Changes in cognitive functioning following treatment of late-life depression

OBJECTIVE: Knowledge of the relationship between various clinical characteristics and cognitive functioning is advancing, but little is known about the cognitive response to treatment for geriatric depression. The purpose of this study was to examine the cognitive response to treatment for patients with late-life depression. METHOD: Subjects included 45 nondemented, elderly depressed patients who achieved remission after 12 weeks of antidepressant treatment and 20 elderly comparison subjects. All subjects were administered a battery of clinical measures, including cognitive screening instruments, before and after treatment. RESULTS: As a group, the elderly depressed patients showed a small improvement in overall cognitive functioning after treatment. Among depressed patients with concomitant cognitive impairment at baseline, performance on the Mattis Dementia Rating Scale domains of conceptualization and initiation/perseveration improved significantly relative to those of depressed patients with normal cognition. Despite the improvement following treatment, the overall level of cognitive functioning in the elderly depressed patients with cognitive impairment at baseline remained mildly impaired, especially in the memory and initiation/perseveration domains. CONCLUSIONS: Elderly depressed patients with cognitive impairment may experience improvement in specific domains following antidepressant treatment but may not necessarily reach normal levels of performance, particularly in memory and executive functions. This subgroup of late-life depression patients is likely at high risk of developing progressive dementia.     

Executive deficits in elderly patients with major unipolar depression

Several studies have evaluated executive function in depressed patients, and the results vary from significant impairment relative to controls to virtually intact performances. To better comprehend executive impairment in elderly patients with major unipolar depression, the performance of 21 elderly depressed patients was compared with that of 19 elderly normal controls on executive tasks. The relationships between memory deficits and depression severity and between memory deficits and executive dysfunction were also examined. Depressed patients' performance was significantly worse than that of controls on almost all executive tasks. Their score for logical memory was significantly correlated with that for several executive tasks. Executive performance was also correlated with depression severity. Unipolar depressed patients present executive deficits. Memory failure in these patients may reflect impairment in retrieval processes, which in turn depends on executive function. Executive deficits are associated with depression severity. These results may be useful in the differential diagnosis between depression and early Alzheimer's disease.     

Age at initial onset of depression and waking EEG variables in the elderly

Depressive illness with initial onset after age 60 has different clinical and prognostic features compared to depression beginning at a younger age. We evaluated waking electroencephalograms (EEGs) in 61 elderly depressed patients (32 early onset, 29 late onset) without cognitive impairment and not receiving psychotropic medications. The groups were comparable for age, severity of Hamilton depression score, education, and Folstein Mini-Mental State scores. Conventional visual EEG analysis revealed no significant differences in the mean alpha rhythm, incidence of abnormal records, or types of EEG abnormalities. Computerized spectral EEG analysis was also performed in 48 patients (23 early onset, 25 late onset). There were no significant differences in the pooled parasagittal mean frequency, theta--beta difference, combined delta and theta percentage, or relative power of the frequency bands. Thus, waking EEGs do not differentiate between elderly patients with the initial onset of the depression before or after age 60.     

Greater depression severity associated with less improvement in depression-associated cognitive deficits in older subjects.

OBJECTIVES: Elderly depressed patients often exhibit cognitive deficits, which may improve with drug therapy. The authors investigated the relationship of baseline depression severity and cognitive improvement with antidepressant treatment in depressed patients with mild cognitive impairment. METHODS: Mini-Mental State Exam (MMSE) and Montgomery-Asberg Depression Rating Scale (MADRS) scores were measured in 52 depressed geriatric patients without dementia at baseline, 6, and 12 months, during an intent-to-treat period. A repeated-measures regression model tested the effect of MADRS score on MMSE. RESULTS: MMSE changes were significant and linear over time, with an average increase of 0.72 in the MMSE per 6-month interval. The final model showed that for every point increase in baseline MADRS, the average 6-month increase in MMSE decreased by 0.12. Repeated MADRS measurements did not significantly alter its predictive value. CONCLUSION: Greater baseline depression severity in older subjects with mild cognitive deficits is associated with less improvement in those deficits even with successful antidepressant therapy.     

Late-onset depression with mild cognitive deficits: electrophysiological evidences for a preclinical dementia syndrome

Mild cognitive impairment (MCI) is present in up to 60% of patients with late-onset depression and constitutes a major diagnostic problem in geriatric psychiatry. Searching for sensitive markers for the detection of early brain changes suggestive of dementia, we compared this depressive risk population with mildly to moderately demented patients and cognitively unimpaired depressed patients using EEG power and coherence. We found a considerable similarity between Alzheimer's disease patients and cognitively impaired depressed patients regarding the cognitive profile and EEG pattern. Changes in EEG power and coherence at frontotemporal leads in depressive patients with MCI thereby allowed discrimination from cognitively unimpaired patients with a sensitivity of 88% and a specifity of 81%.     

EEG findings in depressive pseudodementia and dementia with secondary depression

We report EEG findings in 33 elderly patients with mixed symptoms of depression and dementia, followed longitudinally to confirm diagnosis. Two groups of patients, dementia with depressive features (mixed-DEM, group I, n = 23) and patients with depressive pseudodementia (mixed-DEP, group II, n = 10), were defined. In addition, we also included, for comparison purposes, 35 patients with probable AD without depressive features (group III), 23 patients with major depression without cognitive impairment (group IV), and 61 healthy elderly controls (group V). We found significant group differences on waking EEGs between those mixed patients who did well after treatment for depression (depressive pseudodementia) compared to patients having dementia with secondary depression. The differences paralleled those between the 'pure' groups of demented and depressed patients. In patients with either depression or depressive pseudodementia, the EEG was usually normal or showed only mild abnormalities. In contrast, the majority of patients with either dementia or dementia with secondary depression had abnormal EEGs, with approximately one-third having moderate (or severe) abnormalities. Although the EEG was usually normal or only mildly abnormal in patients with pseudodementia or depression, these groups (II and IV) did show a significant slowing of the dominant posterior rhythm compared to controls. They also had a higher percentage of generalized abnormal EEGs than controls and this difference was significant between group IV (depression) and controls.     

Correlation between cortical theta activity and hippocampal volumes in health, mild cognitive impairment, and mild dementia.

Cognitive decline is known to be associated with both increased theta power over frontal regions and hippocampal atrophy. The aim of this study was to reveal the relation between these parameters in groups with mild dementia, mild cognitive impairment, and healthy control subjects. The authors examined a preliminary randomly selected sample of 39 right-handed subjects joining the Leipzig Longitudinal Study of the Aged, consisting of 17 normal elderly subjects, 12 patients with mild cognitive impairment, and 10 patients with mild dementia assessed by Clinical Dementia Rating. All subjects were between 75 and 85 years old (mean age, 78 years; standard deviation, 2.78 years) and underwent EEG and brain MRI. Mean spectral power densities were calculated, and hippocampal body volume was measured. Significant negative linear correlations between theta power over frontal regions and hippocampal volumes were found. The results support the assumption about a relationship between hippocampal atrophy and theta power, and may be helpful for a better understanding of the course of Alzheimer's disease.     

Depression and cognition in older adults

PURPOSE OF REVIEW: Recognition that depression is associated with neurocognitive impairment and renewed recent interest in milder forms of cognitive impairment in older people (typified by the concept of mild cognitive impairment) have stimulated researchers to investigate the relationship between depression and cognitive impairment. This review identifies and clarifies recent progress in this rapidly developing research area. RECENT FINDINGS: Neurocognitive impairment persists in most depressed older people after clinical recovery, and slowed information processing speed and possibly executive dysfunction and vascular risk factors underlie this. Most studies suggest that this neurocognitive impairment in turn leads to increased mild cognitive impairment as well as dementia. White matter disease appears to directly contribute to depression in older people and this worsens over time. Polymorphisms in the serotonin transporter gene may be a key risk factor as well, and depression worsens vascular outcome in peripheral arterial disease. SUMMARY: Clinicians should be aware that neurocognitive deficits persist and have an adverse effect on outcome, and that vascular risk factors may contribute to these deficits.     

老年抑郁症患者抗抑郁药治疗期间认知与抑郁症状的变化及其与ApoEε4等位基因的关系

Background

Co-occurring cognitive impairment in geriatric depression may not improve with antidepressant treatment and it may progress to dementia.

Aim

Assess the relationship between changes in cognitive and depressive symptoms among patients with geriatric depression and their association with the APOE epsilon 4 allele before and after antidepressant treatment.

Methods

The presence of the APOE epsilon 4 allele was assessed in 64 incident cases of geriatric depression and 31 elderly individuals without depression and the Geriatric Depression Scale (GDS), Mini-Mental State Examination (MMSE), digit span test, and Trail Making Tests A and B (TMT-A, TMT-B) were administered to these subjects at baseline and 12 months after baseline, during which time the depressed group received standardized treatment with selective serotonin reuptake inhibitors (SSRIs).

Results

Prior to treatment patients with geriatric depression had significantly worse cognitive functioning than control subjects and 31 (48%) met criteria for mild cognitive impairment (MCI). After treatment depressed patients with and without comorbid MCI both had significant improvements in their depressive and cognitive symptoms, but those with MCI had more residual symptoms. The severity of cognitive symptoms was not associated with the severity of depressive symptoms at baseline, but they were positively correlated at the 12-month follow-up. The APOE epsilon 4 allele was identified in 14% (9/64) of the patients and in 3% (1/31) of the controls (Fisher''s Exact Test, p=0.158). Compared to depressed patients without the allele, depressed patients with the allele had more severe cognitive deficits both before and after treatment, though only some of these differences were statistically significant.

Conclusions

There is substantial cognitive impairment in elderly individuals with geriatric depression. Both the depressive and cognitive symptoms improve with standard SSRI treatment, but individuals with comorbid MCI have more residual depressive and cognitive symptoms after treatment. The APOE epsilon 4 allele is associated with greater cognitive impairment in geriatric depressed patients and may be associated with less responsiveness of cognitive symptoms to antidepressant treatment.     

Cognitive disturbance in outpatient depressed younger adults: evidence of modest impairment.

BACKGROUND: Investigations of cognitive disturbances among patients with mood disorders have yielded inconsistent results. Although marked neuropsychologic deficits have been reported in elderly patients and in midlife patients with severe depression, the severity of cognitive impairments in medically healthy younger ambulatory adults with depression has not been well characterized. METHODS: A comprehensive battery of standard neuropsychologic tests and experimental computerized measures of cognitive functioning were administered to unmedicated ambulatory younger adults with mild to moderate nonbipolar depression and to a group of age- and gender-equated healthy subjects. RESULTS: Patients demonstrated a notable absence of widespread cognitive impairment. Deficits in executive functions were observed on the Wisconsin Card Sort Test but not on several other tests. Despite the absence of significant impairment on tests of attention, memory, and motor performance in the total sample, symptom severity and age of illness onset were correlated with poorer performance on some tests of cognitive functioning even after correction for age. CONCLUSIONS: These findings, derived from a large sample of unmedicated depressed outpatients, indicate that major depressive disorder in healthy younger ambulatory adults does not cause appreciable impairments in cognitive functioning in the absence of clinical and course-of-illness features.     

Cognitive and demographic determinants of dementia in depressed patients with subjective memory complaints

BACKGROUND: Previous studies showed that late-life depression with subjective memory complaints (SMC) may be associated with an increased risk of developing dementia. However, not all such patients have cognitive decline. The aim of this longitudinal study was to identify possible clinical determinants of progressive deterioration in depressed elderly patients with SMC. METHOD: Forty-one consecutive patients referred to a memory clinic because of persistent SMC were investigated and received an ICD-10 diagnosis of mild to moderate depression. Over a mean follow-up period of 15 months, 9 of them (22%) developed dementia. Statistical analysis included Mann-Whitney U and Fisher's exact tests as well as univariate and multivariate logistic regression analyses to assess the relationship between cognitive decline and clinical, demographical and neuropsychological characteristics at baseline. RESULTS: Age at baseline was associated with subsequent dementia, and performance on immediate verbal prose recall and a visual organization test at the initial assessment were worse in those who showed cognitive decline. In a multivariate model, age and immediate recall predicted 32.7% of the cognitive variability, with an additional 2.4% when a visual organization test was added. There was no correlation between cognitive performance and severity of depression at baseline. The study was limited by a small sample size, the nondistinction of depressive subtypes and the absence of a formal neuropsychological assessment on follow-up. CONCLUSION: Impairment of the executive component of working memory as well as limited access to visual knowledge may predict cognitive deterioration in depressed patients with subjective memory complaints.     

Neurocognitive profiles in elderly patients with frontotemporal degeneration or major depressive disorder.

Major depressive disorder (MDD) and frontotemporal dementia (FTD) are both disorders in elderly populations that involve the prefrontal cortex and appear to have similar neurocognitive deficits. This review examined whether there are testable deficits in cognition that are consistent across individuals within the same neuropathological condition that could be used to facilitate early diagnoses. Medline and PsychInfo databases were searched for cognitive studies of depressed and FTD patients that used a matched control group and reported findings with means and standard deviations (N = 312). Effect sizes for FTD patients with mild and moderately advanced disease were compared to effect sizes within subgroups of depressed patients, such as inpatients, outpatients and community volunteers. Moderately advanced FTD patients were more impaired than depressed patients over all domains, particularly in language ability, although depressed inpatients appeared similar to FTD patients in some domains. Effect sizes for FTD patients who were in the mild, or early, stage of the disease (MMSE = 28) were similar to those of depressed outpatients but slightly worse than those of community volunteers in all domains except semantic memory and executive ability. In the latter two domains, even mild FTD patients had notably large deficits. All FTD patients showed more severe deficits in some domains relative to other domains. In contrast, depressed patients tended to vary by clinical presentation or disease severity, but the magnitude of impairment for each subgroup remained relatively consistent across domains and they did not have the severe focal deficits in one or two domains demonstrated by FTD patients.     

La dépression vasculaire : évolution des malades et du concept

Late life depression differs from early life depression by no history of mood disorders, and by presence of vascular risk factors, cognitive decline and hyperintensities on MRI. A sub-type of depression is the vascular depression. We present a 6.2 years follow-up of five vascular depressed patients. The severity of depression was high with suicide attempt in three cases. Apathy and pharmacological resistance were reported. Non pharmacological management was more efficacious. Vascular dementia was the final diagnosis for three patients whose two had neuropathological diagnosis. It would be necessary to ameliorate the delimitation of the definition of vascular depression to distinguish them from mild cognitive impairment and from vascular dementia. The specificity of the treatment and the characteristics of the follow-up are arguments to realize a MRI when a patient has a late life depression.     

The diagnostic value of EEG in Alzheimer disease: correlation with the severity of mental impairment.

The aim of our study was to analyze EEG changes in patients with Alzheimer disease (AD) and to determine how closely EEG reflects the progression of mental impairment in people with AD. Ninety-five patients with probable AD according to National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association criteria treated in our Clinic for Memory Disorders were selected for this study. Patients were divided into three subgroups with mild, marked, and severe dementia according to the results of psychometric scales. The EEG findings were classified using an eight-degree scale according to the background activity, presence and amount of theta and delta waves, focal changes, lateralization of focal changes, synchronization, and presence of sharp and spike waves. A significant correlation between the degree of EEG abnormalities and cognitive impairment was found. We did not observe any correlation between the presence of delta waves and the results of neuropsychological tests. Our study revealed an important diagnostic value of EEG in the estimation of the severity of dementia parallel to psychometric scales.     

Impairment of neocortical metabolism predicts progression in Alzheimer's disease

Progression rates of Alzheimer's disease (AD) vary considerably, and they are particularly difficult to predict in patients with mild cognitive impairment. We performed a prospective multicenter cohort study in 186 patients with possible or probable AD, mostly with presenile onset. In a cross-sectional analysis at entry, impairment of glucose metabolism in temporoparietal or frontal association areas measured with positron emission tomography was significantly associated with dementia severity, clinical classification as possible versus probable AD, presence of multiple cognitive deficits and history of progression. A prospective longitudinal analysis showed a significant association between initial metabolic impairment and subsequent clinical deterioration. In patients with mild cognitive deficits at entry, the risk of deterioration was up to 4.7 times higher if the metabolism was severely impaired than with mild or absent metabolic impairment. Copyrightz1999S.KargerAG, Basel     

Neuropsychological profile of patients with Parkinson's disease without dementia

Cognitive deficits are often associated with Parkinson's disease (PD), although their prevalence in PD patients without dementia is still unknown. In order to describe the neuropsychological profile of PD patients without dementia, a sample of 103 PD patients was compared with a control group consisting of 38 healthy elderly subjects. Psychometric assessment consisted of the Mini Mental State Examination, the Dementia Rating Scale and a battery of neuropsychological tests. The Beck Depression Inventory was used to assess depression in PD patients. Dementia was diagnosed in 27 patients. Among non-demented subjects, 34 (45%) had no cognitive impairment and 42 (55%) had a mild cognitive impairment. Subjects with mild cognitive impairment were older, had a later onset of the disease, and more severe motor symptoms than cognitively intact subjects. Identification of mild cognitive impairment is important, since these symptoms are important for patient management and may also facilitate to determine prognosis.     

Dementia of depression in Parkinson's disease and stroke

Depression is a frequent finding in patients with neurological disorders. These depressions, however, have similar phenomenology, duration, biological markers, and response to treatment as depressions in patients with no known brain injuries (i.e., functional depression). In the present article, we review evidence that suggests the dementia of depression exists among severely depressed patients with cerebrovascular lesions or Parkinson's disease (PD). We conclude that: a) in patients with either stroke lesions or PD, depression is significantly associated with cognitive deficits; b) this association is only true for patients with major depression (i.e., it is not present in patients with minor depression); and c) patients with poststroke depression and patients with PD and depression have a severity and profile of cognitive deficits similar to those found in patients with primary major depression.     

Confrontation naming deficit in dementia of depression

Unlike patients with irreversible dementia, elderly depressed patients with cognitive impairment are thought to have relatively preserved recognition, memory, and language abilities. To test this hypothesis, the authors compared memory and naming performance in elderly hospitalized patients with major depression alone, reversible dementia of depression, or irreversible dementia. All patient groups performed worse than nondemented, nondepressed control subjects on memory tasks. Patients with dementia of depression performed worse than depressed patients with normal cognition on tests of free recall, delayed recall, and verbal delayed memory but not on tests of delayed visual memory. Patients with dementia of depression and patients with irreversible dementia were severely compromised in both speed and accuracy on the confrontation naming task.     

Depression in patients with mild cognitive impairment increases the risk of developing dementia of Alzheimer type: a prospective cohort study

BACKGROUND: Mild cognitive impairment has been regarded as a precursor to dementia of Alzheimer type, but not all patients with mild cognitive impairment develop dementia. OBJECTIVE: To determine whether depression may increase the risk of developing dementia. SETTING: The outpatient clinics of a community general hospital. DESIGN: Prospective cohort study. METHODS: A cohort of 114 patients with amnestic mild cognitive impairment was followed up for a mean period of 3 years. At baseline, the patients underwent memory tests, the Spanish version of the Mini-Mental State Examination, a verbal fluency test, the Geriatric Depression Scale, and the Clinical Dementia Rating Scale for staging purposes. Psychiatric examination for depression was based on structured interview and Diagnostic and Statistical Manual of Mental Disorder, Fourth Edition criteria. We also carried out either computed tomography or magnetic resonance imaging of the brain. MAIN OUTCOME MEASURES: We carried out periodic evaluations based on the Mini-Mental State Examination, verbal fluency test, Geriatric Depression Scale, Blessed Dementia Rating Scale, and Clinical Dementia Rating Scale. The end point was the development of probable Alzheimer disease according to the criteria of the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association. RESULTS: Depression was observed in 41 patients (36%) at baseline. After a mean period of 3 years, 59 patients (51.7%) developed dementia of Alzheimer type, and 6 died. Of the depressed patients, 35 (85%) developed dementia in comparison with 24 (32%) of the nondepressed patients (relative risk, 2.6; 95% confidence interval, 1.8-3.6). The survival analysis also showed that depressed patients developed dementia earlier than the nondepressed. Most patients with depression at baseline exhibited a poor response to antidepressants. CONCLUSIONS: We conclude that patients with mild cognitive impairment and depression are at more than twice the risk of developing dementia of Alzheimer type as those without depression. Patients with a poor response to antidepressants are at an especially increased risk of developing dementia.     

Quantitative measurement of delta activity in Alzheimer's disease

Quantitative measurements of delta activity were made in 10 healthy elderly controls and 31 subjects with Alzheimer's disease. Delta activity did not discriminate between the healthy elderly controls and the early mild Alzheimer's disease subjects. However, delta activity was a significantly greater percentage of total EEG power in the moderate-to-advanced Alzheimer's subjects when compared to either the healthy controls or mild Alzheimer subjects. In the T3 and T4 electrodes, delta activity in the moderate-to-advanced Alzheimer subjects was 78.3% and 47.6% higher, respectively, than in control subjects. Furthermore, delta activity was an excellent predictor of dementia severity within the 31 subjects with Alzheimer's disease.