CLINICAL TRIALS IN THE PRECLINICAL TO MCI STAGES OF AD: CROSS-CULTURAL VALIDATION AND NORMATIVE STUDY OF THE TOMMORROW NEUROPSYCHOLOGICAL BATTERY

Abstract

Clinical trials in preclinical Alzheimer’s disease (AD) require reliable and validated measures appropriate for the detection of subtle cognitive changes. In preparation for international site initiation in the TOMMORROW Study, a trial to delay the clinical onset of Mild Cognitive Impairment due to AD (MCI-AD), we conducted a multicultural and multilingual validation and normative study of a neurocognitive battery. The battery was culturally adapted for use in Italy, Switzerland (German language), and Russia to support the systematic application of operationalized criteria to detect MCI-AD in these countries. A total of 675 individuals comprised of 200 healthy controls [∼50/age strata/country; ages 65-88, including men and women with a range of low and high education] and 25 AD subjects from each country were recruited. Construct validity, test-retest, and alternate form reliability were assessed in healthy controls. Criterion and discriminant validity of the cognitive measures were tested in the entire sample (healthy controls and AD cases) using logistic regression, discriminant analysis, and Receiver Operating Characteristic analysis. Measure equivalence was examined in relationship to normative values from English-speaking populations in the United States. The translated and culturally adapted tests demonstrated high test-retest reliabilities as well as good construct and criterion validity. Tests performed comparably to the “gold standard” English versions with respect to direction, magnitude, and patterns of correlations and main effects. Several tests showed some cultural variability, underscoring the importance of country-specific norms. Gender influenced verbal episodic memory (women> men) and visual naming (men> women) performances in the German version. Education affected visual memory, naming, and attention measures in Italian; whereas, performance on a test of executive function (Trails B) required greater average time to completion in Russian when compared to the English language versions. The TOMMORROW neuropsychological battery has now been translated, culturally adapted, validated and normed for ages 65-88 in German, Italian, and Russian languages. The battery is in use currently in German (Switzerland & Germany) and English speaking sites participating in the trial, providing further opportunities for multilingual investigation of its utility in detecting MCI-AD and measuring change in preclinical AD.