Kristin Kahle-Wrobleski

Sensitivity and Specificity of the Mini-Mental State Examination for Identifying Dementia in the Oldest-Old: The 90+ Study

OBJECTIVES: To evaluate the sensitivity and specificity of the Mini‐Mental State Examination (MMSE) in identifying dementia in the oldest‐old when stratified by age and education.

Synaptic proteins, neuropathology and cognitive status in the oldest-old

An increasing number of individuals in our population are surviving to over 90 years and a subset is at risk for developing dementia. However, senile plaque and neurofibrillary tangle pathology do not consistently differentiate individuals with and without dementia. Synaptic protein loss is a feature of aging and dementia and may dissociate 90+ individuals with and without dementia. Synaptophysin (SYN), postsynaptic density 95 (PSD-95) and growth-associated protein 43 (GAP-43) were studied in the frontal cortex of an autopsy series of 32 prospectively followed individuals (92-105 years) with a range of cognitive function. SYN protein levels were decreased in individuals with dementia and increased in those with clinical signs of cognitive impairment insufficient for a diagnosis of dementia. SYN but neither PSD-95 nor GAP-43 protein levels were significantly correlated with mini-mental status examination (MMSE) scores. Frontal cortex SYN protein levels may protect neuronal function in oldest-old individuals and reflect compensatory responses that may be involved with maintaining cognition.

Neuropsychological data in nondemented oldest old: The 90+ Study

Although the oldest old are the fastest growing segment of the population, little is known about their cognitive performance. Our aim was to compile a relatively brief test battery that could be completed by a majority of individuals aged 90 or over, compensates for sensory losses, and incorporates previously validated, standardized, and accessible instruments. Means, standard deviations, and percentiles for 10 neuropsychological tests covering multiple cognitive domains are reported for 339 nondemented members of the 90+ Study. Cognitive performance declined with age for two-thirds of the tests. Performance on some tests was also affected by gender, education, and depression scores.

Clinical and Economic Characteristics of Milestones Along the Continuum of Alzheimer's Disease: Transforming Functional Scores into Levels of Dependence

BACKGROUNDnBecause Alzheimers disease (AD) is characterized by a gradual decline, it can be difficult to identify distinct clinical milestones that signal disease advancement. Adapting a functional scale may be a useful way of staging disease progression that is more informative for healthcare systems.nnnOBJECTIVESnTo adapt functional scale scores into discrete levels of dependence as a way of staging disease progression that is more informative to care providers and stakeholders who rely on the functional impact of diseases to determine access to supportive services and interventions.nnnDESIGNnAnalysis of data from the GERAS study.nnnSETTINGnGERAS is an 18-month prospective, multicenter, naturalistic, observational cohort study reflecting the routine care of patients with AD in France, Germany, and the United Kingdom.nnnPARTICIPANTSnData were from baseline results of 1497 community-living patients, aged ≥55 years, diagnosed with probable AD and their caregivers.nnnMEASUREMENTSnWe used data from the Alzheimers Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) and mapped items onto established categories of functional dependence, validated using clinical and economic measures. Cognitive function, behavioral symptoms, caregiver burden, and cost were assessed. Based on stages of functional dependence described by the Dependence Scale, individual ADCS-ADL items were used to approximate 6 dependence levels.nnnRESULTSnThere was a significant relationship between assigned level of dependence derived from the ADCS-ADL score and cognitive severity category. As the assigned level of dependence increased, the associated clinical and economic indicators demonstrated a pattern of greater disease severity.nnnCONCLUSIONSnThis mapping provides initial support for dependence levels as appropriate interim clinical milestones that characterize the functional deficits associated with AD.

Patient Characteristics and Outcomes Associated with Receiving an Earlier Versus Later Diagnosis of Probable Alzheimer’s Disease

Background: Effectiveness of Alzheimer’s disease (AD) treatments may depend critically on the timeliness of intervention. Objective: To compare characteristics and outcomes of patients diagnosed with probable AD (prAD) based on time elapsed from first onset of cognitive decline. Methods: Patients with ≥1 prAD diagnosis and ≥1 follow-up visit were selected from the National Alzheimer’s Coordinating Center (NACC) Uniform Data Set (UDS; 9/2005-6/2015) and stratified based on the time between the perceived onset of cognitive decline at baseline and first prAD diagnosis (i.e., earlier versus later diagnosis). Characteristics at baseline and prAD diagnosis, clinically meaningful progression, and medication use following prAD diagnosis were compared. Results: Median time from perceived onset of cognitive decline to prAD diagnosis was 4.5 years (earlier diagnosis: ≤3.46; later diagnosis: >5.71). Earlier-diagnosed patients (nu200a=u200a1,476) were younger at baseline (74.3 versus 76.3 years) and had better cognitive and functional scores than later-diagnosed patients (nu200a=u200a1,474). At first prAD diagnosis, earlier-diagnosed patients had lower mean global Clinical Dementia Rating (CDR) score (0.8 versus 1.1), higher mean Mini-Mental State Examination (MMSE) (22.6 versus 20.0), and lower mean Functional Activities Questionnaire (11.6 versus 17.3). Earlier- and later-diagnosed patients experienced similar time to a decrease of ≥3 points in MMSE (median 23.2 versus 23.1 months, pu200a=u200a0.83), but earlier-diagnosed patients had longer time to a CDR score of ≥2 points, and longer times to initiation of AD medication and antipsychotic agents (all pu200a<u200a0.01). Conclusion: Earlier prAD diagnosis in NACC data is associated with higher cognitive function and lower functional impairment at diagnosis.

THE PATIENT VOICE: EXPLORING TREATMENT PREFERENCES IN PARTICIPANTS WITH MILD COGNITIVE CONCERNS TO INFORM REGULATORY DECISION MAKING

was not used in the original derivation of iADRS, it can provide additional information on the performance of iADRS. Methods: EXPEDITION3 was an 80-week, placebo-controlled study of solanezumab (400mg/4 weeks). The study enrolled individuals with mild AD dementia. Mixed model repeated measure (MMRM) was used for treatment group comparisons. iADRS scores were computed using the ADAS-Cog13(iADRS 1⁄4[-1(ADASCog13)+85]+iADL). Results: A statistically significant difference between placebo and active drug was observed for change iADRS score (change from baseline) at Week 28 (p1⁄40.028) through Week 80 (p1⁄40.015) (Figure 1). Spearman rank correlations between iADRS and MMSE for baseline scores and baseline to endpoint changes were 0.533 and 0.611, respectively; correlations between iADRS and CDR were -0.644 and -0.600, respectively. Baseline iADRS and sociodemographic variable correlations were -0.130 for age and 0.002 (p>0.05) for gender. All correlations were statistically significant (p<0.001) unless stated otherwise. Conclusions: These EXPEDITION3 findings suggest that the combination of cognitive and functional measures in the iADRS provide an important measure of both cognition and function in a treatment trial of individuals with mild AD dementia. The correlations of iADRS score with MMSE and CDR scores support convergent validity, and age and gender did not greatly influence iADRS scores. The iADRS may provide a useful integrated measurement tool for the AD research community.