Charles P. Hughes

Mild senile dementia of Alzheimer type: research diagnostic criteria, recruitment, and description of a study population.

Clinical investigations of senile dementia of the Alzheimer type require establishment of explicit clinical diagnostic criteria before histological confirmation is possible. Criteria for selection of mildly impaired subjects with senile dementia of Alzheimer type, free of other major disease, are proposed. Problems of recruitment of this select population for a longitudinal study are discussed. A study population with matched healthy control subjects has been enrolled and described. Short term follow-up has provided preliminary support for the diagnostic criteria.

Predictive features in mild senile dementia of the Alzheimer type

Forty-three subjects with mild senile dementia of the Alzheimer type, diagnosed and staged by clinical research criteria, were studied with clinical, psychometric, EEG, visual evoked potential, and CT measures. During the 12 months following entry into the study, 21 subjects progressed to moderate or severe dementia, 21 remained mild, and one was lost to follow-up. Many of the clinical and psychometric measures of impairment were predictive of the progression to moderate or severe dementia. Electrophysiologic and CT measures were not. In a discriminant function analysis, the scores on two measures (the digit symbol subtest of the Wechsler Adult Intelligence Scale and an Aphasia Battery) correctly predicted the stage of dementia 1 year later in 95% of the subjects.

Cerebral blood flow, oxygen utilization, and blood volume in dementia

Patients with dementia had significant decreases in cerebral blood flow and cerebral oxygen utilization and a mild, but not significant, increase in cerebral blood volume. These studies were not useful in distinguishing patients with cerebral atrophy from patients with normal pressure hydrocephalus, as similar changes in cerebral circulation and metabolism were seen in both groups. Changes in cerebral blood flow after acute decrease in the intracranial pressure also were not helpful in differentiating patients with normal pressure hydrocephalus from patients with cerebral atrophy.

Visual evoked potentials in mild senile dementia of alzheimer type

Visual evoked potentials (VEPs) to chessboard shift and to flash stimulation were recorded from 40 subjects with senile dementia of Alzheimer type (SDAT) and 40 individually matched control subjects. All of the SDAT subjects had only a mild degree of dementia and were still living in the community. Analysis of variance showed significant differences between demented and control group means for 3 chessboard shift VEP measures, the demented group having longer latency of peaks P3 and N3, and larger amplitude of segment N2-P3. These three are the earliest reported changes in the VEP in Alzheimer disease, since the flash VEPs showed no measure in which the demented and control group means differed significantly.

Observations on the afferent and efferent connections of the avian isthmo-optic nucleus.

The efferent and afferent connections of the avian isthmo-optic nucleus (ION) were studied using light microscopic techniques. Injections of [3H]proline into the nucleus resulted in labeling of centrifugal endings in the retina at the junction of the inner plexiform layer and inner nuclear layer, but produced no other transported label to any thalamic or mesencephalic nucleus. The origin of the tectal afferents to the ION was demonstrated by means of injections of [3H]proline into the most superficial layers of the optic tectum and by stereotaxic injections of horseradish peroxidase into the ION. The tectal efferent cell bodies were located in lamin h of the optic tectum and at the junction of laminae h and i.

Afferent projections to the ventral lateral geniculate nucleus in the cat

Horseradish peroxidase (HRP) injections were made into the dorsal lateral geniculate nucleus (LGNd) and ventral lateral geniculate nucleus (LGNv) of the cat in order to define afferent projections to LGNv. These were found from the superior colliculus, contralateral LGNv, dorsal median raphe nucleus, locus coeruleus, ipsilateral pretectum, and various portions of visual cortex. While many cortical areas project to LGNv (17, 18, 19, 21 and lateral suprasylvian), the heaviest input arises from areas 17 and 20. The cell bodies of origin are in layer 5 in contrast to layer 6 which projects to LGNd.

Visual function in the ventral lateral geniculate nucleus of the cat

The visual receptive fields of 293 single units in the ventral lateral geniculate nucleus of the cat were studied. In addition to the wide variety of types described by others, a group of units responding differentially to color was identified that included units responding particularly to blue and others with opponent color properties. Some units with spontaneous firing and without definite visual receptive fields were inhibited by stimulation of the optic chiasm (OX). A study of latency of firing to OX stimulation suggested that these cells were driven by retinal ganglion cells of the W type. One-third of all units studied were binocularly driven.

Nosologic problems in dementia. A clinical and pathologic study of 11 cases.

After recognized clinical and pathologic entities producing dementia in adults are systematically excluded, the literature still contains sporadic reports of patients in whom dementia is the primary or earliest problem but in whom pathologic correlations are unclear. Included here would be many of Kirschbaum’s’ cases of Jakob-Creutzfeldt disease in which spongiform glial changes are not prominent. These patients invariably have neurologic signs in addition to dementia, show abnormal results on many laboratory and other tests, and exhibit some pathologic findings at autopsy. However, the important aspect in many is that the dementia is progressive and severe while neuronal loss is variable in degree and distribution. We recognize that organic mental disease is a category within which definitive clinical and pathologic correlates are woefully inadequate. However, if the definition of dementia as a progressive loss of intellectual function from some previously established level is accepted, it can then be said that in a large number of patients this problem begins after childhood. Many possess an obvious systemic pathophysiologic disturbance that can be related logically to the dementing process. While the precise pathogenesis in the brain and morphologic correlations are obscure, clinical experience in improvement of the dementia after treatment of the basic problem convincingly establishes a relationship for these disorders. They include: pulmonary, cardiac, hepatic and renal decompensation; hormonal imbalance, such as Cushing’s disease, and thyroid dysfunction; disorders 344 Neurology f Volume 23 /April 1973 of calcium metabolism; toxins such as heavy metals; drugs of many types, particularly sedatives and anticonvulsants; and vitamin deficiencies such as pernicious anemia. The dementia often associated with chronic alcoholism is probably related to several of these factors. Another category includes entities that have dementia as a prominent feature and are accompanied by consistent pathologic change. These include: Alzheimer’s disease, senile dementia, Pick’s disease, Huntington’s chorea, the parkinsonism-dementia complex of Guam,’ spongiform en~ephalopathy ,~ Lafora’s disease, Unverricht’s disease, Parkinson’s disease, the adult onset lipidoses, thalamic degeneration: progressive subcortical g l i ~ s i s , ~ the dementing syndromes associated with the hereditary ataxias and cerebellar degenerations, and the syndrome of low pressure hydrocephalus.6 There remains a group of patients in whom a clinically apparent dementia is unrelated to an underlying basic disease and in whom no distinctive pathologic correlates are found at biopsy or autopsy. The purpose of this report is to emphasize that these patients exist in the hope of stimulating more specific studies that can elucidate the true nature of their disease. The present cases are grouped as examples of

Neuroaxonal dystrophy in subacute dementia

SummaryA case has been reported in which neuroaxonal dystrophy is present in a patient who had a clinical syndrome compatible with subacute dementia. These findings, accompanied by demyelination and gliosis were restricted to the rostral half of the corpus callosum and the cortical spinal tract. The interrelationship between neuroaxonal dystrophy and dementia is discussed.