Reduced Brain Glucose Metabolism Research Articles

Treatment with Blackberry Extract and Metformin in Sporadic Alzheimer's Disease Model: Impact on Memory, Inflammation, Redox Status, Phosphorylated Tau Protein and Insulin Signaling.

Natural products offer promising potential for the development of new therapies for Alzheimer's disease (AD). Blackberry fruits are rich in phytochemical compounds capable of modulating pathways involved in neuroprotection. Additionally, drug repurposing and repositioning could also accelerate the development of news treatments for AD. In light of the reduced brain glucose metabolism in AD, an alternative approach has been the use of the drug metformin. Thus, the aim of this study was to evaluate the effect of treatment with blackberry extract in a model of AD induced by streptozotocin (STZ) and compare it with metformin treatment. Male rats were divided into groups: I-Control; II-STZ; III-STZ + blackberry extract (100mg/kg); IV-STZ + blackberry extract (200mg/kg) and V-STZ + metformin (150mg/kg). The animals received intracerebroventricular injection of STZ or buffer. Seven days after the surgical procedure, the animals were treated orally with blackberry extract or metformin for 21days. Blackberry extract and metformin prevented the memory impairment induced by STZ. In animals of group II, an increase in acetylcholinesterase activity, phosphorylated tau protein, IL-6, oxidative damage, and gene expression of GSK-3β and Nrf2 was observed in the hippocampus. STZ induced a decrease in IL-10 levels and down-regulated the gene expression of Akt1, IRS-1 and FOXO3a. Blackberry extract and metformin prevented the alterations in acetylcholinesterase activity, IL-6, GSK3β, Nrf2, and oxidative damage. In conclusion, blackberry extract exhibits multi-target actions in a model of AD, suggesting new therapeutic potentials for this neurodegenerative disease.

Ketone bodies mediate alterations in brain energy metabolism and biomarkers of Alzheimer's disease.

Alzheimer's disease (AD) is the most common form of dementia. AD is a progressive neurodegenerative disorder characterized by cognitive dysfunction, including learning and memory deficits, and behavioral changes. Neuropathology hallmarks of AD such as amyloid beta (Aβ) plaques and neurofibrillary tangles containing the neuron-specific protein tau is associated with changes in fluid biomarkers including Aβ, phosphorylated tau (p-tau)-181, p-tau 231, p-tau 217, glial fibrillary acidic protein (GFAP), and neurofilament light (NFL). Another pathological feature of AD is neural damage and hyperactivation of astrocytes, that can cause increased pro-inflammatory mediators and oxidative stress. In addition, reduced brain glucose metabolism and mitochondrial dysfunction appears up to 15 years before the onset of clinical AD symptoms. As glucose utilization is compromised in the brain of patients with AD, ketone bodies (KBs) may serve as an alternative source of energy. KBs are generated from the β-oxidation of fatty acids, which are enhanced following consumption of ketogenic diets with high fat, moderate protein, and low carbohydrate. KBs have been shown to cross the blood brain barrier to improve brain energy metabolism. This review comprehensively summarizes the current literature on how increasing KBs support brain energy metabolism. In addition, for the first time, this review discusses the effects of ketogenic diet on the putative AD biomarkers such as Aβ, tau (mainly p-tau 181), GFAP, and NFL, and discusses the role of KBs on neuroinflammation, oxidative stress, and mitochondrial metabolism.

Association of the fibronectin type III domain-containing protein 5 rs1746661 single nucleotide polymorphism with reduced brain glucose metabolism in elderly humans.

Fibronectin type III domain-containing protein 5 (FNDC5) and its derived hormone, irisin, have been associated with metabolic control in humans, with described FNDC5 single nucleotide polymorphisms being linked to obesity and metabolic syndrome. Decreased brain FNDC5/irisin has been reported in subjects with dementia due to Alzheimer's disease. Since impaired brain glucose metabolism develops in ageing and is prominent in Alzheimer's disease, here, we examined associations of a single nucleotide polymorphism in the FNDC5 gene (rs1746661) with brain glucose metabolism and amyloid-β deposition in a cohort of 240 cognitively unimpaired and 485 cognitively impaired elderly individuals from the Alzheimer's Disease Neuroimaging Initiative. In cognitively unimpaired elderly individuals harbouring the FNDC5 rs1746661(T) allele, we observed a regional reduction in low glucose metabolism in memory-linked brain regions and increased brain amyloid-β PET load. No differences in cognition or levels of cerebrospinal fluid amyloid-β42, phosphorylated tau and total tau were observed between FNDC5 rs1746661(T) allele carriers and non-carriers. Our results indicate that a genetic variant of FNDC5 is associated with low brain glucose metabolism in elderly individuals and suggest that FNDC5 may participate in the regulation of brain metabolism in brain regions vulnerable to Alzheimer's disease pathophysiology. Understanding the associations between genetic variants in metabolism-linked genes and metabolic brain signatures may contribute to elucidating genetic modulators of brain metabolism in humans.

Cross-sectional investigation of insulin resistance in youths with autism spectrum disorder. Any role for reduced brain glucose metabolism?

The autism spectrum disorder (ASD) is an etiologically heterogeneous disorder. Dysfunctions of the intermediate metabolism have been described in some patients. We speculate these metabolic abnormalities are associated with brain insulin resistance (IR), i.e., the reduced glucose metabolism at the level of the nervous central system. The Homeostasis model assessment of insulin resistance (HOMA-IR) is very often used in population studies as estimate of peripheral IR and it has been recently recognized as proxy of brain IR. We investigated HOMA-IR in 60 ASD patients aged 4–18 years and 240 healthy controls, also aged 4–18 years, but unmatched for age, sex, body weight, or body mass index (BMI). At multivariable linear regression model, the HOMA-IR was 0.31 unit higher in ASD individuals than in controls, after having adjusted for sex, age, BMI z-score category, and lipids that are factors known to influence HOMA-IR. Findings of this preliminary study suggest it is worth investigating brain glucose metabolism in larger population of patients with ASD by using gold standard technique. The recognition of a reduced glucose metabolism in some areas of the brain as marker of autism might have tremendous impact on our understanding of the pathogenic mechanisms of the disease and in terms of public health.

Hyperbaric oxygen ameliorates cognitive impairment in patients with Alzheimer’s disease and amnestic mild cognitive impairment

AbstractBackgroundIt is reported that environmental factors such as hypoxia could contribute to the pathogenesis of Alzheimer’s disease (AD). Therapeutics like hyperbaric oxygen treatment which improves tissue oxygen supply and ameliorates hypoxic conditions in the brain may be a strategy for AD and amnestic mild cognitive impairment (aMCI) treatment. The present work aims to investigate the potential therapeutic effect of hyperbaric oxygen treatment in patients with AD and aMCI.MethodWe included 42 AD and 11 aMCI patients in this study. All participants were continuously treated with hyperbaric oxygen treatment once daily for 20 days and assessed by neuropsychiatric assessments before and at 1, 3, and 6 months after the hyperbaric oxygen treatment. We also applied fluorodeoxyglucose positron emission tomography (FDG‐PET) in some of the patients.ResultHyperbaric oxygen treatment could improve the global cognitive functions, especially visuospatial and executive functions, language and abstract thinking abilities at 1 month after treatment in AD patients and improved the memory of aMCI patients in 1, 3, and 6 months after treatment. The ADL scores were improved in 1, 3, and 6 months after treatment in AD patients. Hyperbaric oxygen treatment also ameliorated the reduced brain glucose metabolism in AD and aMCI patients.ConclusionBased on the previous studies and our recent findings, hyperbaric oxygen treatment may be a potential therapeutic and preventive strategy for AD and aMCI.

Abstract P424: Low Liver Enzymes, Cognitive Performance and Dementia. The Atherosclerosis Risk in Communities Neurocognitive Study (aric-ncs)

Introduction: Low levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) among older adults are associated with mortality, and reportedly with lower cognitive performance, biomarkers of neurodegeneration, and dementia. We tested the associations of liver enzymes with cognition in ARIC-NCS. Methods: We studied 3191 participants (mean age 79 years, 59% female, 23% black) free of chronic liver disease and cirrhosis, and with AST:ALT ratio ≤2 at visit in 2016-2017. Serum ALT and AST were examined continuously and by quintiles, with the 3 rd quintile as the distribution-based modal reference range. Cognitive status (normal, mild cognitive impairment [MCI], dementia) was ascertained by an expert adjudication panel. A composite global cognition score was estimated from memory, executive function, and language tests. We used demographic and ApoE4 adjusted multinomial logistic and linear regressions. Results: Participants were classified as cognitively unimpaired (2375), MCI (602) or dementia (214). Lower levels of ALT and AST, and a higher AST:ALT ratio were associated with higher prevalence of dementia and lower global cognition scores ( Figure ). The prevalence odds ratio of dementia and MCI for the 1 st quintile, vs 3 rd quintile of ALT, were 1.73 (95% CI:1.06-2.81) and 1.27 (0.92-1.76), respectively. The corresponding estimates for AST were 1.71 (1.03-2.84) and 1.17 (0.87-1.59). Global cognition scores were lower in the 1 st vs 3 rd quintiles of ALT and AST by 0.13 (0.06-0.21) and 0.08 (0-0.15) standard deviation units, respectively. Additional adjustment for alcohol intake did not change the results. Conclusions: Liver hypometabolism is linked to reduced brain glucose metabolism, impaired production of neurotransmitters and synaptic maintenance, systemic insulin resistance and inflammation, while hepatic metabolite profiles are altered in dementia. Prospective assessments are warranted to characterize the role of hepatic metabolic dysfunction in cognitive impairment among older adults.

Overactive Bladder in Women: an Update for Primary Care Physicians

Overactive bladder (OAB) is a widely prevalent urinary condition affecting women of all ages, with increasing incidence in advancing age. A primary care provider is likely to encounter a significant proportion of women experiencing lower urinary tract symptoms (LUTS). This review serves primary care physicians as a thorough reference for a common condition causing LUTS in women. Most emerging data addressing overactive bladder relates to the different treatment modalities available. The side effect profile of antimuscarinic drugs remains an ongoing concern among OAB patients, especially with recent data linking the use of this class of drugs with Alzheimer’s and future development of dementia. In addition, it was recently demonstrated that individuals taking medications of medium-to-high anticholinergic activity had reduced brain glucose metabolism and increased brain atrophy. Combination treatments seem to be more efficacious than monotherapies, as has been proven when using mirabegron with antimuscarinics. Many studies have also validated the use of neuromodulation as a safe and effective treatment for OAB. Overactive bladder is a widely prevalent urinary condition affecting women of all ages. It is regarded as multifactorial with several proposed theories to explain its occurrence. Several tests are available to aid in diagnosing OAB. Symptom severity and patient-related factors including patient preferences drive treatment.

Hyperbaric oxygen ameliorates cognitive impairment in patients with Alzheimer's disease and amnestic mild cognitive impairment.

IntroductionIt has been reported that environmental factors such as hypoxia could contribute to the pathogenesis of Alzheimer's disease (AD). Therapeutics like hyperbaric oxygen treatment, which improves tissue oxygen supply and ameliorates hypoxic conditions in the brain, may be an alternative therapy for AD and amnestic mild cognitive impairment (aMCI). The present work aims to investigate the potential therapeutic effect of hyperbaric oxygen treatment for AD and aMCI.MethodsWe recruited 42 AD, 11 aMCI, and 30 control AD patients in this study. AD and aMCI patients were treated with 40 minutes of hyperbaric oxygen once a day for 20 days and assessed by neuropsychiatric assessments including Mini‐Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Activities of Daily Living (ADL) scale before and at 1‐, 3‐, and 6‐month follow‐up after treatment. Control AD patients who were not given hyperbaric oxygen treatment had similar clinical profile as hyperbaric oxygen treated AD. We examined 10 of the AD/aMCI patients with fluorodeoxyglucose positron emission tomography.ResultsIn self‐comparison study, one course of hyperbaric oxygen treatment significantly improved the cognitive function assessed by MMSE and MoCA in AD patients after 1‐month follow‐up; such treatment also significantly improved MMSE score at 3‐month follow‐up and MoCA score at 1‐ and 3‐month follow‐up in aMCI patients. The ADL scale was significantly improved in AD patients after 1‐ and 3‐month follow‐up. Compared to the control AD patients, the MMSE and MoCA in hyperbaric oxygen treated AD patients were significantly improved after 1‐month follow‐up. Hyperbaric oxygen treatment also ameliorated the reduced brain glucose metabolism in some of the AD and aMCI patients.ConclusionBased on previous studies and our recent findings, we propose that hyperbaric oxygen treatment may be a promising alternative therapy for AD and aMCI.

Association Between Reduced Brain Glucose Metabolism and Cortical Thickness in Alcoholics: Evidence of Neurotoxicity.

Excessive alcohol consumption is associated with reduced cortical thickness (CT) and lower cerebral metabolic rate of glucose (CMRGlu), but the correlation between these 2 measures has not been investigated. We tested the association between CT and cerebral CMRGlu in 19 participants with alcohol use disorder (AUD) and 20 healthy controls. Participants underwent 2-Deoxy-2-[18F]fluoroglucose positron emission tomography to map CMRGlu and magnetic resonance imaging to assess CT. Although performance accuracy on a broad range of cognitive domains did not differ significantly between AUD and HC, AUD had widespread decreases in CT and CMRGlu. CMRGlu, normalized to cerebellum (rCMRGlu), showed significant correlation with CT across participants. Although there were large group differences in CMRGlu (>17%) and CT (>6%) in medial orbitofrontal and BA 47, the superior parietal cortex showed large reductions in CMRGlu (~17%) and minimal CT differences (~2.2%). Though total lifetime alcohol (TLA) was associated with CT and rCMRGlu, the causal mediation analysis revealed significant direct effects of TLA on rCMRGlu but not on CT, and there were no significant mediation effects of TLA, CT, and rCMRGlu. The significant correlation between decrements in CT and CMRGlu across AUD participants is suggestive of alcohol-induced neurotoxicity, whereas the findings that the most metabolically affected regions in AUD had minimal atrophy and vice versa indicates that changes in CT and CMRGlu reflect distinct responses to alcohol across brain regions.

Association of Altered Liver Enzymes With Alzheimer Disease Diagnosis, Cognition, Neuroimaging Measures, and Cerebrospinal Fluid Biomarkers

Increasing evidence suggests an important role of liver function in the pathophysiology of Alzheimer disease (AD). The liver is a major metabolic hub; therefore, investigating the association of liver function with AD, cognition, neuroimaging, and CSF biomarkers would improve the understanding of the role of metabolic dysfunction in AD. To examine whether liver function markers are associated with cognitive dysfunction and the "A/T/N" (amyloid, tau, and neurodegeneration) biomarkers for AD. In this cohort study, serum-based liver function markers were measured from September 1, 2005, to August 31, 2013, in 1581 AD Neuroimaging Initiative participants along with cognitive measures, cerebrospinal fluid (CSF) biomarkers, brain atrophy, brain glucose metabolism, and amyloid-β accumulation. Associations of liver function markers with AD-associated clinical and A/T/N biomarkers were assessed using generalized linear models adjusted for confounding variables and multiple comparisons. Statistical analysis was performed from November 1, 2017, to February 28, 2019. Five serum-based liver function markers (total bilirubin, albumin, alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase) from AD Neuroimaging Initiative participants were used as exposure variables. Primary outcomes included diagnosis of AD, composite scores for executive functioning and memory, CSF biomarkers, atrophy measured by magnetic resonance imaging, brain glucose metabolism measured by fludeoxyglucose F 18 (18F) positron emission tomography, and amyloid-β accumulation measured by [18F]florbetapir positron emission tomography. Participants in the AD Neuroimaging Initiative (n = 1581; 697 women and 884 men; mean [SD] age, 73.4 [7.2] years) included 407 cognitively normal older adults, 20 with significant memory concern, 298 with early mild cognitive impairment, 544 with late mild cognitive impairment, and 312 with AD. An elevated aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio and lower levels of ALT were associated with AD diagnosis (AST to ALT ratio: odds ratio, 7.932 [95% CI, 1.673-37.617]; P = .03; ALT: odds ratio, 0.133 [95% CI, 0.042-0.422]; P = .004) and poor cognitive performance (AST to ALT ratio: β [SE], -0.465 [0.180]; P = .02 for memory composite score; β [SE], -0.679 [0.215]; P = .006 for executive function composite score; ALT: β [SE], 0.397 [0.128]; P = .006 for memory composite score; β [SE], 0.637 [0.152]; P < .001 for executive function composite score). Increased AST to ALT ratio values were associated with lower CSF amyloid-β 1-42 levels (β [SE], -0.170 [0.061]; P = .04) and increased amyloid-β deposition (amyloid biomarkers), higher CSF phosphorylated tau181 (β [SE], 0.175 [0.055]; P = .02) (tau biomarkers) and higher CSF total tau levels (β [SE], 0.160 [0.049]; P = .02) and reduced brain glucose metabolism (β [SE], -0.123 [0.042]; P = .03) (neurodegeneration biomarkers). Lower levels of ALT were associated with increased amyloid-β deposition (amyloid biomarkers), and reduced brain glucose metabolism (β [SE], 0.096 [0.030]; P = .02) and greater atrophy (neurodegeneration biomarkers). Consistent associations of serum-based liver function markers with cognitive performance and A/T/N biomarkers for AD highlight the involvement of metabolic disturbances in the pathophysiology of AD. Further studies are needed to determine if these associations represent a causative or secondary role. Liver enzyme involvement in AD opens avenues for novel diagnostics and therapeutics.

GLUCOSE METABOLISM AS A THERAPEUTIC TARGET IN ALZHEIMER’S DISEASE

Reduced brain glucose metabolism is a consistent feature of Alzheimer's disease (AD), and predicts progression from amnestic mild cognitive impairment (aMCI) to AD dementia. Greater decreases in F18fluorodeoxyglucose uptake with positron emission tomography (FDG-PET) correlate with greater cognitive impairment along the continuum from normal cognitive status to aMCI to AD dementia. In spite of the tight linkage of glucose metabolism to brain function and the decline in AD, only a very limited number of studies have tried to understand why glucose utilization is diminished or tried to reverse this AD-related deficit. Thiamine-dependent enzymes are critical components of glucose metabolism and are reduced in brains of AD patients. Increasing thiamine in humans or animals increases glucose utilization, improves brain metabolism and cognition, including memory. The most effective way to increase blood and brain thiamine is with benfotiamine because of superior pharmacokinetics. Our aim is to test the effect of administering benfotiamine on brain glucose metabolism (FDG-PET) and clinical impact as measured by changes in Assessment Scale-Cognitive subscale (ADAS-Cog) over time in patients with aMCI or AD. A randomized, double-blind, placebo-controlled clinical trial with benfotiamine in patients with aMCI or mild AD was initiated. The primary objective is to determine whether increasing thiamine availability with benfotiamine can slow cognitive decline compared to placebo, as measured by a change in the ADAS Cog score over the twelve-month trial. The secondary objective is to test whether benfotiamine will slow the decline in glucose utilization in patients as measured by FDG-PET. Using blocked, stratified randomization, 76 patients will be assigned to the treatment or placebo group. Stratification is based on Mini Mental Status Exam score (>21) to better understand if treatment responses differ according to initial cognitive impairment. Of the 464 patients screened, 45 patients have been enrolled. Patient characteristics will be detailed in the poster. The trial will determine whether benfotiamine provides clinical or underlying biological benefit for aMCI/AD patients and if this correlates with changes in glucose utilization.

Glucose deficit triggers tau pathology and synaptic dysfunction in a tauopathy mouse model

Clinical investigations have highlighted a biological link between reduced brain glucose metabolism and Alzheimer’s disease (AD). Previous studies showed that glucose deprivation may influence amyloid beta formation in vivo but no data are available on the effect that this condition might have on tau protein metabolism. In the current paper, we investigated the effect of glucose deficit on tau phosphorylation, memory and learning, and synaptic function in a transgenic mouse model of tauopathy, the h-tau mice. Compared with controls, h-tau mice with brain glucose deficit showed significant memory impairments, reduction of synaptic long-term potentiation, increased tau phosphorylation, which was mediated by the activation of P38 MAPK Kinase pathway. We believe our studies demonstrate for the first time that reduced glucose availability in the central nervous system directly triggers behavioral deficits by promoting the development of tau neuropathology and synaptic dysfunction. Since restoring brain glucose levels and metabolism could afford the opportunity to positively influence the entire AD phenotype, this approach should be considered as a novel and viable therapy for preventing and/or halting the disease progression.

Insulin resistance and reduced brain glucose metabolism in the aetiology of Alzheimer’s disease

Significant epidemiological and clinical evidence has emerged that suggests Alzheimer’s disease (AD) can be added to the list of chronic illnesses that are primarily caused by modern diets and lifestyles at odds with human physiology. High intakes of refined carbohydrates insufficient physical activity, suboptimal sleep quantity and quality, and other factors that may contribute to insulin resistance combine to create a perfect storm of glycation and oxidative stress in the brain. Specific neurons lose the ability to metabolise and harness energy from glucose, ultimately resulting in neuronal degeneration and death. Simultaneously, chronic peripheral hyperinsulinaemia prevents ketogenesis, thus depriving struggling neurons of a highly efficient alternative fuel substrate. The intimate association between type 2 diabetes and AD suggests that they have common underlying causes, namely insulin resistance and perturbed glucose metabolism. Preclinical evidence of AD is detectable decades before over symptoms appear, indicating that AD progresses over time, with observable signs manifesting only after the brain’s compensatory mechanisms have failed and widespread neuronal atrophy begins to interfere with cognition and performance of daily life tasks. That dietary and environmental triggers play pivotal roles in causing AD suggests that nutrition and lifestyle based interventions may hold the key to ameliorating or preventing this debilitating condition for which conventional pharmaceutical treatments are largely ineffective. Results from small scale clinical studies indicate that dietary and lifestyle strategies may be effective for reversing dementia and cognitive impairment. Increased research efforts should be dedicated towards this promising avenue in the future.

Basal Forebrain Cholinergic Deficits Reduce Glucose Metabolism and Function of Cholinergic and GABAergic Systems in the Cingulate Cortex.

PurposeReduced brain glucose metabolism and basal forebrain cholinergic neuron degeneration are common features of Alzheimer's disease and have been correlated with memory function. Although regions representing glucose hypometabolism in patients with Alzheimer's disease are targets of cholinergic basal forebrain neurons, the interaction between cholinergic denervation and glucose hypometabolism is still unclear. The aim of the present study was to evaluate glucose metabolism changes caused by cholinergic deficits.Materials and MethodsWe lesioned basal forebrain cholinergic neurons in rats using 192 immunoglobulin G-saporin. After 3 weeks, lesioned animals underwent water maze testing or were analyzed by 18F-2-fluoro-2-deoxyglucose positron emission tomography.ResultsDuring water maze probe testing, performance of the lesioned group decreased with respect to time spent in the target quadrant and platform zone. Cingulate cortex glucose metabolism in the lesioned group decreased, compared with the normal group. Additionally, acetylcholinesterase activity and glutamate decarboxylase 65/67 expression declined in the cingulate cortex.ConclusionOur results reveal that spatial memory impairment in animals with selective basal forebrain cholinergic neuron damage is associated with a functional decline in the GABAergic and cholinergic system associated with cingulate cortex glucose hypometabolism.

Preliminary Study of Brain Glucose Metabolism Changes in Patients with Lung Cancer of Different Histological Types

Background:Cerebral glucose metabolism changes are always observed in patients suffering from malignant tumors. This preliminary study aimed to investigate the brain glucose metabolism changes in patients with lung cancer of different histological types.Methods:One hundred and twenty patients with primary untreated lung cancer, who visited People's Hospital of Zhengzhou University from February 2012 to July 2013, were divided into three groups based on histological types confirmed by biopsy or surgical pathology, which included adenocarcinoma (52 cases), squamous cell carcinoma (43 cases), and small-cell carcinoma (25 cases). The whole body 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) of these cases was retrospectively studied. The brain PET data of three groups were analyzed individually using statistical parametric maps (SPM) software, with 50 age-matched and gender-matched healthy controls for comparison.Results:The brain resting glucose metabolism in all three lung cancer groups showed regional cerebral metabolic reduction. The hypo-metabolic cerebral regions were mainly distributed at the left superior and middle frontal, bilateral superior and middle temporal and inferior and middle temporal gyrus. Besides, the hypo-metabolic regions were also found in the right inferior parietal lobule and hippocampus in the small-cell carcinoma group. The area of the total hypo-metabolic cerebral regions in the small-cell carcinoma group (total voxel value 3255) was larger than those in the adenocarcinoma group (total voxel value 1217) and squamous cell carcinoma group (total voxel value 1292).Conclusions:The brain resting glucose metabolism in patients with lung cancer shows regional cerebral metabolic reduction and the brain hypo-metabolic changes are related to the histological types of lung cancer.

Brain MRI, SPECT and PET in Early Alzheimer’s Disease: A Minor Mismatch between Volumetric and Functional Findings

Background: Limited data are available in the literature comparing brain SPECT, PET and volumetric MRI in the same cohort of patients with Alzheimer’s disease. Objectives: The main goal was to show a correlation between two different functional imaging substrates, as determined by FDG-PET and SPECT, with structural MRI findings as defined by voxel-based volumetric measurements (VBM), in the same cohort of patients with AD. Methods: 20 patients (9 male) with confirmed clinical diagnosis of Alzheimer’s disease (AD) and mild dementia according to NINCDS/ADRDA and DSM-III-R criteria were selected to be included in the present study. Twenty normal elderly volunteers constituted the Control Group. The two groups were paired for age, sex and educational level (p>0.05). The same clinical protocol was applied in patients and controls. Brain SPECT, PET and MR were performed with an interval among them shorter than 4 weeks. Results: Reduced brain glucose metabolism (MRglc) by PET occurred predominantly in the posterior cingulum and precuneus, followed by bilateral posterior parietal, lower temporal and frontal cortices (p<0.001). Similar findings were shown on SPECT, albeit with lesser statistical significance compared to FDG-PET (Z score of 3.89 vs. 5.32). SPECT depicted subtle blood flow reduction in mesial temporal lobes on SPM, a finding not reproduced by PET. MRI showed significant atrophy in hippocampus and superior temporal cortex, bilaterally, but not in the posterior cingulate gyrus, parietal or frontal lobes. Conclusion: A not perfect correlation was seen among the findings seen on SPECT, PET and MRI in the same cohort of patients with AD, suggesting that structural and functional methods reveal distinct substrates of the disease. Keywords: Alzheimer's disease, dementia, FDG, PET, SPECT, volumetric MRI.

A behavioral and micro positron emission tomography imaging study in a rat model of hypothyroidism

Hypothyroidism leads to somatic, neuropsychological, and psychiatric changes that are similar to depression. The mechanisms underlying the behavioral abnormalities in adult onset hypothyroidism remain ambiguous. Hypothyroidism was induced in adult male Wistar rats by the maintenance of 0.05% propylthiouracil (PTU) in drinking water for 5 weeks (hypothyroid group; HP group); control rats (CON group) received an equivalent amount of water. The open field and sucrose preference tests were employed, and the link between behavioral changes and brain glucose metabolism was evaluated using micro positron emission tomography imaging. The open field test revealed slightly decreased locomotor activity and significantly reduced rearing and defecation in the hypothyroid group. Hypothyroid rats were also characterized by decreased body weight, sucrose preference, and relative sucrose intake compared to control rats. Hypothyroidism induced reduced brain glucose metabolism in the bilateral motor cortex, the caudate putamen, the cortex cingulate, the nucleus accumbens, and the frontal association cortex. A decreased sucrose preference was positively correlated with metabolic glucose changes in the caudate putamen and the nucleus accumbens. The results indicate that the activity pattern in adult onset hypothyroidism is different from the activity pattern when hypothyroidism is induced in the developmental period of the central nervous system. Decreased sucrose preference in hypothyroid rats may be attributed to anhedonia. Furthermore, these findings suggest there may be a common mechanism underlying adult onset hypothyroidism and depression.

Reduced brain glucose metabolism in hypertension

After correcting for multiple comparison, in subjects with high WML burden (n1⁄415) higher Bvol was related to higher mean systolic (rho1⁄4.62, p1⁄4.02), mean diastolic (rho1⁄4.61, p1⁄4.02) and mean daily MAP (mean arterial pressure) (rho1⁄4.63, p1⁄4.01) as derived from 24-hour ambulatory blood pressure monitoring. The relationship between systolic, diastolic, MAP derived from one time office measurements and Bvol, were weaker and did not survive the Bonferroni correction. There was no relationship between blood pressure measurements and Bvol in the subgroup with mild or absent WML. These findings support the notion that in brain with vascular damage higher BP is related to less atrophy. Moreover, they confirm that 24hour ABPM measurements are better predictor of brain volumes than one-time, in office BP examination.

Role of Medium Chain Triglycerides (Axona®) in the Treatment of Mild to Moderate Alzheimer's Disease.

Treatment of Alzheimer's disease (AD) with acetylcholinesterase inhibitors or N-methyl-D-aspartate (NMDA) receptor antagonists provides symptomatic relief but do not prevent its progression. Thus, additional approaches aimed at slowing the progression of the disease have been investigated. Reports detailing reduced brain glucose metabolism in the early stages of AD led to the hypothesis that alternate energy sources aimed at increasing neuronal metabolism may protect neurons and thus benefit patients with AD. Medium-chain triglycerides (MCTs) are metabolized to ketone bodies that serve as an alternative source of energy for neurons. Data from clinical trials suggest that MCTs improve cognition in patients with mild to moderate AD in apolipoprotein E4-negative patients. Adverse events observed were mild and included minor gastrointestinal problems such as diarrhea, dyspepsia, and flatulence. However, since genomic profiles are not routinely conducted in patients with AD in a clinical setting, the role of MCTs in clinical practice seems to be minimal.

Maternal age affects brain metabolism in adult children of mothers affected by Alzheimer's disease

Cognitively normal (NL) individuals with a maternal history of late-onset Alzheimer's disease (MH) show reduced brain glucose metabolism on FDG-PET as compared to those with a paternal history (PH) and those with negative family history (NH) of Alzheimer's disease (AD). This FDG-PET study investigates whether metabolic deficits in NL MH are associated with advancing maternal age at birth. Ninety-six NL individuals with FDG-PET were examined, including 36 MH, 24 PH, and 36 NH. Regional-to-whole brain gray matter standardized FDG uptake value ratios were examined for associations with parental age across groups using automated regions-of-interest and statistical parametric mapping. Groups were comparable for clinical and neuropsychological measures. Brain metabolism in AD-vulnerable regions was lower in MH compared to NH and PH, and negatively correlated with maternal age at birth only in MH. There were no associations between paternal age and metabolism in any group. Evidence for a maternally inherited, maternal age-related mechanism provides further insight on risk factors and genetic transmission in late-onset AD.