Functional topography of the neocortex predicts covariation in complex cognitive and basic motor abilities.

Although higher-order cognitive and lower-order sensorimotor abilities are generally regarded as distinct and studied separately, there is evidence that they not only covary but also that this covariation increases across the lifespan. This pattern has been leveraged in clinical settings where a simple assessment of sensory or motor ability (e.g. hearing, gait speed) can forecast age-related cognitive decline and risk for dementia. However, the brain mechanisms underlying cognitive, sensory, and motor covariation are largely unknown. Here, we examined whether such covariation in midlife reflects variability in common versus distinct neocortical networks using individualized maps of functional topography derived from BOLD fMRI data collected in 769 45-year-old members of a population-representative cohort. Analyses revealed that variability in basic motor but not hearing ability reflected individual differences in the functional topography of neocortical networks typically supporting cognitive ability. These patterns suggest that covariation in motor and cognitive abilities in midlife reflects convergence of function in higher-order neocortical networks and that gait speed may not be simply a measure of physical function but rather an integrative index of nervous system health.

Childhood self-control forecasts the pace of midlife aging and preparedness for old age.

The ability to control one's own emotions, thoughts, and behaviors in early life predicts a range of positive outcomes in later life, including longevity. Does it also predict how well people age? We studied the association between self-control and midlife aging in a population-representative cohort of children followed from birth to age 45 y, the Dunedin Study. We measured children's self-control across their first decade of life using a multi-occasion/multi-informant strategy. We measured their pace of aging and aging preparedness in midlife using measures derived from biological and physiological assessments, structural brain-imaging scans, observer ratings, self-reports, informant reports, and administrative records. As adults, children with better self-control aged more slowly in their bodies and showed fewer signs of aging in their brains. By midlife, these children were also better equipped to manage a range of later-life health, financial, and social demands. Associations with children's self-control could be separated from their social class origins and intelligence, indicating that self-control might be an active ingredient in healthy aging. Children also shifted naturally in their level of self-control across adult life, suggesting the possibility that self-control may be a malleable target for intervention. Furthermore, individuals' self-control in adulthood was associated with their aging outcomes after accounting for their self-control in childhood, indicating that midlife might offer another window of opportunity to promote healthy aging.

Dementia, dementia's risk factors and premorbid brain structure are concentrated in disadvantaged areas: National register and birth-cohort geographic analyses.

INTRODUCTION: Dementia risk may be elevated in socioeconomically disadvantaged neighborhoods. Reasons for this remain unclear, and this elevation has yet to be shown at a national population level. METHODS: We tested whether dementia was more prevalent in disadvantaged neighborhoods across the New Zealand population (N = 1.41 million analytic sample) over a 20-year observation. We then tested whether premorbid dementia risk factors and MRI-measured brain-structure antecedents were more prevalent among midlife residents of disadvantaged neighborhoods in a population-representative NZ-birth-cohort (N = 938 analytic sample). RESULTS: People residing in disadvantaged neighborhoods were at greater risk of dementia (HR per-quintile-disadvantage-increase = 1.09, 95% confidence interval [CI]:1.08-1.10) and, decades before clinical endpoints typically emerge, evidenced elevated dementia-risk scores (CAIDE, LIBRA, Lancet, ANU-ADRI, DunedinARB; ß's 0.31-0.39) and displayed dementia-associated brain structural deficits and cognitive difficulties/decline. DISCUSSION: Disadvantaged neighborhoods have more residents with dementia, and decades before dementia is diagnosed, residents have more dementia-risk factors and brain-structure antecedents. Whether or not neighborhoods causally influence risk, they may offer scalable opportunities for primary dementia prevention.

Replicability of structural brain alterations associated with general psychopathology: evidence from a population-representative birth cohort.

Transdiagnostic research has identified a general psychopathology factor-often called the 'p' factor-that accounts for shared variation across internalizing, externalizing, and thought disorders in diverse samples. It has been argued that the p factor may reflect dysfunctional thinking present in serious mental illness. In support of this, we previously used a theory-free, data-driven multimodal neuroimaging approach to find that higher p factor scores are associated with structural alterations within a cerebello-thalamo-cortical circuit (CTCC) and visual association cortex, both of which are important for monitoring and coordinating information processing in the service of executive control. Here we attempt to replicate these associations by conducting region-of-interest analyses using data from 875 members of the Dunedin Longitudinal Study, a five-decade study of a population-representative birth cohort, collected when they were 45 years old. We further sought to replicate a more recent report that p factor scores can be predicted by patterns of distributed cerebellar morphology as estimated through independent component analysis. We successfully replicated associations between higher p factor scores and both reduced gray matter volume of the visual association cortex and fractional anisotropy of pontine white matter pathways within the CTCC. In contrast, we failed to replicate prior associations between cerebellar structure and p factor scores. Collectively, our findings encourage further focus on the CTCC and visual association cortex as core neural substrates and potential biomarkers of general psychopathology.

Left Atrial Appendage Thrombus Detected During Hyperacute Stroke Imaging Is Associated With Atrial Fibrillation.

BACKGROUND AND PURPOSE: Left atrial appendage (LAA) is the likely embolic source in atrial fibrillation (AF)-related cardioembolic strokes. We sought to determine the prevalence of LAA thrombus on hyperacute stroke imaging and its association with AF. METHODS: We retrospectively examined the clinical and radiological features of patients assessed through the hyperacute stroke imaging pathway over a 12-month period at Christchurch Hospital. The LAA was included in the computed tomography angiogram scan-range as part of the multimodal imaging protocol. Two radiological readers blinded to clinical information independently assessed for the presence of LAA thrombus. The association between AF and LAA thrombus was determined by multivariable logistic regression analysis. RESULTS: Of 303 patients included in the analysis, the overall prevalence of LAA thrombus was 6.6% and 14.9% in patients with known AF. Patients with LAA thrombus were older (85 versus 75 years, P<0.01), more commonly had known or newly diagnosed AF (75% versus 30%, P<0.01) and heart failure (30% versus 8%, P=0.01), and was associated with intracranial large vessel occlusion (65% versus 39%, P=0.02). In the multivariable model, AF (odds ratio, 3.71 [95% CI, 1.25-11.01] P=0.02) was independently associated with LAA thrombus after adjusting for age and congestive heart failure. Interrater reliability was moderate (kappa=0.56). CONCLUSIONS: LAA thrombus is a potential radiological marker of AF and can be assessed as a part of hyperacute stroke imaging.

Test-retest reliability and sample size estimates after MRI scanner relocation.

OBJECTIVE: Many factors can contribute to the reliability and robustness of MRI-derived metrics. In this study, we assessed the reliability and reproducibility of three MRI modalities after an MRI scanner was relocated to a new hospital facility. METHODS: Twenty healthy volunteers (12 females, mean age (standard deviation) â€‹= â€‹41 (11) years, age range [25-66]) completed three MRI sessions. The first session (S1) was one week prior to the 3T GE HDxt scanner relocation. The second (S2) occurred nine weeks after S1 and at the new location; a third session (S3) was acquired 4 weeks after S2. At each session, we acquired structural T1-weighted, pseudo-continuous arterial spin labelled, and diffusion tensor imaging sequences. We used longitudinal processing streams to create 12 summary MRI metrics, including total gray matter (GM), cortical GM, subcortical GM, white matter (WM), and lateral ventricle volume; mean cortical thickness; total surface area; average gray matter perfusion, and average diffusion tensor metrics along principal white matter pathways. We compared mean MRI values and variance at the old scanner location to multiple sessions at the new location using Bayesian multi-level regression models. K-fold cross validation allowed identification of important predictors. Whole-brain analyses were used to investigate any regional differences. Furthermore, we calculated within-subject coefficient of variation (wsCV), intraclass correlation coefficient (ICC), and dice similarity index (SI) of cortical segmentations across scanner relocation and within-site. Additionally, we estimated sample sizes required to robustly detect a 4% difference between two groups across MRI metrics. RESULTS: All global MRI metrics exhibited little mean difference and small variability (bar cortical gray matter perfusion) both across scanner relocation and within-site repeat. T1- and DTI-derived tissue metrics showed â€‹< â€‹|0.3|% mean difference and <1.2% variance across scanner location and <|0.4|% mean difference and <0.8% variance within the new location, with between-site intraclass correlation coefficient (ICC) â€‹> â€‹0.80 and within-subject coefficient of variation (wsCV) â€‹< â€‹1.4%. Mean cortical gray matter perfusion had the highest between-session variability (6.7% [0.3, 16.7], estimate [95% uncertainty interval]), and hence the smallest ICC (0.71 [0.44,0.92]) and largest wsCV (13.4% [5.4, 18.1]). No global metric exhibited evidence of a meaningful mean difference between scanner locations. However, surface area showed evidence of a mean difference within-site repeat (between S2 and S3). Whole-brain analyses revealed no significant areas of difference between scanner relocation or within-site. For all metrics, we found no support for a systematic difference in variance across relocation sites compared to within-site test-retest reliability. Necessary sample sizes to detect a 4% difference between two independent groups varied from a maximum of n â€‹= â€‹362 per group (cortical gray matter perfusion), to total gray matter volume (n â€‹= â€‹114), average fractional anisotropy (n â€‹= â€‹23), total gray matter volume normalized by intracranial volume (n â€‹= â€‹19), and axial diffusivity (n â€‹= â€‹3 per group). CONCLUSION: Cortical gray matter perfusion was the most variable metric investigated (necessitating large sample sizes to identify group differences), with other metrics showing substantially less variability. Scanner relocation appeared to have a negligible effect on variability of the global MRI metrics tested. This manuscript reports within-site test-retest variability to act as a tool for calculating sample size in future investigations. Our results suggest that when all other parameters are held constant (e.g., sequence parameters and MRI processing), the effect of scanner relocation is indistinguishable from within-site variability, but may need to be considered depending on the question being investigated.

Assessment of Disease Progression in Patients With Repaired Tetralogy of Fallot Using Cardiac Magnetic Resonance Imaging: A Systematic Review.

AIMS: Tetralogy of Fallot (ToF) is the most common cyanotic congenital heart disease with a growing population of adult survivors. Late pulmonary outflow tract and pulmonary valve postoperative complications are frequent, leading to long-term risks such as right heart failure and sudden death secondary to arrhythmias. Cardiac magnetic resonance imaging (CMR) is the gold standard for assessment of cardiac function in patients with repaired ToF. We aimed to determine the most useful CMR predictors of disease progression and the optimal frequency of CMR. METHODS AND RESULTS: We systematically reviewed PubMed from inception until 29 April 2019 for longitudinal studies assessing the relationship between CMR features and disease progression in repaired ToF. Fourteen (14) studies were identified. Multiple studies showed that impaired right and left ventricular function predict subsequent disease progression. Right ventricular end diastolic volume, while being associated with disease progression when analysed alone, was generally not associated with disease progression on multivariate analysis. Severity of tricuspid regurgitation and pulmonary regurgitation likewise did not show a consistent association with subsequent events. A number of non-CMR factors were also identified as being associated with disease progression, in particular QRS duration and older age at repair. Restrictive right ventricular physiology was not consistently an independent predictor of events. CONCLUSION: Impaired right and left ventricular function are the most consistent independent predictors of disease progression in repaired ToF. The optimal timing of repeat cardiac imaging remains controversial. Large scale prospective studies will provide important information to guide clinical decision making in this area.

General functional connectivity: Shared features of resting-state and task fMRI drive reliable and heritable individual differences in functional brain networks.

Intrinsic connectivity, measured using resting-state fMRI, has emerged as a fundamental tool in the study of the human brain. However, due to practical limitations, many studies do not collect enough resting-state data to generate reliable measures of intrinsic connectivity necessary for studying individual differences. Here we present general functional connectivity (GFC) as a method for leveraging shared features across resting-state and task fMRI and demonstrate in the Human Connectome Project and the Dunedin Study that GFC offers better test-retest reliability than intrinsic connectivity estimated from the same amount of resting-state data alone. Furthermore, at equivalent scan lengths, GFC displayed higher estimates of heritability than resting-state functional connectivity. We also found that predictions of cognitive ability from GFC generalized across datasets, performing as well or better than resting-state or task data alone. Collectively, our work suggests that GFC can improve the reliability of intrinsic connectivity estimates in existing datasets and, subsequently, the opportunity to identify meaningful correlates of individual differences in behavior. Given that task and resting-state data are often collected together, many researchers can immediately derive more reliable measures of intrinsic connectivity through the adoption of GFC rather than solely using resting-state data. Moreover, by better capturing heritable variation in intrinsic connectivity, GFC represents a novel endophenotype with broad applications in clinical neuroscience and biomarker discovery.

The New Zealand 1986 very low birth weight cohort as young adults: mapping the road ahead.

BACKGROUND: Very low birth weight (less than 1500 g) is associated with increased morbidity and costs of health care in childhood. Emerging evidence suggests these infants face a range of health and social problems as young adults. We studied all New Zealand very low birth weight infants born in 1986 (when 58% were exposed to antenatal corticosteroids) in infancy, with later follow-up at 7 to 8 years and 23 to 24 years. We now aim to assess the cohort at 26-28 years compared with controls. METHODS/DESIGN: The case sample will comprise a minimum of 250 members of the 1986 New Zealand national very low birth weight cohort (77% of survivors). Outcomes will be compared with a control group of 100 young adults born at term in 1986. Following written informed consent, participants will travel to Christchurch for 2 days of assessments undertaken by experienced staff. Medical assessments include growth measures, vision, respiratory function, blood pressure and echocardiogram, renal function, dental examination and blood tests. Cognitive and neuropsychological functioning will be assessed with standard tests, and mental health and social functioning by participant interview. A telephone interview will be conducted with a parent or significant other person nominated by the respondent to gain a further perspective on the young person's health and functioning. All those born at less than 28 weeks' gestation, plus a random subset of the cohort to a total of 150 cases and 50 controls, will be offered cranial magnetic-resonance imaging. Statistical analysis will examine comparison with controls and long-term trajectories for the very low birth weight cohort. DISCUSSION: The research will provide crucial New Zealand data on the young adult outcomes for very low birth weight infants and address gaps in the international literature, particularly regarding cardiovascular, respiratory, visual and neurocognitive outcomes. These data will inform future neonatal care, provide evidence-based guidelines for care of preterm graduates transitioning to adult care, and help shape health education and social policies for this high risk group. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12612000995875 . Registered 1 October 2012.

Evaluation of deep-learning TSE images in clinical musculoskeletal imaging.

In this study, we compared the fat-saturated (FS) and non-FS turbo spin echo (TSE) magnetic resonance imaging knee sequences reconstructed conventionally (conventional-TSE) against a deep learning-based reconstruction of accelerated TSE (DL-TSE) scans. A total of 232 conventional-TSE and DL-TSE image pairs were acquired for comparison. For each consenting patient, one of the clinically acquired conventional-TSE proton density-weighted sequences in the sagittal or coronal planes (FS and non-FS), or in the axial plane (non-FS), was repeated using a research DL-TSE sequence. The DL-TSE reconstruction resulted in an image resolution that increased by at least 45% and scan times that were up to 52% faster compared to the conventional TSE. All images were acquired on a MAGNETOM Vida 3T scanner (Siemens Healthineers AG, Erlangen, Germany). The reporting radiologists, blinded to the acquisition time, were requested to qualitatively compare the DL-TSE against the conventional-TSE reconstructions. Despite having a faster acquisition time, the DL-TSE was rated to depict smaller structures better for 139/232 (60%) cases, equivalent for 72/232 (31%) cases and worse for 21/232 (9%) cases compared to the conventional-TSE. Overall, the radiologists preferred the DL-TSE reconstruction in 124/232 (53%) cases and stated no preference, implying equivalence, for 65/232 (28%) cases. DL-TSE reconstructions enabled faster acquisition times while enhancing spatial resolution and preserving the image contrast. From these results, the DL-TSE provided added or comparable clinical value and utility in less time. DL-TSE offers the opportunity to further reduce the overall examination time and improve patient comfort with no loss in diagnostic accuracy.

A blood biomarker of the pace of aging is associated with brain structure: replication across three cohorts.

Biological aging is the correlated decline of multi-organ system integrity central to the etiology of many age-related diseases. A novel epigenetic measure of biological aging, DunedinPACE, is associated with cognitive dysfunction, incident dementia, and mortality. Here, we tested for associations between DunedinPACE and structural MRI phenotypes in three datasets spanning midlife to advanced age: the Dunedin Study (age=45 years), the Framingham Heart Study Offspring Cohort (mean age=63 years), and the Alzheimer's Disease Neuroimaging Initiative (mean age=75 years). We also tested four additional epigenetic measures of aging: the Horvath clock, the Hannum clock, PhenoAge, and GrimAge. Across all datasets (total N observations=3380; total N individuals=2322), faster DunedinPACE was associated with lower total brain volume, lower hippocampal volume, greater burden of white matter microlesions, and thinner cortex. Across all measures, DunedinPACE and GrimAge had the strongest and most consistent associations with brain phenotypes. Our findings suggest that single timepoint measures of multi-organ decline such as DunedinPACE could be useful for gauging nervous system health.

Early-phase amyloid PET reproduces metabolic signatures of cognitive decline in Parkinson's disease.

INTRODUCTION: Recent work suggests that amyloid beta (Aß) positron emission tomography (PET) tracer uptake shortly after injection ("early phase") reflects brain metabolism and perfusion. We assessed this modality in a predominantly amyloid-negative neurodegenerative condition, Parkinson's disease (PD), and hypothesized that early-phase 18F-florbetaben (eFBB) uptake would reproduce characteristic hypometabolism and hypoperfusion patterns associated with cognitive decline in PD. METHODS: One hundred fifteen PD patients across the spectrum of cognitive impairment underwent dual-phase Aß PET, structural and arterial spin labeling (ASL) magnetic resonance imaging (MRI), and neuropsychological assessments. Multiple linear regression models compared eFBB uptake to cognitive performance and ASL MRI perfusion. RESULTS: Reduced eFBB uptake was associated with cognitive performance in brain regions previously linked to hypometabolism-associated cognitive decline in PD, independent of amyloid status. Furthermore, eFBB uptake correlated with cerebral perfusion across widespread regions. DISCUSSION: EFBB uptake is a potential surrogate measure for cerebral perfusion/metabolism. A dual-phase PET imaging approach may serve as a clinical tool for assessing cognitive impairment. Highlights: Images taken at amyloid beta (Aß) positron emission tomography tracer injection may reflect brain perfusion and metabolism.Parkinson's disease (PD) is a predominantly amyloid-negative condition.Early-phase florbetaben (eFBB) in PD was associated with cognitive performance.eFBB uptake reflects hypometabolism-related cognitive decline in PD.eFBB correlated with arterial spin labeling magnetic resonance imaging measured cerebral perfusion.eFBB distinguished dementia from normal cognition and mild cognitive impairment.Findings were independent of late-phase Aß burden.Thus, eFBB may serve as a surrogate measure for brain metabolism/perfusion.

Magnetic resonance imaging of breast implants: Optimizing tissue contrast.

INTRODUCTION: Patients with breast implants need to undergo regular screening MRI procedures. One of the key requirements of this screening scan is the ability to suppress one or more tissues (water, fat, or silicone) simultaneously. However, the presence of "foreign" implants within the breast biological space affects the MRI scanner's normal operating mode. Often, this requires operator's supervision to make sure the correct image contrast is achieved. METHODS: We built a phantom that represents the commonly encountered tissues (water, fat, and silicone) in breast implant imaging. The phantom was used to optimise imaging parameters and highlight common challenges encountered while imaging breast implants. We scanned the phantom on seven different MRI scanners (including 1.5T and 3T) and produced vendor-specific cheat-sheets on how to image breast implants. Ethical approval was not required for this article type. CONCLUSION: Performing a breast MRI procedure with implants in-situ can be challenging. Employing a purpose-built phantom, we provide easy-to-use cheat sheets, with examples, outlining steps that can be taken to ensure appropriate tissue suppression and image contrast in breast implant MRI. We hope these cheat-sheets will help MRI practitioners to confidently and efficiently achieve accurate image contrasts across a number of implant scenarios which will aid in improving diagnostic accuracy, treatment plans, and thus prognosis for the patient.

Functional Topography of the Neocortex Predicts Covariation in Complex Cognitive and Basic Motor Abilities.

Although higher-order cognitive and lower-order sensorimotor abilities are generally regarded as distinct and studied separately, there is evidence that they not only covary but also that this covariation increases across the lifespan. This pattern has been leveraged in clinical settings where a simple assessment of sensory or motor ability (e.g., hearing, gait speed) can forecast age-related cognitive decline and risk for dementia. However, the brain mechanisms underlying cognitive, sensory, and motor covariation are largely unknown. Here, we examined whether such covariation in midlife reflects variability in common versus distinct neocortical networks using individualized maps of functional topography derived from BOLD fMRI data collected in 769 45-year old members of a population-representative cohort. Analyses revealed that variability in basic motor but not hearing ability reflected individual differences in the functional topography of neocortical networks typically supporting cognitive ability. These patterns suggest that covariation in motor and cognitive abilities in midlife reflects convergence of function in higher-order neocortical networks and that gait speed may not be simply a measure of physical function but rather an integrative index of nervous system health.

Associations Between Thinner Retinal Neuronal Layers and Suboptimal Brain Structural Integrity in a Middle-Aged Cohort.

Purpose: The retina has potential as a biomarker of brain health and Alzheimer's disease (AD) because it is the only part of the central nervous system which can be easily imaged and has advantages over brain imaging technologies. Few studies have compared retinal and brain measurements in a middle-aged sample. The objective of our study was to investigate whether retinal neuronal measurements were associated with structural brain measurements in a middle-aged population-based cohort. Participants and Methods: Participants were members of the Dunedin Multidisciplinary Health and Development Study (n=1037; a longitudinal cohort followed from birth and at ages 3, 5, 7, 9, 11, 13, 15, 18, 21, 26, 32, 38, and most recently at age 45, when 94% of the living Study members participated). Retinal nerve fibre layer (RNFL) and ganglion cell-inner plexiform layer (GC-IPL) thickness were measured by optical coherence tomography (OCT). Brain age gap estimate (brainAGE), cortical surface area, cortical thickness, subcortical grey matter volumes, white matter hyperintensities, were measured by magnetic resonance imaging (MRI). Results: Participants with both MRI and OCT data were included in the analysis (RNFL n=828, female n=413 [49.9%], male n=415 [50.1%]; GC-IPL n=825, female n=413 [50.1%], male n=412 [49.9%]). Thinner retinal neuronal layers were associated with older brain age, smaller cortical surface area, thinner average cortex, smaller subcortical grey matter volumes, and increased volume of white matter hyperintensities. Conclusion: These findings provide evidence that the retinal neuronal layers reflect differences in midlife structural brain integrity consistent with increased risk for later AD, supporting the proposition that the retina may be an early biomarker of brain health.

A blood biomarker of accelerated aging in the body associates with worse structural integrity in the brain: replication across three cohorts.

Biological aging is the correlated decline of multi-organ system integrity central to the etiology of many age-related diseases. A novel epigenetic measure of biological aging, DunedinPACE, is associated with cognitive dysfunction, incident dementia, and mortality. Here, we tested for associations between DunedinPACE and structural MRI phenotypes in three datasets spanning midlife to advanced age: the Dunedin Study (age=45 years), the Framingham Heart Study Offspring Cohort (mean age=63 years), and the Alzheimer's Disease Neuroimaging Initiative (mean age=75 years). We also tested four additional epigenetic measures of aging: the Horvath clock, the Hannum clock, PhenoAge, and GrimAge. Across all datasets (total N observations=3,380; total N individuals=2,322), faster DunedinPACE was associated with lower total brain volume, lower hippocampal volume, and thinner cortex. In two datasets, faster DunedinPACE was associated with greater burden of white matter hyperintensities. Across all measures, DunedinPACE and GrimAge had the strongest and most consistent associations with brain phenotypes. Our findings suggest that single timepoint measures of multi-organ decline such as DunedinPACE could be useful for gauging nervous system health.

Grey matter atrophy in cognitively impaired Parkinson's disease.

OBJECTIVE: Mild cognitive impairment and dementia are common non-motor features of Parkinson's disease (PD). The aim of this study was to characterise grey matter changes associated with clearly defined stages of cognitive impairment in PD using structural MRI. METHODS: 96 PD subjects were classified using detailed cognitive testing as PD with normal cognition (PD-N, n=57), PD with mild cognitive impairment (PD-MCI, n=23) or PD with dementia (PD-D, n=16); 34 controls matched for mean age and sex ratio also participated. Grey matter volume differences were evaluated using voxel based morphometry of grey matter segments derived from T1 weighted 3 T MRI, and multiple linear regression assessed the relationship between cognitive and motor impairments and grey matter concentration. RESULTS: Compared with controls, no grey matter differences were found in PD-N. PD-MCI showed limited grey matter atrophy in the temporal, parietal and frontal cortex as well as the bilateral caudal hippocampus, amygdala and right putamen. PD-D subjects exhibited far more extensive atrophy in regions involved in PD-MCI but also had reduced grey matter volume in other large areas of the temporal lobe (including the parahippocampi), the intracalcarine and lingual gyri, posterior cingulate gyrus, frontal regions and bilateral caudate. Grey matter loss in PD correlated with global cognitive score but not motor impairment in most of these regions. INTERPRETATION: Marked grey matter atrophy occurs in PD with dementia but far less extensive changes are evident in PD-MCI. Some grey matter atrophy precedes the development of dementia but may be accelerated once frank dementia begins.

Arterial spin labelling reveals an abnormal cerebral perfusion pattern in Parkinson's disease.

There is a need for objective imaging markers of Parkinson's disease status and progression. Positron emission tomography and single photon emission computed tomography studies have suggested patterns of abnormal cerebral perfusion in Parkinson's disease as potential functional biomarkers. This study aimed to identify an arterial spin labelling magnetic resonance-derived perfusion network as an accessible, non-invasive alternative. We used pseudo-continuous arterial spin labelling to measure cerebral grey matter perfusion in 61 subjects with Parkinson's disease with a range of motor and cognitive impairment, including patients with dementia and 29 age- and sex-matched controls. Principal component analysis was used to derive a Parkinson's disease-related perfusion network via logistic regression. Region of interest analysis of absolute perfusion values revealed that the Parkinson's disease pattern was characterized by decreased perfusion in posterior parieto-occipital cortex, precuneus and cuneus, and middle frontal gyri compared with healthy controls. Perfusion was preserved in globus pallidus, putamen, anterior cingulate and post- and pre-central gyri. Both motor and cognitive statuses were significant factors related to network score. A network approach, supported by arterial spin labelling-derived absolute perfusion values may provide a readily accessible neuroimaging method to characterize and track progression of both motor and cognitive status in Parkinson's disease.

Pervasively Thinner Neocortex as a Transdiagnostic Feature of General Psychopathology.

OBJECTIVE: Neuroimaging research has revealed that structural brain alterations are common across broad diagnostic families of disorders rather than specific to a single psychiatric disorder. Such overlap in the structural brain correlates of mental disorders mirrors already well-documented phenotypic comorbidity of psychiatric symptoms and diagnoses, which can be indexed by a general psychopathology or p factor. The authors hypothesized that if general psychopathology drives the convergence of structural alterations common across disorders, then 1) there should be few associations unique to any one diagnostic family of disorders, and 2) associations with the p factor should overlap with those for the broader diagnostic families. METHODS: Analyses were conducted on structural MRI and psychopathology data collected from 861 members of the population-representative Dunedin Multidisciplinary Health and Development Study at age 45. RESULTS: Study members with high scores across three broad diagnostic families of disorders (externalizing, internalizing, thought disorder) exhibited highly overlapping patterns of reduced global and widely distributed parcel-wise neocortical thickness. Study members with high p factor scores exhibited patterns of reduced global and parcel-wise neocortical thickness nearly identical to those associated with the three broad diagnostic families. CONCLUSIONS: A pattern of pervasively reduced neocortical thickness appears to be common across all forms of mental disorders and may represent a transdiagnostic feature of general psychopathology. As has been documented with regard to symptoms and diagnoses, the underlying brain structural correlates of mental disorders may not exhibit specificity, and the continued pursuit of such specific correlates may limit progress toward more effective strategies for etiological understanding, prevention, and intervention.

Disparities in the pace of biological aging among midlife adults of the same chronological age have implications for future frailty risk and policy.

Some humans age faster than others. Variation in biological aging can be measured in midlife, but the implications of this variation are poorly understood. We tested associations between midlife biological aging and indicators of future frailty-risk in the Dunedin cohort of 1037 infants born the same year and followed to age 45. Participants' Pace of Aging was quantified by tracking declining function in 19 biomarkers indexing the cardiovascular, metabolic, renal, immune, dental, and pulmonary systems across ages 26, 32, 38, and 45 years. At age 45 in 2019, participants with faster Pace of Aging had more cognitive difficulties, signs of advanced brain aging, diminished sensory-motor functions, older appearance, and more pessimistic perceptions of aging. People who are aging more rapidly than same-age peers in midlife may prematurely need supports to sustain independence that are usually reserved for older adults. Chronological age does not adequately identify need for such supports.