AAGP 12th Annual Meeting

28 Am J Geriatr Psychiatry Supplement, Fall 1999

mented elderly women with depressive symptoms haveworse cognitive function and greater cognitive declinethan women with few or no depressive symptoms.Methods: As part of an ongoing prospective study, theauthors evaluated 5,781 elderly mostly white commu-nity-dwelling women. Women completed the GeriatricDepression Scale short form. Three cognitive tests,Trails B, Digit Symbol, and a modified MMSE were ad-ministered at baseline and approximately 4 years later.Baseline, follow-up and change scores for the cognitivetests were analyzed by ANCOVA and Kruskall-Wallis; theodds of cognitive deterioration (� 3 point decline onmodified MMSE) were determined by logistic regres-sion. Results: At baseline, 211 (4%) of the women had� 6 depressive symptoms. Only 8% of these womenwere receiving antidepressant medication. Increasingsymptoms of depression were associated with worseperformance at baseline and follow-up on all three testsof cognitive function (P�0.0001 for all comparisons).For example, baseline Trails B time (mean�SD) was123�56 seconds among women with 0–2 symptoms ofdepression; 150�76 seconds with 3–5 symptoms; and154�76 seconds with 6 or more symptoms. After ad-justing for baseline score, cognitive change scores werealso inversely associated with number of depressivesymptoms (P�0.0001 for all comparisons). Odds ratiosfor cognitive deterioration using 0–2 symptoms as ref-erence were 1.6 (95% CI 1.3–2.1) for 3–5 symptoms and2.3 (95% CI 1.6–3.3) for � 6 symptoms. The resultswere similar after adjustment for education, age, healthstatus, exercise, alcohol use, functional status, andclinic site. Conclusions: Depressive symptoms in olderwomen are associated with both poor cognitive func-tion and subsequent cognitive decline. Mechanisms un-derlying the association between these two commonconditions need further exploration.

Member-In-Training Award

THE EFFECT OF NORTRIPTYLINE AND PAROXE-TINE ON EXTRAPYRAMIDAL SIGNS AND SYMP-TOMS: A PROSPECTIVE DOUBLE-BLIND STUDY INDEPRESSED ELDERLY PATIENTS. David C. Mamo,M.D.; Robert A. Sweet, M.D.; Benoit H. Mulsant,M.D.; Bruce G. Pollock, M.D., Ph,D.; Mark D.Miller, M.D.; Jaqueline A. Stack, M.S.N.; Amy E.Begly, M.A.; Charles F. Reynolds III, M.D., Sup-ported by USPHS Grants MH 52247, MH01153,MH43832, MH01509, MH00295 from the NationalInstitute of Mental Health. [Paroxetine tabletswere provided by SmithKline Beecham.]

Background: Since the first report of SSRI-induceddystonia in 1979 a number of case reports have ap-

peared in the literature suggesting that treatment with

selective serotonin reuptake inhibitors (SSRIs) may re-sult in extrapyramidal signs and symptoms (EPS). Theliterature also suggests that on rare occasions tricyclicantidepressants (TCAs) may induce EPS. Elderly patientsmay be especially vulnerable to antidepressant-inducedEPS. The authors therefore examined the change frombaseline EPS measured using an objective rating scale ina sample of elderly depressed patients participating inan ongoing randomized, double-blind comparison ofnortriptyline and paroxetine. Method: 53 depressed el-derly subjects were randomized to either nortriptylineor paroxetine treatment. The subjects were assessed forEPS using the UKU side-effect rating scale, before andafter 6 weeks of antidepressant treatment. Results: 40subjects completed 6 weeks of treatment and are in-cluded in this analysis. Nortripyline and paroxetine-treated subjects did not differ in baseline demographiccharacteristics and clinical measures. Mild baseline EPSwere present in both groups. There was no statisticaldifference between groups in the baseline UKU ratingfor dystonia, rigidity, hypokinesia, hyperkinesia, tremor,and akathisia. Both groups showed an improvement inall EPS following 6 weeks of antidepressant treatment.The reduction in EPS ratings with treatment did not dif-fer between groups. Conclusion: Both nortriptyline andparoxetine treatment reduced EPS in elderly depressedsubjects. Similar studies with other SSRIs are needed.

AAMI: FACT OR FICTION? R. A. Bullock; S.E. Voss,Kingshill Research Centre, Victoria Hospital,Okus Road, Swindon, UK

Much research in recent years has focused on age-associated memory impairment (AAMI) (Hannien

et al., 1996; Nielson et al., 1998), in order to promotea condition that has become accepted as a nosologicalentity. It has been proposed that as many as 15% of casesof AAMI convert to AD (Pendlebury, 1998), and thisconversion rate seems to be increasing as time goes by.Is this truly a conversion or is AAMI early dementia? Atthe Kingshill Research Centre, we assessed 348 patientsdiagnosed with dementia and 203 healthy elderly con-trol subjects, using a battery of neuropsychologicaltests. The control subjects were a mixture of “normals”and those with subjective memory deficits, who did notreach diagnostic criteria for dementia. A factor analysison the data indicated the existence of three factors inthe patient group, relating to 1) recall, 2) recognition,and 3) information processing (Voss et al., in press). Nomeaningful factors were evident in the control group.The control group was then divided into two groups;those with mild cognitive impairment and those with-out any cognitive impairment. A further factor analysis

Abstracts

Am J Geriatr Psychiatry Supplement, Fall 1999 29

indicated that the neuropsychological results from themildly impaired group strongly resembled the patientdata. These findings support the argument that the ex-istence of an organic disorder is bipolar, rather than ona continuum. The authors then looked at cognitive def-icits in those with subjective memory complaints,which were found to differ significantly from those witha diagnosis of dementia in terms of test scores and interms of the factors. Further evidence to support thisview was provided by the finding that when a group ofcontrols (MMSE 25–30) were compared to a group ofearly AD patient (MMSE 25–30), they differed signifi-cantly on all tests in the neuropsychological test battery.The authors would therefore propose that a patient ei-ther has or does not have dementia and that AAMI mayrepresent the existence of early dementia. “Conversion”therefore, is not an issue. Why create it? There are dif-ficulties in giving a diagnosis of AD at such an early stageof the disease. Is AAMI a more acceptable way of intro-ducing diagnosis and treatment?

HIPPOCAMPAL VOLUME AND GERIATRIC DEPRES-SION: THE EFFECT OF AGE OF ONSET. David C.Steffens, MD; Christopher E. Byrum, MD; MarthaE. Payne, MPH; Daniel L. Greenberg, BA; DouglasR. McQuoid, BS; Timothy F. Blitchington, MS;James R. MacFall, PhD; K. Ranga Rama KrishnanMD. Duke University Medical Center.

Introduction: The role of the hippocampus in mooddisorders is poorly understood. One method of in-

vestigation of the hippocampus in depression has beento measure its volume on magnetic resonance imaging(MRI) scans. Previous studies of hippocampal volume(HV) in major depression have been contradictory, withsome reporting smaller volumes with greater length ofdepressive symptoms, and others finding no significantrelationship. Late-life depression increases the risk ofdementia, which is itself associated with smaller HV.The authors examined the relationships between HVand geriatric depression and age of onset of depression.Methods: 66 depressed elderly patients and 18 nonde-pressed elderly control subjects who were enrolled inDuke’s NIMH-funded Mental Health Clinical ResearchCenter (MHCRC) for the Study of Depression in the El-derly each had a standardized MRI scan. Subjects wereadministered the Duke Depression Evaluation Schedulefor the Elderly, a semi-structured interview that in-cluded the Diagnostic Interview Schedule for depres-sion to document DSM-IV major depression symptomsand age of onset of depression. Final diagnosis of de-pression was assigned after clinical interview by one ofthe MHCRC’s geriatric psychiatrists. In a series of mod-

els using analysis of variance (ANOVA) the authors ex-amined HV in depressed vs. control subjects controllingfor age, gender and total brain volume. The authors per-formed similar ANOVA analysis for the depressed groupto examine the effect of age of onset of depression.Results: Depressive subjects had smaller volumes thancontrol subjects, and among the depressived group,those with older age of onset had smaller HV. In modelsof depressed vs. control subjects, age, gender, presenceof major depression, and total brain volume were in-dependent predictors of HV. Among the elderly de-pressed group, age, age of onset, and total brain volumewere independently associated with HV. In a separatemodel, number of previous depressive episodes was nota significant predictor of HV. Conclusions: This studyprovides further evidence of a role for the hippocampusin mood disorders. The pathological process responsi-ble for the association of smaller HV in geriatric de-pression remains unclear. The authors’ finding thatamong the depressed group, those with older age ofonset supports their observation that late-onset depres-sion is a risk factor for subsequent cognitive decline.Higher cortisol levels associated with late-life depres-sion and dementia may support Sapolsky’s stress-relatedmodel of hippocampal degeneration mediated by glu-cocorticoid neurotoxicity.

LACK OF CORTICAL BLOOD FLOW REDUCTION INNORMAL AGING: RESULTS OF A PET STUDY WITHPARTIAL VOLUME CORRECTION. C.C. Meltzer;M.N. Cantwell; P. Greer; D. Ben-Eliezer; J.C. Price

It remains controversial as to whether cerebral perfu-sion and metabolism decline in normal aging. In vivo

imaging with positron emission tomography (PET) per-mits quantitative evaluation of brain physiology, how-ever, previous PET studies have inconsistently found re-ductions in cerebral blood flow (CBF), oxygenmetabolism, and glucose metabolism with aging. Thismay be due, in part, to a lack of correction for the di-lutional effect of age-related cerebral volume loss onPET measurements. PET measurements of cerebralblood flow were obtained in 27 healthy individuals age19–76 and corrected for partial volume effects due tocerebral atrophy using an MR-based algorithm (Meltzeret al. 1990). Emission scanning for 3 minutes after in-jection of 50 mCi [15O]water was performed on a Sie-mens/CTI 951/31R tomograph with dynamic arterialsampling. Volumetric SPGR MR images were registeredto the PET using the method of Woods et al. (1993).Regions-of-interest were hand drawn on the MR andtransferred to the PET for regional sampling. A one-tis-sue compartment kinetic model was applied to regional