Hélène Amieva

Incidence and outcome of mild cognitive impairment in a population-based prospective cohort

Objective: To estimate the age-specific incidence rate of mild cognitive impairment (MCI) according to sex and educational level and to explore the course of MCI, particularly its progression to AD, in a population-based cohort. Methods: A community-based cohort of nondemented elderly people (Personnes Agées QUID [PAQUID]) was followed longitudinally for 5 years. MCI was defined as memory complaints with objective memory impairment, without dementia, impairment of general cognitive functioning, or disability in activities of daily living. Incidence rates were calculated using the person–years method. A descriptive analysis at the different follow-up times was performed to study the course of MCI. Results: At baseline, there were 58 prevalent cases of MCI (2.8% of the sample). During a 5-year follow-up, 40 incident cases of MCI occurred in 1,265 subjects at risk. The global incidence rate of MCI was 9.9/1,000 person–years. MCI was a good predictor of AD with an annual conversion rate of 8.3% and a good specificity, but it was very unstable over time: Within 2 to 3 years, only 6% of the subjects continued to have MCI, whereas >40% reverted to normal. Conclusions: Conventionally defined MCI has reasonable predictive value and specificity for AD. However, MCI was very unstable across time in this study. Furthermore, the definition of MCI seems to be too restrictive and should probably be extended to other categories of individuals also at high risk of developing AD.

Adherence to a Mediterranean Diet, Cognitive Decline, and Risk of Dementia

CONTEXT Higher adherence to a Mediterranean-type diet is linked to lower risk for mortality and chronic diseases, but its association with cognitive decline is unclear. OBJECTIVE To investigate the association of a Mediterranean diet with change in cognitive performance and risk for dementia in elderly French persons. DESIGN, SETTING, AND PARTICIPANTS Prospective cohort study of 1410 adults (> or = 65 years) from Bordeaux, France, included in the Three-City cohort in 2001-2002 and reexamined at least once over 5 years. Adherence to a Mediterranean diet (scored as 0 to 9) was computed from a food frequency questionnaire and 24-hour recall. MAIN OUTCOME MEASURES Cognitive performance was assessed on 4 neuropsychological tests: the Mini-Mental State Examination (MMSE), Isaacs Set Test (IST), Benton Visual Retention Test (BVRT), and Free and Cued Selective Reminding Test (FCSRT). Incident cases of dementia (n = 99) were validated by an independent expert committee of neurologists. RESULTS Adjusting for age, sex, education, marital status, energy intake, physical activity, depressive symptomatology, taking 5 medications/d or more, apolipoprotein E genotype, cardiovascular risk factors, and stroke, higher Mediterranean diet score was associated with fewer MMSE errors (beta = -0.006; 95% confidence interval [CI], -0.01 to -0.0003; P = .04 for 1 point of the Mediterranean diet score). Performance on the IST, BVRT, or FCSRT over time was not significantly associated with Mediterranean diet adherence. Greater adherence as a categorical variable (score 6-9) was not significantly associated with fewer MMSE errors and better FCSRT scores in the entire cohort, but among individuals who remained free from dementia over 5 years, the association for the highest compared with the lowest group was significant (adjusted for all factors, for MMSE: beta = -0.03; 95% CI, -0.05 to -0.001; P = .04; for FCSRT: beta = 0.21; 95% CI, 0.008 to 0.41; P =.04). Mediterranean diet adherence was not associated with the risk for incident dementia (fully adjusted model: hazard ratio, 1.12; 95% CI, 0.60 to 2.10; P = .72), although power to detect a difference was limited. CONCLUSIONS Higher adherence to a Mediterranean diet was associated with slower MMSE cognitive decline but not consistently with other cognitive tests. Higher adherence was not associated with risk for incident dementia.

Prodromal Alzheimer's disease: Successive emergence of the clinical symptoms†

Whereas cognitive deficits are known to be detectable long before the typical symptoms of Alzheimers disease (AD) are evident, previous studies have failed to determine when cognitive functioning actually begins to decline before dementia. Utilizing the long follow‐up of the PAQUID study, we examined the emergence of the first clinical symptoms over a 14‐year period of follow‐up before the dementia phase of AD.

Cognitive Impairment Improves the Predictive Validity of the Phenotype of Frailty for Adverse Health Outcomes: The Three-City Study

OBJECTIVES: To determine whether adding cognitive impairment to frailty improves its predictive validity for adverse health outcomes.

Natural history of decline in instrumental activities of daily living performance over the 10 years preceding the clinical diagnosis of dementia: a prospective population-based study.

OBJECTIVES: To study the subtle changes in instrumental activities of daily living (IADLs) over the 10 years preceding the clinical diagnosis of dementia.

Cognitive impairment as marker of diffuse brain abnormalities in early relapsing remitting multiple sclerosis

Objectives: To establish the frequency of cognitive impairment in a population based sample of patients with recently diagnosed relapsing-remitting multiple sclerosis (RRMS), and to determine the relation between cognitive abnormalities and the extent of macroscopic and microscopic tissue damage revealed by magnetic resonance imaging (MRI) and magnetisation transfer (MT) imaging. Methods: 58 patients with RRMS consecutively diagnosed in the previous six months in Aquitaine and 70 healthy controls underwent a battery of neuropsychological tests. Lesion load and atrophy indices (brain parenchymal fraction and ventricular fraction) were measured on brain MRI. MT ratio (MTR) histograms were obtained from lesions, normal appearing white matter (NAWM), and normal appearing grey matter (NAGM). Gadolinium enhanced lesions were counted. Results: 44 RRMS patients could be individually matched with healthy controls for age, sex, and education. Patients performed worse in tests of verbal and spatial memory, attention, information processing speed, inhibition, and conceptualisation. Measures of attention and information processing speed were correlated with lesion load, mean NAWM MTR, and the peak location of the NAGM MTR histogram in the patients. Multivariate regression analysis showed that lesion load and mean NAWM MTR were among the MR indices that were most significantly associated with impairment of attention and information processing speed in these early RRMS cases. Conclusions: Cognitive impairment appears to be common in the early stages of RRMS, mainly affecting attention, information processing speed, memory, inhibition, and conceptualisation. The severity of these deficits reflects the extent of the lesions and the severity of tissue disorganisation outside lesions.

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.

Compensatory mechanisms in higher-educated subjects with Alzheimer’s disease: a study of 20 years of cognitive decline

A better knowledge of long-term trajectories of cognitive decline is a central feature of the study of the process leading to Alzheimers dementia. Several factors may mitigate such decline, among which is education, a major risk factor for Alzheimers disease. The aim of our work was to compare the pattern and duration of clinical trajectories before Alzheimers dementia in individuals with low and high education within the PAQUID cohort involving 20 years of follow-up. The sample comprises 442 participants with incident Alzheimers disease (27.2% were male)--171 with low education (mean age=86.2 years; standard deviation=5.3 years) and 271 with higher education (mean age=86.5; standard deviation=5.4)--and 442 control subjects matched according to age, sex and education. At each visit and up to the 20-year follow-up visit, several cognitive and clinical measures were collected and incident cases of Alzheimers disease clinically diagnosed. The evolution of clinical measures in pre-demented subjects and matched controls was analysed with a semi-parametric extension of the mixed effects linear model. The results show that the first signs of cognitive decline occurred 15 to 16 years before achieving dementia threshold in higher-educated subjects whereas signs occurred at 7 years before dementia in low-educated subjects. There seemed to be two successive periods of decline in higher-educated subjects. Decline started ∼15 to 16 years before dementia with subtle impairment restricted to some cognitive tests and with no impact during the first 7 to 8 years on global cognition, cognitive complaints, or activities of daily living scales. Then, ∼7 years before dementia, global cognitive abilities begin to deteriorate, along with difficulties dealing with complex activities of daily living, the increase in self-perceived difficulties and depressive symptoms. By contrast, lower-educated subjects presented a single period of decline lasting ∼7 years, characterized by decline concomitantly affecting specific and more global cognitive function along with alteration in functional abilities. This study demonstrates how early cognitive symptoms may emerge preceding Alzheimers dementia particularly in higher-educated individuals, for whom decline occurred up to 16 years before dementia. It also demonstrates the protective role of education in the clinical trajectory preceding Alzheimers dementia. We suggest that the initial decline in cognition occurs at the onset of comparable Alzheimers disease pathology in both groups, and is associated with immediate decline to dementia in the lower education group. In contrast, higher education protects against further cognitive decline for ∼7 years until pathology becomes more severe.

Education, occupation, leisure activities, and brain reserve: a population-based study

The influence of education, occupation, and leisure activities on the passive and active components of reserve capacity remains unclear. We used the voxel-based morphometry (VBM) technique in a population-based sample of 331 nondemented people in order to investigate the relationship between these factors and the cerebral volume (a marker of brain reserve). The results showed a positive and significant association between education, occupation, and leisure activities and the cognitive performances on Isaacs set test. Among these factors, only education was significantly associated with a cerebral volume including gray and white matter (p = 0.01). In voxel-based morphometry analyses, the difference in gray matter volume was located in the temporoparietal lobes and in the orbitofrontal lobes bilaterally (a p-value corrected <0.05 by false discovery rate [FDR]). Although smaller, the education-related difference in white matter volume appeared in areas connected to the education-related difference in gray matter volume. Education, occupation attainment, and leisure activities were found to contribute differently to reserve capacity. Education could play a role in the constitution of cerebral reserve capacity.

What aspects of social network are protective for dementia? Not the quantity but the quality of social interactions is protective up to 15 years later.

Objective: To test the association between several social networks variables reflecting both structural characteristics and quality of relationships with the risk of dementia and Alzheimers disease 5 and up to 15 years later. Methods: The study sample is gathered from the Paquid cohort, a French population-based study of 3,777 elderly people evaluated at baseline and regularly revisited during a 15-year interval. The sample consisted of 2,089 subjects who completed the social network questionnaire and were free of dementia at the time of enrollment and also at the next two follow-ups to minimize the problem of reverse causality. The questionnaire collected at baseline included marital status, number of ties, nature of social network, satisfaction, perception of being understood/misunderstood, and reciprocity in relationships. Results: The incident cases of dementia considered were those diagnosed at 5-year and subsequent follow-ups, resulting in 461 dementia and 373 Alzheimers disease cases. The multivariate Cox model, including the six social network variables and adjusted for numerous potential confounders, showed significant associations with satisfaction and reciprocity in relationships. Participants who felt satisfied with their relations had a 23% reduced dementia risk. Participants who reported that they received more support than they gave over their lifetime had a 55% and 53% reduced risk for dementia and Alzheimers disease, respectively. Conclusion: The only variables associated with subsequent dementia or Alzheimers disease were those reflecting the quality of relationships. The delay between social network assessment and dementia diagnosis was from 5 up to 15 years, thus minimizing the problem of reverse causality. MMSE = Mini Mental Status Examination; IADL = Instrumental Activities of Daily Living; RR = relative risk; CI = confidence interval.