Odorant Item Specific Olfactory Identification Deficit May Differentiate Alzheimer Disease From Aging.

Objectives: To explore whether the ability to recognize specific odorant items is differentially affected in aging versus Alzheimer disease (AD); to refine olfactory identification deficit (OID) as a biomarker of prodromal and early AD.

Design: Prospective multicenter cross-sectional study with a longitudinal arm.

Setting: Outpatient memory diagnostic clinics in New York and Texas.

Statistical Model of Dynamic Markers of the Alzheimer's Pathological Cascade.

Objectives: Alzheimer's disease (AD) is a progressive disease reflected in markers across assessment modalities, including neuroimaging, cognitive testing, and evaluation of adaptive function. Identifying a single continuum of decline across assessment modalities in a single sample is statistically challenging because of the multivariate nature of the data. To address this challenge, we implemented advanced statistical analyses designed specifically to model complex data across a single continuum.

Detection of Risky Driving Behaviors in the Naturalistic Environment in Healthy Older Adults and Mild Alzheimer's Disease.

Analyzing naturalistic driving behavior recorded with in-car cameras is an ecologically valid method for measuring driving errors, but it is time intensive and not easily applied on a large scale. This study validated a semi-automated, computerized method using archival naturalistic driving data collected for drivers with mild Alzheimer's disease (AD; = 44) and age-matched healthy controls (HC; = 16). The computerized method flagged driving situations where safety concerns are most likely to occur (i.

Tau and Amyloid Positron Emission Tomography Imaging Predict Driving Performance Among Older Adults with and without Preclinical Alzheimer's Disease.

Abnormal levels of Alzheimer's disease (AD) biomarkers, measured by positron emission tomography imaging using amyloid-based radiotracers and cerebrospinal fluid, are associated with impaired driving performance in older adults. We examined whether preclinical AD staging, defined using amyloid imaging and tau imaging using the radiotracer T807 (AKA flortaucipir or AV-1451), was associated with receiving a marginal/fail rating on a standardized road test (n = 42). Participants at Stage 2 (positive amyloid and tau scans) of preclinical AD were more likely to receive a marginal/fail rating compared to participants at Stage 0 or 1.

Sembragiline in Moderate Alzheimer's Disease: Results of a Randomized, Double-Blind, Placebo-Controlled Phase II Trial (MAyflOwer RoAD).

Background: Sembragiline is a potent, selective, long-acting, and reversible MAO-B inhibitor developed as a potential treatment for Alzheimer's disease (AD).

Objective: To evaluate the safety, tolerability, and efficacy of sembragiline in patients with moderate AD.

Methods: In this Phase II study (NCT01677754), 542 patients with moderate dementia (MMSE 13-20) on background acetylcholinesterase inhibitors with/without memantine were randomized (1:1:1) to sembragiline 1 mg, 5 mg, or placebo once daily orally for 52 weeks.

Validation of olfactory deficit as a biomarker of Alzheimer disease.

Background: We evaluated smell identification as a biomarker for Alzheimer disease (AD) by assessing its utility in differentiating normal aging from an amnestic disorder and determining its predictive value for conversion from amnestic mild cognitive impairment (aMCI) to AD.

Methods: Cross-sectional study (AD = 262, aMCI = 110, controls = 194) measuring smell identification (University of Pennsylvania Smell Identification Test [UPSIT]) and cognitive status was performed, as well as longitudinal analysis of aMCI participants (n = 96) with at least 1 year follow-up (mean 477.6 ± 223.

Efficacy and Safety of Donepezil in Chinese Patients with Severe Alzheimer's Disease: A Randomized Controlled Trial.

Background: Donepezil has been used worldwide for the treatment of severe Alzheimer's disease (AD). Whether it is also appropriate for severe AD in Chinese patients remains unknown.

Objective: To determine whether donepezil is effective and tolerable for Chinese patients with severe AD.

Cognitively-Related Basic Activities of Daily Living Impairment Greatly Increases the Risk of Death in Alzheimers Disease.

Introduction: Some Alzheimer's disease (AD) patients die without ever developing cognitively impaired basic activities of daily living (basic ADL), which may reflect slower disease progression or better compensatory mechanisms. Although impaired basic ADL is related to disease severity, it may exert an independent risk for death. This study examined the association between impaired basic ADL and survival of AD patients, and proposed a multistate approach for modeling the time to death for patients who demonstrate different patterns of progression of AD that do or do not include basic ADL impairment.

Lipoprotein-associated phospholipase A2, homocysteine, and Alzheimer's disease.

Introduction: Lipoprotein-associated phospholipase A2 (Lp-PLA2) and homocysteine (Hcy) have been linked to inflammation and Alzheimer's disease (AD). Using a case-control design, we examined their independent effects and interactions with cardiovascular disease equivalent (CVDE), on AD risk.

Methods: AD cases and controls were from the Texas Alzheimer's Research and Care Consortium study.

A hidden Markov model approach to analyze longitudinal ternary outcomes when some observed states are possibly misclassified.

Understanding the dynamic disease process is vital in early detection, diagnosis, and measuring progression. Continuous-time Markov chain (CTMC) methods have been used to estimate state-change intensities but challenges arise when stages are potentially misclassified. We present an analytical likelihood approach where the hidden state is modeled as a three-state CTMC model allowing for some observed states to be possibly misclassified.

Rapidly Versus Slowly Progressing Patients With Alzheimer's Disease: Differences in Baseline Cognition.

Rate of progression of cognitive deficits is variable among patients with Alzheimer's disease (AD). The purpose of the current study was to compare demographic characteristics and performance on neuropsychological measures at baseline evaluation between rapidly and slowly progressing patients. Participants were divided into 2 groups based on change in Alzheimer's Disease Assessment Scale-Cognitive subscale score from baseline to 2-year follow-up, and baseline performance was compared between the groups.

How Do Scores on the ADAS-Cog, MMSE, and CDR-SOB Correspond?

Objective: Clinicians and researchers who measure cognitive dysfunction often use the Alzheimer's Disease Assessment Scale--Cognitive Subscale (ADAS-Cog), the Mini-Mental State Examination (MMSE), or the Clinical Dementia Rating scale (CDR-SOB). But, the use of different measures can make it difficult to compare data across patients or studies. What is needed is a simple chart that shows how scores on these three important measures correspond to each other.

Validation of the Spanish version of the Baylor Profound Mental Status Examination.

Background: There are no short valid instruments to evaluate cognitive status in severe Alzheimer's disease (AD) patients in the Spanish language.

Objective: To validate the Spanish version of the Baylor Profound Mental Status Examination (BPMSE-Sp).

Methods: The Baylor Profound Mental Status Examination (BPMSE) was translated to Spanish and back translated.

Delayed-start analysis: Mild Alzheimer's disease patients in solanezumab trials, 3.5 years.

Introduction: Solanezumab is an anti-amyloid monoclonal antibody in clinical testing for treatment of Alzheimer's disease (AD). Its mechanism suggests the possibility of slowing the progression of AD.

Methods: A possible disease-modifying effect of solanezumab was assessed using a new statistical method including noninferiority testing.

Development of a patient-reported outcome instrument to assess complex activities of daily living and interpersonal functioning in persons with mild cognitive impairment: The qualitative research phase.

Introduction: As drug development research efforts move toward studying patients earlier in the course of Alzheimer's disease (AD), it is important to incorporate the patient's perspective into measurement of outcomes.

Methods: This article summarizes the qualitative work of the Patient-Reported Outcome Consortium's Cognition Working Group in the development of a new self-reported outcome measure in persons with mild cognitive impairment (MCI) due to suspected AD, herein referred to as MCI.

Results: The draft measure captures the patient's voice for two functional domains, complex activities of daily living and interpersonal functioning.

Peripheral and central effects of γ-secretase inhibition by semagacestat in Alzheimer's disease.

Introduction: The negative efficacy study examining the γ-secretase inhibitor semagacestat in mild to moderate Alzheimer's disease (AD) included a number of biomarkers of the disease as well as safety outcomes. We analyzed these data to explore relationships between drug exposure and pharmacodynamic effects and to examine the correlations among outcome measures.

Methods: The study was a multicenter, randomized, placebo-controlled trial of two dose regimens of semagacestat and a placebo administered for 18 months to individuals with mild to moderate AD.

Adding delayed recall to the ADAS-cog improves measurement precision in mild Alzheimer's disease: Implications for predicting instrumental activities of daily living.

As research increasingly focuses on preclinical stages of Alzheimer's disease (AD), instruments must be retooled to identify early cognitive markers of AD. A supplemental delayed recall subtest for the Alzheimer's Disease Assessment Scale-cognitive (ADAS-cog; Mohs, Rosen, & Davis, 1983; Rosen, Mohs, & Davis, 1984) is commonly implemented, but it is not known precisely where along the spectrum of cognitive dysfunction this subtest yields incremental information beyond what is gained from the standard ADAS-cog, or whether it can improve prediction of functional outcomes. An item response theory approach can analyze this in a psychometrically rigorous way.

Comparing caregiver and clinician predictions of fitness to drive in people with Alzheimer's disease.

This observational study investigated family caregiver and clinician ratings of 75 drivers with Alzheimer's disease against scores on a standardized road test and a naturalistic driving evaluation. Clinician ratings by a physician specialized in dementia were significantly associated with road test error scores (r=.25, p=.

Relationships between testosterone levels and cognition in patients with Alzheimer disease and nondemented elderly men.

Background/aims: Previous research suggests that low levels of testosterone may be associated with the development of Alzheimer disease (AD), as well as poorer performance on certain neuropsychological tests and increased risk of depression.

Methods: This study utilized data from 61 nondemented older men and 68 men with probable AD.

Results: Testosterone levels did not differ between the groups.

Association of fish oil supplement use with preservation of brain volume and cognitive function.

Objective: The aim of this study was to investigate whether the use of fish oil supplements (FOSs) is associated with concomitant reduction in cognitive decline and brain atrophy in older adults.

Methods: We conducted a retrospective cohort study to examine the relationship between FOS use during the Alzheimer's Disease Neuroimaging Initiative and indicators of cognitive decline. Older adults (229 cognitively normal individuals, 397 patients with mild cognitive impairment, and 193 patients with Alzheimer's disease) were assessed with neuropsychological tests and brain magnetic resonance imaging every 6 months.

Ordered subset analysis of copy number variation association with age at onset of Alzheimer's disease.

Genetic heterogeneity is a common problem for genome-wide association studies of complex human diseases. Ordered-subset analysis (OSA) reduces genetic heterogeneity and optimizes the use of phenotypic information, thus improving power under some disease models. We hypothesized that in a genetically heterogeneous disorder such as Alzheimer's disease (AD), utilizing OSA by age at onset (AAO) of AD may increase the power to detect relevant loci.

Association of dementia with early rehospitalization among Medicare beneficiaries.

Preventable hospital readmissions have been recognized as indicators of hospital quality, a source of increased healthcare expenditures, and a burden for patients, families, and caregivers. Despite growth of initiatives targeting risk factors associated with potentially avoidable hospital readmissions, the impact of dementia on the likelihood of rehospitalization is poorly characterized. Therefore, the primary objective of this retrospective cohort study was to investigate whether dementia was an independent predictor of 30-day readmissions.

Predicting road test performance in drivers with stroke.

OBJECTIVE. The aim of this study was to develop a brief screening battery to predict the on-road performance of drivers who had experienced a stroke. METHOD.

Phase 3 trials of solanezumab for mild-to-moderate Alzheimer's disease.

Background: Alzheimer's disease is characterized by amyloid-beta plaques, neurofibrillary tangles, gliosis, and neuronal loss. Solanezumab, a humanized monoclonal antibody, preferentially binds soluble forms of amyloid and in preclinical studies promoted its clearance from the brain.

Methods: In two phase 3, double-blind trials (EXPEDITION 1 and EXPEDITION 2), we randomly assigned 1012 and 1040 patients, respectively, with mild-to-moderate Alzheimer's disease to receive placebo or solanezumab (administered intravenously at a dose of 400 mg) every 4 weeks for 18 months.