Coexistence of Alzheimer disease neuropathology with herpes simplex encephalitis.

Several unusual features were observed during routine histopathological confirmation of a clinical diagnosis of Alzheimer's disease (AD) in an 85-year-old, right-handed, married male. The patient presented with a 12-year history of slowly progressive cognitive impairment, which increased in severity just prior to death. Detailed postmortem examination of the frontal lobes revealed a significant number of neuritic plaques and neurofibrillary tangles. Multifocal spongiform encephalopathic changes, mononuclear perivascular infiltrates, subcortical demyelination and gliosis were also found. Of particular interest were well-defined neuronal and astrocytic intranuclear inclusion bodies (Cowdry type I and I), suggestive of viral disease. Electron microscopy, immunohistochemical and immunohistofluorescent studies confirmed a Herpes simplex type I encephalitis (HSV-I). These histological results and the clinical history of progression suggest that reactivation of a latent viral infection may have contributed to the rapid progression of dementia prior to death. The present analysis underscores the fact that multiple etiologic factors may act simultaneously to produce dementia. While one such process may be identified or diagnosed (in the present case AD), it is necessary to be open to the possibility that another mechanism may come into play during the time course of that illness. A differential diagnosis may be difficult when the symptoms of the two disease processes are very similar. Such may be the case if there is reactivation of a previously undiagnosed herpes virus infection. With the development of PCR and in situ hybridization diagnosis will be simplified and more definitive.

Lay person-based screening for early detection of Alzheimer's disease: development and validation of an instrument.

Symptoms of cognitive impairment reported to telephone interviewers by caregivers of 272 patients were analyzed with respect to research diagnoses of dementia. All patients received neuropsychological evaluation for establishing the research diagnoses. A data mining program that used machine learning algorithms produced an optimized binary decision tree for differentiating patient groups according to all available information. The results of this analysis were used to help four dementia experts create a dementia screening instrument amenable to application and scoring by nonclinical personnel. The validity of the resulting instrument was then evaluated in an independent sample of 103 patients administered neuropsychological testing within the previous 60 days. The psychometric properties of the empirically derived scale and its performance for discriminating control from probable or possible Alzheimer's patients indicate strong potential for use as a dementia screener for the general population.

Traumatic brain injury: influence of blood alcohol level on post-acute cognitive function.

Alcohol intoxication frequently contributes to the occurrence of traumatic brain injury. Few studies, however, have examined whether acute pre-injury alcohol intoxication or premorbid history of alcohol abuse exacerbate cognitive impairments that commonly result from traumatic brain injury. This study examined the influence of blood alcohol level at time of hospital admission on cognitive functioning during the post-acute stage of recovery from traumatic brain injury. After controlling for pre-injury history of alcohol abuse, hospital admission blood alcohol level was predictive of poorer delayed verbal memory, greater decrement in verbal memory over time, and poorer visuospatial functioning. Moreover, there were non-significant trends for higher blood alcohol levels to predict poorer performance on measures of immediate verbal memory and perseveration.

An integrated program for dementia evaluation and care management.

The growth of the geriatric population and the emergence of managed care dictate new approaches to dementia care. Management of Alzheimer's disease (AD) is a critical issue for health care policy as well as quality of life for patients and caregivers. The Alzheimer's Disease Education Program (ADEP) seeks to improve the quality of care for individuals with AD and to reduce the burden of caregiving experienced by families. Objectives of ADEP include early detection of AD through dementia screening followed by caregiver education and support. This article outlines an effective method of dementia evaluation and management.

The P1 component of the middle latency auditory potential may differentiate a brainstem subgroup of Alzheimer disease.

The P1 component of the middle latency auditory evoked potential (MLAEP) was found to be absent in 47.5% of 101 patients with Alzheimer disease (AD). Lack of a P1 component recently has been associated with a more rapid decline in cognitive performance. The blink reflex (BR) was tested in 36 patients with probable AD and 17 elderly control subjects. All subjects also underwent P1 recording. Patients lacking a P1 potential showed a significant increase in latency of the contralateral R2 response of the BR. The P1 component and the R2 response may differentiate a subgroup of AD patients with involvement of the brainstem, especially the reticular formation.

The P1 component of the middle latency auditory evoked potential predicts a practice effect during clinical trials in Alzheimer's disease.

Thirty-five patients with probable Alzheimer's disease who were enrolled in an experimental drug trial of linopirdine underwent repeated testing that included recording the middle latency auditory evoked potential (MLAEP), the Mini-Mental State Examination (MMSE), and the Alzheimer's Disease Assessment Scale Cognitive Subscale (ADASCOG). Patients lacking the P1 component of the MLAEP exhibited a significantly greater decline in cognitive function as measured by the ADASCOG over 56 weeks. This decline appeared to be due to a less robust practice effect, which was maximal in all patients at 16 weeks. At the end of 56 weeks the entire group of patients was near baseline with respect to the ADASCOG. This lack of the annualized decline expected from other longitudinal studies may be explained by practice and placebo effects. The MMSE did not exhibit a practice effect and showed the expected decline in scores.

Boston Naming Test: shortened versions for use in Alzheimer's disease.

Four new 15-item versions of the Boston Naming Test (BNT), a 15-item version used by the Consortium To Establish a Registry for Alzheimer's Disease (CERAD), and three 30-item BNT versions were studied in 26 subjects with Alzheimer's disease (AD) and 26 nondemented, neurologically normal controls. The four 15-item versions were statistically equivalent. On each version, controls performed significantly better than AD subjects, and scores on each could be extrapolated to a complete 60-item BNT score. The CERAD version also differentiated between AD and control subjects, but it was not equivalent to our four versions and could not be as easily extrapolated to a 60-item score. Even and Odd 30-item BNT versions were confirmed to be equivalent, and we further validated a 30-item Empirical Version designed to maximally discriminate between AD and normal subjects. Equivalent 15- or 30-item versions of the BNT will be useful in repeated assessments requiring independent forms of a naming task, as well as in situations where administration of the complete BNT is not practical.

The middle latency auditory evoked potential may be abnormal in dementia.

The P1 potential (50 msec) of the middle latency auditory evoked potential was lacking in 12 of 31 (39%) patients with probable Alzheimer's disease and seven of 12 (58%) demented patients with Parkinson's disease. Component P1 was not present in one normal control subject and one nondemented Parkinson's disease patient. Clinical and experimental evidence suggests that abnormalities of P1 in dementia may be due to cholinergic dysfunction.

The agraphia of Alzheimer's disease.

Hypothesizing that agraphia in Alzheimer's disease (AD) reflects disturbances in multiple cognitive domains, we evaluated writing samples from 33 patients meeting strict criteria for probable AD. We found agraphia to be common on a standard narrative writing task. When compared with 41 education- and age-matched normal control subjects, AD patients had significantly lower writing scores, wrote significantly fewer words, mentioned significantly fewer categories of information, and were significantly more likely to make writing errors. On stepwise regression procedures, neuropsychological measures of visuoperceptual impairment and disease severity were the strongest predictors of agraphia, but other analyses indicated that measures of language, praxis, and attention could also contribute significantly to agraphia. On two writing tasks, we failed to confirm the previous contention that agraphia is a marker for familial AD. However, there was a highly significant interaction between family history, oral naming, and writing: patients with nonfamilial AD, but not those with a family history of dementia, showed a strong correlation between naming and writing performance. We conclude that agraphia in AD can be variously determined and that agraphia is not a reliable marker for familial disease.

Rotary Diamond Chart--a new visual field screening device.

The Rotary Diamond Chart (RDC) is presented as a new clinical method suitable for screening general optometry patients for visual field defects. A pilot study was conducted using both the rotary diamond chart and a central 76-point threshold-related screening test (Allergan-Humphrey) on 21 consecutive clinical patients. Full-threshold field testing was then completed on those subjects failing either screening test. The RDC detected five of six visual field defects including one very subtle defect which was not detected by the automated screening test. The sensitivity of the RDC visual field screening assessment was 83.33 percent with a specificity of 100 percent. These results suggest that the RDC is an effective clinical visual field screening test. It is easy for the clinician to use and for the patient to understand.

Naming consistency in Alzheimer's disease.

Although lexical semantic deficits are postulated to play a prominent role in the anomia of Alzheimer's disease, it is unclear whether the primary disturbance is one of lexical access or one of lexical semantic loss. Response consistency on a naming task is one means of evaluating the underlying source of naming impairment. Access dysfunction usually implies variable word-finding difficulty, while a theory of lexical loss predicts that many word names would be consistently unavailable. Nineteen Alzheimer's disease patients were administered a visual confrontation naming task (the Boston Naming Test) on two occasions 6 months apart. Eighty percent of errors occurred consistently at both times; only 20% of errors occurred on only one occasion. Response consistency occurred significantly more often than expected under the assumption of no response consistency. Findings support the hypothesis that anomia in Alzheimer's disease is in part due to a loss of lexical semantic information.

Stroop Color-Word Test performance in patients with Alzheimer's disease.

Patients with Alzheimer's disease (AD) (n = 36) and normal older adults (n = 36) were individually administered the Stroop Color-Word Test. Eight of 36 (22%) AD patients exhibited confusion between the colors blue and green, while no control subject had difficulty distinguishing among the colors. In a second experiment, a subset of the original sample (15 AD patients and 8 control subjects) was retested using the Stroop. Only 2 AD patients showed color confusion on both test occasions, while 7 AD patients exhibited color confusion on one occasion. No control subject exhibited confusion between colors the second time. These results indicate that color confusion in AD patients is inconsistent. Due to the high incidence of color confusion in AD patients, the Stroop should be used with caution in patient populations.

Selective attention in Alzheimer's disease: characterizing cognitive subgroups of patients.

Picture recognition was studied in 20 patients with AD and in 20 control subjects, using a procedure that matched these groups for initial performance. The groups did not differ significantly in overall forgetting, although 10 patients displayed improved recognition performance 72 hr after learning. These same patients were impaired in a test of attentional focusing, as revealed by post hoc analyses. A predictive experiment involving 20 new patients with AD confirmed the initial findings: a subgroup of patients displayed improved recognition performance 72 hr after learning and impairments in attentional focusing. Neuropsychological tests thus identify a subgroup of patients with impaired selective attention, perhaps related to locus coeruleus neuropathology.

Rate of forgetting in H.M.: 6-month recognition.

The picture-recognition performance of H.M. and six control subjects was evaluated 6 months after initial learning, using materials from an earlier study in which H.M. received additional study time in order to equate his yes-no and delayed-match-to-sample (DMS) performance 10 min after learning to that of control subjects. In the study detailed here, 6-month recognition performance was assessed with no intervening exposure to the target items. H.M. performed at chance levels when tested using the standard yes-no recognition procedure. When the yes-no procedure was modified so that distractor stimuli required positive responses, H.M.'s performance was comparable with that of control subjects. In addition, H.M.'s DMS and delayed-nonmatch-to-sample (DNMS) performance were comparable with that of control subjects 6 months after learning. Conclusions regarding H.M.'s 6-month recognition performance are thus dependent on the procedures used to assess memory.

Long-term occupational exposure and the diagnosis of dementia.

Several experiments are reported which concern the possible role of long-term occupational exposure in the etiology of dementia. A case study of a male with memory impairment thought to be due to Alzheimer's disease is reported. Neuropsychological testing revealed impairments in short-term memory, which gradually cleared over months. Analyses uncovered extremely high serum levels of a solvent (perchlorethylene) this individual had used for decades in a dry-cleaning business. A case-series is also reported in which four individuals with similar patterns of neuropsychological performance were noted to share occupational exposure to metal vapors. The results of a preliminary case-control study are also reported in which an increased incidence of long-term occupational exposure to metals and solvents was noted in patients with Alzheimer's disease. These results suggest that the role of long-term occupational exposure needs to be thoroughly investigated in patients diagnosed with Alzheimer's disease and other neurological disorders.

Selective attention in Alzheimer's disease: CSF correlates of behavioral impairments.

CSF levels of HVA, 5-HIAA, and free MHPG, the major metabolites of dopamine, serotonin, and norepinephrine respectively, were measured in 22 patients with AD. These 22 patients were also administered tests of picture-recognition and attentional focusing as part of an earlier experiment. A significant association between deficits in attentional focusing and reduced levels of free MHPG in CSF was noted. These results suggest that behavioral measures can identify patients with noradrenergic involvement.

Forgetting in H.M.: a second look.

Forgetting was assessed in the amnesic patient H.M. using forced-choice and yes-no picture recognition at four delay intervals: 10 min, 24 hr, 72 hr, and 1 week after learning. In order to make H.M.'s initial recognition performance comparable to that of control subjects who viewed each slide for 1 sec, H.M. viewed each slide for 20 sec. H.M. displayed normal forgetting in forced-choice and yes-no recognition, although he was impaired in yes-no recognition at the 24-hr delay interval. These data contradict Huppert and Piercy's hypothesis that medical temporal-lobe pathology is associated with rapid forgetting.