Neuron numbers and dendritic extent in normal aging and Alzheimer's disease
TL;DR: In this article, the authors reviewed evidence regarding neuron numbers and dendritic extent in normal aging rodent, monkey and human brain and in Alzheimer's disease and concluded that neuron loss and change in dendric extent are regionally specific, and corresponding brain regions do not always change in similar ways in rodents and primates.
About: This article is published in Neurobiology of Aging.The article was published on 1987-11-01. It has received 742 citations till now. The article focuses on the topics: Aging brain & Brain morphometry.
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3,135 citations
TL;DR: Stereological principles of neuron counting support the conclusion that a marked decrement of layer II neurons distinguishes even very mild AD from nondemented aging.
Abstract: The entorhinal cortex (EC) plays a crucial role as a gateway connecting the neocortex and the hippocampal formation. Layer II of the EC gives rise to the perforant pathway, the major source of the excitatory input to the hippocampus, and layer IV receives a major hippocampal efferent projection. The EC is affected severely in Alzheimer disease (AD), likely contributing to memory impairment. We applied stereological principles of neuron counting to determine whether neuronal loss occurs in the EC in the very early stages of AD. We studied 20 individuals who at death had a Clinical Dementia Rating (CDR) score of 0 (cognitively normal), 0.5 (very mild), 1 (mild), or 3 (severe cognitive impairment). Lamina-specific neuronal counts were carried out on sections representing the entire EC. In the cognitively normal (CDR = 0) individuals, there were ∼650,000 neurons in layer II, 1 million neurons in layer IV, and 7 million neurons in the entire EC. The number of neurons remained constant between 60 and 90 years of age. The group with the mildest clinically detectable dementia (CDR = 0.5), all of whom had sufficient neurofibrillary tangles (NFTs) and senile plaques for the neuropathological diagnosis of AD, had 32% fewer EC neurons than controls. Decreases in individual lamina were even more dramatic, with the number of neurons in layer II decreasing by 60% and in layer IV by 40% compared with controls. In the severe dementia cases (CDR = 3), the number of neurons in layer II decreased by ∼90%, and the number of neurons in layer IV decreased by ∼70% compared with controls. Neuronal number in AD was inversely proportional to NFT formation and neuritic plaques, but was not related significantly to diffuse plaques or to total plaques. These results support the conclusion that a marked decrement of layer II neurons distinguishes even very mild AD from nondemented aging.
1,696 citations
TL;DR: Major advances in understanding of age-related changes in the medial temporal lobe and prefrontal cortex are discussed and how these changes in functional plasticity contribute to behavioural impairments in the absence of significant pathology.
Abstract: The mechanisms involved in plasticity in the nervous system are thought to support cognition, and some of these processes are affected during normal ageing. Notably, cognitive functions that rely on the medial temporal lobe and prefrontal cortex, such as learning, memory and executive function, show considerable age-related decline. It is therefore not surprising that several neural mechanisms in these brain areas also seem to be particularly vulnerable during the ageing process. In this review, we discuss major advances in our understanding of age-related changes in the medial temporal lobe and prefrontal cortex and how these changes in functional plasticity contribute to behavioural impairments in the absence of significant pathology.
1,358 citations
TL;DR: The qualitative and quantitative differences between aging and Alzheimer's disease with respect to neuron loss are discussed, and age-related changes in functional and biochemical attributes of hippocampal circuits that might mediate functional decline in the absence of neuron death are explored.
Abstract: Neurodegenerative disorders are characterized by extensive neuron death that leads to functional decline, but the neurobiological correlates of functional decline in normal aging are less well defined. For decades, it has been a commonly held notion that widespread neuron death in the neocortex and hippocampus is an inevitable concomitant of brain aging, but recent quantitative studies suggest that neuron death is restricted in normal aging and unlikely to account for age-related impairment of neocortical and hippocampal functions. In this article, the qualitative and quantitative differences between aging and Alzheimer's disease with respect to neuron loss are discussed, and age-related changes in functional and biochemical attributes of hippocampal circuits that might mediate functional decline in the absence of neuron death are explored. When these data are viewed comprehensively, it appears that the primary neurobiological substrates for functional impairment in aging differ in important ways from those in neurodegenerative disorders such as Alzheimer's disease.
1,317 citations
TL;DR: Small but consistent rightward asymmetry was found in the whole cerebral hemispheres, superior parietal, fusiform and orbito-frontal cortices, postcentral and prefrontal white matter, and in the parietal white matter.
Abstract: In a prospective cross-sectional study, we used computerized volumetry of magnetic resonance images to examine the patterns of brain aging in 148 healthy volunteers. The most substantial age-related decline was found in the volume of the prefrontal gray matter. Smaller age-related differences were observed in the volume of the fusiform, inferior temporal and superior parietal cortices. The effects of age on the hippocampal formation, the postcentral gyrus, prefrontal white matter and superior parietal white matter were even weaker. No significant age-related differences were observed in the parahippocampal and anterior cingulate gyri, inferior parietal lobule, pericalcarine gray matter, the precentral gray and white matter, postcentral white matter and inferior parietal white matter. The volume of the total brain volume and the hippocampal formation was larger in men than in women even after adjustment for height. Inferior temporal cortex showed steeper aging trend in men. Small but consistent rightward asymmetry was found in the whole cerebral hemispheres, superior parietal, fusiform and orbito-frontal cortices, postcentral and prefrontal white matter. The left side was larger than the right in the dorsolateral prefrontal, parahippocampal, inferior parietal and pericalcarine cortices, and in the parietal white matter. However, there were no significant differences in age trends between the hemispheres.
1,248 citations
References
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TL;DR: Biochemical, electrophysiological, and pharmacological evidence supporting a role for cholinergic dysfunction in age-related memory disturbances is critically reviewed and an attempt has been made to identify pseudoissues, resolve certain controversies, and clarify misconceptions that have occurred in the literature.
Abstract: Biochemical, electrophysiological, and pharmacological evidence supporting a role for cholinergic dysfunction in age-related memory disturbances is critically reviewed. An attempt has been made to identify pseudoissues, resolve certain controversies, and clarify misconceptions that have occurred in the literature. Significant cholinergic dysfunctions occur in the aged and demented central nervous system, relationships between these changes and loss of memory exist, similar memory deficits can be artificially induced by blocking cholinergic mechanisms in young subjects, and under certain tightly controlled conditions reliable memory improvements in aged subjects can be achieved after cholinergic stimulation. Conventional attempts to reduce memory impairments in clinical trials hav not been therapeutically successful, however. Possible explanations for these disappointments are given and directions for future laboratory and clinical studies are suggested.
5,318 citations
TL;DR: Demonstration of selective degeneration of neurons of the nucleus basalis of Meynert represents the first documentation of a loss of a transmitter-specific neuronal population in a major disorder of higher cortical function and points to a critical subcortical lesion in Alzheimer's patients.
Abstract: Recent evidence indicates that the nucleus basalis of Meynert, a distinct population of basal forebrain neurons, is a major source of cholinergic innervation of the cerebral cortex. Postmortem studies have previously demonstrated profound reduction in the presynaptic markers for cholinergic neurons in the cortex of patients with Alzheimer's disease and senile dementia of the Alzheimer's type. The results of this study show that neurons of the nucleus basalis of Meynert undergo a profound (greater than 75 percent) and selective degeneration in these patients and provide a pathological substrate of the cholinergic deficiency in their brains. Demonstration of selective degeneration of such neurons represents the first documentation of a loss of a transmitter-specific neuronal population in a major disorder of higher cortical function and, as such, points to a critical subcortical lesion in Alzheimer's patients.
3,544 citations
TL;DR: Examination of temporal lobe structures from Alzheimer patients reveals a specific cellular pattern of pathology of the subiculum of the hippocampal formation and layers II and IV of the entorhinal cortex that isolates the hippocampus from much of its input and output and probably contributes to the memory disorder in Alzheimer patients.
Abstract: Examination of temporal lobe structures from Alzheimer patients reveals a specific cellular pattern of pathology of the subiculum of the hippocampal formation and layers II and IV of the entorhinal cortex. The affected cells are precisely those that interconnect the hippocampal formation with the association cortices, basal forebrain, thalamus, and hypothalamus, structures crucial to memory. This focal pattern of pathology isolates the hippocampal formation from much of its input and output and probably contributes to the memory disorder in Alzheimer patients.
2,055 citations
Journal Article•
2,031 citations
TL;DR: The nucleus basalis of Meynert provides diffuse cholinergic input to the neocortex and loss of this neuronal population may represent an anatomical correlate of the well‐documented cholinerential derangement in Alzheimer disease.
Abstract: The nucleus basalis of Meynert provides diffuse cholinergic input to the neocortex. When compared with an age- and sex-matched control, the nucleus basalis from a patient with Alzheimer disease demonstrated substantial reduction of neurons. Loss of this neuronal population may represent an anatomical correlate of the well-documented cholinergic derangement in Alzheimer disease.
1,704 citations