Helen C. Kales

Dementia prevention, intervention, and care

Acting now on dementia prevention, intervention, and care will vastly improve living and dying for individuals with dementia and their families, and in doing so, will transform the future for society. Dementia is the greatest global challenge for health and social care in the 21st century. It occurs mainly in people older than 65 years, so increases in numbers and costs are driven, worldwide, by increased longevity resulting from the welcome reduction in people dying prematurely. The Lancet Commission on Dementia Prevention, Intervention, and Care met to consolidate the huge strides that have been made and the emerging knowledge as to what we should do to prevent and manage dementia. Globally, about 47 million people were living with dementia in 2015, and this number is projected to triple by 2050. Dementia affects the individuals with the condition, who gradually lose their abilities, as well as their relatives and other supporters, who have to cope with seeing a family member or friend become ill and decline, while responding to their needs, such as increasing dependency and changes in behaviour. Additionally, it affects the wider society because people with dementia also require health and social care. The 2015 global cost of dementia was estimated to be US

Assessment and management of behavioral and psychological symptoms of dementia

818 billion, and this figure will continue to increase as the number of people with dementia rises. Nearly 85% of costs are related to family and social, rather than medical, care. It might be that new medical care in the future, including public health measures, could replace and possibly reduce some of this cost.

Nonpharmacologic Management of Behavioral Symptoms in Dementia

Behavioral and psychological symptoms of dementia include agitation, depression, apathy, repetitive questioning, psychosis, aggression, sleep problems, wandering, and a variety of inappropriate behaviors. One or more of these symptoms will affect nearly all people with dementia over the course of their illness. These symptoms are among the most complex, stressful, and costly aspects of care, and they lead to a myriad of poor patient health outcomes, healthcare problems, and income loss for family care givers. The causes include neurobiologically related disease factors; unmet needs; care giver factors; environmental triggers; and interactions of individual, care giver, and environmental factors. The complexity of these symptoms means that there is no “one size fits all solution,” and approaches tailored to the patient and the care giver are needed. Non-pharmacologic approaches should be used first line, although several exceptions are discussed. Non-pharmacologic approaches with the strongest evidence base involve family care giver interventions. Regarding pharmacologic treatments, antipsychotics have the strongest evidence base, although the risk to benefit ratio is a concern. An approach to integrating non-pharmacologic and pharmacologic treatments is described. Finally, the paradigm shift needed to fully institute tailored treatments for people and families dealing with these symptoms in the community is discussed.

Antipsychotics, Other Psychotropics, and the Risk of Death in Patients With Dementia: Number Needed to Harm

Behavioral symptoms such as repetitive speech, wandering, and sleep disturbances are a core clinical feature of Alzheimer disease and related dementias. If untreated, these behaviors can accelerate disease progression, worsen functional decline and quality of life, cause significant caregiver distress, and result in earlier nursing home placement. Systematic screening for behavioral symptoms in dementia is an important prevention strategy that facilitates early treatment of behavioral symptoms by identifying underlying causes and tailoring a treatment plan. First-line nonpharmacologic treatments are recommended because available pharmacologic treatments are only modestly effective, have notable risks, and do not effectively treat some of the behaviors that family members and caregivers find most distressing. Examples of nonpharmacologic treatments include provision of caregiver education and support, training in problem solving, and targeted therapy directed at the underlying causes for specific behaviors (eg, implementing nighttime routines to address sleep disturbances). Based on an actual case, we characterize common behavioral symptoms and describe a strategy for selecting evidence-based nonpharmacologic dementia treatments. Nonpharmacologic management of behavioral symptoms in dementia can significantly improve quality of life and patient-caregiver satisfaction.

Risk of mortality among individual antipsychotics in patients with dementia.

IMPORTANCE Antipsychotic medications are associated with increased mortality in older adults with dementia, yet their absolute effect on risk relative to no treatment or an alternative psychotropic is unclear. OBJECTIVE To determine the absolute mortality risk increase and number needed to harm (NNH) (ie, number of patients who receive treatment that would be associated with 1 death) of antipsychotic, valproic acid and its derivatives, and antidepressant use in patients with dementia relative to either no treatment or antidepressant treatment. DESIGN, SETTING, AND PARTICIPANTS A retrospective case-control study was conducted in the Veterans Health Administration from October 1, 1998, through September 30, 2009. Participants included 90,786 patients 65 years or older with a diagnosis of dementia. Final analyses were conducted in August 2014. EXPOSURES A new prescription for an antipsychotic (haloperidol, olanzapine, quetiapine, and risperidone), valproic acid and its derivatives, or an antidepressant (46,008 medication users). MAIN OUTCOMES AND MEASURES Absolute change in mortality risk and NNH over 180 days of follow-up in medication users compared with nonmedication users matched on several risk factors. Among patients in whom a treatment with medication was initiated, mortality risk associated with each agent was also compared using the antidepressant group as the reference, adjusting for age, sex, years with dementia, presence of delirium, and other clinical and demographic characteristics. Secondary analyses compared dose-adjusted absolute change in mortality risk for olanzapine, quetiapine, and risperidone. RESULTS Compared with respective matched nonusers, individuals receiving haloperidol had an increased mortality risk of 3.8% (95% CI, 1.0%-6.6%; P < .01) with an NNH of 26 (95% CI, 15-99); followed by risperidone, 3.7% (95% CI, 2.2%-5.3%; P < .01) with an NNH of 27 (95% CI, 19-46); olanzapine, 2.5% (95% CI, 0.3%-4.7%; P = .02) with an NNH of 40 (95% CI, 21-312); and quetiapine, 2.0% (95% CI, 0.7%-3.3%; P < .01) with an NNH of 50 (95% CI, 30-150). Compared with antidepressant users, mortality risk ranged from 12.3% (95% CI, 8.6%-16.0%; P < .01) with an NNH of 8 (95% CI, 6-12) for haloperidol users to 3.2% (95% CI, 1.6%-4.9%; P < .01) with an NNH of 31 (95% CI, 21-62) for quetiapine users. As a group, the atypical antipsychotics (olanzapine, quetiapine, and risperidone) showed a dose-response increase in mortality risk, with 3.5% greater mortality (95% CI, 0.5%-6.5%; P = .02) in the high-dose subgroup relative to the low-dose group. When compared directly with quetiapine, dose-adjusted mortality risk was increased with both risperidone (1.7%; 95% CI, 0.6%-2.8%; P = .003) and olanzapine (1.5%; 95% CI, 0.02%-3.0%; P = .047). CONCLUSIONS AND RELEVANCE The absolute effect of antipsychotics on mortality in elderly patients with dementia may be higher than previously reported and increases with dose.

Management of Neuropsychiatric Symptoms of Dementia in Clinical Settings: Recommendations from a Multidisciplinary Expert Panel

OBJECTIVE The use of antipsychotics to treat the behavioral symptoms of dementia is associated with greater mortality. The authors examined the mortality risk of individual agents to augment the limited information on individual antipsychotic risk. METHOD The authors conducted a retrospective cohort study using national data from the U.S. Department of Veterans Affairs (fiscal years 1999-2008) for dementia patients age 65 and older who began outpatient treatment with an antipsychotic (risperidone, olanzapine, quetiapine, or haloperidol) or valproic acid and its derivatives (as a nonantipsychotic comparison). The total sample included 33,604 patients, and individual drug groups were compared for 180-day mortality rates. The authors analyzed the data using multivariate models and propensity adjustments. RESULTS In covariate-adjusted intent-to-treat analyses, haloperidol was associated with the highest mortality rates (relative risk=1.54, 95% confidence interval [CI]=1.38-1.73) followed by risperidone (reference), olanzapine (relative risk=0.99, 95% CI=0.89-1.10), valproic acid and its derivatives (relative risk=0.91, 95% CI=0.78-1.06), and quetiapine (relative risk=0.73, 95% CI=0.67-0.80). Propensity-stratified and propensity-weighted models as well as analyses controlling for site of care and medication dosage revealed similar patterns. The mortality risk with haloperidol was highest in the first 30 days but decreased significantly and sharply thereafter. Among the other agents, mortality risk differences were most significant in the first 120 days and declined in the subsequent 60 days during follow-up. CONCLUSIONS There may be differences in mortality risks among individual antipsychotic agents used for treating patients with dementia. The use of valproic acid and its derivatives as alternative agents to address the neuropsychiatric symptoms of dementia may carry associated risks as well.

Trends in Antipsychotic Use in Dementia 1999-2007

Noncognitive neuropsychiatric symptoms (NPS) of dementia (aggression, agitation, depression, anxiety, delusions, hallucinations, apathy, disinhibition) affect individuals with dementia nearly universally across dementia stages and etiologies. NPS are associated with poor outcomes for individuals with dementia and caregivers, including excess morbidity and mortality, greater healthcare use, and earlier nursing home placement, as well as caregiver stress, depression, and difficulty with employment. Although the Food and Drug Administration has not approved pharmacotherapy for NPS, psychotropic medications are frequently used to manage these symptoms, but in the few cases of proven pharmacological efficacy, significant risk of adverse effects may offset benefits. There is evidence of efficacy and limited potential for adverse effects of nonpharmacological treatments, typically considered first line, but their uptake as preferred treatments remains inadequate in real‐world clinical settings. Thus, the field currently finds itself in a predicament in terms of management of these difficult symptoms. It was in this context that the University of Michigan Program for Positive Aging, working in collaboration with the Johns Hopkins Alzheimers Disease Research Center and Center for Innovative Care in Aging sponsored and convened a multidisciplinary expert panel in Detroit, Michigan, in fall 2011 with three objectives: to define critical elements of care for NPS in dementia; to construct an approach describing the sequential and iterative steps of managing NPS in real‐world clinical settings that can be used as a basis for integrating nonpharmacological and pharmacological approaches; and to discuss how the approach generated could be implemented in research and clinical care.

Adherence to depression treatment in older adults: a narrative review.

CONTEXT Use of atypical antipsychotics for neuropsychiatric symptoms of dementia increased markedly in the 1990s. Concerns about their use began to emerge in 2002, and in 2005, the US Food and Drug Administration warned that use of atypical antipsychotics in dementia was associated with increased mortality. OBJECTIVE To examine changes in atypical and conventional antipsychotic use in outpatients with dementia from 1999 through 2007. DESIGN Time-series analyses estimated the effect of the various warnings on atypical and conventional antipsychotic usage using national Veterans Affairs data across 3 periods: no warning (1999-2003), early warning (2003-2005), and black box warning (2005-2007). SUBJECTS Patients aged 65 years or older with dementia (n = 254 564). MAIN OUTCOME MEASURES Outpatient antipsychotic use (percentage of patients, percentage of quarterly change, and difference between consecutive study periods). RESULTS In 1999, 17.7% (95% confidence interval [CI], 17.2-18.1) of patients with dementia were using atypical or conventional antipsychotics. Overall use began to decline during the no-warning period (rate per quarter, -0.12%; 95% CI, -0.16 to -0.07; P < .001). Following the black box warning, the decline continued (rate, -0.26%; 95% CI, -0.34 to -0.18; P < .001), with a significant difference between the early and black box warning periods (P = .006). Use of atypical antipsychotics as a group increased during the no-warning period (rate, 0.23; 95% CI, 0.17-0.30; P < .001), started to decline during the early-warning period (rate, -0.012; 95% CI, -0.14 to 0.11; P = .85), and more sharply declined during the black box warning period (rate, -0.27; 95% CI, -0.36 to -0.18; P < .001). Olanzapine and risperidone showed declining rates and quetiapine showed an increase during the early-warning period, but rates of use for all 3 antipsychotics declined during the black box warning period. In the black box warning period, there was a small but significant increase in anticonvulsant prescriptions (rate, 0.117; 95% CI, 0.08-0.16; P < .001). CONCLUSIONS Use of atypical antipsychotics began to decline significantly in 2003, and the Food and Drug Administration advisory was temporally associated with a significant acceleration in the decline.

Enhanced identification of eligibility for depression research using an electronic medical record search engine

Depression in older adults has been detected, diagnosed and treated more frequently in recent years. However, substantial gaps in effective treatment remain. Adherence to depression treatment can be viewed as the ‘next frontier’ in the treatment of late-life depression. Using the Theory of Reasoned Action, a model of health behaviours, this paper conceptualizes and reviews the current evidence for key patient-level factors associated with depression treatment adherence among older adults. We categorize these factors according to how their impact on adherence might be affected by specialized treatment approaches or interventions as: (i) modifiable; (ii) potentially modifiable; and (iii) non-modifiable. Based on current evidence, modifiable factors associated with depression treatment adherence include patient attitudes, beliefs and social norms. Patient attitudes include perceptions of the effectiveness of depression treatment, preferences for the type of depression treatment and concepts regarding the aetiology of depression (e.g. resistance to viewing depression as a medical illness). There is also evidence from the literature that spiritual and religious beliefs may be important determinants of adherence to depression care. Social norms such as the impact of caregiver agreement with treatment recommendations and stigma may also affect adherence to depression treatment. Other factors may be less modifiable per se, but they may have an impact on adherence that is potentially modifiable by specialized interventions. Based upon a review of the current literature, potentially modifiable factors associated with adherence to depression treatment include co-morbid anxiety, substance use, cognitive status, polypharmacy and medical co-morbidity, social support and the cost of treatment. Finally, non-modifiable factors include patient gender and race. Importantly, non-modifiable factors may interact with modifiable factors to affect health behavioural intent (e.g. race and spiritual beliefs). Thus, adherence to depression treatment in older adults is associated with multiple factors. Strategies to improve patient adherence need to be multidimensional, including consideration of age-related cognitive and co-morbidity factors, environmental and social factors, functional status and belief systems. Evidence-based interventions involving greater patient, caregiver, provider and public health education should be developed to decrease stigma, negative attitudes and other modifiable barriers to detection, diagnosis, treatment and adherence to depression treatment. These interventions should also be tailored to the individual as well as to the treatment setting. While important progress has been made in increasing detection of depression in older adults, greater focus now needs to be placed on treatment engagement and continuation of improvements in quality of life, reducing suffering and achieving better outcomes.

Evaluation of the FDA Warning Against Prescribing Citalopram at Doses Exceeding 40 mg

PURPOSE Electronic medical records (EMRs) have become part of daily practice for many physicians. Attempts have been made to apply electronic search engine technology to speed EMR review. This was a prospective, observational study to compare the speed and clinical accuracy of a medical record search engine vs. manual review of the EMR. METHODS Three raters reviewed 49 cases in the EMR to screen for eligibility in a depression study using the electronic medical record search engine (EMERSE). One week later raters received a scrambled set of the same patients including 9 distractor cases, and used manual EMR review to determine eligibility. For both methods, accuracy was assessed for the original 49 cases by comparison with a gold standard rater. RESULTS Use of EMERSE resulted in considerable time savings; chart reviews using EMERSE were significantly faster than traditional manual review (p=0.03). The percent agreement of raters with the gold standard (e.g. concurrent validity) using either EMERSE or manual review was not significantly different. CONCLUSIONS Using a search engine optimized for finding clinical information in the free-text sections of the EMR can provide significant time savings while preserving clinical accuracy. The major power of this search engine is not from a more advanced and sophisticated search algorithm, but rather from a user interface designed explicitly to help users search the entire medical record in a way that protects health information.