Greater abnormalities of brain cerebrospinal fluid volumes in younger than in older patients with Alzheimer's disease

E. V. Sullivan, P. K. Shear, D. H. Mathalon, K. O. Lim, J. A. Yesavage, J. R. Tinklenberg and A. Pfefferbaum
Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Calif.

OBJECTIVE--This study used a semiautomated analysis technique to quantify differences in regional brain cerebrospinal fluid volumes observed with computed tomography between healthy adults and patients with Alzheimer's disease (AD). DESIGN--Cross-sectional, between-subject design, using an age-regression model. SETTING--Palo Alto (Calif) Department of Veterans Affairs Medical Center. PATIENTS AND OTHER PARTICIPANTS--The 117 patients with probable or definite AD were recruited from the Geriatric Psychiatry Research Unit and National Institute of Mental Health Clinical Research Center of the Palo Alto Department of Veterans Affairs Medical Center. The 114 healthy volunteers were recruited from the local community. MAIN OUTCOME MEASURES--Cerebrospinal fluid volumes estimated from computed tomographic scans and neuropsychological test scores. RESULTS--The computed tomographic estimates of ventricular and sulcal cerebrospinal fluid volumes increased significantly in all sampled brain regions in normal aging and were vastly larger in AD than in normal aging. Furthermore, younger patients with AD had significantly greater cerebrospinal fluid volume enlargement than did older patients with AD compared with healthy controls of their age. When the AD group was divided on the basis of reported age at symptom onset, patients in the early-onset group (onset before age 65 years) were quantitatively more abnormal than and showed a different pattern of abnormality from the patients in the late-onset group. This onset difference was also evident in neuropsychological test performance. CONCLUSIONS--This cross-sectional study revealed a number of converging findings that suggested greater abnormality in the early-onset than in the late-onset group of patients with AD. The possibility remains, however, that the two onset groups represent different stages along a continuum of pathologic changes.

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