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Clinicopathologic correlates in Alzheimer disease: assessment of clinical and pathologic diagnostic criteria.

The neuropathologic findings from a group of 123 patients who have come to autopsy from the Rochester Alzheimer Disease Project (RADP) are presented. Among these 123 cases, there were 94 demented subjects who met the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer Disease and Related Disorders Association (NINCDS-ADRDA) clinical criteria for the diagnosis of "probable Alzheimer disease," and 29 normal elderly controls. Autopsy confirmation of Alzheimer disease (AD) was based on the age-graded National Institutes of Health (NIH) consensus conference pathologic criteria. Using the NINCDS-ADRDA clinical criteria and the NIH pathologic criteria, the diagnostic accuracy was 88%, the sensitivity was 98%, and the specificity was 69%. Additional strict clinical and pathologic criteria developed by the RADP were applied in the final review of these cases to exclude all confounding causes of dementia, including cerebral infarcts. After applying these additional criteria, a subset of 62 cases of "pure" AD and "pure" control subjects was identified for a more detailed examination of neuritic plaques (NP) and neurons containing neurofibrillary tangles (NFT). The NP and NFT were counted in three subfields of hippocampus and two areas of association neocortex. The density of diffuse plaques (plaques lacking dystrophic neurites) was estimated on a semiquantitative basis. Results show that the AD patients and control groups could be distinguished from each other easily on the basis of mean NP and NFT counts, but there was sufficient overlap in the counts to present difficulty in diagnosing any individual case. Abundant diffuse plaque involvement and NFT in the neocortex were, however, seen only in AD cases.

Aged↗

Sexual behavioral changes in Alzheimer disease.

The frequency and correlates of sexual behavioral changes in Alzheimer disease (AD) were assessed in two studies. In the first study, we reviewed the medical records of 135 consecutive community-living patients who fit the criteria of the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer Disease and Related Disorders Association for probable or possible AD, and we asked spouses to complete a questionnaire that included two questions about sexual activity. Indifference to sexual activity was reported by 70% of the spouses, and sexual behavioral modifications were reported by 50%. No correlation was found between sexual changes and the general characteristics of the patients, the severity of the disease, or depressive symptomatology. Sexual changes were correlated to the severity of behavioral and mood disorders, mainly to a reduction of activity and emotional deficit. Seventy-seven of the patients had a second examination after an interval of 18.9 +/- 9.9 months. The links between sexual changes and the other variables were similar to those found by the first examination. In the second study, a questionnaire was sent by mail to the spouses of 100 patients. No relationship was found between sexual changes and the severity of cognitive deficits, previous sexual agreement, age, or gender. Sexual changes were considered a factor of maladjustment for the couple by 46% of the spouses.

Aged↗

Donepezil versus vitamin E in Alzheimer's disease: Part 2: mild versus moderate-severe Alzheimer's disease.

SUMMARY: Early studies showed that the latency of P300 (P3) event related potential increases or diminishes when anticholinergic or cholinergic drugs are administered. We tested the hypothesis that new cholinesterase inhibitors like Donepezil (DPZ) may have an effect on the often abnormal P300 of patients with Alzheimer's Disease (AD), and therefore, that P300 recordings might simplify the evaluation of responses to cholinesterase inhibitor in patients with mild and moderate-severe AD. We evaluated 60 patients with AD: 30 patients with "mild" (Mini Mental State Examination 26-19) and 30 patients with "moderate-severe" (Mini Mental State Examination 18-10), according to the National Institute of Neurological and Communicative Disorders and Alzheimer's Disease and Related Disorders Association criteria in comparison with 40 age-matched controls. All subjects underwent P300 recordings and neuropsychologic examinations (Alzheimer's Disease Assessment Scale-Cognition and Wechsler Adult Intelligence Scale) during the 6-month follow-up. Patients were divided into four groups of 15 patients each: Group I DPZ (10 mg/day) and Group I Vitamin E (2000 IU/day) with "mild" AD; Group II DPZ and Group II Vitamin E with "moderate-severe" AD and same drug dosages. In patients treated with Vitamin E, we observed P3 latency increments (delta) by 11.8 +/- 1.8 ms in Group I and by 12.8 +/- 2.8 ms in Group II at 6 months; neuropsychologic test scores significantly worsened at 6 months (p < 0.001) in Group II patients. Donepezil induced significant P3 latency reductions (11.2 +/- 2.4 ms) in nine patients of Group I and all patients of Group II (16.1 +/- 4.0 ms), reaching a maximum at 3 months (23.2 +/- 2.7 ms). Alzheimer's Disease Assessment Scale-Cognition and Wechsler Adult Intelligence Scale scores improved during the same period, and the difference between Vitamin E and DPZ treated patients was highly significant for P3 (analysis of variance) and for P3-Alzheimer's Diseases Assessment Scale-Cognition (analysis of covariance) with p < 0.001 for pooled groups of patients with AD and Group II (DPZ) versus Group II (Vitamin E). Combined P3 event related potentials measurements, neuropsychologic test comparison evidences significant effects of DPZ in mild and in moderate-severe AD.

Aged↗

Anterior choroidal artery infarction presenting as a progressive cognitive deficit.

PURPOSE: The authors describe a patient in whom neuroimaging using Tc-99m HMPAO SPECT, F-18 fluorodeoxyglucose (F-18 FDG) coincidence imaging, and magnetic resonance imaging (MRI) identified an anterior choroidal artery infarction. Neuroimaging played a critical role in confirming this diagnosis, because the patient had symptoms of progressive cognitive decline and satisfied the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for Alzheimer's disease (AD). METHODS: Tc-99m HMPAO brain SPECT was performed using a triple-head gamma camera. F-18 FDG scanning was obtained 40 minutes after intravenous injection of 5 mCi F-18 FDG using a coincidence camera. A brain MRI scan was performed using a 1.5-Tesla scanner. RESULTS: Tc-99m HMPAO SPECT showed focal hypoperfusion to the right parahippocampal cortex. F-18 FDG coincidence imaging showed a more extensive reduction in glucose metabolism compared with SPECT. The MRI scan confirmed the presence of a small segmental choroidal artery infarction. The Tc-99m HMPAO and F-18 FDG scans were not consistent with AD. CONCLUSIONS: This case illustrates the value of the regional cerebral blood flow SPECT for evaluating memory impairment in the elderly. Decreased regional cerebral blood flow to the posterior temporoparietal region is consistent with AD, whereas regional cerebral blood flow diminution in a vascular territory is consistent with vascular dementia. In this case, the patient was clinically diagnosed with AD, and SPECT was performed to establish the baseline regional cerebral blood flow before the cholinesterase inhibitor donepezil was administered. An infarction was diagnosed on the regional cerebral blood flow brain SPECT scan, which was later confirmed by MRI. Infarctions of the parahippocampal cortex may resuft in memory impairment, which can appear clinically similar to AD.

Aged↗

Identification of neonatal hearing impairment: characteristics of infants in the neonatal intensive care unit and well-baby nursery.

OBJECTIVE: The objective of this study was to describe the demographic data, medical status, and incidence of risk factors for hearing impairment in the neonatal intensive care unit (NICU) and well-baby populations in a multicenter prospective study designed to assess neonatal hearing impairment and to evaluate factors that might affect neonatal hearing test performance. DESIGN: This was a prospective multicenter study funded by the National Institutes of Health-National Institute on Deafness and Other Communication Disorders to evaluate the effectiveness of auditory brain stem response, transient evoked otoacoustic emissions, and distortion product otoacoustic emissions for newborn hearing screening. Research staff at each site obtained informed consent and detailed demographic and medical data, including information on established risk factors for hearing loss on 4478 high-risk infants cared for in the NICU, 2348 infants from the well-baby nurseries with no risk factor, and 353 infants from the well-baby nurseries with risk factors. For follow-up purposes the sample was divided further to include a subgroup called selects. Selects were either infants from the well-baby nursery who had an established risk factor for hearing impairment (N = 353) or did not pass the neonatal hearing screen protocol (N = 80). In this study, we focus on the distribution of infants by nursery and risk factors only. Particular effort was made to enroll infants with risk factors for hearing loss in both the NICU and well-baby nurseries. Descriptive analyses are used to describe characteristics of this sample. RESULTS: All 10 of the risk factors established by the Joint Committee on Infant Hearing in 1994 were identified in the NICU population. The four most common were ototoxic medications (44.4%), very low birth weight (17.8%), assisted ventilation > 5 days (16.4%), and low Apgar scores at 1 or 5 min (13.9%). In contrast, only six risk factors were present in the well-baby nurseries: family history (6.6%), craniofacial abnormalities (3.4%), low Apgar scores (2.8%), syndromes (0.5%), ototoxic medications (0.2%), and congenital infection (0.1%). CONCLUSION: These descriptive risk factor data reflect both the newborn populations at the study sites and the bias for enrolling infants at risk for hearing loss. The high-risk NICU sample reflects the characteristics typically found in graduates of the NICU. The data summarized in this study will be used to assess the relationships between risk factor and hearing test outcome.

Adult↗

Employment in individuals with multiple sclerosis.

The major objectives of this research were to examine unemployment in the MS population on a national level, and to identify factors which might influence an MS individual's employment status. Data used were from the National Multiple Sclerosis Survey conducted by the National Institute of Neurological and Communicative Disorders and Stroke. Data analysis was restricted to a subset of the sample who had worked at some time in their lives. Of 949 persons 79.7% were currently unemployed. While 65.2% had worked at the time of first symptom, only 27.2% were working at the time of the interview, an average of 17 years later. Path analyses revealed the overwhelming importance of mobility for remaining employed, particularly for males. Additional differences found between male and female path models were interpreted in terms of social role theory.

Disability Evaluation↗

Traumatic brain injury in a child psychiatry outpatient clinic: a controlled study.

OBJECTIVE: To demonstrate the similarity of children with a history of traumatic brain injury (TBI), particularly mild TBI, to matched children without such a history, within a child psychiatry outpatient clinic. METHOD: This is a chart review of patients presenting to a child psychiatry outpatient clinic over a 3-year period. Children with TBI were matched by age, sex, race, and social class to children with no history of TBI. Axis I and II diagnoses, use of special education services, and IQ scores were compared. RESULTS: Seventy-four (5.6%) of 1,333 consecutive clinic cases had a definite TBI. Of these, 64 were mild. Only 3 of 59 comparisons that were made between TBI and control subjects were significant. A developmental communication disorder cluster was significantly more frequent in the TBI group. Autism and a pervasive developmental disorder cluster were significantly more frequent in the control group. CONCLUSION: In a child psychiatry clinic, patients with a history of TBI are virtually indistinguishable from matched children without TBI. Caution should be exercised before attributing the child's problems, especially long-term problems, to the TBI unless the injury was severe or the child is exhibiting related phobic or posttraumatic stress symptomatology.

Brain Injuries↗

The diagnostic value of EEG in Alzheimer disease: correlation with the severity of mental impairment.

The aim of our study was to analyze EEG changes in patients with Alzheimer disease (AD) and to determine how closely EEG reflects the progression of mental impairment in people with AD. Ninety-five patients with probable AD according to National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association criteria treated in our Clinic for Memory Disorders were selected for this study. Patients were divided into three subgroups with mild, marked, and severe dementia according to the results of psychometric scales. The EEG findings were classified using an eight-degree scale according to the background activity, presence and amount of theta and delta waves, focal changes, lateralization of focal changes, synchronization, and presence of sharp and spike waves. A significant correlation between the degree of EEG abnormalities and cognitive impairment was found. We did not observe any correlation between the presence of delta waves and the results of neuropsychological tests. Our study revealed an important diagnostic value of EEG in the estimation of the severity of dementia parallel to psychometric scales.

Adult↗

Linguistic impairment in early psychosis.

Twenty-four, first-admission, psychotic subjects and 24 control subjects were administered a linguistic instrument to elicit impairments in syntax, semantics, cohesion, and use of metaphors. In the same session, the subjects were also rated on the Scale for Thought, Language, and Communication Disorders (TLC). Results indicated a significant impairment of all four linguistic categories in psychotic subjects. The impairment in semantics, however, was differentiated the most between the patient and control groups. The psychotic patients scored significantly higher on the TLC. Scores of impairment on the linguistic tasks did not correlate with scores on the TLC.

Adolescent↗

Empathy and social-emotional factors in recovery from stroke.

There is growing interest in evaluating the social and emotional effects of stroke, with the aim of improving recovery and outcome. Recent investigations indicate that post-stroke depression and social impairment are cross-cultural consequences that affect between one-third and two-thirds of patients. These conditions appear to be undertreated, even though studies confirm measurable benefits of medical and caregiver education interventions. A further improvement in outcome can be expected from the comprehensive recognition and management of other social and emotional alterations that encompass emotion-related communication disorders, reduced emotional arousal, initiation and expression, and impaired social cognition, empathy and related interpersonal competencies.

Empathy↗

Outcome of cochlear implantation in pediatric auditory neuropathy.

OBJECTIVE: Auditory neuropathy, characterized by absence or abnormality of auditory brainstem responses and normal otoacoustic emissions, is often associated with particularly poor response to amplification. Outcome data from four such pediatric patients who received cochlear implants are discussed. STUDY DESIGN: Four patients from the Carolina Children's Communicative Disorders Program were identified as having received a diagnosis of auditory neuropathy before implantation with a Clarion cochlear implant. Speech data collected after implantation were compared with data from control pediatric implant patients, matched for age at implantation and duration of implant use. Electrically evoked auditory brainstem response data and electrically evoked acoustic reflex data were also obtained. METHODS: Routine clinical procedures were used to obtain speech outcome data. A 75-micros biphasic 21.1-Hz pulse train served as the eliciting stimulus for both evoked auditory brainstem responses and reflex measures, which were obtained contralateral to the implant. RESULTS: Speech data were comparable with those obtained from the general population of pediatric patients receiving cochlear implants at this center. Identifiable evoked auditory brainstem response data were obtained in all subjects on at least two of the three electrodes tested, and variability was comparable with that observed in other children with implants. A robust electrically evoked acoustic reflex with no decay was observed at estimated M-level in all children. CONCLUSION: The data gathered to date suggest that the outcome of cochlear implantation in these four patients is not significantly different from that in other pediatric implant patients. Physiologic data suggest that the implant was able to overcome the desynchronization hypothesized to underlie auditory neuropathy.

Child, Preschool↗

Test-retest reliability of cortical evoked potentials using naturally produced speech sounds.

OBJECTIVE: To determine if naturally produced speech stimuli evoke distinct neural response patterns that can be reliably recorded in individuals. DESIGN: Auditory cortical evoked potentials were obtained from seven normal-hearing young adults in response to four naturally produced speech tokens (/bi/, /pi/, /[U0283]i/, and /si/). Stimuli were tokens from the standardized UCLA version of the Nonsense Syllable Test (NST) ( Dubno & Schaefer, 1992). Using a repeated measures design, subjects were tested and then retested within an 8-day period. RESULTS: Auditory cortical evoked potentials elicited by naturally produced speech sounds were reliably recorded in individuals. Also, naturally produced speech tokens, representing different acoustic cues, evoked distinct neural response patterns. CONCLUSIONS: 1) Cortical evoked potentials elicited by naturally produced speech sounds can be reliably recorded in individuals. 2) Naturally produced speech tokens, representing different acoustic cues, evoke distinct neural response patterns. 3) Given the reliability of the response, this work has potential application to the study of neural processing of speech in individuals with communication disorders as well as changes over time after various types of auditory rehabilitation.

Acoustic Stimulation↗

Falls and age in patients with Alzheimer's disease.

The study's objective was to estimate the prevalence of falls in community-residing patients with Alzheimer's disease (AD) and to investigate the relationship between falls and age in AD. This was a study of 326 community-residing patients with AD according to National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer's Disease and Related Disorders Association criteria. The patients and their caregivers were asked about falls, behavioral disturbances, and medication use within the last 2 weeks. The patients were also rated on standardized measures of cognitive impairment, stage of dementia, depression, daily activities, general health, and extrapyramidal symptoms. Falls occurred in 24 (7.4%) patients with AD during the last 2 weeks. Using multiple logistic regression analyses, falls were independently associated with old age (odds ratio = 1.2; p = .03; 95% confidence interval = 1.0 to 1.4) but not with other variables examined. The authors conclude that falls in community-residing patients with AD are significantly associated with old age. Population-based prospective studies are needed to investigate further the risk factors for falls in AD.

Accidental Falls↗

Relationship of laterality of stroke to emotional and functional outcome.

The role of hemispheric laterality and emotion in the stroke population has been studied less than in other brain-damaged populations. Neuroscience nurses caring for stroke patients need knowledge about the anatomical placement of ischemic deficits and the relationship of emotions to that placement to understand observed affect and behavior. Knowing how to assess negative affect and behavior will help nurses design interventions to produce optimal recovery.

Aged↗

Effects of donepezil on Alzheimer's disease: the relationship between cognitive function and rapid eye movement sleep.

The aim of this study was to observe the effects of donepezil on both the cognitive function and sleep patterns in patients of Alzheimer's Type Dementia (ATD), especially to determine the relationship between the improvement of cognitive function and the amount of rapid eye movement (REM) sleep. A total of 12 patients (7 females, 5 males; age, 73.0 +/- 6.8) meeting the NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association) criteria of probable AD were studied. These patients presented with mild to moderate dementia, which was confirmed by a Clinical Dementia Rating score of 1 or 2. Following baseline examinations consisting of the Alzheimer's Disease Assessment Scale-cognitive component-Japanese version (ADAS-Jcog) and polysomnography (PSG), 5 mg of donepezil was administered to the patients at breakfast every day. All patients were reassessed 6 weeks later using the same examinations. With sleep patterns, the percentage of REM sleep to total sleep time increased after the administration of donepezil. In addition, it was also found that sleep efficiency was increased and sleep latency was shortened by this administration. Although the ADAS-Jcog score did not decrease significantly, there was significant positive correlation between the decrease of the ADAS-Jcog score and the increase in the percentage of REM sleep. These results indicate the increase action of REM sleep due to activate central cholinergic systems and the possibility to improve sleep conditions due to one-time administration after breakfast of donepezil in mild to moderate ATD. It is concluded that the increase in REM sleep may reflect the improvement of cognitive function in ATD patients.

Aged↗

A broader phenotype of autism: the clinical spectrum in twins.

The diagnostic boundaries of the behavioural phenotype for autism were examined in 28 MZ pairs and 20 DZ same-sex twin pairs, where one or both twins had autism. In the non-autistic cotwin (i.e. in twin pairs discordant for autism) it was common to find language impairments in childhood and social deficits persisting into adulthood. Concordance for this broader phenotype was much greater in MZ pairs than DZ pairs, indicating a strong genetic component. Behavioural and cognitive manifestations of autism were compared both within and between MZ twin pairs. The variation was as great within MZ twin pairs as between pairs, suggesting that it does not index genetic heterogeneity (although aetiological heterogeneity probably exists). Current diagnostic practices need re-evaluation.

Activities of Daily Living↗

Speech, language and hearing in Moebius syndrome: a study of 22 patients.

A comprehensive profile of communicative disorders in patients with Moebius syndrome was attempted. Seven patients were evaluated by the authors and the findings were added to 15 contributed case-histories. Most patients demonstrated some degree of dysarthria due to congenital paralysis of the facial nerves. Other problems such as cleft palate, hearing loss, mental retardation and delayed development of language were found in a few of the patients. As most of the older children in the sample and in reports in the literature eventually developed intelligible speech, a program of oral language stimulation and compensatory articulatory adjustments would appear to be the procedure of choice.

Abducens Nerve↗