Vascular Aging in the Choroid Plexus: A 7T Ultrasmall Superparamagnetic Iron Oxide (USPIO)-MRI Study.

BACKGROUND: The choroid plexus (ChP), a densely vascularized structure, has drawn increasing attention for its involvement in brain homeostasis and waste clearance. While the volumetric changes have been explored in many imaging studies, few studies have investigated the vascular degeneration associated with aging in the ChP. PURPOSE: To investigate the sub-structural characteristics of the ChP, particularly the vascular compartment using high-resolution 7T imaging enhanced with Ferumoxytol, an ultrasmall super-paramagnetic iron oxide, which greatly increase the susceptibility contrast for vessels. STUDY TYPE: Prospective. SUBJECTS: Forty-nine subjects without neurological disorders (age: 21-80 years; 42 ± 17 years; 20 females). FIELD STRENGTH/SEQUENCE: 7-T with 2D and 3D T2* GRE, 3D MPRAGE T1, 2D TSE T2, and 2D FLAIR. ASSESSMENT: The vascular and stromal compartments of the ChP were segmented using K-means clustering on post-contrast 2D GRE images. Visual and qualitative assessment of ChP vascular characteristics were conducted independently by three observers. Vascular density (Volvessel/VolChP ratio) and susceptibility change (Δχ) induced by Ferumoxytol were analyzed on 3D GRE-derived susceptibility-weighted imaging and quantitative susceptibility mapping, respectively. STATISTICAL TESTS: Independent t-test, Mann-Whitney U test, and Chi-square test were utilized for group comparisons. The relationship between age and ChP's vascular alterations was examined using Pearson's correlation. Intra-class coefficient was calculated for inter-observer agreement. A P value <0.05 was considered statistically significant. RESULTS: 2D GRE images demonstrated superior contrast and accurate delineation of ChP substructures (ICC = 0.86). Older subjects exhibited a significantly smaller vascular density (16.5 ± 4.34%) and lower Δχ (22.10 ± 12.82 ppb) compared to younger subjects (24.85 ± 6.84% and 34.64 ± 12.69 ppb). Vascular density and mean Δχ within the ChP negatively correlated with age (r = -0.48, and r = -0.45). DATA CONCLUSION: Ferumoxytol-enhanced 7T images can demonstrate ChP alterations in elderly with decreased vascular density and expansion of nonvascular compartment. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

Drivers of Memory Loss Underreport in Mild Cognitive Impairment Due to Alzheimer Versus Vascular Disease.

BACKGROUND: We examined drivers of self and study partner reports of memory loss in mild cognitive impairment (MCI) from Alzheimer (AD-MCI) and vascular disease (Va-MCI). METHODS: We performed retrospective cross-sectional analyses of participants with AD-MCI (n=2874) and Va-MCI (n=376) from the National Alzheimer Coordinating Center data set. Statistical analysis utilized 2-sided t test or the Fisher exact test. RESULTS: Compared with AD-MCI, Va-MCI subjects (24.5% vs. 19.7%, P =0.031) and study partners (31.4% vs. 21.6%, P <0.0001) were more likely to deny memory loss. Black/African Americans were disproportionately represented in the group denying memory loss in AD-MCI (20.0% vs. 13.2%, P <0.0001) and Va-MCI (33.7% vs. 18.0%, P =0.0022). Study partners of participants with these features also disproportionately denied memory loss: female (AD-MCI: 60.1% vs. 51.7%, P =0.0002; Va-MCI: 70.3% vs. 52.3%, P =0.0011), Black/African American (AD-MCI: 23.5% vs. 11.98%, P <0.0001; Va-MCI: 48.8% vs. 26.5%, P =0.0002), and <16 years of education (AD-MCI only: 33.9% vs. 16.3%, P =0.0262). In AD-MCI and Va-MCI, participants with anxiety were disproportionately represented in the group endorsing memory loss (AD: 28.2% vs. 17.4%, P <0.0001; Va: 31.5% vs. 16.1%, P =0.0071), with analogous results with depression. CONCLUSION: The findings would suggest extra vigilance in interview-based MCI detection of persons at-risk for self-based or informant-based misreport.

Improving measurement of blood-brain barrier permeability with reduced scan time using deep-learning-derived capillary input function.

PURPOSE: In Dynamic contrast-enhanced MRI (DCE-MRI), Arterial Input Function (AIF) has been shown to be a significant contributor to uncertainty in the estimation of kinetic parameters. This study is to assess the feasibility of using a deep learning network to estimate local Capillary Input Function (CIF) to estimate blood-brain barrier (BBB) permeability, while reducing the required scan time. MATERIALS AND METHOD: A total of 13 healthy subjects (younger (<40 y/o): 8, older (> 67 y/o): 5) were recruited and underwent 25-min DCE-MRI scans. The 25 min data were retrospectively truncated to 10 min to simulate a reduced scan time of 10 min. A deep learning network was trained to predict the CIF using simulated tissue contrast dynamics with two vascular transport models. The BBB permeability (PS) was measured using 3 methods: (i) Ca-25min, using DCE-MRI data of 25 min with individually sampled AIF (Ca); (ii) Ca-10min, using truncated 10min data with AIF (Ca); and (iii) Cp-10min, using truncated 10 min data with CIF (Cp). The PS estimates from the Ca-25min method were used as reference standard values to assess the accuracy of the Ca-10min and Cp-10min methods in estimating the PS values. RESULTS: When compared to the reference method(Ca-25min), the Ca-10min and Cp-10min methods resulted in an overestimation of PS by 217 ± 241 % and 48.0 ± 30.2 %, respectively. The Bland Altman analysis showed that the mean difference from the reference was 8.85 ± 1.78 (x10-4 min-1) with the Ca-10min, while it was reduced to 1.63 ± 2.25 (x10-4 min-1) with the Cp-10min, resulting in an average reduction of 81%. The limits of agreement also reduced by up to 39.2% with the Cp-10min. We found a 75% increase of BBB permeability in the gray matter and a 35% increase in the white matter, when comparing the older group to the younger group. CONCLUSIONS: We demonstrated the feasibility of estimating the capillary-level input functions using a deep learning network. We also showed that this method can be used to estimate subtle age-related changes in BBB permeability with reduced scan time, without compromising accuracy. Moreover, the trained deep learning network can automatically select CIF, reducing the potential uncertainty resulting from manual user-intervention.

Impact of white matter hyperintensities on subjective cognitive decline phenotype in a diverse cohort of cognitively normal older adults.

OBJECTIVES: Subjective cognitive decline (SCD) is a preclinical stage of AD. White matter hyperintensities (WMH), an MRI marker of cerebral small vessel disease, associate with AD biomarkers and progression. The impact of WMH on SCD phenotype is unclear. METHODS/DESIGN: A retrospective, cross-sectional analysis was conducted on a diverse cohort with SCD evaluated at the NYU Alzheimer's Disease Research Center between January 2017 and November 2021 (n = 234). The cohort was dichotomized into none-to-mild (n = 202) and moderate-to-severe (n = 32) WMH. Differences in SCD and neurocognitive assessments were evaluated via Wilcoxon or Fisher exact tests, with p-values adjusted for demographics using multivariable logistic regression. RESULTS: Moderate-to-severe WMH participants reported more difficulty with decision making on the Cognitive Change Index (1.5 SD 0.7 vs. 1.2 SD 0.5, p = 0.0187) and worse short-term memory (2.2 SD 0.4 vs. 1.9 SD 0.3, p = 0.0049) and higher SCD burden (9.5 SD 1.6 vs. 8.7 SD 1.7, p = 0.0411) on the Brief Cognitive Rating Scale. Moderate-to-severe WMH participants scored lower on the Mini-Mental State Examination (28.0 SD 1.6 vs. 28.5 SD 1.9, p = 0.0491), and on delayed paragraph (7.2 SD 2.0 vs. 8.8 SD 2.9, p = 0.0222) and designs recall (4.5 SD 2.3 vs. 6.1 SD 2.5, p = 0.0373) of the Guild Memory Test. CONCLUSIONS: In SCD, WMH impact overall symptom severity, specifically in executive and memory domains, as well as objective performance on global and domain-specific tests in verbal memory and visual working/associative memory.

Vigorous, regular physical exercise may slow disease progression in Alzheimer's disease.

INTRODUCTION: Mild to moderate exercise may decrease Alzheimer's disease (AD) risk, but the effects of vigorous, regular physical exercise remain unclear. METHODS: Two patients with initial diagnoses of amnestic mild cognitive impairment (MCI) demonstrated positive AD biomarkers throughout 16 and 8 years of follow-up, with final diagnoses of mild AD and amnestic MCI, respectively. RESULTS: Patient 1 was diagnosed with amnestic MCI at age 64. Neuropsychological testing, magnetic resonance imaging (MRI), fluorodeoxyglucose-positron emission tomography (FDG-PET), amyloid imaging PET, and cerebrospinal fluid (CSF) biomarkers during follow-ups remained consistent with AD. By age 80, progression was minimal with Montreal Cognitive Assessment (MoCA) 26 of 30. Patient 2 was diagnosed with amnestic MCI at age 72. Neuropsychological testing, MRI, FDG-PET, and amyloid imaging PET during follow-ups remained consistent with AD. At age 80, MoCA was 27 of 30 with no clinical progression. Both patients regularly performed vigorous, regular exercise that increased after retirement/work reduction. DISCUSSION: Vigorous, regular exercise may slow disease progression in biomarker-positive amnestic MCI and mild AD.

Cortical myelin profile variations in healthy aging brain: A T1w/T2w ratio study.

Demyelination is observed in both healthy aging and age-related neurodegenerative disorders. While the significance of myelin within the cortex is well acknowledged, studies focused on intracortical demyelination and depth-specific structural alterations in normal aging are lacking. Using the recently available Human Connectome Project Aging dataset, we investigated intracortical myelin in a normal aging population using the T1w/T2w ratio. To capture the fine changes across cortical depths, we employed a surface-based approach by constructing cortical profiles traveling perpendicularly through the cortical ribbon and sampling T1w/T2w values. The curvatures of T1w/T2w cortical profiles may be influenced by differences in local myeloarchitecture and other tissue properties, which are known to vary across cortical regions. To quantify the shape of these profiles, we parametrized the level of curvature using a nonlinearity index (NLI) that measures the deviation of the profile from a straight line. We showed that NLI exhibited a steep decline in aging that was independent of local cortical thinning. Further examination of the profiles revealed that lower T1w/T2w near the gray-white matter boundary and superficial cortical depths were major contributors to the apparent NLI variations with age. These findings suggest that demyelination and changes in other T1w/T2w related tissue properties in normal aging may be depth-specific and highlight the potential of NLI as a unique marker of microstructural alterations within the cerebral cortex.

Exploration of Rapid Automatized Naming and Standard Visual Tests in Prodromal Alzheimer Disease Detection.

BACKGROUND: Visual tests in Alzheimer disease (AD) have been examined over the last several decades to identify a sensitive and noninvasive marker of the disease. Rapid automatized naming (RAN) tasks have shown promise for detecting prodromal AD or mild cognitive impairment (MCI). The purpose of this investigation was to determine the capacity for new rapid image and number naming tests and other measures of visual pathway structure and function to distinguish individuals with MCI due to AD from those with normal aging and cognition. The relation of these tests to vision-specific quality of life scores was also examined in this pilot study. METHODS: Participants with MCI due to AD and controls from well-characterized NYU research and clinical cohorts performed high and low-contrast letter acuity (LCLA) testing, as well as RAN using the Mobile Universal Lexicon Evaluation System (MULES) and Staggered Uneven Number test, and vision-specific quality of life scales, including the 25-Item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) and 10-Item Neuro-Ophthalmic Supplement. Individuals also underwent optical coherence tomography scans to assess peripapillary retinal nerve fiber layer and ganglion cell/inner plexiform layer thicknesses. Hippocampal atrophy on brain MRI was also determined from the participants' Alzheimer disease research center or clinical data. RESULTS: Participants with MCI (n = 14) had worse binocular LCLA at 1.25% contrast compared with controls (P = 0.009) and longer (worse) MULES test times (P = 0.006) with more errors in naming images (P = 0.009) compared with controls (n = 16). These were the only significantly different visual tests between groups. MULES test times (area under the receiver operating characteristic curve [AUC] = 0.79), MULES errors (AUC = 0.78), and binocular 1.25% LCLA (AUC = 0.78) showed good diagnostic accuracy for distinguishing MCI from controls. A combination of the MULES score and 1.25% LCLA demonstrated the greatest capacity to distinguish (AUC = 0.87). These visual measures were better predictors of MCI vs control status than the presence of hippocampal atrophy on brain MRI in this cohort. A greater number of MULES test errors (rs = -0.50, P = 0.005) and worse 1.25% LCLA scores (rs = 0.39, P = 0.03) were associated with lower (worse) NEI-VFQ-25 scores. CONCLUSIONS: Rapid image naming (MULES) and LCLA are able to distinguish MCI due to AD from normal aging and reflect vision-specific quality of life. Larger studies will determine how these easily administered tests may identify patients at risk for AD and serve as measures in disease-modifying therapy clinical trials.

Comparison of serum neurodegenerative biomarkers among hospitalized COVID-19 patients versus non-COVID subjects with normal cognition, mild cognitive impairment, or Alzheimer's dementia.

INTRODUCTION: Neurological complications among hospitalized COVID-19 patients may be associated with elevated neurodegenerative biomarkers. METHODS: Among hospitalized COVID-19 patients without a history of dementia (N = 251), we compared serum total tau (t-tau), phosphorylated tau-181 (p-tau181), glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), ubiquitin carboxy-terminal hydrolase L1 (UCHL1), and amyloid beta (Aß40,42) between patients with or without encephalopathy, in-hospital death versus survival, and discharge home versus other dispositions. COVID-19 patient biomarker levels were also compared to non-COVID cognitively normal, mild cognitive impairment (MCI), and Alzheimer's disease (AD) dementia controls (N = 161). RESULTS: Admission t-tau, p-tau181, GFAP, and NfL were significantly elevated in patients with encephalopathy and in those who died in-hospital, while t-tau, GFAP, and NfL were significantly lower in those discharged home. These markers correlated with severity of COVID illness. NfL, GFAP, and UCHL1 were higher in COVID patients than in non-COVID controls with MCI or AD. DISCUSSION: Neurodegenerative biomarkers were elevated to levels observed in AD dementia and associated with encephalopathy and worse outcomes among hospitalized COVID-19 patients.

Clinical Profiles of Arteriolosclerosis and Alzheimer Disease at Mild Cognitive Impairment and Mild Dementia in a National Neuropathology Cohort.

OBJECTIVE: We sought to evaluate early clinical differences between cerebral arteriolosclerosis (pARTE), Alzheimer disease (pAD), and AD with arteriolosclerosis (ADARTE). METHODS: Using National Alzheimer's Coordinating Center neuropathology diagnoses, we defined pARTE (n=21), pAD (n=203), and ADARTE (n=158) groups. We compared demographics, medical history, psychometrics, neuropsychiatric symptoms, and apolipoprotein E (APOE) allele variants across neuropathology groups. Retrospective timepoints were first evaluation with Global Clinical Dementia Rating (CDR) score of 0.5 and 1.0, via the CDR Dementia Staging Instrument, corresponding to mild cognitive impairment (MCI) and mild dementia, respectively. RESULTS: In MCI, clinical differences were minimal but pARTE subjects were older, had later onset cognitive decline, and progressed less severely than pAD. In mild dementia, pAD subjects were younger and had earlier onset of decline. Neuropsychiatric (depression) and psychometric (Logical Memory Delayed Recall, Trails B) differences also emerged between the groups. In MCI, APOE4 associated with worse Logical Memory Delayed Recall in pAD and ADARTE. In mild dementia, APOE4 associated with better animal fluency in pAD, but with better Trails A performance and more neuropsychiatric symptoms (Neuropsychiatric Inventory Questionnaire) in ADARTE. CONCLUSIONS: Differences between pARTE, pAD, and ADARTE emerge at mild dementia rather than MCI. APOE4 has varied cognitive and psychiatric impact dependent on neuropathology group and stage.

Postsynaptic integrative properties of dorsal CA1 pyramidal neuron subpopulations.

The population activity of CA1 pyramidal neurons (PNs) segregates along anatomical axes with different behaviors, suggesting that CA1 PNs are functionally subspecialized based on somatic location. In dorsal CA1, spatial encoding is biased toward CA2 (CA1c) and in deep layers of the radial axis. In contrast, nonspatial coding peaks toward subiculum (CA1a) and in superficial layers. While preferential innervation by spatial vs. nonspatial input from entorhinal cortex (EC) may contribute to this specialization, it cannot fully explain the range of in vivo responses. Differences in intrinsic properties thus may play a critical role in modulating such synaptic input differences. In this study we examined the postsynaptic integrative properties of dorsal CA1 PNs in six subpopulations along the transverse (CA1c, CA1b, CA1a) and radial (deep, superficial) axes. Our results suggest that active and passive properties of deep and superficial neurons evolve over the transverse axis to promote the functional specialization of CA1c vs. CA1a as dictated by their cortical input. We also find that CA1b is not merely an intermediate mix of its neighbors, but uniquely balances low excitability with superior input integration of its mixed input, as may be required for its proposed role in sequence encoding. Thus synaptic input and intrinsic properties combine to functionally compartmentalize CA1 processing into at least three transverse axis regions defined by the processing schemes of their composite radial axis subpopulations.NEW & NOTEWORTHY There is increasing interest in CA1 pyramidal neuron heterogeneity and the functional relevance of this diversity. We find that active and passive properties evolve over the transverse and radial axes in dorsal CA1 to promote the functional specialization of CA1c and CA1a for spatial and nonspatial memory, respectively. Furthermore, CA1b is not a mean of its neighbors, but features low excitability and superior integrative capabilities, relevant to its role in nonspatial sequence encoding.

Psychometric Cognitive Decline Precedes the Advent of Subjective Cognitive Decline in the Evolution of Alzheimer's Disease.

BACKGROUND: We have described the clinical stages of the brain aging and Alzheimer's disease (AD) continuum. In terms of the pre-dementia stages of AD, we introduced the terminology "mild cognitive impairment" (MCI) for the first pre-dementia stage and "subjective cognitive decline" (SCD) for the pre-MCI stage. We now report the characteristics of a pre-SCD condition eventuating in likely AD. OBJECTIVE: The aim of this study was to characterize a pre-SCD condition eventuating in AD. METHOD: Sixty healthy persons with "no cognitive decline" (NCD) were recruited and 47 were followed (mean baseline age, 64.1 ± 8.9 years; mean follow-up time, 6.7 ± 3.1 years). Outcome was determined at the final assessment prior to 2002 as "decliner," if SCD or worse, or "nondecliner" if NCD. RESULTS: After controlling for age, gender, years of education, and follow-up time, there was a between-group difference in the decline rate (p < 0.001). Also, after controlling for demographic variables and follow-up time, the combinatorial psychometric score was lower at baseline in the future decliners (p = 0.035). Of the 9 psychometric variables, after controlling for demographic variables and follow-up time, 3 were significantly lower at baseline in future decliners. Since AD is known to be age related and all subjects in this study were otherwise healthy, we also did an analysis without controlling for age. The combinatorial psychometric score was highly significantly better at baseline in the future nondecliners than in the future decliners (p = 0.008). CONCLUSION: This is ostensibly the first study to link psychometric cognitive decline to the subsequent SCD stage of eventual AD.

Olfactory identification deficits and increased mortality in the community.

OBJECTIVE: To examine the association between odor identification deficits and future mortality in a multiethnic community cohort of older adults. METHODS: Participants were evaluated with the 40-item University of Pennsylvania Smell Identification Test (UPSIT). Follow-up occurred at 2-year intervals with information on death obtained from informant interviews and the National Death Index. RESULTS: During follow-up (mean = 4.1 years, standard deviation = 2.6), 349 of 1,169 (29.9%) participants died. Participants who died were more likely to be older (p < 0.001), be male (p < 0.001), have lower UPSIT scores (p < 0.001), and have a diagnosis of dementia (p < 0.001). In a Cox model, the association between lower UPSIT score and mortality (hazard ratio [HR] = 1.07 per point interval, 95% confidence interval [CI] = 1.05-1.08, p < 0.001) persisted after controlling for age, gender, education, ethnicity, language, modified Charlson medical comorbidity index, dementia, depression, alcohol abuse, head injury, smoking, body mass index, and vision and hearing impairment (HR = 1.05, 95% CI = 1.03-1.07, p < 0.001). Compared to the fourth quartile with the highest UPSIT scores, HRs for mortality for the first, second, and third quartiles of UPSIT scores were 3.81 (95% CI = 2.71-5.34), 1.75 (95% CI = 1.23-2.50), and 1.58 (95% CI = 1.09-2.30), respectively. Participant mortality rate was 45% in the lowest quartile of UPSIT scores (anosmia) and 18% in the highest quartile of UPSIT scores. INTERPRETATION: Impaired odor identification, particularly in the anosmic range, is associated with increased mortality in older adults even after controlling for dementia and medical comorbidity.

Dynamic cerebral autoregulation is transiently impaired for one week after large-vessel acute ischemic stroke.

BACKGROUND: Dynamic cerebral autoregulation (DCA) is the continuous counterregulation of cerebral blood flow to fluctuations in blood pressure. DCA can become impaired after acute stroke, but it remains unclear to what extent and over what interval this occurs. METHODS: We included 28 patients (NIHSS = 12 ± 6.5, age = 68.4 ± 17.1, 16F) with acute large-vessel ischemic stroke in the middle cerebral artery territory and 29 healthy controls (mean age 54.9 ± 9, 16F). DCA was assessed by simultaneous measurement of blood pressure together with blood flow velocities using finger plethysmography/arterial catheter and transcranial Doppler over three 10-minute recordings on days 0-2, 3-6 and ≥7 days after stroke. Transfer function analysis was applied to calculate average phase shift (PS) in the low frequency range (0.06-0.12 Hz). Less PS indicated poorer autoregulation. The affected side was compared with the unaffected side and controls. Univariate comparisons of data were performed using t tests at single time points, and generalized estimating equations with an exchangeable correlation matrix to examine the change in PS over time. RESULTS: At mean 1.3 ± 0.5 days after stroke the average PS in the affected hemisphere was 29.6 ± 10.5 vs. 42.5 ± 13 degrees in the unaffected hemisphere (p = 0.004). At 4.1 ± 1 days, the PS in affected and unaffected hemisphere was 23.2 ± 19.1 vs. 41.7 ± 18.5 degrees, respectively (p = 0.003). At mean 9.75 ± 2.2 days stroke there was no difference between the affected and the unaffected hemisphere (53.2 ± 28.2 vs. 50.7 ± 29.2 degrees, p = 0.69). Control subjects had an average PS = 47.9 ± 16.8, significantly different from patients' affected hemisphere at the first two measurements (p = 0.001), but not the third (p = 0.37). The PS in controls remained unchanged on repeat testing after an average 19.1 days (48.4 ± 17.1, p = 0.61). Using the last recording as the reference, the average PS in the affected hemisphere was -23.54 (-44.1, -3) degrees lower on recording one (p = 0.025), and -31.6 (-56.1, -7.1) degrees lower on recording two (p < 0.011). Changes in the unaffected hemisphere over time were nonsignificant. DISCUSSION: These data suggest that dynamic cerebral autoregulation is impaired in the affected hemisphere throughout the first week after large-vessel ischemic stroke, and then normalizes by week two. These findings may have important implications for acute blood pressure management after stroke.

Comparison of Non-invasive and Invasive Arterial Blood Pressure Measurement for Assessment of Dynamic Cerebral Autoregulation.

BACKGROUND: There is a growing interest in measuring cerebral autoregulation in patients with acute brain injury. Non-invasive finger photo-plethysmography (Finapres) is the method of choice to relate arterial blood pressure to changes in cerebral blood flow. Among acutely ill patients, however, peripheral vasoconstriction often limits the use of Finapres requiring direct intravascular blood pressure measurement. We evaluated how these two different forms of blood pressure monitoring affect the parameters of dynamic cerebral autoregulation (DCA). METHODS: We performed 37 simultaneous recordings of BP and cerebral blood flow velocity in 15 patients with acute brain injury. DCA was estimated in the frequency domain using transfer function analysis to calculate phase shift, gain, and coherence. In addition the mean velocity index (Mx) was calculated for assessment of DCA in the time domain. RESULTS: The mean patient age was 58.1 ± 15.9 years, 80 % (n = 12) were women. We found good inter-method agreement between Finapres and direct intravascular measurement using Bland-Altman and correlation analyses. Finapres gives higher values for the efficiency of dynamic CA compared with values derived from radial artery catheter, as indicated by biases in the phase (26.3 ± 11.6° vs. 21.7 ± 10.5°, p = 0.001) and Mx (0.571 ± 0.137 vs. 0.649 ± 0.128, p < 0.001). Gain in the low frequency range did not significantly differ between the two arterial blood pressure methods. The average coherence between CBFV and ABP was higher when BP was measured with arterial catheter for frequencies above 0.05 Hz (0.8 vs. 0.73, p < 0.001). CONCLUSION: Overall, both methods yield similar results and can be used for the assessment of DCA. However, there was a small but significant difference for both mean Mx and phase shift, which would need to be adjusted for during monitoring of patients when using both methods. When available, invasive arterial blood pressure monitoring may improve accuracy and thus should be the preferred method for DCA assessment in the ICU.

Comparison of non-invasive and invasive arterial blood pressure measurement for assessment of dynamic cerebral autoregulation.

BACKGROUND: There is a growing interest in measuring cerebral autoregulation in patients with acute brain injury. Non-invasive finger photo-plethysmography (Finapres) is the method of choice to relate arterial blood pressure to changes in cerebral blood flow. Among acutely ill patients, however, peripheral vasoconstriction often limits the use of Finapres requiring direct intravascular blood pressure measurement. We evaluated how these two different forms of blood pressure monitoring affect the parameters of dynamic cerebral autoregulation (DCA). METHODS: We performed 37 simultaneous recordings of BP and cerebral blood flow velocity in 15 patients with acute brain injury. DCA was estimated in the frequency domain using transfer function analysis to calculate phase shift, gain, and coherence. In addition the mean velocity index (Mx) was calculated for assessment of DCA in the time domain. RESULTS: The mean patient age was 58.1 ± 15.9 years, 80 % (n = 12) were women. We found good inter-method agreement between Finapres and direct intravascular measurement using Bland­Altman and correlation analyses. Finapres gives higher values for the efficiency of dynamic CA compared with values derived from radial artery catheter, as indicated by biases in the phase (26.3 ± 11.6° vs. 21.7 ± 10.5°, p = 0.001) and Mx (0.571 ± 0.137 vs. 0.649 ± 0.128, p < 0.001). Gain in the low frequency range did not significantly differ between the two arterial blood pressure methods. The average coherence between CBFV and ABP was higher when BP was measured with arterial catheter for frequencies above 0.05 Hz (0.8 vs. 0.73, p < 0.001). CONCLUSION: Overall, both methods yield similar results and can be used for the assessment of DCA. However, there was a small but significant difference for both mean Mx and phase shift, which would need to be adjusted for during monitoring of patients when using both methods. When available, invasive arterial blood pressure monitoring may improve accuracy and thus should be the preferred method for DCA assessment in the ICU.

Impact of dendritic spine loss on excitability of hippocampal CA1 pyramidal neurons: a computational study of early Alzheimer disease.

Synaptic spine loss is an early pathophysiologic hallmark of Alzheimer disease (AD) that precedes overt loss of dendritic architecture and frank neurodegeneration. While spine loss signifies a decreased engagement of postsynaptic neurons by presynaptic targets, the degree to which loss of spines and their passive components impacts the excitability of postsynaptic neurons and responses to surviving synaptic inputs is unclear. Using passive multicompartmental models of CA1 pyramidal neurons (PNs), implicated in early AD, we find that spine loss alone drives a boosting of remaining inputs to their proximal and distal dendrites, targeted by CA3 and entorhinal cortex (EC), respectively. This boosting effect is higher in distal versus proximal dendrites and can be mediated by spine loss restricted to the distal compartment, enough to impact synaptic input integration and somatodendritic backpropagation. This has particular relevance to very early stages of AD in which pathophysiology extends from EC to CA1.

Diffusion imaging markers of accelerated aging of the lower cingulum in subjective cognitive decline.

Introduction: Alzheimer's Disease (AD) typically starts in the medial temporal lobe, then develops into a neurodegenerative cascade which spreads to other brain regions. People with subjective cognitive decline (SCD) are more likely to develop dementia, especially in the presence of amyloid pathology. Thus, we were interested in the white matter microstructure of the medial temporal lobe in SCD, specifically the lower cingulum bundle that leads into the hippocampus. Diffusion tensor imaging (DTI) has been shown to differentiate SCD participants who will progress to mild cognitive impairment from those who will not. However, the biology underlying these DTI metrics is unclear, and results in the medial temporal lobe have been inconsistent. Methods: To better characterize the microstructure of this region, we applied DTI to cognitively normal participants in the Cam-CAN database over the age of 55 with cognitive testing and diffusion MRI available (N = 325, 127 SCD). Diffusion MRI was processed to generate regional and voxel-wise diffusion tensor values in bilateral lower cingulum white matter, while T1-weighted MRI was processed to generate regional volume and cortical thickness in the medial temporal lobe white matter, entorhinal cortex, temporal pole, and hippocampus. Results: SCD participants had thinner cortex in bilateral entorhinal cortex and right temporal pole. No between-group differences were noted for any of the microstructural metrics of the lower cingulum. However, correlations with delayed story recall were significant for all diffusion microstructure metrics in the right lower cingulum in SCD, but not in controls, with a significant interaction effect. Additionally, the SCD group showed an accelerated aging effect in bilateral lower cingulum with MD, AxD, and RD. Discussion: The diffusion profiles observed in both interaction effects are suggestive of a mixed neuroinflammatory and neurodegenerative pathology. Left entorhinal cortical thinning correlated with decreased FA and increased RD, suggestive of demyelination. However, right entorhinal cortical thinning also correlated with increased AxD, suggestive of a mixed pathology. This may reflect combined pathologies implicated in early AD. DTI was more sensitive than cortical thickness to the associations between SCD, memory, and age. The combined effects of mixed pathology may increase the sensitivity of DTI metrics to variations with age and cognition.