Wisse, Laura EM, Xie, Long, Lyu, Xueying, Das, Sandhitsu R., de Flores, Robin, Lane, Jacqueline, Yushkevich, Paul A., Wolk, David A., and Initiative, Disease Neuroimaging
Alzheimer's & Dementia: The Journal of the Alzheimer's Association; Dec2022 Supplement 6, Vol. 18 Issue 6, p1-4, 4p
Background: Mild Cognitive Impairment with Suspected non‐Alzheimer's Pathophysiology (SNAP‐MCI) represents a group of patients with Alzheimer's disease (AD) like neurodegeneration without beta‐amyloid pathology. While this group likely has a heterogeneous etiology, tau pathology, as in Primary Age‐Related Tauopathy (PART), has been hypothesized to play a major role. We investigate tau positron emission tomography (PET) uptake in the medial temporal lobe (MTL) in SNAP‐MCI and the association of MTL Tau‐PET uptake with structural measures and delayed recall in beta‐amyloid negative (A‐) MCI patients. Method: 237 MCI patients and 301 A‐ controls with available beta‐amyloid and tau PET and magnetic resonance images (within 200 days) were included. Baseline hippocampal volume and entorhinal cortex (ERC) and Brodmann areas (BA)35 thickness were obtained using an in‐house developed pipeline and annualized atrophy rates were estimated in an unbiased fashion using follow‐up MRIs within 4.5 years. Βeta‐amyloid status (A+/‐) was determined by a standard cut‐off (Florbetapir: 1.11; Florbetaben: 1.08) and neurodegeneration status (N+/‐) by hippocampal volumes, corrected for intracranial volume, using the 90th percentile of A+ AD patients as the cut‐off. Tau‐PET standardized uptake value ratio (SUVR) in the ERC/BA35 was calculated. A composite z‐score of delayed recall at baseline and change over 2 years was obtained. Result: SNAP‐MCI had significantly higher ERC/BA35 Tau‐PET SUVR than A‐ controls (Table 1, corrected for age) and qualitatively higher than A‐N‐ MCI (p=0.10). ERC/BA35 Tau‐PET SUVR in A‐N‐ MCI was not significantly different from A‐ controls. In A‐ MCI patients, ERC/BA35 Tau‐PET SUVR was significantly associated with BA35 thickness and hippocampal, ERC and BA35 atrophy rates, corrected for beta‐amyloid PET SUVR (Table 2; Figure 1). MTL structural measures, but not ERC/BA35 Tau‐PET SUVR, were associated with cross‐sectional and longitudinal delayed recall measures (Table 3; Figure 2). Conclusion: SNAP‐MCI had elevated ERC/BA35 Tau‐PET SUVR and ERC/BA35 Tau‐PET SUVR was associated with MTL structural measures in A‐ MCI patients. This indicates that tau pathology might be an important driver of neurodegeneration in the absence of beta‐amyloid pathology, supporting the notion that PART contributes to SNAP‐MCI. Additionally, MTL structure was associated with memory performance, consistent with SNAP not being a benign condition. [ABSTRACT FROM AUTHOR]
Yang, David, Best, John R., Chambers, Colleen, Feldman, Howard H., Pettersen, Jacqueline A, Henri‐Bhargava, Alexander, Lee, Philip E, Nygaard, Haakon B., Funnell, Clark R, Foti, Dean J, Hsiung, Ging‐Yuek Robin, and DeMarco, Mari L.
Alzheimer's & Dementia: The Journal of the Alzheimer's Association; Dec2022 Supplement 6, Vol. 18 Issue 6, p1-2, 2p
Background: While previous studies have demonstrated the effect of Alzheimer's disease (AD) CSF testing in changing diagnosis, we lack an understanding of how this testing affects clinical management. Therefore, we assessed changes in clinical management associated with AD CSF biomarker testing when ordered as part of routine clinical management. Method: The 'Investigating the Impact of Alzheimer's Disease Diagnostics in British Columbia' (IMPACT‐AD BC) study (NCT05002699) is a longitudinal study examining the impact of AD CSF testing on clinical management, personal utility and health care economics in British Columbia, Canada. After AD CSF testing was ordered as part of routine care (where the clinical scenario met the appropriate use criteria), the patient and their physician were eligible to participate in the study. The primary outcome was the change in management (pre‐ v. post‐biomarker results) in a composite measure including 1) AD drug therapy, 2) other relevant drug therapy, 3) other diagnostic procedures, and 4) referral or counselling. Result: Participants (n = 129) had a median age of 63 (IQR:58‐68); 49% were female. Cognitive impairment at baseline consisted of 7% with subjective cognitive impairment, 53% with mild cognitive impairment, and 40% with dementia. CSF biomarker profiles were consistent with an amyloid‐beta pathology (i.e., A+) in 72% of cases. Changes in clinical management because of testing occurred in 83% of cases including: referrals and counseling (57%), imaging (47%) and other diagnostic procedures (e.g., neuropsychological testing) (42%), and use of AD drug therapies (40%). For those with a non‐AD pre‐biomarkers diagnosis, 42% were changed to AD post‐biomarkers; for those with an AD pre‐biomarkers diagnosis, 18% were changed to non‐AD post‐biomarkers. Conclusion: This study has revealed substantial changes in clinical management as a direct result of AD CSF biomarker testing in routine care. An understanding of the implications of biomarker testing will in turn help us: improve appropriate utilization, understand the broader impacts on persons living with dementia and on the health care system, and prepare for expanded use of this testing with the availability of disease‐modifying therapeutics. [ABSTRACT FROM AUTHOR]
Martinez, Vanessa A., Betts, Robin K., Scruth, Elizabeth A., Buckley, Jacqueline D., Cadiz, Vilma R., Bertrand, Linda D., Paulson, Shirley S., Dummett, Brian Alex, Abhyankar, Stella S., Reyes, Vivian M., Hatton, Joeffrey R., Sulit, Reynaldo, and Liu, Vincent X.
The left atrium is an early sensor of left ventricular (LV) dysfunction. Still, the prognostic value of left atrial (LA) function (strain) on cardiac magnetic resonance (CMR) in dilated cardiomyopathy (DCM) remains unknown. The goal of this study was to evaluate the prognostic value of CMR-derived LA strain in DCM. Patients with DCM from the Maastricht Cardiomyopathy Registry with available CMR imaging were included. The primary endpoint was the combination of sudden or cardiac death, heart failure (HF) hospitalization, or life-threatening arrhythmias. Given the nonlinearity of continuous variables, cubic spline analysis was performed to dichotomize. A total of 488 patients with DCM were included (median age: 54 [IQR: 46-62] years; 61% male). Seventy patients (14%) reached the primary endpoint (median follow-up: 6 [IQR: 4-9] years). Age, New York Heart Association (NYHA) functional class >II, presence of late gadolinium enhancement (LGE), LV ejection fraction (LVEF), LA volume index (LAVI), LV global longitudinal strain (GLS), and LA reservoir and conduit strain were univariably associated with the outcome (all P < 0.02). LA conduit strain was a stronger predictor of outcome compared with reservoir strain. LA conduit strain, NYHA functional class >II, and LGE remained associated in the multivariable model (LA conduit strain HR: 3.65 [95% CI: 2.01-6.64; P < 0.001]; NYHA functional class >II HR: 1.81 [95% CI: 1.05-3.12; P = 0.033]; and LGE HR: 2.33 [95% CI: 1.42-3.85; P < 0.001]), whereas age, N-terminal pro–B-type natriuretic peptide, LVEF, left atrial ejection fraction, LAVI, and LV GLS were not. Adding LA conduit strain to other independent predictors (NYHA functional class and LGE) significantly improved the calibration, accuracy, and reclassification of the prediction model (P < 0.05). LA conduit strain on CMR is a strong independent prognostic predictor in DCM, superior to LV GLS, LVEF, and LAVI and incremental to LGE. Including LA conduit strain in DCM patient management should be considered to improve risk stratification. [Display omitted] [ABSTRACT FROM AUTHOR]