A psychiatric and neuropsychological study of patients with untreated Graves' disease

We studied 13 untreated Graves' disease subjects in a clinical research unit using endocrine, psychiatric, and neuropsychological assessments. We used SADS interviews, RDC, standardized symptom rating scales, and motor activity monitoring to update earlier studies and quantified psychiatric symptoms to elucidate any correlations between endocrine and psychiatric status. Nine of 13 subjects had major depression, 8/13 had generalized anxiety disorder, and 3/13 were hypomanic. Anxiety levels were much higher than in other hospitalized medical patients. Using a broad battery of neuropsychological testing, we found mild deficits in attention, memory, and complex problem solving that were consistent with previous studies of hyperthyroid patients. The severity of psychiatric symptoms could easily result in an inappropriate referral to a psychiatrist prior to the diagnosis of hyperthyroidism. The relationship between psychiatric symptoms and possible CNS effects of excess levels of thyroid hormone is discussed.     

Diagnosis of late life depression: the view from primary care.

In the typical primary care practice, in which patients with a wide range of diseases and symptoms present with numerous needs, concerns, and requests, a chronic disease that lacks quantitative, biologically based diagnostic testing, such as depression, can present a daunting diagnostic challenge to even the best and most dedicated primary care physician. Depression does not compete well for patient and physician time and energy with other medical problems and medical co-morbidity in patients who seek care from their primary care physician. Primary care patients may be more comfortable with and accepting of depression being framed as a "normal" chronic disease rather than a psychiatric "brain" disease subject to cultural and generational stigmas, nihilism, and prejudice. Insurance parity in mental health care would make depression and other mental illness more legitimate in the eyes of patients, family members, employers, and physicians. Of particular value would be new and creative approaches to collaborative care, including telephone monitoring, nurse clinician outreach, and improved availability of psychiatric consultation in primary care, because elderly depressed patients often see the care of their depression as part of the integrated care of multiple chronic medical diseases, rather than a separate psychiatric problem to be referred for specialty care.     

抑郁症和早期阿尔茨海默病的记忆和执行功能

目的 研究抑郁症和早期阿尔茨海默病(AD)的神经心理学特征,试图运用神经心理学评估对两者进行鉴别。方法 对32例单相抑郁症、38例早期AD和34例对照进行WHO-UCLA词语学习、词语流畅、复杂图形和逻辑记忆的评估。结果 早期AD组神经心理学测验得分最低,抑郁症组次之,对照组最高,3组之间有显著性差异(P<0.01);抑郁症组仅表现为词语学习和逻辑记忆的自由回忆以及语义流畅的损害(P<0.05),而早期AD组表现为全面的认知功能损害(P<0.01);逐步判别分析提示,复杂图形延迟自由回忆、词语学习长时延迟自由回忆和语义流畅是区分抑郁症组和早期AD组的重要指标。结论 抑郁症和早期AD认知功能损害的特征不同,长时延迟自由回忆、再认和语义流畅能够区分早期AD和抑郁症。     

The earliest cognitive change in a person with familial Alzheimer''s disease: presymptomatic neuropsychological features in a pedigree with familial Alzheimer''s disease confirmed at necropsy.

Comprehensive, longitudinal neuropsychological assessments are reported in a person "at risk" from autosomal dominant, necropsy confirmed familial Alzheimer's disease. The first assessment showed a moderately selective verbal memory deficit in the context of mild general intellectual impairment. Subsequent testing showed the progressive deterioration of visual memory and a mild decline of perceptual and spatial skills. Language and literacy skills, however, remained comparatively intact. The neuropsychological profiles obtained at each assessment are presented in profile maps. These permit direct longitudinal comparison of cognitive function, and may serve in the comparison of different potential cases of familial Alzheimer's disease. This case sought medical attention for memory difficulties 26 months after the first neuropsychological assessment. These results mark the first cognitive manifestations in a pedigree with familial Alzheimer's disease which, in this case, were seen presymptomatically. The findings are discussed in relation to neuropsychological studies of affected cases, and in terms of their reflecting the heterogeneous nature of familial Alzheimer's disease.     

Effect of repetitive TMS and fluoxetine on cognitive function in patients with Parkinson's disease and concurrent depression.

Previous studies show that cognitive functions are more impaired in patients with Parkinson's disease (PD) and depression than in nondepressed PD patients. We compared the cognitive effects of two types of antidepressant treatments in PD patients: fluoxetine (20 mg/day) versus repetitive transcranial magnetic stimulation (rTMS, 15 Hz, 110% above motor threshold, 10 daily sessions) of the left dorsolateral prefrontal cortex. Twenty-five patients with PD and depression were randomly assigned either to Group 1 (active rTMS and placebo medication) or to Group 2 (sham rTMS and fluoxetine). A neuropsychological battery was assessed by a rater blind to treatment arm at baseline and 2 and 8 weeks after treatment. Patients in both groups had a significant improvement of Stroop (colored words and interference card) and Hooper and Wisconsin (perseverative errors) test performances after both treatments. Furthermore, there were no adverse effects after either rTMS or fluoxetine in any neuropsychological test of the cognitive test battery. The results show that rTMS could improve some aspects of cognition in PD patients similar to that of fluoxetine. The mechanisms for this cognitive improvement are unclear, but it is in the context of mood improvement.     

Rapid eye movement sleep density. An objective indicator in severe medical-depressive syndromes.

The electroencephalographic sleep patterns of 12 patients with a final diagnosis of primary depression and those of 12 patients admitted to the Clinical Research Unit with this diagnosis, but subsequently also found to be suffering from severe medical disease, were compared. Patients with depression concurrent with severe medical disease have significantly less phasic conjugate rapid eye movement (REM) activity during REM sleep than subjects with the diagnosis of a primary depression. These findings suggest that quantification of REM density may be used clinically to distinguish between medical-depressive syndromes and primary affective disorders.     

An open study of repetitive transcranial magnetic stimulation in treatment-resistant depression with Parkinson's disease.

OBJECTIVE: Major depression is a common concomitant of chronic central nervous system disorders, notably Parkinson's disease (PD). Repetitive transcranial magnetic stimulation (rTMS) has been investigated as a potential treatment for depression in PD and for the movement disorder of PD, but comprehensive testing in multiple areas of performance has seldom been carried out within a single study. We studied the effect of left dorsolateral prefrontal rTMS on several different functional domains. METHODS: Fourteen PD patients with treatment-resistant depression entered an open, 10-day inpatient study of 10-Hz rTMS, undergoing extensive psychiatric, neuropsychological, and motor testing from baseline to 6 weeks after treatment. Motor testing included a defined "off" state. RESULTS: rTMS was well tolerated. Highly significant improvement in depression scores was seen 3 days and 3-6 weeks after treatment. Improvement was also found in anxiety, movement scores (especially in the off state), and some neuropsychological measures. We found no evidence of increased risk from rTMS in this population. CONCLUSIONS: Further controlled trials of rTMS in PD appear worthwhile, and should include a defined "off" state. SIGNIFICANCE: TMS may be beneficial for depressed PD patients in multiple functional domains.     

Neurocognitive profiles in older adults with and without major depression

OBJECTIVES: To delineate the differences between older persons with and without a diagnosis of major depression. METHODS: Participants were recruited from three outpatient clinics serving older patients at St Michael's Hospital. To be included in the study, participants had to speak English and have no evidence of significant sensory deficits that would interfere with neuropsychological testing. Participants were excluded if they had active delirium, active CNS disease (including dementia), active substance abuse, unstable medical disease, recent ECT treatment and a current/past diagnosis of a psychotic disorder. The diagnosis of major depression was made by qualified professionals in accordance with established guidelines. Participants were administered structured measures assessing global cognition, medical co-morbidity, subjective memory complaints, mood and detailed neurocognitive testing evaluating working memory, attention and speed of processing. Differences between depressed and non-depressed subjects with respect to these measures were analyzed using analysis of variance (ANOVA). RESULTS: Thirty-six participants were included in this study. The depressed (n = 17) and non-depressed (n = 19) groups were well matched in terms of age, education, medical co-morbidity and mini-mental state exam (MMSE) score. While the depressed subgroup had significantly higher subjective memory, language and cognitive complaints, there were no significant differences observed between the two subgroups on measures of memory and learning, attention and speed of information processing, fine motor dexterity and verbal fluency. CONCLUSION: This study suggests that while significant depressive symptoms are strongly associated with increased cognitive complaints, they are not associated necessarily with objective cognitive impairment.     

Attention: neuropsychological predictor of competency in Alzheimer's disease

This study was undertaken to examine the relationship between two different competencies, financial and medical decision making, and explore whether neuropsychological testing can identify a common underlying cognitive operation impaired in patients with AD. The objective was to examine the neuropsychological predictors of financial and medical decision-making competencies in patients with Alzheimer's disease (AD). Twenty individuals with mild to moderate AD and 20 control subjects matched for age and education were evaluated at a university medical center. All participants were administered a financial competency questionnaire, a competency test for medical decision making, and a set of standardized neuropsychological tests selected to reflect cognitive processes theoretically related to competency. In addition, an informant provided information regarding banking history for each participant. AD patients performed more poorly on all measures, including both measures of competency, which were highly related (R = .718, P < .001). Two tests, Trails A and Word List Recall, were significantly correlated with both competency measures, with Trails A predicting over 85% of the variance in competency scores. Trails A discriminated competent from not competent participants with an accuracy ranging from 77% to 82%. Measures of financial and medical decision-making competency were significantly correlated among patients with AD. One brief neuropsychological test of attention, Trails A, proved to be highly predictive of performance on both competency measures and useful in the discrimination of competent performance on these measures and by informant report.     

Cognitive Impairment in Systemic Lupus Erythematosus and Neuropsychiatric Systemic Lupus Erythematosus: A Population-Based Neuropsychological Study

We present a cross-sectional, population-based neuropsychological study of systemic lupus erythematosus (SLE) patients identified within Tampere University Hospital district, Finland with 440,000 inhabitants. Patients with definite SLE in the age range of 16-65 years (n =46) and matched controls (n =46) underwent neurological examination and comprehensive neuropsychological testing. On the basis of medical examination, the SLE patients were divided into neuropsychiatric (NP+; n =15) and nonneuropsychiatric (NP—; n =31) cases. The neuropsychological test results revealed more prevalent cognitive impairment in the NP+ patients, indicating that this subgroup mostly accounts for neuropsychological changes in SLE. Most characteristic changes in NP+ were observed in domains of memory, psychomotor speed, and complex attention. This suggests nonspecific CNS involvement, which is in line with neurological manifestations of the disease.     

Cognitive impairment in systemic lupus erythematosus and neuropsychiatric systemic lupus erythematosus: a population-based neuropsychological study

We present a cross-sectional, population-based neuropsychological study of systemic lupus erythematosus (SLE) patients identified within Tampere University Hospital district, Finland with 440,000 inhabitants. Patients with definite SLE in the age range of 16-65 years (n = 46) and matched controls (n = 46) underwent neurological examination and comprehensive neuropsychological testing. On the basis of medical examination, the SLE patients were divided into neuropsychiatric (NP+; n = 15) and nonneuropsychiatric (NP-; n = 31) cases. The neuropsychological test results revealed more prevalent cognitive impairment in the NP+ patients, indicating that this subgroup mostly accounts for neuropsychological changes in SLE. Most characteristic changes in NP+ were observed in domains of memory, psychomotor speed, and complex attention. This suggests nonspecific CNS involvement, which is in line with neurological manifestations of the disease.     

Persistent mild cognitive impairment in geriatric depression

BACKGROUND: Cognitive impairment often occurs with geriatric depression and impairments may persist despite remission of depression. Although clinical definitions of mild cognitive impairment (MCI) have typically excluded depression, a neuropsychological model of MCI in depression has utility for identifying individuals whose cognitive impairments may persist or progress to dementia. METHODS: At baseline and 1-year follow-up, 67 geriatric patients with depression had a comprehensive clinical examination that included depression assessment and neuropsychological testing. We defined MCI by a neuropsychological algorithm and examined the odds of MCI classification at Year 1 for remitted depressed individuals with baseline MCI, and examined clinical, functional and genetic factors associated with MCI. RESULTS: Fifty-four percent of the sample had MCI at baseline. Odds of MCI classification at Year 1 were four times greater among patients with baseline MCI than those without. Instrumental activities of daily living were associated with MCI at Year 1, while age and APOE genotype was not. CONCLUSIONS: These results confirm previous observations that MCI is highly prevalent among older depressed adults and that cognitive impairment occurring during acute depression may persist after depression remits. Self-reported decline in functional activities may be a marker for persistent cognitive impairment, which suggests that assessments of both neuropsychological and functional status are important prognostic factors in the evaluation of geriatric depression.     

The nature and determinants of neuropsychological functioning in late-life depression

CONTEXT: Cognitive impairment in late-life depression (LLD) is highly prevalent, disabling, poorly understood, and likely related to long-term outcome. OBJECTIVES: To determine the characteristics and determinants of neuropsychological functioning LLD. DESIGN: Cross-sectional study of groups of LLD patients and control subjects. SETTING: Outpatient, university-based depression research clinic. PARTICIPANTS: One hundred patients without dementia 60 years and older who met DSM-IV criteria for current episode of unipolar major depression (nonpsychotic) and 40 nondepressed, age- and education-equated control subjects. MAIN OUTCOME MEASURES: A comprehensive neuropsychological battery. RESULTS: Relative to control subjects, LLD patients performed poorer in all cognitive domains. More than half exhibited significant impairment (performance below the 10th percentile of the control group). Information processing speed and visuospatial and executive abilities were the most broadly and frequently impaired. The neuropsychological impairments were mediated almost entirely by slowed information processing (beta =.45-.80). Education (beta =.32) and ventricular atrophy (beta =.28) made additional modest contributions to variance in measures of language ability. Medical and vascular disease burden, apolipoprotein E genotype, and serum anticholinergicity did not contribute to variance in any cognitive domain. CONCLUSIONS: Late-life depression is characterized by slowed information processing, which affects all realms of cognition. This supports the concept that frontostriatal dysfunction plays a key role in LLD. The putative role of some risk factors was validated (eg, advanced age, low education, depression severity), whereas others were not (eg, medical burden, age at onset of first depressive episode). Further studies of neuropsychological functioning in remitted LLD patients are needed to parse episode-related and persistent factors and to relate them to underlying neural dysfunction.     

Depression in veterans with Parkinson's disease: frequency, co-morbidity, and healthcare utilization

OBJECTIVE: To determine the frequency of depression in Parkinson's disease (PD) in routine clinical care, and to examine its association with co-morbid psychiatric and medical conditions and healthcare utilization. METHODS: Depression diagnoses and healthcare utilization data for all male veterans with PD age 55 or older seen in fiscal year 2002 (n = 41,162) were analyzed using Department of Veterans Affairs (VA) national databases. Frequencies of co-morbid disorders and healthcare utilization were determined for depressed and non-depressed patients; associations with depression were examined using multivariate logistic regression models. RESULTS: A depression diagnosis was recorded for 18.5% of PD patients, including major depression in 3.9%. Depression decreased in frequency and severity with increasing age. In multivariate logistic regression models, depressed patients had significantly greater psychiatric and medical co-morbidity, including dementia, psychosis, stroke, congestive heart failure, diabetes, and chronic obstructive pulmonary disease than non-depressed patients (all p < 0.01). Depressed PD patients were also significantly more likely to have medical (OR = 1.34, 95% CI = 1.25-1.44) and psychiatric hospitalizations (OR = 2.14, 95% CI = 1.83-2.51), and had more outpatient visits (p < 0.01), than non-depressed PD patients in adjusted models. CONCLUSION: Depression in PD in non-tertiary care settings may not be as common or as severe as that seen in specialty care, though these findings also may reflect under-recognition or diagnostic imprecision. The occurrence of depression in PD is associated with greater psychiatric and medical co-morbidity, and greater healthcare utilization. These findings suggest that screening for depression in PD is important and should be embedded in a comprehensive psychiatric, neuropsychological, and medical evaluation.     

Prediction of all-cause dementia using neuropsychological tests within 10 and 5 years of diagnosis in a community-based sample

While neuropsychological tests have been identified for the early prediction of Alzheimer's disease, this has not been established for prediction of all-cause dementia. This would be helpful for clinicians concerned about the risk of progression to dementia in patients who may present with a variety of medical and neurological conditions. We wanted to determine whether neuropsychological tests could accurately predict incident dementia within 10 and five years of diagnosis in a community-based sample. The Canadian Study of Health and Aging was conducted in three waves over a 10-year period (1991-2002). We studied 1472 non-demented participants who completed neuropsychological testing in 1991 and received a diagnostic assessment for dementia in 2001 (n = 284). We also studied 1231 non-demented participants who completed neuropsychological testing in 1996 and received a diagnostic assessment in 2001 (n = 634). Diagnosticians were blinded to performance on the predictive tests. Age, education, and sex were included as covariates in all regression analysis. Ten-year prediction: 2 tests, Rey Auditory Verbal Learning Test (RAVLT) short delayed verbal recall and Wechsler Adult Intelligence Test Revised (WAIS-R) Digit Symbol, were significant predictors of dementia (sensitivity = 78%, specificity = 72%, positive likelihood ratio = 2.81). Five-year prediction: 4 tests, Wechsler Memory Scale Information, RAVLT short delayed verbal recall, animal fluency, and WAIS-R Digit Symbol, significantly predicted incident dementia (sensitivity = 75%, specificity = 74%, positive likelihood ratio = 2.90). Regression models were supported with bootstrapping estimates. Neuropsychological tests can accurately predict progression to all-cause dementia within 10 years of diagnosis in a large community-based sample of non-demented participants.     

Fatigue in primary genetic mitochondrial disease: No rest for the weary

Rates of perceived fatigue, anxiety, depression, sleepiness and mitochondrial disease severity were assessed prospectively in 2017–2018 using established validated questionnaires in 48 adult patients with genetically confirmed primary mitochondrial disease. Fatigue was found to be very common among patients with primary mitochondrial disease, with 34 to 48 (71–100%) patients reporting fatigue depending on the measure used, and the severity of fatigue correlating with the severity of disease. Moderate-to-severe depression (10/48; 20.8%) anxiety (28/48; 58.3%) and sleep problems (16/48; 33.3%) were frequent in our patients with fatigue and these conditions were even more prevalent in those with severe fatigue. In conclusion, perceived fatigue was common in patients with primary mitochondrial disease and appeared to correlate with disease severity. Depression, anxiety and sleep disorders were more common in the cohort than those with other chronic diseases but with rates similar to that seen in multiple sclerosis. The severity of perceived fatigue correlated with an increased risk of these comorbid conditions. The Fatigue Severity Scale may more selectively measure non-anxiety/sleep-related fatigue in primary mitochondrial disease and additional testing is planned.     

Screening for multiple sclerosis cognitive impairment using a self-administered 15-item questionnaire

Since there is a need for cost-effective screening techniques to identify neuropsychological impairment in multiple sclerosis (MS) patients, and because existing methods require cognitive testing with subsequent interpretation by a neuropsychologist, a brief self-report procedure was developed to screen for neuropsychological impairment in MS. In the first phase of the study, a pool of 80 items was generated based on a literature review and consultation with healthcare professionals. The set was reduced to 15 via Rasch analysis. Using these items, a brief (five minute) MS Neuropsychological Screening Questionnaire (MSNQ), including patient- and informant-report forms, was composed. In phase II, 50 MS patients and their caregivers completed the MSNQ. A comprehensive neuropsychological test battery was also administered. Analyses covered the reliability of the MSNQ and correlations between both patient- and informant-report scores and objective neuropsychological testing. Cronbach's alpha coefficients were 0.93 and 0.94 for the patient- and informant-report forms, respectively, and both forms of the test were strongly correlated with a more general cognitive complaints questionnaire. The patient MSNQ form correlated significantly with measures of depression but not with objective tests of cognitive function. In contrast, the informant form was correlated with patient cognitive performance but not depression. A cut-off score of 27 on the informant form of the MSNQ optimally separated patients based on a neuropsychological summary score encompassing measures of processing speed and memory. There were two false-negatives and one false-positive, giving the test a sensitivity of 0.83 and a specificity of 0.97. It is concluded, therefore, that this self-administered neuropsychological screening test is reliable and predicts neuropsychological impairment in MS patients with a reasonable degree of accuracy.     

Alzheimer's disease and depression: neuropsychological impairment and progression of the illness

The authors longitudinally evaluated the cognitive functions of patients with probable Alzheimer's disease who also met criteria for major depression and compared them with matched patients with Alzheimer's disease who were not depressed. They found no significant difference in the pattern of neuropsychological deficits between the two groups; composite scores on attention, language, memory, learning, and visuospatial functions did not differentiate the two groups at baseline or at 1-year follow-up. The results of this preliminary report suggest that depression does not modify the neuropsychological features and the rate of progression of Alzheimer's disease.     

Neuropsychological processing associated with recovery from depression after stereotactic subcaudate tractotomy

OBJECTIVE: The authors compared patients who underwent stereotactic subcaudate tractotomy for depression, who were still depressed or recovered from depression, to identify therapeutic mechanisms. METHOD: Ten depressed and eight recovered psychosurgery patients, along with nine never-depressed subjects and nine who had recovered from depression with medication, completed the Iowa Gambling Task, a measure of decision making in the face of feedback. Psychosurgery patients also completed general neuropsychological testing. RESULTS: Recovered psychosurgery patients exhibited insensitivity to negative feedback on the Iowa Gambling Task compared to the other three groups. This difference between the groups remained when general neuropsychological performance was covaried out. CONCLUSIONS: These findings suggest acquired relative insensitivity to negative information as a specific mechanism mediating the antidepressant effect of stereotactic subcaudate tractotomy. Such insensitivity is not secondary to deficits in general neuropsychological functioning and is not a function of recovery from depression per se.