Regional Cerebral Hypometabolism Research Articles

Brain metabolism during delirium

AbstractBackgroundAltered cerebral glucose metabolism manifested by increased cerebrospinal fluid (CSF) lactate and decreased neuron specific enolase during delirium has been found in CSF analyses in multiple settings, although without change in CSF or blood glucose. These changes correlate with markers of delirium severity and outcomes of delirium.However, patients with delirium are acutely unwell in hospital and have multiple comorbidities. The contribution of acute illness and dementia have not been excluded.MethodWe studied two groups of acutely unwell older people in hospital after excluding underlying dementia by history and the Informant Questionnaire on Cognitive Decline in the Elderly. The first group had delirium and the second group had no delirium. All patients underwent a 18F‐fluorodeoxyglucose positron emission tomography (FDG‐PET) scan in hospital while unwell, and during delirium for the first group. Confounders on FDG‐PET such as structural brain lesions and medications that affect brain metabolism were excluded.Then we also compared the delirium FDG‐PET scans to a group with Alzheimer’s dementia.ResultPatients with delirium demonstrated a unique, novel pattern of brain hypometabolism that reflected symptoms of delirium. The affected areas included: bilateral thalami; right posterior cingulate cortex (PCC); right superior frontal, right infero‐lateral anterior temporal and left superior parietal cortices. The areas highly negatively correlated with delirium severity scores (Spearman’s rank correlation coefficients between ρ = ‐0.39 and ‐0.71; p values from 0.089 to 0.001) and performance on a range of relevant neuropsychological tests, for example thalami and Trail Making Test B (Spearman’s ρ = ‐0.52; p = 0.028). Direct comparison to AD scans significant thalamic hypometabolism (p<0.01) in delirium, but the PCC was not different.ConclusionIn patients with acute illness but without dementia, delirium is accompanied by regional cerebral hypometabolism in a distribution that is not consistent with any known pattern of dementia. While there is some overlap with AD, thalamic hypometabolism is atypical of AD and consistent with the clinical features of delirium.ReferencesNitchingham AR, Pereira JV‐B, Wegner EA, Oxenham V, Close J Caplan GA. Regional cerebral hypometabolism on 18F‐FDG PET/CT scan in delirium is independent of acute illness and dementia. Alzheimers & Dementia 2022; 1‐10.

Exploration of visual hallucinations – FDG‐PET associations in DLB and MCI‐LB with and without visual hallucinations

AbstractBackgroundSeveral hypotheses exist regarding the neurologic substrate underlying visual hallucinations (VH) in Dementia with Lewy Bodies (DLB). Studies have suggested an association with regional cerebral hypometabolism in the primary visual or visual association cortices on FDG‐PET. We compared regional cerebral glucose metabolism and posterior cingulate island sign (CIS) ratios in DLB and in Mild Cognitive Impairment with Lewy Bodies (MCI‐LB) participants with (VH+) and without (VH‐) VH.MethodParticipants with clinically probable DLB or MCI‐LB and an FDG‐PET scan were identified from the Mayo ADRC database. Responses on the Visual Hallucinations and Delusions Questionnaire and Neuropsychiatric Inventory were used to assess presence or absence of VH. Standardized uptake value ratios (SUVr) were used to calculate regional cerebral glucose hypometabolism in the primary visual cortex (PVC), lateral occipital cortex (LOC), and whole occipital cortex (WOC). The CIS ratio was defined as posterior cingulate divided by the sum of the precuneus plus cuneus FDG‐PET uptake ratio.ResultTwo cohorts were identified (27 DLB and 18 MCI‐LB, 87% male). Eighteen DLB participants were VH+ and 9 were VH‐, whereas 5 MCI‐LB were VH+ and 13 were VH‐. There were no statistically significant differences in demographic (age, sex, education) and clinical features (MoCA, CDR, presence of other core DLB features, and UPDRS) between VH+ vs VH‐ in those with DLB, and between VH+ vs VH‐ in those with MCI‐LB. Similarly, there were no statistically significant differences in DLB between VH+ vs VH‐ in PVC (1.55±0.14 vs 1.58±0.15), LOC (1.22±0.16 vs 1.28±0.12), WOC (1.29±0.15 vs 1.34±0.11), or CIS ratio (1.16±0.08 vs 1.14±0.10), nor in MCI‐LB between VH+ vs VH‐ in PVC (1.68±0.19 vs 1.58±0.14), LOC (1.40±0.21 vs 1.32±0.14), WOC (1.45±0.20 vs 1.37±0.14), or CIS ratio (1.17±0.08 vs 1.19±0.10) (P>0.05 for all comparisons).ConclusionThese findings do not support a direct correlation between regional cerebral glucose metabolism and VH in DLB or MCI‐LB. Further work in DLB and MCI‐LB with larger numbers is warranted. Other neurologic substrates and mechanisms, such as REM sleep intrusions during wakefulness, neurotransmitter dysfunction, and disruption of functional connectivity across brain regions should be explored as contributors to VH in DLB.

Regional cerebral hypometabolism on 18F-FDG PET/CT scan in delirium is independent of acute illness and dementia.

Delirium is associated with new onset dementia and accelerated cognitive decline; however, its pathophysiology remains unknown. Cerebral glucose metabolism previously seen in delirium may have been attributable to acute illness and/or dementia. We aimed to statistically map cerebral glucose metabolism attributable to delirium. We assessed cerebral glucose metabolism using 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) in sick, older patients with and without delirium, all without clinical dementia (N=20). Strict exclusion criteria were adopted to minimize the effect of established confounders on FDG-PET. Patients with delirium demonstrated hypometabolism in the bilateral thalami and right superior frontal, right posterior cingulate, right infero-lateral anterior temporal, and left superior parietal cortices. Regional hypometabolism correlated with delirium severity and performance on neuropsychological testing. In patients with acute illness but without clinical dementia, delirium is accompanied by regional cerebral hypometabolism. While some hypometabolic regions may represent preclinical Alzheimer's disease (AD), thalamic hypometabolism is atypical of AD and consistent with the clinical features that are unique to delirium.

Sirtuin 3 attenuates amyloid-β induced neuronal hypometabolism.

Alzheimer’s disease (AD) is manifested by regional cerebral hypometabolism. Sirtuin 3 (Sirt3) is localized in mitochondria and regulates cellular metabolism, but the role of Sirt3 in AD-related hypometabolism remains elusive. We used expression profiling and weighted gene co-expression network analysis (WGCNA) to analyze cortical neurons from a transgenic mouse model of AD (APPSwInd). Based on WGCNA results, we measured NAD+ level, NAD+/ NADH ratio, Sirt3 protein level and its deacetylation activity, and ATP production across both in vivo and in vitro models. To investigate the effect of Sirt3 on amyloid-β (Aβ)-induced mitochondria damage, we knocked down and over-expressed Sirt3 in hippocampal cells. WGCNA revealed Sirt3 as a key player in Aβ-related hypometabolism. In APP mice, the NAD+ level, NAD+/ NADH ratio, Sirt3 protein level and activity, and ATP production were all reduced compared to the control. As a result, learning and memory performance were impaired in 9-month-old APP mice compared to wild type controls. Using hippocampal HT22 cells model, Sirt3 overexpression increased Sirt3 deacetylation activity, rescued mitochondria function, and salvaged ATP production, which were damaged by Aβ. Sirt3 plays an important role in regulating Aβ-induced cerebral hypometabolism. This study suggests a potential direction for AD therapy.

Differential patterns of regional cerebral hypometabolism according to the level of cerebral amyloid deposition in patients with amnestic mild cognitive impairment

Although amnestic mild cognitive impairment (aMCI) with high cerebral deposition of amyloid-beta proteins (Aβ) could be classified as a prodromal state of Alzheimer’s disease (AD) dementia, aMCI with the absence of or very little cerebral Aβ deposition is likely related to other pathophysiological processes. Thus, the present study aimed to investigate the differential patterns of regional cerebral glucose metabolism (rCMglu) according to the level of Aβ burden in the brains of patients with aMCI. This study included 25 patients with aMCI and 33 cognitively normal (CN) elderly individuals who underwent a comprehensive clinical examination, 11C-labelled Pittsburgh Compound B (PiB) positron emission tomography (PET) scans, and 18F-fluorodeoxyglucose (FDG) PET scans. Based on cerebral PiB retention, the aMCI subjects were divided into low Aβ (aMCI−, n=10) and high Aβ (aMCI+, n=15) subgroups, and differences in rCMglu among the CN group and aMCI subgroups were estimated on a voxel-by-voxel basis. Compared with the CN group, rCMglu was decreased in the bilateral medial temporal regions of the aMCI− subgroup and in the medial temporal cortices as well as the right precuneus of the aMCI+ subgroup. Additionally, rCMglu was lower in the right precuneus of the aMCI+ subgroup compared with the aMCI− subgroup. The present findings indicate that, even though both aMCI subgroups were phenomenologically very similar, the patients with aMCI− exhibited a markedly different regional pattern of functional neurodegeneration compared with the aMCI+ patients.

DIFFERENTIAL REGIONAL CEREBRAL HYPOMETABOLISM PATTERNS ACCORDING TO THE LEVEL OF CEREBRAL AMYLOID DEPOSITION IN MILD COGNITIVE IMPAIRMENT

DIFFERENTIAL REGIONAL CEREBRAL HYPOMETABOLISM PATTERNS ACCORDING TO THE LEVEL OF CEREBRAL AMYLOID DEPOSITION IN MILD COGNITIVE IMPAIRMENT

DIFFERENTIAL REGIONAL CEREBRAL HYPOMETABOLISM PATTERNS ACCORDING TO THE LEVEL OF CEREBRAL AMYLOID DEPOSITION IN MILD COGNITIVE IMPAIRMENT

DIFFERENTIAL REGIONAL CEREBRAL HYPOMETABOLISM PATTERNS ACCORDING TO THE LEVEL OF CEREBRAL AMYLOID DEPOSITION IN MILD COGNITIVE IMPAIRMENT

Severe somatization in women is associated with altered cerebral glucose metabolism.

Somatization is a clinical phenomenon characterized by multiple, medically unexplained somatic symptoms. The pathophysiology remains unknown. We aimed to test the hypothesis of a central nervous system dysfunction in the pathophysiology of this disorder. We studied 10 female patients diagnosed as having somatization disorder or undifferentiated somatoform disorder with no current Axis I disorders according to DSM-IV. They were compared with 17 healthy female volunteers using brain [18F]-fluorodeoxyglucose-PET with MRI reference. The patients had lower cerebral metabolism rates of glucose (P<0.05) in both caudate nuclei, left putamen and right precentral gyrus compared with healthy volunteers. This is the first study to demonstrate changes in brain metabolism in somatizing women. The regional cerebral hypometabolism is probably associated with the pathophysiology of somatization.

Early regional cerebral glucose hypometabolism in transgenic mice overexpressing the V717F β-amyloid precursor protein

In the present study, we examined whether the relative levels of regional brain [ 14C]2-deoxyglucose (2-DG) uptake are altered in a transgenic mouse model of Alzheimer's disease which overexpresses a mutated form of the human β-amyloid precursor protein (mutation V717F). We show that the relative levels of 2-DG uptake are significantly reduced in the septum, thalamus, dentate gyrus and parietal cortex of 3-month-old transgenic mice as compared with wild-type littermates. In 10-month-old transgenic mice, these alterations also extend to the CA3 hippocampal region, the cingulate, retrosplenial, occipital and temporal cortices, suggesting an age-dependent decrease in the regional 2-DG uptake. These results suggest that expression of a mutated APP gene induces an early regional cerebral hypometabolism independently of amyloid deposition per se.

High-resolution fluorodeoxyglucose positron emission tomography shows both global and regional cerebral hypometabolism in multiple sclerosis.

The authors study brain regional glucose metabolism prospectively in multiple sclerosis (MS) using high-resolution 2-[18-F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) in 25 MS patients of the Dent Neurologic Institute compared with 6 healthy subjects. Glucose metabolism is measured in 20 regions of interest using a line-profile technique. Compared with control subjects, a 9% reduction in total brain glucose metabolism is noted in MS patients (p < 0.05). Hypometabolism is widespread, including the cerebral cortex, subcortical nuclei, supratentorial white matter, and infratentorial structures. This reduction represents absolute regional decreases ranging from 3% to 18%. The most dramatic absolute reductions occur in the superior mesial frontal cortex, superior dorsolateral frontal cortex, mesial occipital cortex, lateral occipital cortex, deep inferior parietal white matter, and pons. The regional hypometabolism in the superior mesial frontal cortex and superior dorsolateral frontal cortex is statistically significant (p < 0.05), whereas the changes in the mesial occipital cortex (p = 0.07) and the lateral occipital cortex (p = 0.09) approach significance. The authors' findings suggest that widespread cerebral dysfunction occurs in MS, and that diaschisis or neuronal system disconnection resulting from white matter disease plays a major role. Cortical gray matter hypometabolism may also reflect direct MS involvement. The quantitative cerebral abnormalities detected by FDG PET may serve as a marker of disease activity in understanding the pathophysiological expression and therapeutic response of MS.

Ictal motor signs and interictal regional cerebral hypometabolism.

Early motor manifestations are the main components of focal seizures involving the frontal lobe. We examined the relationship between the initial ictal motor manifestations and interictal abnormalities of cerebral glucose consumption (rCMRGlc) as assessed by PET in 48 consecutive patients with focal seizures of neocortical origin. Group data analysis revealed that patients with predominantly unilateral clonic seizures had a significant contralateral perirolandic hypometabolism and to a lesser degree a contralateral frontomesial hypometabolism. Patients with predominantly focal tonic manifestations showed a hypometabolism within the frontomesial and perirolandic regions that was unilateral in all patients with lateralized tonic seizures. Patients with versive seizures had mainly contralateral metabolic depressions without a consistent regional pattern. Patients with hypermotor seizures had metabolic depressions involving frontomesial, anterior cingulate, perirolandic, and anterior insular/frontal operculum areas. In all patient groups, bilateral and symmetric hypometabolism of the thalamus and cerebellum was observed. We propose that this pattern of distinctly abnormal metabolic brain regions demonstrates not only possible epileptogenic zones but also symptomatogenic brain regions as shown by the associations between clinical manifestations and sets of abnormal brain regions, particularly if epileptogenic zones are in a clinically silent neocortical brain region. The detection and possible differentiation of symptomatogenic and epileptogenic zones might improve the effectiveness of presurgical noninvasive studies.