Striatal Volume Research Articles

Hidden brain atrophy in ultra-high field MR images in a transgenic rat model of Huntington's disease

The predominant neuropathological sign of Huntington's disease (HD) is a profound and progressive neuronal cell loss in the striatum and the neo-cortex. These histopathological changes have been widely investigated in post-mortem brains obtained from animal models of HD. However, imaging studies in rodents have so far led to conflicting results, where the outcomes have not been in line with histopathological findings. Herein, we aimed to further characterize the progression of neurodegeneration in a transgenic rat model of HD at different ages.Volumetric changes were measured in vivo via ultra-high field MR imaging (7T) and subsequent stereological analysis in the striatum, lateral ventricles, and cerebral cortex of tgHD rats were investigated at 9, 12, and 18-months of age.Histological assessment showed significant atrophy in the striatum, enlarged ventricular volumes, and a thinning of the cerebral cortex in tgHD rats at the late phase of the disease when compared to the wild-type (WT) littermates. Whereas only a reduction in striatal cell volume was observed at the early stage of the disease. MR imaging on the other hand, did not show detectable volumetric change in the investigated structures between tgHD and WT rats at different time-points.Our findings demonstrate neuronal shrinkage precedes striatal atrophy in tgHD rats. As in human HD, the manifestation of striatal atrophy appears prior to cortical thinning in tgHD rats. Surprisingly, contemporary in vivo ultra-high field MR imaging failed to detect these volumetric changes. These findings suggest that contemporary MRI protocols are unsuitable for detecting HD related alterations in rodent brain.

Behavioral features in child and adolescent huntingtin gene-mutation carriers.

IntroductionWe compared neuropsychiatric symptoms between child and adolescent huntingtin gene‐mutation carriers and noncarriers. Given previous evidence of atypical striatal development in carriers, we also assessed the relationship between neuropsychiatric traits and striatal development.MethodsParticipants between 6 and 18 years old were recruited from families affected by Huntington's disease and tested for the huntingtin gene expansion. Neuropsychiatric traits were assessed using the Pediatric Behavior Scale and the Behavior Rating Inventory of Executive Function. Striatal volumes were extracted from 3T neuro‐anatomical images. Multivariable linear regression models were conducted to evaluate the impact of group (i.e., gene nonexpanded [GNE] or gene expanded [GE]), age, and trajectory of striatal growth on neuropsychiatric symptoms.ResultsThere were no group differences in any behavioral measure with the exception of depression/anxiety score, which was higher in the GNE group compared to the GE group (estimate = 4.58, t(129) = 2.52, FDR = 0.051). The growth trajectory of striatal volume predicted depression scores (estimate = 0.429, 95% CI 0.15:0.71, p = .0029), where a negative slope of striatal volume over time was associated with lower depression/anxiety.ConclusionsThe current findings show that GE children may have lower depression/anxiety compared to their peers. Previously, we observed a unique pattern of early striatal hypertrophy and continued decrement in volume over time among GE children and adolescents. In contrast, GNE individuals largely show striatal volume growth. These findings suggest that the lower scores of depression and anxiety seen in GE children and adolescents may be associated with differential growth of the striatum.

P580. Two Schizophrenia Neuroanatomical Signatures From the PHENOM Consortium and Their Association With Psychopathology, Cognition, and Genetics in the Population-Level Samples

The presence and significance of risk factors of schizophrenia at the population level are debated. Herein we replicate the two recently found neuroanatomical signatures of schizophrenia from the PHENOM consortium—first with widespread reductions of gray matter volume and second with increased striatal volume—and investigate their presence in population-level samples. We further examine their association with psychosis spectrum symptoms (PS), cognition, and schizophrenia genetic risk.

Striatal volumes as potential biomarkers in Eating Disorders: A pilot study

IntroductionDifferences in bulimic and impulsive behaviours in Eating Disorders (ED) have been associated with cortico-striatal circuit dysfunction at a neurobiological level. We sought to investigate neo-striatal volume as a biomarker in ED subgroups as well as the possible relationship with trauma history. Material and methodsWe studied 24 female patients: Anorexia Nervosa AN (n=8), Bulimia Nervosa BN (n=9), comorbid ED with borderline personality disorder (EDc; n=7), and a group of Healthy Controls (n=19). Binge eating behaviours and impulsivity scales were used to characterize our sample as well as Trauma Questionnaires and Magnetic resonance imaging (MRI) volumetric manual measurements of caudate and putamen nuclei (striatum). ResultsOur preliminary results showed a significantly larger left putaminal volume in AN compared to the other three groups [C (p=0.008), BN (p<.001) and EDc (p=.001)] and a smaller right putaminal volume in EDc compared to controls (p=.045) and AN (p=.039).Some negative correlations were found between bilateral putaminal volumes and self-reported general and early traumatization scores. ConclusionThis pilot study suggested that striatal volumes might differentiate AN from BN and EDc at a neurobiological level with implications for treatment strategies. Larger scale studies should be carried out that allow replication of these data.

Larger striatal volume is associated with increased adult psychopathy

Prior studies have inconsistently reported increased volumes of the striatum in adults with psychopathy. A meta-analysis presented here indicates an overall effect size of d = 0.44. Nevertheless, variability in findings exist, and questions remain on confounding clinical conditions and generalizability to females. This study tests the hypothesis that striatal volumes are increased in adults with psychopathic traits, and that this relationship is mediated by stimulation-seeking and impulsivity. Striatal volume was assessed using magnetic resonance imaging in 108 adult community-dwelling males alongside psychopathy using the Psychopathy Checklist – Revised. Subsidiary, exploratory analyses were conducted on a small sample of females. Correlational analyses showed that increased striatal volumes were associated with more psychopathic traits (p = .001). Effects were observed for all striatal regions, controlling for age, substance dependence and abuse, antisocial personality disorder, attention deficit hyperactivity disorder, social adversity, and total brain volume. An analysis of 18 psychopathic individuals showed that striatal volumes were increased 9.4% compared with 18 matched controls (p = .01). Psychopathy in females was also significantly associated with increased striatal volume (p = .02). Stimulation-seeking and impulsivity partly mediated the striatal-psychopathy relationship, accounting for 49.4% of this association. Findings from these two samples replicate and build on initial studies indicating striatal enlargement in adults with psychopathy, yielding an updated effect size of d = 0.48. Results are consistent with the notion that striatal abnormalities in individuals with psychopathy partly reflect increased sensation-seeking and impulsivity, and support the hypothesis of abnormal reward processing in psychopathy.

Altered canonical and striatal-frontal resting state functional connectivity in children with pathogenic variants in the Ras/mitogen-activated protein kinase pathway.

Mounting evidence supports the role of the Ras/mitogen-activated protein kinase (Ras/MAPK) pathway in neurodevelopmental disorders. Here, the authors used a genetics-first approach to examine how Ras/MAPK pathogenic variants affect the functional organization of the brain and cognitive phenotypes including weaknesses in attention and inhibition. Functional MRI was used to examine resting state functional connectivity (RSFC) in association with Ras/MAPK pathogenic variants in children with Noonan syndrome (NS). Participants (age 4–12 years) included 39 children with NS (mean age 8.44, SD=2.20, 25 females) and 49 typically developing (TD) children (mean age 9.02, SD=9.02, 33 females). Twenty-eight children in the NS group and 46 in the TD group had usable MRI data and were included in final analyses. The results indicated significant hyperconnectivity for the NS group within canonical visual, ventral attention, left frontoparietal and limbic networks (p<0.05 FWE). Higher connectivity within canonical left frontoparietal and limbic networks positively correlated with cognitive function within the NS but not the TD group. Further, the NS group demonstrated significant group differences in seed-based striatal-frontal connectivity (Z>2.6, p<0.05 FWE). Hyperconnectivity within canonical brain networks may represent an intermediary phenotype between Ras/MAPK pathogenic variants and cognitive phenotypes, including weaknesses in attention and inhibition. Altered striatal-frontal connectivity corresponds with smaller striatal volume and altered white matter connectivity previously documented in children with NS. These results may indicate delayed maturation and compensatory mechanisms and they are important for understanding the pathophysiology underlying cognitive phenotypes in NS and in the broader population of children with neurodevelopmental disorders.

Brain aging and cardiovascular factors in HIV: a longitudinal volume and shape MRI study.

We aimed to examine the relative contributions of HIV infection, age, and cardiovascular risk factors to subcortical brain atrophy in people with HIV (PWH). Longitudinal observational study. Virally suppressed PWH with low neuropsychological confounds (n = 75) and demographically matched HIV-negative controls (n = 31) completed baseline and 18-month follow-up MRI scans, neuropsychological evaluation, cardiovascular assessments, and HIV laboratory tests. PWH were evaluated for HIV-associated neurocognitive disorder (HAND). Subcortical volumes were extracted with Freesurfer after removal of white matter hyperintensities. Volumetric and shape analyses were conducted using linear mixed-effect models incorporating interactions between age, time, and each of HIV status, HAND status, HIV disease factors, and cardiovascular markers. Across baseline and follow-up PWH had smaller volumes of most subcortical structures compared with HIV-negative participants. In addition, over time older PWH had a more rapid decline in caudate volumes (P = 0.041), predominantly in the more severe HAND subgroups (P = 0.042). Higher CD4+ cell counts had a protective effect over time on subcortical structures for older participants with HIV. Increased cardiovascular risk factors were associated with smaller volumes across baseline and follow-up for most structures, although a more rapid decline over time was observed for striatal volumes. There were no significant shape analyses findings. The study demonstrates a three-hit model of general (as opposed to localized) subcortical injury in PWH: HIV infection associated with smaller volumes of most subcortical structures, HIV infection and aging synergy in the striatum, and cardiovascular-related injury linked to early and more rapid striatal atrophy.

Striatal gray matter volumes, externalizing traits, and N-back task performance: An exploratory study of sex differences using the human connectome project data

The striatum is implicated in externalizing traits and cognitive dysfunction. The ventral and dorsal striatal subregions may play differentiable roles in externalizing behaviors and executive functions. We employed voxel-based morphometry to estimate the striatal gray matter volumes (GMVs) of 968 young adults (510 women) of the Human Connectome Project. We examined sex differences in striatal GMVs, tested how striatal GMVs related to an externalizing trait (Extn), and 2-back memory efficiency (Eff2), and examined whether these relationships exhibited sex differences. Men showed significantly higher ventral striatum (VS) and lentiform nucleus (LN) GMVs as well as higher Extn and Eff2 than women. Across all subjects, greater caudate and LN GMVs were correlated significantly with lower Eff2 though with limited effect sizes ( r = −0.140, p &lt; .001 and r = −0.093, p = .004, respectively) and the latter correlation was carried primarily by women ( z = −3.070, p = .002, slope test). VS GMV showed positive correlation with Extn ( r = 0.085, p = .008). Together, striatal GMVs are significantly but only weakly associated with externalizing behaviors and cognitive dysfunction in young adults. As key hubs of the fronto-striatal circuits, the ventral and dorsal striatum may contribute differently to externalizing psychopathology.

Associations between pre-treatment limbic and striatal volumes and antidepressant outcomes after serial ketamine infusion in treatment resistant depression

Associations between pre-treatment limbic and striatal volumes and antidepressant outcomes after serial ketamine infusion in treatment resistant depression

Understanding Anhedonia from a Genomic Perspective.

Anhedonia, or the decreased ability to experience pleasure, is a cardinal symptom of major depression that commonly occurs within other forms of psychopathology. Supportive of long-held theory that anhedonia represents a genetically influenced vulnerability marker for depression, evidence from twin studies suggests that it is moderately-largely heritable. However, the genomic sources of this heritability are just beginning to be understood. In this review, we survey what is known about the genomic architecture underlying anhedonia and related constructs. We briefly review twin and initial candidate gene studies before focusing on genome-wide association study (GWAS) and polygenic efforts. As large samples are needed to reliably detect the small effects that typically characterize common genetic variants, the study of anhedonia and related phenotypes conflicts with current genomic research requirements and frameworks that prioritize sample size over precise phenotyping. This has resulted in few and underpowered studies of anhedonia-related constructs that have largely failed to reliably identify individual variants. Nonetheless, the polygenic architecture of anhedonia-related constructs identified in these studies has genetic overlap with depression and schizophrenia as well as related brain structure (e.g., striatal volume), providing important clues to etiology that may usefully guide refinement in nosology. As we await the accumulation of larger samples for more well-powered GWAS of reward-related constructs, novel analytic techniques that leverage GWAS summary statistics (e.g., genomic structural equation modeling) may currently be used to help characterize how the genomic architecture of anhedonia is shared and distinct from that underlying other constructs (e.g., depression, neuroticism, anxiety).

Individual differences in amygdala volumes predict changes in functional connectivity between subcortical and cognitive control networks throughout adolescence

Adolescence is a critical period of structural and functional neural maturation among regions serving the cognitive control of emotion. Evidence suggests that this process is guided by developmental changes in amygdala and striatum structure and shifts in functional connectivity between subcortical (SC) and cognitive control (CC) networks. Herein, we investigate the extent to which such developmental shifts in structure and function reciprocally predict one another over time. 179 youth (9-15 years-old) completed annual MRI scans for three years. Amygdala and striatum volumes and connectivity within and between SC and CC resting state networks were measured for each year. We tested for reciprocal predictability of within-person and between-person changes in structure and function using random-intercept cross-lagged panel models. Within-person shifts in amygdala volumes in a given year significantly and specifically predicted deviations in SC-CC connectivity in the following year, such that an increase in volume was associated with decreased SC-CC connectivity the following year. Deviations in connectivity did not predict changes in amygdala volumes over time. Conversely, broader group-level shifts in SC-CC connectivity were predictive of subsequent deviations in striatal volumes. We did not see any cross-predictability among amygdala or striatum volumes and within-network connectivity measures. Within-person shifts in amygdala structure year-to-year robustly predicted weaker SC-CC connectivity in subsequent years, whereas broader increases in SC-CC connectivity predicted smaller striatal volumes over time. These specific structure function relationships may contribute to the development of emotional control across adolescence.

P.0626 Habit formation and striatal volumes in cannabis use disorder

P.0626 Habit formation and striatal volumes in cannabis use disorder

Striatal glutamate, subcortical structure and clinical response to first-line treatment in first-episode psychosis patients

IntroductionRecent studies have observed that patients with treatment-resistant schizophrenia as well as patients with schizophrenia who do not respond within a medication trial exhibit excess activity of the glutamate system. In this study we sought to replicate the within-trial glutamate abnormality and to investigate the potential for structural differences and treatment-induced changes to improve identification of medication responders and non-responders. MethodsWe enrolled 48 medication-naïve patients in a 4-week trial of risperidone and classified them retrospectively into responders and non-responders using clinical criteria. Proton magnetic resonance spectroscopy and T1-weighted structural MRI were acquired pre- and post-treatment to quantify striatal glutamate levels and several measures of subcortical brain structure. ResultsPatients were classified as 29 responders and 19 non-responders. Striatal glutamate was higher in the non-responders than responders both pre- and post-treatment (F1,39 = 7.15, p = .01). Volumetric measures showed a significant group x time interaction (t = 5.163, <1%FDR), and group x time x glutamate interaction (t = 4.23, <15%FDR) were seen in several brain regions. Striatal volumes increased at trend level with treatment in both groups, and a positive association of striatal volumes with glutamate levels was seen in the non-responders. ConclusionsCombining anatomic measures with glutamate levels offers the potential to enhance classification of responders and non-responders to antipsychotic medications as well as to provide mechanistic understanding of the interplay between neuroanatomical and neurochemical changes induced by these medications.Ethical statementThe study was approved by the Ethics and Scientific committees of the Instituto Nacional de Neurología y Neurocirugía in Mexico City. All participants over 18 years fully understood and signed the informed consent; in case the patient was under 18 years, informed consent was obtained from both parents. Participants did not receive a stipend.

Histological Correlates of Neuroanatomical Changes in a Rat Model of Levodopa-Induced Dyskinesia Based on Voxel-Based Morphometry.

Long-term therapy with levodopa (L-DOPA) in patients with Parkinson’s disease (PD) often triggers motor complications termed as L-DOPA-induced dyskinesia (LID). However, few studies have explored the pathogenesis of LID from the perspective of neuroanatomy. This study aimed to investigate macroscopic structural changes in a rat model of LID and the underlying histological mechanisms. First, we established the hemiparkinsonism rat model through stereotaxic injection of 6-hydroxydopamine (6-OHDA) into the right medial forebrain bundle, followed by administration of saline (PD) or L-DOPA to induce LID. Magnetic resonance imaging (MRI) and behavioral evaluations were performed at different time points. Histological analysis was conducted to assess the correlations between MRI signal changes and cellular contributors. Voxel-based morphometry (VBM) analysis revealed progressive bilateral volume reduction in the cortical and subcortical areas in PD rats compared with the sham rats. These changes were partially reversed by chronic L-DOPA administration; moreover, there was a significant volume increase mainly in the dorsolateral striatum, substantia nigra, and piriform cortex of the lesioned side compared with that of PD rats. At the striatal cellular level, glial fibrillary acidic protein-positive (GFAP+) astrocytes were significantly increased in the lesioned dorsolateral striatum of PD rats compared with the intact side and the sham group. Prolonged L-DOPA treatment further increased GFAP levels. Neither 6-OHDA damage nor L-DOPA treatment influenced the striatal expression of vascular endothelial growth factor (VEGF). Additionally, there was a considerable increase in synapse-associated proteins (SYP, PSD95, and SAP97) in the lesioned striatum of LID rats relative to the PD rats. Golgi-Cox staining analysis of the dendritic spine morphology revealed an increased density of dendritic spines after chronic L-DOPA treatment. Taken together, our findings suggest that striatal volume changes in LID rats involve astrocyte activation, enrichment of synaptic ultrastructure and signaling proteins in the ipsilateral striatum. Meanwhile, the data highlight the enormous potential of structural MRI, especially VBM analysis, in determining the morphological phenotype of rodent models of LID.

Central nervous system atrophy predicts future dynamics of disability progression in a real-world multiple sclerosis cohort.

Background and purposeIn an era of individualized multiple sclerosis (MS) patient management, biomarkers for accurate prediction of future clinical outcomes are needed. We aimed to evaluate the potential of short‐term magnetic resonance imaging (MRI) atrophy measures and serum neurofilament light chain (sNfL) as predictors of the dynamics of disability accumulation in relapse‐onset MS.MethodsBrain gray and white matter, thalamic, striatal, pallidal and cervical spinal cord volumes, and lesion load were measured over three available time points (mean time span 2.24 ± 0.70 years) for 183 patients (140 relapsing‐remitting [RRMS] and 43 secondary‐progressive MS (SPMS); 123 female, age 46.4 ± 11.0 years; disease duration 15.7 ± 9.3 years), and their respective annual changes were calculated. Baseline sNfL was also measured at the third available time point for each patient. Subsequently, patients underwent annual clinical examinations over 5.4 ± 3.7 years including Expanded Disability Status Scale (EDSS) scoring, the nine‐hole peg test and the timed 25‐foot walk test.ResultsHigher annual spinal cord atrophy rates and lesion load increase predicted higher future EDSS score worsening over time in SPMS. Lower baseline thalamic volumes predicted higher walking speed worsening over time in RRMS. Lower baseline gray matter, as well as higher white matter and spinal cord atrophy rates, lesion load increase, baseline striatal volumes and baseline sNfL, predicted higher future hand dexterity worsening over time. All models showed reasonable to high prediction accuracy.ConclusionThis study demonstrates the capability of short‐term MRI metrics to accurately predict future dynamics of disability progression in a real‐world relapse‐onset MS cohort. The present study represents a step towards the utilization of structural MRI measurements in patient care.

Identifying profiles of brain structure and associations with current and future psychopathology in youth

Brain structure is often studied as a marker of youth psychopathology by examining associations between volume or thickness of individual regions and specific diagnoses. However, these univariate approaches do not address whether the effect of a particular region may depend on the structure of other regions. Here, we identified subgroups of individuals with distinct profiles of brain structure and examined how these profiles were associated with concurrent and future youth psychopathology. We used latent profile analysis to identify distinct neuroanatomical profiles of subcortical region volume and orbitofrontal cortical thickness in the ABCD study (N = 9376, mean age = 9.91, SD = 0.62). We identified a five-profile solution consisting of a reduced subcortical volume profile, a reduced orbitofrontal thickness profile, a reduced limbic and elevated striatal volume profile, an elevated orbitofrontal thickness and reduced striatal volume profile, and an elevated orbitofrontal thickness and subcortical volume profile. While controlling for age, sex, and intracranial volume, profiles exhibited differences in concurrent psychopathology measured dimensionally and categorically and in psychopathology at 1-year follow-up measured dimensionally. Results show that profiles of brain structure have incremental validity for associations with youth psychopathology beyond intracranial volume.

Hippocampal and striatal volumes correlate with spatial memory impairment in Huntington's disease.

Spatial memory impairments are observed in people with Huntington's disease (HD), however, the domain of spatial memory has received little focus when characterizing the cognitive phenotype of HD. Spatial memory is traditionally thought to be a hippocampal-dependent function, while the neuropathology of HD centers on the striatum. Alongside spatial memory deficits in HD, recent neurocognitive theories suggest that a larger brain network is involved, including the striatum. We examined the relationship between hippocampal and striatal volumes and spatial memory in 36 HD gene expansion carriers, including premanifest (n=24) and early manifest HD (n=12), and 32 matched healthy controls. We assessed spatial memory with Paired Associates Learning, Rey-Osterrieth Complex Figure Test, and the Virtual House task, which assesses three components of spatial memory: navigation, object location, and plan drawing. Caudate nucleus, putamen, and hippocampal volumes were manually segmented on T1-weighted MR images. As expected, caudate nucleus and putamen volumes were significantly smaller in the HD group compared to controls, with manifest HD having more severe atrophy than the premanifest HD group. Hippocampal volumes did not differ significantly between HD and control groups. Nonetheless, on average, the HD group performed significantly worse than controls across all spatial memory tasks. The spatial memory components of object location and recall of figural and topographical drawings were associated with striatal and hippocampal volumes in the HD cohort. We provide a case to include spatial memory impairments in the cognitive phenotype of HD, and extend the neurocognitive picture of HD beyond its primary pathology within the striatum.

Language Disorder in Progressive Supranuclear Palsy and Corticobasal Syndrome: Neural Correlates and Detection by the MLSE Screening Tool.

Background: Progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) affect speech and language as well as motor functions. Clinical and neuropathological data indicate a close relationship between these two disorders and the non-fluent variant of primary progressive aphasia (nfvPPA). We use the recently developed Mini Linguistic State Examination tool (MLSE) to study speech and language disorders in patients with PSP, CBS, and nfvPPA, in combination with structural magnetic resonance imaging (MRI).Methods: Fifty-one patients (PSP N = 13, CBS N = 19, nfvPPA N = 19) and 30 age-matched controls completed the MLSE, the short form of the Boston Diagnostic Aphasia Examination (BDAE), and the Addenbrooke’s Cognitive Examination III. Thirty-eight patients and all controls underwent structural MRI at 3 Tesla, with T1 and T2-weighted images processed by surface-based and subcortical segmentation within FreeSurfer 6.0.0 to extract cortical thickness and subcortical volumes. Morphometric differences were compared between groups and correlated with the severity of speech and language impairment.Results: CBS and PSP patients showed impaired MLSE performance, compared to controls, with a similar language profile to nfvPPA, albeit less severe. All patient groups showed reduced cortical thickness in bilateral frontal regions and striatal volume. PSP and nfvPPA patients also showed reduced superior temporal cortical thickness, with additional thalamic and amygdalo-hippocampal volume reductions in nfvPPA. Multivariate analysis of brain-wide cortical thickness and subcortical volumes with MLSE domain scores revealed associations between performance on multiple speech and language domains with atrophy of left-lateralised fronto-temporal cortex, amygdala, hippocampus, putamen, and caudate.Conclusions: The effect of PSP and CBS on speech and language overlaps with nfvPPA. These three disorders cause a common anatomical pattern of atrophy in the left frontotemporal language network and striatum. The MLSE is a short clinical screening tool that can identify the language disorder of PSP and CBS, facilitating clinical management and patient access to future clinical trials.

Hybrid 2-[18F] FDG PET/MRI in premanifest Huntington's disease gene-expansion carriers: The significance of partial volume correction.

BackgroundHuntington’s disease (HD) is an inherited, progressive neurodegenerative disease that has no cure. Striatal atrophy and hypometabolism has been described in HD as far as 15 years before clinical onset and therefore structural and functional imaging biomarkers are the most applied biomarker modalities which call for these to be exact; however, most studies are not considering the partial volume effect and thereby tend to overestimate metabolic reductions, which may bias imaging outcome measures of interventions.ObjectiveEvaluation of partial volume effects in a cohort of premanifest HD gene-expansion carriers (HDGECs).Methods21 HDGECs and 17 controls had a hybrid 2-[18F]FDG PET/MRI scan performed. Volume measurements and striatal metabolism, both corrected and uncorrected for partial volume effect were correlated to an estimate of disease burden, the CAG age product scaled (CAPS).ResultsWe found significantly reduced striatal metabolism in HDGECs, but not in striatal volume. There was a negative correlation between the CAPS and striatal metabolism, both corrected and uncorrected for the partial volume effect. The partial volume effect was largest in the smallest structures and increased the difference in metabolism between the HDGEC with high and low CAPS scores. Statistical parametric mapping confirmed the results.ConclusionsA hybrid 2-[18F]FDG PET/MRI scan provides simultaneous information on structure and metabolism. Using this approach for the first time on HDGECs, we highlight the importance of partial volume effect correction in order not to underestimate the standardized uptake value and thereby the risk of overestimating the metabolic effect on the striatal structures, which potentially could bias studies determining imaging outcome measures of interventions in HDGECs and probably also symptomatic HD.

Mild Parkinsonian Signs, Energy Decline, and Striatal Volume in Community-Dwelling Older Adults

Mild parkinsonian signs (MPS), highly prevalent in older adults, predict disability. It is unknown whether energy decline, a predictor of mobility disability, is also associated with MPS. We hypothesized that those with MPS had greater decline in self-reported energy level (SEL) than those without MPS, and that SEL decline and MPS share neural substrates. Using data from the Health, Aging and Body Composition Study, we analyzed 293 Parkinson's disease-free participants (83 ± 3 years old, 39% Black, 58% women) with neuroimaging data, MPS evaluation by Unified Parkinson Disease Rating Scale in 2006-2008, and ≥3 measures of SEL since 1999-2000. Individual SEL slopes were computed via linear mixed models. Associations of SEL slopes with MPS were tested using logistic regression models. Associations of SEL slope with volume of striatum, sensorimotor, and cognitive regions were examined using linear regression models adjusted for normalized total gray matter volume. Models were adjusted for baseline SEL, mobility, demographics, and comorbidities. Compared to those without MPS (n = 165), those with MPS (n = 128) had 37% greater SEL decline in the prior 8 years (p = .001). Greater SEL decline was associated with smaller right striatal volume (adjusted standardized β = 0.126, p = .029). SEL decline was not associated with volumes in other regions. The association of SEL decline with MPS remained similar after adjustment for right striatal volume (adjusted odds ratio = 2.03, 95% CI: 1.16-3.54). SEL decline may be faster in those with MPS. Striatal atrophy may be important for declining energy but does not explain the association with MPS.