Dementia, quantitative neuroimaging, and apolipoprotein E genotype.

BACKGROUND AND PURPOSE: Quantitative MR imaging differences in an elderly population of subjects with various clinical disorders (including dementia, particularly Alzheimer's disease and vascular dementia) and disorders of mild cognitive impairment were examined. Potential quantitative MR differences were assessed by presence or absence of the apolipoprotein E (APOE) epsilon4 allele and by level of cognitive deficit. METHODS: One hundred eighty subjects with a diagnosis of dementia or other clinical disorders were identified from an eligible population of 5,677 elderly individuals. Age, duration of disease, and head size (where appropriate) were considered as covariates. APOE genotype was determined by polymerase chain reaction using buccal material. Axial and coronal intermediate- and T2-weighted MR images were quantified using a multispectral segmentation algorithm. Cognitive status was assessed by means of a modified Mini-Mental Status Examination. RESULTS: All types of dementing illness showed significant volume reductions in the majority of structures examined, particularly in the total brain, hippocampus, and white and gray matter, and increased CSF and ventricular volumes. Subjects with mild cognitive impairment showed fewer atrophic changes but were still distinguishable from the 24 control subjects. Presence of an epsilon4 allele was associated with smaller hippocampal volume in subjects with Alzheimer's disease and vascular dementia within just 1 year of disease onset. For other analyses, atrophy related to the presence of the epsilon4 allele disappeared after controlling for age and length of disease. CONCLUSION: The effects of the epsilon4 allele on brain morphology may be subtly expressed early in the development of dementia, but do not specifically affect cerebral atrophy thereafter. Cognitive impairment is associated with atrophy irrespective of diagnosis and presence of epsilon4.

Polysubstance abuse and traumatic brain injury: quantitative magnetic resonance imaging and neuropsychological outcome in older adolescents and young adults.

Few studies have examined the consequences of alcohol and drug abuse on TBI though they commonly co-occur. Both TBI and substance abuse independently result in neuropathological changes in the brain such as ventricular enlargement and cortical atrophy, thus it is reasonable to hypothesize that the combination of the two would result in more significant cerebral damage. In this study, 3 groups of patients--traumatically brain injured (TBI) with substance abuse (N = 19), TBI without substance abuse (N = 19), and substance abuse with no TBI (N = 16)--were compared with normal controls (N = 20) on several quantitative MRI (QMRI) measures. Since TBI most frequently occurs in older adolescents and young men, we examined only male participants between 16 and 30 years of age. Comparing young substance abusers to controls resulted in no QMRI differences. When controlling for head injury severity, the effects of substance abuse in combination with TBI resulted in greater atrophic changes than seen in any other group. TBI and substance abuse patients' neuropsychological test performances also were examined, and no differences were found among patient groups on any measures. These findings have implications for the deleterious interaction of substance abuse combining with TBI to result in greater neuropathological changes that can be detected by QMRI techniques.

Corpus striatum and traumatic brain injury.

The possibility of a 'subcortical' syndrome differentially affecting memory in traumatic brain injury (TBI) subjects was examined. Magnetic resonance imaging scans of 46 traumatic brain injured male patients were compared with those of 34 male control subjects. Surface area measurements of the corpus striatum were calculated for both groups. Results demonstrated no significant differences in corpus striatum surface area measurements. Additionally, TBI patients were grouped according to severity of injury, as well as degree of corpus striatum atrophy, and neuropsychological outcome was examined. There were modest (r = 0.35) but significant correlations between corpus striatum degeneration and the delayed recall trial and total score of the Rey Auditory Verbal Learning Test, but no other correlations between neuropsychological and corpus striatal surface area were significant. Because subcortical pathology may have a differential effect on memory, recognition and recall memory were further analysed, but no significant differences were found. TBI subjects with the smallest corpus striatum values did not test significantly different from TBI patients with normal corpus striatum values or differences in cortical atrophy, as determined by a ventricle-to-brain ratio. These findings suggest that there is not a unique pattern of subcortical pathology involving the corpus striatum in TBI.

Apolipoprotein E epsilon 4 allele and hippocampal volume in twins with normal cognition.

We examined the relation of APOE-epsilon 4, hippocampal volume, and cognitive performance in ten pairs of cognitively normal twins who had a mean age of 62.5 years (SD = 7.8). There were no significant differences in neuropsychological measures of the groups categorized by the presence of an epsilon 4 allele. However, the mean normalized right and left hippocampal volumes were smaller in the epsilon 4 groups compared to the group without epsilon 4. Combined with prior reports, these findings suggest that epsilon 4 is associated with differences in brain morphology that may be evident when no symptoms of dementia are present.

MR-based brain and cerebrospinal fluid measurement after traumatic brain injury: correlation with neuropsychological outcome.

PURPOSE: To determine the magnitude and time course of changes in the volume of brain and intracranial cerebrospinal fluid (CSF) spaces in patients who have sustained traumatic brain injury and to assess the relationship between these findings and long-term cognitive traumatic outcome. METHODS: Axial intermediate and T2-weighted MR images of 123 patients with traumatic brain injury were quantified using a multispectral segmentation algorithm. Measurements were corrected for differences in age, sex, and head size using a previously reported normative database. Brain morphology was compared across groups formed on the basis of chronicity of injury. Cognitive functioning and severity of injury were statistically correlated with brain measurements. RESULTS: Time-dependent expansion of CSF spaces and decreases in brain volume were observed. Increases in ventricular CSF volume, particularly in the temporal horns and third ventricle, preceded subsequent changes in total brain and subarachnoid CSF. High and moderate correlation was observed between volume measures and cognitive outcome and injury severity. Particularly strong was the relation between the volume of the left temporal horn and verbal IQ scores. CONCLUSION: Predictable time-dependent atrophic changes occurring after traumatic brain injury can be quantified using MR volumetric studies. Our results suggest significant contributions by both diffuse and focal mechanisms of injury. In the postacute period (more than 70 days after injury), MR volumetric studies may be predictive of eventual cognitive outcome.

Hippocampal volume in normal aging and traumatic brain injury.

PURPOSE: To present a normative database of hippocampal and temporal horn volume and to clarify the relationship between these measures and cognitive outcome in patients with traumatic brain injury. METHODS: Ninety-six healthy volunteers and 94 patients with traumatic brain injury were examined with coronal intermediate and T2-weighted MR imaging. Multispectral segmentation and volume analyses were performed. The volumetry of the hippocampus and temporal horn was characterized in the control subjects. Volumetric measures in a group of patients with traumatic brain injury who had received MR imaging 3 months or less after injury were compared with measurements in other patients in the chronic phase of recovery. The relationship between neuropsychological testing and volumetric measures was analyzed with particular emphasis on the correlation between cognitive outcome and hippocampal and temporal horn volumes. RESULTS: No significant age group differences were found in the normative group from age 16 to 65. Left and right hippocampal volumes were interrelated and did not differ from each other. This was also true for the temporal horns. Hippocampal and temporal horn volumes were not significantly related. Women had larger hippocampi relative to cranial volume. Comparisons between patients with traumatic brain injury and control subjects showed significant yet modest bilateral atrophic changes in hippocampal and temporal horn enlargement in the patients with brain injury. Hippocampal and temporal horn volumes correlated significantly with each other in the group with traumatic brain injury. Cognitive outcome was modestly related to hippocampal and temporal horn volumes. However, in a specific subgroup whose images were acquired between 71 and 210 days after injury, strong correlations were noted in which temporal horn volume correlated highly with IQ and hippocampal volume correlated with verbal memory function. CONCLUSION: Hippocampal and temporal horn volumes appear to be independent variables in healthy control subjects. Traumatic brain injury results in significant hippocampal atrophy and temporal horn enlargement. The hippocampus and temporal horn volumes were inversely correlated in the group with traumatic brain injury, suggesting a differential relationship of these structures in patients with brain injury as compared with control subjects. In the subacute phase, the volume of the temporal horn may be indicative of intellectual outcome and that of the hippocampus appears to be indicative of verbal memory function.

Traumatic brain injury, alcohol and quantitative neuroimaging: preliminary findings.

Magnetic resonance (MR) quantitative neuroimaging analysis was undertaken with a large group of normal (n = 197) and traumatically brain injured (TBI, n = 99) adults. Of the TBI subjects 18 patients were identified with a history of substance-related abuse (TBI/Abuse group). Both the TBI/ Abuse group and the remaining sample of TBI patients (n = 81, TBI/Non-abuse group) without a history of substance-related abuse differed significantly from the control group on most quantitative MR imaging analyses. The TBI/Abuse group displayed the greatest degree of atrophic change. However, the TBI/Abuse group had a significantly lower Glasgow Coma Scale (GCS) score, ostensibly suggesting that those with substance-related abuse suffered more severe brain injury than non-abuse TBI patients. When a subset (n = 18) of the TBI/Non-abuse group was matched by GCS, gender and age to the TBI/Abuse group, both groups differed significantly from the control group on most morphometric measures, but did not differ from one another. Results are discussed in terms of the potential adverse role that substance-related abuse, particularly alcohol, plays in the individual who sustains traumatic injury to the brain.

Lesion volume, injury severity, and thalamic integrity following head injury.

Magnetic resonance (MR) scans of 63 traumatic brain injury (TBI) patients were analyzed to examine the relationship between injury severity, lesion volume (nonthalamic cortical/subcortical lesions), ventricle-to-brain ratio (VBR), and thalamic volume. For comparison, 33 normal control subjects were used. Patients with visible nonthalamic structural lesions showed significantly smaller thalamic volumes than patients without visible lesions or control subjects. Results also indicated that patients with visible lesions had significantly more severe injuries than patients without lesions. Patients with moderate-severe injuries had significantly smaller thalamic volumes and greater VBRs than patients with mild-moderate injuries. Although several variables related to thalamic volume, the presence of nonthalamic lesions was sufficient to result in smaller thalamic volume. Decreased thalamic volume following head injury suggests that subcortical brain structures may be susceptible to transneuronal degeneration following cortical lesions, and that this can be detected by in vivo MR-based volumetric analysis.

Lesion volume, injury severity, and thalamic integrity following head injury.

Magnetic resonance scans of 63 TBI patients were analyzed to examine the relationship between injury severity, lesion volume (nonthalamic cortical/subcortical lesions), ventricle-to-brain ratio (VBR), and thalamic volume. For comparison, 33 normal control subjects were used. Patients with visible nonthalamic structural lesions showed significantly smaller thalamic volumes than patients without visible lesions or control subjects. Results also indicated that patients with visible lesions had significantly more severe injuries than patients without lesions. Patients with moderate-severe injuries had significantly smaller thalamic volumes and greater VBRs than patients with mild-moderate injuries. Although several variables related to thalamic volume, the presence of nonthalamic lesions was sufficient to result in smaller thalamic volume. Decreased thalamic volume following head injury suggests that subcortical brain structures may be susceptible to transneuronal degeneration following cortical lesions, and that this can be detected by in vivo MR-based volumetric analysis.

Frontal lobe lesions, diffuse damage, and neuropsychological functioning in traumatic brain-injured patients.

This study quantified lesion volume in relation to damage location and executive functioning in traumatic brain-injured (TBI) patients. Magnetic resonance (MR) scans of 68 TBI patients were analyzed by taking volumetric measures of lesion sites. Patients were grouped according to the presence/absence of frontal lobe lesions. Measures of frontal lesion volume were studied as predictors for outcome on designated tests of executive functioning (Halstead Category Test and Wisconsin Card Sorting Test). Results showed no significant differences in level of deficit between groups. In addition, no significant differences were found between groups on other tests of neuropsychological functioning (Trail Making Test, Parts A and B, and Wechsler Adult Intelligence Scale-Revised). These results suggest that tests that are traditionally used to detect "frontal lobe" damage may not be adequate for distinguishing specific frontal lobe dysfunction, and do not add anything unique about frontal lobe integrity and neuropsychological functioning in TBI patients.

Severe anoxia with and without concomitant brain atrophy and neuropsychological impairments.

Significant anoxia may cause a variety of neuropathologic changes as well as cognitive deficits. We have recently seen 3 patients who have suffered severe anoxic episodes all with initial Glasgow Coma Scores (GCS) of 3 with sustained coma for 10-14 d. All 3 patients had extended hospitalizations and rehabilitation therapy. A neuropsychological test battery was administered and volumetric analyses of MRI scans were carried out in each case at least 6 mo postinjury. Two of the patients display distinct residual cognitive and neuropathologic changes while 1 patient made a remarkable recovery without evidence of significant morphological abnormality. These three cases demonstrate, that even with similar admission GCS, the outcome is variable and the degree of neuropsychological impairment appears to match the degree of morphologic abnormalities demonstrated by quantitative MR image analysis. An important finding of this study is that even though subjects with an anoxic insult exhibit severe cognitive and memory impairments along with concomitant morphologic changes, their attention/concentration abilities appear to be preserved. MR morphometry provides an excellent means by which neural structural changes can be quantified and compared to neuropsychological and behavioral outcomes.

Quantitative volumetric analysis of brain MR: normative database spanning 5 decades of life.

PURPOSE: To present a normative volumetric database, spanning 5 decades of life, of cerebrospinal fluid, subarachnoid cerebrospinal fluid, total brain volume, total ventricular volume (component ventricular volumes of lateral, temporal horn, and third and fourth ventricles) and estimates of white and gray matter, based on a multispectral segmentation of brain MR. This database is presented as a reference for future studies comparing pathologic states. METHOD: One hundred ninety-four healthy subjects, ranging in age from 16 to 65 years, received standard axial intermediate- and T2-weighted spin-echo MR images. Multispectral segmentation and volume analysis were performed using ANALYZE. RESULTS: Normative volumetric estimates, both uncorrected and corrected for differences in total intracranial volume, were obtained for all subjects and presented by decade and sex. Age-related cerebrospinal fluid changes were evident for both male and female subjects. Most gender differences were eliminated by correction for differences in total intracranial volume. Standard and fast spin-echo acquisition methods gave comparable volume estimates. Total brain volume measurements from MR compare favorably with data from large autopsy series. CONCLUSION: Although there may be limitations to generalizations, these normative data tables can provide a comparison index for contrasting pathologic groups with a normative sample.

Age-related hearing loss and bone mass in a population of rural women aged 60 to 85 years.

Demineralization of the cochlear capsule in conjunction with age-related bone mass loss may be one biologic factor contributing to hearing loss in the elderly. In other metabolic bone diseases, including Paget's disease of the bone and cochlear otosclerosis, demineralization of the cochlea has been associated with sensorineural hearing loss. In 1988/1989, the relation between hearing loss and bone mass of the radius and femoral neck was studied cross-sectionally in 369 women aged 60 to 85 years from three rural communities. Hearing sensitivity was measured using audiometry, and bone mineral density of the radius and femoral neck was measured using single- and dual-photon densitometry, respectively. Three variables, ascertained by interview, were associated with an increased odds for hearing loss: age, family history of hearing loss before the age of 50 years, and current use of more than two nonestrogen, nonthiazide prescription medications. After consideration of the effect of these three variables, women with femoral neck bone mass values below the mean value of 0.696 g/cm2 for this population had a 1.9 greater odds of having a hearing loss (confidence interval: 1.30, 2.50). This study demonstrated a consistent adjusted association between femoral neck bone mass and age-related hearing loss in a population of rural women aged 60 to 85 years. No consistent association was observed between radial bone mass and hearing loss.

Ventricular dilation, cortical atrophy, and neuropsychological outcome following traumatic brain injury.

Day-of-injury computed tomographic scans were compared with postinjury magnetic resonance imaging of 38 patients with traumatic brain injury. Ventricles and several white and gray matter structures were measured. Results demonstrated significant changes in ventricular sizes and all measures of white matter. Changes in gray matter were nonsignificant, except in the putamen/globus pallidus. Patients were grouped according to ventricular change, and neuropsychological outcome was examined. The group with the highest ventricular change had significantly lower memory scores but did not show significant differences on tests of intellectual functioning. A three-dimensional image analysis was performed to enhance visualization of the injured brain.

The role of caudate nucleus and corpus callosum atrophy in trauma-induced anterior horn dilation.

Day-of-injury computerized tomography (CT) scans were compared to post-injury (at least 6 weeks) magnetic resonance (MR) imaging of 30 traumatic brain-injured (TBI) patients. Scans were matched as closely as possible at the head of the caudate nucleus (CN), a grey matter structure, and the anterior horns (AH) of the lateral ventricle. The CN and AH surface areas and width of the corpus callosum (CC), a white-matter structure, were measured. Results demonstrated a non-significant change in CN surface area, while AH showed a significant increase. CC showed a significant decrease in width. Lack of significant change in the CN, combined with a significant decrease in CC width, suggests that AH dilation is probably due to surrounding white as opposed to grey-matter atrophy.

Longitudinal study of hearing aid effectiveness. I: Objective measures.

This report is the first of two detailing a longitudinal follow-up of hearing aid users. Sixty-five subjects were followed for 12 months post-hearing aid fitting. Objective tests included insertion gain, the Speech Perception in Noise (SPIN) test (Kalikow, Stevens & Elliot, 1977; Bilger, Neutzel, Rabinowitz, & Rzeczkowski, 1984) and the Nonsense Syllable Test (NST) (Levitt & Resnick, 1978) presented in quiet and noise backgrounds. Initially each subject's hearing aid was fit to the revised National Acoustic Laboratories prescriptive formula (NAL-R) (Byrne & Dillon, 1986) using insertion gain measures. Use gain, measured at 6 and 12 months post-fitting, indicated that subjects generally used those prescribed values, except for subjects in the steeply sloping configuration subgroup. The NST and SPIN tests were administered at the fitting and at 1, 3, 6, and 12 months post-fitting. No change in performance, or training effect, was found for the group or for factors of experience, degree of hearing loss, configuration of hearing loss, use time, or circuit type. Failure to demonstrate a training effect may be attributed, in part, to the fact that initial speech recognition testing was done with the hearing aid volume set at the prescribed values. None of the circuits used showed performance superiority, except when comparing scores for the NST obtained in a quiet background to those obtained in a background of speech-weighted noise. In that comparison, the users of adaptive filter circuits exhibited less deterioration of performance in a noise background.

Longitudinal study of hearing aid effectiveness. II: Subjective measures.

This report is the second of two detailing a longitudinal follow-up of hearing aid users. The experimental group (N = 65) was followed closely for a 12-month period after obtaining amplification. Factors of degree of hearing loss, configuration of hearing loss, previous experience with hearing aids, daily use time, and circuit type were defined. Subjective tests included the "Understanding Speech" subsection of the Hearing Performance Inventory (HPI) (Giolas, Owens, Lamb, & Schubert, 1979; Lamb, Owens, & Schubert, 1983), an expectations checklist, a qualitative judgment task, and a satisfaction questionnaire that included items of use time, battery life, and main reason for satisfaction rating. Only those items of the HPI describing fairly quiet backgrounds showed significant change (improvement) over the year. The expectation checklist showed a mean reduction in score indicative of performance exceeding expectations. The qualitative judgment task did not significantly differentiate among the circuits used, although the linear circuit was judged as having better sound quality than those circuits considered to be noise-reduction. Correlations with the objective tests reported previously in Part I suggest a weak relationship between speech recognition performance and self-assessment of communication performance. Questions of the validity of subjective measures, the best time frame for obtaining outcome measures, and the usefulness of group data are addressed.

Differentiation of types of presbycusis using the masking-level difference.

Masking-level differences in quiet at 500 Hz were used to demonstrate evidence of elevated noise levels within the auditory systems of subjects with assumed neural presbycusis. The following five groups of subjects were evaluated: normal-hearing young and old adults; and older adults with metabolic, sensory, or neural presbycusis. The group with assumed neural presbycusis--that is, bilateral high-frequency sensorineural hearing loss and poor word-recognition performance--had masking-level differences (a) in quiet that were significantly larger than those for the other groups and (b) in noise that were significantly smaller than those for the other groups. The data suggest that elevated internal noise levels accompany neural presbycusis.