Hemodynamic and metabolic changes during hypercapnia with normoxia and hyperoxia using pCASL and TRUST MRI in healthy adults.

Blood oxygenation level-dependent (BOLD) or arterial spin labeling (ASL) MRI with hypercapnic stimuli allow for measuring cerebrovascular reactivity (CVR). Hypercapnic stimuli are also employed in calibrated BOLD functional MRI for quantifying neuronally-evoked changes in cerebral oxygen metabolism (CMRO2). It is often assumed that hypercapnic stimuli (with or without hyperoxia) are iso-metabolic; increasing arterial CO2 or O2 does not affect CMRO2. We evaluated the null hypothesis that two common hypercapnic stimuli, 'CO2 in air' and carbogen, are iso-metabolic. TRUST and ASL MRI were used to measure the cerebral venous oxygenation and cerebral blood flow (CBF), from which the oxygen extraction fraction (OEF) and CMRO2 were calculated for room-air, 'CO2 in air' and carbogen. As expected, CBF significantly increased (9.9% ± 9.3% and 12.1% ± 8.8% for 'CO2 in air' and carbogen, respectively). CMRO2 decreased for 'CO2 in air' (-13.4% ± 13.0%, p < 0.01) compared to room-air, while the CMRO2 during carbogen did not significantly change. Our findings indicate that 'CO2 in air' is not iso-metabolic, while carbogen appears to elicit a mixed effect; the CMRO2 reduction during hypercapnia is mitigated when including hyperoxia. These findings can be important for interpreting measurements using hypercapnic or hypercapnic-hyperoxic (carbogen) stimuli.

Seeking progress in disease modification in Parkinson disease.

OBJECTIVE: Disease modification in Parkinson disease (PD) has remained an elusive goal, in spite of large investments over several decades. Following a large meeting of experts, this review article discusses the state of the science, possible reasons for past PD trials' failures to demonstrate disease-modifying benefit, and potential solutions. METHODS: The National Institute of Neurological Disorders and Stroke (NINDS) convened a meeting including leaders in the field and representatives of key stakeholder groups to discuss drug therapy with the goal of disease modification in PD. RESULTS: Important lessons can be learned from previous attempts, as well as from other fields. The selection process for therapeutic targets and agents differs among various organizations committed to therapeutic development. The areas identified as critical to target in future research include the development of relevant biomarkers, refinements of the targeted patient populations, considerations of novel trial designs, and improving collaborations between all stakeholders. CONCLUSIONS: We identify potential barriers to progress in disease modification for Parkinson's and propose a set of research priorities that may improve the likelihood of success.

Cerebral blood flow territory instability in patients with atherosclerotic intracranial stenosis.

BACKGROUND: Stroke risk stratification in patients with symptomatic intracranial atherosclerotic arterial disease (ICAD) remains an important clinical objective owing to the high 14-19% recurrent stroke rate in these patients on standard-of-care medical management. There thus remains a need for hemodynamic markers that may allow for the selection of personalized therapies for high-risk symptomatic patients. PURPOSE: To determine if shifting of cerebral blood flow (CBF) territories in response to changes in cerebral perfusion pressure (CPP) may provide a marker for stroke risk in ICAD patients. STUDY TYPE: Prospective. POPULATION: Twenty ICAD patients who experienced a stroke within 45 days of study enrollment and 10 healthy controls. SEQUENCE: 3.0T MRI including anatomical imaging (T1 -weighted, T2 -weighted/FLAIR), 3D MR angiography, and normocapnic and hypercapnic vessel-encoded CBF-weighted arterial spin labeling. ASSESSMENT: Patients were scanned within 45 days of overt stroke and monitored (duration = 13.2 ± 4.4 months) for the endpoint of non-cardioembolic stroke or transient ischemic attack. Flow territory shifting (shifting index) was calculated from the first scan by determining whether a voxel shifted from its primary arterial source from normocapnia to hypercapnia. STATISTICAL TESTS: A Mann-Whitney U-test (significance: P < 0.05) was performed to determine whether patients meeting the endpoint had greater shifting indices relative to controls or patients not meeting the endpoint. RESULTS: Shifting indices (mean ± standard error) were significantly higher in patients meeting endpoint criteria relative to controls (P = 0.0057; adjusted P = 0.036) and patients not meeting endpoint criteria (P = 0.0047; adjusted P = 0.036). DATA CONCLUSION: Flow territory shifting may provide a marker of recurrent stroke risk in symptomatic ICAD patients on standard-of-care medical management therapies. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:1441-1451.

Hemodynamic mechanisms underlying elevated oxygen extraction fraction (OEF) in moyamoya and sickle cell anemia patients.

Moyamoya is a bilateral, complex cerebrovascular condition characterized by progressive non-atherosclerotic intracranial stenosis and collateral vessel formation. Moyamoya treatment focuses on restoring cerebral blood flow (CBF) through surgical revascularization, however stratifying patients for revascularization requires abilities to quantify how well parenchyma is compensating for arterial steno-occlusion. Globally elevated oxygen extraction fraction (OEF) secondary to CBF reduction may serve as a biomarker for tissue health in moyamoya patients, as suggested in patients with sickle cell anemia (SCA) and reduced oxygen carrying capacity. Here, OEF was measured (TRUST-MRI) to test the hypothesis that OEF is globally elevated in patients with moyamoya (n = 18) and SCA (n = 18) relative to age-matched controls (n = 43). Mechanisms underlying the hypothesized OEF increases were evaluated by performing sequential CBF-weighted, cerebrovascular reactivity (CVR)-weighted, and structural MRI. Patients were stratified by treatment and non-parametric tests applied to compare study variables (significance: two-sided P < 0.05). OEF was significantly elevated in moyamoya participants (interquartile range = 0.38-0.45) compared to controls (interquartile range = 0.29-0.38), similar to participants with SCA (interquartile range = 0.37-0.45). CBF was inversely correlated with OEF in moyamoya participants. Elevated OEF was only weakly related to reductions in CVR, consistent with basal CBF level, rather than vascular reserve capacity, being most closely associated with OEF.

Impact of vessel wall lesions and vascular stenoses on cerebrovascular reactivity in patients with intracranial stenotic disease.

PURPOSE: To compare cerebrovascular reactivity (CVR) and CVR lagtimes in flow territories perfused by vessels with vs. without proximal arterial wall disease and/or stenosis, separately in patients with atherosclerotic and nonatherosclerotic (moyamoya) intracranial stenosis. MATERIALS AND METHODS: Atherosclerotic and moyamoya patients with >50% intracranial stenosis and <70% cervical stenosis underwent angiography, vessel wall imaging (VWI), and CVR-weighted imaging (n = 36; vessel segments evaluated = 396). Angiography and VWI were evaluated for stenosis locations and vessel wall lesions. Maximum CVR and CVR lagtime were contrasted between vascular territories with and without proximal intracranial vessel wall lesions and stenosis, and a Wilcoxon rank-sum was test used to determine differences (criteria: corrected two-sided P < 0.05). RESULTS: CVR lagtime was prolonged in territories with vs. without a proximal vessel wall lesion or stenosis for both patient groups: moyamoya (CVR lagtime = 45.5 sec ± 14.2 sec vs. 35.7 sec ± 9.7 sec, P < 0.001) and atherosclerosis (CVR lagtime = 38.2 sec ± 9.1 sec vs. 35.0 sec ± 7.2 sec, P = 0.001). For reactivity, a significant decrease in maximum CVR in the moyamoya group only (maximum CVR = 9.8 ± 2.2 vs. 12.0 ± 2.4, P < 0.001) was observed. CONCLUSION: Arterial vessel wall lesions detected on noninvasive, noncontrast intracranial VWI in patients with intracranial stenosis correlate on average with tissue-level impairment on CVR-weighted imaging. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017;46:1167-1176.

Prior Infarcts, Reactivity, and Angiography in Moyamoya Disease (PIRAMD): a scoring system for moyamoya severity based on multimodal hemodynamic imaging.

OBJECTIVE Quantification of the severity of vasculopathy and its impact on parenchymal hemodynamics is a necessary prerequisite for informing management decisions and evaluating intervention response in patients with moyamoya. The authors performed digital subtraction angiography and noninvasive structural and hemodynamic MRI, and they outline a new classification system for patients with moyamoya that they have named Prior Infarcts, Reactivity, and Angiography in Moyamoya Disease (PIRAMD). METHODS Healthy control volunteers (n = 11; age 46 ± 12 years [mean ± SD]) and patients (n = 25; 42 ± 13.5 years) with angiographically confirmed moyamoya provided informed consent and underwent structural (T1-weighted, T2-weighted, FLAIR, MR angiography) and hemodynamic (T2*- and cerebral blood flow-weighted) 3-T MRI. Cerebrovascular reactivity (CVR) in the internal carotid artery territory was assessed using susceptibility-weighted MRI during a hypercapnic stimulus. Only hemispheres without prior revascularization were assessed. Each hemisphere was considered symptomatic if localizing signs were present on neurological examination and/or there was a history of transient ischemic attack with symptoms referable to that hemisphere. The PIRAMD factor weighting versus symptomatology was optimized using binary logistic regression and receiver operating characteristic curve analysis with bootstrapping. The PIRAMD finding was scored from 0 to 10. For each hemisphere, 1 point was assigned for prior infarct, 3 points for reduced CVR, 3 points for a modified Suzuki Score ≥ Grade II, and 3 points for flow impairment in ≥ 2 of 7 predefined vascular territories. Hemispheres were divided into 3 severity grades based on total PIRAMD score, as follows: Grade 1, 0-5 points; Grade 2, 6-9 points; and Grade 3, 10 points. RESULTS In 28 of 46 (60.9%) hemispheres the findings met clinical symptomatic criteria. With decreased CVR, the odds ratio of having a symptomatic hemisphere was 13 (95% CI 1.1-22.6, p = 0.002). The area under the curve for individual PIRAMD factors was 0.67-0.72, and for the PIRAMD grade it was 0.845. There were 0/8 (0%), 10/18 (55.6%), and 18/20 (90%) symptomatic PIRAMD Grade 1, 2, and 3 hemispheres, respectively. CONCLUSIONS A scoring system for total impairment is proposed that uses noninvasive MRI parameters. This scoring system correlates with symptomatology and may provide a measure of hemodynamic severity in moyamoya, which could be used for guiding management decisions and evaluating intervention response.

Planning-free cerebral blood flow territory mapping in patients with intracranial arterial stenosis.

A noninvasive method for quantifying cerebral blood flow and simultaneously visualizing cerebral blood flow territories is vessel-encoded pseudocontinuous arterial spin labeling MRI. However, obstacles to acquiring such information include limited access to the methodology in clinical centers and limited work on how clinically acquired vessel-encoded pseudocontinuous arterial spin labeling data correlate with gold-standard methods. The purpose of this work is to develop and validate a semiautomated pipeline for the online quantification of cerebral blood flow maps and cerebral blood flow territories from planning-free vessel-encoded pseudocontinuous arterial spin labeling MRI with gold-standard digital subtraction angiography. Healthy controls (n = 10) and intracranial atherosclerotic disease patients (n = 34) underwent 3.0 T MRI imaging including vascular (MR angiography) and hemodynamic (cerebral blood flow-weighted arterial spin labeling) MRI. Patients additionally underwent catheter and/or CT angiography. Variations in cross-territorial filling were grouped according to diameters of circle of Willis vessels in controls. In patients, Cohen's k-statistics were computed to quantify agreement in perfusion patterns between vessel-encoded pseudocontinuous arterial spin labeling and angiography. Cross-territorial filling patterns were consistent with circle of Willis anatomy. The intraobserver Cohen's k-statistics for cerebral blood flow territory and digital subtraction angiography perfusion agreement were 0.730 (95% CI = 0.593-0.867; reader one) and 0.708 (95% CI = 0.561-0.855; reader two). These results support the feasibility of a semiautomated pipeline for evaluating major neurovascular cerebral blood flow territories in patients with intracranial atherosclerotic disease.

Crossed cerebellar diaschisis after stroke identified noninvasively with cerebral blood flow-weighted arterial spin labeling MRI.

BACKGROUND AND PURPOSE: Crossed cerebellar diaschisis (CCD) is most commonly investigated using hemodynamic PET and SPECT imaging. However, noninvasive MRI offers advantages of improved spatial resolution, allowing hemodynamic changes to be compared directly with structural findings and without concerns related to ionizing radiation exposure. The aim of this study was to evaluate relationships between CCD identified from cerebral blood flow (CBF)-weighted arterial spin labeling (ASL) MRI with cerebrovascular reactivity (CVR)-weighted blood oxygenation level dependent (BOLD) MRI, Wallerian degeneration, clinical motor impairment, and corticospinal tract involvement. METHODS: Subjects (n=74) enrolled in an ongoing observational stroke trial underwent CBF-weighted ASL and hypercapnic CVR-weighted BOLD MRI. Hemispheric asymmetry indices for basal cerebellar CBF, cerebellar CVR, and cerebral peduncular area were compared between subjects with unilateral supratentorial infarcts (n=18) and control subjects without infarcts (n=16). CCD required (1) supratentorial infarct and (2) asymmetric cerebellar CBF (>95% confidence interval relative to controls). RESULTS: In CCD subjects (n=9), CVR (p=0.04) and cerebral peduncular area (p<0.01) were significantly asymmetric compared to controls. Compared to infarct subjects not meeting CCD criteria (n=9), CCD subjects had no difference in corticospinal tract location for infarct (p=1.0) or motor impairment (p=0.08). CONCLUSIONS: CCD correlated with cerebellar CVR asymmetry and Wallerian degeneration. These findings suggest that noninvasive MRI may be a useful alternative to PET or SPECT to study structural correlates and clinical consequences of CCD following supratentorial stroke.

In vivo quantification of hyperoxic arterial blood water T1.

Normocapnic hyperoxic and hypercapnic hyperoxic gas challenges are increasingly being used in cerebrovascular reactivity (CVR) and calibrated functional MRI experiments. The longitudinal arterial blood water relaxation time (T1a) change with hyperoxia will influence signal quantification through mechanisms relating to elevated partial pressure of plasma-dissolved O2 (pO2) and increased oxygen bound to hemoglobin in arteries (Ya) and veins (Yv). The dependence of T1a on Ya and Yv has been elegantly characterized ex vivo; however, the combined influence of pO2, Ya and Yv on T1a in vivo under normal ventilation has not been reported. Here, T1a is calculated during hyperoxia in vivo by a heuristic approach that evaluates T1 -dependent arterial spin labeling (ASL) signal changes to varying gas stimuli. Healthy volunteers (n = 14; age, 31.5 ± 7.2 years) were scanned using pseudo-continuous ASL in combination with room air (RA; 21% O2/79% N2), hypercapnic normoxic (HN; 5% CO2/21% O2/74% N2) and hypercapnic hyperoxic (HH; 5% CO2/95% O2) gas administration. HH T1a was calculated by requiring that the HN and HH cerebral blood flow (CBF) change be identical. The HH protocol was then repeated in patients (n = 10; age, 61.4 ± 13.3 years) with intracranial stenosis to assess whether an HH T1a decrease prohibited ASL from being performed in subjects with known delayed blood arrival times. Arterial blood T1a decreased from 1.65 s at baseline to 1.49 ± 0.07 s during HH. In patients, CBF values in the affected flow territory for the HH condition were increased relative to baseline CBF values and were within the physiological range (RA CBF = 36.6 ± 8.2 mL/100 g/min; HH CBF = 45.2 ± 13.9 mL/100 g/min). It can be concluded that hyperoxic (95% O2) 3-T arterial blood T1aHH = 1.49 ± 0.07 s relative to a normoxic T1a of 1.65 s.

The cumulative influence of hyperoxia and hypercapnia on blood oxygenation and R*2.

Cerebrovascular reactivity (CVR)-weighted blood-oxygenation-level-dependent magnetic resonance imaging (BOLD-MRI) experiments are frequently used in conjunction with hyperoxia. Owing to complex interactions between hyperoxia and hypercapnia, quantitative effects of these gas mixtures on BOLD responses, blood and tissue R2*, and blood oxygenation are incompletely understood. Here we performed BOLD imaging (3 T; TE/TR=35/2,000 ms; spatial resolution=3 × 3 × 3.5 mm(3)) in healthy volunteers (n=12; age=29±4.1 years) breathing (i) room air (RA), (ii) normocapnic-hyperoxia (95% O2/5% N2, HO), (iii) hypercapnic-normoxia (5% CO2/21% O2/74% N2, HC-NO), and (iv) hypercapnic-hyperoxia (5% CO2/95% O2, HC-HO). For HC-HO, experiments were performed with separate RA and HO baselines to control for changes in O2. T2-relaxation-under-spin-tagging MRI was used to calculate basal venous oxygenation. Signal changes were quantified and established hemodynamic models were applied to quantify vasoactive blood oxygenation, blood-water R2*, and tissue-water R2*. In the cortex, fractional BOLD changes (stimulus/baseline) were HO/RA=0.011±0.007; HC-NO/RA=0.014±0.004; HC-HO/HO=0.020±0.008; and HC-HO/RA=0.035±0.010; for the measured basal venous oxygenation level of 0.632, this led to venous blood oxygenation levels of 0.660 (HO), 0.665 (HC-NO), and 0.712 (HC-HO). Interleaving a HC-HO stimulus with HO baseline provided a smaller but significantly elevated BOLD response compared with a HC-NO stimulus. Results provide an outline for how blood oxygenation differs for several gas stimuli and provides quantitative information on how hypercapnic BOLD CVR and R2* are altered during hyperoxia.

Dual echo vessel-encoded ASL for simultaneous BOLD and CBF reactivity assessment in patients with ischemic cerebrovascular disease.

PURPOSE: Blood oxygenation level-dependent (BOLD)-weighted and vessel-encoded arterial spin labeling (VE-ASL) MRI provide complementary information and can be used in sequence to gauge hemodynamic contributions to cerebrovascular reactivity. Here, cerebrovascular reactivity is assessed using dual echo VE-ASL MRI to understand how VE labeling preparations influence BOLD and ASL contrast in flow-limited and healthy perfusion territories. METHODS: Patients (n = 12; age = 55 +/- 14 years; 6F/6M) presenting with ischemic steno-occlusive cerebrovascular disease underwent 3.0T angiographic imaging, T1 -weighted structural, and planning-free dual echo hypercarbic hyperoxic (i.e., carbogen) VE-ASL MRI. Vasculopathy extent, timecourses, and cerebrovascular reactivity (signal change and Z-statistic) for different VE-ASL images were contrasted across flow territories and Bonferroni-corrected P-values reported. RESULTS: BOLD cerebrovascular reactivity (i.e., long-TE VE-ASL) Z-statistics were similarly sensitive to asymmetric disease (P ≤ 0.002) regardless of labeling scenario. Cerebral blood flow reactivity correlated significantly with BOLD reactivity (Z-statistic). However, BOLD signal changes did not differ significantly between labeling scenarios (P > 0.003) or across territories (P > 0.002), indicating BOLD signal changes in response to carbogen offer low sensitivity to lateralizing disease. CONCLUSION: Dual echo VE-ASL can provide simultaneous cerebral blood flow and qualitative BOLD contrast consistent with lateralizing disease severity in patients with asymmetric steno-occlusive disease. The methodological strengths and limitations of composite BOLD and VE-ASL measurements in the clinic are discussed.

The vascular steal phenomenon is an incomplete contributor to negative cerebrovascular reactivity in patients with symptomatic intracranial stenosis.

'Vascular steal' has been proposed as a compensatory mechanism in hemodynamically compromised ischemic parenchyma. Here, independent measures of cerebral blood flow (CBF) and blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) responses to a vascular stimulus in patients with ischemic cerebrovascular disease are recorded. Symptomatic intracranial stenosis patients (n=40) underwent a multimodal 3.0T MRI protocol including structural (T1-weighted and T2-weighted fluid-attenuated inversion recovery) and hemodynamic (BOLD and CBF-weighted arterial spin labeling) functional MRI during room air and hypercarbic gas administration. CBF changes in regions demonstrating negative BOLD reactivity were recorded, as well as clinical correlates including symptomatic hemisphere by infarct and lateralizing symptoms. Fifteen out of forty participants exhibited negative BOLD reactivity. Of these, a positive relationship was found between BOLD and CBF reactivity in unaffected (stenosis degree<50%) cortex. In negative BOLD cerebrovascular reactivity regions, three patients exhibited significant (P<0.01) reductions in CBF consistent with vascular steal; six exhibited increases in CBF; and the remaining exhibited no statistical change in CBF. Secondary findings were that negative BOLD reactivity correlated with symptomatic hemisphere by lateralizing clinical symptoms and prior infarcts(s). These data support the conclusion that negative hypercarbia-induced BOLD responses, frequently assigned to vascular steal, are heterogeneous in origin with possible contributions from autoregulation and/or metabolism.

Routine clinical evaluation of cerebrovascular reserve capacity using carbogen in patients with intracranial stenosis.

BACKGROUND AND PURPOSE: A promising method for identifying hemodynamic impairment that may serve as a biomarker for stroke risk in patients with intracranial stenosis is cerebrovascular reactivity (CVR) mapping using noninvasive MRI. Here, abilities to measure CVR safely in the clinic using hypercarbic hyperoxic (carbogen) gas challenges, which increase oxygen delivery to tissue, are investigated. METHODS: In sequence with structural and angiographic imaging, blood oxygenation level-dependent carbogen-induced CVR scans were performed in patients with symptomatic intracranial stenosis (n=92) and control (n=10) volunteers, with a subgroup of patients (n=57) undergoing cerebral blood flow-weighted pseudocontinuous arterial spin labeling CVR. Subjects were stratified for 4 substudies to evaluate relationships between (1) carbogen and hypercarbic normoxic CVR in healthy tissue (n=10), (2) carbogen cerebral blood flow CVR and blood oxygenation level-dependent CVR in intracranial stenosis patients (n=57), (3) carbogen CVR and clinical measures of disease in patients with asymmetrical intracranial atherosclerotic (n=31) and moyamoya (n=29) disease, and (4) the CVR scan and immediate and longer-term complications (n=92). RESULTS: Noninvasive blood oxygenation level-dependent carbogen-induced CVR values correlate with (1) lobar hypercarbic normoxic gas stimuli in healthy tissue (R=0.92; P<0.001), (2) carbogen-induced cerebral blood flow CVR in patients with intracranial stenosis (R=0.30-0.33; P<0.012), and (3) angiographic measures of disease severity both in atherosclerotic and moyamoya patients after appropriate processing. No immediate stroke-related complications were reported in response to carbogen administration; longer-term neurological events fell within the range for expected events in this patient population. CONCLUSIONS: Carbogen-induced CVR elicited no added adverse events and provided a surrogate marker of cerebrovascular reserve consistent with intracranial vasculopathy.

Bolus arrival time and cerebral blood flow responses to hypercarbia.

The purpose of this study was to evaluate how cerebral blood flow and bolus arrival time (BAT) measures derived from arterial spin labeling (ASL) MRI data change for different hypercarbic gas stimuli. Pseudocontinuous ASL (pCASL) was applied (3.0T; spatial resolution=4 × 4 × 7 mm(3); repetition time/echo time (TR/TE)=3,600/11 ms) sequentially in healthy volunteers (n=12; age=30±4 years) for separate experiments in which (i) normocarbic normoxia (i.e., room air), hypercarbic normoxia (i.e., 5% CO2/21% O2/74% N2), and hypercarbic hyperoxia (i.e., carbogen: 5% CO2/95% O2) gas was administered (12 L/minute). Cerebral blood flow and BAT changes were quantified using models that account for macrovascular signal and partial volume effects in all gray matter and regionally in cerebellar, temporal, occipital, frontal, and parietal lobes. Regional reductions in BAT of 4.6% to 7.7% and 3.3% to 6.6% were found in response to hypercarbic normoxia and hypercarbic hyperoxia, respectively. Cerebral blood flow increased by 8.2% to 27.8% and 3.5% to 19.8% for hypercarbic normoxia and hypercarbic hyperoxia, respectively. These findings indicate that changes in BAT values may bias functional ASL data and thus should be considered when choosing appropriate experimental parameters in calibrated functional magnetic resonance imaging or ASL cerebrovascular reactivity experiments that use hypercarbic gas stimuli.

Functional impairment in mild cognitive impairment evidenced using performance-based measurement.

Older adults (OAs) with mild cognitive impairment (MCI) are traditionally thought to have preservation of activities of daily living (ADLs). However, recent evidence suggests OAs with MCI may have difficulty completing ADLs and specifically instrumental ADLs (IADLs). The ADLs are frequently evaluated through self- or collateral report questionnaires, while performance-based measures are infrequently utilized, despite the decreased bias and increased accuracy and sensitivity associated with these instruments. This investigation compared ADLs between community-dwelling OAs with (n = 20) and without MCI (n = 30) using a self-report questionnaire (Older American Resources and Services Activities of Daily Living Scale; OARS), a collateral report questionnaire (OARS), and a performance-based measure (the Direct Assessment of Functional Status-Revised). Consistent with our hypothesis, OAs with MCI had decreased ADLs and IADLs on the performance-based measure compared to cognitively intact OAs, while there were no differences in ADLs or IADLs on self-report questionnaires or collateral report questionnaires. Our results suggest OAs with MCI have decreased ability to complete IADLs. However, this investigation suggests these deficits may not be detected by questionnaires and are more likely to be found with performance-based testing.

Minimal functional brain differences between older adults with and without mild cognitive impairment during the stroop.

This investigation compared the neural correlates of inhibition in normal older adults (OAs) and OAs with mild cognitive impairment (MCI). It was hypothesized the MCI group would require a greater amount of resources for inhibition, and therefore display greater functional activation in specific regions of interest (ROIs). Twenty-six OAs without and 17 with MCI completed the Stroop task during functional neuroimaging, and completed additional out-of-scanner neuropsychological measures. During inhibition, there were minimal functional Magnetic Resonance Imaging (fMRI) differences found between groups in a priori specified ROIs and with post-hoc multiple regression analyses. However, these minimal differences did not survive corrected thresholds. Robust differences were found with several tasks of a neuropsychological screening battery. The results of this study suggest only very minimal group differences in fMRI activation during inhibition which may not reliably identify MCI, and this condition may be best detected by traditional neuropsychological techniques.

Lateral temporal hyper-activation as a novel biomarker of mild cognitive impairment.

Memory dysfunction in mild cognitive impairment (MCI) due to Alzheimer's pathology is primarily associated with episodic memory deficits linked to deterioration of the medial temporal lobes (MTLs). Currently, there is a call to discover novel biomarkers of MCI in order to improve research criteria. Functional activation differences in MCI during episodic memory-task performance are often evidenced in the MTLs, and frontal and parietal lobes, but it has been suggested that examination of working memory (WM) differences may be more useful in detecting MCI. In the current study, MCI and control participants performed a complex WM span (CWMS) task while functional magnetic resonance imaging (fMRI) data were acquired. Results indicated hyper-activation of the lateral temporal lobes, MTLs, and frontal and parietal regions during encoding and maintenance, and hyper-activation of the lateral temporal, frontal, and parietal lobes during CWMS recall for the MCI participants. Medial and lateral temporal differences during encoding and maintenance are consistent with previous findings, but lateral temporal differences are often not elaborated upon. Hyper-activation of the lateral temporal lobes during WM encoding and maintenance, and also during recall, suggests that this region may provide valuable information regarding WM impairment in MCI and Alzheimer's. Given that whole-brain functional imaging of the MTLs is often limited due to artifact and partial voluming of sub-fields, examination of lateral temporal differences may provide a novel biomarker related to WM impairment in MCI.

Openness to experience is related to better memory ability in older adults with questionable dementia.

The personality traits Openness to experience and Neuroticism of the five-factor model have previously been associated with memory performance in nondemented older adults, but this relationship has not been investigated in samples with memory impairment. Our examination of 50 community-dwelling older adults (29 cognitively intact; 21 with questionable dementia as determined by the Clinical Dementia Rating Scale) showed that demographic variables (age, years of education, gender, and estimated premorbid IQ) and current depressive symptoms explained a significant amount of variance of Repeatable Battery of Neuropsychological Status Delayed Memory (adjusted R (2) = 0.23). After controlling for these variables, a measure of global cognitive status further explained a significant portion of variance in memory performance (ΔR(2) = 0.13; adjusted R(2) = 0.36; p < .01). Finally, adding Openness to this hierarchical linear regression model explained a significant additional portion of variance (ΔR(2) = 0.08; adjusted R(2) = 0.44; p < .01) but adding Neuroticism did not explain any additional variance. This significant relationship between Openness and better memory performance above and beyond one's cognitive status and demographic variables may suggest that a lifelong pattern of involvement in new cognitive activities could be preserved in old age or protect from memory decline. This study suggests that personality may be a powerful predictor of memory ability and clinically useful in this heterogeneous population.

DICCCOL: dense individualized and common connectivity-based cortical landmarks.

Is there a common structural and functional cortical architecture that can be quantitatively encoded and precisely reproduced across individuals and populations? This question is still largely unanswered due to the vast complexity, variability, and nonlinearity of the cerebral cortex. Here, we hypothesize that the common cortical architecture can be effectively represented by group-wise consistent structural fiber connections and take a novel data-driven approach to explore the cortical architecture. We report a dense and consistent map of 358 cortical landmarks, named Dense Individualized and Common Connectivity-based Cortical Landmarks (DICCCOLs). Each DICCCOL is defined by group-wise consistent white-matter fiber connection patterns derived from diffusion tensor imaging (DTI) data. Our results have shown that these 358 landmarks are remarkably reproducible over more than one hundred human brains and possess accurate intrinsically established structural and functional cross-subject correspondences validated by large-scale functional magnetic resonance imaging data. In particular, these 358 cortical landmarks can be accurately and efficiently predicted in a new single brain with DTI data. Thus, this set of 358 DICCCOL landmarks comprehensively encodes the common structural and functional cortical architectures, providing opportunities for many applications in brain science including mapping human brain connectomes, as demonstrated in this work.