Roos J. Jutten

A composite measure of cognitive and functional progression in Alzheimer's disease: Design of the Capturing Changes in Cognition study

Cognitive testing in Alzheimers disease (AD) is essential for establishing diagnosis, monitoring progression, and evaluating treatments. Assessments should ideally be brief, reliable, valid, and reflect clinically meaningful changes. There is a lack of instruments that meet all these criteria. In the Capturing Changes in Cognition (Catch‐Cog) study, we seek to correct these deficiencies through the development and validation of a composite measure combining cognition and function: the cognitive‐functional composite (CFC). We expect that the CFC is able to detect clinically relevant changes over time in early dementia stages of AD.

Detecting functional decline from normal aging to dementia: Development and validation of a short version of the Amsterdam IADL Questionnaire

Detecting functional decline from normal aging to dementia is relevant for diagnostic and prognostic purposes. Therefore, the Amsterdam IADL Questionnaire (A‐IADL‐Q) was developed: a 70‐item proxy‐based tool with good psychometric properties. We aimed to design a short version while preserving its psychometric quality.

Assessing Everyday Activities Across the Dementia Spectrum with the Amsterdam IADL Questionnaire

BACKGROUND Instrumental activities of daily living (IADL) are complex activities which involve multiple cognitive processes, and which are expected to be susceptible to the early effects of cognitive impairment. Informant-based questionnaires are the most common tools used to assess IADL performance in dementia, but must be adjusted for use in early stages of impairment. OBJECTIVE To investigate the differences in IADL on the continuum of cognitive decline (i.e. no cognitive decline - subjective cognitive decline - mild cognitive impairment- mild dementia - moderate dementia) using the Spanish version of the Amsterdam IADL Questionnaire (A-IADL-Q). METHODS A total of 500 volunteer participants were included: 88 participants with no signs of cognitive decline, 109 participants with subjective cognitive complaints, 114 participants with mild cognitive impairment (MCI), 81 participants with mild dementia and 108 participants with moderate dementia. IADL was assessed with the A-IADL-Q, a computerized and adaptive questionnaire that calculates scores according to the specific pattern of responses of each participant. The data were examined by ANOVAs and regression analysis. Multinomial logistic regression analysis was used to evaluate the capacity of the A-IADL-Q to distinguish between diagnostic groups. RESULTS Participants with no cognitive decline and those with subjective cognitive decline obtained higher A-IADL-Q scores than MCI participants, and participants with MCI obtained higher scores than patients with dementia. The A-IADL-Q showed excellent discrimination between non-cognitive impairment and dementia, and significant but low discrimination between non-cognitive impairment and MCI. CONCLUSION A-IADL-Q can discriminate IADL functioning between groups across the dementia spectrum.

A novel cognitive-functional composite measure to detect changes in early Alzheimer's disease: Test–retest reliability and feasibility

To improve the detection of changes in Alzheimers disease (AD), we designed the cognitive‐functional composite (CFC). As a first validation step, we investigated its test–retest reliability and feasibility of use.

IMPAIRMENT IN COMPLEX ACTIVITIES OF DAILY LIVING IS RELATED TO NEURODEGENERATION IN ALZHEIMER’S DISEASE SPECIFIC REGIONS

Today’s emotion happy/smiling 1 33,3% 2 66,7% 1.000 good 10 50,0% 10 50,0% neutral/calm 1 100,0% 0 0,0% Face expressionbefore neutral/calm 5 38,5% 8 61,5% 0.413 happy/smiling 7 63,6% 4 36,4% Face expressionduring neutral/calm 8 100,0% 0 0,0% 0.001 excited/tense 4 25,0% 12 75,0% Verbal expressionafter sad 2 100,0% 0 0,0% <0.001 angry 2 100,0% 0 0,0% neutral/calm 5 100,0% 0 0,0% excited/tense 3 20,0% 12 80,0% Face expressionafter neutral/calm 9 100,0% 0 0,0% <0.001 excited/tense 0 0,0% 12 100,0% angry 2 100,0% 0 0,0% sad 1 100,0% 0 0,0% Poster Presentations: Tuesday, July 24, 2018 P1183

COMPARING THE COGNITIVE-FUNCTIONAL COMPOSITE WITH TRADITIONAL TESTS OF COGNITION AND FUNCTION: FINDINGS FROM THE CATCH-COG STUDY COHORT

Background: Decline in episodic memory is a hallmark clinical feature of Alzheimer’s disease that is evident in early stages of disease. Current models propose that AD begins with accumulation of beta-amyloid (Ab), followed by aggregation of tau, which in turn gives rise to loss of brain volume, impairment in cognition, and ultimately dementia. AD has a lengthy preclinical period, with this accumulation process beginning up to 30 years prior to the onset of dementia. Evidence of elevated Ab levels in both cognitively normal (CN) older adults and individuals with mild cognitive impairment (MCI) indicates that the AD process has begun. This study aimed to characterise the nature and extent of episodic memory decline, associated with Ab in individuals classified as CN and MCI. Methods:Participants (N1⁄4109; 50 AbCN, 25 Ab+ CN, 12 AbMCI, 22 Ab+ MCI) from the Australian Imaging, Biomarkers, and Lifestyle (AIBL) study underwent repeated assessment with a verbal list learning task (International Shopping List Test; ISLT) over 18-months. Results:Compared to AbCNs, Ab+ CNs showed a significant decline in ISLT total score, of a moderate magnitude (Cohen’s d 1⁄4 -0.55[-1.04, -0.07]. AbCNs showed significant improvement on their ISLT total performance over time. Compared to AbCNs, AbMCIs ISLT total and delayed recall scores did not significantly decline over time (Cohen’s d’s 1⁄4 -0.69[-1.33, 0.04] and 0, respectively); however significant decline was evident in Ab+ MCIs on both total and delayed recall (Cohen’s d’s 1⁄4 -1.21 [-1.75, -0.67] and -0.91[-1.44, -0.39], respectively). Conclusions: Significant decline in verbal memory was evident in Ab+ MCIs only, while performance in the AbCNs significantly increased. Further, results indicate that AbMCIs are characteristically different from Ab+ MCIs, and that a lack of decline in episodic memory, particularly delayed verbal recall, in MCI is indicative of a process separate from Alzheimer’s disease. Lastly, results suggest that cognitive abnormality in Ab+ CNs may be conceptualised as a reduced benefit from repeated exposure to stimuli.

Discontinuation and nonpublication of interventional clinical trials conducted in patients with mild cognitive impairment and Alzheimer's disease

Discontinuation and nonpublication of interventional clinical trials represents a waste of already scarce resources. We sought to identify the prevalence of discontinuation and nonpublication of interventional clinical trials conducted in patients afflicted by mild cognitive impairment and Alzheimers disease.

ASSESSING EVERYDAY ACTIVITIES WITH THE SPANISH VERSION OF THE AMSTERDAM IADL QUESTIONNAIRE: GROUP DIFFERENCES AND RELATION WITH COGNITIVE AND PSYCHOSOCIAL MEASURES

was adequate (Pearson’s coefficient 1⁄4. 70, p<. 001) and interrater reliability, excellent (intraclass correlation1⁄4. 99, p<.001). Normative data shown in percentiles were stratified by age and education (See Table). Conclusions: This study suggests that the DCQ is a valid and reliable cognitive screening test. Application of the DCQ on populations with atypical dementias is underway to derive sensitivity and specificity values for various dementias.

QUALITY ASPECTS OF A NOVEL COGNITIVE-FUNCTIONAL COMPOSITE FOR THE MEASUREMENT OF DISEASE PROGRESSION IN ALZHEIMER’S DISEASE: FEASIBILITY, TEST-RETEST RELIABILITY AND PRACTICE EFFECTS

positive allosteric modulator (PAM) to establish functional biomarkers of central target engagement in healthy young adults. Conclusions: Together with safety measures, these novel cognitive biomarkers used in Phase 1/2 POC studies show promise to help establish the dose range to be used in future clinical studies aimed at improving cognitive function in AD and may also be useful as functional biomarkers for Phase 3 clinical trials.