To examine the possibility that senile dementia may be associated with a loss of noradrenergic neurons that innervate the cerebral cortex, we used a Quantimet 720 image analyzer to estimate the number of neurons in the nucleus locus ceruleus in elderly patients with the clinical diagnosis of senile dementia. In all but one case, the diagnosis was established histopathologically as senile dementia of the Alzheimer type (SDAT). In a subgroup characterized by a high dementia score and relatively young age at death, there was a loss of about 80% of locus ceruleus neurons. This loss of neurons indicates a deficit of noradrenergic innervation to cerebral cortex in a group of patients which may represent a variant of SDAT.

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Primary efficacy measures showed sertraline and nortriptyline to be similarly effective. With secondary outcome measures there was consistent evidence of an advantage for the sertraline-treated group. The clinical impact of these measures on the long-term well-being of elderly depressed patients should be examined in a study of maintenance treatment.

Development of pia-arachnoidal membranes in the mouse occurs in four stages: the first (prenatal days 10-13) follows closure of the neural tube and is a period of initial vascularization of the developing telencephalon; the second (prenatal days 14-16) is a period of delineation during which the limits of the subarachnoid space are defined; the third (prenatal day 17 to birth) is a period of ensheathment of pia-arachnoidal blood vessels; and the fourth (birth to postnatal day 21) includes addition of smooth muscle to larger vessels, the appearance of macrophages in the subarachnoid space, and a general increase in extracellular collagenous and elastic fibers. The mesenchyme over the telencephalic surface in the 10-day fetus has a typically large extracellular space. By the 13th fetal day cerebrospinal fluid begins to seep into and replace it. The mesenchymal extracellular compartment is reduced peripherally, resulting in a compacted pia-arachnoidal tissue which limits the peripheral extent of the subarachnoid space. By the 21st postnatal day a subarachnoid space typical of the adult animal has been established.