Major depressive disorder. Psychopathology, medical management and dental implications.

BACKGROUND: Major depressive disorder, or MDD, is a psychiatric illness in which mood, thoughts and behavioral patterns are impaired for long periods. The illness distresses the person and impairs his or her social functioning and quality of life. MDD is characterized by marked sadness or a loss of interest or pleasure in daily activities, and is accompanied by weight change, sleep disturbance, fatigue, difficulty concentrating, physical impairment and a high suicide rate. In 2000, the World Health Organization, or WHO, identified MDD as the fourth ranked cause of disability and premature death in the world. WHO projected that by 2020, MDD would rise in disease burden to be second only to ischemic heart disease. The disorder is common in the United States, with a lifetime prevalence rate of 17 percent and a recurrence rate of more than 50 percent. CONCLUSIONS: MDD may be associated with extensive dental disease, and people may seek dental treatment before becoming aware of their psychiatric illness. MDD frequently is associated with a disinterest in performing appropriate oral hygiene techniques, a cariogenic diet, diminished salivary flow, rampant dental caries, advanced periodontal disease and oral dysesthesias. Many medications used to treat the disease magnify the xerostomia and increase the incidence of dental disease. Appropriate dental management requires a vigorous dental education program, the use of saliva substitutes and anticaries agents containing fluoride, and special precautions when prescribing or administering analgesics and local anesthetics. CLINICAL IMPLICATIONS: Dentists cognizant of these signs and symptoms have an opportunity to recognize patients with occult MDD. After confirmation of the diagnosis and institution of treatment by a mental health practitioner, dentists usually can provide a full range of services that may enhance patients' self-esteem and contribute to the psychotherapeutic aspect of management.

Does behavioral improvement with haloperidol or trazodone treatment depend on psychosis or mood symptoms in patients with dementia?

OBJECTIVES: Several previous studies have examined the effects of pharmacological interventions for agitated behavior in patients with dementia. However, the choice of medication in clinical practice continues to be directed largely by local pharmacotherapy culture rather than empirical treatment guidelines. We examined the relationship between behavioral improvement and co-occurring delusions and mood symptoms in patients with dementia who were treated with haloperidol, an antipsychotic medication, or trazodone, a serotonergic antidepressant. DESIGN: Randomized, double-blind, parallel-group, 9-week treatment trial. SETTING: Inpatient geropsychiatry unit. PARTICIPANTS: Twenty-eight patients with dementia and agitated or aggressive behaviors. INTERVENTION: Haloperidol 1 to 5 mg/day or trazodone 50 to 250 mg/day. MEASUREMENTS: Cohen-Mansfield Agitation Inventory (CMAI), Hamilton Depression Rating Scale (Ham-D), and delusional thoughts subscale and hallucinations subscale of the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD). RESULTS: CMAI scores improved in each treatment group over the 9 weeks of treatment (P < .001 in each group). Within the haloperidol treatment group, CMAI improvement was not associated with baseline delusional thoughts score or with change in delusional thoughts score over the course of treatment. Within the trazodone treatment group, CMAI improvement was associated with baseline score on total Ham-D (r = -0.60, P = .02), Ham-D items measuring subjective mood symptoms (r = -0.50, P = .07), and Ham-D items measuring neurovegetative signs (r = -0.49, P = .08). CMAI improvement was also associated with improvement in Ham-D total score over the course of treatment (r = 0.62, P = .02). CONCLUSIONS: Mild depressive symptoms in patients with dementia and agitated behavior are associated with greater behavioral improvement by trazodone-treated patients. In contrast, the presence of delusions in concert with behavioral disturbance does not necessarily predict greater behavioral improvement with haloperidol treatment than in subjects without signs of psychosis.

Executive dysfunction in Alzheimer's disease: association with neuropsychiatric symptoms and functional impairment.

Relationships between measures of executive skills and neuropsychiatric and functional status were examined in a group of 31 patients with Alzheimer's disease. Deficits in four executive skills tests were significantly associated with the Agitation/Disinhibition factor score and Total Neuropsychiatric score on the Neurobehavioral Rating Scale, as well as the Activities subscore on the Blessed Dementia Scale. The majority of these associations remained significant after covariance for Mini-Mental State Examination scores. Executive dysfunction is associated with clinically relevant neuropsychiatric symptoms and functional impairment in Alzheimer's disease. These associations may be independent of other cognitive deficits such as memory, language, and visuospatial skills, and may not be appreciated on routine clinical evaluations. Executive skills deficits, neuropsychiatric symptoms, and functional disability may emerge from shared neurobiological mechanisms.

A double-blind comparison of trazodone and haloperidol for treatment of agitation in patients with dementia.

The authors compared the efficacy and side effects of trazodone and haloperidol for treating agitated behaviors associated with dementia. Twenty-eight elderly patients with dementia and agitated behaviors were randomly assigned to double-blind treatment with either trazodone (50-250 mg/day) or haloperidol (1-5 mg/day) for 9 weeks. There was no significant difference in improvement between the medication groups. Adverse effects, however, were more common in the group treated with haloperidol. Improvement in individual areas suggested that repetitive, verbally aggressive, and oppositional behaviors responded preferentially to trazodone, whereas symptoms of excessive motor activity and unwarranted accusations responded preferentially to haloperidol. These results indicate that moderate doses of trazodone and haloperidol are equally effective for treatment of overall agitated behaviors in patients with dementia, but specific symptoms may respond preferentially to a particular agent.

Cortical abnormalities associated with subcortical lesions in vascular dementia. Clinical and position emission tomographic findings.

OBJECTIVE: To examine the effects of subcortical lesions on cortical metabolic rate and clinical symptoms in patients with vascular dementia. METHOD: Eleven elderly patients with vascular dementia who demonstrated no lesion involving the cerebral cortex on magnetic resonance imaging underwent 18F-fluorodeoxyglucose positron emission tomography to assess global cortical metabolism and metabolic activity in each cortical lobe. Subcortical lesions on magnetic resonance imaging (periventricular hyperintensities, deep white matter hyperintensities, and subcortical lacunar infarcts) were measured using a graded scale of severity. Cognitive and noncognitive symptoms were assessed with the Neurobehavioral Rating Scale. RESULTS: Reduced cortical metabolism was generally associated with the severity of subcortical pathologic changes, but there was substantial heterogeneity in the relationship between subcortical lesions and cortical metabolic activity. Mean global cortical metabolism was lower in patients with periventricular hyperintensities in anterior subcortical regions than in those without such lesions. The metabolic rate in the frontal cortex was lower in patients with a lacunar infarct of the basal ganglia or thalamus than in those without. Neurobehavioral Rating Scale total score, the Verbal Output Disturbance factor score, and the Anxiety/Depression factor score were correlated with the severity of white matter lesions. CONCLUSIONS: Cortical metabolic dysfunction is related to ischemic subcortical lesions in patients with vascular dementia. Metabolism in the frontal cortex may be particularly dependent on pathologic alterations of subcortical nuclei. Anxiety, depression, and the overall severity of neuropsychiatric symptoms in vascular dementia are associated with the extent of white matter ischemia.

The relationship between psychiatric symptoms and regional cortical metabolism in Alzheimer's disease.

Cognitive and noncognitive psychiatric symptoms were systematically evaluated in 21 patients with Alzheimer's disease by using the Neurobehavioral Rating Scale. Regional cerebral metabolic activity was measured in each patient by [18F]fluorodeoxyglucose PET. Significant correlations emerged between global cortical metabolic activity and the Agitation/Disinhibition factor score, Cognition factor score, and total score. Relationships between noncognitive symptoms and metabolic activity were regionally specific, with significant correlations between Agitation/Disinhibition factor score and metabolism in the frontal and temporal lobes, between Psychosis factor score and metabolism in the frontal lobe, and between Anxiety/Depression factor score and metabolism in the parietal lobe. These results suggest that psychiatric symptoms are fundamental expressions of the cortical dysfunction of Alzheimer's disease.

p(C) analysis facilitates dementia diagnosis.

A modified receiver operating characteristic (ROC) analysis technique was applied to a sample of 161 consecutive volunteers seen in a dementia clinic. Clinical, imaging, neuropsychological, and laboratory evaluation guided experienced clinicians in clinical diagnosis, taken as the "gold standard." Two symptom inventories, the Hachinski Ischemic Score and the Dementia of the Alzheimer's Type Inventory, were obtained by clinicians who were blind to final clinical diagnosis; scores on these inventories correlate with the likelihoods of multi-infarct dementia and Alzheimer's disease, respectively. A disjunctive sequential testing strategy was analyzed such that subthreshold scores on the first test identified patients for whom the second test was considered. Both tests were analyzed at all possible cutoff-point combinations and in both possible testing sequences. Diagnoses based on these tests were compared with the clinical "gold standard" diagnoses to determine the accuracy of the testing procedures. The best strategy correctly classified 154/161 (95.6%) of the dementia patients and required cutoff points (5 for the HIS and 10 for the Dementia of the Alzheimer's Type Inventory) that were lower than those usually recommended for either test used alone (i.e., 7 and 14, respectively). The Hachinski Ischemic Score--then Dementia of the Alzheimer's Type Inventory testing sequence was superior to the reverse strategy. A sensitivity analysis (varying prevalences of Alzheimer's disease, multi-infarct dementia, and other dementias) revealed similar test performances across a wide range of prevalences. These data suggest that simple clinical tests that take approximately 30 minutes to administer can produce diagnostic classifications of dementia that are similar to those of clinicians experienced in dementia diagnosis.

Parkinson's disease: making the diagnosis, selecting drug therapies.

Parkinson's disease is a progressive neurodegenerative condition of unknown cause and with no known cure. The diagnosis is based on clinical findings of rest tremor, muscle rigidity, bradykinesia, and gait instability. Over 40% of patients develop a dementia syndrome that is largely distinct from Alzheimer's disease. Depression is common, also occurring in more than 40% of patients with PD. Careful evaluation in necessary to help distinguish Parkinson's disease from secondary causes of parkinsonism. Carbidopa/levodopa, dopamine agonists, and monoamine oxidase type B inhibitors are the mainstays of treatment. Anticholinergics and other agents may also be useful. Pharmacologic treatment must be carefully titrated to control symptoms and to avoid side effects. In advanced disease, dose-related dyskinesias, end-of-dose wearing-off effect, and unpredictable sudden motor fluctuations become very disabling and difficult to manage.

Regional metabolic dependency in obstructive sleep apnea.

Abnormalities of oxygen use occur in obstructive sleep apnea, as do impaired cerebral perfusion and alterations of cerebral function. In this case study, the authors quantitated the local cerebral glucose metabolic rate in two patients with obstructive sleep apnea (one with and one without oxygen supply dependency) and assessed cerebral glucose use by increasing oxygen delivery through passive leg elevation. Obstructive sleep apnea was confirmed by visual analysis of nocturnal pulse oximetry traces in two patients and its severity assessed from the respiratory disturbance index and minimum oxygen saturation. Awake local cerebral glucose metabolic rate (microM/min/100 g) was determined by positron-emission tomography using [18F]-2-Fluoro-2-Deoxy-D-Glucose at baseline and on the following day during passive leg elevation. Conditions otherwise were unchanged. The patient with global oxygen supply dependency exhibited a significant increase in the local cerebral glucose metabolic rate. In contrast, the patient without global supply dependency had no change in the local cerebral glucose metabolic rate. These case studies demonstrate the first evidence of improvement in regional metabolic consumption in response to increased oxygen delivery and in the presence of global oxygen supply dependency.

A comparison of psychiatric symptoms in vascular dementia and Alzheimer's disease.

OBJECTIVE: Psychiatric symptoms account for much of the morbidity of vascular dementia and Alzheimer's disease. The goals of this study were to extend previous observations of the psychopathology and behavioral problems associated with vascular dementia and to compare the profile of symptoms in patients with vascular dementia to that in patients with Alzheimer's disease. METHOD: Twenty-eight pairs of patients (one with vascular dementia and one with Alzheimer's disease) were matched with respect to education, age, and severity of dementia. Their psychiatric symptoms were assessed with the Neurobehavioral Rating Scale, a 28-item observer-rated instrument, and the Hamilton Depression Rating Scale, and the symptoms in the two diagnostic groups were compared. RESULTS: Blunted affect, depressed mood, emotional withdrawal, motor retardation, low motivation, anxiety, unusual thoughts, and somatic concerns occurred in more than one-third of the patients with vascular dementia. There was no significant relation between severity of cognitive impairment and severity of these noncognitive symptoms. The patients with vascular dementia had more impairment than the patients with Alzheimer's disease, as indicated by the Neurobehavioral Rating Scale total scores and scores on the behavioral retardation, anxiety/depression, and verbal output disturbance factors. They also had a higher total score on the Hamilton depression scale and higher scores on 14 of the 17 Hamilton depression items. CONCLUSIONS: Patients with vascular dementia have more severe behavioral retardation, depression, and anxiety than those with Alzheimer's disease when the groups have similar levels of cognitive impairment. This probably reflects the contrasting brain regions typically involved in the two disorders.

Assessment of cognitive, psychiatric, and behavioral disturbances in patients with dementia: the Neurobehavioral Rating Scale.

OBJECTIVE: To assess the validity of the Neurobehavioral Rating Scale (NRS) in patients with Alzheimer's disease (AD) or multi-infarct dementia (MID) and to characterize the cognitive, psychiatric, and behavioral disturbances that occur in these patients. DESIGN: Cross-sectional evaluation. SETTING: West Los Angeles VAMC Geropsychiatry Inpatient Unit, Neurobehavior Inpatient Unit, and Dementia Clinic; UCLA Alzheimer's Disease Clinic. PATIENTS: Convenience sample of 61 patients with AD and 22 patients with MID. MAIN OUTCOME MEASURE: The NRS, a 27-item observer-rated instrument that measures cognitive, psychiatric, and behavioral disturbances. RESULTS: The NRS demonstrated content and convergent validity in this patient group. Principal components analysis of the NRS ratings identified a six-factor solution, and each factor contained clinically related symptoms. The factors were Cognition/Insight, Agitation/Disinhibition, Behavioral Retardation, Anxiety/Depression, Verbal Output Disturbance, and Psychosis. Among the patients with AD, agitation, disinhibition, hostility, poor insight, poor motivation, suspiciousness, and delusions were more severe in patients with more advanced dementia. Depressive symptoms occurred with equal severity in patients with mild and advanced dementia, but depressed mood was more severe in patients with earlier age of onset of AD. CONCLUSION: The NRS is a useful instrument for structured assessment of a broad range of cognitive, psychiatric, and behavioral disturbances in patients with dementia.

Behavioral manifestations associated with multiple sclerosis.

The behavioral manifestations associated with MS include both cognitive and emotional disturbances. Overall intellect is slightly affected in about half of patients, and 20% to 33% demonstrate more severe impairments. Memory disturbances are particularly common, and retrieval function is especially affected. Difficulties with concept formation and other executive functions can be subtle yet have significant impact on daily living. Depression is frequent in MS, sometimes despite an outward euphoria that is more prevalent with advancing disease. Psychosis occurs rarely, but bipolar disorder is more frequent than in the general population. MS may be associated with a variety of personality changes, but it is impossible to generalize about this or to identify an "MS personality." Disturbances of emotional control are relatively frequent. Comprehensive management of these problems uses multiple modalities including good neurologic care, cognitive rehabilitation, counseling and support groups, and pharmacotherapy.

Behavioral neurology of multi-infarct dementia.

Multi-infarct dementia (MID) is a heterogeneous entity in which a variety of cerebrovascular disorders leads to intellectual impairment. A variety of patterns of behavioral changes may be observed in MID, depression, psychosis, and personality change are common. The neurobehavioral syndromes of MID are determined by the specific arteries involved and the location and extent of tissue infarction.

Alzheimer disease and the dementia of Parkinson disease: comparative investigations.

Intellectual abnormalities are common in Parkinson disease (PD), occurring in a majority of patients and exhibiting a spectrum of severity from mild to severe. Alzheimer disease (AD) has been posited as the cause of dementia in PD. Comparative neuropsychological studies, however, show differences in memory, language, and frontal lobe functions between AD and PD patients even when the two groups have comparably severe dementia syndromes. The AD-type neuropathology occurs in 10-60% of PD patients, and dementia is usually overt when AD pathology is identified at autopsy. The AD changes are less frequent than intellectual deterioration in PD, and dementia has been observed in PD patients without AD pathology. Therefore, concurrent AD cannot be the cause of all cases of dementia in PD. Cholinergic deficits occur in some PD patients, but cholinergic deficits have been described in patients without dementia and dementia has been documented in patients without cholinergic system abnormalities. Dopaminergic disturbances contribute to the dementia of PD. Differences in neuropeptide concentrations, electrophysiologic responses, and cerebral metabolism also support pathophysiologic distinctions between AD and the dementia of PD. Genetic investigations suggest a role for heredity in AD, whereas PD appears to be an acquired, nongenetic disorder. These studies indicate that despite areas of overlap in clinical symptoms and neuropathology, AD and the dementia of PD are largely distinct.

Seizures: common causes and treatment in the elderly.

Seizures occur in the elderly with a frequency, on an age-specific basis, that is as high as in the neonatal period. However, the spectrum of etiologies and the management of seizures reflect the effects of aging and give rise to certain special considerations. Structural brain diseases such as stroke and tumor account for the majority of cases of new seizures over age 65. Correct identification of the cause of seizures is important for initiating the appropriate therapy. Selection of an anti-convulsant depends partially upon the side effects to be avoided in specific patients. Complete remission of late-life seizures is uncommon, although excellent seizure control can usually be achieved with the correct medication.

Treatable dementias.

Dementia is an acquired impairment of intellect produced by brain dysfunction. In the past, dementia was regarded as inevitably chronic, progressive and irreversible. More recently dementia has been viewed as a clinical syndrome that may be produced by both irreversible and reversible conditions. Recognition of the presence of a dementia syndrome should be followed by an evaluation for potentially treatable causes of the intellectual deterioration. Dementia treatment includes therapy for reversible or curable dementias and nonspecific interventions that may improve the condition of patients with progressive dementia syndromes.

Altered mental status in the elderly.

Misdiagnosis of treatable dementia in the aged is costly to society and the family, and is unmeasurable in personal tragedy. The 4 Ds of the elderly--dementia, depression, delirium, and delusion--are discussed. Family physicians are encouraged to seek out treatable disease.