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Visceral adipose tissue (VAT) dysfunction has been recently recognized as a potential contributor to the development of Alzheimer's disease (AD). This study aimed to explore the relationship between VAT metabolism and cerebral glucose metabolism in patients with cognitive impairment. This cross-sectional prospective study included 54 patients who underwent 18F-fluorodeoxyglucose (18F-FDG) brain and torso positron emission tomography/computed tomography (PET/CT), and neuropsychological evaluations. VAT metabolism was measured by 18F-FDG torso PET/CT, and cerebral glucose metabolism was measured using 18F-FDG brain PET/CT. A voxel-based analysis revealed that the high-VAT-metabolism group exhibited a significantly lower cerebral glucose metabolism in AD-signature regions such as the parietal and temporal cortices. In the volume-of-interest analysis, multiple linear regression analyses with adjustment for age, sex, and white matter hyperintensity volume revealed that VAT metabolism was negatively associated with cerebral glucose metabolism in AD-signature regions. In addition, higher VAT metabolism was correlated with poorer outcomes on cognitive assessments, including the Korean Boston Naming Test, Rey Complex Figure Test immediate recall, and the Controlled Oral Word Association Test. In conclusion, our study revealed significant relationships among VAT metabolism, cerebral glucose metabolism, and cognitive function. This suggests that VAT dysfunction actively contributes to the neurodegenerative processes characteristic of AD, making VAT dysfunction targeting a novel AD therapy approach. [ABSTRACT FROM AUTHOR]

The visceral adipose tissue (VAT) has been recognized as an endocrine organ, and VAT dysfunction could be a risk factor for Alzheimer's disease (AD). We aimed to evaluate the association of VAT metabolism with AD pathology. This cross-sectional study included 54 older subjects with cognitive impairment who underwent 2-deoxy-2-[fluorine-18]-fluoro-D-glucose (18F-FDG) torso positron emission tomography (PET) and 18F-florbetaben brain PET. 18F-FDG uptake in VAT on 18F-FDG PET images was used as a marker of VAT metabolism, and subjects were classified into high and low VAT metabolism groups. A voxel-based analysis revealed that the high VAT metabolism group exhibited a significantly higher cerebral amyloid-β (Aβ) burden than the low VAT metabolism group. In the volume-of-interest analysis, multiple linear regression analyses with adjustment for age, sex, and white matter hyperintensity volume revealed that 18F-FDG uptake in VAT was significantly associated with the cerebral Aβ burden (β = 0.359, p = 0.007). In conclusion, VAT metabolism was associated with AD pathology in older subjects. Our findings suggest that VAT dysfunction could contribute to AD development. [ABSTRACT FROM AUTHOR]

Background: Although several studies have reported an association between thyroid dysfunction and Alzheimer's disease (AD), the effect of mild thyroid dysfunction within the normal range of thyrotropin (TSH) on the development of AD remains unclear. The aim of this study was to evaluate the association between thyroid hormones and the pathology of AD in euthyroid subjects. Methods: Sixty-nine subjects with a TSH level between 0.5 and 4.5 μIU/L who underwent 18F-florbetaben positron emission tomography were included in this prospective cross-sectional study. The levels of serum free thyroxine (fT4) and TSH were quantified using radioimmunoassay. Neuropsychological tests were performed to assess cognitive function. Differences in cerebral amyloid-β (Aβ) burden were compared between high-normal TSH (TSH ≥2.5 μIU/mL) and low-normal TSH (TSH <2.5 μIU/mL) groups. Multiple linear regression analyses, adjusted for age, sex, education level, and Neuropsychiatric Inventory scores, were performed to evaluate relationships between thyroid hormone levels and both cerebral Aβ burden and cognitive function. Results: The cerebral Aβ burden in the high-normal TSH group was significantly higher than in the low-normal TSH group (1.53 ± 0.31 vs. 1.35 ± 0.22, p = 0.009). The fT4 levels were negatively correlated with cerebral Aβ burden (β = −0.240, p = 0.035), and TSH levels were positively correlated with cerebral Aβ burden (β = 0.267, p = 0.020). The fT4 level was also positively associated with cognitive function, as inferred from neuropsychological test scores. Conclusions: Thyroid hormone concentrations were associated with AD pathology in euthyroid subjects. Our findings suggest that AD is likely to occur even in individuals with high-normal TSH levels. [ABSTRACT FROM AUTHOR]

Los daños en la sustancia blanca (DSB), detectados como hiperintensidades en las imágenes de RM ponderadas en T2, representan la enfermedad de pequeños vasos cerebrales, y están considerados como un factor de riesgo potencial de trastornos de la memoria y disfunción cognitiva. No se ha evidenciado suficientemente que la disfunción cognitiva en pacientes con enfermedad de Alzheimer esté causada por DSB y la patología β-amiloide (Aβ). El objetivo de estudio fue evaluar la relación entre los DSB y el metabolismo de la glucosa cerebral en pacientes con disfunción cognitiva, tras el ajuste de la carga cerebral de Aβ. Incluimos en este estudio transversal a ochenta y tres sujetos con desempeño cognitivo que oscilaba entre normal y demencia, a quienes se realizó RM cerebral y PET con Florbetaben (18F) y PET con 18F-FDG. Utilizamos la escala Fazekas para cuantificar los DSB en la RM cerebral ponderada en T2. Estimamos cuantitativamente la carga cerebral de Aβ y el metabolismo de la glucosa cerebral utilizando el análisis del volumen de interés. Evaluamos las diferencias del metabolismo de la glucosa cerebral regional entre los grupos de bajo DSB (escala Fazekas < 2) y alto DSB (escala Fazekas ≥ 2). Realizamos un análisis de regresión lineal múltiple ajustado por edad, sexo y carga cerebral de Aβ, para evaluar la relación entre la puntuación de la escala Fazekas y el metabolismo de la glucosa cerebral. El metabolismo de la glucosa cerebral regional para los lóbulos bilateral frontal, temporal, córtices parietales, y lóbulos límbicos en el grupo de alto DSB fueron significativamente menores que los del grupo de bajo DSB. Existieron correlaciones negativas significativas entre la puntuación de la escala Fazekas y el metabolismo de la glucosa cerebral regional en los córtices bilateral frontal, bilateral temporal y córtices parietales izquierdos, y lóbulos límbicos bilaterales. Los análisis de regresión lineal múltiple revelaron que la puntuación de la escala Fazekas era un determinante independiente del metabolismo de la glucosa en los córtices bilateral frontal y temporal y los lóbulos límbicos. Los DSB están asociados a un descenso del metabolismo de la glucosa cerebral. Nuestros hallazgos sugieren que la enfermedad de los pequeños vasos, así como lo patología de Aβ, pueden contribuir a la disfunción cognitiva en pacientes con enfermedad de Alzheimer. White matter lesions (WMLs), detected as hyperintensities on T2-weighted MRI, represent small vessel disease in the brain and are considered a potential risk factor for memory and cognitive impairment. It has not been sufficiently evident that cognitive impairment in patients with Alzheimer's disease is caused by WMLs as well as β-amyloid (Aβ) pathology. The aim of this study was to evaluate relationship between WMLs and cerebral glucose metabolism in patients with cognitive impairment after adjustment of cerebral Aβ burden. Eighty-three subjects with cognitive performance ranging from normal to dementia, who underwent brain MRI and 18F-florbetaben positron emission tomography (PET) and 18F-fluorodeoxyglucose PET, were included in this cross-sectional study. The Fazekas scale was used to quantify WMLs on brain T2-weighted MRI. The cerebral Aβ burden and cerebral glucose metabolism were quantitatively estimated using volume-of-interest analysis. Differences in the regional cerebral glucose metabolism were evaluated between low-WML (Fazekas scale < 2) and high-WML (Fazekas scale ≥ 2) groups. Multiple linear regression analysis adjusted for age, sex and cerebral Aβ burden was performed to evaluate the relationship between the Fazekas scale score and cerebral glucose metabolism. The regional cerebral glucose metabolism for the bilateral frontal, temporal, and parietal cortices, and limbic lobes in the high-WML group were significantly lower than those in the low-WML group. There were significant negative correlations between the Fazekas scale score and regional cerebral glucose metabolism in the bilateral frontal, bilateral temporal and left parietal cortices, and bilateral limbic lobes. Multiple linear regression analysis revealed that the Fazekas scale score was an independent determinant of the glucose metabolism in the bilateral frontal and temporal cortices and limbic lobes. WMLs are associated with decreased cerebral glucose metabolism. Our findings suggest that small vessel disease, as well as Aβ pathology, may contribute to cognitive impairment in patients with Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Introduction: White matter lesions (WMLs), detected as hyperintensities on T2-weighted MRI, represent small vessel disease in the brain and are considered a potential risk factor for memory and cognitive impairment in older adults. The purpose of this study was to evaluate the association between WMLs and cerebral amyloid-β (Aβ) burden in patients with cognitive impairment. Methods: A total of 83 patients with cognitive impairment, who underwent brain MRI and F-18 florbetaben PET, were included prospectively: 19 patients were cognitively unimpaired, 30 exhibited mild cognitive impairment (MCI), and 34 exhibited dementia. The Fazekas scale was used to quantify WMLs on T2-weighted brain MR images. Cerebral Aβ burden was quantitatively estimated using volume-of-interest analysis. Differences in cerebral Aβ burden were evaluated between low-WML (Fazekas scale ≤1) and high-WML (Fazekas scale ≥2) groups. The relationship between the Fazekas rating and cerebral Aβ burden was evaluated using linear regression analysis after adjusting for age and sex. Results: In the overall cohort, the high-WML group exhibited significantly higher Aβ burden compared with the low-WML group (P = 0.011) and cerebral Aβ burden was positively correlated with Fazekas rating (β = 0.299, P = 0.006). In patients with MCI, the high-WML group exhibited significantly higher Aβ burden compared with the low-WML group (P = 0.019) and cerebral Aβ burden was positively correlated with Fazekas rating (β = 0.517, P = 0.003). Conclusion: The presence of WMLs was associated with cerebral Aβ burden in patients with MCI. Our findings suggest that small vessel disease in the brain is related to Alzheimer’s disease pathology. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether subcortical grey matter atrophy predicts progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD), and to compare subcortical volumes between AD, MCI and controls. To assess the correlation between subcortical grey matter volumes and severity of cognitive impairment.Methods: We included 773 participants with three-dimensional T1-weighted MRI at 3 T, made up of 181 controls, who had subjective memory symptoms with normal cognition, 201 MCIs and 391 AD. During follow-up (2.0 ± 0.9 years), 35 MCIs converted to AD (progressive MCI) and 160 MCIs remained stable (stable MCI). We segmented volumes of six subcortical structures of the amygdala, thalamus, caudate nucleus, putamen, globus pallidus and nucleus accumbens, and of the hippocampus, using FMRIBs integrated registration and segmentation tool.Results: Analysis of variances, adjusted for sex and age, showed that all structures, except the globus pallidus, were smaller in AD than in controls. In addition, the amygdala, thalamus, putamen, nucleus accumbens and hippocampus were smaller in MCIs than in controls. Across groups, all subcortical greymatter volumes, except the globus pallidus, showed a positive correlation with cognitive function, as measured by Mini Mental State Examination (MMSE) (0.16Conclusions: In addition to the hippocampus, the nucleus accumbens volume loss was also associated with increased risk of progression from MCI to AD. Furthermore, volume loss of subcortical grey matter structures was associated with severity of cognitive impairment. [ABSTRACT FROM AUTHOR]

Background/Aims: The apolipoprotein E (APOE) genotype in response to pharmacological treatments in patients with Alzheimer's disease (AD) remains a matter of controversy. This analysis investigated the effect of the APOE genotype on the clinical response to rivastigmine transdermal patch monotherapy or memantine plus rivastigmine patch in patients with mild to moderate AD. Methods: Two hundred and six (n = 206) patients with probable AD and Mini-Mental State Examination (MMSE) scores of 10-20 were randomized to rivastigmine patch monotherapy or memantine plus rivastigmine patch for 24 weeks. Of the 206 patients with probable AD, 146 patients who consented to genetic testing for APOE were included and assessed for this subgroup study. Results: There were no significant differences on MMSE, NPI, ADAS-cog, ADCS-ADL, CDR-SB, NPI and FAB between rivastigmine patch monotherapy and memantine plus rivastigmine patch according to the APOE genotype. However, patients with moderately severe AD (MMSE ≤15) who were APOE ε4 carriers showed higher responder rates on ADCS-ADL with memantine plus rivastigmine patch compared to rivastigmine patch monotherapy. Conclusion: Moderately severe AD patients with the APOE ε4 allele may respond more favorably to memantine plus rivastigmine patch than ε4 noncarriers. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]