EEG sleep in elderly depressed, demented, and healthy subjects

In a prospective study of EEG sleep patterns in 25 elderly depressives, 25 elderly demented patients, and 25 healthy, elderly control subjects, the sleep of depressives was characterized by reduced REM sleep latency, increased REM percent and first REM period density, and altered temporal distribution of REM sleep, as well as by diminished sleep maintenance (correlated significantly with Hamilton ratings of depression: multiple R = -0.42, p less than 0.05). In contrast, the sleep of demented patients showed reduced REM sleep percent, but normal REM temporal distribution, increased loss of spindles and K-complexes (the latter correlating significantly with severity of cognitive impairment as measured by the Folstein score: multiple R = -0.59, p less than 0.01), and less severe sleep maintenance difficulty than for depressives. An examination of REM latency demonstrated a skewed distribution in depression (i.e., 42% of nights with sleep-onset REM periods), but a normal distribution in the controls and demented subjects. A REM latency cut-off score of 30 min correctly classified 68% of all patients (kappa = 0.36; p less than 0.005), compared with 78% correctly identified in our retrospective study (Reynolds et al. 1983).     

Dexamethasone suppression test in depression with reversible dementia

Depression with reversible dementia occurs frequently in the elderly and may be a diagnostic problem. The 1-mg dexamethasone suppression test (DST) was performed in 175 elderly psychiatric patients. Abnormal DSTs occurred in both patients with primary degenerative dementia (n = 43, 34.9%) and those with major depression without cognitive dysfunction (n = 59, 66.1%). This finding suggests the presence of common hypothalamic abnormalities in these two disorders. There was no difference in the incidence of abnormal DSTs among depressives with a reversible dementia (n = 28, 78.6%), cognitively intact depressives (n = 59, 66.2%), and depressives who also had primary degenerative dementia (n = 24, 70.8%). An abnormal DST is not clinically useful in predicting the outcome of dementia in depressed patients with cognitive dysfunction.     

Electroencephalographic sleep in depressive pseudodementia

Twenty-six patients with mixed symptoms of depression and cognitive impairment were studied with serial clinical ratings and sleep electroencephalograms during a one-night sleep-deprivation procedure. A subgroup of these patients with depressive pseudodementia (n = 8) had less severe symptoms of dementia at baseline and showed significant improvements in both Hamilton Depression Rating Scale scores and Profile of Mood States tension scores following sleep deprivation, while another subgroup of patients having primary degenerative dementia with depression (n = 18) showed no change or worsening in Hamilton depression and Profile of Mood States tension ratings. Baseline sleep measures demonstrated significantly higher rapid eye movement (REM) percent and phasic REM activity/intensity in pseudodemented compared with demented patients. While both groups had increases in sleep efficiency, sleep maintenance, and slow-wave sleep following sleep deprivation, recovery night 2 was characterized by greater first REM period duration in depressive pseudodementia than in dementia. These differences in REM sleep rebound (using an REM period 1 cutoff of greater than or equal to 25 minutes) permitted correct identification of 88.5% of patients. Implications of these data for current theories regarding sleep, aging, and psychopathology are discussed.     

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.     

Reliable discrimination of elderly depressed and demented patients by electroencephalographic sleep data

Using electroencephalographic sleep data from a sample of 235 elderly subjects, discriminant function analyses of sleep alterations in depression and dementia were performed. Overall, 80% of patients were correctly classified using a backward discriminant function analysis, and 81% with a general stepwise discriminant function analysis. Four measures contributed to the separation of depressed and demented patients: rapid eye movement (REM) sleep latency (lower in depressives); REM sleep percent (higher in depressives); indeterminate non-REM sleep percent (higher in demented patients, reflecting greater loss of spindles and K complexes); and early morning awakening (more marked in depressives). When both discriminant functions were subjected to cross-validation in independent subsamples, both procedures correctly identified 78% of patients. The classification functions derived from nondemented depressed and nondepressed demented patients were applied to a mixed-symptom group (n = 42). Overall, 27 patients (64%) with either depressive pseudodementia or dementia with depressive features were correctly classified using the same four predictor variables. These findings suggest that sleep physiological alterations of depression and dementia reflect between-group differences in sleep continuity, sleep architecture, and REM sleep temporal distribution, and that the differences are statistically reliable, in both diagnostically pure and mixed clinical presentations. These findings are discussed in the context of current hypotheses of sleep regulation and its mechanisms.     

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.     

Longitudinal follow-up of depressive symptoms among normal versus cognitively impaired elderly

OBJECTIVES: This prospectively designed longitudinal study assesses prevalence, incidence and prognosis of depressive symptoms among cognitively normal elderly volunteers compared with patients with mild cognitive impairment (MCI), dementia of Alzheimer type (DAT), and vascular dementia (VAD). Possible relationships between depressive symptoms, cognitive performance, disease types, and effects of antidepressant treatment were analyzed. METHODS: Two hundred and ninety four subjects exhibiting different levels of cognitive performance were admitted to this study. Demographics, cardiovascular and neurodegenerative risk factors, together with measures of neuropsychological test performance, were obtained at sequential visits. Depressive symptoms were selectively treated with antidepressant medications. RESULTS: One hundred and forty six subjects with normal cognition, 19 subjects with MCI, 42 patients with DAT, and 32 patients with VAD were followed for a mean of 3.5 years. With the passage of time, there were trends showing prevalence of depressive symptoms to decrease among DAT and to increase among VAD patients. VAD patients exhibited the highest incidences of new-onset depressive symptoms, followed in incidence by DAT and MCI groups. Depressive symptoms among VAD and MCI patients were more persistent and refractory to antidepressant medications than for DAT patients. Trends suggested that antidepressant treatment might benefit MCI and VAD subjects more than DAT patients. Motivationally related depressive symptoms accounted for major components of elevated Hamilton depression rating scale scores. CONCLUSIONS: Depressive symptoms among DAT patients have higher rates of spontaneous resolution, without requiring intensive drug treatment, than among VAD patients in whom depressive symptoms are more persistent and refractory to drug treatment. Early depressive symptoms among subjects with MCI may represent a preclinical sign and should be considered as a risk factor for impending DAT or VAD among the elderly.     

Depressive symptoms among cognitively normal versus cognitively impaired elderly subjects

OBJECTIVES: The present cross-sectional study analyzed the prevalence and severity of depressive symptoms among patients with Alzheimer's disease (DAT), vascular dementia (VAD), and among the cognitively normal elderly. Putative risk factors contributing to depression were likewise evaluated. METHODS: Seventy-six DAT patients, 51 VAD patients, and 121 cognitively normal subjects were admitted to the study. Questionnaires concerning demography and their vascular and familial risk factors together with results of neuropsychological testing by combined Mini-Mental Status Examinations (MMSE), Cognitive Capacity Screening Examinations (CCSE), and Hamilton Depression Rating Scales (HDRS) were obtained so that resulting data would be statistically analyzed. RESULTS: Prevalence of depressive symptoms among VAD, DAT, and cognitively normal elderly were 31.4%, 19.9%, and 13.2%, respectively. 25.5% of VAD and 13.2% of DAT patients had depression of mild to moderate degrees. Regression analysis revealed that diagnosis of VAD and DAT, heart disease, and past history of depression was significantly associated with high HDRS scores. There was no correlation between degree of depression and severity of cognitive impairments. CONCLUSION: Mild to moderate depression is a common comorbidity with organic dementia, especially VAD, but associated depression is independent of severity of cognitive impairments.     

Coexisting depression and dementia in a community survey of the elderly

We report here on the coexistence of dementia and depression in a community population aged 75 years and older. Complete information about mood and cognition was available for 286 cognitively intact subjects selected for assessment because of their low scores on the Mini-Mental State, and for 158 mildly and moderately demented subjects. Severely demented subjects, who were incapable of providing information, were excluded. Five percent (8/158) of demented subjects also fulfilled criteria for major depressive disorder Diagnostic and Statistical Manual of Mental Disorders, third edition (DSM-III) compared with 9% (27/286) of cognitively intact subjects. No substantial differences existed in the symptoms reported by demented depressives and nondemented depressives, but subjects who suffered from both disorders were so markedly apathetic that their depression might easily have been overlooked had specific enquiries not been made. Depression was particularly associated with dementia secondary to multi-infarct and Parkinson's disease. When reviewed one year later, 2 of the 18 surviving depressed, nondemented subjects showed evidence of dementia. Both presented unusual diagnostic difficulties, however, and no evidence emerged that large numbers of elderly people will be misclassified in community surveys that include a mental state examination, cognitive testing, and an informant interview.     

Utility of a modified Mini-Mental State Examination with extended delayed recall in screening for mild cognitive impairment and dementia among community dwelling elders

The objective of this study was to test the utility of additional delayed recall of the three recall items of the Folstein Mini Mental State Evaluation (MMSE) as a screening measure for mild cognitive impairment and dementia in the elderly. It used a cross-sectional study of subjects, who were administered a brief memory screening battery which included the MMSE and extended delayed recall of the three MMSE recall items at 5 minute intervals. The criteria for cognitive status was determined on the basis of the neurological and neuropsychological evaluation. One hundred and two elderly persons who were recruited through a memory screening program were diagnosed as cognitively normal (N=52), mild cognitively impaired (N=24), or demented (N=26). The observed sensitivity of 83.3% and specificity of 90.4% was achieved across three delayed recall trials in differentiating cases with mild cognitive impairment (without dementia) from individuals with normal cognition and was superior to the total MMSE score alone (sensitivity/specificity: 70.8%/84.6%). Cumulative recall for the three MMSE items across only two delayed recall trials demonstrated a sensitivity of 96.2% and specificity of 90.4% in differentiating between cases of dementia versus cases diagnosed with no cognitive impairment. The three trial delayed recall score enhanced prediction of mild cognitive impairment in at-risk elderly living with the community and may have promise in the development of future screening batteries.     

Dementia with coexistent major depression

Eleven percent (N = 25) of 232 dementia patients seen in an active geropsychiatry service also met criteria for major depression. Ten patients with dementia/depression were prospectively compared with 10 non-depressed demented and 33 nondemented depressed patients on pretreatment and posttreatment ratings of depression and cognition/memory. Seventy percent (N = 7) of the dementia/depression group and 73% (N = 24) of the depression-only group responded to antidepressant therapy. Signs and symptoms of depression complicating dementia were similar to depressive phenomena in the depression-only group. Depression with dementia appeared to lower performance on cognitive tests. Following treatment, although cognitive impairment remained in the demented range, test performance improved.     

Treatment of cognitive impairment after poststroke depression : a double-blind treatment trial

BACKGROUND AND PURPOSE: Patients with poststroke major depression have a greater severity of cognitive impairment than nondepressed patients even when matched for size and location of stroke lesion. Prior treatment studies have consistently failed to show an improvement in cognitive function even when poststroke mood disorders responded to antidepressant therapy. We examined the response of cognitive function to treatment with nortriptyline or placebo in a double-blind trial. METHODS: Patients with major (n=33) or minor (n=14) depression participated in a double-blind treatment study with nortriptyline or placebo. They were examined for change in depressive mood, measured by the Hamilton Rating Scale for Depression (HAM-D), and change in cognitive impairment, assessed by the Mini-Mental State Examination (MMSE), after treatment with nortriptyline or placebo. Cognitive treatment response, as measured by the MMSE, was compared between patients whose depression did and did not respond to treatment. RESULTS: Patients whose poststroke depression remitted (predominantly associated with nortriptyline treatment) had significantly greater recovery in cognitive function over the course of the treatment study than patients whose mood disorder did not remit (predominantly associated with placebo treatment). CONCLUSIONS: Our findings support the contention that poststroke major depression leads to a "dementia of depression." Prior studies failed to show an effect of treatment because the effect size was too small. Successful treatment of depression may constitute one of the major methods of promoting cognitive recovery in victims of stroke.     

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.     

Clock tests in depression, Alzheimer's disease, and elderly controls

OBJECTIVE: While clock-drawing tests are commonly used to screen for cognitive impairment in the elderly, little is known about the performance of elderly depressives. METHODS: We compared thirty-three patients with major depression to forty-two Alzheimer's disease and thirty age-matched controls on clock-drawing, copying, and reading. RESULTS: Patients with Alzheimer's disease had significantly lower scores on clock-drawing, copying, and reading than patients with depression or the controls (p < 0.05). Patients with depression did not differ significantly from controls on quantitative scores or qualitative errors. CONCLUSIONS: Clock tests may be useful for identifying depressed patients with underlying dementia.     

Family history of dementia and current depression in nondemented community-dwelling older adults

Since it has been postulated that mood disturbance in nondemented older adults may represent a prodromal feature of dementia for a subgroup of patients, it would be expected that patients with these symptoms would evidence a greater prevalence of family history of dementia. In a sample of 3225 community-dwelling cognitively intact elderly recruited from a free memory-screening program, we found that current depression was more common in participants with a positive versus a negative family history of dementia in first-degree relatives (17% versus 11%; Fisher's Exact Test, P < .0001). This relationship remained significant after controlling for age, education, gender, ethnicity, and Folstein Mini-Mental State Examination score (OR = 1.5; 95% CI = 1.2-1.9, Wald X2 = 15.5, P < .001). The results suggest that symptoms of depression may herald the onset of an incipient dementia syndrome in a subset of geriatric patients. Alternatively, the results may be indicative of familial aggregation of dementia and depression.     

The apolipoprotein E epsilon4 allele and antidepressant efficacy in cognitively intact elderly depressed patients.

BACKGROUND: Patients vary in response to antidepressant medications. Apolipoprotein E (APOE) genotype affects vulnerability to stress and risk for cognitive impairment. We sought to determine if the APOE epsilon4 allele influences response in geriatric depression to mirtazapine and paroxetine, two frequently prescribed antidepressants. We hypothesized that epsilon4 carriers would show impaired antidepressant response. METHODS: The study was a double-blind, randomized, 8-week trial with a 16-week extension phase involving 246 cognitively intact patients aged 65 years or older with major depression. Patients were treated with mirtazapine 15-45 mg (n = 124) or paroxetine 20-40 mg (n = 122). The outcome measures were the Hamilton Depression Rating Scale, the Geriatric Depression Scale, and the Clinical Global Impression Scale. APOE genotype was determined by restriction isotyping. RESULTS: Patients carrying the epsilon4 allele showed a rapid onset of mirtazapine action, whereas paroxetine-treated patients with the epsilon4 allele were slow to respond. This difference could not be attributed to dosage, compliance, severity of adverse events, ethnicity, baseline depression or cognition, gender, or age. CONCLUSIONS: The APOE epsilon4 allele may affect antidepressant treatment outcome, but the effect depends on the medication. Further studies should determine if this result applies to other samples and medications.     

Cognitive outcome following tricyclic and electroconvulsive treatment of major depression in the elderly

OBJECTIVE: This study sought to ascertain the affective and cognitive outcome after tricyclic and electroconvulsive treatment of elderly medical-psychiatric patients meeting diagnostic criteria for major depression, some of whom had normal cognitive functioning and some of whom were cognitively impaired before treatment. METHOD: Patients who met criteria for major depression on the basis of a structured diagnostic interview and who scored 17 or more on the Hamilton Rating Scale for Depression were evaluated with the Mattis Dementia Rating Scale. The patients were then treated in a nonrandom manner with either tricyclic antidepressants or ECT (followed by tricyclic maintenance therapy). The majority of the patients treated with ECT had not responded previously to tricyclics. Follow-up psychometric testing was repeated in 6 months. RESULTS: Among the patients with normal pretreatment cognitive functioning, cognition was generally stable. Among the patients with pretreatment cognitive impairment, a substantial number--including those receiving ECT--demonstrated improvement in cognition. While the majority of patients improved with respect to both their affective and cognitive states, certain treatment-refractory subgroups were nevertheless identified. CONCLUSIONS: The data suggest that cognitive dysfunction associated with depression may improve after treatment in a substantial number of elderly patients, including those receiving ECT. Relapse rates, however, may be relatively high, and residual symptoms may persist, which emphasizes the need for optimal initial and long-term antidepressant strategies for this population.     

A controlled multicenter clinical study of citalopram and placebo in elderly depressed patients with and without concomitant dementia.

A total of 149 patients in 7 centers in Denmark, Norway and Sweden entered a 6-week double-blind trial intended to assess the antidepressant effect and safety of citalopram vs placebo in depressed elderly patients (65 years of age or older) who might also suffer from somatic disorders and/or senile dementia. Results of ratings on the Hamilton Rating Scale for Depression, the Montgomery-Åsberg Depression Rating Scale and the Clinical Global Impression Scale provided consistent evidence that the citalopram-treated patients improved more than the placebo-treated patients. Results of ratings on the Gottfries-Bråne-Steen dementia rating scale indicated that both cognitive and emotional functioning improved significantly more in the citalopram-treated subgroup of patients with dementia than in the placebo-treated subgroup.     

Independent predictors of cognitive decline in healthy elderly persons

BACKGROUND: Several studies have shown that individually memory, hippocampal volume, and motor measures presage the onset of dementia. It is unclear if these independently contribute to the prediction of mild cognitive impairment. OBJECTIVE: To determine the ability of memory, hippocampal volume, and a gait speed to independently predict cognitive decline in healthy elderly persons. DESIGN: A prospective, longitudinal, observational cohort study with a mean follow-up of 6 years. PARTICIPANTS: One hundred eight optimally healthy elderly cognitively intact subjects. MAIN OUTCOME MEASURES: Any cognitive impairment noted on the Clinical Dementia Rating Scale (score = 0.5) or persistent or progressive cognitive impairment. Cox modeling determined if time to onset of cognitive impairment was associated with baseline logical memory II test score (a measure of delayed recall), hippocampal volume (magnetic resonance imaging), or gait speed (time to walk 30 ft [9 m]) independent of age, sex, depression, or the allele producing the epsilon4 type of apolipoprotein E (APOE epsilon4). RESULTS: Questionable dementia occurred in 48 participants in a mean (SD) of 3.7 (2.4) years. This progressed to persistent cognitive impairment in 38 of these participants in a mean (SD) of 4.4 (2.4) years. Logical memory II test performance and hippocampal volume each predicted onset of questionable dementia, independent of age and sex. Time to walk 30 ft additionally contributed independently to the prediction of time to onset of persistent cognitive impairment. Possessing the APOE epsilon4 allele and depression did not enter either model significantly. CONCLUSIONS: Models combining multiple risk factors should refine the prediction of questionable dementia and persistent cognitive impairment, harbingers of dementia. Individuals at risk for cognitive impairment may represent a high-risk group for intervention.     

Drug treatment in depressed elderly in the Dutch community

OBJECTIVES: In older people, a diagnosis of depression is frequently missed, and proper treatment is subsequently hampered. We investigated antidepressant and benzodiazepine use in an older community sample, and assessed possible risk factors associated with non-treatment in depressed elderly. METHODS: Data were used from the baseline measurements of the Longitudinal Aging Study Amsterdam (LASA). In a random, age and sex stratified community sample of 3107 older Dutch people (55 to 85 years), respondents were screened on depression with the Center for Epidemiologic Studies Depression Scale (CES-D). In the depressed subsample depressive disorder according to DSM-III was assessed using the Diagnostic Interview Schedule (DIS). The use of antidepressants and anxiolytics (benzodiazepines) in the depressed subsample was measured, and associations with age, sex, cognitive impairment, physical health and anxiety symptoms were investigated. RESULTS: Only 16% of the respondents with a major depressive disorder used antidepressants. More than half of them used non-therapeutic dosages. Lower antidepressant use was associated with cognitive impairment. Benzodiazepine use was more likely than antidepressant use, which was especially evident in females in the major depressive disorder group. CONCLUSIONS: Depressed older people were undertreated, particularly when they were cognitively impaired. A high rate of benzodiazepine use was found, particularly in females.