Publications by authors named "Helene Amieva"

152 Publications

Distinct Hippocampal Subfields Atrophy in Older People With Vascular Brain Injuries.

Stroke 2021 Mar 4:STROKEAHA120031743. Epub 2021 Mar 4.

University of Bordeaux, CNRS, UMR 5293, Institut des Maladies Neurodégénératives, France (G.P., L.N., B.M., V.P.).

Background And Purpose: Many neurological or psychiatric diseases affect the hippocampus during aging. The study of hippocampal regional vulnerability may provide important insights into the pathophysiological mechanisms underlying these processes; however, little is known about the specific impact of vascular brain damage on hippocampal subfields atrophy.

Methods: To analyze the effect of vascular injuries independently of other pathological conditions, we studied a population-based cohort of nondemented older adults, after the exclusion of people who were diagnosed with neurodegenerative diseases during the 14-year clinical follow-up period. Using an automated segmentation pipeline, 1.5T-magnetic resonance imaging at inclusion and 4 years later were assessed to measure both white matter hyperintensities and hippocampal subfields volume. Annualized rates of white matter hyperintensity progression and annualized rates of hippocampal subfields atrophy were then estimated in each participant.

Results: We included 249 participants in our analyses (58% women, mean age 71.8, median Mini-Mental State Evaluation 29). The volume of the subiculum at baseline was the only hippocampal subfield volume associated with total, deep/subcortical, and periventricular white matter hyperintensity volumes, independently of demographic variables and vascular risk factors (β=-0.17, =0.011; β=-0.25, =0.020 and β=-0.14, =0.029, respectively). In longitudinal measures, the annualized rate of subiculum atrophy was significantly higher in people with the highest rate of deep/subcortical white matter hyperintensity progression, independently of confounding factors (β=-0.32, =0.014).

Conclusions: These cross-sectional and longitudinal findings highlight the links between vascular brain injuries and a differential vulnerability of the subiculum within the hippocampal loop, unbiased of the effect of neurodegenerative diseases, and particularly when vascular injuries affect deep/subcortical structures.
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http://dx.doi.org/10.1161/STROKEAHA.120.031743DOI Listing
March 2021

Similarities in cognitive abilities in older couples: a study of mutual influences.

J Clin Exp Neuropsychol 2021 Feb 8;43(1):78-90. Epub 2021 Feb 8.

Bordeaux Population Health Research Center, Univ. Bordeaux, Inserm, UMR 1219, Bordeaux, France.

: Similarities between spouses in cognitive functions have been mainly explained by the assortative mating phenomenon and the convergence for age and education. The mutual influence between spouses is another explanation particularly relevant in the elderly population. Today, it remains difficult to determine whether cognitive similarities exclusively result from the convergence effect or from the mutual influence. Using a novel methodology, the present study aimed to assess the impact of the marital relationship on cognitive similarities among elderly couples.: 1723 couples from the Three-City Cohort Study were classified in two groups of couples with homogeneous and heterogeneous age and education. We also constituted two groups of pseudo-couples by a random association of individuals, with homogeneous and heterogeneous age and education. Dyadic analyses were conducted in the four groups, regarding the similarities in lexicosemantic abilities, executive functions, memory and global cognitive functioning.: Similarities were found on lexicosemantic abilities both in mate-assorted couples and in couples heterogeneous in age and education but no similarity was found in pseudo-couples.: Beyond the convergence effect, the fact that the spouses co-construct their lifestyles may contribute to cognitive similarities in the lexicosemantic domain.
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http://dx.doi.org/10.1080/13803395.2021.1874882DOI Listing
February 2021

Free water: A marker of age-related modifications of the cingulum white matter and its association with cognitive decline.

PLoS One 2020 20;15(11):e0242696. Epub 2020 Nov 20.

EPHE, PSL, Bordeaux, France.

Diffusion MRI is extensively used to investigate changes in white matter microstructure. However, diffusion measures within white matter tissue can be affected by partial volume effects due to cerebrospinal fluid and white matter hyperintensities, especially in the aging brain. In previous aging studies, the cingulum bundle that plays a central role in the architecture of the brain networks supporting cognitive functions has been associated with cognitive deficits. However, most of these studies did not consider the partial volume effects on diffusion measures. The aim of this study was to evaluate the effect of free water elimination on diffusion measures of the cingulum in a group of 68 healthy elderly individuals. We first determined the effect of free water elimination on conventional DTI measures and then examined the effect of free water elimination on verbal fluency performance over 12 years. The cingulum bundle was reconstructed with a tractography pipeline including a white matter hyperintensities mask to limit the negative impact of hyperintensities on fiber tracking algorithms. We observed that free water elimination increased the ability of conventional DTI measures to detect associations between tissue diffusion measures of the cingulum and changes in verbal fluency in older individuals. Moreover, free water content and mean diffusivity measured along the cingulum were independently associated with changes in verbal fluency. This suggests that both tissue modifications and an increase in interstitial isotropic water would contribute to cognitive decline. These observations reinforce the importance of using free water elimination when studying brain aging and indicate that free water itself could be a relevant marker for age-related cingulum white matter modifications and cognitive decline.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242696PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678997PMC
January 2021

Trajectory of Quality of Life Before and After Entering a Nursing Home: A Longitudinal Study.

J Geriatr Psychiatry Neurol 2020 Oct 8:891988720964259. Epub 2020 Oct 8.

Inserm U1219 Bordeaux Population Health Center, Université de Bordeaux, Bordeaux, France.

Objectives: The objective of this longitudinal study was to compare the trajectory of subjective quality of life in 2 groups of older adults: those who entered a nursing home and those who remained living in the community with similar clinical conditions.

Method: PAQUID is a prospective population-based study. It included, at baseline, 3777 community-dwelling participants aged 65 years and over. Participants were followed-up for up to 27 years. Among people living at home at baseline, 2 groups were compared: participants who entered a nursing home over a 20-year follow-up (n = 528) and those who remained community dwellers (n = 2273). We used latent process mixed models to estimate the relationship between mean trajectory of subjective quality of life and admission into a nursing home. We computed univariate and multivariate models taking into account potential confounders (age, gender, education, income, comorbidities, dementia, disability and depression).

Results: Nursing home placement was significantly associated with a drop in quality of life between the last visit before and after institutionalization. Nevertheless, we found no difference in quality of life trajectory after this initial drop.

Conclusion: Older adults exhibit an acute drop in quality of life after nursing home admission, probably reflecting the associated psychological distress. Even though their quality of life does not go back to pre-admission levels, the residents do not show a steeper decline when compared to the "natural" evolution of quality of life in older adults living in the community, which suggests a relative adaptation to their new living conditions.
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http://dx.doi.org/10.1177/0891988720964259DOI Listing
October 2020

Study of mutual influence between trait anxiety and risk of depression among older couples facing cancer.

J Geriatr Oncol 2020 Sep 28. Epub 2020 Sep 28.

University of Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR 1219, 146 rue Léo Saignat, CS61292, F-33076 Bordeaux Cedex, France. Electronic address:

Introduction: The present study aims to examine the process of mutual influence in older couples with cancer diagnosis by studying their risk of depression.

Materials And Methods: 282 couples with one spouse diagnosed with cancer were selected from the Three-City cohort study. Dyadic analyses were used to determine whether trait anxiety affects the risk of depression and whether a mutual influence process occurs prior and post cancer diagnosis. Cross-sectional analyses were performed at two time-points: before and after receiving the diagnosis.

Results: A higher level of anxiety among cancer patients resulted in a decreased risk of depression among spousal caregivers. Moreover, a higher anxiety among spousal caregivers increased their own risk of depression, but it didn't influence depression risk among cancer patients. While there is an intra-individual relationship between a higher level of trait anxiety and a greater risk of depression prior to cancer diagnosis, there is no cross-influence between spouses.

Discussion: The study findings indicate that a dyadic psychological adjustment process might help older adults to cope with cancer by limiting the risk of depression among spousal caregivers.
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http://dx.doi.org/10.1016/j.jgo.2020.09.017DOI Listing
September 2020

Changes Over Time of Diffusion MRI in the White Matter of Aging Brain, a Good Predictor of Verbal Recall.

Front Aging Neurosci 2020 14;12:218. Epub 2020 Aug 14.

Université de Bordeaux, INCIA, UMR 5287-équipe NeuroImagerie et Cognition Humaine, Bordeaux, France.

: Extensive research using water-diffusion MRI reported age-related modifications of cerebral White Matter (WM). Moreover, water-diffusion parameter modifications have been frequently associated with cognitive performances in the elderly sample, reinforcing the idea of aging inducing microstructural disconnection of the brain which in turn impacts cognition. However, only few studies really assessed over-time modifications of these parameters and their relationship with episodic memory outcome of elderly. : One-hundred and thirty elderly subjects without dementia (74.1 ± 4.1 years; 47% female) were included in this study. Diffusion tensor imaging (DTI) was performed at two-time points (3.49 ± 0.68 years apart), allowing the assessment of changes in water-diffusion parameters over time using a specific longitudinal pipeline. White matter hyperintensity (WMH) burden and gray matter (GM) atrophy were also measured on FLAIR and T1-weighted sequences collected during these two MRI sessions. Free and cued verbal recall scores assessed at the last follow-up of the cohort were used as episodic memory outcome. Changes in water-diffusion parameters over time were included in serial linear regression models to predict retrieval or storage ability of elderly. : GM atrophy and an increase in mean diffusivity (MD) and WMH load between the two-time points were observed. The increase in MD was significantly correlated with WMH load and the different memory scores. In models accounting for the baseline cognitive score, GM atrophy, or WMH load, MD changes still significantly predict free verbal recall, and not total verbal recall, suggesting the specific association with the retrieval deficit in healthy aging. : In elderly, microstructural WM changes are good predictors of lower free verbal recall performances. Moreover, this contribution is not only driven by WMH load increase. This last observation is in line with studies reporting early water-diffusion modification in WM tissue during aging, resulting lately in the appearance of WMH on conventional MRI.
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http://dx.doi.org/10.3389/fnagi.2020.00218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456903PMC
August 2020

Cognitive and functional changes in prediagnostic phase of Parkinson disease: A population-based study.

Parkinsonism Relat Disord 2020 Aug 15;79:40-46. Epub 2020 Aug 15.

Institut des Maladies Neurodégénératives-Clinique (IMNc), University Hospital Bordeaux, Bordeaux, France; Institut des Maladies Neurodégénératives, CNRS, UMR 5293, Bordeaux University, Bordeaux, France.

Introduction: Prodromal non-motor symptoms precede, often by decades, motor signs and diagnosis of Parkinson's disease. It is however still uncertain if cognitive changes belong to the spectrum of non-motor prodromal Parkinson's disease. Thanks to the very long-term follow-up of the PAQUID population-based cohort, we assessed trajectories of cognitive complaints and functioning over a 13-year period before the diagnosis of late onset Parkinson's disease.

Methods: This study relies on a matched nested case-control sample selected from the cohort. Of the 3777 initial subjects of the cohort, 43 developed incident Parkinson's disease over the follow-up. The mean age at diagnosis was 78.0 (standard deviation = 5.8) years and 46.5% were men. These cases were matched to 86 elderly control subjects. Scores of different cognitive domains, daily function, and depressive symptoms were described throughout the follow-up using mixed-effects models.

Results: No significant global cognitive decline preceded the diagnosis of late onset Parkinson's disease. However, psychomotor speed appeared significantly slower 2 years before the diagnosis and depressive symptoms 12 years before. Global score of instrumental activities of daily living became altered 2-3 years preceding the diagnosis of late onset Parkinson's disease, including the use of public transportation that was altered ten years before the diagnosis.

Conclusion: In late onset Parkinson's disease, while global cognitive functions seem preserved, psychomotor speed starts to decline 2 years before the diagnosis and activities of daily living are also impacted. Depressive symptoms appear very early in the prediagnosic phase.
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http://dx.doi.org/10.1016/j.parkreldis.2020.08.022DOI Listing
August 2020

Association between chronic pain and long-term cognitive decline in a population-based cohort of elderly participants.

Pain 2021 Feb;162(2):552-560

INSERM, U1219, Bordeaux Population Health Center, University of Bordeaux, Bordeaux, France.

Abstract: Chronic pain (CP) was associated with impaired cognitive performance in several cross-sectional studies conducted in older adults; however, fewer longitudinal studies assessed this link that remains still debated. With a prospective design, the present analysis was aimed at evaluating the relationship between CP and the change in several tests assessing memory, attention, verbal fluency, and processing speed. The study population was selected from the PAQUID study, a cohort of community dwellers aged 65 years and older; 693 subjects receiving a pain assessment were included. Chronic pain was evaluated using a questionnaire administered at 3-year follow-up. Cognitive performances were assessed every 2 to 3 years between 3 and 15 years assessing general cognition (Mini-Mental State Examination), verbal and visual memory (word paired-associate test and Benton test), attention and speed processing (Wechsler Digit Symbol Substitution Test and Zazzo's Cancellation Task), and language skills and executive functions (Isaacs Set Test). The link between CP and the change in cognitive function was assessed with latent process mixed models controlled for age, sex, education, comorbidities, depression, and analgesic drugs. The association between CP and each of the cognitive scores was then tested with the same procedure. A significant relationship was observed between CP and poorer 15-year scores on global cognitive performance (P = 0.004), and specifically, the Digit Symbol Substitution Test (P = 0.002) was associated with a higher slope of decline (P = 0.02). Chronic pain is associated with a higher cognitive decline, particularly in processing speed. This result reinforces the importance of actively treating CP with pharmacological and nonpharmacological strategies to prevent its consequences, including cognitive consequences.
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http://dx.doi.org/10.1097/j.pain.0000000000002047DOI Listing
February 2021

Age-related change in episodic memory: role of functional and structural connectivity between the ventral posterior cingulate and the parietal cortex.

Brain Struct Funct 2020 Sep 29;225(7):2203-2218. Epub 2020 Jul 29.

EPHE, PSL, 33000, Bordeaux, France.

While the neural correlates of age-related episodic memory decline have been extensively studied, the precise involvement of the Posterior Cingulate Cortex (PCC) and posterior parietal cortex (the precuneus and the angular gyrus), remains unclear. The present study examined functional and structural neural correlates of age-related episodic memory change assessed over 12 years in 120 older adults (range 76-90 years). Episodic memory performance was measured using the Free and Cued Selective Reminding Test (FCSRT); functional connectivity metrics were computed from resting-state fMRI images and structural connectivity metrics were assessed through microstructural properties of reconstructed tract using a native space pipeline. We found that FCSRT change was significantly associated with the functional connectivity between the ventral PCC and three parietal regions, the ventral superior, the inferior part of the precuneus, and the rostro dorsal part of the angular gyrus. This association was independent of hippocampal volume. In addition, we found the that change in FCSRT scores was associated with fractional anisotropy of the tract connecting the ventral PCC and the ventral superior part of the precuneus. Change in episodic memory in aging was therefore related to a combination of high functional connectivity and low structural connectivity between the ventral PCC and the ventral superior part of the precuneus.
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http://dx.doi.org/10.1007/s00429-020-02121-7DOI Listing
September 2020

Validation of Short Form of Preferences for Routines Scale: Norms in Older Adults.

Int J Aging Hum Dev 2020 Jul 23:91415020940213. Epub 2020 Jul 23.

27086 Inserm, Bordeaux Population Health Research Center, University of Bordeaux, France.

High level of preferences for routines is an indicator of psychological vulnerability in older adults. However, the psychometric properties of the Preferences for Routines Scale (PRS) initially validated in a small selected sample of older adults revealed a low Cronbach's α (.50) in the general elderly population. The present study aims to improve the PRS using the data from the "AMI" and "PAQUID" population-based studies. Among 718 older persons, the most discriminative items are identified using item response theory methodology. A short form of the PRS (PRS-S) included five of the ten items of the original scale and showed improved internal consistency and test-retest reliability. The factors associated with the PRS-S are similar to those found in previous studies. Norms are provided according to gender and educational level. The reduction of the number of items tends to facilitate its administration and promote its use in both clinical and epidemiologic research contexts.
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http://dx.doi.org/10.1177/0091415020940213DOI Listing
July 2020

The disability process: is there a place for frailty?

Age Ageing 2020 08;49(5):764-770

University of Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR 1219, Bordeaux, France.

Background: frailty and disability are very common in older adults; they share some risk factors and pathophysiological mechanisms. Yet, they are different clinical entities.

Objectives: this study aimed to explore a potential hierarchical relationship between frailty and disability along the continuum of the disablement process.

Design: prospective cohort study.

Setting: the French Three-City (3C) study.

Subjects: the sample included 943 participants aged 75 and older.

Methods: the Fried frailty phenotype, Instrumental Activities of Daily Living (IADL) and basic Activities of Daily Living (ADL) were used. We distinguished between four mutually excluding groups: (i) robust (no frailty and no disability); (ii) pure frailty (no disability); (iii) frailty with IADL disability (no ADL disability) and (iv) frailty with IADL and ADL disabilities. We used Cox's regression models to study the 4-year mortality risk associated with each status.

Results: Eight-two per cent of participants were classified according to the assumed hierarchy: 61.3% was robust, 5.4% frail, 10.5% frail and IADL-disabled and 4.8% frail, IADL and ADL-disabled. An extra group of 17% was identified with IADL-disabled individuals without frailty. This extra group was similar to pure frailty in terms of characteristics and risk of death, placing them along the continuum at an intermediate stage between robustness and the two most disabled sub-groups.

Conclusions: our findings suggest that including frailty along the continuum could be relevant to describe the whole disablement process. Frailty would occur upstream of the process and might be relevant to identify an opportune time window, where specific monitoring and clinical interventions could be implemented in order to interrupt the process at a potentially more reversible stage.
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http://dx.doi.org/10.1093/ageing/afaa031DOI Listing
August 2020

Does Treating Hearing Loss in Older Adults Improve Cognitive Outcomes? A Review.

J Clin Med 2020 Mar 16;9(3). Epub 2020 Mar 16.

Inserm U1219 Bordeaux Population Health Center, Université de Bordeaux, 33076 Bordeaux, France.

Hearing loss is the third most prevalent health condition in older age. In recent years, research has consistently reported an association between hearing loss and mental health outcomes, including poorer cognitive performances. Whether treating hearing loss in elders improves cognition has been directly or indirectly addressed by several studies. This review aims at providing a synthesis of those results. Regarding the literature on hearing aids' use and cognition, although the lack of interventional studies has to be underlined, observational data suggest that hearing aids positively impact long-term cognition, even though more research is necessary to ascertain this statement and provide information on the length or frequency of use required in order to observe benefits. Regarding cochlear implants in elders experiencing more severe auditory deprivation, the literature is scarcer. The available studies have many limitations and do not allow the drawing of clear conclusions. Taken together, the results are encouraging. Nevertheless, because hearing loss is suspected to account for 9% of dementia cases, and also because hearing loss is one of the few potentially modifiable factors from a dementia prevention perspective, the need to stimulate research to have clearer knowledge of the benefits of treating hearing loss on cognitive outcomes is urgent.
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http://dx.doi.org/10.3390/jcm9030805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141203PMC
March 2020

Gait speed and body mass index: Results from the AMI study.

PLoS One 2020 10;15(3):e0229979. Epub 2020 Mar 10.

Geriatric Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy.

Background: While physical frailty and malnutrition/obesity (parameters easily measured by a nurse) are not the same, older persons who are malnourished/obese are more likely to be frail and there is a potential overlap between these conditions. The objective was to examine the relationship between gait speed (GS) and body mass index (BMI) in men and women aged 75 years and older.

Design: Cross-sectional analysis.

Setting, Participants: Data from the Aging Multidisciplinary Investigation (AMI), a French prospective cohort study with participants randomly selected from the farmer Health Insurance rolls.

Measurements: Usual GS was measured over a 4 meters-track. BMI was categorized using clinical cut-points for European populations: (e.g, <20.0 kg/m2; 20.0-24.9 kg/m2; 25.0-29.9 kg/m2; 30.0-34.9 kg/m2; ≥35.0 kg/m2).

Results: The current analyses were performed in 449 participants. Mean age was 81 years. Being malnourished/obese was significantly associated with slow GS. Unadjusted and age-adjusted models showed that underweight, overweight and obesity statuses were significantly associated with slow GS for both women (0.83m/s [0.61; 1.04], 0.87m/s [0.72; 1.02], 0.70 m/s [0.41; 0.98], respectively) and men (0.83m/s [0.61; 1.04], 1.11m/s [1.03; 1.20], 0.97m/s [0.75; 1.19], respectively).

Conclusion: Malnourished/obese are associated with slow GS in older persons. These variables could be contributed at comprehensively and complementarily assessing the older person.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0229979PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7064171PMC
June 2020

Influence of pre-admission factors on quality of life and adaptation in nursing home residents with dementia: the QOL-EHPAD study protocol.

BMC Geriatr 2020 03 6;20(1):92. Epub 2020 Mar 6.

Inserm U1219 Bordeaux Population Health Center, Université de Bordeaux, 33076, Bordeaux, France.

Background: In 2015 in France, 585,560 people were nursing home residents. A large body of studies has identified predictors of poor quality of life and poor adaptation in institution, mostly for residents without dementia. With 42 to 72% of these residents diagnosed with dementia, it is crucial to identify what factors prior to admission might have an impact on quality of life once the admission is finalized, in order to target specific domains of intervention, while the person still lives at home and after his/her admission.

Methods: QOL-EHPAD is a prospective, multi-centred, observational cohort study. At baseline, we will collect retrospective data on the life of 150 persons with dementia and their caregivers. These data will refer to the conditions of admission to a nursing home (emergency admission, involvement in the decision, admission from home or from the hospital) and to the 6 months prior to the admission of the person with dementia: sociodemographic and medical data, psychological tests, information on quality of life, satisfaction, behaviour, and nutrition. Similar data about life in the nursing home will be collected after 6 months, along with information on adaptation of the person with dementia to his/her new living environment. We will use univariate regression analyses followed by stepwise linear regression models to identify which factors pertaining to life at home are associated with quality of life and adaptation after 6 months.

Discussion: This study will provide data on the impact of institutionalization on quality of life and the determinants of a successful institutionalization in people with dementia. This could be helpful in setting up targeted interventions to prepare admission into a nursing home before the actual admission and to accompany both the caregiver and the person with dementia throughout this process.
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http://dx.doi.org/10.1186/s12877-020-1434-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7059284PMC
March 2020

Differential annualized rates of hippocampal subfields atrophy in aging and future Alzheimer's clinical syndrome.

Neurobiol Aging 2020 06 1;90:75-83. Epub 2020 Feb 1.

Univ. Bordeaux, CNRS, Institut des Maladies Neurodégénératives, Bordeaux, France; Centre Mémoire de Ressources et de Recherches, Pôle de Neurosciences Cliniques, CHU de Bordeaux, Bordeaux, France. Electronic address:

Several studies have investigated the differential vulnerability of hippocampal subfields during aging and Alzheimer's disease (AD). Results were often contradictory, mainly because these works were based on concatenations of cross-sectional measures in cohorts with different ages or stages of AD, in the absence of a longitudinal design. Here, we investigated 327 participants from a population-based cohort of nondemented older adults with a 14-year clinical follow-up. MRI at baseline and 4 years later were assessed to measure the annualized rates of hippocampal subfields atrophy in each participant using an automatic segmentation pipeline with subsequent quality control. On the one hand, CA4 dentate gyrus was significantly more affected than the other subfields in the whole population (CA1-3: -0.68%/year; subiculum: -0.99%/year; and CA4-DG: -1.39%/year; p < 0.0001). On the other hand, the annualized rate of CA1-3 atrophy was associated with an increased risk of developing Alzheimer's clinical syndrome over time, independently of age, gender, educational level, and ApoE4 genotype (HR = 2.0; CI 95% 1.4-3.0). These results illustrate the natural history of hippocampal subfields atrophy during aging and AD by showing that the dentate gyrus is the most vulnerable subfield to the effects of aging while the cornu-ammonis is the primary target of AD pathophysiological processes, years before symptom onset.
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http://dx.doi.org/10.1016/j.neurobiolaging.2020.01.011DOI Listing
June 2020

Subjective Age in the Oldest Old: What is the Association with Disability and Sensory Impairment?

J Am Acad Audiol 2020 04 15;31(4):257-261. Epub 2020 Apr 15.

Univ. Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR 1219, F-33000 Bordeaux, France.

Background And Purpose: Disability and sensory impairment are particularly pronounced among the oldest old population (80 years and older). Considering these specificities, we analyzed the association of such parameters with subjective age, a strong predictor of health-related outcomes. We assumed that greater disability and sensory impairment (hearing and visual) would be linked with an older subjective age.

Research Design: Prospective population-based study.

Study Sample: Data were gathered from the 27 year follow-up of the PAQUID cohort, visit where the question on subjective age was collected. Our sample included 75 participants older than 93 years, with a mean age of 96 years.

Data Collection And Analysis: Disability was assessed with Activities of Daily Living and sensory impairments by asking participants if they have visual or hearing difficulties. A multiple linear regression model was performed with subjective age as the dependent variable. Independent variables were functional disability and visual and hearing impairments.

Results: On average, the participants felt 12 years younger than their actual age. Multiple regression analyses controlled for age, gender, education, depression, and dementia indicated that self-reported hearing loss ( = 0.03) was associated with an older subjective age, whereas no significant associations were observed for disability ( = 0.42) and self-reported visual loss ( = 0.18).

Conclusions: Hearing impairment, in contrast to visual impairment and disability, is associated with feeling older. These results are discussed in light of health consequences and age stigma carried by hearing impairment.
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http://dx.doi.org/10.3766/jaaa.18087DOI Listing
April 2020

Association of Seropositivity to Borrelia burgdorferi With the Risk of Neuropsychiatric Disorders and Functional Decline in Older Adults: The Aging Multidisciplinary Investigation Study.

JAMA Neurol 2020 02;77(2):210-214

University Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR 1219, Bordeaux, France.

Importance: Exposure to Borrelia burgdorferi (Bb) has been reported to be associated with certain neuropsychiatric disorders.

Objective: To establish the association between seropositivity to Bb and incidental neuropsychiatric disorders (eg, cognitive decline, incident dementia, and depressive symptoms) as well as functional decline.

Design, Setting, And Participants: This prospective, 6-year follow-up cohort study was conducted in a rural southwestern region of France and included 689 retired farmers 65 years or older randomly recruited from the Farmer Health Insurance System who agreed to submit a blood sample and were participants in the Aging Multidisciplinary Investigation study, an ongoing epidemiological prospective study of aging initiated in 2007. The data were analyzed from April to May 2019.

Exposures: Borrelia burgdorferi serology testing was performed in a 2-tiered approach. During the follow-up period, cognitive decline, incident dementia, depressive symptoms, and functional decline were repeatedly assessed.

Main Outcomes And Measures: Diagnosis of dementia relied on a 3-step procedure; cognitive decline was determined using the Mini-Mental State Examination and depressive symptomatology was assessed using the Center for Epidemiologic Studies Depression scale. For disability, scores on instrumental and basic activities of daily living were investigated.

Results: Of 689 participants, 432 (62.2%) were men and the mean (SD) age was 75.8 (6.4) years. The seroprevalence rate of Bb was 6.5%. At baseline, compared with Bb- participants, those who were Bb+ were older, predominantly men, and had lower depressive symptoms. No association between seropositivity and any of the studied outcomes (ie, cognitive decline, depressive symptoms, or functional decline) was found in the crude analysis and after adjusting for confounding variables. Regarding incident dementia, no increased risk was found among Bb+ participants (hazard ratio, 0.42; 95% CI, 0.1-1.17; adjusted for diverse confounders).

Conclusions And Relevance: To our knowledge, this is one of the few longitudinal studies exploring the risk of neuropsychiatric disorders and functional decline associated with exposure to Bb. Despite its limitations (eg, a lack of information if clinical manifestations of Lyme borreliosis existed, date of exposure, or treatment received), this study suggests that seropositivity to Bb is not a risk factor for incidental neuropsychiatric disorders and functional decline.
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http://dx.doi.org/10.1001/jamaneurol.2019.3292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6777246PMC
February 2020

Is Low Psychomotor Speed a Marker of Brain Vulnerability in Late Life? Digit Symbol Substitution Test in the Prediction of Alzheimer, Parkinson, Stroke, Disability, and Depression.

Dement Geriatr Cogn Disord 2019 29;47(4-6):297-305. Epub 2019 Aug 29.

INSERM, U1219, Bordeaux Population Health Center, University of Bordeaux, Bordeaux, France.

Background: Dementia, stroke, depression, and disability are frequent in late life and are major causes of quality of life disruption and family burden. Even though each of these disorders relies on specific pathogenic processes, a common clinical manifestation is psychomotor slowing.

Objective: We assessed the relevance of a simple marker of low psychomotor speed in predicting several brain outcomes: dementia, Alzheimer's disease (AD), Parkinson's disease (PD), stroke, depressive symptoms, and disability in activities of daily living (ADL) and instrumental ADL (IADL).

Methods: PAQUID is a population-based study involving 3,777 individuals aged 65 or older prospectively followed-up with repeated clinical evaluations. After 10 years, 437 participants developed dementia, 333 developed AD, 71 developed PD, 207 reported incident stroke, 404 developed disability in ADL, 994 in IADL, and 494 developed depressive symptomology. Psychomotor speed was measured with the digit symbol substitution test (DSST). Cox proportional hazards models controlled for several confounders assessed the risk of incident outcomes.

Results: Participants with low DSST performance had increased risk of incident all-type dementia (hazard ratio [HR] 3.41, p < 0.0001) and AD-type dementia (HR 3.18, p < 0.0001). Higher risk for PD (HR 2.98, p = 0.04), IADL (HR 1.82, p < 0.0001), ADL disability (HR 1.95, p = 0.001), depressive symptoms (HR 1.53, p = 0.03), and a statistical trend for stroke (HR 1.88, p = 0.09) was also found.

Conclusion: Low psychomotor speed is associated with an increased risk of developing various brain outcomes: dementia, AD, PD, disability, depressive symptoms, and marginally stroke. Low psychomotor speed may be the consequence of a number of discrete cerebral abnormalities and could be considered as a marker of brain vulnerability. In clinical practice, a low score in DSST should be seen as a warning sign of possible negative evolution.
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http://dx.doi.org/10.1159/000500597DOI Listing
January 2020

A hypothesis testing procedure for random changepoint mixed models.

Stat Med 2019 09 17;38(20):3791-3803. Epub 2019 Jun 17.

INSERM, Bordeaux Population Health Research Center, University of Bordeaux, Bordeaux, France.

In biomedical research, random changepoint mixed models are used to take into account an individual breakpoint in a biomarker trajectory. This may be observed in the cognitive decline measured by psychometric tests in the prediagnosis phase of Alzheimer's disease. The existence, intensity and duration of this accelerated decline can depend on individual characteristics. The main objective of our work is to propose inferential methods to assess the existence of this phase of accelerated decline, ie, the existence of a random changepoint. To do so, we use a mixed model with two linear phases and test the nullity of the parameter measuring the difference of slopes between the two phases. Because we face the issue of nuisance parameters being unidentifiable under the null hypothesis, the supremum of the classic score test statistic on these parameters is used. The asymptotic distribution of the supremum under the null is approached with a perturbation method based on the multiplier bootstrap. The performance of our testing procedure is assessed via simulations and the test is applied to the French cohort PAQUID of elderly subjects to study the shape of the prediagnosis decline according to educational level. The test is significant for both educational levels and the estimated trajectories confirmed that educational level is a good marker for cognitive reserve.
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http://dx.doi.org/10.1002/sim.8195DOI Listing
September 2019

Evolution of brain atrophy subtypes during aging predicts long-term cognitive decline and future Alzheimer's clinical syndrome.

Neurobiol Aging 2019 07 22;79:22-29. Epub 2019 Mar 22.

EPHE, PSL, Bordeaux, France; Univ. Bordeaux, CNRS, UMR 5287, Institut de Neurosciences cognitives et intégratives d'Aquitaine, Bordeaux, France.

It is currently unknown whether brain atrophy subtypes defined in Alzheimer's disease are clinically relevant during aging. We investigated participants (n = 368) from a population-based cohort of nondemented older adults who received longitudinal neuropsychological assessments during 12 years. Magnetic resonance imaging scans at baseline and 4 years later were used to define participants with "hippocampal predominant atrophy," "cortical predominant atrophy," "homogenous atrophy," and "no evidence of brain subtype atrophy" based on the dynamics of hippocampal-to-cortical volume ratio evolution. After adjustment on age, gender, educational level, and ApoE4 genotype, participants with "hippocampal predominant atrophy" declined faster regarding global cognition, verbal fluency, and verbal episodic memory. In Cox proportional-hazards models, "hippocampal predominant atrophy" was associated with an increased risk of developing Alzheimer's clinical syndrome over time (hazard ratio = 5.73; 95% CI 2.71-12.15), independently of age and ApoE4 genotype, the 2 other significant predictive factors. As a possible surrogate of confined tauopathy and early Alzheimer's disease pathology, future studies should consider the definition of "hippocampal predominant atrophy" based on hippocampal-to-cortical volume ratio evolution rather than hippocampal volume alone.
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http://dx.doi.org/10.1016/j.neurobiolaging.2019.03.006DOI Listing
July 2019

Non-REM Sleep Characteristics Predict Early Cognitive Impairment in an Aging Population.

Front Neurol 2019 13;10:197. Epub 2019 Mar 13.

USR CNRS 3413 SANPSY Sommeil, Addiction et NeuroPSYchiatrie, Bordeaux, France.

Recent research suggests that sleep disorders or changes in sleep stages or EEG waveform precede over time the onset of the clinical signs of pathological cognitive impairment (e.g., Alzheimer's disease). The aim of this study was to identify biomarkers based on EEG power values and spindle characteristics during sleep that occur in the early stages of mild cognitive impairment (MCI) in older adults. This study was a case-control cross-sectional study with 1-year follow-up of cases. Patients with isolated subjective cognitive complaints (SCC) or MCI were recruited in the Bordeaux Memory Clinic (MEMENTO cohort). Cognitively normal controls were recruited. All participants were recorded with two successive polysomnography 1 year apart. Delta, theta, and sigma absolute spectral power and spindle characteristics (frequency, density, and amplitude) were analyzed from purified EEG during NREM and REM sleep periods during the entire second night. Twenty-nine patients (8 males, age = 71 ± 7 years) and 29 controls were recruited at T0. Logistic regression analyses demonstrated that age-related cognitive impairment were associated with a reduced delta power (odds ratio (OR) 0.072, < 0.05), theta power (OR 0.018, < 0.01), sigma power (OR 0.033, < 0.05), and spindle maximal amplitude (OR 0.002, < 0.05) during NREM sleep. Variables were adjusted on age, gender, body mass index, educational level, and medication use. Seventeen patients were evaluated at 1-year follow-up. Correlations showed that changes in self-reported sleep complaints, sleep consolidation, and spindle characteristics (spectral power, maximal amplitude, duration, and frequency) were associated with cognitive impairment ( < 0.05). A reduction in slow-wave, theta and sigma activities, and a modification in spindle characteristics during NREM sleep are associated very early with a greater risk of the occurrence of cognitive impairment. Poor sleep consolidation, lower amplitude, and faster frequency of spindles may be early sleep biomarkers of worsening cognitive decline in older adults.
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http://dx.doi.org/10.3389/fneur.2019.00197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6424890PMC
March 2019

The Social Vulnerability Index: Assessing Replicability in Predicting Mortality Over 27 Years.

J Am Geriatr Soc 2019 06 1;67(6):1305-1306. Epub 2019 Feb 1.

Univ. Bordeaux, Bordeaux Population Health Research Center, team Psychoepidemiology of aging and chronic diseases, UMR 1219, F-33000 Bordeaux, France.

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http://dx.doi.org/10.1111/jgs.15812DOI Listing
June 2019

Vision loss and 12-year risk of dementia in older adults: the 3C cohort study.

Eur J Epidemiol 2019 Feb 4;34(2):141-152. Epub 2019 Jan 4.

Inserm, Bordeaux Population Health Research Center, UMR 1219, Univ. Bordeaux, 33000, Bordeaux, France.

To analyze the longitudinal relationships between vision loss and the risk of dementia in the first 2 years, from 2 to 4 years and beyond 4 years after inclusion and to determine the roles of depressive symptomatology and engagement in cognitively stimulating activities in these associations. This study is based on the Three-City (3C) study, a population-based cohort of 7736 initially dementia-free participants aged 65 years and over with 12 years of follow-up. Near visual impairment (VI) was measured and distance visual function (VF) loss was self-reported. Dementia was diagnosed and screened over the 12-year period. At baseline, 8.7% had mild near VI, 4.2% had moderate to severe near VI, and 5.3% had distance VF loss. Among the 882 dementia cases diagnosed over the 12-year follow-up period, 140 cases occurred in the first 2 years, 149 from 2 to 4 years and 593 beyond 4 years after inclusion. In Cox multivariate analysis, moderate to severe near VI was associated with an increased risk of dementia in the first 2 years (HR 2.0, 95% CI 1.2-3.3) and from 2 to 4 years (HR 1.8, 95% CI 1.1-3.1) but the association was not significant beyond 4 years after inclusion even if pointing in similar direction (HR 1.3, 95% CI 0.95-1.9). Mild near VI was associated with an increased risk of dementia only in the first 2 years (HR 1.6, 95% CI 1.1-2.5). Moreover, self-reported distance VF loss was associated with an increased risk beyond 4 years after inclusion (HR 1.5, 95% CI 1.1-2.0) but the association was no longer significant after taking into account baseline cognitive performances. Further adjustment for engagement in cognitively stimulating activities only slightly decreased these associations. However, there was an interaction between vision loss and depressive symptomatology, with vision loss associated with dementia only among participants with depressive symptomatology. These results suggest that poor vision, in particular near vision loss, may represent an indicator of dementia risk at short and middle-term, mostly in depressed elderly people.
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http://dx.doi.org/10.1007/s10654-018-00478-yDOI Listing
February 2019

A Subjective Quality of Life Proxy for Older Adults in the PAQUID Cohort Study.

J Geriatr Psychiatry Neurol 2018 11;31(6):303-311

1 Inserm U1219 Bordeaux Population Health Center, Université de Bordeaux, Bordeaux, France.

Objectives: Quality of life is regarded as a major outcome in epidemiologic research, especially in the older population. Nevertheless, some cohort studies lack a specific instrument to evaluate it. The aim of this study was to propose a subjective quality of life proxy using easily accessible items, available in most epidemiologic studies.

Method: We used data from the PAQUID (Personnes Agées Quid) cohort study (1991-1992, France). A subjective quality of life proxy was created based on items on positive affects, subjective health, and life satisfaction. Logistic and linear regression models as well as Cox survival models were used to assess the association between the proxy score and depression, dependence, cognitive complaints, adverse life events, comorbidities, and death. Analyses were replicated in an independent cohort study, AMI (Approche Multidisciplinaire intégrée; 2007-2008, France). All models were adjusted for age, sex, Mini-Mental State Examination score, and place of residence.

Results: In the PAQUID sample (n = 2135), we found significant associations between the proxy score and the selected health outcomes. We found the same associations in the AMI cohort.

Conclusion: This proxy might be useful when no gold standard for quality of life assessment is available or when in need of a short but reliable instrument that will not require extended administration time.
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http://dx.doi.org/10.1177/0891988718809870DOI Listing
November 2018

A comprehensive approach of the determinants of use of care in dementia: the Recaredem (recourse to care in dementia) cross-sectional study.

Int Psychogeriatr 2018 Oct 30:1-11. Epub 2018 Oct 30.

Bordeaux Population Health Research Center, INSERM,University of Bordeaux,Bordeaux,France.

ABSTRACTBackground:Given the rate of the undiagnosed cases of dementia and the consequences of inappropriate care, understanding the factors that explain the use of medical and health care in dementia is a critical concern. Our objective was to identify the psychosocial and medical determinants of use of care in dementia.

Methods: The study sample consisted of 308 participants: the persons with dementia (n = 99) selected from three French population-based cohorts (i.e. PAQUID, 3C, AMI), their family caregivers (primary, n = 96, and secondary, n = 51), and their general practitioners (n = 62). Use of care in dementia was considered according to two indicators: (1) recourse to secondary care, (2) number of community and health services used.

Results: Multiple logistic models including sociodemographics and psychosocial variables revealed that the determinants of nonuse of care are similar both for the recourse to secondary care and for the number of community and health services used: lack of education and the contribution of the people with dementia to the decisions regarding their own care and dementia care services in the community area. In addition, satisfaction of the primary caregiver with the services used by his/her relative is associated with non-recourse to secondary care.

Conclusions: Taken together, these results highlight the predominant role of psychosocial factors in the use of care in dementia and the importance of addressing this issue through an integrative approach including psychological, social, medical, and family dimensions.
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http://dx.doi.org/10.1017/S1041610218001497DOI Listing
October 2018

France Will No More Reimburse Available Symptomatic Drugs Against Alzheimer's Disease.

J Alzheimers Dis 2018 ;66(2):425-427

Fédération des Centres Mémoire, Lyon, France.

The French Minister of Health published a decree on May 29th of 2018 removing the drugs used to fight against symptoms due to Alzheimer's disease (donepezil, rivastigmine, galantamine, memantine) from the list of available reimbursed drugs. This follows the advice delivered by the High Authority for Health in 2016 and 2018 stating an "insufficient medical benefit and dangerousness because of significant side effects". The main French scientific and medical societies and professional associations want to state here their deep disagreement regarding this unfair decision. The evidence-based medicine related to these drugs reaches a high level in literature, whereas the clinical relevance of these treatments must be considered with co-prescription of psychosocial interventions and related approaches. As no serious pharmacovigilance signal has been provided by health authorities, the ratio of benefits/risks favors these drugs.
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http://dx.doi.org/10.3233/JAD-180843DOI Listing
October 2019

The relationship between hearing loss in older adults and depression over 12 years: Findings from the Three-City prospective cohort study.

Int J Geriatr Psychiatry 2018 12 13;33(12):1654-1661. Epub 2018 Sep 13.

Bordeaux Population Health Research Center, Univ. Bordeaux, Inserm, Team LEHA, UMR 1219, F-33000, Bordeaux, France.

Objective: The present study aims to examine the longitudinal relationship between hearing loss (HL) with depression in older adults over 12 years of follow-up.

Method: Eight thousand three hundred forty-four French community-dwelling adults aged 65 and above participated in the Three-City prospective population-based study. Baseline relationships between self-reported mild and severe HL with depression-assessed by both the Mini International Neuropsychiatric Interview and by the Centre for Epidemiology Studies Depression scale-were explored using logistic regression analyses. Logistic mixed models assessed whether baseline HL was associated with incident depression diagnosis or symptom onset over 12 years in those who were depression-free at baseline.

Results: At baseline, mild and severe HL were associated with depression symptoms as assessed by the CESD (OR = 1.29, 95% CIs 1.14-1.47; OR = 1.51, 95% CIs 1.22-1.87; respectively), although only mild HL was significantly related to major depression diagnosis (OR = 1.51, 95% CIs 1.07-2.12). Over 12 years, mild and severe HL were associated with incident depression as assessed by the CESD in those without depression at baseline (OR = 1.36, 95% CIs 1.15-1.61; OR = 1.69, 95% CIs 1.15-2.30; respectively), but was not associated with a major depression diagnosis.

Conclusions: Both mild and severe thresholds of HL are associated with depression symptoms over time, but not with incident diagnosis of major depression. Improved and ongoing detection of subthreshold depression amongst older adults with HL may improve quality of life for this population.
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http://dx.doi.org/10.1002/gps.4968DOI Listing
December 2018

Correlates of depressive symptoms among older adults living with HIV.

Int J Geriatr Psychiatry 2018 Jun 13. Epub 2018 Jun 13.

Bordeaux Population Health Research Center, UMR 1219, Univ. Bordeaux, Inserm, Bordeaux, France.

Objective: To establish the correlates of depressive symptoms among Mexican community-dwelling older people living with HIV (PLWHIV).

Methods: Cross-sectional, 2-center study of 328 participants aged 50 or older being followed in the outpatient HIV clinics of 2 tertiary care hospitals in Mexico. Data were obtained through a comprehensive geriatric assessment. Multivariate logistic regression analyses were performed to identify the correlates of depressive symptoms.

Results: Mean age of participants was 58.4 years (SD = 7.2), and 82.9% were men. Depressive symptoms were present in 15.9% of participants. The multivariate logistic regression models showed that frailty and disability for activities of daily living were both independently associated with depressive symptoms.

Conclusion: Frailty and disability were independent correlates of depressive symptoms in older PLWHIV. Future studies should attempt to explore the role of physical frailty and disability on psychosocial morbidity among older PLWHIV.
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http://dx.doi.org/10.1002/gps.4922DOI Listing
June 2018

Temporal Trends in the Level and Decline of Cognition and Disability in an Elderly Population: The PAQUID Study.

Am J Epidemiol 2018 10;187(10):2168-2176

University of Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR1219, Bordeaux, France.

In line with declining trends in dementia incidence, we compared the cognitive and functional evolution of 2 "generations" of elderly individuals aged 78-88 years, who were included 10 years apart in the French Personnes Agées Quid cohort (n = 612 in 1991-1992 and n = 628 in 2001-2002) and followed-up for 12 years with assessments of cognition and disability. The impact of specific risk factors on this evolution was evaluated. Differences between the generations in baseline levels and decline over time were estimated using a joint model to account for differential attrition. Compared with the first generation, the second generation had higher performances at baseline on 4 cognitive tests (from P < 0.005). Differences in global cognition, verbal fluency, and processing speed, but not in working memory, were mostly explained by improvement in educational level. The second generation also exhibited less cognitive decline in verbal fluency and working memory. Progression of disability was less over the follow-up period for the second generation than for the first. The cognitive state of this elderly population improved, partially due to improvements in educational level.
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http://dx.doi.org/10.1093/aje/kwy118DOI Listing
October 2018

Association Between Frailty and HIV-Associated Neurodegenerative Disorders Among Older Adults Living with HIV.

AIDS Res Hum Retroviruses 2018 05 13;34(5):449-455. Epub 2018 Mar 13.

1 Department of Geriatrics, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán , Mexico City, Mexico .

The population of aging adults living with human immunodeficiency virus (HIV) is growing worldwide and evidence suggests that frailty occurs prematurely among them. In turn, frailty has been associated with cognitive decline. It is unknown, however, if people with both frailty and HIV infection have a higher risk of cognitive impairment compared with nonfrail HIV-infected persons. Therefore, the main objective of this study was to determine the association between the phenotype of frailty and HIV-associated neurocognitive disorders (HAND) among adults aged 50 years or older living with HIV/AIDS. A cross-sectional study was conducted on 206 adults living with HIV receiving care in a university-affiliated tertiary care hospital in Mexico City. Frailty was defined as per the Fried criteria. The presence of HAND was established according to the Antinori criteria: HIV-associated asymptomatic neurocognitive impairment (ANI), HIV-associated mild neurocognitive disorder (MND), or cognitively nonimpaired. Multinomial logistic regression models were used to test the independent association between frailty and HAND adjusting for potential confounders. Mean age of participants was 60.5 ± 6.3 years and 84.9% were male. Prevalence of HAND and frailty phenotype was 66.0% and 2.9%, respectively. The unadjusted analysis showed that both prefrail and frail statuses were associated with MND but not with ANI. However, after adjustment, the association with MND remained significant only among prefrail participants and no longer for frail persons (risk ratio [RR] = 5.7, 95% confidence intervals [CI] 1.09-29.82; p = .039 and RR = 18.3, 95% CI 0.93-362.6; p = .056, respectively). Prefrailty is associated with symptomatic neurocognitive disorders in older adults living with HIV. The spectrum of the frailty phenotype in this already vulnerable population should serve as an indicator of concomitant cognitive decline.
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http://dx.doi.org/10.1089/AID.2017.0100DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6909770PMC
May 2018