WORKING MEMORY UPDATING IN ELDERLY WITH MILD COGNITIVE IMPAIRMENT

1. The XIII conference of the European Society of Cognitive Psychology Granada, Spain - September 2003 WORKING MEMORY UPDATING IN ELDERLY WITH MILD COGNITIVE IMPAIRMENT Annapaola Prestia 1, Nadia Gamboz 1, Maria Luisa Onor 2, Eugenio Aguglia 2 and Carlo Semenza 1 1 Department of Psychology 2 Department of Technological, Morphological and Clinical Sciences University of Trieste, Italy

2. MILD COGNITIVE IMPAIRMENT Mild Cognitive Impairment (MCI) is a supposedly transitional stage between normal aging and dementia (see Peterson, Doody et al. 2001, and Bischkopf, Busse & Angermeyer, 2002, for a recent review of the current diagnostic criteria of the preclinical phase of AD). The amnesic mild cognitive impairment (aMCI; Peterson, Doody et al. 2001), encompassing many of the current diagnostic criteria for MCI, is characterised by a selective and isolated impairment of episodic memory. Elderly with aMCI show verbal episodic memory performances equivalent to those of patients affected by mild AD, while their other cognitive functions and the ability to deal with daily living activities are preserved (Collie & Maruff, 2000)   

3. IS aMCI A RELIABLE PREDICTOR OF DEMENTIA ? The prognostic value of aMCI is still under debate. Many factors contribute in making it difficult understand weather aMCI represents a preclinical stage of AD or weather it is an independent nosografic entity (Bischkopf, et al., 2002): not all cases of aMCI convert to dementia (12 % of cases per year) there aren’t at present validated early markers able to identify the elderly with aMCI more at risk to develop AD neuropsicological (large screening batteries), radiological (hippocampal atrophy) and biological (tau protein, A-42) markers are under investigation. 

4. It is reasonable to argue that combining neuropsicological radiological and biological measures and monitoring longitudinally the rate of change would undeniably be more informative on the outcome of aMCI than any of these measures alone. Such a diagnostic procedure is, however, still out of reach for a clinicians who is mainly concerned with individual early diagnosis of AD. It is therefore necessary to emphasise also the search for tools accessible to clinicians that can detect AD in its early stages.   

5. AIMS OF THE PRESENT INVESTIGATION To assess whether inefficient working memory updating represents a cognitive marker of MCI, in addition to verbal episodic memory deficit To assess whether inefficient working memory updating is a reliable predictor of incipient AD   WHY WORKING MEMORY UPDATING ?  Current evidences suggest that executive functioning, subserved by frontal lobes, is the first non-memory domain to be impaired in AD, and that the deficits initially involve the operations the require the manipulation of information (Perry & Hodges, 1999) Recent investigations indicated that the updating of verbal working memory is mediated by the prefrontal regions (Clark, Egan, McFarlane, Morris et al., 2000) 

6. Participants Material METHOD Neuropsychological Memory Screening: Words list free recall task, immediate and delayed prose recall task, backward and forward version of the verbal digit span task Working Memory Updating: Running Memory Task, Working memory updating task

7. Running Memory Task (adapted from Morris & Jones, 1990) Twelve stings of consonants of different lengths. The strings consisted of four, six and eight consonants, displayed on the computer screen for 2 seconds. At the end of each string participants were asked to repeat serially the last four items. Ex. L G Q P H S T D (adapted from Palladino, Cornoldi, De Beni & Pazzaglia, 2001) Working memory updating task Twelve lists, 10 words long, matched for word familiarity and word length. Each list consisted of measurable instances from two semantic category. The words were displayed on the computer screen for 2 seconds. Variables manipulated within participants: Working memory load (n.of targets to recall): 2 or 4; Processing load (n. of updates): 1 or 2. At the end of each list participants were asked to repeat serially the last or the last two smaller items from each category. Ex. (4 targets - 2 updates) ELBOW FINGER MOUSE FROG CHEST NOSE GIRAFFE HORSE FOREHEAD DONKEY

8. RESULTS

9. 12 MONTH FOLLOW UP Old Adults Standard Deviation Units * W > 6, p < .02 7 aMCI  Mild to moderate AD 9 aMCI Depression 2 aMCI  Stable MCI 2 aMCI Dementia other than AD

10.  Results indicated significant differences between aMCI patients and healthy controls in almost all memory tasks, except the digit span task. Results also indicated that variance across aMCI patients’ performances in the updating tasks was twice as large as that of the elderly control group, and larger than variance across performances in episodic memory tasks. Follow up analysis indicated that those aMCI patients who developed AD after 12 month from the first assessment had significantly worst performances, compared to healthy controls, that the aMCI patients who had depression in the working memory updating task and running memory task, while performances in the episodic memory tasks were equivalent Four of the 5 aMCI patients who initially showed the worst performances in the updating task, compared to healthy controls, developed AD   

11. DISCUSSION While conventional neuropsychological test contribute to diagnose aMCI by detecting and quantifying an episodic memory impairment, working memory updating abilities may promptly identify those aMCI patients who are more at risk to convert to dementia, as indicated by their more pronounced impairment of updating processes. What next ……. More investigations on carefully selected groups of aMCI are necessary to validate the predictive value to conversion to AD of working memory updating tasks. It is recommendable collect normative data on healthy old adults.

12. REFERENCES Clark, R. Egan, G., McFarlane, A., Morris, P., Weber, D., Sonkkilla, C., J.,Marcina, and Tochon-Danguy, H. (2000). Updating working memory for words: A PET activation study. Human Brain Mapping, 9, 42-54. Collie A. and Maruff P. (2000). The neuropsychology of preclinical Alzheimer’s disease and mild cognitive impairment. Neuroscience and Biobehavioral Reviews, 24, 365-374. Palladino P., Cornoldi C., De Beni R., and Pazzaglia F. (2001). Working memory and updating processes in reading comprehension. Memory & Cognition, 29, 344-354. Morris N., Jones D.M. (1990). Memory updating in working memory: The role of the central executive. British Journal of Psychology, 81, 111-121. Perry, R. and Hodges, J. (1999). Atten tion and executive deficits in Alzheimer’s disease. A critical review. Brain, 122, 383-404. Bischkopf, J., Busse, A., and Angermeyer, M. (2002). Mild cognitive impairment-a review of prevalence, incidence and outcome according to current approaches. Acta Psychiatrica Scandinavica, 106, 403-414. Petersen R.C., Doody R., Kurz A., Mohs r.C., Morris J.C., Rabins P.V., Ritchie K. Rossor M., Thal L., Winbald B. (2001). Current concepts in mild cognitive impairment. Archives of Neurology, 58, 1985-92.