Explaining the association between social and lifestyle factors and cognitive functions: a pathway analysis in the Memento cohort.

BACKGROUND: This work aimed to investigate the potential pathways involved in the association between social and lifestyle factors, biomarkers of Alzheimer's disease and related dementia (ADRD), and cognition. METHODS: The authors studied 2323 participants from the Memento study, a French nationwide clinical cohort. Social and lifestyle factors were education level, current household incomes, physical activity, leisure activities, and social network from which two continuous latent variables were computed: an early to midlife (EML) and a latelife (LL) indicator. Brain magnetic resonance imaging (MRI), lumbar puncture, and amyloid-positron emission tomography (PET) were used to define three latent variables: neurodegeneration, small vessel disease (SVD), and AD pathology. Cognitive function was defined as the underlying factor of a latent variable with four cognitive tests. Structural equation models were used to evaluate cross-sectional pathways between social and lifestyle factors and cognition. RESULTS: Participants' mean age was 70.9 years old, 62% were women, 28% were apolipoprotein-ε4 carriers, and 59% had a Clinical Dementia Rating (CDR) score of 0.5. Higher early to midlife social indicator was only directly associated with better cognitive function (direct ß = 0.364 (0.322; 0.405), with no indirect pathway through ADRD biomarkers (total ß = 0.392 (0.351; 0.429)). In addition to a direct effect on cognition (direct ß = 0.076 (0.033; 0.118)), the association between latelife lifestyle indicator and cognition was also mostly mediated by an indirect effect through lower neurodegeneration (indirect ß = 0.066 (0.042; 0.090) and direct ß = - 0.116 (- 0.153; - 0.079)), but not through AD pathology nor SVD. CONCLUSIONS: Early to midlife social factors are directly associated with higher cognitive functions. Latelife lifestyle factors may help preserve cognitive functions through lower neurodegeneration.

Evidencing inhibitory deficits in Alzheimer's disease through interference effects and shifting disabilities in the Stroop test.

To investigate the contribution of inhibitory deficits in the deterioration of executive function abilities in Alzheimer's disease (AD), a modified version of the Stroop test was submitted to 44 AD patients and 44 elderly controls. Half of the subjects performed successively the Interference Stroop task, the two control tasks and the Reverse Stroop task, and half performed the Reverse Stroop task, the control tasks and finally the Interference Stroop task. This experimental design allowed to assess inhibitory deficits by measuring classical interference effects but also by measuring the ability to shift between tasks instructions. Results confirmed AD patients' difficulty in suppressing the automatic response of reading in the Interference Stroop task. Moreover, AD patients presented worsened performances in the Interference task when administered after the Reverse task, and a Reverse Stroop effect was found in the patients revealing their difficulty in suppressing a previously relevant rule in order to learn a new one.

Annual rate and predictors of conversion to dementia in subjects presenting mild cognitive impairment criteria defined according to a population-based study.

Elderly subjects diagnosed with mild cognitive impairment (MCI) are becoming the target of intervention trials. The criteria used for MCI are principally issued from prospective clinical studies, although longitudinal population-based studies having identified several cognitive predictors of dementia can be of great contribution in the definition of these criteria. This study was conducted to explore the external validity of MCI criteria issued from a longitudinal population-based study, and subsequently to identify the best predictors of the short-term conversion to Alzheimer's disease 2 years after the MCI diagnosis. Ninety elderly volunteers with memory complaint diagnosed with MCI on the basis of their functional and neuropsychological performances were followed up within 2 years. The potential predictors of the conversion to dementia collected at baseline included age, gender, educational level, size of temporal lobe, apolipoprotein E genotype and a series of neuropsychological measures (Mac Nair Scale, Mini-Mental State Examination, Benton Visual Retention Test, Isaacs Set Test, Digit Symbol Substitution Task, Letter Cancellation Task, digit span tasks and finger-tapping test). Within the 2 years, 29 subjects (32.2%) presented a conversion to dementia. The risk of conversion to dementia was associated with age and size of temporal lobe but not with gender, education, or apolipoprotein E4 genotype. Several neuropsychological measures were associated with the risk of conversion to dementia, but in a logistic regression performed with the significant variables found in the univariate analysis, only the Letter Cancellation Test was shown to be an independent predictor. In conclusion, the quite elevated conversion rates obtained show the usefulness, when defining MCI criteria, of considering not only memory impairment but also impairment in other cognitive areas, as well as mild impairment on higher-order activities of daily living. Among the variables considered, the Letter Cancellation Test proved to be a major predictor of short-term conversion to dementia.

Cognitive slowing and learning of target detection skills in pre-demented subjects.

Alzheimer's disease produces a generalized slowing of cognitive processing increasing with the progression of dementia. However little is known about this phenomenon in the pre-demented stages. Our purpose was to investigate cognitive slowing in pre-demented subjects and their ability to develop target detection skills while performing a cancellation task. The results on 16 pre-demented subjects and 32 matched controls show that cognitive slowing is already present 3 years before subjects fulfill dementia criteria, at a stage where errors are still not different between pre-demented and control subjects. Additionally, the two groups significantly improved their time performances all along the test suggesting that both groups including the pre-demented group were able to progressively acquire a target detection skill.