Grossly, the brain volume diminishes by about 2% to 3% per decade after age 50, resulting in convolutional and white matter atrophy and enlargement of the subarach-noid space and lateral ventricles. The leptomeninges thicken, with prominent arachnoid granulations. Histo-logically, lipofuscin, a yellowish-brown pigment (the wear-and-tear pigment), accumulates in the perikaryon of the neurons. The neuronal density may be reduced in the hippocampus, the frontal cortex, and the cerebellum. The number of fibrous astrocytes and microglial cells increases. Corpora amylacea accumulate around the blood vessels and beneath the ependyma and pia mater.

The pyramidal neurons of the hippocampus may display a small number of neuritic plaques, neurofibrillary tangles, granulovacuolar degeneration, and Hirano bodies (see Fig. 2.22). The spinal cord may display small, thin calcified plaques attached to the leptomeninges.

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