Ali, Farwa

Trunk and pelvis range of motion (ROM) is essential to perform activities of daily living. The ROM may become limited with aging or with neuromusculoskeletal disorders. Inertial measurement units (IMU) with out-of-the box software solutions are increasingly being used to assess motion. We hypothesize that the accuracy (validity) and reliability (consistency) of the trunk and pelvis ROM during steady-state gait in normal individuals as measured using the Opal APDM 6 sensor IMU system and calculated using Mobility Lab version 4 software will be comparable to a gold-standard optoelectric motion capture system. Thirteen healthy young adults participated in the study. Trunk ROM, measured using the IMU was within 5–7 degrees of the motion capture system for all three planes and within 10 degrees for pelvis ROM. We also used a triad of markers mounted on the sternum and sacrum IMU for a head-to-head comparison of trunk and pelvis ROM. The IMU measurements were within 5–10 degrees of the triad. A greater variability of ROM measurements was seen for the pelvis in the transverse plane. IMUs and their custom software provide a valid and reliable measurement for trunk and pelvis ROM in normal individuals, and important considerations for future applications are discussed.

AbstractBackground and purposePrimary lateral sclerosis (PLS) is a neurodegenerative disorder that primarily affects the central motor system. In rare cases, clinical features of PLS may overlap with those of progressive supranuclear palsy (PSP). We investigate neuroimaging features that can help distinguish PLS with overlapping features of PSP (PLS‐PSP) from PSP.MethodsSix patients with PLS‐PSP were enrolled between 2019 and 2023. We compared their clinical and neuroimaging characteristics with 18 PSP–Richardson syndrome (PSP‐RS) patients and 20 healthy controls. Magnetic resonance imaging, 18F‐flortaucipir positron emission tomography (PET), quantitative susceptibility mapping, and diffusion tensor imaging tractography (DTI) were performed to evaluate eight brain regions of interest. Area under the receiver operating characteristic curve (AUROC) was calculated.ResultsFive of the six PLS‐PSP patients (83.3%) were male. Median age at symptom onset was 61.5 (52.5–63) years, and all had mixed features of PLS and PSP. Volumes of the pallidum, caudate, midbrain, and cerebellar dentate were smaller in PSP‐RS than PLS‐PSP, providing good discrimination (AUROC = 0.75 for all). The susceptibilities in pallidum, midbrain, and cerebellar dentate were greater in PSP‐RS compared to PLS‐PSP, providing excellent discrimination (AUROC ≥ 0.90 for all). On DTI, fractional anisotropy (FA) in the posterior limb of the internal capsule from the corticospinal tract was lower in PLS‐PSP compared to PSP‐RS (AUROC = 0.86), but FA in the superior cerebellar peduncle was lower in PSP‐RS (AUROC = 0.95). Pallidum flortaucipir PET uptake was greater in PSP‐RS compared to PLS‐PSP (AUROC = 0.74).ConclusionsRegional brain volume, tractography, and magnetic susceptibility, but not tau‐PET, are useful in distinguishing PLS‐PSP from PSP.

AbstractBackgroundMidbrain atrophy is a characteristic feature of progressive supranuclear palsy (PSP), observed in PSP‐Richardson's syndrome (PSP‐RS) and to a lesser extent PSP‐parkinsonism (PSP‐P).ObjectiveOur aim was to critically evaluate the utility of manual magnetic resonance imaging measurements of the midbrain tectal plate as a diagnostic biomarker in PSP.MethodsLength of the tectal plate and width of the superior and inferior colliculi were measured in 40 PSP (20 PSP‐RS and 20 PSP‐P) patients and compared with 20 Parkinson's disease and 20 healthy control subjects.ResultsTectal plate length was reduced in both PSP groups compared with Parkinson's disease and control subjects and was most abnormal in PSP‐RS followed by PSP‐P. Reduced tectal plate length was associated with worse PSP Rating Scale scores.ConclusionsSimple manual measurements of tectal plate length show utility as a diagnostic biomarker in PSP, particularly for PSP‐RS.

Abstract Progressive supranuclear palsy is a neurodegenerative disease characterized by the deposition of four-repeat tau in neuronal and glial lesions in the brainstem, cerebellar, subcortical and cortical brain regions. There are varying clinical presentations of progressive supranuclear palsy with different neuroimaging signatures, presumed to be due to different topographical distributions and burden of tau. The classic Richardson syndrome presentation is considered a subcortical variant, whilst progressive supranuclear palsy with predominant speech and language impairment is considered a cortical variant, although the pathological underpinnings of these variants are unclear. In this case-control study, we aimed to determine whether patterns of regional tau pathology differed between these variants and whether tau burden correlated with neuroimaging. Thirty-three neuropathologically confirmed progressive supranuclear palsy patients with either the Richardson syndrome (n = 17) or speech/language (n = 16) variant and ante-mortem magnetic resonance imaging were included. Tau lesion burden was semi-quantitatively graded in cerebellar, brainstem, subcortical and cortical regions and combined to form neuronal and glial tau scores. Regional magnetic resonance imaging volumes were converted to Z-scores using 33 age- and sex-matched controls. Diffusion tensor imaging metrics, including fractional anisotropy and mean diffusivity, were calculated. Tau burden and neuroimaging metrics were compared between groups and correlated using linear regression models. Neuronal and glial tau burden were higher in motor and superior frontal cortices in the speech/language variant. In the subcortical and brainstem regions, only the glial tau burden differed, with a higher burden in globus pallidus, subthalamic nucleus, substantia nigra and red nucleus in Richardson’s syndrome. No differences were observed in the cerebellar dentate and striatum. Greater volume loss was observed in the motor cortex in the speech/language variant and in the subthalamic nucleus, red nucleus and midbrain in Richardson’s syndrome. Fractional anisotropy was lower in the midbrain and superior cerebellar peduncle in Richardson’s syndrome. Mean diffusivity was greater in the superior frontal cortex in the speech/language variant and midbrain in Richardson’s syndrome. Neuronal tau burden showed associations with volume loss, lower fractional anisotropy and higher mean diffusivity in the superior frontal cortex, although these findings did not survive correction for multiple comparisons. Results suggest that a shift in the distribution of tau, particularly neuronal tau, within the progressive supranuclear palsy network of regions is driving different clinical presentations in progressive supranuclear palsy. The possibility of different disease epicentres in these clinical variants has potential implications for the use of imaging biomarkers in progressive supranuclear palsy.

AbstractBackgroundQuantified accelerated aging, or “age gap,” defined as the difference between a person’s estimated age using a biological measurement, such as a brain image, and their true age, has strong associations with multiple neurodegenerative etiologies. As an alternative to imaging‐based measurements, in this study we developed an age prediction model based on gait patterns and used this model to quantify accelerated aging as an indicator of cognitive impairment and predictor of future cognitive decline.MethodA database of 16,917 pressure sensitive walkway exams from 5,307 participants in the Mayo Clinic Study of Aging was used to develop an age estimation model that included two main components. First, a novel dimensionality reduction and feature selection algorithm was used to extract gait features. Second, a regularized linear model was trained using these features to produce a sparse, clinically interpretable estimator. This model was used to calculate a gait age gap metric, which was tested for association with measures of cognitive impairment and future cognitive decline.ResultThe distributions of gait age gap in age‐matched participants defined as having no cognitive impairment (CU, n = 573), mild cognitive impairment (MCI, n = 520), or a clinical diagnosis of dementia due to Alzheimer’s (AD, n = 53) are shown in Fig 1a. A significant shift in the mean is observed between all three groups. Fig 1b. shows the distributions of baseline gait age gap values amongst individuals categorized by cognitive decline: stable CU (n = 644), MCI converters (n = 89), stable MCI (n = 78), and significant impairment converters (SI, n = 35). The baseline gait age gap in stable CU individuals was found to be significantly lower than in the already impaired or converter groups.ConclusionIn this study, we developed a model for estimating accelerated aging from gait variables in the form of a gait age gap metric. This metric was shown to be strongly associated with AD‐driven cognitive impairment as well as predictive of future cognitive decline. These results highlight the potential clinical utility of quantitative gait analysis in behavioral neurologic assessment of cognitive impairment in AD.