Relationship between level of insight and severity of dementia in Alzheimer disease. CERAD Clinical Investigators. Consortium to Establish a Registry for Alzheimer's Disease.

Although the cognitive and psychiatric symptoms associated with Alzheimer disease have received increasing attention over the past decade, the study of insight in this illness has been relatively neglected. This paper reports on the relationship between level of insight and severity of dementia in a large sample of patients with Alzheimer disease, largely with mild to moderately severe dementia. The study is based on data from 670 patients with a research diagnosis of probable Alzheimer disease who were enrolled in the Consortium to Establish a Registry for Alzheimer's Disease (CERAD). The degree of insight was rated by the examiner on the basis of the patient's answers to questions probing awareness of his or her memory deficits or other symptoms of cognitive impairment. Severity of dementia was assessed using the Clinical Dementia Rating Scale, Short Blessed Test, Blessed Dementia Rating Scale, and Folstein Mini-Mental State Examination. Two-year longitudinal follow-up data on insight level and dementia severity were available for 148 of the 670 patients. Decreased level of insight correlated significantly with severity of dementia as measured by all rating instruments. For the patients followed for 2 years, 33.1% declined in level of insight from the entry level. This decline was statistically associated with more severe dementia as measured by the Blessed Dementia Rating Scale. This study confirms the generally accepted belief that patients with Alzheimer disease experience a progressive loss of insight as the severity of dementia increases. Due to methodologic limitations, we are unable to draw conclusions about loss of insight in patients with very mild cognitive impairment.

End-stage Alzheimer's disease. Glasgow Coma Scale and the neurologic examination.

OBJECTIVE: To characterize the cognitive and neurologic features of patients with end-stage Alzheimer's disease using a standard neurologic examination and the Glasgow Coma Scale. DESIGN: Case series. SETTING: Local community nursing homes. PATIENTS: Forty patients with Alzheimer's disease were drawn from previously enrolled subjects in the Rochester Alzheimer's Disease Project with Clinical Dementia Rating scores of 3, 4, or 5. MAIN OUTCOME MEASURES: Scores on the Glasgow Coma Scale and cognitive screening examinations and the prevalence of neurologic manifestations such as primitive reflexes and extrapyramidal signs were compared across the Clinical Dementia Rating groups. RESULTS: When compared with patients in the Clinical Dementia Rating stages 3 and 4, patients with a stage 5 scored significantly lower on the Glasgow Coma Scale, with the discriminating subscales being verbal and motor responses. Primitive reflexes, myoclonus, and dyskinesia were increasingly prevalent in the more terminal stages. Cognitive screening assessments did not discriminate between groups. CONCLUSIONS: Rudimentary neurologic functions can be readily assessed and, when viewed together with the Glasgow Coma Scale, may circumvent the "floor effect" frequently encountered when using the currently available cognitive and functional scales and, thereby, better define patients with end-stage Alzheimer's disease.

Alzheimer's disease: the problem of incorrect clinical diagnosis.

We reviewed the medical records of eight patients clinically diagnosed with Alzheimer's disease who were found on autopsy to have neuropathologic findings inconsistent with Alzheimer's disease. The clinical criteria for the diagnosis of probable Alzheimer's disease from the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) were retrospectively applied to these patients. The patients presented with clinical features atypical for Alzheimer's disease early in the course of the disease, including focal neurologic findings, gait abnormalities, motor speech abnormalities, and extrapyramidal features. Attention to these clinical red flags may decrease the likelihood of misdiagnosis of Alzheimer's disease in a patient with a non-Alzheimer's disease cause of dementia.

Increased levels of truncated nerve growth factor receptor in urine of mildly demented patients with Alzheimer's disease.

OBJECTIVE: In Alzheimer's disease, cholinergic basal forebrain neurons, which have receptors for nerve growth factor (NGF), degenerate, while NGF receptors increase in some areas of the neocortex. Levels of the truncated, extracellular portion of the NGF receptor (NGF-Rt) are elevated in urine of patients with peripheral neuropathies and in animals with peripheral-nerve injury, but it has not been determined whether urine levels of NGF-Rt are altered by the presence and/or progression of dementia-related neuropathologic changes in patients with Alzheimer's disease. In this study, we developed an enzyme-linked immunosorbent assay to determine whether urine levels of NGF-Rt are altered in patients with Alzheimer's disease. DESIGN: Survey of urine NGF-Rt levels in neurologically normal (n = 19), mildly demented (n = 31), and moderately to severely demented (n = 31) patients. SETTING: Subjects were participants in the Rochester Alzheimer's Disease Project and mildly demented patients about to begin a clinical drug study. PATIENTS: All patients met established criteria for a clinical diagnosis of probable Alzheimer's disease. Aged, nondemented, neurologically normal controls were selected from the families of the demented subjects. RESULTS: Urine NGF-Rt levels were substantially elevated in mildly demented patients relative to those of nondemented controls. CONCLUSIONS: These results suggest that an enzyme-linked immunosorbent assay on urine samples may provide an antemortem measure of dementia-related neuropathologic changes, but further study is needed to determine the source and potential clinical utility of increased NGF-Rt levels in urine of mildly demented patients.

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.

Behavioral disturbance in severe Alzheimer's disease: a comparison of family member and nursing staff reporting.

OBJECTIVE: The purpose of this study is to describe the behavioral disturbances in a group of patients with severe Alzheimer's disease and to compare family members' and nursing staff members' perceptions regarding these behaviors. DESIGN: Cross-sectional survey. SUBJECTS: The 33 subjects resided in nine different long-term care facilities in the Rochester, NY area and were selected from a group of patients enrolled in a longitudinal research study of Alzheimer's disease, based on having severe disease. OUTCOME MEASURES: Caregivers were surveyed with a self-administered questionnaire. The primary outcome measures were the prevalences of 13 behaviors and the magnitude of caregiver concern reported by each group of caregivers. RESULTS: Compared with family members, nurses reported more concern with vegetative behaviors (incontinence, dietary change, and sleep disturbance; P = 0.055). There was statistical evidence that the number of behaviors reported by the nurses decreased with increasing disease severity (P = 0.002). Although not statistically significant, the magnitude of concern reported by the nurses also decreased with increasing disease severity (P = 0.063). Family members and nurses frequently disagreed about the presence of many behaviors exhibited by individual patients, and the responses of caregivers within the same group were highly variable. CONCLUSION: Institutionalized patients with severe Alzheimer's disease continue to exhibit troublesome behaviors although overall behavioral disturbance and concern appear to decrease with increasing disease severity. The assessment of these behaviors and their impact on caregivers can be very subjective, depending in part on the role of the caregiver.

The role of brain single photon emission computed tomography in the diagnosis of primary progressive aphasia.

We present two cases of primary progressive aphasia studied with neuropsychologic measures, computed tomography or magnetic resonance imaging, and single-photon emission computed tomography with technetium Tc99m-labeled hexamethylpropyleneamine oxime. Clinical and neuropsychologic observations revealed a marked, progressive loss of language functions over time with relative preservation of nonlanguage cognitive functions in both patients. The brain single-photon emission computed tomographic scan revealed marked left frontal and minimal left temporal and parietal hypoperfusion in case 1 and marked left posterior frontal and minimal left temporal hypoperfusion in case 2. The value of brain single-photon emission computed tomography in distinguishing primary progressive aphasia from Alzheimer's disease is described.

Tardive dyskinesia in Alzheimer's disease: clinical features and neuropathologic correlates.

Medical record review was conducted on 14 patients with neuropathologically confirmed Alzheimer's disease, all of whom had been treated with antipsychotic medications, to determine the relationship between neuropathology and the development of tardive dyskinesia. Four cases were found to have chart descriptions of hyperkinetic movement disorders consistent with tardive dyskinesia. When the group with tardive dyskinesia was compared to the group without tardive dyskinesia, there were no statistically significant differences regarding gender, age of onset of dementia, duration of dementia, age at death, or duration of antipsychotic treatment. Neuropathologic comparisons revealed greater degenerative changes in the substantia nigra in those patients with tardive dyskinesia. These preliminary observations suggest that patients with Alzheimer's disease and significant coexisting substantia nigra pathologic changes may be at higher risk for developing tardive dyskinesia when treated with antipsychotic medication.

Anton's syndrome in a patient with posttraumatic optic neuropathy and bifrontal contusions.

We describe a patient who manifested Anton's syndrome after sustaining head trauma that resulted in optic nerve damage and bifrontal contusions. Denial of monocular blindness, generalized anosognosia, and confabulation were prominent neurobehavioral features. Anton's syndrome is most commonly encountered in patients with bilateral occipital cortex lesions. Patients previously described who demonstrated Anton's syndrome secondary to a peripheral lesion have had an associated delirium or profound dementia. Our case demonstrates that Anton's syndrome may occur in association with blindness from a peripheral lesion, even in the absence of a delirium or significant dementia. We suggest that the bifrontal dysfunction may have been a critical factor in the production of Anton's syndrome. Implications for the role of frontal lobe dysfunction in the genesis of anosognosia and confabulation are discussed.

Visuoconstructional impairment in dementia syndromes.

Dementia of the Alzheimer type (DAT) affects most neuropsychological domains including language, memory, and visuo-spatial skills. The latter are usually assessed by poorly quantifiable copying tasks. We assessed constructional abilities using the Developmental Test of Visuomotor Integration (VMI) comprised of a series of model drawings of increasing complexity. Twenty-six patients meeting NINCDS-ADRDA criteria for DAT, 21 normal aged subjects with normal mental status examinations, and 14 patients with vascular dementia were tested. In DAT, we found significant correlations between visuoconstructive ability and memory registration, delayed recall, and language functions such as confrontation naming and word-list generation. Less marked, but significant correlations were found in the vascular dementia group between visuoconstructive ability and memory registration and word-list generation. A few normal elderly subjects were unable to copy the most challenging figures. The study demonstrates that: (1) VMI is a convenient method for quantifying constructional deficits in DAT and other dementing illnesses; (2) constructional deficits are highly correlated with dementia severity and memory and language deficits in DAT; (3) neuropsychological deficits are less highly inter-correlated in vascular dementia than in DAT; and (4) abnormal constructional skills are present in some normal elderly.

The "yips": a focal dystonia of golfers.

The "yips" is an involuntary motor disturbance affecting golfers. A 69-item questionnaire was constructed and distributed to 1,050 professional and amateur golfers in an effort to define and characterize this syndrome. Of the male golfers there was a 42% response rate and 28% reported suffering from the yips. The disorder was described most frequently as jerks, tremors, and spasms affecting the preferred arm distally and primarily during putting. When compared with unaffected golfers, afflicted golfers were significantly older and had more cumulative years of golfing. In 24%, activities other than golfing were affected and 25% reported involvement of body regions beyond the arms. These data support the hypothesis that the yips represents a focal dystonia and shares many features with other occupational dystonias.

Pharmacologic treatment of psychiatric and neurodevelopmental disorders in children and adolescents (Part 1).

A review is presented of the diagnosis and drug treatment of the more common psychiatric and developmental disorders in the pediatric population. Where applicable, DSM III (Diagnostic and Statistical Manual of Psychiatric Disorders, III) criteria are utilized to describe the behavioral syndromes. The indications for usage and appropriate dosages of antipsychotics, antidepressants, anxiolytics, stimulants, and lithium are described. Those disorders discussed are attention deficit disorder, conduct disorders, anxiety disorders, sleep disorders, schizophrenia, autism, Tourette's syndrome, mental retardation, depressive illness, manic depressive illness, eating disorders, and enuresis.