Screening and Assessment for Alzheimer's Disease in the Days of Biological Biomarkers.

The 1980s saw an upsurge of research in Alzheimer's disease (AD). The necessity of standardized assessment batteries became apparent, leading to the development of standardized instruments, such as the CERAD, the CAMDEX, the CSI 'D', and later the TOOLBOX. The advent of new biological markers has led to speculation in the research community about the necessity for these instruments. As the association of biomarkers with subsequent clinical dementia remains unclear, assessment batteries are still necessary, especially with growing evidence that prodromal symptoms of AD may not be cognitive decline but emotional or behavioral symptoms. Inclusion of ethnic minority groups is also essential.

Understanding the healthcare experiences and needs of African immigrants in the United States: a scoping review.

BACKGROUND: Africans immigrants in the United States are the least-studied immigrant group, despite the research and policy efforts to address health disparities within immigrant communities. Although their healthcare experiences and needs are unique, they are often included in the "black" category, along with other phenotypically-similar groups. This process makes utilizing research data to make critical healthcare decisions specifically targeting African immigrants, difficult. The purpose of this Scoping Review was to examine extant information about African immigrant health in the U.S., in order to develop lines of inquiry using the identified knowledge-gaps. METHODS: Literature published in the English language between 1980 and 2016 were reviewed in five stages: (1) identification of the question and (b) relevant studies, (c) screening, (d) data extraction and synthesis, and (e) results. Databases used included EBSCO, ProQuest, PubMed, and Google Scholar (hand-search). The articles were reviewed according to title and abstract, and studies deemed relevant were reviewed as full-text articles. Data was extracted from the selected articles using the inductive approach, which was based on the comprehensive reading and interpretive analysis of the organically emerging themes. Finally, the results from the selected articles were presented in a narrative format. RESULTS: Culture, religion, and spirituality were identified as intertwined key contributors to the healthcare experiences of African immigrants. In addition, lack of culturally-competent healthcare, distrust, and complexity, of the U.S. health system, and the exorbitant cost of care, were identified as major healthcare access barriers. CONCLUSION: Knowledge about African immigrant health in the U.S. is scarce, with available literature mainly focusing on databases, which make it difficult to identify African immigrants. To our knowledge, this is the first Scoping Review pertaining to the healthcare experiences and needs of African immigrants in the U.S.

Adherence and Tolerability of Alzheimer's Disease Medications: A Pragmatic Randomized Trial.

BACKGROUND/OBJECTIVES: Post-marketing comparative trials describe medication use patterns in diverse, real-world populations. Our objective was to determine if differences in rates of adherence and tolerability exist among new users to acetylcholinesterase inhibitors (AChEI's). DESIGN: Pragmatic randomized, open label comparative trial of AChEI's currently available in the United States. SETTING: Four memory care practices within four healthcare systems in the greater Indianapolis area. PARTICIPANTS: Eligibility criteria included older adults with a diagnosis of possible or probable Alzheimer's disease (AD) who were initiating treatment with an AChEI. Participants were required to have a caregiver to complete assessments, access to a telephone, and be able to understand English. Exclusion criteria consisted of a prior severe adverse event from AChEIs. INTERVENTION: Participants were randomized to one of three AChEIs in a 1:1:1 ratio and followed for 18 weeks. MEASUREMENTS: Caregiver-reported adherence, defined as taking or not taking study medication, and caregiver-reported adverse events, defined as the presence of an adverse event. RESULTS: 196 participants were included with 74.0% female, 30.6% African Americans, and 72.9% who completed at least twelfth grade. Discontinuation rates after 18 weeks were 38.8% for donepezil, 53.0% for galantamine, and 58.7% for rivastigmine (P = .063) in the intent to treat analysis. Adverse events and cost explained 73.1% and 25.4% of discontinuation. No participants discontinued donepezil due to cost. Adverse events were reported by 81.2% of all participants; no between-group differences in total adverse events were statistically significant. CONCLUSIONS: This pragmatic comparative trial showed high rates of adverse events and cost-related non-adherence with AChEIs. Interventions improving adherence and persistence to AChEIs may improve AD management. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01362686 (https://clinicaltrials.gov/ct2/show/NCT01362686).

Does targeted cognitive training reduce educational disparities in cognitive function among cognitively normal older adults?

OBJECTIVE: The aim of this study was to investigate educational differences in treatment responses to memory, reasoning, and speed of processing cognitive training relative to no-contact control. METHODS: Secondary analyses of the Advanced Cognitive Training for Independent and Vital Elderly trial were conducted. Two thousand eight hundred older adults were randomized to memory, reasoning, or speed of processing training or no-contact control. A repeated-measures mixed-effects model was used to investigate immediate post-training and 1-year outcomes with sensitivity analyses out to 10 years. Outcomes were as follows: (1) memory composite of Hopkins Verbal Learning Test, Rey Auditory Verbal Learning Test, and Rivermead Behavioral Memory Test; (2) reasoning composite of letter series, letter sets, and word series; and (3) speed of processing measured using three trials of useful field of view and the digit symbol substitution test. RESULTS: The effects of reasoning and memory training did not differ by educational attainment. The effect of speed of processing training did. Those with fewer than 12 years of education experienced a 50% greater effect on the useful field of view test compared with those with 16 or more years of education. The training advantage for those with fewer than 12 years of education was maintained to 3 years post-training. CONCLUSION: Older adults with less than a secondary education are at elevated risk of dementia, including Alzheimer's disease. The analyses here indicate that speed of processing training is effective in older adults with low educational attainment.

Assessing psychological well-being: self-report instruments for the NIH Toolbox.

OBJECTIVE: Psychological well-being (PWB) has a significant relationship with physical and mental health. As a part of the NIH Toolbox for the Assessment of Neurological and Behavioral Function, we developed self-report item banks and short forms to assess PWB. STUDY DESIGN AND SETTING: Expert feedback and literature review informed the selection of PWB concepts and the development of item pools for positive affect, life satisfaction, and meaning and purpose. Items were tested with a community-dwelling US Internet panel sample of adults aged 18 and above (N = 552). Classical and item response theory (IRT) approaches were used to evaluate unidimensionality, fit of items to the overall measure, and calibrations of those items, including differential item function (DIF). RESULTS: IRT-calibrated item banks were produced for positive affect (34 items), life satisfaction (16 items), and meaning and purpose (18 items). Their psychometric properties were supported based on the results of factor analysis, fit statistics, and DIF evaluation. All banks measured the concepts precisely (reliability ≥0.90) for more than 98% of participants. CONCLUSION: These adult scales and item banks for PWB provide the flexibility, efficiency, and precision necessary to promote future epidemiological, observational, and intervention research on the relationship of PWB with physical and mental health.

Health outcomes and cost of care among older adults with schizophrenia: a 10-year study using medical records across the continuum of care.

OBJECTIVES: The population of older patients with schizophrenia is increasing. This study describes health outcomes, utilization, and costs over 10 years in a sample of older patients with schizophrenia compared with older patients without schizophrenia. METHODS: An observational cohort study of 31,588 older adults (mean age: 70.44 years) receiving care from an urban public health system, including a community mental health center, during 1999-2008. Of these, 1,635 (5.2%) were diagnosed with schizophrenia and 757 (2.4%) had this diagnosis confirmed in the community mental health center. Patients' electronic medical records were merged with Medicare claims, Medicaid claims, the Minimum Dataset, and the Outcome and Assessment Information Set. Information on medication use was not available. MEASUREMENTS: Rates of comorbid conditions, healthcare utilization, costs, and mortality. RESULTS: Patients with schizophrenia had significantly higher rates of congestive heart failure (45.05% versus 38.84%), chronic obstructive pulmonary disease (52.71% versus 41.41%), and hypothyroidism (36.72% versus 26.73%) than the patients without schizophrenia (p <0.001). They had significantly lower rates of cancer (30.78% versus 43.18%) and significantly higher rates of dementia (64.46% versus 32.13%). The patients with schizophrenia had significantly higher mortality risk (hazard ratio: 1.25, 95% confidence interval: 1.07-1.47) than the patients without schizophrenia. They also had significantly higher rates of healthcare utilization. The mean costs for Medicare and Medicaid were significantly higher for the patients with schizophrenia than for the patients without schizophrenia. CONCLUSIONS: The management of older adult patients with schizophrenia is creating a serious burden for our healthcare system, requiring the development of integrated models of healthcare.

Using the NIH Toolbox in special populations: considerations for assessment of pediatric, geriatric, culturally diverse, non-English-speaking, and disabled individuals.

BACKGROUND: In order to develop health outcomes measures that are relevant and applicable to the general population, it is essential to consider the needs and requirements of special subgroups, such as the young, elderly, disabled, and people of different ethnic and cultural backgrounds, within that population. METHODS: The NIH Toolbox project convened several working groups to address assessment issues for the following subgroups: pediatric, geriatric, cultural, non-English-speaking, and disabled. Each group reviewed all NIH Toolbox instruments in their entirety. RESULTS: Each working group provided recommendations to the scientific study teams regarding instrument content, presentation, and administration. When feasible and appropriate, instruments and administration procedures have been modified in accordance with these recommendations. CONCLUSION: Health outcome measurement can benefit from expert input regarding assessment considerations for special subgroups.

NIH toolbox for assessment of neurological and behavioral function.

At present, there are many studies that collect information on aspects of neurologic and behavioral function (cognition, sensation, movement, emotion), but with little uniformity among the measures used to capture these constructs. Further, available measures are generally expensive, normed on homogenous nondiverse populations, not easily administered, do not cover the lifespan (or have easily linked pediatric and adult counterparts for the purposes of longitudinal comparison), and not based on the current thinking in the neuroscience community. There is also a paucity of measurement tools to gauge normal children in the motor and sensation domain areas, and many of these measures rely heavily on proxy reporting. Investigators have expressed the need for brief assessment tools that could address these issues and be used as a form of "common currency" across diverse study designs and populations. This ability to assess functionality along a common metric and "crosswalk" across measures is essential to the process of being able to pool data, which is often necessary when a large and diverse sample is needed. When individual studies employ unique assessment batteries, comparisons between studies and combining data from multiple studies can be problematic. The contract for the NIH Toolbox for the Assessment of Neurological and Behavioral Function (www.nihtoolbox.org) was initiated by the NIH Blueprint for Neuroscience Research (www.neuroscienceblueprint.nih.gov) to develop a set of state-of-the-art measurement tools to enhance collection of data in large cohort studies and to advance the biomedical research enterprise.

Emotion assessment using the NIH Toolbox.

One of the goals of the NIH Toolbox for Assessment of Neurological and Behavioral Function was to identify or develop brief measures of emotion for use in prospective epidemiologic and clinical research. Emotional health has significant links to physical health and exerts a powerful effect on perceptions of life quality. Based on an extensive literature review and expert input, the Emotion team identified 4 central subdomains: Negative Affect, Psychological Well-Being, Stress and Self-Efficacy, and Social Relationships. A subsequent psychometric review identified several existing self-report and proxy measures of these subdomains with measurement characteristics that met the NIH Toolbox criteria. In cases where adequate measures did not exist, robust item banks were developed to assess concepts of interest. A population-weighted sample was recruited by an online survey panel to provide initial item calibration and measure validation data. Participants aged 8 to 85 years completed self-report measures whereas parents/guardians responded for children aged 3 to 12 years. Data were analyzed using a combination of classic test theory and item response theory methods, yielding efficient measures of emotional health concepts. An overview of the development of the NIH Toolbox Emotion battery is presented along with preliminary results. Norming activities led to further refinement of the battery, thus enhancing the robustness of emotional health measurement for researchers using the NIH Toolbox.

How valid are family proxy assessments of stroke patients' health-related quality of life?

BACKGROUND AND PURPOSE: Proxy respondents are often needed to report outcomes in stroke survivors, but they typically systematically rate impairments worse than patients themselves. The magnitude of this difference, the degree of agreement between patients and proxies, and the factors influencing agreement are not well known. METHODS: We compared patient and family proxy health-related quality of life (HRQL) responses in 225 patient-proxy pairs enrolled in a clinical trial for poststroke depression. We used paired t-tests and the intraclass correlation (ICC) statistic to evaluate the agreement between patient and proxy domain scores and the overall Stroke-specific Quality of Life (SS-QOL) score. We used multivariate linear regression to model patient- and proxy-reported SS-QOL scores. RESULTS: Patients were older (63 versus 55 years) and less often female (48% versus 74%) than proxies. Proxies rated all domains of SS-SQOL slightly worse than patients. The Mood, Energy, and Thinking domains had the greatest disparity with mean patient-proxy differences of 0.45, 0.37, and 0.37 points, respectively. The ICC for each domain ranged from 0.30 (role function) to 0.59 (physical function). Proxy overall SS-QOL score was also lower (worse) than patient score (3.7 versus 3.4, P<0.001) with ICC of 0.41. Agreement was higher among patient-proxy pairs with higher patient depression scores and with lower proxy report of caregiving burden. CONCLUSIONS: Proxies systematically report more dysfunction in multiple aspects of HRQL than stroke patients themselves. Agreement between patient and proxy HRQL domain scores is modest at best and is affected by patient depression and proxy perception of burden. These differences may be large enough to impact the outcome assessment in stroke clinical trials.

Who refuses the diagnostic assessment for dementia in primary care?

OBJECTIVE: Early screening and detection of dementia in primary care remains controversial. At least half of the patients identified as cognitively impaired by screening instruments do not meet criteria for dementia and some patients refuse further evaluation following a positive screen. The aim of this study was to identify the characteristics of patients who refuse a clinical diagnostic assessment for dementia after screening. DESIGN: Cross sectional study. SETTING: Seven primary care practice centers in Indianapolis. PARTICIPANTS: Four hundred and thirty-four individuals aged 65 and older who screened positive for dementia with a mean age of 74.6, 67% women, and 68% African-American. MAIN OUTCOME MEASURE: Patients' acceptance of undergoing a dementia diagnostic assessment that included neuropsychological testing, caregiver interview, and medical chart review. RESULTS: Among patients with positive screening results for dementia, approximately half (47.7%) refused further assessment to confirm their screening results. In a bivariate analysis, possible factors associated with a higher probability of refusing dementia assessment were older age and better screening score. In a multiple logistic regression model, performing well on the temporal orientation of the screening instrument was associated with a higher probability of refusing diagnostic assessment for dementia (OR = 1.37; p = 0.001). Also, African-American patients aged 80 and older were more likely to refuse the diagnostic assessment than African-Americans less than 80 years of age (OR = 3.1, p < 0.001), while there was no significant age association for white patients (OR = 0.9, p = 0.728). CONCLUSIONS: Older primary care patients who perceived themselves as having no cognitive symptoms refused dementia diagnostic assessment despite their positive screening results. We must improve our understanding of the decision-making process driving patients' beliefs and behaviors about the benefits and risks of dementia screening and diagnosis before implementing any broad-based screening initiatives for dementia.

Perspectives on depression, mild cognitive impairment, and cognitive decline.

CONTEXT: The public health implications of depression and cognitive impairment in late life are enormous. Cognitive impairment and late-life depression are associated with increased risk for subsequent dementia; however, investigations of these phenomena appear to be proceeding along separate tracks. OBJECTIVES AND DATA SOURCE: The National Institute of Mental Health organized the conference "Perspectives on Depression, Mild Cognitive Impairment, and Cognitive Decline" to consider how the varied perspectives might be better integrated to examine the associations among depression, mild cognitive impairment, and cognitive decline and to illuminate the common or distinct mechanisms involved in these associations. DATA SYNTHESIS: The following 2 broad questions were addressed: (1) What gaps in our knowledge have the greatest public health significance? (2) Can we more efficiently use our research dollars and participant resources to fill these gaps? Meeting participants included grantees from the National Institute of Mental Health and the National Institute on Aging and program staff from the National Institute of Mental Health, the National Institute on Aging, and the National Institute of Neurological Disorders and Stroke. CONCLUSIONS: One of the most important recommendations to emerge from the meeting discussions is for increased collaboration among clinical and epidemiological investigators whose work focuses in the area of depression with those working primarily in the area of memory disorders. Directions for future research were identified.

Global prevalence of dementia: a Delphi consensus study.

BACKGROUND: 100 years after the first description, Alzheimer's disease is one of the most disabling and burdensome health conditions worldwide. We used the Delphi consensus method to determine dementia prevalence for each world region. METHODS: 12 international experts were provided with a systematic review of published studies on dementia and were asked to provide prevalence estimates for every WHO world region, for men and women combined, in 5-year age bands from 60 to 84 years, and for those aged 85 years and older. UN population estimates and projections were used to estimate numbers of people with dementia in 2001, 2020, and 2040. We estimated incidence rates from prevalence, remission, and mortality. FINDINGS: Evidence from well-planned, representative epidemiological surveys is scarce in many regions. We estimate that 24.3 million people have dementia today, with 4.6 million new cases of dementia every year (one new case every 7 seconds). The number of people affected will double every 20 years to 81.1 million by 2040. Most people with dementia live in developing countries (60% in 2001, rising to 71% by 2040). Rates of increase are not uniform; numbers in developed countries are forecast to increase by 100% between 2001 and 2040, but by more than 300% in India, China, and their south Asian and western Pacific neighbours. INTERPRETATION: We believe that the detailed estimates in this paper constitute the best currently available basis for policymaking, planning, and allocation of health and welfare resources.

Implementing a screening and diagnosis program for dementia in primary care.

BACKGROUND: Primary care physicians are positioned to provide early recognition and treatment of dementia. We evaluated the feasibility and utility of a comprehensive screening and diagnosis program for dementia in primary care. METHODS: We screened individuals aged 65 and older attending 7 urban and racially diverse primary care practices in Indianapolis. Dementia was diagnosed according to International Classification of Diseases (ICD)-10 criteria by an expert panel using the results of neuropsychologic testing and information collected from patients, caregivers, and medical records. RESULTS: Among 3,340 patients screened, 434 scored positive but only 227 would agree to a formal diagnostic assessment. Among those who completed the diagnostic assessment, 47% were diagnosed with dementia, 33% had cognitive impairment-no dementia (CIND), and 20% were considered to have no cognitive deficit. The overall estimated prevalence of dementia was 6.0% (95% confidence interval (CI) 5.5% to 6.6%) and the overall estimate of the program cost was $128 per patient screened for dementia and $3,983 per patient diagnosed with dementia. Only 19% of patients with confirmed dementia diagnosis had documentation of dementia in their medical record. CONCLUSIONS: Dementia is common and undiagnosed in primary care. Screening instruments alone have insufficient specificity to establish a valid diagnosis of dementia when used in a comprehensive screening program; these results may not be generalized to older adults presenting with cognitive complaints. Multiple health system and patient-level factors present barriers to this formal assessment and thus render the current standard of care for dementia diagnosis impractical in primary care settings.