[Importance of cognitive disorders in internal medicine: Pathophysiology, diagnosis, management. The example of systemic lupus erythematosus]. / Importance des troubles cognitifs en médecine interne : physiopathologie, évaluation, prise en charge. L'exemple du lupus systémique.

Systemic diseases, which are in France mainly monitored in internal medicine, affect multiple organs or tissues. While cutaneous or articular manifestations are the most common, neurological involvement is often associated with severity. Diagnosis of peripheral (e.g, neuropathies) or central (e.g, myelitis) nervous disorders is quite easy through clinical examination and dedicated complementary tests. However, neuropsychological manifestations that affect cognition, including memory, attention, executive functions or reasoning, are difficult to diagnose, sometimes trivialized by practitioners. Their causes are often numerous and interrelated. Nevertheless, these cognitive manifestations are closely related to patients' quality of life, affecting their social life, family dynamics and professional integration but also the treatment adherence. The purpose of this review, focused on the example of systemic lupus erythematosus, is to raise awareness of cognitive dysfunction in systemic diseases including their management from diagnosis to treatments. The final aim is to go further into setting up research groups and care programs for patients with cognitive impairment followed in internal medicine.

Determinants of Medical Direct Costs of Care among Patients of a Memory Center.

BACKGROUND: Alzheimer's disease and related diseases (ADRD) are a major cause of health-related cost increase. OBJECTIVES: This study aimed to estimate the real medical direct costs of care of patients followed at a memory center, and to investigate potential associations between patients' characteristics and costs. DESIGN: Cross-sectional analyses conducted on matched data between clinical data of a cohort of patients and the claims database of the French Primary Health Insurance Fund. SETTING: Memory center in France. PARTICIPANTS: Patients attending a memory center with subjective cognitive complaint. MEASUREMENTS: Medical or nonmedical direct costs (transportation) reimbursed by the French health insurance during the one year after the first memory visit, and socio-demographic, clinical, cognitive, functional, and behavioral characteristics were analyzed. RESULTS: Among 2,746 patients (mean ± SD age 79.9 ± 8 years, 42.4% of patients with dementia), the total direct cost was on average € 9,885 per patient during the year after the first memory visit: € 7,897 for patients with subjective cognitive complaint, € 9,600 for patients with MCI, and € 11,505 for patients with dementia. A higher functional and cognitive impairment, greater behavioral disorders, and a higher caregiver burden were independently associated with a higher total direct cost. A one-point decrease in the Instrumental Activities of Daily Living score was associated with a € 1,211 cost increase. The cost was higher in patients with Parkinson's disease, and Lewy body disease compared to patients with AD. Diabetes mellitus, anxiety disorders and number of drugs were also significantly associated with greater costs. CONCLUSIONS: Higher real medical direct costs were independently associated with cognitive, functional, and behavioral impairment, diabetes mellitus, anxiety disorders, number of drugs, etiologies as well as caregiver burden in patients attending a memory center. The identification of factors associated to higher direct costs of care offers additional direct targets to evaluate how interventions conducted in patients with NCD impact direct costs of care.

Specificities of acute phase stroke management in the elderly.

Health professionals are currently facing the challenge of managing an increasing number of old patients presenting with acute stroke, due to rapid aging of the population. Compared to their younger counterparts, elderly patients differ in many ways in the setting of acute stroke. Apart from a striking high stroke incidence, which increases exponentially as age increases, cardioembolism also becomes, as patients age, the main cause of ischemic stroke. Delirium, which can challenge the diagnosis, is frequent at the acute phase of stroke, and may be related to an underlying dementia, which is almost exclusively observed in the elderly during stroke. At all levels, management of elderly stroke patients is suboptimal, especially when they are cognitively impaired, with insufficiencies including admission to stroke units, applying standards of care and investigation, reperfusion therapy for ischemic stroke, and finally transfer to rehabilitation centers. A paradigm shift must take place to limit age-related discrimination for acute-phase management of stroke.

[White matter hyperintensities in ageing: Pathophysiology, associated cognitive disorders and prevention]. / Hypersignaux de la substance blanche chez la personne âgée : physiopathologie, troubles cognitifs associés et pistes de prévention.

White matter hyperintensities (WMH), also known as leukoaraïosis are very common neuroradiological manifestations in the elderly. The main risk factors for WMH are age and high blood pressure. The vascular origin of these lesions is classically accepted and WMH are considered as one feature of the small vessel disease. WMH may be associated with clinical symptoms, depending notably on their importance according to age. They are associated with increased mortality, strokes and changes in cognition with a higher risk of dementia (vascular dementia or Alzheimer's disease). Modification of vascular risk factors could have a beneficial effect, but few evidences from controlled trials are available.

[Medication management of hypertension and heart failure in older patients: What happens to therapeutic changes after hospitalization?] / Prise en charge médicamenteuse de l'hypertension artérielle et de l'insuffisance cardiaque chez la personne âgée : les modifications effectuées à l'hôpital sont-elles poursuivies en ville ?

PURPOSE: The objective of this study was to objectivize if the cardiovascular therapeutic changes performed during hospitalization of older patients with hypertension and/or heart failure (HF), were maintained in ambulatory 3 month after hospitalization. METHODS: This is a longitudinal study conducted in a geriatric unit. Patients over 65 years with hypertension and/or HF, who had at least one change in cardiovascular medicaton during hospitalization, and who accepted the 3-month follow-up were included in the longitudinal study. At admission, during hospitalization and 3 months after hospitalization data concerning cardiovascular medication were collected. RESULTS: During hospitalization, 142 (73.6%) patients had at least one change in hypertension and/or HF medication. Overall, 249 changes were performed. Forty-one patients received follow-up at 3 months. At 3 months, therapeutic changes were maintained by 48.8% of the general practitioners (n=20 patients). For the rest, 41.5% of the patients had benefited from new therapeutic changes (28 changes for 10 patients) and 9.7% of the general practitioners (n=4 patients) had restored the initial prescription before hospitalization. CONCLUSIONS: Medication review performed by geriatricians and pharmacists during hospitalization resulted in 249 changes. These changes aimed at limiting iatrogenic disease, by reducing overtreatment and potentially inappropriate prescriptions. Difficulties in the patient care continuity between the hospital and ambulatory setting have been identified.

How to explore the needs of informal caregivers of individuals with cognitive impairment in Alzheimer's disease or related diseases? A systematic review of quantitative and qualitative studies.

BACKGROUND: This study aims to review the methodologies used to identify the needs, the existing needs assessment instruments and the main topics of needs explored among caregivers of patients with mild cognitive impairment to dementia. METHODS: MEDLINE, PsycINFO, The Cochrane Library and Web of science were searched from January 1980 to January 2017. Research studies in English or French were eligible for inclusion if they fulfilled the following criteria: quantitative, qualitative and mixed method studies that used instrument, focus group or semi-structured interviews to assess the informal caregiver's needs in terms of information, coping skills, support and service. RESULTS: Seventy studies (n = 39 quantitative studies, n = 25 qualitative studies and n = 6 mixed method studies) met the inclusion criteria and were included. Thirty-six quantitative instruments were identified but only one has been validated for the needs assessment of dementia caregivers: the Carer's Needs Assessment for Dementia (CNA-D). The main areas of needs explored in these instruments were: information, psychosocial, social, psychoeducational and other needs. CONCLUSIONS: No instrument has been developed and validated to assess the needs of informal caregivers of patients with cognitive impairment, whatever the stage and the etiology of the disease. As the perceived needs of caregivers may evolve with the progression of the disease and the dementia transition, their needs should be regularly assessed.

Factors associated with changes in exposure to anticholinergic and sedative medications in elderly hospitalized patients: multicentre longitudinal study.

BACKGROUND AND PURPOSE: Elderly patients exposed to drugs with anticholinergic or sedative properties may have an increased risk of adverse events. This study aimed to assess the relationship between patient characteristics and changes of exposure to anticholinergic and sedative medications during their hospital stay. METHODS: A multicentre longitudinal study was set up on hospitalized patients (aged ≥65 years) using at least one drug at admission. The primary outcome was change of exposure to anticholinergic and sedative drugs between admission and discharge. Sociodemographic characteristics of the patients, comorbidities, life habits and information about the hospital stay (origin of admission, reasons for hospitalization) were collected. RESULTS: The study included 337 patients (mean age, 85.4 years) with an average hospital stay of 30.1 ± 37.5 days. The drug burden index increased during the hospital stay among males (P = 0.03), patients for whom the reason for hospitalization was either a stroke (P = 0.001) or inability to stay in their own home (P = 0.001), and patients with diabetes mellitus (P = 0.009). In the adjusted model, drug burden index increased among patients hospitalized for stroke, inability to stay in their own home or post-surgery, and for patients with diabetes mellitus or hypertension. CONCLUSIONS: The drug management of elderly patients during hospital stays may increase exposure to anticholinergic and sedative drugs. Although the anticholinergic and sedative properties may be in relation to the therapeutic purpose, they also represent an unexpected risk. Physicians and clinical pharmacists should consider performing optimization of the drug prescriptions for patients at risk.

PHARMAID study protocol: Randomized controlled trial to assess the impact of integrated pharmaceutical care at a psychosocial intervention on caregiver's burden in Alzheimer's disease or related diseases.

INTRODUCTION: Alzheimer's Disease and Related Diseases (ADRD) are associated with a caregiver burden that increases with the progression of the disease. Psychosocial interventions reported a moderate improvement on caregivers' burden. Patients with ADRD and their older caregivers are also exposed to a higher risk of developing drug-related problems. The main objective of the PHARMAID study is to measure the impact of personalized pharmaceutical collaborative care integrated to a multidisciplinary psychosocial program on the burden of caregivers. METHODS: The PHARMAID study is a 18-month randomized controlled trial that started in September 2016. This paper describes the study protocol. PHARMAID plans to enroll 240 dyads, i.e. ADRD patients and caregivers, whose inclusion criteria are: outpatient with mild or major neurocognitive disorders due to ADRD, living at home, receiving support from a family caregiver. Three parallel groups will compare a control group with two experimental groups: psychosocial intervention and integrated pharmaceutical care at a psychosocial intervention. The main outcome is the caregiver's burden assessed by the Zarit Burden Index at 6, 12 and 18months. DISCUSSION: This is the first trial designed to assess the specific impact of the integration of pharmaceutical care in a multidisciplinary psychosocial program on the caregiver's burden. The results will inform policymakers on strategies to implement in the near future. TRIAL REGISTRATION NUMBER: [ClinicalTrials.gov: NCT02802371] Registered in June 2016.

Neuroimaging correlates of neuropsychiatric symptoms in Alzheimer's disease: a review of 20 years of research.

Assessing morphological, perfusion and metabolic brain changes preceding or associated with neuropsychiatric symptoms (NPSs) will help in the understanding of pathophysiological underlying processes in Alzheimer's disease (AD). This review aimed to highlight the main findings on significant associations between neuroimaging and NPSs, the pathophysiology to elucidate possible underlying mechanisms, and methodological issues to aid future research. Research papers published from January 1990 to October 2015 were identified in the databases PsycInfo, Embase, PubMed and Medline, using key words related to NPSs and imaging techniques. In addition to a semi-systematic search in the databases, we also performed hand searches based on reported citations identified to be of interest. Delusions, apathy and depression symptoms were particularly associated with brain changes in AD. The majority of studies disclosed an association between frontal lobe structural and/or metabolic changes and NPSs, implicating, interestingly, for all 12 NPSs studied, the anterior cingulate cortex although temporal, subcortical and parietal regions, and insula were also involved. Given the high degree of connectivity of these brain areas, frontal change correlates of NPSs may help in the understanding of neural network participation. This review also highlights crucial methodological issues that may reduce the heterogeneity of results to enable progress on the pathophysiological mechanisms and aid research on NPS treatments in AD. Based on a broad review of the current literature, a global brain pattern to support the huge heterogeneity of neuroimaging correlates of NPSs in AD and methodological strategies are suggested to help direct future research.

Relationship between anxiety and cognitive performance in an elderly population with a cognitive complaint.

BACKGROUND AND PURPOSE: Almost half of elderly patients being consulted in memory clinics present anxiety disorders, either with or without an associated depressive syndrome. This study investigates the relationship between the level of anxiety and cognitive performance in a population complaining of memory difficulties. METHODS: The study population (n = 149) was selected from the EVATEM cohort, which included subjects aged 65 years or older. All subjects presented memory complaints and patients with depression were excluded. Anxiety level was assessed with the Hamilton Anxiety Rating Scale. A standard neuropsychological battery, including a free and cued episodic memory test, was administered to examine the different processes of verbal episodic memory, visual memory, executive, visuoconstructive and instrumental functions. RESULTS: Subjects with moderate to severe anxiety had worse performance than subjects with no anxiety in retrieval and storage processes of verbal episodic memory (respectively P = 0.004 and P = 0.02) and in visual recognition memory (P = 0.01). No relationship was found between anxiety and executive, visual-constructive or instrumental functions. CONCLUSION: Anxiety impacts several stages of verbal memory, notably the processes of storage and retrieval, and visual recognition memory within a population having cognitive complaints. This study suggests that anxiety should be considered as a factor of memory vulnerability for patients being treated in memory clinics.

Evaluation of a mobile team dedicated to behavioural disorders as recommended by the Alzheimer Cooperative Valuation in Europe joint action: observational cohort study.

BACKGROUND AND PURPOSE: Preventing behavioural crises appears to be crucial to promote quality of life of the patient-caregiver dyad, to reduce inappropriate hospitalizations and to delay institutionalization. The Alzheimer Cooperative Valuation in Europe promotes mobile care to prevent patients from severe behavioural and psychological symptoms in dementia. This study assessed the potential efficacy of a mobile team for Alzheimer's disease on hospitalization sparing and behavioural disorder reduction. METHODS: A cohort study was set up from 1 January 2012 to 31 December 2013 by the Clinical and Research Memory Centre of Lyon (France). It included patients with behavioural and psychological symptoms living at home or in a nursing home. An interview explored the alternative patient pathways used by general practitioners (GPs) if the mobile team had not existed (hospitalization sparing). The Neuropsychiatry Inventory score was assessed at inclusion and 30 days later. The sample included 424 consecutive patients with Alzheimer's disease or related disorders and behavioural disorders at any cognitive and functional stage of the disease, taken in charge by the mobile team. RESULTS: Amongst the 424 patients (84.0 ± 7.2 years), 220 (51.9%) hospitalizations were considered by their GPs and 181 (82.3%) were avoided. The Neuropsychiatric Inventory score declined after mobile team intervention (45.8-29.9, P < 0.001). Sleep and appetite disorders, endangered situation and caregiver burnout were associated with higher risk of hospitalization at 30 days. CONCLUSIONS: The mobile team for Alzheimer's disease allows a high proportion of hospitalizations related to behavioural disorders to be avoided and may help to reduce behavioural disorders.

Performance of cognitive tests, individually and combined, for the detection of cognitive disorders amongst community-dwelling elderly people with memory complaints: the EVATEM study.

BACKGROUND AND PURPOSE: Dementia is a leading cause of dependence amongst the aged population. Early identification of cognitive impairment could help to delay advanced stages of dependence. This study aimed at assessing the performance of three neuropsychological tests to detect cognitive disorders in elderly subjects with memory complaints. METHODS: The EVATEM study is a prospective multicentre cohort with a 1-year follow-up. Subjects with memory complaints were selected during preventive health examinations, and three neuropsychological tests (five-word, cognitive disorders examination, verbal fluency) were administered. Two groups were identified in memory clinics: (i) cognitively healthy individuals (CHI) and (ii) mild cognitive impairment or demented individuals (MCI-DI). Cross-sectional analyses were performed on data at inclusion. The relationship between the diagnosis of MCI-DI/CHI and the neuropsychological tests was assessed using logistic regressions. The performance of the neuropsychological tests, individually and combined, to detect cognitive disorders was calculated. RESULTS: Of 585 subjects, 31.11% had cognitive disorders (MCI, 176 subjects; DI, six subjects). Amongst the three tests studied, the odds ratio for MCI-DI was higher for the five-word test <10 [odds ratio 3.2 (1.81; 5.63)]. The best performance was observed when the three tests were combined: specificity 90.5% and sensitivity 42.4% compared to respectively 89.2% and 28.3% for the five-word test. CONCLUSIONS: Despite the poor sensitivity of the five-word test, it seems to be the most adapted for the diagnosis of MCI-DI in older adults with a memory complaint, in prevention centres, taking into account its high specificity and its rapid administration compared to the other tests.

Application of the European Test of Olfactory Capabilities in patients with olfactory impairment.

A central issue in olfaction concerns the characterization of loss of olfactory function: partial (hyposmia) or total (anosmia). This paper reports the application in a clinical setting of the European Test of Olfactory Capabilities (ETOC), combining odor detection and identification. The study included three phases. In phase 1, anosmics, hyposmics and controls were tested with the 16-items version of the ETOC. In phase 2, a short version of the ETOC was developed: patients with and controls without olfactory impairment were tested on a 6-items ETOC. In phase 3, to predict olfactory impairments in new individuals, the 16-items ETOC was administered on samples of young and older adults, and the 6-items version was applied in samples of young, elderly participants and Alzheimer patients. In phase 1, linear discriminant analysis (LDA) of ETOC scores classified patients and controls with 87.5 % accuracy. In phase 2, LDA provided 84 % correct classification. Results of phase 3 revealed: (1) 16-items ETOC: whereas in young adults, 10 % were classified as hyposmic and 90 % as normosmic, in elderly, 1 % were classified as anosmic, 39 % hyposmic and 60 % normosmic; (2) 6-items ETOC: 15 % of the young adults were classified as having olfactory impairment, compared to 28 % in the older group and 83 % in Alzheimer patients. In conclusion, the ETOC enables characterizing the prevalence of olfactory impairment in young subjects and in normal and pathological aging. Whereas the 16-items ETOC is more discriminant, the short ETOC may provide a fast (5-10 min) tool to assess olfaction in clinical settings.

[Role of clinical pharmacist in the therapeutical optimization in geriatric outpatient hospital]. / Place du pharmacien clinicien dans l'optimisation thérapeutique en hôpital de jour gériatrique.

SETTING: Cares in outpatient hospital for elderly patients is a period of interest for multidisciplinary reassessment and pharmaceutical care of the prescription. The objective is to present the implementation of the pharmaceutical care activity at the outpatient hospital. METHODS: Between August and October 2011, elderly patients hospitalized in the outpatient hospital for a brief appraisal had a pharmaceutical care. The clinician introduced pharmaceutical reviews in the synthesis letter for general practitioner. An analysis of the activity was carried out over 3 months. RESULTS: A pharmaceutical care had been realized for 67 patients, mean age of 81.7 years. Among medical related problems identified, 39.6% were for potentially unnecessary medication. A stop was proposed for 44% of pharmaceutical interventions. A total of 91 pharmaceutical interventions and 13 recommendations were made and 34% of patients had potentially inappropriate medication. CONCLUSION: According to the objective to reduce the therapeutics contributing to the iatrogenesis, this approach allowed us to undertake a multidisciplinary collaboration oriented toward the relay between hospital and city cares.

[Effectiveness of a cognitive-behavioral unit on behavioral and psychological symptoms of dementia]. / Efficacité d'une unité cognitivo-comportementale sur les symptômes psychologiques et comportementaux des démences.

INTRODUCTION: Cognitive-behavioral units (CBUs) have been created in the context of the national Alzheimer plan 2008/2012 for the management of behavioral disorders of patients suffering from Alzheimer's disease or related diseases. The Alzheimer plan promotes the evaluation of these units through the observation of the evolution of behavioral and psychological symptoms of dementia (BPSD). The aim of this study was to assess the effects of the memory center of Lyon (hospices civils de Lyon) CBU on BPSD. PATIENTS: The neuropsychiatric inventory (NPI) was rated by the patients' caregiver (NPI-F) at admission to the CBU and 2 weeks after the discharge. The NPI was also rated by the nursing staff (NPI-NS) 3 days after admission in the CBU and at discharge. RESULTS: All patients admitted in the CBU between July and October 2001 were included in the study for a total of 28 patients. A significant reduction of NPI-F scores between admission (58.93 ± 24.8) and 2 weeks after the discharge (27.07 ± 19.70) (P<0.0001) was observed. Improvement was specifically observed for delusions, agitation, depression, anxiety, disinhibition and aberrant motor activity symptoms. No significant changes were found on NPI-NS scores. CONCLUSION: This study discloses benefits of CBUs in terms of BPSD reduction in patients 2 weeks after CBU discharge. These units have the potential to achieve their principal objective of reducing behavioral problems.

Vitamin D insufficiency and mild cognitive impairment: cross-sectional association.

BACKGROUND: Low serum 25-hydroxyvitamin D (25OHD) concentrations have been associated with dementia. The association with mild cognitive impairment (MCI) has not yet been explored. Our aim was to examine the association between vitamin D status and MCI status amongst older community-dwellers with subjective memory complaint. METHODS: Ninety-five non-demented Caucasian community-dwellers with subjective memory complaint (mean, 71.1 ± 6.4 years; 54.7% women) included in the Gait and Alzheimer Interaction Tracking (GAIT) study were categorized into two groups according to Winblad et al. consensus criteria [i.e., subjects with MCI or cognitively healthy individuals (CHI)]. Serum 25OHD concentration was divided into quartiles, the fourth quartile corresponding to the highest 25OHD concentration. The cross-sectional associations between 25OHD concentrations and MCI were modeled using logistic regressions. Age, gender, body mass index, number of comorbidities, education level, Mini-Mental State Examination score, Frontal Assessment Battery score, Geriatric Depression Scale score, creatinine clearance, and season tested were considered as potential confounders. RESULTS: Compared to CHI, patients with MCI (n = 43; mean, 71.4 ± 5.6 years; 34.9% women) had lower mean serum 25OHD concentrations (P = 0.006) and belonged more often to the lower quartiles compared to the highest quartile (P = 0.03). Increased serum 25OHD concentration was associated with a lower risk of MCI [adjusted odds ratio (OR) = 0.96, P = 0.002]. Accordingly, lower quartiles of 25OHD were positively associated with MCI whilst using the highest quartile as reference (adjusted OR = 25.46, P = 0.002 for the first quartile; adjusted OR = 6.89, P = 0.03 for the second quartile; and adjusted OR = 10.29, P = 0.02 for the third quartile). CONCLUSIONS: Low 25OHD concentrations were associated with MCI status in older non-demented community-dwellers with subjective memory complaint.