The effect of remission of poststroke depression on activities of daily living in a double-blind randomized treatment study.

Poststroke depression has been associated with impaired recovery of activities of daily living (ADL) during the first 2 years after stroke. This study examined the effect of remission of poststroke depression on recovery in ADL in a double-blind randomized treatment study. Based on a semistructured psychiatric exam and DSM-IV diagnostic criteria, a consecutive series of 23 patients who met criteria for major depression (N = 16) or minor depression (N = 7) were selected and randomly assigned to either active treatment (nortriptyline) or placebo. Functional physical (i.e., ADL) impairment was assessed using the Johns Hopkins Functioning Inventory (JHFI). Patients whose depressive disorder remitted at follow-up had significantly greater recovery in ADL functions compared with patients whose depression did not remit. There were no differences in demographic variables, lesion characteristics, and neurological symptoms between the two groups, which would explain the significantly greater improvement among the remitted patients. Because both major and minor depression patients who remitted showed greater improvement in ADL than nonremitted patients some of whom were treated with active and some with placebo medication, nonpharmacotherapeutic mechanisms related to recovery from depression appear to mediate this enhanced recovery.

Prevalence and correlates of parkinsonism in patients with primary depression.

The authors examined the prevalence, clinical correlates, and longitudinal changes of parkinsonism in 94 patients with primary depression and 20 healthy control subjects. Parkinsonism was present in 20% of patients with primary depression. This syndrome was significantly associated with older age, more severe depression, and more severe cognitive impairment. In a subgroup of depressed patients, parkinsonism was reversible upon recovery from the mood disorder.

A double-blind, placebo-controlled study of fluoxetine in depressed patients with Alzheimer's disease.

OBJECTIVE: To examine the efficacy of fluoxetine in the treatment of depression in patients with probable Alzheimer's disease (AD). METHODS: This double-blind, parallel-design study included a consecutive series of 41 AD subjects meeting DSM-IV criteria for major or minor depression who were randomized to receive fluoxetine (up to 40 mg/day) or identical-appearing placebo. All patients received biweekly evaluations consisting of the Hamilton Depression Scale (HAM-D) and the Clinical Global Impression as primary efficacy measures, and the Mini-Mental State Exam, Hamilton Rating Scale for Anxiety, and the Functional Independence Measure as secondary efficacy measures. RESULTS: Complete remission of depression was found in 47% of subjects treated with fluoxetine and in 33% of subjects treated with placebo. Both the fluoxetine and the placebo groups showed a significant decline in HAM-D scores over time, but the magnitude of mood improvement was similar for both groups. Fluoxetine was well tolerated, and most side effects were mild. CONCLUSION: Fluoxetine treatment for depression in AD did not differ significantly from treatment with placebo. Our study also confirms the presence of a placebo effect in the treatment of depression in AD.

Syndromic validity of apathy in Alzheimer's disease.

OBJECTIVE: The study examined the usefulness and clinical correlates of specific diagnostic criteria for apathy in Alzheimer's disease. Whereas apathy is a frequent behavioral change in patients with Alzheimer's disease, the lack of standardized diagnostic criteria may explain the wide discrepancies in estimates of the frequency and demographic and clinical correlates of apathy. METHOD: A consecutive series of 319 patients who met the criteria for probable Alzheimer's disease established by the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association, 117 patients who met the DSM-IV criteria for depression without dementia, and 36 healthy individuals were assessed with a structured psychiatric interview. On the basis of modified Marin's criteria for apathy, they were classified into groups with or without apathy. RESULTS: Apathy was diagnosed in 37% of the 319 Alzheimer's disease patients, compared to none of the healthy comparison subjects. In 24% of the Alzheimer's disease sample, apathy coexisted with either dysthymic disorder or major depressive disorder, whereas 13% had apathy without depression. Apathy was diagnosed in 32% of the depressed nondemented patients, mostly in those with major depressive disorder. Apathy in Alzheimer's disease was significantly associated with severe impairments in activities of daily living and cognitive functions, older age, and poor awareness of behavioral and cognitive changes. CONCLUSIONS: This study provides partial validation of specific clinical criteria for apathy in Alzheimer's disease.

Improved recovery in activities of daily living associated with remission of poststroke depression.

BACKGROUND AND PURPOSE: Poststroke depression is associated with impaired recovery of activities of daily living (ADL) function compared with similar nondepressed patients. We examined the differences on recovery of ADL functions among poststroke depressed patients with remission of their depression compared with poststroke depressed patients without mood recovery over the first 3 to 6 months after stroke. METHODS: On the basis of a semistructured psychiatric examination and DSM-IV diagnostic criteria, a consecutive series of patients with poststroke major or minor depression (n=55) were selected. Their impairment in ADL function was assessed by means of the Johns Hopkins Functioning Examination during acute hospitalization and either 3 or 6 months later. RESULTS: Patients whose mood improved at follow-up (n=21) had significantly greater recovery in ADL functions at follow-up than patients whose mood did not improve (n=34). There were no differences in demographic variables, lesion characteristics, and neurological symptoms between the two groups. Furthermore, patients with either major or minor depression at the initial evaluation showed the same amount of recovery in ADL function if they improved at follow-up. CONCLUSIONS: Our findings suggest that remission of poststroke depression over the first few months after stroke is associated with greater recovery in ADL function than continued depression. Early effective treatment of depression may have a positive effect on the rehabilitation outcome of stroke patients.

The specificity of depressive symptoms in patients with Alzheimer's disease.

OBJECTIVE: This study assessed the specificity of depressive symptoms in patients with Alzheimer's disease and examined the discrepancies between patient and caregiver symptom reports. METHOD: The study group was composed of a series of 233 patients with Alzheimer's disease, 47 patients with depression but without dementia, and 20 healthy comparison subjects; the latter two groups were comparable in age with the patients with Alzheimer's disease. The patients and comparison subjects received a comprehensive psychiatric evaluation, which included administration of the Hamilton Depression Rating Scale and the Structured Clinical Interview for DSM-IV. RESULTS: Patients with Alzheimer's disease with a score of 2 or higher on the "depressed mood" item of the Hamilton depression scale, as scored by their respective caregivers, comprised a group with depressed mood (N=92), whereas patients who scored 0 on this item comprised a group without depressed mood (N=62). A statistical comparison of the scores on the remaining Hamilton depression scale items (2-16) between the Alzheimer's disease patients with and without depressed mood revealed significant differences on all items, except "loss of appetite." However, there were no significant differences on any single Hamilton depression scale item between the Alzheimer's disease patients without depressed mood and the age-comparable healthy comparison subjects. CONCLUSIONS: Depressive symptoms are not widespread among patients with Alzheimer's disease but are significantly related to an underlying depressed mood. Patients with Alzheimer's disease may not be fully aware of the extent of their depressive symptoms.

Impairments of social cognition and decision making in Alzheimer's disease.

OBJECTIVE: To investigate the nature of deficits in social cognition and real-life decision making in a group of patients with Alzheimer's disease (AD). DESIGN: A comprehensive neuropsychological and psychiatric assessment, including the Moral Judgment Interview and the Bechara's Card Test, was carried out in 25 patients with AD and 20 age-comparable normal controls. SETTING: Outpatient clinic. RESULTS: AD patients had significantly lower scores in the Moral Judgment Interview and obtained significantly less earnings in the card test when compared to the normal control group. The Moral Judgment Interview score correlated significantly with Raven's Progressive Matrices and Block Design, whereas the card test correlated significantly with both the Benton Visual Retention Test and the Buschke Selective Reminding Test. No significant correlations were observed between the experimental tasks and the psychiatric variables. CONCLUSIONS: AD patients demonstrated significant deficits on tasks assessing social cognition and real-life decision making. These impairments correlated with deficits on specific neuropsychological tasks, but not with behavioral problems frequently found in AD patients.

The neuropsychiatry of stroke.

Stroke represents a major public health problem in the United States, but relatively little work has been directed toward identifying and treating the common neuropsychiatric disorders occurring after stroke. This review discusses clinical and pathological correlates of depression, anxiety disorder, catastrophic reactions, pathological affect, or psychosis after stroke, as well as their epidemiology. Depressive disorder and anxiety disorder have been shown to inhibit physical recovery from stroke. It seems likely that other psychiatric disorders also inhibit recovery and limit quality of life. There are very few controlled trials examining the effectiveness of treatments for these disorders after stroke. Both depression and pathological affect, however, can be effectively treated with antidepressant medications.

Pathophysiology of secondary depressions in the elderly.

Although the pathophysiology of depression is not fully understood in either primary depression (i.e., no known neuropathology related to depression) or secondary depression (i.e., neuropathologic disorder that leads to depression), a number of studies have begun to identify aspects of the pathophysiology of both primary and secondary depression. This article reviews the findings of studies examining the pathophysiology of depression following stroke, Parkinson's disease, or Huntington's disease and compares them to findings in primary depression. Studies examining glucose metabolic rates or blood flow changes in regional brain areas found that stroke, Parkinson's disease, and Huntington's disease, as well as primary depression, were all associated with decreased activity or brain lesions in the orbital frontal cortex and basal ganglia. There were also abnormalities noted in the basal temporal lobes, cingulate cortex, and thalamus in some but not all disorders. Studies in stroke have also noted depletions of serotonin receptors in left temporal cortex associated with depression. These findings are consistent with the hypothesis that the pathophysiology of secondary and primary depression involves the dysfunction of one or more of the cortical-basal ganglia-thalamic neuronal loops. This dysfunction may be mediated by decreased serotonin release. These studies may ultimately lead to more focused and specific treatments.

Frontal lobe syndrome reassessed: comparison of patients with lateral or medial frontal brain damage.

Examination of mood and behaviour changes after frontal damage may contribute to understanding the functional role of distinct prefrontal areas in depression and anxiety. Depression and anxiety disorders, symptoms, and behaviour were compared in eight patients with single lateral and eight patients with single medial frontal lesions matched for age, sex, race, education, socioeconomic status, side, and aetiology of lesion 2 weeks and 3 months after brain injury. DSM IV major depressive and generalised anxiety disorders were more frequent in patients with lateral compared with medial lesions at 2 weeks but not at 3 months. At 3 months, however, patients with lateral damage showed greater severity of depressive symptoms, and greater impairment in both activities of daily living and social functioning. At initial evaluation depressed mood and slowness were more frequent, whereas at 3 months slowness, lack of energy, and social unease were more frequent in the lateral than the medial group. Patients with lateral lesions showed greater reduction of emotion and motivation (apathy) during both examinations. Medial frontal injury may fail to produce emotional dysregulation or may inhibit experience of mood changes, anxiety, or apathy. Lateral prefrontal damage may disrupt mood regulation and drive while leaving intact the ability to experience (negative) emotions.

Prevalence and correlates of aggressive behavior in Alzheimer's disease.

The authors assessed a consecutive series of 196 patients with probable Alzheimer's disease (AD) for the presence of aggressive behavior, using a standardized neurological, neuropsychiatric, and neuropsychological battery that included both the Overt Aggression Scale and the Irritability Scale. Twelve percent of patients showed aggressive episodes (5% with verbal aggression, 7% with physical aggression) during the 4 weeks preceding the psychiatric evaluation. Physical aggression was significantly associated with more frequent delusions and more severe irritability.

Prevalence and correlates of anxiety in Alzheimer's disease.

We assessed a consecutive series of 398 patients with probable Alzheimer's disease (AD) for the presence of Generalized Anxiety Disorder (GAD) using a standardized neuropsychiatric evaluation. Five percent of patients showed GAD during the 4 weeks preceding the psychiatric evaluation. AD patients with GAD showed significantly higher scores of depression, irritability, overt aggression, mania, and pathological crying than AD patients without GAD. The most severe symptoms of anxiety were those of tension, fears, insomnia, and physical complaints.

Depression in classic versus akinetic-rigid Parkinson's disease.

We examined the prevalence of major depression and dysthymia in 78 patients with the classic variant of Parkinson's disease (PD) (that is, tremor plus rigidity and/or bradykinesia), and in 34 patients with the akinetic-rigid variant. Although the prevalence of dysthymia was similar in both groups (classic PD, 31%; and akinetic-rigid PD, 32%), patients with akinetic-rigid PD had a significantly higher prevalence of major depression (38% versus 15%, respectively; p < 0.01). A stepwise regression analysis demonstrated that bradykinesia was the extrapyramidal sign with the highest correlation with Hamilton depression scale scores. Our findings demonstrate a significant association between major depression and the akinetic-rigid type of PD.

Neuropsychological, psychiatric, and cerebral perfusion correlates of leukoaraiosis in Alzheimer's disease.

OBJECTIVE: To examine neurological, neuropsychological, psychiatric, and cerebral perfusion correlates of leukoaraiosis in Alzheimer's disease. METHODS: A consecutive series of patients with probable Alzheimer's disease was assessed with a comprehensive neuropsychological battery, a structured psychiatric evaluation, the unified Parkinson's disease rating scale, MRI, and single photon emission computed tomography with technetium 99m hexamethylpropyleneamine oxime (HMPAO) and regional cerebral perfusion measurements. RESULTS: Patients with Alzheimer's disease and leukoaraiosis were significantly more apathetic and had significantly more extrapyramidal signs than patients with Alzheimer's disease without leukoaraiosis. Patients with Alzheimer's disease with leukoaraiosis also had significantly lower bilateral perfusion in the basal ganglia, thalamus, and frontal lobes than patients with Alzheimer's disease without leukoaraiosis. On the other hand, there were no significant differences between groups in age, duration of illness, depression scores, severity of delusions, or deficits on specific neuropsychological tasks. CONCLUSIONS: Leukoaraiosis in Alzheimer's disease may produce significant basal ganglia, and thalamic and frontal lobe dysfunction, which may be associated with more severe apathy and extrapyramidal signs.

Prospective longitudinal study of depression and anosognosia in Alzheimer's disease.

BACKGROUND: The aim was to examine the longitudinal evolution of depression and anosognosia in patients with probable Alzheimer's disease (AD). METHOD: Sixty-two of a consecutive series of 116 AD patients that were examined with a structured psychiatric interview had a follow-up evaluation between one and two years after the initial evaluation. RESULTS: At the initial evaluation 19% of the 62 patients had major depression, 34% had dysthymia, and 47% were not depressed. After a mean follow-up of 16 months, 58% of patients with major depression at the initial evaluation were still depressed, whereas only 28% of patients with initial dysthymia and 21% of the non-depressed patients were depressed at follow-up. During the follow-up period, all three groups showed similar declines in cognitive status and activities of daily living. At the initial evaluation, 39% of the patients had anosognosia, and there was a significant increment of anosognosia during the follow-up period. CONCLUSIONS: While dysthymia in AD is a brief emotional disorder, major depression is a longer-lasting mood change. Anosognosia is another prevalent disorder among AD patients, and increases with the progression of the illness.

Two domains of anosognosia in Alzheimer's disease.

OBJECTIVE: To examine the presence of different dimensions of unawareness in patients with probable Alzheimer's disease. METHODS: A consecutive series of 170 patients with probable Alzheimer's disease were assessed with the anosognosia questionnaire-dementia (AQ-D) which includes items related to cognitive deficits and behavioural problems. RESULTS: A factor analysis of the AQ-D produced two factors: a "cognitive unawareness" factor, which loaded on items of memory, spatial and temporal orientation, calculation, abstract reasoning, and praxis, and a "behavioural unawareness" factor which loaded on items of irritability, selfishness, inappropriate emotional display, and instinctive disinhibition. A stepwise forward regression analysis showed significant correlations between the cognitive unawareness factor and more severe cognitive deficits, delusions, and apathy, but less depression. On the other hand, the behavioural unawareness factor correlated significantly with higher mania and pathological laughing scores. Whereas the cognitive unawareness factor showed a significant correlation with cognitive tests assessing verbal comprehension and long term memory, and was significantly associated with a longer duration of illness, no significant correlations were found between the behavioural unawareness factor and the neuropsychological tasks. CONCLUSION: Unawareness of cognitive deficits and unawareness of behavioural problems may constitute independent phenomena in Alzheimer's disease. Whereas unawareness of cognitive deficits is related to the severity of intellectual impairment and the presence of delusional apathetic mood, unawareness of behavioural problems may be part of a disinhibition syndrome.

Neuropsychological and psychiatric differences between Alzheimer's disease and Parkinson's disease with dementia.

OBJECTIVE: To examine neuropsychological and neuropsychiatric differences between patients with probable Alzheimer's disease and patients with Parkinson's disease and dementia. METHODS: Thirty three patients with probable Alzheimer's disease and 33 patients with Parkinson's disease and dementia were matched for age, sex, and mini mental state examination scores and given a battery of neuropsychological and neuropsychiatric tests. RESULTS: Patients with Parkinson's disease with dementia had a significantly higher prevalence of major depression than patients with Alzheimer's disease; patients with Alzheimer's disease showed more severe anosognosia and disinhibition than patients with Parkinson's disease. Whereas no significant between group differences were found on tests of memory and language, demented patients with Parkinson's disease had a significantly greater impairment on a test of visual reasoning than patients with Alzheimer's disease. CONCLUSION: There were significant psychiatric differences between patients with Alzheimer's disease and demented patients with Parkinson's disease, but neuropsychological differences were restricted to a single cognitive domain.

Catatonia in depression: prevalence, clinical correlates, and validation of a scale.

OBJECTIVES: To examine the clinical correlates of catatonia in depression, to validate a scale for catatonia, and to assess the validity of the DSM-IV criteria of the catatonic features specifier for mood disorders. METHODS: A series of 79 consecutive patients with depression and 41 patients with Parkinson's disease without depression were examined using the modified Rogers scale (MRS), the unified Parkinson's disease rating scale (UPDRS), and the structured clinical interview for DSM-III-R (SCID). RESULTS: Sixteen of the 79 depressed patients (20%) had catatonia. Depressed patients with catatonia had significantly higher scores on the MRS than non-catatonic depressed patients matched for severity of depression, or non-depressed patients with Parkinson's disease matched for severity of motor impairment. Depressed patients with catatonia were older, had a significantly higher frequency of major depression, more severe cognitive impairments, and more severe deficits in activities of daily living than depressed non-catatonic patients. The DSM-IV criteria of catatonia separated depressed catatonic patients from patients with Parkinson's disease matched for motor impairment, with a specificity of 100%. Catatonic signs did not improve after apomorphine. CONCLUSIONS: catatonia is most prevalent among elderly patients with severe depression. The study showed the validity of the MRS for the diagnosis of catatonia in depressed patients, as well as the specificity of the DSM-IV criteria of the catatonic features specifier.

Neuropsychological, psychiatric, and cerebral blood flow findings in vascular dementia and Alzheimer's disease.

BACKGROUND AND PURPOSE: Psychiatric, neuropsychological, and cerebral blood flow differences between patients with ischemic vascular dementia (IVD) or Alzheimer's disease (AD) were examined. METHODS: A consecutive series of patients who met either the criteria of the National Institute of Neurological Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association for probable AD or the State of California AD Diagnostic and Treatment Centers criteria for probable IVD were included in the study. Twenty consecutive patients with IVD were matched for age, sex, and Mini-Mental State Examination scores with 40 consecutive patients with probable AD. Patients underwent a psychiatric interview, a neuropsychological assessment, and single-photon emission CT imaging with 99mTc-hexamethylpropyleneamine oxime. RESULTS: Patients with IVD showed significantly more severe anosognosia (P<.05) and emotional lability (P<.01) than AD patients, but no significant between-group differences were found in the frequency and severity of depression. IVD patients showed significantly more severe deficits in tests of planning, sequencing (P<.05), and verbal fluency (P<.05) as well as significantly more severe cerebral blood flow deficits in the basal ganglia (P<.01) and the frontal lobes (P<.001) than AD patients. CONCLUSIONS: Patients with IVD showed a relatively more severe dysfunction of the frontal lobes as demonstrated by single-photon emission CT and expressed in specific psychiatric and neuropsychological changes than AD patients matched for age, sex, and severity of dementia.

A double-blind placebo-controlled study of clomipramine in depressed patients with Alzheimer's disease.

Twenty-one depressed patients with probable Alzheimer's disease (AD) were randomized to receive a 6-week treatment with clomipramine or placebo in a study with a double-blind crossover design. Main outcome measures were Hamilton Depression, Mini-Mental State (MMSE), and Functional Independence Measure (FIM) scores. Mood improved significantly on both clomipramine and placebo, but clomipramine was significantly more effective than placebo during the first 6-week treatment period. Patients started on clomipramine maintained improvement during the washout and placebo periods, whereas patients started on placebo worsened during the washout period. However, patients on clomipramine showed significantly lower MMSE scores overall than patients on placebo. No significant drug effects were found on FIM scores. Clomipramine proved to be a useful treatment of depression in patients with probable AD.