Am J Psychiatry 1997; 154:25-30
Copyright © 1997 by American Psychiatric Association
Effects of Alzheimer's disease severity on cerebrospinal fluid norepinephrine concentration
R Elrod, ER Peskind, L DiGiacomo, KI Brodkin, RC Veith and MA Raskind
Psychiatry Service, VA Puget Sound Health Care System, Seattle, WA 98108, USA.
OBJECTIVE: Although loss of noradrenergic neurons in the locus ceruleus has
been consistently demonstrated postmortem in Alzheimer's disease, several
small studies suggest that indices of central noradrenergic activity
increase with the severity of Alzheimer's disease in living patients. The
authors estimated the effect of Alzheimer's disease severity on central
noradrenergic activity by comparing the CSF norepinephrine concentrations
of subjects with Alzheimer's disease in earlier and advanced stages. The
effect of normal aging on CSF norepinephrine also was determined. METHOD:
Lumbar punctures were performed in 49 subjects with Alzheimer's disease of
mild or moderate severity, 25 subjects with advanced Alzheimer's disease,
42 normal older subjects, and 54 normal young subjects. Advanced
Alzheimer's disease was defined prospectively by a Mini-Mental State score
of less than 12. Norepinephrine was measured by radioenzymatic assay.
RESULTS: CSF norepinephrine concentration was significantly higher in the
patients with advanced Alzheimer's disease (mean = 279 pg/ml, SD = 122)
than in those with mild to moderate severity (mean = 198 pg/ml, SD = 89),
normal older subjects (mean = 219 pg/ml, SD = 88), or normal young subjects
(mean = 154 pg/ml, SD = 53). CSF and plasma norepinephrine levels and mean
arterial blood pressure all were higher in the older subjects than in the
young subjects. CONCLUSIONS: Despite the loss of locus ceruleus neurons in
Alzheimer's disease, the aging-associated high concentration of CSF
norepinephrine is retained in the earlier stages of Alzheimer's disease and
increases further as the disease progresses. Increased brain noradrenergic
activity may contribute to the agitated behaviors or cognitive deficits of
patients with advanced Alzheimer's disease.
