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The Nature and Determinants of Neuropsychological Functioning in Late-Life Depression
Meryl A. Butters, PhD;
Ellen M. Whyte, MD;
Robert D. Nebes, PhD;
Amy E. Begley, MA;
Mary Amanda Dew, PhD;
Benoit H. Mulsant, MD;
Michelle D. Zmuda, BS;
Rishi Bhalla, PhD;
Carolyn Cidis Meltzer, MD;
Bruce G. Pollock, MD, PhD;
Charles F. Reynolds III, MD;
James T. Becker, PhD
Arch Gen Psychiatry. 2004;61:587-595.
Context Cognitive impairment in late-life depression (LLD) is highly prevalent, disabling, poorly understood, and likely related to long-term outcome.
Objectives To determine the characteristics and determinants of neuropsychological functioning LLD.
Design Cross-sectional study of groups of LLD patients and control subjects.
Setting Outpatient, university-based depression research clinic.
Participants One hundred patients without dementia 60 years and older who met DSM-IV criteria for current episode of unipolar major depression (nonpsychotic) and 40 nondepressed, age- and education-equated control subjects.
Main Outcome Measures A comprehensive neuropsychological battery.
Results Relative to control subjects, LLD patients performed poorer in all cognitive domains. More than half exhibited significant impairment (performance below the 10th percentile of the control group). Information processing speed and visuospatial and executive abilities were the most broadly and frequently impaired. The neuropsychological impairments were mediated almost entirely by slowed information processing ( = .45-.80). Education ( = .32) and ventricular atrophy ( = .28) made additional modest contributions to variance in measures of language ability. Medical and vascular disease burden, apolipoprotein E genotype, and serum anticholinergicity did not contribute to variance in any cognitive domain.
Conclusions Late-life depression is characterized by slowed information processing, which affects all realms of cognition. This supports the concept that frontostriatal dysfunction plays a key role in LLD. The putative role of some risk factors was validated (eg, advanced age, low education, depression severity), whereas others were not (eg, medical burden, age at onset of first depressive episode). Further studies of neuropsychological functioning in remitted LLD patients are needed to parse episode-related and persistent factors and to relate them to underlying neural dysfunction.
From the Departments of Psychiatry (Drs Butters, Whyte, Nebes, Dew, Mulsant, Bhalla, Meltzer, Pollock, Reynolds, and Becker and Mss Begley and Zmuda), Radiology (Dr Meltzer), and Neurology (Drs Meltzer and Becker), University of Pittsburgh Medical Center, and the Geriatric Research Education Clinical Center of the Pittsburgh VA Healthcare System (Drs Whyte and Mulsant), Pittsburgh, Pa.
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