parental occupation exhibited lower self-esteem. Our findings demonstrate distinct influence of parental occupation on cortical thickness and surface area in children and adolescents, potentially reflecting different neurobiological mechanisms by which parental occupation may impact brain development.

Exploring Individual Brain Variability during Development based on Patterns of Maturational Coupling of Cortical Thickness: A Longitudinal MRI Study.

Structural covariance has recently emerged as a tool to study brain connectivity in health and disease. The main assumption behind the phenomenon of structural covariance is that changes in brain structure during development occur in a coordinated fashion. However, no study has yet explored the correlation of structural brain changes within individuals across development. Here, we used longitudinal magnetic resonance imaging scans from 141 normally developing children and adolescents (scanned 3 times) to introduce a novel subject-based maturational coupling approach. For each subject, maturational coupling was defined as similarity in the trajectory of cortical thickness (across the time points) between any two cortical regions. Our approach largely captured features seen in population-based structural covariance, and confirmed strong maturational coupling between homologous and near-neighbor cortical regions. Stronger maturational coupling among several homologous regions was observed for females compared to males, possibly indicating greater interhemispheric connectivity in females. Developmental changes in maturational coupling within the default-mode network (DMN) aligned with developmental changes in structural and functional DMN connectivity. Our findings indicate that patterns of maturational coupling within individuals may provide mechanistic explanation for the phenomenon of structural covariance, and allow investigation of individual brain variability with respect to cognition and disease vulnerability.

Effects of dopaminergic depletion and brain atrophy on neuropsychiatric symptoms in de novo Parkinson's disease.

BACKGROUND: Neuropsychiatric symptoms impact the patients' quality of life and caregivers' burdens in Parkinson's disease (PD). We aimed to investigate the effects of striatal dopaminergic depletion and brain atrophy on the neuropsychiatric symptoms of patients with PD. METHODS: Two hundred and seven patients with de novo drug-naïve PD underwent dopamine transporter (DAT) positron emission tomography and brain MRI scanning. In addition, the patients were assessed with caregiver-administered neuropsychiatric inventory (NPI) questionnaires. To evaluate the effects of DAT uptake, subcortical volume and cortical thinning on the patients' neuropsychiatric symptoms, we performed logistic regression and negative binomial regression analyses on the NPI data after controlling for possible confounders. RESULTS: Frontal cortical thinning was associated with the presence of nighttime behaviour and irritability, and the thinning correlated with the severity of the nighttime behaviour. Temporal cortical thinning was associated with the presence of aggression/agitation, and it correlated with the severity of the aggression/agitation. Subcortical atrophy in the accumbens was associated with the presence of disinhibition and correlated with the severity of the disinhibition. Putamen atrophy and insular thinning were independently associated with the presence of apathy, but only insular thinning correlated with the severity of the apathy. Of the predictors, only frontal cortical thinning correlated with the total NPI score. CONCLUSIONS: The results of this study suggested that accumbens atrophy and frontotemporal cortical thinning, especially frontal cortical thinning, independently contributed to neuropsychiatric symptoms in patients with PD, while DAT uptake did not affect the neuropsychiatric symptoms.

Olfactory dysfunction in Alzheimer's disease- and Lewy body-related cognitive impairment.

INTRODUCTION: Olfactory dysfunction is common in Alzheimer's disease- and Lewy body-related disorders, but its neural correlates have not been clearly elucidated. METHODS: We retrospectively recruited 237 patients with Alzheimer's disease-related cognitive impairment (ADCI) and 217 with Lewy body-related cognitive impairment (LBCI). They were identically evaluated using the Cross-Cultural Smell Identification Test, neuropsychological tests, and brain magnetic resonance imaging. RESULTS: LBCI had more severe olfactory dysfunction than ADCI. Patients with more severe cognitive dysfunction had worse olfactory function in both groups. In ADCI, lower Cross-Cultural Smell Identification Test scores correlated with a lower cortical thickness in brain regions typically affected in Alzheimer's disease, most prominently in the right parahippocampal cortex, whereas in LBCI, the scores correlated with white matter abnormalities in regions vulnerable to Lewy body, including subcortical regions of the orbitofrontal and frontoparietal cortices. DISCUSSION: Our results suggest that cortical atrophy in ADCI and white matter abnormalities in LBCI play important roles in olfactory dysfunction.

Dementia-Predicting Cognitive Risk Score and Its Correlation with Cortical Thickness in Parkinson Disease.

BACKGROUND: We developed a risk score system to predict risks of developing dementia in individual Parkinson disease (PD) patients using baseline neuropsychological tests. METHODS: A total of 216 nondemented PD patients underwent a baseline neuropsychological evaluation and were followed up for a mean of 2.7 (±1.1) years. Univariate Cox regression models controlled for age, gender, and education selected neuropsychological tests individually predicting dementia risk. Then, a multivariate Cox regression model combined them into a cognitive risk score system. Cortical areas correlating with cognitive risk score were investigated using a separate MRI data set from 207 nondemented PD patients. RESULTS: Fifty-two patients (23.9%) developed dementia. The univariate Cox regression analyses identified the confrontational naming and semantic fluency tests, frontal/executive function tests, immediate verbal memory test, and visuospatial function test as predicting dementia risk. The calculated cognitive risk score (range 53-188) predicted future dementia with moderate accuracy (integrated area under the curve = 0.79; 95% CI: 0.73-0.85). A higher cognitive risk score correlated with cortical thinning in the right anteromedial temporal cortex, bilateral posterior cingulate cortex, right anterior cingulate cortex, left parahippocampal gyrus, and right superior frontal cortex in a separate MRI data set. CONCLUSION: The cognitive risk score system is a useful approach to predict the dementia risk among PD patients.

NEOCIVET: Towards accurate morphometry of neonatal gyrification and clinical applications in preterm newborns.

Cerebral cortical folding becomes dramatically more complex in the fetal brain during the 3rd trimester of gestation; the process continues in a similar fashion in children who are born prematurely. To quantify this morphological development, it is necessary to extract the interface between gray matter and white matter, which is particularly challenging due to changing tissue contrast during brain maturation. We employed the well-established CIVET pipeline to extract this cortical surface, with point correspondence across subjects, using a surface-based spherical registration. We then developed a variant of the pipeline, called NEOCIVET, that quantified cortical folding using mean curvature and sulcal depth while addressing the well-known problems of poor and temporally-varying gray/white contrast as well as motion artifact in neonatal MRI. NEOCIVET includes: i) a tissue classification technique that analyzed multi-atlas texture patches using the nonlocal mean estimator and subsequently applied a label fusion approach based on a joint probability between templates, ii) neonatal template construction based on age-specific sub-groups, and iii) masking of non-interesting structures using label-fusion approaches. These techniques replaced modules that might be suboptimal for regional analysis of poor-contrast neonatal cortex. The proposed segmentation method showed more accurate results in subjects with various ages and with various degrees of motion compared to state-of-the-art methods. In the analysis of 158 preterm-born neonates, many with multiple scans (n=231; 26-40weeks postmenstrual age at scan), NEOCIVET identified increases in cortical folding over time in numerous cortical regions (mean curvature: +0.003/week; sulcal depth: +0.04mm/week) while folding did not change in major sulci that are known to develop early (corrected p<0.05). The proposed pipeline successfully mapped cortical structural development, supporting current models of cerebral morphogenesis, and furthermore, revealed impairment of cortical folding in extremely preterm newborns relative to relatively late preterm newborns, demonstrating its potential to provide biomarkers of prematurity-related developmental outcome.

Association of Body Fat Percentage and Waist-hip Ratio With Brain Cortical Thickness: A Study Among 1777 Cognitively Normal Subjects.

BACKGROUND: Increasing evidence has emerged that there is a link between body weight and the risk of developing dementia. However, the relationship between adiposity and brain structure has not yet been fully elucidated. We aimed to evaluate the association of body fat composition with cortical thickness in cognitively normal subjects. METHODS: In total, 1777 (887 men and 890 women) cognitively normal subjects, aged 45 years or older, were recruited from the Health Promotion Center in South Korea. Medical records including 3-dimensional magnetic resonance imaging, body fat percentage, waist-hip ratio (WHR), and other factors were reviewed. RESULTS: In men, the percentage of fat was positively associated with cortical thickness and the highest WHR group showed significantly decreased cortical thickness compared with the reference group. WHR showed an inverted U-shaped association with total cortical thickness and frontal lobe thickness in men. Among women, there was no significant association. CONCLUSIONS: Our findings suggest that in men, body fat is positively associated with cortical thickness, whereas abdominal fat is negatively associated with cortical thickness.

Association between body mass index and cortical thickness: among elderly cognitively normal men and women.

BACKGROUND: There is increasing evidence of a relationship between underweight or obesity and dementia risk. Several studies have investigated the relationship between body weight and brain atrophy, a pathological change preceding dementia, but their results are inconsistent. Therefore, we aimed to evaluate the relationship between body mass index (BMI) and cortical atrophy among cognitively normal participants. METHODS: We recruited cognitively normal participants (n = 1,111) who underwent medical checkups and detailed neurologic screening, including magnetic resonance imaging (MRI) in the health screening visits between September 2008 and December 2011. The main outcome was cortical thickness measured using MRI. The number of subjects with five BMI groups in men/women was 9/9, 148/258, 185/128, 149/111, and 64/50 in underweight, normal, overweight, mild obesity, and moderate to severe obesity, respectively. Linear and non-linear relationships between BMI and cortical thickness were examined using multiple linear regression analysis and generalized additive models after adjustment for potential confounders. RESULTS: Among men, underweight participants showed significant cortical thinning in the frontal and temporal regions compared to normal weight participants, while overweight and mildly obese participants had greater cortical thicknesses in the frontal region and the frontal, temporal, and occipital regions, respectively. However, cortical thickness in each brain region was not significantly different in normal weight and moderate to severe obesity groups. Among women, the association between BMI and cortical thickness was not statistically significant. CONCLUSIONS: Our findings suggested that underweight might be an important risk factor for pathological changes in the brain, while overweight or mild obesity may be inversely associated with cortical atrophy in cognitively normal elderly males.

Higher education affects accelerated cortical thinning in Alzheimer's disease: a 5-year preliminary longitudinal study.

BACKGROUND: Epidemiological studies have reported that higher education (HE) is associated with a reduced risk of incident Alzheimer's disease (AD). However, after the clinical onset of AD, patients with HE levels show more rapid cognitive decline than patients with lower education (LE) levels. Although education level and cognition have been linked, there have been few longitudinal studies investigating the relationship between education level and cortical decline in patients with AD. The aim of this study was to compare the topography of cortical atrophy longitudinally between AD patients with HE (HE-AD) and AD patients with LE (LE-AD). METHODS: We prospectively recruited 36 patients with early-stage AD and 14 normal controls. The patients were classified into two groups according to educational level, 23 HE-AD (>9 years) and 13 LE-AD (≤9 years). RESULTS: As AD progressed over the 5-year longitudinal follow-ups, the HE-AD showed a significant group-by-time interaction in the right dorsolateral frontal and precuneus, and the left parahippocampal regions compared to the LE-AD. CONCLUSION: Our study reveals that the preliminary longitudinal effect of HE accelerates cortical atrophy in AD patients over time, which underlines the importance of education level for predicting prognosis.

Amyloid burden, cerebrovascular disease, brain atrophy, and cognition in cognitively impaired patients.

BACKGROUND: We investigated the independent effects of Alzheimer's disease (AD) and cerebrovascular disease (CVD) pathologies on brain structural changes and cognition. METHODS: Amyloid burden (Pittsburgh compound B [PiB] retention ratio), CVD markers (volume of white matter hyperintensities [WMH] and number of lacunae), and structural changes (cortical thickness and hippocampal shape) were measured in 251 cognitively impaired patients. Path analyses were utilized to assess the effects of these markers on cognition. RESULTS: PiB retention ratio was associated with hippocampal atrophy, which was associated with memory impairment. WMH were associated with frontal thinning, which was associated with executive and memory dysfunctions. PiB retention ratio and lacunae were also associated with memory and executive dysfunction without the mediation of hippocampal or frontal atrophy. CONCLUSIONS: Our results suggest that the impacts of AD and CVD pathologies on cognition are mediated by specific brain regions.

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.

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.

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.

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

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.

Cortical Thickness and Brain Glucose Metabolism in Healthy Aging.

BACKGROUND AND PURPOSE: We aimed to determine the effect of demographic factors on cortical thickness and brain glucose metabolism in healthy aging subjects. METHODS: The following tests were performed on 71 subjects with normal cognition: neurological examination, 3-tesla magnetic resonance imaging, 18F-fluorodeoxyglucose positron-emission tomography, and neuropsychological tests. Cortical thickness and brain metabolism were measured using vertex- and voxelwise analyses, respectively. General linear models (GLMs) were used to determine the effects of age, sex, and education on cortical thickness and brain glucose metabolism. The effects of mean lobar cortical thickness and mean lobar metabolism on neuropsychological test scores were evaluated using GLMs after controlling for age, sex, and education. The intracranial volume (ICV) was further included as a predictor or covariate for the cortical thickness analyses. RESULTS: Age was negatively correlated with the mean cortical thickness in all lobes (frontal and parietal lobes, p=0.001; temporal and occipital lobes, p<0.001) and with the mean temporal metabolism (p=0.005). Education was not associated with cortical thickness or brain metabolism in any lobe. Male subjects had a lower mean parietal metabolism than did female subjects (p<0.001), while their mean cortical thicknesses were comparable. ICV was positively correlated with mean cortical thickness in the frontal (p=0.016), temporal (p=0.009), and occipital (p=0.007) lobes. The mean lobar cortical thickness was not associated with cognition scores, while the mean temporal metabolism was positively correlated with verbal memory test scores. CONCLUSIONS: Age and sex affect cortical thickness and brain glucose metabolism in different ways. Demographic factors must therefore be considered in analyses of cortical thickness and brain metabolism.