Amy E. Sanders

Age-specific and sex-specific prevalence and incidence of mild cognitive impairment, dementia, and Alzheimer dementia in blacks and whites: a report from the Einstein Aging Study.

As the population ages, the need to characterize rates of cognitive impairment and dementia within demographic groups defined by age, sex, and race becomes increasingly important. There are limited data available on the prevalence and incidence of amnestic mild cognitive impairment (aMCI) and nonamnestic mild cognitive impairment (naMCI) from population-based studies. The Einstein Aging Study, a systematically recruited community-based cohort of 1944 adults aged 70 or older (1168 dementia free at baseline; mean age, 78.8 y; average follow-up, 3.9 y), provides the opportunity to examine the prevalence and incidence rates for dementia, Alzheimer dementia (AD), aMCI, and naMCI by demographic characteristics. Dementia prevalence was 6.5% (4.9% AD). Overall dementia incidence was 2.9/100 person-years (2.3/100 person-years for AD). Dementia and AD rates increased with age but did not differ by sex. Prevalence of aMCI was 11.6%, and naMCI prevalence was 9.9%. aMCI incidence was 3.8 and naMCI incidence was 3.9/100 person-years. Rates of aMCI increased significantly with age in men and in blacks; sex, education, and race were not significant risk factors. In contrast, naMCI incidence did not increase with age; however, blacks were at higher risk compared with whites, even when controlling for sex and education. Results highlight the public health significance of preclinical cognitive disease.

Association of a Functional Polymorphism in the Cholesteryl Ester Transfer Protein (CETP) Gene With Memory Decline and Incidence of Dementia

CONTEXT Polymorphisms in the cholesteryl ester transfer protein (CETP) gene have been associated with exceptional longevity and lower cardiovascular risk, but associations with memory decline and dementia risk are unclear. OBJECTIVE To test the hypothesis that a single-nucleotide polymorphism (SNP) at CETP codon 405 (isoleucine to valine V405; SNP rs5882) is associated with a lower rate of memory decline and lower risk of incident dementia, including Alzheimer disease (AD). DESIGN, SETTING, AND PARTICIPANTS Prospective cohort study comprising 608 community-dwelling adults without dementia aged 70 years or older from the Einstein Aging Study with CETP genotype available. Fifteen participants with prevalent dementia were excluded, and 70 without follow-up--63 lost to follow-up and 7 new to the study--were excluded from the Cox proportional hazards model, which included 523 participants in the analysis. Standardized neuropsychological and neurological measures were administered annually from 1994-2009. Linear mixed-effects models adjusted for sex, education, race, medical comorbidities, and apolipoprotein (APOE) epsilon4 examined associations of V405 genotype with longitudinal performance on cognitive tests of episodic memory (Free and Cued Selective Reminding Test [FCSRT], possible scores of 0-48), attention (Digit Span), and psychomotor speed (Digit Symbol Substitution). The V405 genotype was the main predictor of incident dementia or AD in similarly adjusted Cox proportional hazards models with age as the time scale. MAIN OUTCOME MEASURES Memory decline and incident dementia. RESULTS Valine allele frequency was 43.5%. A total of 40 cases of incident dementia occurred during follow-up (mean [(SD], 4.3 [3.1] years). Compared with isoleucine homozygotes, valine homozygotes had significantly slower memory decline on the FCSRT (0.43 points per year of age for isoleucine; 95% confidence interval [CI], -0.58 to -0.29 vs 0.21 points per year of age for valine; 95% CI, -0.39 to -0.04; difference in linear age slope, 0.22; 95% CI, 0.02 to 0.41; P = .03) and no significant differences on the Digit Span or Digit Symbol Substitution tests. Valine homozygotes also had lower risk of dementia (hazard ratio, 0.28; 95% CI, 0.10-0.85; P = .02) and AD (hazard ratio, 0.31; 95% CI, 0.10-0.95; P = .04). CONCLUSION This preliminary report suggests that CETP V405 valine homozygosity is associated with slower memory decline and lower incident dementia and AD risk.

Free and Cued Selective Reminding Identifies Very Mild Dementia in Primary Care

The Free and Cued Selective Reminding Test (FCSRT) is used widely to identify very mild dementia; 3 alternative scoring procedures have been proposed based on free recall, total recall, and cue efficiency. We compared the predictive validity of these scoring procedures for the identification of very mild prevalent dementia (CDR=0.5), of incident dementia, and for distinguishing Alzheimer Disease (AD) and nonAD dementias. We tested 244 elderly African American and White primary care patients at 18 month intervals using a screening neuropsychologic battery that included the FCSRT and a comprehensive diagnostic neuropsychologic battery. Median follow-up was 2.6 years. Dementia diagnoses were assigned using standard criteria without access to the results of the screening battery. There were 50 prevalent and 28 incident dementia cases. At scores selected to provide specificities of 90%, free recall was more sensitive to incident and prevalent dementia than the other 2 measures. Patients with impaired free recall were 15 times more likely to have a prevalent dementia and their risk of future dementia was 4 times higher than patients with intact free recall. Neither race nor education affected prediction although older patients were at increased risk of future dementia. Total recall was more impaired in AD dementia than in nonAD dementias. The results indicate that using the FCSRT, free recall is the best measure for detecting prevalent dementia and predicting future dementia. Total recall impairment supports the diagnosis of AD rather than nonAD dementia.

Non-Native Language Use and Risk of Incident Dementia in the Elderly

Cognitive reserve is invoked to explain the protective effects of education and cognitively-stimulating activities against all-cause dementia and Alzheimers disease (AD). For non-native English speakers (n-NES), speaking English may be a cognitive activity associated with lower dementia risk. We hypothesized that n-NES have lower risk of incident dementia/AD and that educational level might modify this relationship. Participants took part in the Einstein Aging Study (Bronx, NY), a longitudinal study of aging and dementia. All (n = 1779) spoke fluent English and self-reported birthplace and whether English was their first language. n-NES additionally reported mother tongue, age of English acquisition, and current percentile-use of a non-English language. Nested Cox proportional hazards models progressively adjusted for gender, race, education, and immigrant and marital status estimated hazard ratios (HR) for incident dementia/AD as a function of n-NES status. 390 (22%) participants were n-NES. 126 incident dementia cases occurred during 4174 person-years of follow-up (median 1.44; range 0-16); 101 individuals met criteria for probable/possible AD. There was no statistically-significant association between n-NES status and incident dementia in the fully-adjusted model (HR 1.26; 95% CI 0.76-2.09; p = 0.36). Results were similar for AD. Stratification of education into three groups revealed increased risk of dementia for n-NES with ≥ 16 years of education (HR 3.97; 95% CI 1.62-9.75; p = 0.003). We conclude that n-NES status does not appear to have an independent protective effect against incident dementia/AD, and that n-NES status may contribute to risk of dementia in an education-dependent manner.

Neuropsychological strategies for detecting early dementia

As new and more effective treatments for Alzheimers disease (AD) emerge, the development of efficient screening strategies in educationally and racially diverse primary care settings has increased in importance. A set of candidate screening tests and an independent diagnostic assessment were administered to a sample of 318 patients treated at a geriatric primary care center. Fifty-six subjects met criteria for dementia. Exploratory analysis led to the development of three two-stage screening strategies that differed in the composition of the first stage or Rapid Dementia Screen, which is applied to all patients over the age of 65. The second stage, applied to those patients who screen positively for dementia, is accomplished with the Free and Cued Selective Reminding Test to detect memory impairment. Using clinical diagnosis as a gold standard, the strategies had high sensitivity and specificity for identifying dementia and performed better for identifying AD than non-AD dementias. Sensitivity and specificity did not differ by race or education. The strategies provide an efficient approach to screening for early dementia.

Quality improvement in neurology Dementia management quality measures

ACOVE= : Assessing Care of Vulnerable Elders; DWG= : Dementia Measures Work Group; EHR= : electronic health record; ICD-9 = : International Classification of Diseases , ninth revision; MU= : Meaningful Use; PCPI= : Physician Consortium for Performance Improvement; PQRS= :

Free and cued selective reminding distinguishes Alzheimer's disease from vascular dementia.

To the Editor: Although clinicians have long been interested in the possible role of cognitive profiles in distinguishing patients with Alzheimer’s disease (AD) from those who have vascular dementia (VaD), this distinction is not straightforward. Because impairment in executive functioning can limit learning in elderly people,1 decrements in performance on conventional memory testsmay result from primary memory deficits or apparent memory deficits due in part to executive and attentional deficits. Thus, the memory profiles of AD and VaD may appear similar when memory is assessed with tests that depend upon frontal and attentional processes. Distinguishing the profiles may require assessing memory with tests that control attention and cognitive processing. It was hypothesized that patientswith VaD would benefitmore from controlled learning procedures than patients with AD, whose hallmark deficit is memory impairment. The Free and Cued Selective Reminding Test (FCSRT) controls the learning conditions by having subjects search a card containing four pictures of items (e.g., grapes, toaster) that go with unique category cues (e.g., fruit, kitchen appliances). After all four items are identified, immediate cued recall of just those four items is tested. After controlled learning has been completed for all 16 items, there are three test trials consisting of free recall, followed by cued recall for those items not retrieved using free recall. The sum of free and cued recall on each trial is called total recall. The FCSRT procedure is described in detail elsewhere.2 These controlled learning procedures were designed to minimize inattention, promote deep semantic processing, and control conditions during encoding that are reinstated at retrieval for maximum recall. The study took place in an urban academic primary care practice following procedures approved by the local institutional review board. Each study participant underwent a neuropsychological evaluation consisting of a screening battery and an independent diagnostic battery used to determine cognitive status.3 Informants completed the structured Clinical Dementia Rating Scale (CDR) interview. 4 Dementia diagnosis and CDR score were established according to consensus of a neuropsychologist (EG), a geriatrician, and a geriatric psychiatrist using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for dementia5 without knowledge of FCSR results. The study neurologist (AES) subsequently assigned dementia subtypes using established criteria for probable or possible AD6 and probable or possible VaD.7 Participants were 344 African-American and Caucasian patients aged 65 and older who scored 18 or higher on the Mini-Mental State Examination (MMSE). Of the 60 participants (17%) who met DSM-IV criteria for dementia, most with very mild dementia (CDR 0.5), 27 (45%) had possible or probable AD, and 14 (23%) had possible or probable VaD. The eight (13%) participants who had mixed dementia (AD+VaD) were grouped with the patients with AD. Twelve patients with other dementias were excluded from this analysis. Two hundred eighty-three patients did not meet criteria for dementia. Established cutscores were used to determine the sensitivity and specificity of free recall8 and total recall2 for patients with AD versus VaD (Table 1). Eighty-three percent of patients with AD and 79% of patients with VaD displayed impaired free recall. Specificity of free recall was 76% (216/283). Impaired free recall in patients without dementia was associated with CDR rating; 82% of patients with impaired free recall and 41% of patients with intact free recall had a CDR of 0.5. As predicted, sensitivity of total recall varied as a function of dementia subtype. Seventy-one percent (25/35) patients with AD had impaired total recall, whereas 79% (11/14) patients with VaD patients had intact total recall. This differentiation was not due to differences in severity of dementia between patient groups as measured by the sum of CDR box scores.4 A logistic regression model was fit to the data with impairment on total recall as the outcome. Dementia subtype was a significant predictor; patients with AD were 9.17 times as likely to have impaired total recall as patients with VaD; they were 7.74 as likely after controlling for dementia severity. Specificity of total recall was excellent; only 6% of patients without dementia had impaired total recall. Table 1 Sensitivity and Specificity of Free Recall and Total Recall for Patients with Alzheimer’s Disease (AD) and Vascular Dementia (VaD) The results confirmed the predictions; impaired free recall was common in patients with AD and VaD, but impaired total recall occurred only in patients with AD, underscoring the centrality of memory deficits to this disorder. In contrast, patients with VaD displayed intact total recall, showing the expected benefit of controlled learning, perhaps because, in patients with VaD, the frontal and attentional system plays a more profound and important role. These results demonstrate the promise of FCSR for distinguishing between AD and non-AD dementias, further enhancing its sensitivity and specificity as a case-finding tool for identifying preclinical and early dementia.3,9,10

Exceptional Parental Longevity Associated with Lower Risk of Alzheimer's Disease and Memory Decline

OBJECTIVES: To determine whether offspring of parents with exceptional longevity (OPEL) have a lower rate of dementia than offspring of parents with usual survival (OPUS).

Quality Improvement in Neurology: Dementia Management Quality Measures

Professional and advocacy organizations have long urged that dementia should be recognized and properly diagnosed. With the passage of the National Alzheimers Project Act in 2011, an Advisory Council for Alzheimers Research, Care, and Services was convened to advise the Department of Health and Human Services. In May 2012, the Council produced the first National Plan to address Alzheimers disease, and prominent in its recommendations is a call for quality measures suitable for evaluating and tracking dementia care in clinical settings. Although other efforts have been made to set dementia care quality standards, such as those pioneered by RAND in its series Assessing Care of Vulnerable Elders (ACOVE), practitioners, healthcare systems, and insurers have not widely embraced implementation. This executive summary (full manuscript available at www.neurology.org) reports on a new measurement set for dementia management developed by an interdisciplinary Dementia Measures Work Group (DWG) representing the major national organizations and advocacy organizations concerned with the care of individuals with dementia. The American Academy of Neurology (AAN), the American Geriatrics Society, the American Medical Directors Association, the American Psychiatric Association, and the American Medical Association–convened Physician Consortium for Performance Improvement led this effort. The ACOVE measures and the measurement set described here apply to individuals whose dementia has already been identified and properly diagnosed. Although similar in concept to ACOVE, the DWG measurement set differs in several important ways; it includes all stages of dementia in a single measure set, calls for the use of functional staging in planning care, prompts the use of validated instruments in patient and caregiver assessment and intervention, highlights the relevance of using palliative care concepts to guide care before the advanced stages of illness, and provides evidence‐based support for its recommendations and guidance on the selection of instruments useful in tracking patient‐centered outcomes. It also specifies annual reassessment and updating of interventions and care plans for dementia‐related problems that affect families and other caregivers as well as individuals with dementia. Here, a brief synopsis of why major reforms in healthcare design and delivery are needed to achieve substantive improvements in the quality of care is first provided, and then the final measures approved for publication, dissemination, and implementation are listed.

Clinical expression of LRRK2 G2019S mutations in the elderly.

Mutations in the leucine‐rich repeat kinase 2 gene (LRRK2, PARK8) are the most commonly identified monogenic etiology of Parkinson disease (PD). Over‐represented in the Ashkenazi Jewish population, these mutations are transmitted in an autosomal dominant manner with age‐dependent reduced penetrance. The natural history and penetrance of these mutations in the elderly is controversial and inadequately studied. We conducted a nested cohort study in a community‐based aging study (the Einstein Aging Study). Six elderly, initially nonmanifesting carriers (NMC) of the LRKK2 G2019S mutation were identified (average age 82.1 ± 7.0, range 72.7–90.8), and five had available longitudinal data. We matched five noncarrier controls to each NMC and followed them for an average of 4.7 years with annual cognitive and motor examinations. PD was identified in one NMC at age 95 and in no control subjects. The remaining carriers did not differ from controls on motor scores at baseline or follow‐up. The baseline Unified Parkinsons Disease Rating Scale motor subscore (UPDRS‐III) in cases was 6.2 ± 6.9 (range 1–19) and in controls was 4.5 ± 6.6 (1–30), P = 0.6; the mean difference in UPDRS‐III slopes over time between cases and controls was 0.1 ± 1.3 and was not statistically significant. Our data, while limited by a small sample size, show that in LRKK2 G2019S mutation carriers, phenoconversion to PD can occur late in life. However, most NMC have motor decline which is indistinguishable from their age mates, suggesting that the larger subset of elderly NMC is not on the motor trajectory to disease.