Temporal trajectory of brain tissue property changes induced by electroconvulsive therapy.

BACKGROUND: After more than eight decades of electroconvulsive therapy (ECT) for pharmaco-resistant depression, the mechanisms governing its anti-depressant effects remain poorly understood. Computational anatomy studies using longitudinal T1-weighted magnetic resonance imaging (MRI) data have demonstrated ECT effects on hippocampus volume and cortical thickness, but they lack the interpretational specificity about underlying neurobiological processes. METHODS: We sought to fill in the gap of knowledge by acquiring quantitative MRI indicative for brain's myelin, iron and tissue water content at multiple time-points before, during and after ECT treatment. We adapted established tools for longitudinal spatial registration of MRI data to the relaxometry-based multi-parameter maps aiming to preserve the initial total signal amount and introduced a dedicated multivariate analytical framework. RESULTS: The whole-brain voxel-based analysis based on a multivariate general linear model showed that there is no brain tissue oedema contributing to the predicted ECT-induced hippocampus volume increase neither in the short, nor in the long-term observations. Improvements in depression symptom severity over time were associated with changes in both volume estimates and brain tissue properties expanding beyond mesial temporal lobe structures to anterior cingulate cortex, precuneus and striatum. CONCLUSION: The obtained results stemming from multi-contrast MRI quantitative data provided a fingerprint of ECT-induced brain tissue changes over time that are contrasted against the background of established morphometry findings. The introduced data processing and statistical testing algorithms provided a reliable analytical framework for longitudinal multi-parameter brain maps. The results, particularly the evidence of lack of ECT impact on brain tissue water, should be considered preliminary considering the small sample size of the study.

[Psychostimulants for late life depression]. / Intérêt et usage des psychostimulants dans le traitement de la dépression du sujet âgé.

OBJECTIVES: The use of psychostimulants in the treatment of depressive disorders is receiving renewed interest. Recent publications suggest a particular interest of psychostimulants in the treatment of depression in the elderly. The aim of this article is to review the literature on the role of psychostimulants in the treatment of depression in older adults. METHODS: The literature review focused on efficacy and tolerability studies of psychostimulants in the treatment of depression for the elderly that were published between 1980 and 2016. The only inclusion criterion applied was an average age of the sample studied greater than or equal to 60 years. RESULTS: Overall, 12 trials were selected: 3 controlled trials and 9 uncontrolled trials. Of the 3 controlled trials, one compared parallel groups and the other two were cross-tests. Among the psychostimulants, methylphenidate was the most studied molecule. The trials demonstrate an efficacy of this molecule in particular as an add-on therapy in old-age depression but for the most part with a level of proof that remains insufficient. CONCLUSIONS: The small size of the samples and the methodological limitations of the studies obviate the possibility of extracting definitive conclusions concerning the place of psychostimulants in the treatment of depression in the elderly. Further studies are required in particular in the treatment of resistant depressive episodes.

Relations between personality changes and cerebrospinal fluid biomarkers of Alzheimer's disease pathology.

Specific changes in personality profiles may represent early non-cognitive symptoms of Alzheimer's disease (AD). Evaluating the subject's personality changes may add significant clinical information, as well as help to better understand the interaction between personality change, cognitive decline, and cerebral pathology. With this study we aimed to describe the relationship between personality changes and cerebrospinal fluid (CSF) markers of AD pathology at early clinical stages of the disease. One hundred and ten subjects, of whom 66 cognitively impaired patients (57 with mild cognitive impairment (MCI), and 9 with mild dementia) and 44 healthy controls, had neuropsychological examination as well as lumbar puncture to determine concentrations of CSF biomarkers of AD pathology (amyloid beta1-42 (Aß1-42), phosphorylated tau (ptau-181), and total-tau (tau)). The Revised NEO Personality Inventory (NEO-PI-R) was administered twice, once to evaluate subjects' current personality and once to assess personality traits retrospectively 5 years before evaluation. Subjects with an AD CSF biomarker profile showed significant increase in neuroticism and decrease in conscientiousness over time as compared to non-AD CSF biomarker group. In regression analysis controlling for global cognition as measured by the MMSE score, increasing neuroticism and decreasing extraversion, openness to experience and conscientiousness were associated with lower Aß1-42 concentrations but not with tau and ptau-181 concentrations. Our findings suggest that early and specific changes in personality are associated with cerebral AD pathology. Concentrations of CSF biomarkers, additionally to severity of the cognitive impairment, significantly contribute in predicting specific personality changes.

A multi-contrast MRI study of microstructural brain damage in patients with mild cognitive impairment.

OBJECTIVES: The aim of this study was to investigate pathological mechanisms underlying brain tissue alterations in mild cognitive impairment (MCI) using multi-contrast 3 T magnetic resonance imaging (MRI). METHODS: Forty-two MCI patients and 77 healthy controls (HC) underwent T1/T2* relaxometry as well as Magnetization Transfer (MT) MRI. Between-groups comparisons in MRI metrics were performed using permutation-based tests. Using MRI data, a generalized linear model (GLM) was computed to predict clinical performance and a support-vector machine (SVM) classification was used to classify MCI and HC subjects. RESULTS: Multi-parametric MRI data showed microstructural brain alterations in MCI patients vs HC that might be interpreted as: (i) a broad loss of myelin/cellular proteins and tissue microstructure in the hippocampus (p ≤ 0.01) and global white matter (p < 0.05); and (ii) iron accumulation in the pallidus nucleus (p ≤ 0.05). MRI metrics accurately predicted memory and executive performances in patients (p ≤ 0.005). SVM classification reached an accuracy of 75% to separate MCI and HC, and performed best using both volumes and T1/T2*/MT metrics. CONCLUSION: Multi-contrast MRI appears to be a promising approach to infer pathophysiological mechanisms leading to brain tissue alterations in MCI. Likewise, parametric MRI data provide powerful correlates of cognitive deficits and improve automatic disease classification based on morphometric features.

Resident health-related quality of life in Swiss nursing homes.

BACKGROUND: Health-related quality of life (HRQOL) levels and their determinants in those living in nursing homes are unclear. The aim of this study was to investigate different HRQOL domains as a function of the degree of cognitive impairment and to explore associations between them and possible determinants of HRQOL. METHOD: Five HRQOL domains using the Minimum Data Set - Health Status Index (MDS-HSI) were investigated in a large sample of nursing home residents depending on cognitive performance levels derived from the Cognitive Performance Scale. Large effect size associations between clinical variables and the different HRQOL domains were looked for. RESULTS: HRQOL domains are impaired to variable degrees but with similar profiles depending on the cognitive performance level. Basic activities of daily living are a major factor associated with some but not all HRQOL domains and vary little with the degree of cognitive impairment. LIMITATIONS: This study is limited by the general difficulties related to measuring HRQOL in patients with cognitive impairment and the reduced number of variables considered among those potentially influencing HRQOL. CONCLUSION: HRQOL dimensions are not all linearly associated with increasing cognitive impairment in NH patients. Longitudinal studies are required to determine how the different HRQOL domains evolve over time in NH residents.

The evolution of personality in patients with mild cognitive impairment.

AIMS: To describe personality traits and their changes in mild cognitive impairment (MCI) and control subjects. METHODS: Sixty-three MCI and 90 control subjects were asked to describe their current personality traits by the Structured Interview for the Five-Factor Model (SIFFM). For each subject, a close relative retrospectively assessed these descriptions both as to the previous and current personality traits, using the Revised NEO Personality Inventory, Form R (NEO-PI-R). RESULTS: Self-assessed MCI subjects reported significantly lower scores in the openness dimension than control subjects [F(1, 150) = 9.84, p = 0.002, ηp(2) = 0.06]. In current observer ratings, MCI subjects had higher scores on neuroticism [F(1, 137) = 7.55, p = 0.007, ηp(2) = 0.05] and lower ones on extraversion [F(1, 137) = 6.40, p = 0.013, ηp(2) = 0.04], openness [F(1, 137) = 9.93, p = 0.002, ηp(2) = 0.07], agreeableness [F(1, 137) = 10.18, p = 0.002, ηp(2) = 0.07] and conscientiousness [F(1, 137) = 25.96, p < 0.001, ηp(2) = 0.16]. Previous personality traits discriminated the groups as previous openness [odds ratio (OR) = 0.97, 95% confidence interval (CI) = 0.95-0.99, p = 0.014] and conscientiousness (OR = 0.96, 95% CI 0.94-0.98, p = 0.001) were negatively related to MCI group membership. In MCI subjects, conscientiousness [F(1, 137) = 19.20, p < 0.001, ηp(2) = 0.12] and extraversion [F(1, 137) = 22.27, p < 0.001, ηp(2) = 0.14] decreased between previous and current evaluations and neuroticism increased [F(1, 137) = 22.23, p < 0.001, ηp(2) = 0.14], whereas no significant change was found in control subjects. CONCLUSIONS: MCI subjects undergo significant personality changes. Thus, personality assessment may aid the early detection of dementia.

[Consensus 2012--diagnosis and treatment of patients with dementia in Switzerland]. / Consensus 2012 sur le diagnostic et le traitement des patients atteints de démence en Suisse.

The 2012 Swiss consensus paper on diagnosis and management of patients suffering from dementia resulted from the work of an expert panel who met on March 23d to 25th in Luzem. Based on a literature review, panel members wrote a first draft that was subsequently circulated among multiple dementia experts in Switzerland. After adaptation and revisions according to comments, all consulted dementia specialists and panel members fully endorse the consensus content. The conference was financed by the Swiss Alzheimer Forum.

Personality traits and behavioural and psychological symptoms in patients with mild cognitive impairment.

BACKGROUND AND AIMS: Both personality changes and behavioural and psychological symptoms (BPS) may be associated with mild cognitive impairment (MCI) in later life and help identify incipient dementia. We wished to investigate the links between personality and BPS in MCI. METHOD: We studied premorbid personality traits as estimated 5 years back and their changes in 83 control subjects and 52 MCI patients using the revised NEO Personality Inventory for the Five-Factor Model completed by a proxy. Information on BPS was obtained using the Neuropsychiatric Inventory (NPI). Analyses were controlled for current depression and anxiety. RESULTS: Premorbid neuroticism and openness to experience were associated with the total NPI score. The changes in neuroticism, extraversion, openness to experiences, and conscientiousness were associated with apathy and affective symptoms. CONCLUSIONS: Personality changes and BPS occur in MCI. The occurrence of affective BPS and apathy is associated with both premorbid personality traits and their changes.

[Psychiatry]. / Psychiatrie.

Contemporary psychiatry uses a variety of complementary approaches which enrich one another. In this paper, we describe the development of a brief psychodynamic approach for hospitalized patients with major depression, as well as the recent commercialization of an atypical neuroleptic depot medication. In addition, we discuss electro-convulsotherapy which, despite it has been widely and understandably condemned on the basis of its abusive and non medical application in certain political contexts, deserves objective assessment on the basis of scientific data stemming from recent research suggesting it is in some contexts a valuable tool.

[Consensus recommendations for the assessment of fitness to drive in cognitively impaired patients]. / Konsensusempfehlungen zur Beurteilung der medizinischen Mindestanforderungen für Fahreignung bei kognitiver Beeinträchtigung.

Memory Clinics provide evidence based diagnosis and treatment of dementia. Whenever a diagnosis of dementia is made, it is important to inform the patients about the possible impact of dementia on driving. Patients and their next of kin require competent advice whenever this difficult question is addressed and the mobility desire and the risks related to driving need to be carefully weight up. The time of diagnosis does not necessarily equate to the time when a person with dementia becomes an unsafe driver. The cause and severity of dementia, comorbidities and the current medication need to be carefully taken into account for this decision. On behalf of the association of the Swiss Memory Clinics, a group of experts has developed recommendations to assess fitness to drive in cognitively impaired older adults.

[Driving and cognitive impairment: how best to anticipate?]. / Conduite automobile et troubles cognitifs: comment anticiper?

Driving requires integrating multiple motor, sensory, and cognitive skills. As people age, cognition becomes increasingly vulnerable due to impairment and dementia. Older drivers suffering from dementia, even at an early stage, have been shown to be significantly more likely to develop unsafe driving. Primary care physicians have the difficult task to assess these persons' driving capacity. This paper briefly describes the consequences of altered cognition on driving capacity and proposes an algorithm to address this challenge.

Psychotropic medication use in Swiss nursing homes.

BACKGROUND: Psychotropic medication is commonly used in nursing homes, to treat behavioural and psychological symptoms of dementia (BPSD) for example. Treatment with antipsychotics may improve BPSD in some residents but can be associated with serious side effects, such as higher mortality, faster disease progression and cerebrovascular events. In the current study, psychotropic medication use was analysed in a representative sample of nursing home residents in the German-speaking part of Switzerland, at entry and during follow-up. METHODS: Retrospective analysis of the Resident Assessment Instrument Minimum Data Set (RAI-MDS) of 90 nursing homes at entry (n = 18853) and during follow-up (n = 12101). RESULTS: At entry, 7580 residents (40.2%) were diagnosed with dementia and 49.0% of them had behavioural symptoms. Residents with dementia received more psychotropic medication than residents without dementia (70.8% vs. 55.0%; p<0.001). The most commonly prescribed medications were antipsychotics (demented 44.8% vs. non-demented 17.4%; p<0.001) and antidepressants (demented 29.6% vs. non-demented 26.7%; p<0.001). Antipsychotics were mainly prescribed for residents with dementia and behavioural disturbances. The longitudinal analysis revealed that most residents with dementia (69.5%) took antipsychotics continuously from entry to the final assessment and the same was true for antidepressants (66.1%). The use of antipsychotics at baseline in residents with dementia predicted (p<0.001) the use of antipsychotics during follow-up. CONCLUSIONS: The long term use of antipsychotics in nursing homes may need to be reconsidered in view of novel treatment recommendations, suggesting that the prescription of antipsychotics for patients with dementia should be a second line treatment, restricted to symptoms of psychosis or severe aggression, and prescribed for the shortest duration possible.

Brain aging in the oldest-old.

Nonagenarians and centenarians represent a quickly growing age group worldwide. In parallel, the prevalence of dementia increases substantially, but how to define dementia in this oldest-old age segment remains unclear. Although the idea that the risk of Alzheimer's disease (AD) decreases after age 90 has now been questioned, the oldest-old still represent a population relatively resistant to degenerative brain processes. Brain aging is characterised by the formation of neurofibrillary tangles (NFTs) and senile plaques (SPs) as well as neuronal and synaptic loss in both cognitively intact individuals and patients with AD. In nondemented cases NFTs are usually restricted to the hippocampal formation, whereas the progressive involvement of the association areas in the temporal neocortex parallels the development of overt clinical signs of dementia. In contrast, there is little correlation between the quantitative distribution of SP and AD severity. The pattern of lesion distribution and neuronal loss changes in extreme aging relative to the younger-old. In contrast to younger cases where dementia is mainly related to severe NFT formation within adjacent components of the medial and inferior aspects of the temporal cortex, oldest-old individuals display a preferential involvement of the anterior part of the CA1 field of the hippocampus whereas the inferior temporal and frontal association areas are relatively spared. This pattern suggests that both the extent of NFT development in the hippocampus as well as a displacement of subregional NFT distribution within the Cornu ammonis (CA) fields may be key determinants of dementia in the very old. Cortical association areas are relatively preserved. The progression of NFT formation across increasing cognitive impairment was significantly slower in nonagenarians and centenarians compared to younger cases in the CA1 field and entorhinal cortex. The total amount of amyloid and the neuronal loss in these regions were also significantly lower than those reported in younger AD cases. Overall, there is evidence that pathological substrates of cognitive deterioration in the oldest-old are different from those observed in the younger-old. Microvascular parameters such as mean capillary diameters may be key factors to consider for the prediction of cognitive decline in the oldest-old. Neuropathological particularities of the oldest-old may be related to "longevity-enabling" genes although little or nothing is known in this promising field of future research.

[Personality and dementia: a new perspective]. / Personnalité et démence: une nouvelle perspective.

This article highlights some of the links between pre-morbid personality and clinical features of dementia. Indeed, personality characteristics forge an individual's coping strategies and thus influence the expression of behavioural and psychiatric syndromes of dementia (BPSD) or its precursor stages. Some personality traits such as neuroticism may impact on cognitive decline. BPSD being among the most important determinants of a patient's and their proxies' burden, a better understanding of the links between pre-morbid personality characteristics and BPSD will help define care strategies.

[Caregivers of elderly patients suffering from mental disorders]. / Entourage des patients âgés avec une pathologie mentale.

Mental disorders in the elderly lead their families to stand in and adopt a variety of roles before institutional care takes over. These pathologies carry a high risk of suffering for families and distress for professional caregivers. Thus, the psychological burden endured by the proxies of an elderly depressed patient, or of one who has committed suicide, or of patient suffering from dementia needs special attention and, in some cases, professional care. The discussion of these paradigmatic situations in this manuscript will be extended by a paragraph on specific stakes raised by alcoholic patients living in nursing homes. It will stress the complexity and requirements of professionalism when approaching the familial and professional circle of the elderly psychiatric patient.

[Caring for the caregiver]. / Les proches des personnes souffrant d'une démence.

Dementing disorders usually evolve over several years and alter cognitive performances, behavior and social abilities. Progressively, the patients lose their independence. Families will play a key role for the demented patient and have to adapt to the evolution of his or her needs. They will have to watch over, guide and help the demented proxy. The families' invaluable contribution and the numerous difficulties they encounter while they care for their demented proxy are insufficiently recognized. The deleterious consequences on the carers are currently better known than the determinants of these consequences. Families often need information, counselling and psychological support. Psycho-educational programs represent one of the possible strategies to help families and carers of patients with dementia.

Stereological analysis of neuropil threads in the hippocampal formation: relationships with Alzheimer's disease neuronal pathology and cognition.

Although neuropil threads are thought to account for 85-90% of cortical tau pathology in brain ageing, their clinical significance remains controversial. Previous studies have measured densities, rather than absolute numbers, and most did not take into account possible interactions among the pathological hallmarks of Alzheimer's disease (AD). We report here stereological estimates of total neurofibrillary tangle (NFT) and neuron numbers as well as total amyloid volume and neuropil thread (NT) length, in the hippocampus and entorhinal cortex of 19 very old individuals (age range: 83-101 years) with various degrees of cognitive decline. Total NT length in all areas studied increased in mildly demented cases but showed a marked decrease in Clinical Dementia Rating (CDR) scale 3 cases. Both total NFT and neuron numbers were related to NT length in the CA1 field and entorhinal cortex. A strong positive relationship was also present between the total NFT numbers in the entorhinal cortex and NT length in the CA1 field and dentate gyrus. Total NT length in the CA1 field was related to both CDR scores and presence or absence of dementia explaining 7% and 37% of their variability respectively. In multivariate models, this relationship was highly dependent on the severity of NFT formation in this area. Our data reveal that NT formation in hippocampal subdivisions and entorhinal cortex accompanies AD neuronal pathology in early stages of the degenerative process, yet its rate may decrease in severe dementia. In terms of clinicopathological correlations, NT length in the hippocampal formation does not represent an independent marker of dementia severity.

The "Protocole d'Examen Cognitif de la Personne Agée - Lausanne" (PECPA-L): a cognitive assessment tool for the French-speaking elderly in Switzerland.

OBJECTIVE: The main objective of this study was to validate and normalize, in the French-speaking population of Switzerland, an empirically derived structured cognitive assessment scale for the elderly. METHOD: 237 healthy elderly and 115 elderly with mild-to-moderate dementia as well as a preliminary sample of 27 subjects with MCI, all community-dwelling, were assessed using the PECPA-L for its validation and normalization using Crohnbach's alpha, rank comparisons, and AUROC measures. RESULTS: The internal consistency of the PECPA-L was good (Crohnbach's Alpha=0.79). The discriminating power of the PECPA-L between the normal elderly and the mildly to moderately demented (AUROC=0.940) and those with MCI (AUROC=0.925) was high. Normal aging does not influence all cognitive domains equally; therefore, the subscores of the PECPA-L vary in their discriminating power between the normal and the demented elderly, with gnosis abilities having the least (AUROC=0.719) and delayed memory performance having the highest (AUROC=0.927) discriminating power. Normative data according to age and education are provided. CONCLUSIONS: The PECPA-L is a highly appropriate tool for the detection and documentation of early cognitive impairment in the French-speaking population in Switzerland while accounting for age and education.

[Is there a treatment for Alzheimer's disease?]. / Peut-on traiter la maladie d'Alzheimer ?

Alzheimer's disease is a frequent neurodegenerative disease, which affects more than one third of elderly persons over 80 years. No curative treatment is currently available for this disease, but symptomatic treatments have produced significant improvements in patients' condition. Cholinesterase inhibitors should be prescribed for early and moderate stages and memantine for more severe stages of the disease. These drugs have an impact on cognitive performances, may delay functional decline and improve behaviour disturbances. From a preventive perspective, evidence of benefit from early management of vascular risk factors is accumulating. In the near future, the improved comprehension of the underlying mechanisms of Alzheimer's disease will hopefully bring new treatments, thats will delay or modify its course.