Sanford I. Finkel

Behavioral and psychological signs and symptoms of dementia: a consensus statement on current knowledge and implications for research and treatment.

The behavioral (e.g., repetitive questioning, hitting) and psychological (e.g., delusions, anxieties) signs and symptoms of dementia can result in suffering, premature institutionalization, increased costs of care, and significant loss in the quality of life for the patient and his or her family and caregivers.

The Alzheimer's Disease Activities of Daily Living International Scale (ADL-IS)

BACKGROUND Activities of daily living (ADL) deficits are integral components of dementia disorders, and ADL measures are among the most robust markers of the course of Alzheimers disease (AD). Despite this acknowledged importance, no clearly useful ADL instrument for cross-cultural application in pharmacologic trials in the early stages of AD had been available. METHOD An international effort was launched to develop an ADL scale for pharmacologic trials in early AD. Steps taken from 1990 to the present included: (1) international scientific working group meetings and reviews, (2) reviews of existing measures, (3) collating of existent, nonredundant items, (4) querying experts for new items, (5) interviews with informants and subjects in the USA, France, and Germany, toward the identification of potential new items, (6) identification of an item pool based upon these procedures, (7) creation of a trial instrument, (8) piloting of this instrument, and (9) refinement of the scale based upon statistical analysis of the pilot data. Final item selection was based upon: (1) relevance for > or = 80% of subjects in severity-stratified USA and German samples; (2) absence of gender and national biases; (3) significant (p <.05) discrimination between (a) normal versus mildly impaired and (b) mildly impaired versus moderately to moderately severely impaired subjects; and (4) Global Deterioration Scale (GDS) scores accounting for > or = 12% of variance in the item after controlling for age and gender. RESULTS An ADL scale consisting of 40 items that correlate with the global and cognitive progress of AD is developed for international usage in pharmacologic trials in incipient, mild, moderate, and moderately severe AD. The scale contains 40 items falling within 13 ADL categories. The 40-item scale is shown to have .81 correlation with GDS staging, .81 with mental status assessment (Mini-Mental State Examination), and .81 with a psychometric test (the SKT) (p values < .001). CONCLUSION This scale can be used to measure therapeutic response in AD.

A Brief Agitation Rating Scale (BARS) for nursing home elderly

Objective: To determine the effectiveness of a brief agitation rating scale (BARS) derived from the Cohen‐Mansfield Agitation Inventory (CMAI).

Comparative efficacy and safety of sertraline versus nortriptyline in major depression in patients 70 and older.

BACKGROUND Few randomized, double-blind studies that examine antidepressant treatment in patients 70 years and older are available. To provide additional data on the safety and efficacy of antidepressants in this rapidly growing population segment, a subgroup analysis of a larger sertraline vs. nortriptyline elderly depression treatment study was performed. METHODS Outpatients (N = 76) who met DSM-III-R criteria for major depression with a minimum Hamilton Depression Rating Scale (HAM-D) severity score of 18 were randomized to 12 weeks of flexible dose treatment with sertraline (50-150 mg) or nortriptyline (25-100 mg). RESULTS Both treatments significantly improved depression as measured by the HAM-D and Clinical Global Impression scales. At Weeks 10, 12, and endpoint, sertraline demonstrated a significantly greater reduction in depression severity compared to nortriptyline as measured by improvement on the 24-item HAM-D (mean adjusted change score of 14.8 vs. 7.6, respectively, at Week 12; p = .001). Sixty-five percent of sertraline-treated patients were responders by Week 12 (50% or greater reduction from baseline in 24-item HAM-D score) compared to 26% of nortriptyline-treated patients (p < .05). Sertraline treatment had a significantly more positive effect, when compared to nortriptyline, across almost all associated measures of cognitive function, energy, anxiety, and quality of life and was better tolerated than nortriptyline, with a lower attrition rate/side effect burden. CONCLUSION The efficacy advantage of sertraline appeared to be even greater in this subgroup of older patients drawn from a larger treatment study of depression that included elderly individuals over the age of 60.

New Focus on Behavioral and Psychological Signs and Symptoms of Dementia

The conceptualization of an international consensus conference for the purpose of beginning to establish an operational definition for “behavioral disturbances of dementia” was born at the 7th International Psychogeriatric Association (IPA) Congress in Sydney, Australia, in November 1995. At that time, a special symposium on “research methodological issues in evaluating behavioral disorders of dementia” took place. From the high level of interest and attendance, it was clear that this matter was a source of great attention and concern by clinicians and researchers working with demented elderly. Although we have been aware that patients with dementias, including Alzheimers disease (AD), manifest psychotic, depressive, and behavioral symptoms over the course of the illness, such symptoms until recently have elicited little interest or research support. Further, research was hampered by the absence of viable measurements and scales developed for this specific population. In addition, rigorous clinical trials were rare and virtually nonexistent in those with moderate and advanced dementias. Prior to 1992, only seven randomly assigned, double-blind trials in this population had been published, only one in a nursing home setting.

Validity of the Severity of Psychiatric Illness Rating Scale in a Sample of Inpatients on a Psychogeriatric Unit

Previous efforts to define the case mix of psychiatric inpatients have generally relied on the use of psychiatric diagnosis, and have had little success elucidating the relationship between clinical outcome and resource utilization. The Severity of Psychiatric Illness (SPI) rating scale, a reliable chart-based system using nine clinical rating dimensions, has been developed by one of the authors for use in studying the case mix of psychiatric inpatients. This report is the first describing this scale. For a sample of 244 psychogeriatric patients, all but one of the dimensions were significantly correlated with at least one of the five baseline clinical assessments, and all but one of the SPI items were correlated with outcome assessment. Four dimensions of the SPI were related to clinical outcomes. The SPI also predicted length of stay (predicting 23% of the variance for patients discharged to their homes). This study provides strong evidence for the construct and predictive validity of the SPI among older adult psychiatric inpatients.

Pharmacology of Antipsychotics in the Elderly: A Focus on Atypicals

Psychoses are the mental and behavioral disorders characterized by hallucinations or delusions that are not attributable to other causes such as intoxication or delirium. These disorders are commonly found in the elderly and can manifest as a result of a disease whose onset occurred at an early age or as a complication of an organic disease in later life. Psychoses have prevalence rates that vary from 6% to 10% in the elderly population. They belong to one of two groups: primary psychotic disorders (e.g., schizophrenia) or psychosis secondary to dementia (e.g., Alzheimer’s disease (AD), Lewy body dementia (LBD)) or other medical conditions (e.g., Parkinson’s disease (PD)). A 4-year study conducted to determine the level of psychosis in AD found that approximately 50% of patients with AD manifest psychotic symptoms within 3 years of their diagnosis, and another study found that more than 60% of patients with AD will manifest psychotic symptoms over approximately 5 years. Some investigators estimated the persistence of behavioral-psychological symptoms, including delusions, hallucinations, agitation, and aggression, in a population-based sample of 329 patients with AD and dementia. They used the Neuropsychiatric Inventory (NPI) scale as an endpoint. Two hundred four (62%) of patients tested were found to have neuropsychiatric symptoms at baseline (total NPI score 40). Eighteen months later, 117 subjects were still alive and available for follow-up, and NPI scores were obtained. Investigators found that, of the 10 neuropsychiatric domains that were tested using the NPI scale at baseline, delusions persisted in 65.5% of individuals at 18 months. These investigators suggested that neuropsychiatric symptoms in dementia are highly persistent and that neuropsychiatric symptoms may be underrecognized in the community. They emphasized the need for evaluating and treating neuropsychiatric symptoms in patients with dementia. Another group of investigators proposed diagnostic criteria for the psychosis of AD, which they believed to be a distinct syndrome that is markedly different from schizophrenia in elderly patients. LBD is the second-most-common cause of neurodegenerative dementia in older people. It occurs as a result of abnormal aggregation of the synaptic protein alpha-synuclein. LBD has many of the clinical and pathological characteristics of dementia that occur during the course of PD. In patients with LBD, severe neuroleptic sensitivity reactions are associated with significantly increased morbidity and mortality; thus, accurate identification of LBD patients is critical to appropriate therapy. PD is another condition predisposing elderly patients to psychotic symptoms at a rate of 20% to 60%. The majority of psychosis in patients with PD results from treatment with antiparkinsonian drugs. Therefore, psychotic symptoms in patients treated with antiparkinsonian drugs should be considered drug-related until proven otherwise. Healthcare providers must investigate psychotic symptoms to identify and appropriately address the underlying medical conditions in their elderly patients. When psychotic symptoms are severe enough to cause distressing agitation and aggressive behavior or otherwise interfere with everyday functioning, the implementation of pharmacological treatment must be considered. Pharmacological treatment usually consists of antipsychotic medications stratified into two categories: conventional antipsychotics (first generation) and atypical antipsychotics (second generation). With their recent advent, atypical antipsychotic medications may be less familiar to healthcare providers than conventional antipsychotics. The consensus among thought leaders is that healthcare providers who are knowledgeable about the pharmacology and therapeutic properties of atypical antipsychotics can greatly improve quality of life in elderly patients with psychotic illness. Conventional and atypical antipsychotics are used to treat psychosis caused by a variety of conditions (e.g., schizophrenia, delirium, and dementia). Conventional antipsychotics are well known for such troubling side effects as extrapyramidal symptoms (EPS) and tardive dyskinesia (TD) and such anticholinergic symptoms as dry mouth, urinary retention, and blurred vision. In a review of data from 11 studies lasting 1 year or longer and involving 2,769 patients, the authors sought to determine the relative risk of developing TD in patients taking atypical antipsychotics. They found that, in adult patients and the elderly, the incidence of TD with atypical antipsychotics appears to be approximately one-fifth that with the conventional antipsychotics. Address correspondence to Sanford Finkel, MD, 3127 Greenleaf Avenue, Wilmette, IL 60091. E-mail: sandy.finkel@cje.net From the Council for Jewish Elderly, Chicago, Illinois; and University of Chicago, Chicago, Illinois.

A Retrospective Chart Review of Antidepressant Use, Effectiveness, and Adverse Effects in Adults Age 70 and Older

The authors assessed the use, side effects, and outcomes of various antidepressants, including selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs), in adults 70 years of age and older by means of a retrospective study of outpatient records. Of these patients (N = 70), 26% improved or recovered. Patients were more likely to improve or recover if they took the antidepressant for at least 3 months. Those on TCAs were as likely to improve or recover and no more likely to discontinue because of side effects than those prescribed SSRIs. Approximately one-third of patients discontinued because of side effects, and SSRI gastrointestinal side effects were more common in patients concomitantly taking nonsteroidal anti-inflammatory drugs. Many older patients who undergo antidepressant therapy discontinue because of side effects; however patients are likely to improve or recover with sustained therapy.

Late-life suicide

Suicide rates for older people are increasing worldwide, thereby creating a major public health concern. There has been an absence of public policy and research interest in this area, although the needs are pressing and promise to be even more so.

Nimodipine potentiates the light-induced suppression of melatonin

In mammals the phase shifting response of the circadian clock to light can be enhanced by administration of the calcium channel antagonist nimodipine. In the present study we assessed the potential for nimodipine to affect the responsiveness of the human circadian clock to light by measuring the light-induced suppression of melatonin levels in plasma. Seven healthy young subjects (3M, 4F, 27.3 +/- 1.8 years old) were admitted on four occasions to the Clinical Research Center at Northwestern University Medical School. Blood was collected during the night to assess the effect of nimodipine (30 mg, orally, 01:30 h) on plasma melatonin levels in the presence or absence of light (500 lux, 2-3 am). Melatonin levels in plasma were measured by radioimmunoassay. Exposure to light for 1 h suppressed melatonin levels in plasma by nearly 38% relative to samples obtained at the same time in the absence of light (P = 0.013). Nimodipine administration did not modify plasma melatonin levels. However, combined treatment with nimodipine and light suppressed melatonin levels in plasma by 59%. Levels of plasma melatonin were significantly lower following treatment with nimodipine and light than following treatment with placebo/light (P = 0.014). Thus, the calcium channel antagonist nimodipine potentiated the suppressive effect of light on melatonin levels in plasma. These results suggest that the calcium channel antagonist nimodipine may also potentiate the response of the human circadian clock to light, and might thus be useful in combination with phototherapy for the treatment of sleep and circadian rhythm disorders.