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MA'AT analysis has been applied to two biologically‐important O‐glycosidic linkages in two disaccharides, α‐D‐Galp‐(1→3)‐β‐D‐GalpOMe (3) and β‐D‐Galp‐(1→3)‐β‐D‐GalpOMe (4). Using density functional theory (DFT) to obtain parameterized equations relating a group of trans‐O‐glycosidic NMR spin‐couplings to either phi (ϕ') or psi (ψ'), and experimental 3JCOCH, 2JCOC, and 3JCOCC spin‐couplings measured in aqueous solution in 13C‐labeled isotopomers, probability distributions of ϕ' and ψ' in each linkage were determined and compared to those determined by aqueous 1‐μs molecular dynamics (MD) simulation. Good agreement was found between the MA'AT and single‐state MD conformational models of these linkages for the most part, with modest (approximately <15°) differences in the mean values of ϕ' and ψ', although the envelope of allowed angles (encoded in circular standard deviations or CSDs) is consistently larger for ϕ' determined from MA'AT analysis than from MD for both linkages. The MA'AT model of the α‐Galp‐(1→3)‐β‐Galp linkage agrees well with those determined previously using conventional NMR methods (3JCOCH values and/or 1H‐1H NOEs), but some discrepancy was observed for the β‐Galp‐(1→3)‐β‐Galp linkage, which may arise from errors in the conventions used to describe the linkage torsion angles. Statistical analyses of X‐ray crystal structures show ranges of ϕ' and ψ' for both linkages that include the mean angles determined from MA'AT analyses, although both angles adopt a wide range of values in the crystalline state, with ϕ' in β‐Galp‐(1→3)‐β‐Galp linkages showing greater‐than‐expected conformational variability. [ABSTRACT FROM AUTHOR]

Introduction: Essential tremor (ET) patients may exhibit a variety of non-motor features, including cognitive decline and depressive symptoms. Studies of several neurodegenerative diseases link depression to cognitive decline, suggesting depression is an early marker of dementia. We examined whether baseline depressive symptoms predict incident dementia in elders with ET. Methods: Hundred and forty-one ET cases aged 70 years or older at baseline, enrolled in a prospective study of cognitive performance, took part in evaluations at baseline and at 18, 36, 54, and 72 months. Participants completed the Geriatric Depression Scale (GDS), a 30-item self-report measure of depressive symptoms, and a battery of neuropsychological tests and functional assessments, from which we derived cognitive diagnoses at each evaluation. Cox proportional hazards regression equations determined incident dementia risk based on participants' baseline depression scores. Results: Mean baseline age was 81.5 ± 6.7 years. Higher baseline GDS scores were associated with increased risk of dementia in an unadjusted model (hazards ratio [HR] = 1.11, 95% confidence interval [CI] = 1.02–1.20, p = 0.01) and after controlling for baseline age, education, number of medications, and tremor onset age (HR = 1.13, 95% CI = 1.02–1.25, p = 0.02). Conclusion: Baseline depression scores predicted incident dementia in elders with ET. With each one-point increase in baseline depression score, there was a 13% increase in incident dementia risk. Given the published data that reported depression may be twice as high in elders with ET compared to controls, this association is particularly worrisome in the ET population. [ABSTRACT FROM AUTHOR]

Objective Given the association between essential tremor (ET) and higher rates of cognitive decline, assessing this decline is an important element of research and clinical care. The Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) are two broad, brief measures that are widely used to monitor cognitive impairment in various neurological disorders. We sought to determine the relative ability of the MoCA and the MMSE to detect cognitive decline in elderly patients with ET. Methods We administered a neuropsychological battery to an ET cohort every 18 months over 4.5 years. We defined the gold standard for change in cognition as the change in neuropsychological test scores over consecutive evaluations and applied the Reliable Change Method to detect meaningful increases/decreases in test scores. We performed receiver operating characteristics (ROC) analysis to quantify the area under the curve (AUC) and compare the ability of the MoCA and the MMSE to detect cognitive decline. Results The AUCs for the MoCA and the MMSE did not differ significantly at any interval or when all intervals were pooled for analysis. Across all intervals, the ability of the MoCA and the MMSE to detect cognitive decline was consistently fair or poor. Conclusions We found that the ability of the MoCA and the MMSE to detect cognitive decline in ET patients over 18-month intervals is inadequate. Unchanged scores on the MoCA and the MMSE in ET over time should be approached with caution. We propose that these screening tools should be supplemented with additional neuropsychological tests. [ABSTRACT FROM AUTHOR]

Background: Remote assessment of essential tremor (ET) is unverified. Objectives: To compare assigned tremor scores from a remote videotaped research protocol with those from an in‐person videotaped research protocol and assess the validity of remote and in‐person videotape‐based diagnoses when compared against the intake diagnosis (ET vs. control). Methods: Participants with intake diagnoses of ET (11) or controls (15) completed a tremor examination that was filmed both remotely and in person. Results: Agreement between the tremor ratings assigned during remote and in‐person videos was substantial (composite κw, 0.67; mean Gwet's AC2 score, 0.92; mean percent agreement, 63.7%). In ET cases with less severe tremor, agreement was lower (p = 0.008). Diagnostic validity was high for both remote and in‐person videos compared to the intake diagnosis. Conclusions: Remote video is a reasonable alternative to in‐person video for the assessment of tremor severity and assignment of ET diagnoses. However, at low tremor amplitudes, agreement declines. [ABSTRACT FROM AUTHOR]