Association of hearing impairment with brain volume changes in older adults.

Hearing impairment in older adults is independently associated in longitudinal studies with accelerated cognitive decline and incident dementia, and in cross-sectional studies, with reduced volumes in the auditory cortex. Whether peripheral hearing impairment is associated with accelerated rates of brain atrophy is unclear. We analyzed brain volume measurements from magnetic resonance brain scans of individuals with normal hearing versus hearing impairment (speech-frequency pure tone average>25 dB) followed in the neuroimaging substudy of the Baltimore Longitudinal Study of Aging for a mean of 6.4 years after the baseline scan (n=126, age 56-86 years). Brain volume measurements were performed with semi-automated region-of-interest (ROI) algorithms, and brain volume trajectories were analyzed with mixed-effect regression models adjusted for demographic and cardiovascular factors. We found that individuals with hearing impairment (n=51) compared to those with normal hearing (n=75) had accelerated volume declines in whole brain and regional volumes in the right temporal lobe (superior, middle, and inferior temporal gyri, parahippocampus, p<.05). These results were robust to adjustment for multiple confounders and were consistent with voxel-based analyses, which also implicated right greater than left temporal regions. These findings demonstrate that peripheral hearing impairment is independently associated with accelerated brain atrophy in whole brain and regional volumes concentrated in the right temporal lobe. Further studies investigating the mechanistic basis of the observed associations are needed.

American Society of Hematology 2020 guidelines for sickle cell disease: prevention, diagnosis, and treatment of cerebrovascular disease in children and adults.

BACKGROUND: Central nervous system (CNS) complications are among the most common, devastating sequelae of sickle cell disease (SCD) occurring throughout the lifespan. OBJECTIVE: These evidence-based guidelines of the American Society of Hematology are intended to support the SCD community in decisions about prevention, diagnosis, and treatment of the most common neurological morbidities in SCD. METHODS: The Mayo Evidence-Based Practice Research Program supported the guideline development process, including updating or performing systematic evidence reviews. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, including GRADE evidence-to-decision frameworks, to assess evidence and make recommendations. RESULTS: The panel placed a higher value on maintaining cognitive function than on being alive with significantly less than baseline cognitive function. The panel developed 19 recommendations with evidence-based strategies to prevent, diagnose, and treat CNS complications of SCD in low-middle- and high-income settings. CONCLUSIONS: Three of 19 recommendations immediately impact clinical care. These recommendations include: use of transcranial Doppler ultrasound screening and hydroxyurea for primary stroke prevention in children with hemoglobin SS (HbSS) and hemoglobin Sß0 (HbSß0) thalassemia living in low-middle-income settings; surveillance for developmental delay, cognitive impairments, and neurodevelopmental disorders in children; and use of magnetic resonance imaging of the brain without sedation to detect silent cerebral infarcts at least once in early-school-age children and once in adults with HbSS or HbSß0 thalassemia. Individuals with SCD, their family members, and clinicians should become aware of and implement these recommendations to reduce the burden of CNS complications in children and adults with SCD.

Brain activation during encoding and recognition of verbal and figural information in older adults.

Positron emission tomography (PET) patterns of cerebral blood flow associated with verbal and figural memory are described in relation to their value as functional probes for studying longitudinal changes that occur in the aging brain. Relative to a matching control task, verbal and figural encoding increase blood flow in prefrontal cortex (PFC), anterior cingulate, insular, lateral and medial temporal, occipital cortex and the cerebellum. Additionally, medial temporal regions exhibited greater activity during figural encoding relative to verbal encoding. During recognition, blood flow increases in prefrontal, cingulate, insular, and lateral temporal and Broca's areas. Analysis of hemispheric asymmetry reveals that the prefrontal cortex exhibits regionally dependent results. Prefrontal region BA 10 demonstrates more bilateral activation during encoding and retrieval, whereas BA 46 shows right greater than left activation during both encoding and retrieval. Overall, the two tasks activate diverse regions within the frontal, temporal and occipital lobes of the brain, including areas that show age-related structural changes, proving their usefulness in the longitudinal assessment of brain function in the elderly.

Comparison of functional MR and H2 15O positron emission tomography in stimulation of the primary visual cortex.

PURPOSE: To locate spoiled gradient-echo functional MR signal changes in relation to brain parenchyma. METHODS: The region of the primary visual cortex was evaluated using functional MR and H2 15O positron emission tomography in each of six male subjects who were being visually stimulated by means of red light-emitting diode flash goggles. RESULTS: The positron emission tomography technique demonstrated substantially greater relative signal change with visual stimulation than did the functional MR technique. Furthermore, the functional MR signal changes were concentrated in loci around the periphery of brain parenchyma exhibiting increased radiotracer activity, as opposed to being collocated. CONCLUSIONS: Signal changes found using functional MR based on gradient-echo techniques reflect primarily phenomena occurring within small veins and underrepresent activity intrinsic to brain parenchyma, thus introducing potential inaccuracies in locating regions of activated brain tissue. Positron emission tomography, however, directly measures changes in metabolically related activity within the parenchyma.

The effect of age on odor-stimulated functional MR imaging.

BACKGROUND AND PURPOSE: The effects of age, sex, and handedness on olfaction have not been adequately addressed with odor-stimulated functional MR imaging studies. We sought to determine the effect of age on functional MR imaging experiments performed with odor stimulation. METHODS: Five right-handed subjects with a mean age of 73 years and five right-handed subjects with a mean age of 24 years underwent gradient-echo echo-planar functional MR imaging using binasal olfactory stimulation. Imaging parameters included 3000/30 (TR/TE) and a 5-mm section thickness in a 6-minute sequence with 30 seconds of pulsed odorants alternating with 30 seconds of room air. The data were normalized to a standard atlas, and individual and group statistical parametric maps (SPMs) were generated for each task. The SPMs were thresholded for a P < .01, and the volumes of activation and distribution of cluster maxima were compared for the two groups. RESULTS: Analysis of the group SPMs revealed activated voxels in the frontal lobes, perisylvian regions, and cingulate gyri, with greater volume in the younger group than in the older group. The right inferior frontal, right perisylvian, and right and left cingulum had the largest number of voxels activated. The most common sites of activation on individual maps in both groups were the right inferior frontal regions and the right and left superior frontal and perisylvian zones. CONCLUSION: Given similar olfactory task paradigms, younger subjects showed a greater number of activated voxels than did older subjects. One must be cognizant of this effect when designing studies of odor-stimulated functional MR imaging.

Safe extracapsular placement of proximal tibia transfixation pins.

OBJECTIVE: To identify the anatomic detail of the knee joint capsular insertion site on the proximal tibia, specifically as it relates to transfixation pins. DESIGN: Identification of capsular anatomy by anatomical dissection of cadaveric specimens, with radiography and arthroscopy of patients. SETTING: Cadaveric dissection. OUTCOME MEASURES: Anatomic observation of the capsular attachment site in relation to the tibial articular surface. RESULTS: The capsule inserts four to fourteen millimeters below the articular surface in a regular pattern. The anterior half of the circumference is close to the joint line (less than six millimeters). Posteromedially and posterolaterally, there are extensions distally to fourteen millimeters, occasionally communicating with the tibiofibular joint. CONCLUSION: Transfixing wires and half-pins can be placed in the proximal tibia without capsular penetration if kept more than fourteen millimeters from the subchondral line. If wire placement closer to the joint is required, wires should be placed in Zone 1 (the anterior half) and at least six millimeters from subchondral bone to avoid capsular penetration.

Longitudinal cognitive decline is associated with fibrillar amyloid-beta measured by [11C]PiB.

OBJECTIVE: To investigate whether longitudinal declines in cognition are associated with higher fibrillar amyloid-beta (Abeta) deposition in vivo in individuals without dementia. METHOD: [(11)C]PiB images were obtained to measure fibrillar Abeta burden in 57 participants without dementia from the Baltimore Longitudinal Study of Aging. Participants (33 men, 24 women) had a mean (SD) age of 78.7 (6.2) years. Six participants (4 men, 2 women) had mild cognitive impairment defined as Clinical Dementia Rating = 0.5. To measure [(11)C]PiB retention, distribution volume ratios (DVR) for 15 regions of interest were estimated by fitting a simplified reference tissue model to the measured time activity curves. Mixed effects regression was used to predict cognitive trajectories over time using data before and including time of PiB (mean follow-up 10.8 years), with mean cortical DVR, age at baseline, sex, and education as independent predictors. Voxel-based analysis identified local associations. RESULTS: [(11)C]PiB retention was higher in older individuals. Greater declines over time in mental status and verbal learning and memory, but not visual memory, were associated significantly with higher PiB retention. Voxel-based analysis showed significant associations in frontal and lateral temporal regions. CONCLUSIONS: Higher Abeta deposition is associated with greater longitudinal decline in mental status and verbal memory in the preceding years. The differential association for verbal but not visual memory may reflect the greater reliance of verbal word list learning on prefrontal regions, which show early Abeta deposition. Prospective imaging may help distinguish between individuals with evolving neuropathology who develop accelerated cognitive decline vs those with normal aging.

Stability Of Default-Mode Network Activity In The Aging Brain.

Activity attributed to the default-mode occurs during the resting state and is thought to represent self-referential and other intrinsic processes. Although activity in default-associated regions changes across the lifespan, little is known about the stability of default-mode activity in the healthy aging brain. We investigated changes in rest-specific activity across an 8 year period in older participants in the Baltimore Longitudinal Study of Aging (BLSA) neuroimaging study. Comparison of resting-state and recognition memory PET regional cerebral blood flow conditions from baseline and 8-year follow-up shows relative stability of rest-specific activity over time in medial frontal/anterior cingulate, hippocampal and posterior cingulate regions commonly associated with the default-mode. In contrast, prefrontal, parahippocampal and occipital cortical regions, which are not typically associated with default-mode activity, show changes over time Overall, activity in the major components of the default-mode network remains stable in healthy older individuals, a finding which may assist in identifying factors that discriminate between normal and pathological aging.

II. Temporal patterns of longitudinal change in aging brain function.

Time-dependent changes in brain activity were assessed in a group of older adults who maintained good physical and cognitive health at years 1, 3, 5, 7, and 9 of the Baltimore Longitudinal Study of Aging neuroimaging study. Each year, these participants underwent PET scans during rest and delayed verbal and figural recognition memory conditions. While memory performance remained stable over the 8 years, both generalized and modality-specific patterns of time-dependent changes in regional cerebral blood flow (rCBF) were found. Many brain regions showed steady, progressive changes in rCBF over the 8 years while others maintained rCBF for a number of years before showing incremental declines or increases in activity. These temporal patterns of change were observed in many regions of the brain, particularly in the frontal and temporal lobes, suggesting that there are distinctive patterns of age-related functional decline and compensatory activity over time. The precise patterns of regional involvement and the temporal dynamics of rCBF change within specific regions vary based on cognitive processing demands.

I. Longitudinal changes in aging brain function.

Changes in brain activity over time were evaluated in a group of older adults in the Baltimore Longitudinal Study of Aging who maintained good physical and cognitive health. Participants underwent PET scans during rest and delayed verbal and figural recognition memory performance at year 1 baseline and at year 9. While memory performance remained stable over the 8 years, longitudinal changes in regional cerebral blood flow were observed within each scan condition. Further analyses revealed distinctive patterns of change related specifically to verbal or figural recognition, as well as longitudinal changes common to all scan conditions. These findings demonstrate that the older brain undergoes functional reorganization with increasing age in healthy, cognitively stable individuals. In view of the stable memory performance, the task-dependent results suggest that age-related changes in brain activity help maintain cognitive function with advancing age.

Major salivary gland imaging.

The algorithm for imaging the salivary glands depends on the clinical scenario with which the patient presents to the clinician. Because of the importance of identifying small calculi in the gland or salivary duct as the cause of the symptom complex, nonenhanced computed tomography is often the best initial study for the evaluation of the painful gland. If an infiltrative neoplasm is highly suspected, nonenhanced and enhanced magnetic resonance (MR) imaging may be superior in demonstrating perineural, meningeal, and skull base invasion. Sialography is reserved for the evaluation of chronic sialadenitides unrelated to sialolithiasis. Thin-section MR techniques for MR sialography may soon replace conventional sialography.

Inhibitory processes in the flash evoked potential of the monkey.

Flash visual evoked potentials (VEP) and concurrent multiple unit activity (MUA) were recorded from closely spaced intracortical sites in unanesthetized monkeys before and after intracortical injection of the GABAA antagonist bicuculline. Laminar VEP profiles were subjected to current source density (CSD) analysis to localize the transmembrane current flows contributing to the generation of the field potentials. Before bicuculline, the first large VEP component, N40, was generated principally within the parvocellular thalamorecipient sublamina 4Cb. After bicuculline injection, the current sinks associated with N40 spread throughout lamina 4, consistent with a release of intracortical inhibition mediated by GABA. A subsequent component, P65, believed to represent recurrent inhibitory activity within 4Cb, was greatly diminished in size after bicuculline injection. The laminar pattern of current sources and sinks coincident with this component was more complicated after bicuculline, reflecting the summation of current flows associated with disinhibited lamina 4 activity. Bicuculline also altered the responses of neuronal elements in laminae 3 and 5, evidenced by large increases in MUA in these laminae that began approximately 50 msec after stimulation. Finally, bicuculline diminished the degree of intracortical ocular dominance, implicating GABAergic mechanisms in the maintenance and refinement of ocular input segregation within cortical columns.

Intracortical generators of the flash VEP in monkeys.

Flash visual evoked potentials (VEPs) in unanesthetized monkeys were recorded from the cortical surface and from closely spaced intracortical sites together with associated multiple unit activity (MUA). The VEP depth profiles were subjected to current source density (CSD) analysis to delineate the laminar pattern of transmembrane current flows manifested by extracellular source and sinks. The initial surface recorded components (P15 and P18) were generated subcortically within the thalamocortical radiations. The distribution of current sources and sinks associated with two subsequent surface negative components. N24 and N40. demonstrates their generation within laminae IVA and IVCb respectively, both parvocellular thalamorecipient layers. Oscillatory potentials resembling those seen in human VEPs are observed riding on N40; analysis of MUA in conjunction with sources and sinks coincident with these wavelets provides evidence that they derive from both thalamocortical and cortical activity. MUA in the 20-60 msec range shows phasic increases throughout lamina IV, which are maximum in amplitude within lamina IVA. This increased firing is concurrent with the sinks observed within the parvocellular thalamorecipient sublaminae IVCb and IVA. A subsequent component, P65, coincident with a decrease in MUA to below the spontaneous level co-located with a lamina IVCb current source, probably arises from intracortically generated inhibitory activity within IVCb. The next VEP component, a surface negative potential at 95 msec, is coincident with current sources and sinks in lamina III, and is consistent with stellate cell input to supragranular elements. VEP components after N95 are not associated with either MUA or CSD activity and are probably generated in extrastriate cortex. Human counterparts of the simian VEP are proposed.

Physiologic variations in dural venous sinus flow on phase-contrast MR imaging.

OBJECTIVE: Our study quantifies normal physiologic variations of dural sinus flow using phase-contrast MR imaging. SUBJECTS AND METHODS: Fifteen volunteers were imaged using nontriggered and triggered phase-contrast MR venography of the superior sagittal and transverse sinuses. Triggered scans were obtained during regular breathing; nontriggered scans were obtained during regular breathing, breath-holding, deep inspiratory breath-holding, and deep expiratory breath-holding. Analysis of variance, Bonferroni method, and Dunn post hoc analysis were used to determine any significant differences in the mean flow and velocity between the different breathing maneuvers. A paired t test was used to compare flow between sinuses during regular breathing. RESULTS: Deep inspiratory breath-holding and deep expiratory breath-holding resulted in a significant decrease in blood flow and velocity in all dural sinuses compared with regular breathing. During deep inspiratory breath-holding, blood flow decreased 30.8% in the superior sagittal sinus, 19.7% in the left transverse sinus, and 19.1% in the right transverse sinus. Similarly, during deep expiratory breath-holding, blood flow decreased 30.2% in the superior sagittal sinus, 20.8% in the left transverse sinus, and 20.3% in the right transverse sinus. The sum of the flow in the transverse sinuses was significantly greater than in the sagittal sinus. Normal pulsatility of dural sinus blood velocity was also characterized for all measured sinuses. CONCLUSION: Characterization of variations in dural sinus velocity and flow as a function of the cardiac cycle and breathing maneuvers, using phase-contrast MR imaging, may help separate physiologic from pathologic changes of flow resulting from conditions that influence the cerebrovascular circulation.

Neural substrates of orthographic lexical access as demonstrated by functional brain imaging.

OBJECTIVE: To delineate regions involved in visual word recognition. BACKGROUND: The processes and regions involved in visual word recognition have been somewhat controversial for over 100 years. METHODS: This study used regional cerebral blood flow as assessed by functional magnetic resonance imaging to study normal subjects (N = 9) on an individual within-subject basis while they were actively engaged on-line in a visual lexical decision task. Standard analysis techniques were used for identifying regions of activation. RESULTS: Across subjects, the task activated a number of regions, including the occipital pole, lateral and basal occipitotemporal (including lingual and fusiform) regions, superior and middle temporal gyri, and supramarginal and angular gyri. Typically, these regions were activated bilaterally; when activation was unilateral, it was on the left. Some of the areas activated (e.g., inferior parietal regions) have not been previously reported to be involved in such types of processing by activation studies but have been implicated in lesion studies. CONCLUSIONS: These results broaden the areas known to be involved in visual word recognition. The bilateral activation associated with visual word recognition is in some respects analogous to the "what" system in visual recognition described in subhuman primates. In addition, the study raises several methodologic issues. The within-subject analysis showed variability in the specific regions activated when subsequently comparing across individuals, raising implications for future functional imaging studies.

Effects of estrogen replacement therapy on PET cerebral blood flow and neuropsychological performance.

Reports that estrogen may protect against age-associated memory decline and Alzheimer's Disease have kindled interest in the effects of estrogen replacement therapy (ERT) on cognition and brain function. As part of a 9-year study in the Baltimore Longitudinal Study of Aging, we are performing annual magnetic resonance imaging, positron emission tomography (PET), and neuropsychological assessments to examine brain structure and function in individuals aged 55 and older. PET measurements of regional cerebral blood flow (rCBF) are obtained under 3 conditions: rest and verbal and figural delayed recognition memory tasks. Fifteen women receiving ERT (with or without the addition of progesterone) were compared with a matched sample of 17 untreated women. There were no significant differences between groups in regional brain volumes or ventricular size. However, ERT users and nonusers showed significant differences in PET-rCBF relative activation patterns during the memory tasks. During verbal memory processing, there were significant interactions in rCBF activations for the right parahippocampal gyrus, right precuneus, right frontal regions, and left hypothalamus. During figural memory processing, significant interactions were observed for right parahippocampal and inferior parietal regions and for left visual association and anterior thalamic regions. ERT users also showed better performance on neuropsychological tests of figural and verbal memory and on some aspects of the PET activation tests, although the two groups did not differ in education, overall verbal ability, or performance on other neuropsychological tests. These findings confirm our previous observation of the beneficial effects of ERT on figural memory. Moreover, differences in rCBF activation patterns between ERT users and nonusers suggest an area for future research to examine mechanisms through which ERT may influence memory and other cognitive abilities.

Cigarette smoking and other risk factors for silent cerebral infarction in the general population.

BACKGROUND AND PURPOSE: Silent cerebral infarctions (SCIs) have a prevalence between 10% and 40% in the transient ischemic attack population and have been associated with increased mortality and morbidity; however, little is known about the prevalence and risk factors for SCI in the general population. This report focuses on the role of cigarette smoking and other risk factors for SCI in the general population. METHODS: MRI scans were performed on 1737 participants selected from the general population as part of the Atherosclerosis Risk in Communities Study. Smoking status and other major cerebrovascular risk factors were assessed, and associations between smoking status and SCIs were established with the use of ANCOVA. RESULTS: Overall, the prevalence of SCI in this population aged 55 to 70 years was 11%. Cigarette smoking had an ordered association (P=0.029) with the presence of SCI, with the odds ratio (OR) of nonsmoking participants exposed to environmental tobacco smoke being 1.06 (95% confidence interval [CI], 0.64 to 1.75) times as great as for nonsmokers not exposed; the OR of past smokers was 1.16 (95% CI, 0.74 to 1.83) times greater, and the OR of current smokers was 1.88 (95% CI, 1.13 to 3.13) times greater. An increased prevalence was also noted among black, older, and hypertensive participants. CONCLUSIONS: This report is among the first to examine the risk factors for SCI in the general population and finds a relatively high overall prevalence (11%). There is an ordered relationship between increasing exposure to cigarette smoke and the presence of SCI that parallels the relationship between smoking and carotid atherosclerosis. The magnitude of the association with smoking is substantial compared with the effect of hypertension and other traditional cerebrovascular risk factors. The reduction in prevalence of SCI between current and past smokers and the trend that increased pack-years of smoking is related to increased prevalence of SCI are both additional arguments for smoking avoidance and cessation.

One-year age changes in MRI brain volumes in older adults.

Longitudinal studies indicate that declines in cognition and memory accelerate after age 70 years. The neuroanatomic and neurophysiologic underpinnings of cognitive change are unclear, as there is little information on longitudinal brain changes. We are conducting a longitudinal neuroimaging study of nondemented older participants in the Baltimore Longitudinal Study of Aging. This report focuses on age and sex differences in brain structure measured by magnetic resonance imaging during the first two annual evaluations. Cross-sectional results from 116 participants aged 59-85 years reveal significantly larger ventricular volumes and smaller gray and white matter volumes in older compared with younger participants and in men compared with women. Regional brain volumes show that the effects of age and sex are not uniform across brain regions. Age differences are greatest for the parietal region. Sex differences tend to be larger for frontal and temporal than parietal and occipital regions. Longitudinal analysis demonstrates an increase of 1526 mm(3) in ventricular volume over 1 year, but no detectable change in total or regional brain volumes. Definition of the pattern and rate of longitudinal brain changes will facilitate the detection of pathological brain changes, which may be predictors of dementia.

Stroke risk in an elderly population with atrial fibrillation.

Patients with nonvalvular atrial fibrillation (AF) have an increased risk of stroke, but the absolute rate of stroke varies widely depending on coexistent vascular disease. We assessed the stroke rate and predictive value of two published schemes for stroke risk stratification in a population-derived cohort of 259 elderly people with nonvalvular AF followed for a median of 5.3 years. The rate of ischemic stroke was 2.8% per year (95% confidence interval [CI] 1.9, 3.9). Thirty-one percent were predicted to be at low risk, and their stroke rate was 1.7% per year (95% CI 0.6, 3.8). Many people with AF in this population-derived cohort had relatively low rates of stroke. Further studies to reliably stratify stroke risk in patients with AF are needed.