Early Detection of Learning Difficulties when Confronted with Novel Information in Preclinical Alzheimer's Disease Stage 1.
We employed a highly demanding experimental associative learning test (the AFE-T) to explore memory functioning in Preclinical Alzheimer's Disease stage 1 (PreAD-1) and stage 2 (PreAD-2). The task consisted in the learning of unknown object/name pairs and our comprehensive setup allowed the analysis of learning curves, immediate recall, long-term forgetting rates at one week, three months, and six months, and relearning curves. Forty-nine cognitively healthy subjects were included and classified according to the presence or absence of abnormal CSF biomarkers (Control, n = 31; PreAD-1, n = 14; PreAD-2, n = 4). Control and PreAD-1 performances on the experimental test were compared by controlling for age and education. These analyses showed clear learning difficulties in PreAD-1 subjects (F = 6.98; p = 0.01). Between-group differences in long-term forgetting rates were less notable, reaching statistical significance only for the three-month cued forgetting rate (F = 4.83; p = 0.03). Similarly, relearning sessions showed only statistical trends between the groups (F = 3.22; p = 0.08). In the whole sample, significant correlations between CSF Aβ42/tau ratio and the AFE-T were found, both in the total learning score (r = 0.52; p < 0.001) and in the three-month cued forgetting rate (r = -0.38; p < 0.01). Descriptive subanalyses involving PreAD-2 suggested greater learning and recall difficulties in these subjects when compared with the PreAD-1 group. The present results suggest that explicit learning difficulties when binding information could be one of the earliest signs of the future emergence of episodic memory difficulties on the Alzheimer's disease continuum. Our findings indicate that the AFE-T is a sensitive test, capable of detecting subtle memory difficulties in PreAD-1.
['Tort-Merino|Adrià|A|', 'Valech|Natalia|N|', 'Peñaloza|Claudia|C|', 'Grönholm-Nyman|Petra|P|', 'León|María|M|', 'Olives|Jaume|J|', 'Estanga|Ainara|A|', 'Ecay-Torres|Mirian|M|', 'Fortea|Juan|J|', 'Martínez-Lage|Pablo|P|', 'Molinuevo|José L|JL|', 'Laine|Matti|M|', 'Rodríguez-Fornells|Antoni|A|', 'Rami|Lorena|L|']
D000368:Aged D000544:Alzheimer Disease D016229:Amyloid beta-Peptides D001057:Apolipoproteins E D015415:Biomarkers D018450:Disease Progression D042241:Early Diagnosis D005260:Female D006801:Humans D007858:Learning D007859:Learning Disabilities D008137:Longitudinal Studies D008297:Male D008568:Memory D008875:Middle Aged D015999:Multivariate Analysis D009483:Neuropsychological Tests D010446:Peptide Fragments D062706:Prodromal Symptoms D012720:Severity of Illness Index D016875:tau Proteins
memory biomarkers Alzheimer’s disease cognitive aging neuropsychology