Predicting Progression to Dementia in Elderly Subjects with Mild Cognitive Impairment Using Both Cognitive and Neuroimaging Predictors

Abstract

The objective of this work was to assess the predictive accuracy of targeted neuroimaging and neuropsychological measures for the detection of incipient dementia in individuals with mild cognitive impairment (MCI), and to examine the potential benefit of combining both classes of measures. Baseline MRI measures included hippocampal volume, cortical thickness, and white matter hyperintensities. Neuropsychological assessment focused on different aspects of episodic memory (i.e., familiarity, free recall, and associative memory) and executive control functions (i.e., working memory, switching, and planning). Global and regional cortical thinning was observed in MCI patients who progressed to dementia compared to those who remained stable, whereas no differences were found between groups for baseline hippocampal volume and white matter hyperintensities. The strongest neuroimaging predictors were baseline cortical thickness in the right anterior cingulate and middle frontal gyri. For cognitive predictors, we found that deficits in both free recall and recognition episodic memory tasks were highly suggestive of progression to dementia. Cortical thinning in the right anterior cingulate gyrus, combined to controlled and familiarity-based retrieval deficits, achieved a classification accuracy of 87.5%, a specificity of 90.9%, and a sensitivity of 83.3%. This predictive model including both classes of measures provided more accurate predictions than those based on neuroimaging or cognitive measures alone. Overall, our findings suggest that detecting preclinical Alzheimer's disease is probably best accomplished by combining complementary information from targeted neuroimaging and cognitive classifiers, and highlight the importance of taking into account both structural and functional changes associated with the disease.

O2‐07‐03: Patterns of Cognitive Decline Prior to Dementia in Persons With Mild Cognitive Impairment

“…This is consistent with the observation that MCI is mainly characterized by memory deficits [3,5], and that both episodic memory and working memory are impaired early in the disease process and are predictors of conversion from MCI to AD [11,36] (for a review, see [37]) and from healthy aging to MCI [38].…”

Early neuropsychological detection of Alzheimer's disease

“…In the same vein, in Schmand et al, 47 combining a verbal episodic memory score, hippocampal volume and cerebrospinal fluid amyloid measure correctly predicted progression from MCI to AD with an accuracy of 70%, whereas classification accuracy was below 70% for each individual measure. Similarly, Peters et al 86 indicated that cortical thickness of the anterior cingulate gyrus combined to specific memory measures yielded a classification accuracy of 87.5% in the discrimination between stable MCI versus MCI who developed AD. These were considered more accurate predictions than those based on neuroimaging (75%) or cognitive measures (82.5%) alone.…”

Role of Hypothalamic-Pituitary-Adrenal Axis, Hypothalamic-Pituitary-Gonadal Axis and Insulin Signaling in the Pathophysiology of Alzheimer’s Disease

“…Another study observed an age-dependent progression in insulin signaling dysregulation that precedes peripheral insulin resistance in two preclinical AD models [87]. Hippocampal dysfunction and structural compromise are one of the early signs during AD onset [87-91]. Insulin plays a very important role in AD progression by various complex mechanisms [92].…”