. Neurodegenerative basis of age-related cognitive decline. Neurology. 2010 Sep 21;75(12):1070-8. PubMed.


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  1. Can “normative cognitive aging and neurodegenerative disease” be differentiated? In this provocative paper from the Nun study by the outstanding group at Rush, the authors suggest, “These data challenge the concept of normative cognitive aging and suggest instead that neurodegenerative disease plays a role in virtually all late-life cognitive decline.” However, it is also possible to argue the contrary.

    Certainly it is true that virtually all elderly brains have evidence of the traditional stigmata of Alzheimer’s disease. And that “normative aging” is accompanied by some degree of cognitive decline. But does this mean that normative aging and neurodegenerative disease are not separable? Additional evidence suggests that the two may be differentiated. Perhaps the earliest evidence to this effect came from the unbiased stereological study of neuron numbers in the subdivisions of the hippocampus in aging and in AD (West et al., 1994). This study reported neuron loss in the subiculum in both normal aging and in AD. However, although CA1 lost large numbers of neurons in AD, there was no appreciable neuronal loss in this region in “normal” aging. Thus, although loss of hippocampal neurons is characteristic of both aging and AD, the regional pattern of cell loss is different in these two situations. Most recently, an array study of the expression of genes related to the synapse will report that, although aging and AD involve similar effects in this subset of transcripts, the pattern of brain regions involved is different between aging and AD, with expression changes being most prevalent in the hippocampus in AD and less so in neocortical regions examined, while in aging it was neocortical regions that were most affected, with hippocampus much less affected (Coleman et al., 2010). It seems probable that these regional differences may be reflected in selected cognitive capacities.

    Thus, it appears that normative aging and AD both exhibit similar plaques and neurofibrillary tangles, loss of neurons, and selected molecular deficits. However, the regional pattern of these changes is different in these two conditions. It’s not an issue of whether these changes take place, but where they take place.

    See also: Coleman PD, N Berchtold, D Cribbs, A Grover, J Rogers and CW Cotman (2010) Microarray study of multiple regions of human brain reveals new concepts of synaptic change in aging and Alzheimer’s disease. Society for Neuroscience Presentation 348.17.


    . Differences in the pattern of hippocampal neuronal loss in normal ageing and Alzheimer's disease. Lancet. 1994 Sep 17;344(8925):769-72. PubMed.

  2. Why is ventriculomegaly, the expansion of the cerebral ventricles, and cerebral volume changes part of normal aging? There can be the differentiation between normal and neurodegenerative aging. Different regions of the aging brain may suffer atrophy and lose volume because elderly who are not active lose sensory modalities, or are slowed due to osteoarthritis. Then the corresponding afferent-efferent neurons in their regional projection areas become less active with reduced need for blood supply, and thus the volume reduces. In this case, there may be little cell death, just shrinkage. With neurodegenerative diseases, there is cell death, with involvement of astrocytes and phagocytosis carrying the dead cell material to the ventricles washed by CSF.

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