Biomedical subjects

D P Devanand

Publications and source records attributed to D P Devanand.

At least 19 recordsLinked to original sources

PubMed2006

Neuropsychological prediction of conversion to Alzheimer disease in patients with mild cognitive impairment.

CONTEXT: The likelihood of conversion to Alzheimer disease (AD) in mild cognitive impairment (MCI) and the "optimal" early markers of conversion need to be established. OBJECTIVES: To evaluate conversion rates to AD in subtypes of MCI and to identify neuropsychological measures most predictive of the time to conversion. DESIGN: Patients were followed up semiannually and controls annually. Subtypes of MCI were determined by using demographically adjusted regression norms on neuropsychological tests. Survival analysis was used to identify the most predictive neuropsychological measures. SETTING: Memory disorders clinic. PARTICIPANTS: One hundred forty-eight patients reporting memory problems and 63 group-matched controls. MAIN OUTCOME MEASURE: A consensus diagnosis of probable AD. RESULTS: At baseline, 108 patients met criteria for amnestic MCI: 87 had memory plus other cognitive domain deficits and 21 had pure memory deficits. The mean duration of follow-up for the 148 patients was 46.6 +/- 24.6 months. In 3 years, 32 (50.0%) of 64 amnestic-"plus" and 2 (10.0%) of 20 "pure" amnestic patients converted to AD (P = .001). In 148 patients, of 5 a priori predictors, the percent savings from immediate to delayed recall on the Selective Reminding Test and the Wechsler Adult Intelligence Scale-Revised Digit Symbol Test were the strongest predictors of time to conversion. From the entire neuropsychological test battery, a stepwise selection procedure retained 2 measures in the final model: total immediate recall on the Selective Reminding Test (odds ratio per 1-point decrease, 1.10; 95% confidence interval, 1.05-1.14; P < .0001) and Digit Symbol Test coding (odds ratio, 1.06; 95% confidence interval, 1.01-1.11; P = .01). The combined predictive accuracy of these 2 measures for conversion by 3 years was 86%. CONCLUSIONS: Mild cognitively impaired patients with memory plus other cognitive domain deficits, rather than those with pure amnestic MCI, constituted the high-risk group. Deficits in verbal memory and psychomotor speed/executive function abilities strongly predicted conversion to AD.

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PubMed2006

Olfactory dysfunction as a predictor of neurodegenerative disease.

Olfactory dysfunction is present in patients diagnosed with Alzheimer's disease or idiopathic Parkinson's disease and can differentiate each of these disorders from related disorders with similar clinical presentations. The pathologic hallmarks of each disease are present in brain regions involved in processing olfactory input. Both the olfactory functional deficits and the corroborating pathologic lesions are present in asymptomatic subjects with increased risk of developing these diseases. Preclinical detection of neurodegenerative diseases is necessary to control their devastating effects on individuals and societies. We address whether olfactory dysfunction can be used to assess risk for developing Alzheimer's disease or Parkinson's disease in asymptomatic individuals. We argue that further characterization and a deeper understanding of olfactory deficits in these neurodegenerative diseases at the molecular, cellular, and systems levels will augment our acumen for preclinical detection and elucidate pathogenic mechanisms to guide the development of new therapeutic modalities.

Animals↗

PubMed2005

Predictive utility of apolipoprotein E genotype for Alzheimer disease in outpatients with mild cognitive impairment.

BACKGROUND: In cognitively impaired patients without dementia, the utility of apolipoprotein E (APOE) genotyping is unclear. OBJECTIVE: To evaluate the predictive utility of the APOE epsilon4 genotype for conversion to probable Alzheimer disease (AD). DESIGN: Naturalistic, longitudinal study. SETTING: Memory disorders outpatient clinic. PATIENTS: A total of 136 patients with memory complaints were determined to have mild cognitive impairment and were evaluated every 6 months. Fifty-seven age- and sex-matched healthy controls were evaluated annually. MAIN OUTCOME MEASURES: Primary outcome measures included conversion to AD. Secondary outcome measures included change over time in Mini-Mental State Examination (MMSE) score and Selective Reminding Test (SRT) delayed recall score. RESULTS: The APOE epsilon4 allele was present in 25% of patients and 21% of healthy controls. During a mean +/- SD follow-up of 35.2 +/- 24.3 months, 35 of 136 patients converted to AD. APOE epsilon4 carrier status did not differ between converters (31%) and nonconverters to AD (23%, P = .3) and did not affect the time trend in MMSE or SRT scores in the entire sample. Four of 5 APOE epsilon4 homozygotes converted to AD compared with 7 of 29 heterozygotes (P = .02). In a Cox proportional hazards model stratified by age quartiles, after controlling for sex, education, MMSE score, and SRT delayed recall score, APOE epsilon4 increased the risk of AD in patients 70 to 85 years old (n = 57; risk ratio, 2.77; 95% confidence interval, 1.1-7.3; P = .03) but not in patients 55 to 69 years old (n = 79; P = .7). CONCLUSIONS: APOE epsilon4 carrier status was associated with conversion to AD in older outpatients after controlling for known demographic and clinical risk factors, and APOE epsilon4 homozygosity was associated with increased risk of conversion to AD. However, APOE epsilon4 carrier status by itself did not predict cognitive decline or conversion to AD, indicating that APOE genotyping in patients with mild cognitive impairment may have limited clinical applicability for prediction of outcome.

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PubMed2005

A 10-item smell identification scale related to risk for Alzheimer's disease.

University of Pennsylvania Smell Identification Test data from control subjects (n = 63), patients with mild cognitive impairment (n = 147), and patients with Alzheimer's disease (n = 100) were analyzed to derive an optimal subset of items related to risk for Alzheimer's disease (ie, healthy through mild cognitive impairment to early and moderate disease stages). The derived 10-item scale performed comparably with the University of Pennsylvania Smell Identification Test in classifying subjects, and it strongly predicted conversion to Alzheimer's disease on follow-up evaluation in patients with mild cognitive impairment. Independent replication is needed to validate these findings.

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PubMed2005

Randomized, double-blind, placebo-controlled trial of fluoxetine treatment for elderly patients with dysthymic disorder.

OBJECTIVE: The authors compared the efficacy and side effects of fluoxetine and placebo in elderly outpatients with dysthymic disorder. METHODS: Patients were randomly assigned to fluoxetine (20 mg-60 mg/day) or placebo for 12 weeks in a double-blind trial. RESULTS: Of 90 randomized patients, 71 completed the trial. In the intent-to-treat sample, random regression analyses of the Hamilton Rating Scale for Depression (Ham-D; 24-item) and Cornell Dysthymia Rating Scale (CDRS) scores at each visit produced significant time x treatment group interactions favoring the fluoxetine group. Analysis of percentage change in Ham-D scores yielded no effect for treatment group, but a similar analysis of percentage change in CDRS scores yielded a main effect for treatment group, favoring fluoxetine over placebo. In the intent-to-treat sample, response rates were 27.3% for fluoxetine and 19.6% for placebo. In the completer sample, response rates were 37.5% for fluoxetine and 23.1% for placebo. CONCLUSION: Fluoxetine had limited efficacy in elderly dysthymic patients. The clinical features of elderly dysthymic patients are typically distinct from those of dysthymic disorder in young adults, and the findings suggest that treatments effective for young adult dysthymic patients may not be as useful in elderly dysthymic patients. Further research is needed to identify efficacious treatments for elderly patients with dysthymic disorder, and investigative tools such as electronic/computerized brain scans and neuropsychological testing may help identify the factors that moderate antidepressant treatment response and resistance.

Age Factors↗

PubMed2005

Homocysteine levels, MTHFR C677T genotype, and MRI Hyperintensities in late-onset major depressive disorder.

OBJECTIVE: Epidemiological studies suggest that elevated plasma homocysteine is associated with an increased risk of depression and cerebrovascular disease. There are no published reports of homocysteine levels and methylenetetrahydrofolate reductase (MTHFR) C677T genotype in clinical samples of patients with late-onset major depressive disorder (MDD). The purpose of this study was to examine the association of homocysteine levels or MTHFR C677T genotype and late-onset MDD and assess whether this may be affected by brain magnetic resonance imaging (MRI) hyperintensities. METHODS: Authors recruited 39 elderly patients with MDD with first episode occurring after age 50 and 20 comparison subjects and assessed total plasma homocysteine levels, MTHFR genotype, and brain MRIs. RESULTS: Plasma total homocysteine levels were higher in elderly patients with late-onset MDD versus comparison subjects. The association did not change after controlling for MRI hyperintensities, and the distribution of MTHFR C677T genotype was not different between the groups. CONCLUSIONS: In this exploratory study, elevated homocysteine levels were associated with late-onset MDD, and the association did not appear to be mediated by vascular pathology as identified by brain MRI hyperintensities.

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PubMed2004

Late onset dysthymic disorder and major depression differ from early onset dysthymic disorder and major depression in elderly outpatients.

BACKGROUND: Age of onset may affect clinical features and prognosis in elderly patients with major depression (MDD), but there is a lack of such data in elderly patients with dysthymic disorder (DD) and systematic comparisons of late onset MDD and DD have not been conducted. METHODS: In a Late Life Depression Clinic, patients > or = 60 years old who met DSM-III-R or DSM-IV criteria for MDD or DD were studied. The 24-item Hamilton Rating Scale for Depression (HRSD) and SCID-P were completed, family history was obtained, and medical illnesses were assessed. RESULTS: In the total sample (n=370; 211 MDD and 159 DD), compared to early onset patients, late onset (onset > or =60 years) patients had a higher rate of cardiovascular disease (chi(2)=4.12, df=1, P<0.05), lower rate of anxiety disorder (chi(2)=4.19, df=1, P<0.05), and a lower rate of family history of affective disorder (chi(2)=9.37, df=1, P<0.002). Late onset DD patients were more likely to have cardiovascular disease than early onset DD patients (chi(2)=5.63, df=1, P<0.02), but the rate of cardiovascular disease did not differ between late and early onset MDD patients (chi(2)=0.35, df=1, P<0.6). Late onset MDD patients were less likely to have a family history of affective disorder than early onset MDD patients (chi(2)=10.71, df=1, P<0.001). Prevalence of anxiety disorders did not differ between the early and late onset MDD patients (chi(2)=0.07, df=1, P<0.79), but was more common in the early onset DD compared to the late onset DD patients (17.98% versus 4.29%, chi(2)=6.98, df=1, P<0.01). Late onset DD did not differ from late onset MDD in the rates of cardiovascular disease, anxiety disorders, and family history of affective disorder. Excluding patients with double depression (n=32) did not alter the cardiovascular or family history findings, but the difference in anxiety disorders between early and late onset DD patients was no longer significant. LIMITATIONS: Academic clinic sample results may not generalize to community populations. CONCLUSIONS: In the elderly, late-onset DD is typically different from early onset DD. Cerebrovascular disease appears to play a role in the etiology of late onset DD. The similarities between late onset DD and late onset MDD suggest a single condition along a continuum.

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PubMed2004

A comparison of family history of psychiatric disorders among patients with early- and late-onset Alzheimer's disease.

OBJECTIVE: Both early-onset Alzheimer's Disease (EOAD) and late-onset Alzheimer's Disease (LOAD) present with cognitive and psychiatric features. Some studies suggest that EOAD patients are more likely than LOAD patients to have psychiatric symptoms. If this is true, relatives of EOAD patients with a similar clinical presentation may be more likely to be misclassified as having a primary noncognitive psychiatric disorder rather than a dementing disorder. Family history studies may underestimate familial aggregation of EOAD. METHODS: The authors compared the presence of psychiatric symptoms in parents and siblings of 131 EOAD patients (diagnosed at or before age 60), with the parents and siblings of 131 LOAD patients (diagnosed at or after age 65). Early onset Alzheimer's Disease and LOAD patients were matched for diagnosis (probable versus possible AD), gender, and ethnic group. Logistic regression analysis was performed on the outcome variable of patient group (EOAD, LOAD) with family history of psychiatric symptoms as the risk factor, adjusting for family size and patient's education. RESULTS: There was a nearly two and one-half-fold increase in family history of psychiatric symptoms among EOAD patients when compared with LOAD patients (RR = 2.4; 95% C.I. 1.2-4.7). CONCLUSIONS: The authors found preliminary evidence of a higher prevalence of a history of psychiatric symptoms among relatives of EOAD patients when compared to LOAD patients. This may be due to differential misclassification of AD, a syndromic disorder with both noncognitive psychiatric and cognitive deficits in relatives of EOAD patients. Alternatively, shared genetic or other familial etiologies may underlie subtypes of EOAD and some psychiatric disorders.

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PubMed2004

An open treatment trial of venlafaxine for elderly patients with dysthymic disorder.

Treatment response and side effects of venlafaxine were evaluated in an open-label trial of elderly outpatients with dysthymic disorder (DD). Patients received flexible dose (up to 300 mg/d) venlafaxine (Effexor XR) for 12 weeks. Of 23 study patients, 18 completed the trial. Fourteen (60.9%) were responders in intent-to-treat analyses with the last observation carried forward, and 77.8% were responders in completer analyses. Nearly half the sample (47.8%) met criteria for remission. In the intent-to-treat sample, increased severity of depression at baseline was associated with superior response, and the presence of cardiovascular disease was associated with poorer response. Venlafaxine open-label treatment was associated with fairly high response rates and generally good tolerability in elderly patients with DD. These results indicate that in elderly patients with DD, placebo-controlled trials of a dual reuptake inhibitor such as venlafaxine would be needed to assess its efficacy or to compare its efficacy to that of other antidepressants.

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PubMed2003

Depression and Bipolar Support Alliance consensus statement on the unmet needs in diagnosis and treatment of mood disorders in late life.

OBJECTIVES: To review progress made during the past decade in late-life mood disorders and to identify areas of unmet need in health care delivery and research. PARTICIPANTS: The Consensus Development Panel consisted of experts in late-life mood disorders, geriatrics, primary care, mental health and aging policy research, and advocacy. EVIDENCE: (1) Literature reviews addressing risk factors, prevention, diagnosis, treatment, and delivery of services and (2) opinions and experiences of primary care and mental health care providers, policy analysts, and advocates. CONSENSUS PROCESS: The Consensus Development Panel listened to presentations and participated in discussions. Workgroups considered the evidence and prepared preliminary statements. Workgroup leaders presented drafts for discussion by the Consensus Development Panel. The final document was reviewed and edited to incorporate input from the entire Consensus Development Panel. CONCLUSIONS: Despite the availability of safe and efficacious treatments, mood disorders remain a significant health care issue for the elderly and are associated with disability, functional decline, diminished quality of life, mortality from comorbid medical conditions or suicide, demands on caregivers, and increased service utilization. Discriminatory coverage and reimbursement policies for mental health care are a challenge for the elderly, especially those with modest incomes, and for clinicians. Minorities are particularly underserved. Access to mental health care services for most elderly individuals is inadequate, and coordination of services is lacking. There is an immediate need for collaboration among patients, families, researchers, clinicians, governmental agencies, and third-party payers to improve diagnosis, treatment, and delivery of services for elderly persons with mood disorders.

Age Factors↗

PubMed2003

Sertraline treatment of elderly patients with depression and cognitive impairment.

BACKGROUND: There is little information on the efficacy and side effects of antidepressant treatment in elderly patients with combined depression and cognitive impairment without dementia (DEP-MCI), and it is unclear if cognitive performance improves with antidepressant response in these patients. METHODS: In 39 elderly DEP-MCI patients, changes in depression and cognitive impairment were evaluated with open sertraline treatment up to 200 mg/day for 12 weeks. RESULTS: Of the 26 completers, 17 were responders and nine were non-responders. Diagnostic subtype of depression was unrelated to response. ANCOVA on WAIS-R digit symbol percent change scores revealed a significant effect for responder status (F = 5.59, p < 0.03), and age (F = 0.24, p < 0.64) and education (F = 1.64, p < 0.22) were not significant covariates. From pre-trial to post-trial, responders improved in WAIS-R digit symbol percent change scores (Mean -10% SD 24) while non-responders declined (Mean 14% SD 18; t = 2.60, p < 0.02). Other neuropsychological measures were unrelated to response. Percent change in HRSD scores showed significant inverse correlations with percent change in several cognitive measures. CONCLUSIONS: DEP-MCI patients showed moderate clinical response to sertraline treatment. When responders were compared to non-responders, cognitive improvement was limited to one measure of attention and executive function. Overall, there was little cognitive improvement with antidepressant treatment. The findings indirectly suggest that lack of improvement in cognition following treatment of depression in DEP-MCI patients may be associated with increased risk of meeting diagnostic criteria for dementia during follow-up.

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PubMed2003

Psychopathological features in Alzheimer's disease: course and relationship with cognitive status.

OBJECTIVES: To examine the course, clinical correlates, and relationship between cognitive status and psychopathological features in patients with probable Alzheimer's disease (AD) followed over a 5-year period. DESIGN: Cohort study with follow-up of 5 years. SETTING: Patients were recruited at three sites: 91 patients at Columbia Medical Center, 84 at Johns Hopkins School of Medicine, and 61 at Massachusetts General Hospital. PARTICIPANTS: Patients diagnosed with probable AD (n = 236) enrolled in a longitudinal study (Predictors study). MEASUREMENTS: Wandering/agitation, physical aggression, hallucinations, and delusions were evaluated at 6-month intervals using the Columbia Scale for Psychopathology in Alzheimer's Disease. Descriptive analyses were used to provide estimates of prevalence and course of psychopathological features. General estimating equations determined the odds of having any of the four psychopathological behaviors as a function of cognitive status. Markov analyses provided 6-month transition probabilities for psychopathological behaviors given patients' cognitive status and the presence or absence of such behaviors in the previous evaluation. RESULTS: For wandering/agitation, prevalence (39-57%) and persistence increased as a function of time and decrement in cognitive status. Physical aggression was less prevalent (6-22%) and increased as a function of cognitive decline but tended to persist only in the more severely impaired patients. Delusions (34-49%) reached a peak at the second year and then declined. The odds of delusions were maximal with intermediate decline but remained persistent regardless of cognitive status. Hallucinations, despite some fluctuations, were relatively stable during the follow-up period (8-17%) and moderately persistent. CONCLUSION: Psychopathological features, particularly wandering/agitation and delusions, in AD were common throughout the disease course. The natural history and persistence of the four psychopathological features varied. These findings provide important information to clinicians and caregivers regarding the course, predictability, and possible treatment of psychopathological behaviors in patients with probable AD.

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PubMed2003

Gabapentin in geriatric mania.

There is little available information on anticonvulsant treatment of mania in elderly patients. Seven elderly patients, each in a manic episode, were treated with gabapentin. All 7 patients experienced improvement in manic symptoms, with minimal to no side effects. They received gabapentin in combination with antipsychotic medications, and in 1 case in combination with valproate. Gabapentin appears to be a safe and effective treatment in geriatric mania when combined with antipsychotic medications or valproate. Gabapentin appears to be well tolerated with no major adverse drug interactions or side effects in elderly manic patients. This case series suggests that controlled studies are warranted to examine gabapentin's efficacy and side effects, particularly as an adjunctive medication, in geriatric mania.

Acetates↗

PubMed2003

Pica in the geriatric mentally ill: unrelenting and potentially fatal.

Pica has rarely been reported in patients with geriatric mental illness. The authors describe 3 male patients with pica in the geriatric unit of a state mental hospital. Two of these patients had a diagnosis of developmental delay with concomitant diagnoses of schizophrenia and schizoaffective disorder, respectively. The third patient was diagnosed with paranoid schizophrenia. In all 3 cases, pica started late in life and was unrelenting and unresponsive to psychotropic medications, with limited to no response to behavioral interventions. In the 2 patients who died, pica was implicated as the direct cause of death in 1 and the likely cause of death in the other. When pica occurs in elderly patients with mental illness, the risk of mortality should be taken into account in clinical management.

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PubMed2002

Comorbid psychiatric disorders in late life depression.

In late life depression, common comorbid psychiatric disorders are alcohol use, anxiety, and personality disorders. Elderly depressed patients are three to four times more likely to have an alcohol use disorder compared with nondepressed elderly subjects, with a prevalence of 15%-30% in patients with late life major depression. While the presence of a comorbid alcohol use disorder may worsen the prognosis for geriatric depression, limited data suggest that successful treatment of depression combined with reducing alcohol use leads to the best possible outcomes. Most studies show that the overall prevalence of anxiety disorders, particularly panic disorder and obsessive-compulsive disorder, is low in geriatric depression, but generalized anxiety disorder may not be uncommon. It remains unclear if the presence of a comorbid anxiety disorder impacts on the treatment and prognosis of late life major depression. Personality disorders occur in 10%-30% of patients with late life major depression or dysthymic disorder, particularly in patients with early onset depressive illness. Cluster C disorders, including the avoidant, dependent, and obsessive-compulsive subtypes predominate, while Cluster B diagnoses, including borderline, narcissistic, histrionic and antisocial, are rare. Overall, the research database on comorbid psychiatric disorders in major and nonmajor late life depression is relatively sparse. Since comorbid psychiatric disorders affect clinical course and prognosis, and may worsen long-term disability in late life depression, considerably more research in this field is needed.

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PubMed2002

Assessment of late life depression.

This article focuses on diagnostic and nosologic challenges intrinsic to geriatric depression, including characteristics interfering with symptom and syndrome ascertainment, the impact of medical and cognitive disorders, the usefulness of screening instruments, and barriers imposed by treatment settings. The article also identifies gaps in existing knowledge and outlines a research agenda. Nosologic characterization of depressives syndromes contributed by specific medical disorders may lead to effective strategies for prevention and treatment of depression. Studies need to examine whether treatment of depression can improve the outcome of medical illnesses requiring active patient involvement in treatment. Considering disability a distinct aspect of health status may add an important dimension to the assessment of depression and result in complementary interventions aimed at depression and disability concurrently. The provisional criteria for depression of Alzheimer's disease, if validated, may facilitate treatment research. Studies need to characterize cognitive dysfunctions associated with later development of dementia or poor treatment response in patients with depression. Care managers working together with primary care physicians can improve the recognition and treatment of depressed elderly patients by obtaining the training in using validated instruments and treatment algorithms.

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PubMed2002

Association between the APOE genotype and psychopathologic symptoms in Alzheimer's disease.

BACKGROUND: Psychiatric symptoms occur frequently in the course of AD, are a frequent contributor to institutionalization, predict cognitive decline and death, and often require treatment with psychotropic medications. Previous studies investigating the association between APOE genotype and psychiatric symptomatology in AD have reported contradictory results. OBJECTIVE: To determine whether APOE genotype predicts incident psychiatric symptomatology in patients with AD. METHODS: Eighty-seven patients with AD at early stages and no psychiatric history were followed semiannually for up to 9.3 years (mean 5.5 years) for development of delusions, illusions, hallucinations, behavioral symptoms, and depression. Cox proportional hazards models were used to examine the relative risk for incident psychiatric symptomatology (outcome) in relation to APOE genotype (predictor). RESULTS: The presence of one epsilon4 allele carried a 2.5-fold risk, whereas the presence of two epsilon4 alleles carried a 5.6-fold risk for development of delusions. The associations remained significant even when age, ethnicity, sex, education, duration of disease, and cognitive and functional performance were controlled for. The presence of two epsilon4 alleles was associated with reduced risk for developing hallucinations in the adjusted analysis only. No significant associations were detected between APOE genotype and the incidence of illusions, behavioral symptoms, or depression. CONCLUSION: The presence of one or more epsilon4 alleles is a significant predictor for the incidence of delusions in the course of AD.

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PubMed2002

Functional deficits in patients with mild cognitive impairment: prediction of AD.

OBJECTIVE: To evaluate the predictive utility of self-reported and informant-reported functional deficits in patients with mild cognitive impairment (MCI) for the follow-up diagnosis of probable AD. METHODS: The Pfeffer Functional Activities Questionnaire (FAQ) and Lawton Instrumental Activities of Daily Living (IADL) Scale were administered at baseline. Patients were followed at 6-month intervals, and matched normal control subjects (NC) were followed annually. RESULTS: Self-reported deficits were higher for patients with MCI than for NC. At baseline, self- and informant-reported functional deficits were significantly greater for patients who converted to AD on follow-up evaluation than for patients who did not convert, even after controlling for age, education, and modified Mini-Mental State Examination scores. While converters showed significantly more informant- than self-reported deficits at baseline, nonconverters showed the reverse pattern. Survival analyses further revealed that informant-reported deficits (but not self-reported deficits) and a discrepancy score indicating greater informant- than self-reported functional deficits significantly predicted the development of AD. The discrepancy index showed high specificity and sensitivity for progression to AD within 2 years. CONCLUSIONS: These findings indicate that in patients with MCI, the patient's lack of awareness of functional deficits identified by informants strongly predicts a future diagnosis of AD. If replicated, these findings suggest that clinicians evaluating MCI patients should obtain both self-reports and informant reports of functional deficits to help in prediction of long-term outcome.

Activities of Daily Living↗