Hybrid PET/MRI with Flutemetamol and FDG in Alzheimer's Disease Clinical Continuum.

AIMS: We aimed to investigate the interaction between ß -amyloid (Aß) accumulation and cerebral glucose metabolism, cerebral perfusion, and cerebral structural changes in the Alzheimer's disease (AD) clinical continuum. BACKGROUND: Utility of positron emission tomography (PET) / magnetic resonance imaging (MRI) hybrid imaging for diagnostic categorization of the AD clinical continuum including subjective cognitive decline (SCD), amnestic mild cognitive impairment (aMCI) and Alzheimer's disease dementia (ADD) has not been fully crystallized. OBJECTIVE: To evaluate the interaction between Aß accumulation and cerebral glucose metabolism, cerebral perfusion, and cerebral structural changes such as cortex thickness or cerebral white matter disease burden and to detect the discriminative yields of these imaging modalities in the AD clinical continuum. METHODS: Fifty patients (20 women and 30 men; median age: 64 years) with clinical SCD (n=11), aMCI (n=17) and ADD (n=22) underwent PET/MRI with [18F]-fluoro-D-glucose (FDG) and [18F]- Flutemetamol in addition to cerebral blood flow (CBF) and quantitative structural imaging along with detailed cognitive assessment. RESULTS: High Aß deposition (increased temporal [18F]-Flutemetamol standardized uptake value ratio (SUVr) and centiloid score), low glucose metabolism (decreased temporal lobe and posterior cingulate [18F]-FDG SUVr), low parietal CBF and right hemispheric cortical thickness were independent predictors of low cognitive test performance. CONCLUSION: Integrated use of structural, metabolic, molecular (Aß) and perfusion (CBF) parameters contribute to the discrimination of SCD, aMCI, and ADD.

Mean Arterial Pressure and Cerebral Hemodynamics Across The Lifespan: A Cross-Sectional Study From Human Connectome Project-Aging.

BACKGROUND: Cerebral perfusion is directly affected by systemic blood pressure, which has been shown to be negatively correlated with cerebral blood flow (CBF). The impact of aging on these effects is not fully understood. PURPOSE: To determine whether the relationship between mean arterial pressure (MAP) and cerebral hemodynamics persists throughout the lifespan. STUDY TYPE: Retrospective, cross-sectional study. POPULATION: Six hundred and sixty-nine participants from the Human Connectome Project-Aging ranging between 36 and 100+ years and without a major neurological disorder. FIELD STRENGTH/SEQUENCE: Imaging data was acquired at 3.0 Tesla using a 32-channel head coil. CBF and arterial transit time (ATT) were measured by multi-delay pseudo-continuous arterial spin labeling. ASSESSMENT: The relationships between cerebral hemodynamic parameters and MAP were evaluated globally in gray and white matter and regionally using surface-based analysis in the whole group, separately within different age groups (young: <60 years; younger-old: 60-79 years; oldest-old: ≥80 years). STATISTICAL TESTS: Chi-squared, Kruskal-Wallis, ANOVA, Spearman rank correlation and linear regression models. The general linear model setup in FreeSurfer was used for surface-based analyses. P < 0.05 was considered significant. RESULTS: Globally, there was a significant negative correlation between MAP and CBF in both gray (ρ = -0.275) and white matter (ρ = -0.117). This association was most prominent in the younger-old [gray matter CBF (ß = -0.271); white matter CBF (ß = -0.241)]. In surface-based analyses, CBF exhibited a widespread significant negative association with MAP throughout the brain, whereas a limited number of regions showed significant prolongation in ATT with higher MAP. The associations between regional CBF and MAP in the younger-old showed a different topographic pattern in comparison to young subjects. DATA CONCLUSION: These observations further emphasize the importance of cardiovascular health in mid-to-late adulthood for healthy brain aging. The differences in the topographic pattern with aging indicate a spatially heterogeneous relationship between high blood pressure and CBF. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 3.

Cerebral vasomotor reactivity across the continuum of subjective cognitive impairment, amnestic mild cognitive impairment and probable Alzheimer's dementia: A transcranial Doppler and PET/MRI study.

Cerebrovascular dysfunction has been suggested as a physiomarker of Alzheimer's disease (AD)-associated neuronal degeneration, but the underlying mechanisms are still debated. Herein cerebral vasomotor reactivity (VMR, breath-hold index: BHI), metabolic activity (lobar SUVs, FDG PET MRI), amyloid load (Centiloid score, Flutemetamol PET MRI), hemispheric cortical thickness, white matter lesion load and cerebral blood flow (ASL) were studied in 43 consecutive subjects (mean age: 64 years, female 13), diagnosed with subjective cognitive impairment (SCI, n = 10), amnestic mild cognitive impairment (aMCI, n = 15), and probable Alzheimer's dementia (AD, n = 18). BHI was significantly reduced in AD and aMCI patients compared to SCI subjects. A highly significant inverse correlation was found between BHI and the centiloid score (r = -0.648, p < 0.001). There was moderate positive correlation between BHI and frontal, temporal and parietal FDG SUV and ASL values, and a borderline negative correlation with age and white matter lesion volume. The link between amyloid burden and VMR was independent and strong in linear regression models where all these parameters were included (ß from -0.580 to -0.476, p < 0.001). In conclusion, our study confirms the negative association of cerebral amyloid accumulation and vasomotor reactivity in Alzheimer's disease with the most direct data to date in humans.

The association between telomere length and ischemic stroke risk and phenotype.

The chronological age of a person is a key determinant of etiology and prognosis in the setting of ischemic stroke. Telomere length, an indicator of biological aging, progressively shortens with every cell cycle. Herein, we determined telomere length from peripheral blood leukocytes by Southern blot analyses in a prospective cohort of ischemic stroke patients (n = 163) and equal number of non-stroke controls and evaluated its association with various ischemic stroke features including etiology, severity, and outcome. A shorter telomere length (i.e. lowest quartile; ≤ 5.5 kb) was significantly associated with ischemic stroke (OR 2.95, 95% CI 1.70-5.13). This significant relationship persisted for all stroke etiologies, except for other rare causes of stroke. No significant association was present between admission lesion volume and telomere length; however, patients with shorter telomeres had higher admission National Institutes of Health Stroke Scale scores when adjusted for chronological age, risk factors, etiology, and infarct volume (p = 0.046). On the other hand, chronological age, but not telomere length, was associated with unfavorable outcome (modified Rankin scale > 2) and mortality at 90 days follow-up. The association between shorter telomere length and more severe clinical phenotype at the time of admission, might reflect reduced resilience of cerebral tissue to ischemia as part of biological aging.

Nonsustained Atrial Fibrillation in Ischemic Stroke Patients and Stroke-Free Controls From the Perspective of Stroke Pathophysiology.

BACKGROUND: Short-lasting (<30 s), nonsustained episodes of atrial fibrillation (NS-AF) are considered a risk factor for future development of paroxysmal or persistent AF. Nonetheless, their causal role in stroke pathogenesis is currently unknown. In this study we determined the frequency of NS-AF, together with the associated clinical and imaging features, in stroke-free controls and ischemic stroke patients. METHODS AND RESULTS: A total of 332 controls, ≥50 years of age and no prior history of stroke or AF, were evaluated with 24-hour Holter monitoring for the presence of <30-s-long AF episodes. The demographic and cardiovascular features of this cohort, together with imaging finding on magnetic resonance imaging, were compared to a consecutive series of ≥50-year-old ischemic stroke patients without AF (n=498). The prevalence of NS-AF was significantly higher among ischemic stroke patients in comparison to controls (37% versus 27%; P=0.002). In multivariable analyses, after adjustment for demographic and cardiovascular risk factors, patients with ischemic stroke were more likely to harbor NS-AF episodes (odds ratio 1.43; 95% CI 1.01-2.02; P=0.041). The association between ischemic stroke and NS-AF weakened when the analyses were restricted to cryptogenic stroke patients (odds ratio 1.31; 95% CI 0.82-2.08). No significant association was observed between the presence of chronic cortical infarcts and NS-AF. CONCLUSIONS: Our study shows a higher prevalence of NS-AF episodes in ischemic stroke patients in comparison to controls. Nonetheless, the lack of a stronger association with cryptogenic strokes and absence of a relationship with chronic cortical infarcts brings into question the causal influence of NS-AF in the ischemic stroke setting.

Non-expert use of quantitative EEG displays for seizure identification in the adult neuro-intensive care unit.

Video-EEG monitoring is the ultimate way to diagnose non-convulsive status epilepticus (NCSE) in intensive care units (ICU). Usually EEG recordings are evaluated once a day by an electrophysiologist, which may lead to delay in diagnosis. Digital EEG trend analysis methods like amplitude integrated EEG (aEEG) and density spectral array (DSA) have been developed to facilitate recognition of seizures. In this study, we aimed to investigate the diagnostic utility of these methods by non-expert physicians and ICU nurses for NCSE identification in an adult neurological ICU. Ten patients with NCSE and ten control patients without seizures were included in the study. The raw EEG recordings of all subjects were converted to both aEEG and DSA and displayed simultaneously without conventional EEG. After training for seizure recognition with both methods, two physicians and two nurses analyzed the visual displays individually, and marked seizure timings. Their results were compared with those of a study epileptologist. Participants analyzed 615h of EEG data with 700 seizures. Overall, 63% of the seizures were recognized by all, 15.6% by three, 11.6% by two, 8.3% by one rater and only 1.5% were missed by all of them (sensitivity was 88-99%, and specificity was 89-95% when the ratings were assessed as 1-h epochs). False positive rates were 1 per 2h in the study and 1 per 6h in the control groups. Interrater agreement was high (κ=0.79-0.81). Bilateral independent seizures and ictal recordings with lower amplitude and shorter duration were more likely to be missed. There was no difference in performance between the rating of physicians and nurses. Our study demonstrates that bedside nurses, ICU fellows and residents can achieve acceptable level of accuracy for seizure identification using the digital EEG trend analysis methods following brief training. This may help earlier notification of the electrophysiologist who is not always available in ICUs.