Correlates of daily functioning in older adults with autism spectrum disorder.

Objectives: Studies of adults with autism spectrum disorder (ASD) have demonstrated poor outcomes related to independence and everyday living skills compared to the general population. In a sample of 74 adults with ASD who require a high level of support we sought to identify correlates of daily functioning.Methods: We administered questionnaires to residential staff and identified participants' independence level in basic and instrumental activities of daily living.Results: There was no association of age with daily functioning. Higher daily functioning was associated with a better general medical health rating. Functional independence was greater in participants with IQ range of 55 to 65 compared to those with IQ below 55. Language difficulties and behavioral disturbances were not significantly correlated with independence in daily living skills. In this sample, individual had held a median of three different types of jobs in supported employment.Conclusion: Daily functioning in adults with autism generally does not decline with age, but because this was cross-sectional data, this requires further confirmation. Community programs designed for adults with ASD who require a high level of support should focus on overall medical health and promotion of daily living skill building.

Dementia.

Alzheimer disease (AD) and other dementia syndromes are becoming more common; an estimated 5.5 million adults aged 65 years or older are living with AD in the United States. It is important for primary care physicians to gain knowledge in this field because most community-dwelling older adults receive their care from them. This article discusses the latest findings in approaches to prevent cognitive decline as well as dementia screening, diagnosis, and treatment. Approaches to address quality of life for persons with dementia and their caregivers are also discussed.

Neuropathologic, genetic, and longitudinal cognitive profiles in primary age-related tauopathy (PART) and Alzheimer's disease.

INTRODUCTION: Primary age-related tauopathy (PART) is a recently described entity that can cause cognitive impairment in the absence of Alzheimer's disease (AD). Here, we compared neuropathological features, tau haplotypes, apolipoprotein E (APOE) genotypes, and cognitive profiles in age-matched subjects with PART and AD pathology. METHODS: Brain autopsies (n = 183) were conducted on participants 85 years and older from the Baltimore Longitudinal Study of Aging and Johns Hopkins Alzheimer's Disease Research Center. Participants, normal at enrollment, were followed with periodic cognitive evaluations until death. RESULTS: Compared with AD, PART subjects showed significantly slower rates of decline on measures of memory, language, and visuospatial performance. They also showed lower APOE ε4 allele frequency (4.1% vs. 17.6%, P = .0046). DISCUSSION: Our observations suggest that PART is separate from AD and its distinction will be important for the clinical management of patients with cognitive impairment and for public health care planning.

Health Services Utilization in Older Adults with Dementia Receiving Care Coordination: The MIND at Home Trial.

OBJECTIVE: To investigate effects of a novel dementia care coordination program on health services utilization. DATA SOURCES/STUDY SETTING: A total of 303 community-dwelling adults aged ≥70 with a cognitive disorder in Baltimore, Maryland (2008-2011). STUDY DESIGN: Single-blind RCT evaluating efficacy of an 18-month care coordination intervention delivered through community-based nonclinical care coordinators, supported by an interdisciplinary clinical team. DATA COLLECTION/EXTRACTION METHODS: Study partners reported acute care/inpatient, outpatient, and home- and community-based service utilization at baseline, 9, and 18 months. PRINCIPAL FINDINGS: From baseline to 18 months, there were no significant group differences in acute care/inpatient or total outpatient services use, although intervention participants had significantly increased outpatient dementia/mental health visits from 9 to 18 months (p = .04) relative to controls. Home and community-based support service use significantly increased from baseline to 18 months in the intervention compared to control (p = .005). CONCLUSIONS: While this dementia care coordination program did not impact acute care/inpatient services utilization, it increased use of dementia-related outpatient medical care and nonmedical supportive community services, a combination that may have helped participants remain at home longer. Future care model modifications that emphasize delirium, falls prevention, and behavior management may be needed to influence inpatient service use.

Aging and Autism Spectrum Disorder: A Naturalistic, Longitudinal Study of the Comorbidities and Behavioral and Neuropsychiatric Symptoms in Adults with ASD.

Little is known about Autism Spectrum Disorder (ASD) in persons over age 50. In a retrospective, naturalistic review of 74 individuals aged 30 and older meeting DSM-5 criteria for ASD, the point prevalence of behavioral and neuropsychiatric symptoms (BNPS) declined significantly for 12 of 13 BNPS over a mean of 25 years while many other features of ASD remained stable. GI disorders (68.9%) and seizure disorders (23%) were common, and 25.7% of the sample had a BMI >30. Females were more likely to engage in screaming (p < 0.05) and oppositional behavior (p < 0.05). Current age did not have a significant effect on BNPS prevalence.

Guideline Watch (October 2014): Practice Guideline for the Treatment of Patients With Alzheimer's Disease and Other Dementias.

(Reprinted with permission from American Psychiatric Association, http://psychiatryonline.org/guidelines).

Study partners perform essential tasks in dementia research and can experience burdens and benefits in this role.

Most studies that enroll individuals with dementia require a study partner for each participant. Study partners-usually family members-perform several key roles: accompanying the participant to visits, providing information about the participant, and assisting with procedures such as taking medication. Little is known, however, about their experiences when performing these roles. Dementia researchers and institutional review boards need to know these experiences because the study partner role is one key factor in a study's success. This prospective qualitative study, using up to three semi-structured interviews with 62 study partners involved in a range of dementia studies, documented their subjective experiences. Content analysis demonstrates that study partners perform a range of tasks-often within the context of being a caregiver-that enable cognitively impaired individuals to participate in dementia research. These tasks present study partners with unique burdens and benefits, some of which dementia researchers and institutional review boards can address.

Survival in Frontotemporal Dementia Phenotypes: A Meta-Analysis.

BACKGROUND: Survival in frontotemporal dementia (FTD) is not well understood. We conducted a mixed effects meta-analysis of survival in FTD to examine phenotype differences and contributory factors. METHODS: The PubMed, Medline, EMBASE, CINAHL, PsycINFO and Cochrane databases were searched for studies describing survival or natural history of behavioral variant FTD (bvFTD), progressive non-fluent aphasia (PNFA), semantic dementia (SD), FTD with amyotrophic lateral sclerosis (FTD-ALS), progressive supranuclear palsy and corticobasal degeneration. There were no language restrictions. RESULTS: We included 27 studies (2,462 subjects). Aggregate mean and median survival were derived for each phenotype and, for comparison, Alzheimer's disease (AD) (using data from the selected studies). Survival was shortest in FTD-ALS (2.5 years). Mean survival was longest in bvFTD and PNFA (8 years) and median survival in SD (12 years). AD was comparable in survival to all except FTD-ALS. Age and sex did not affect survival; the education effect was equivocal. Heterogeneity in FTD survival was largely, but not wholly, explained by phenotypes. CONCLUSIONS: Survival differs for FTD phenotypes but, except for FTD-ALS, compares well to AD survival. Elucidating the potential causes of within-phenotype heterogeneity in survival (such as complicating features and comorbidities) may open up opportunities for tailored interventions.

Heterogeneity of Treatment Response to Citalopram for Patients With Alzheimer's Disease With Aggression or Agitation: The CitAD Randomized Clinical Trial.

OBJECTIVE: Pharmacological treatments for agitation and aggression in patients with Alzheimer's disease have shown limited efficacy. The authors assessed the heterogeneity of response to citalopram in the Citalopram for Agitation in Alzheimer Disease (CitAD) study to identify individuals who may be helped or harmed. METHOD: In this double-blind parallel-group multicenter trial of 186 patients with Alzheimer's disease and clinically significant agitation, participants were randomly assigned to receive citalopram or placebo for 9 weeks, with the dosage titrated to 30 mg/day over the first 3 weeks. Five planned potential predictors of treatment outcome were assessed, along with six additional predictors. The authors then used a two-stage multivariate method to select the most likely predictors; grouped participants into 10 subgroups by their index scores; and estimated the citalopram treatment effect for each. RESULTS: Five covariates were likely predictors, and treatment effect was heterogeneous across the subgroups. Patients for whom citalopram was more effective were more likely to be outpatients, have the least cognitive impairment, have moderate agitation, and be within the middle age range (76-82 years). Patients for whom placebo was more effective were more likely to be in long-term care, have more severe cognitive impairment, have more severe agitation, and be treated with lorazepam. CONCLUSIONS: Considering several covariates together allowed the identification of responders. Those with moderate agitation and with lower levels of cognitive impairment were more likely to benefit from citalopram, and those with more severe agitation and greater cognitive impairment were at greater risk for adverse responses. Considering the dosages used and the association of citalopram with cardiac QT prolongation, use of this agent to treat agitation may be limited to a subgroup of people with dementia.

The longitudinal impact of depression on disability in Parkinson disease.

OBJECTIVE: Depression in Parkinson disease (PD) is a common problem that worsens quality of life and causes disability. However, little is known about the longitudinal impact of depression on disability in PD. This study examined the association between disability and DSM-IV-TR depression status across six years. METHODS: Longitudinal cohort study with assessments at study entry, year two, four, and six conducted in the Morris K. Udall Parkinson Disease Research Center. Recruitment totaled 137 adult men and women with idiopathic PD in which up to six years of data on demographic, motor, and non-motor variables was collected. Movement disorder specialists used the structured interview for DSM-IV-TR depressive disorders and the Northwestern Disability Scale to assess depression and disability. A generalized linear mixed model was fitted with Northwestern Disability Scale score as the dependent variable to determine the effect of baseline depression status on disability. RESULTS: A total of 43 participants were depressed at baseline compared to 94 without depression. Depressed participants were more likely to be female, were less educated, were less likely to take dopamine agonists, and more likely to have motor fluctuations. Controlling for these variables, symptomatic depression predicted greater disability compared to both never depressed (p = 0.0133) and remitted depression (p = 0.0009). Disability associated with symptomatic depression at baseline was greater over the entire six-year period compared to participants with remitted depressive episodes or who were never depressed. CONCLUSIONS: Persisting depression is associated with a long-term adverse impact on daily functioning in PD. Adequate treatment or spontaneous remission of depression improves ADL function.

Time to Response to Citalopram Treatment for Agitation in Alzheimer Disease.

OBJECTIVE: Agitation is a common and significant problem in Alzheimer disease (AD). In the recent Citalopram for Agitation in Alzheimer's Disease (CitAD) study, citalopram was efficacious for the treatment of AD agitation. Here we examined the time course and predictors of response to treatment. METHODS: Response in CitAD was defined as a modified Alzheimer Disease Cooperative Study Clinical Global Impression of Change (CGIC) score of 1 or 2 or a Neurobehavioral Rating Scale agitation subscale (NBRS-A) score reduction ≥ 50% from baseline. "Stable early response" was defined as meeting the aforementioned criteria at both weeks 3 and 9, "late response" was response at week 9 but not at week 3, and "unstable response" was response at week 3 but not at week 9. RESULTS: In the primary analyses, citalopram was superior to placebo on both the CGIC and the NBRS-A response measures. Little between-group differences were found in response rates in the first 3 weeks of the study (21% versus 19% on the CGIC). Citalopram patients were more likely than placebo patients to be a late responder (18% versus 8% on CGIC, Fisher's exact p = 0.09; 31% versus 15% on NBRS-A, Fisher's exact p = 0.02). Approximately half of citalopram responders (45%-56%) at end of study achieved response later in the study compared with 30%-44% of placebo responders. CONCLUSION: Treatment with citalopram for agitation in AD needs to be at least 9 weeks in duration to allow sufficient time for full response. Study duration is an important factor to consider in the design of clinical trials for agitation in AD.

Change in agitation in Alzheimer's disease in the placebo arm of a nine-week controlled trial.

BACKGROUND: Placebo responses raise significant challenges for the design of clinical trials. We report changes in agitation outcomes in the placebo arm of a recent trial of citalopram for agitation in Alzheimer's disease (CitAD). METHODS: In the CitAD study, all participants and caregivers received a psychosocial intervention and 92 were assigned to placebo for nine weeks. Outcomes included Neurobehavioral Rating Scale agitation subscale (NBRS-A), modified AD Cooperative Study-Clinical Global Impression of Change (CGIC), Cohen-Mansfield Agitation Inventory (CMAI), the Neuropsychiatric Inventory (NPI) Agitation/Aggression domain (NPI A/A) and Total (NPI-Total) and ADLs. Continuous outcomes were analyzed with mixed-effects modeling and dichotomous outcomes with logistic regression. RESULTS: Agitation outcomes improved over nine weeks: NBRS-A mean (SD) decreased from 7.8 (3.0) at baseline to 5.4 (3.2), CMAI from 28.7 (6.7) to 26.7 (7.4), NPI A/A from 8.0 (2.4) to 4.9 (3.8), and NPI-Total from 37.3 (17.7) to 28.4 (22.1). The proportion of CGI-C agitation responders ranged from 21 to 29% and was significantly different from zero. MMSE improved from 14.4 (6.9) to 15.7 (7.2) and ADLs similarly improved. Most of the improvement was observed by three weeks and was sustained through nine weeks. The major predictor of improvement in each agitation measure was a higher baseline score in that measure. CONCLUSIONS: We observed significant placebo response which may be due to regression to the mean, response to a psychosocial intervention, natural course of symptoms, or nonspecific benefits of participation in a trial.

Neuropsychiatric symptoms as predictors of progression to severe Alzheimer's dementia and death: the Cache County Dementia Progression Study.

OBJECTIVE: Little is known about factors influencing the rate of progression of Alzheimer's dementia. Using data from the Cache County Dementia Progression Study, the authors examined the link between clinically significant neuropsychiatric symptoms in mild Alzheimer's dementia and progression to severe dementia or death. METHOD: The Cache County Dementia Progression Study is a longitudinal study of dementia progression in incident cases of this condition. Survival analyses included unadjusted Kaplan-Meier plots and multivariate Cox proportional hazard models. Hazard ratio estimates controlled for age at dementia onset, dementia duration at baseline, gender, education level, General Medical Health Rating, and apolipoprotein E epsilon 4 genotype. RESULTS: Three hundred thirty-five patients with incident Alzheimer's dementia were studied. Sixty-eight (20%) developed severe dementia over the follow-up period. Psychosis (hazard ratio=2.007), agitation/aggression (hazard ratio=2.946), and any one clinically significant neuropsychiatric symptom (domain score ≥4, hazard ratio=2.682) were associated with more rapid progression to severe dementia. Psychosis (hazard ratio=1.537), affective symptoms (hazard ratio=1.510), agitation/aggression (hazard ratio=1.942), mildly symptomatic neuropsychiatric symptoms (domain score of 1-3, hazard ratio=1.448), and clinically significant neuropsychiatric symptoms (hazard ratio=1.951) were associated with earlier death. CONCLUSIONS: Specific neuropsychiatric symptoms are associated with shorter survival time from mild Alzheimer's dementia to severe dementia and/or death. The treatment of specific neuropsychiatric symptoms in mild Alzheimer's dementia should be examined for its potential to delay time to severe dementia or death.

A randomized controlled trial of a community-based dementia care coordination intervention: effects of MIND at Home on caregiver outcomes.

OBJECTIVE: To assess whether MIND at Home, a community-based, multicomponent, care coordination intervention, reduces unmet caregiving needs and burden in informal caregivers of persons with memory disorders. METHODS: An 18-month randomized controlled trial of 289 community-living care recipient (CR)-caregiver (informal caregivers, i.e., unpaid individuals who regularly assisted the CR) dyads from 28 postal code areas of Baltimore, Maryland was conducted. All dyads and the CR's primary care physician received the written needs assessment results and intervention recommendations. Intervention dyads then received an 18-month care coordination intervention delivered by nonclinical community workers to address unmet care needs through individualized care planning, referral and linkage to dementia services, provision of caregiver dementia education and skill-building strategies, and care progress monitoring by an interdisciplinary team. Primary outcome was total percent of unmet caregiver needs at 18 months. Secondary outcomes included objective and subjective caregiver burden measures, quality of life (QOL), and depression. RESULTS: Total percent of unmet caregiver needs declined in both groups from baseline to 18 months, with no statistically significant between-group difference. No significant group differences occurred in most caregiver burden measures, depression, or QOL. There was a potentially clinically relevant reduction in self-reported number of hours caregivers spent with the CR for MIND participants compared with control subjects. CONCLUSION: No statistically significant impacts on caregiver outcomes were found after multiple comparison adjustments. However, MIND at Home appeared to have had a modest and clinically meaningful impact on informal caregiver time spent with CRs.

Dementia caregivers' coping strategies and their relationship to health and well-being: the Cache County Study.

OBJECTIVES: Prior research identifies that psychological outcomes among dementia caregivers are associated with their use of coping strategies. Few studies have tested the association of coping and health longitudinally. METHOD: This study examined factors associated with the use of coping strategies over time and their associations with physical and mental health outcomes in a population-based sample of 226 dementia caregivers in Cache County, Utah, USA. Caregivers annually completed the Ways of Coping Checklist-Revised, the Beck Anxiety Inventory, and a health interview. Care-recipient cognitive and functional abilities were obtained using the Mini-Mental State Exam and the Clinical Dementia Rating. Neuropsychiatric symptoms were assessed using the Neuropsychiatric Inventory. RESULTS: Caregivers most frequently identified providing care as a problem (37.6%). Linear mixed models of caregiver coping strategies found that the use of most strategies were stable except for increasing Avoidance among adult child caregivers (ß = 0.14, p = 0.048). On average, increased Wishful Thinking (ß = 2.48, p < 0.001) or Blames Self (ß = 1.06, p = 0.002) was associated with higher anxiety scores. Increased use of Blames Others among males (interaction, ß = 0.28, p = 0.02) and greater use of Wishful Thinking among younger caregivers (interaction, ß = -0.01, p = 0.01) were associated with more caregiver health conditions. Coping strategies were not associated with change in anxiety or health conditions over time. CONCLUSION: Our results emphasize the importance of caregiver coping strategies on caregiver health and well-being and may identify subgroups of persons at risk for worse outcomes.

Latent classes of course in Alzheimer's disease and predictors: the Cache County Dementia Progression Study.

OBJECTIVE: Several longitudinal studies of Alzheimer's disease (AD) report heterogeneity in progression. We sought to identify groups (classes) of progression trajectories in the population-based Cache County Dementia Progression Study (N = 328) and to identify baseline predictors of membership for each group. METHODS: We used parallel-process growth mixture models to identify latent classes of trajectories on the basis of Mini-Mental State Exam (MMSE) and Clinical Dementia Rating sum of boxes scores over time. We then used bias-corrected multinomial logistic regression to model baseline predictors of latent class membership. We constructed receiver operating characteristic curves to demonstrate relative predictive utility of successive sets of predictors. RESULTS: We fit four latent classes; class 1 was the largest (72%) and had the slowest progression. Classes 2 (8%), 3 (11%), and 4 (8%) had more rapid worsening. In univariate analyses, longer dementia duration, presence of psychosis, and worse baseline MMSE and Clinical Dementia Rating sum of boxes were associated with membership in class 2, relative to class 1. Lower education was associated with membership in class 3. In the multivariate model, only MMSE remained a statistically significant predictor of class membership. Receiver operating characteristic areas under the curve were 0.98, 0.88, and 0.67, for classes 2, 3, and 4 relative to class 1. CONCLUSIONS: Heterogeneity in AD course can be usefully characterized using growth mixture models. The majority belonged to a class characterized by slower decline than is typically reported in clinical samples. Class membership could be predicted using baseline covariates. Further study may advance our prediction of AD course at the population level and in turn shed light on the pathophysiology of progression.