[Show abstract][Hide abstract] ABSTRACT: Microstructural changes of White Matter (WM) associated with aging have been widely described through Diffusion Tensor Imaging (DTI) parameters. In parallel, White Matter Hyperintensities (WMH) as observed on a T2-MRI are extremely common in older individuals. However, few studies have investigated both phenomena conjointly. The present study investigates aging effects on DTI parameters in absence and in presence of WMH. Diffusion maps were constructed based on 21 directions DTI scans of young adults (n=19, mean age=33 SD=7.4) and two age-matched groups of older adults, one presenting low-level-WMH (n=20, mean age=78, SD= 3.2) and one presenting high-level-WMH (n=20, mean age=79, SD= 5.4). Older subjects with low-level-WMH presented modifications of DTI parameters in comparison to younger subjects, fitting with the DTI pattern classically described in aging, i.e. Fractional Anisotropy (FA) decrease/Radial Diffusivity (RD) increase. Furthermore, older subjects with high-level-WMH showed higher DTI modifications in Normal Appearing White Matter (NAWM) in comparison to those with low-level-WMH. Finally, in older subjects with high-level-WMH, FA or RD values of NAWM were associated with to WMH burden. Therefore, our findings suggest that DTI modifications and the presence of WMH would be two inter-dependent processes but occurring within different temporal windows. DTI changes would reflect the early phase of white matter changes and WMH would appear as a consequence of those changes.
Full-text · Article · Feb 2016 · Frontiers in Aging Neuroscience
[Show abstract][Hide abstract] ABSTRACT: We aimed to describe the hierarchical structure of Instrumental Activities of Daily Living (IADL) and basic Activities of
Daily Living (ADL) and trajectories of dependency before death in an elderly population using item response theory methodology.
Data were obtained from a population-based French cohort study, the Personnes Agées QUID (PAQUID) Study, of persons aged ≥65
years at baseline in 1988 who were recruited from 75 randomly selected areas in Gironde and Dordogne. We evaluated IADL and
ADL data collected at home every 2–3 years over a 24-year period (1988–2012) for 3,238 deceased participants (43.9% men).
We used a longitudinal item response theory model to investigate the item sequence of 11 IADL and ADL combined into a single
scale and functional trajectories adjusted for education, sex, and age at death. The findings confirmed the earliest losses
in IADL (shopping, transporting, finances) at the partial limitation level, and then an overlapping of concomitant IADL and
ADL, with bathing and dressing being the earliest ADL losses, and finally total losses for toileting, continence, eating,
and transferring. Functional trajectories were sex-specific, with a benefit of high education that persisted until death in
men but was only transient in women. An in-depth understanding of this sequence provides an early warning of functional decline
for better adaptation of medical and social care in the elderly.
No preview · Article · Jan 2016 · American Journal of Epidemiology
[Show abstract][Hide abstract] ABSTRACT: Background:
Sophisticated and expensive biomarkers are proposed for the diagnostic of Alzheimer's disease (AD). The amyloid process seems to be early in AD, and brain amyloid load affects the frontal lobe.
To determine if certain simple clinical signs, especially frontal-related signs, could help reach an earlier and better diagnosis.
In the frame of the 3-City cohort, we conducted a nested case-control study comparing incident cases of AD to controls matched for age, gender, and education. The standardized neurological exam included extrapyramidal signs (akinesia, rigidity, rest tremor), pyramidal symptoms (spastic rigidity, Babinski reflex), primitive reflexes (snout, palmomental reflex grasping), and tremor (essential, intentional, head) at the time of diagnosis and two years before.
We compared 106 incident AD subjects (mean age at diagnosis 82.2 (SD = 5.9); median MMSE at diagnosis = 23) to 208 matched controls. In patients younger than 80, palmomental reflexes were more frequent in AD than controls, two years before diagnosis (25.0 versus 7.0% , p = 0.03) and at time of diagnosis (30.3 versus 12.3% , p = 0.02). No difference was observed for other signs two years before diagnosis or for patients older than 80.
Before diagnosis, the clinical examination of AD patients is not strictly normal; the primitive reflexes appear to be pathological. It might be in connection with the frontal amyloid load at an early stage of the disease. Clinical examination can reveal simple and interesting signs that deserve consideration as well as the other more invasive and expensive biomarkers.
Preview · Article · Dec 2015 · Journal of Alzheimer's disease: JAD
[Show abstract][Hide abstract] ABSTRACT: Objective:
Reciprocal relationships between positive affect (PA) and health are now subject of a heuristic debate in psychology and behavioral medicine. Two radically opposed approaches address the link between subjective well being (SWB) and physical health: top-down (i.e., psychosomatic hypothesis) and bottom-up (i.e., disability/ability hypothesis) approaches. The aim of the present study was to test these two approaches by investigating thirteen-year longitudinal relationships between PA, as an affective dimension of SWB, and functional health in older people.
The study included 3754 participants aged 62-101 years assessed 6 times over a thirteen-year period. PA was measured by the mean of the positive affect subscale of the CES-D scale. Functional health was assessed by four composite items: a single-item self-rating of hearing impairment, a single-item self-rating of vision impairment, the number of medically prescribed drugs, and a single-item self-rating of dyspnoea. We used cross-lagged modeling with latent variables, which is appropriate for testing specific theories. Mean arterial pressure, diabetes mellitus and hypercholesterolemia status, sequelae of stroke, gender, level of education, and age at baseline were use as control variables in the models.
Results indicated that good health significantly predicted subsequent levels of PA (average β = -0.58, p < 0.001), but PA did not predict subsequent levels of good health (β = 0.01, ns).
This finding, obtained from a sample of older people, is in keeping with the bottom-up approach, and supports the popular adage "As long as you've got your health". Limitations of this finding are reviewed and discussed. Models including longitudinal mediators, such as biomarkers and life style patterns, are needed to clarify the nature of the link between these constructs.
Full-text · Article · Nov 2015 · Social Science [?] Medicine
[Show abstract][Hide abstract] ABSTRACT: Background:
Although non-drug interventions are widely used in patients with Alzheimer's disease, few large scale randomized trials involving a long-term intervention and several cognitive-oriented approaches have been carried out. ETNA3 trial compares the effect of cognitive training, reminiscence therapy, and an individualized cognitive rehabilitation program in Alzheimer's disease to usual care.
This is a multicenter (40 French clinical sites) randomized, parallel-group trial, with a two-year follow-up comparing groups receiving standardized programs of cognitive training (group sessions), reminiscence therapy (group sessions), individualized cognitive rehabilitation program (individual sessions), and usual care (reference group). Six hundred fifty-three outpatients with Alzheimer's disease were recruited. The primary efficacy outcome was the rate of survival without moderately severe to severe dementia at two years. Secondary outcomes were cognitive impairment, functional disability, behavioral disturbance, apathy, quality of life, depression, caregiver's burden, and resource utilization.
No impact on the primary efficacy measure was evidenced. For the two group interventions (i.e. cognitive training and reminiscence), none of the secondary outcomes differed from usual care. The larger effect was seen with individualized cognitive rehabilitation in which significantly lower functional disability and a six-month delay in institutionalization at two years were evidenced.
These findings challenge current management practices of Alzheimer's patients. While cognitive-oriented group therapies have gained popularity, this trial does not show improvement for the patients. The individualized cognitive rehabilitation intervention provided clinically significant results. Individual interventions should be considered to delay institutionalization in Alzheimer's disease.
Full-text · Article · Nov 2015 · International Psychogeriatrics
[Show abstract][Hide abstract] ABSTRACT: Background:
Benzodiazepine use has been associated with increased risk of dementia. However, it remains unclear whether the risk relates to short or long half-life benzodiazepines and whether it extends to other psychotropic drugs.
Prospective cohort study among 8240 individuals ≥65, interviewed on medication use. Incident dementia confirmed by an end point committee after a multistep procedure.
During a mean of 8 years of follow-up, 830 incident dementia cases were observed. Users of benzodiazepines at baseline had a 10% increased risk of dementia (adjusted hazard ratio [HR], 1.10; 95% confidence interval, 0.90-1.34). However, long half-life (>20 hours) benzodiazepine users had a marked increased risk of dementia (HR = 1.62; 1.11-2.37) compared with short half-life users (HR = 1.05; 0.85-1.30). Users of psychotropics had an increased risk of dementia (HR = 1.47; 1.16-1.86).
Results of this large, prospective study show increased risk of dementia for long half-life benzodiazepine and psychotropic use.
No preview · Article · Nov 2015 · Alzheimer's & dementia: the journal of the Alzheimer's Association
[Show abstract][Hide abstract] ABSTRACT: Background:
Identifying modifiable lifestyle correlates of cognitive decline and risk of dementia is complex, particularly as few population-based longitudinal studies jointly model these interlinked processes. Recent methodological developments allow us to examine statistically defined sub-populations with separate cognitive trajectories and dementia risks.
Engagement in social, physical, or intellectual pursuits, social network size, self-perception of feeling well understood, and degree of satisfaction with social relationships were assessed in 2854 participants from the Paquid cohort (mean baseline age 77 years) and related to incident dementia and cognitive change over 20-years of follow-up. Multivariate repeated cognitive information was exploited by defining the global cognitive functioning as the latent common factor underlying the tests. In addition, three latent homogeneous sub-populations of cognitive change and dementia were identified and contrasted according to social environment variables.
In the whole population, we found associations between increased engagement in social, physical, or intellectual pursuits and increased cognitive ability (but not decline) and decreased risk of incident dementia, and between feeling understood and slower cognitive decline. There was evidence for three sub-populations of cognitive aging: fast, medium, and no cognitive decline. The social-environment measures at baseline did not help explain the heterogeneity of cognitive decline and incident dementia diagnosis between these sub-populations.
We observed a complex series of relationships between social-environment variables and cognitive decline and dementia. In the whole population, factors such as increased engagement in social, physical, or intellectual pursuits were related to a decreased risk of dementia. However, in a sub-population analysis, the social-environment variables were not linked to the heterogeneous patterns of cognitive decline and dementia risk that defined the sub-groups.
Full-text · Article · Oct 2015 · BMC Public Health
[Show abstract][Hide abstract] ABSTRACT: Objective: To determine whether and how age at retirement influences the risk of dementia. The association between the age at retirement, the number of working years and the risk of dementia was evaluated over 12 years of follow-up. Design: A prospective population-based study. Setting: Three-City cohort, a French population-based study of community-dwelling individuals aged 65 to 95. Participants: The sample consisted of 1,658 non-demented participants at baseline. Measurements: All participants were evaluated at home at the initial visit and at two years interval for a period of 12 years. An active research of dementia was conducted at each follow-up; all suspected cases were analysed by an independent committee of neurologists. Information regarding retirement age and number of working years was collected at baseline using a structured questionnaire. Results: The multivariate Cox model, including both the age at retirement and the number of working years and adjusted for potential confounders, revealed that the risk of dementia was independently associated with the age at retirement (p=0.022) but not with the number of working years (p=0.296). Conclusion: Although our results are in accordance with previous studies (i.e., older age at retirement is associated with decreased risk of dementia), it provides additional information regarding the possible explanation for such results. Given that a longer working life did not reduce the risk of dementia, the age at retirement cannot be considered as a new factor of cognitive reserve but rather seems to be a psycho-social vulnerability factor. Further evidence is necessary to identify work and retirement related factors that influence the association between the age at retirement and the risk of dementia.
Full-text · Article · Oct 2015 · The Journal of Nutrition Health and Aging
[Show abstract][Hide abstract] ABSTRACT: There is an obvious lack of validated norms for elderly persons aged 85 and older for the large majority of the neuropsychological
tests used in clinical practice. Yet this range of “oldest-old” individuals drastically increases worldwide and is the more
likely to develop dementia. Providing clinicians validated and updated norms to accurately evaluate cognitive functioning
in this population is an important issue in geriatrics. This study provides normative scores for 7 neuropsychological tests
commonly used in clinical practice. Data were collected in a sample of 283 subjects aged 85 and older, included in the PAQUID
study, a population-based cohort conducted in France. Normative scores were calculated according to 2 age ranges and 2 educational
levels, and are presented in percentiles. The norms provided in the present study involve 7 tests that are widely used in
the neuropsychological assessment of geriatrics populations and should be of help for clinicians.
No preview · Article · Sep 2015 · Archives of Clinical Neuropsychology
[Show abstract][Hide abstract] ABSTRACT: Introduction:
Few recent studies have suggested declining trends in dementia frequency. French cohorts with long follow-up allowed us to explore incidence evolution trends.
Two different populations of subjects aged ≥65 years included in 1988-1989 (n = 1469) and 1999-2000 (n = 2104) were followed up over 10 years, with systematic assessment for cognition and dementia. Multistates illness-death models were used to compare dementia incidence using both clinical and algorithmic diagnoses.
Using the algorithmic diagnosis, incidence declined significantly overall and for women (age-adjusted hazard ratio [HR] = 0.62; confidence interval [CI] = 0.48-0.80 for women between the two populations). Differences in education, vascular factors, and depression accounted only to some extent for this reduction (women full-adjusted HR = 0.73; CI = 0.57-0.95). No significant decreasing trends were found for men or when using the clinical diagnosis for either sex.
Our study provides further support for a decrease in dementia incidence between the 1990s and the 2000s. Changes in diagnostic boundaries mask this reduction.
Full-text · Article · Jul 2015 · Alzheimer's & dementia: the journal of the Alzheimer's Association