Brain tissue pulsatility mediates cognitive and electrophysiological changes in normal aging: Evidence from ultrasound tissue pulsatility imaging (TPI).

Aging is characterized by a cognitive decline of fluid abilities and is also associated with electrophysiological changes. The vascular hypothesis proposes that brain is sensitive to vascular dysfunction which may accelerate age-related brain modifications and thus explain age-related neurocognitive decline. To test this hypothesis, cognitive performance was measured in 39 healthy participants from 20 to 80 years, using tests assessing inhibition, fluid intelligence, attention and crystallized abilities. Brain functioning associated with attentional abilities was assessed by measuring the P3b ERP component elicited through an auditory oddball paradigm. To assess vascular health, we used an innovative measure of the pulsatility of deep brain tissue, due to variations in cerebral blood flow over the cardiac cycle. Results showed (1) a classical effect of age on fluid neurocognitive measures (inhibition, fluid intelligence, magnitude and latency of the P3b) but not on crystallized measures, (2) that brain pulsatility decreases with advancing age, (3) that brain pulsatility is positively correlated with fluid neurocognitive measures and (4) that brain pulsatility strongly mediated the age-related variance in cognitive performance and the magnitude of the P3b component. The mediating role of the brain pulsatility in age-related effect on neurocognitive measures supports the vascular hypothesis of cognitive aging.

Sleep and mood changes in advanced age after blue-blocking (yellow) intra ocular lens (IOLs) implantation during cataract surgical treatment: a randomized controlled trial.

OBJECTIVES: Both advanced age and depression are characterized by changes in sleep patterns. Light exposure is one of the main synchronizers of circadian cycles and influences sleep by inhibiting melatonin secretion, which is mostly sensitive to light of low wavelengths (blue). Blue-blocking (yellow) intraocular lenses (IOLs) have supplanted the usual UV-blocking (clear) IOLs during cataract surgery to prevent age-related macular degeneration, however, the impact of yellow IOLs on sleep and mood is unclear. The purpose of this study was to compare the effects of yellow and clear IOLs on sleep and mood in aged patients undergoing bilateral cataract surgery. METHODS: A randomized controlled superiority study was conducted within three ophthalmic surgical wards in France. A total of 204 subjects (mean age 76.2 ± 7.5 years) were randomized into yellow or clear IOLs groups. Patients completed a sleep diary, the pictorial sleepiness scale and the Beck Depression Inventory (BDI) one week before and eight weeks after the last surgical procedure. RESULTS: According to an Intent To Treat (ITT) analysis, no significant difference was found between yellow and clear IOLs groups regarding sleep time, sleep latency, total sleep duration, quality of sleep and BDI scores. The rate of patients whose BDI score increased at the cutoff score of ≥5 after surgery was significantly higher in the yellow IOL group (n = 11, 13.1%) compared with the clear IOL group (n = 4; 4.7%); p = 0.02. CONCLUSIONS: Using yellow IOLs for cataract surgery doesn't significantly impact sleep but may induce mood changes in aging.

Fluoxetine induces paradoxical effects in C57BL6/J mice: comparison with BALB/c mice.

The C57BL6/J mouse is the most commonly used strain in genetic investigations and behavioural tests. However, only a few studies have used C57BL6/J mice to assess the effects of antidepressant compounds. We carried out a study to compare the behavioural effects of fluoxetine (FLX) in a model of depression in two mice strains: C57BL6/J and BALB/c. We used an 8-week unpredictable chronic mild stress (UCMS) protocol during which FLX was administered (15 mg/kg, oral) from the third week to the end of the protocol. We found that UCMS induced degradation of the coat state in the two strains. Moreover, as expected, we observed that FLX elicited antidepressant-like effects in the BALB/c mice by reducing the coat state deterioration and the latency of grooming in splash test. However, in the C57BL6/J mice, it did not induce this action, but instead triggered an opposite effect: an increased sniffing latency in the novelty suppression of feeding test. We conclude that FLX exerts a paradoxical effect in the C57Bl6/J strain. This observation is consistent with some clinical features of hyper-reactivity to FLX observed in humans. Therefore, the UCMS protocol used in C57Bl6/J mice could be a good model to study the mechanisms of the paradoxical effects caused by selective serotonin reuptake inhibitors.

Audiometric evaluation in patients with Alzheimer's disease.

The objective of this study is to assess the validity of ASSR as a complementary diagnostic test for peripheral hearing loss by proving a significant correlation between behavioral thresholds and ASSR. The design used in this study is monocentric prospective study from November 2014 to April 2015. The setting used in this study is the ENT-Head and Neck Surgery Department and Geriatrics Department in a French Regional and University Hospital. The participants are patients over 75 years with cognitive impairment (Alzheimer's disease or mild-cognitive impairment) with a Mini-Mental State Examination score under 27/30 and without hearing aids. Exclusion criteria were: otoscopic and middle ear abnormalities, retro-cochlear lesion, other types of dementia, and central nervous system disease altering cerebral lateralization. The intervention used in this study is pure-tone audiometry, speech audiometry, dichotic listening test, and auditory steady-state responses recording. The correlations between these exams were studied with Pearson's correlation coefficient and Student's t test. Results were significant if p < 0.05. Twenty-three ears were analyzed from 12 patients. There were six women and six men with cognitive impairment, mean age 82.1 (±4.6) years, and mean MMSE score that was 21.3/30 (±5.7). The correlation between pure-tone audiometry and ASSR was significant for all frequencies: r = 0.55 (p = 0.006) for 500 Hz, r = 0.58 (p = 0.005) for 1000 Hz, r = 0.61 (p = 0.003) for 2000 Hz, and r = 0.66 (p = 0.002) for 4000 Hz. There was no significant correlation between the MMSE and the difference between ASSR and PTA on each frequency. The dichotic listening test showed a right ear advantage (50.9 %, p = 0.039). The ASSR in patients with cognitive impairment and understanding troubles is a promising complementary technique to estimate the hearing thresholds.

There is no correlation between peripheral inflammation and cognitive status at diagnosis in Alzheimer's disease.

BACKGROUND: Besides the neurofibrillary tangles and amyloid plaques, an inflammatory process is involved at central and peripheral levels in Alzheimer's disease (AD). We aimed to determine whether peripheral inflammatory parameter levels, in plasma and in peripheral blood mononuclear cells (PBMCs), could be correlated with the cognitive status at the time of AD diagnosis. METHODS: Patients were included at diagnosis with MMSE score between 16 and 25 and were naive of symptomatic treatment for AD. C-reactive protein >10 mg/L and any acute or chronic inflammation were considered as exclusion criteria. Cognitive assessment also included the ADAScog scale. Plasma interleukins (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α and the chemokine ligand 5 (CCL5) were measured using Luminex(®) X-MAP(®) technology. A subgroup of patients also underwent measures of these parameters in extracellular and intracellular compartments of PBMCs (ancillary study). RESULTS: One hundred and nine patients were included; mean age 79.4 ± 6.8 years with 37 patients in the ancillary study. The mean values of IL-1ß, TNF-α, IL-6 and CCL5 values were 1.49, 7.18, 3.09 and 69,615.81 pg/mL, respectively. No correlation between plasma cytokines or chemokine levels and cognitive scores was found. In PBMCs, the levels of cytokines were detectable but did not either show any correlation with cognitive scores. CONCLUSION: Our data indicate that at diagnosis, peripheral levels of cytokines and CCL5 display low values without any correlation with the cognitive status. Further results of our study will show if these circulating markers are related to the progression of AD.

Sinking skin flap syndrome (or Syndrome of the trephined): A review.

BACKGROUND: Bone defects of the skull are observed in various pathological conditions, including head trauma and conditions requiring surgery of the skull. Independent of the consequences of the original aetiology that necessitated the craniectomy, the bone defect alone may be the cause of the symptoms, called 'trephined syndrome' or 'sinking skin flap syndrome'. Despite the early recognition of neurological symptoms directly linked to craniectomy, the description of this syndrome has often relied on a small series or single clinical case reports. OBJECTIVES: To list the previously reported symptoms of SSFS. DATA SOURCES: We selected the references for this review by searching PubMed, focusing on articles published prior to June 2013 and using references from relevant articles. STUDY ELIGIBILITY CRITERIA: We used the following search terms: 'trephined syndrome', 'syndrome of the trephined', 'Sinking skin flap', and 'sinking skin flap syndrome'. There were no language restrictions. The final reference list was generated on the basis of its relevance to the topics covered in this review. CONCLUSIONS: Clinicians need to be aware of sinking skin flap syndrome and to look for abnormal neurological developments in patients with craniectomy in order to avoid unnecessary testing and to prevent its occurrence. Accordingly, cranioplasty can be undertaken as soon as necessary.

Using the Brief Assessment of Cognition in Schizophrenia (BACS) to assess cognitive impairment in older patients with schizophrenia and bipolar disorder.

OBJECTIVES: A growing body of evidence suggests that impairment in cognitive functioning is an important clinical feature of both schizophrenia and bipolar disorder, and that these cognitive alterations worsen with age. Although cognitive assessments are increasingly becoming a part of research and clinical practice in schizophrenia, a standardized and easily administered test battery for elderly patients with bipolar disorder is still lacking. The Brief Assessment of Cognition in Schizophrenia (BACS) captures those domains of cognition that are the most severely affected in patients with schizophrenia and the most strongly correlated with functional outcome. The primary aim of our study was to investigate the clinical usefulness of the BACS in assessing cognitive functioning in elderly euthymic patients with bipolar disorder, and to compare their cognitive profile to that of elderly patients with schizophrenia. METHODS: Elderly euthymic patients with bipolar disorder or schizophrenia were assessed using the BACS and a standard cognitive test battery. RESULTS: Fifty-seven elderly patients (aged 60 years and older) with bipolar disorder (n = 42) or schizophrenia (n = 15) were invited to participate. All of the patients were assessed by the BACS as being cognitively impaired. The patients with bipolar disorder scored significantly higher on the global scale and the verbal memory and attention sub-scores of the BACS than the patients with schizophrenia. DISCUSSION: The BACS appears to be a feasible and informative cognitive assessment tool for elderly patients with bipolar disorder. We believe that these preliminary results merit further investigation.

The effect of age and educational level on the cognitive processes used to comprehend the meaning of pictograms.

BACKGROUND AND AIMS: Pictograms, designed to be a universal communication system, are often created from several concrete and easily recognizable drawings. Does understanding depend on a logical approach? Or is it the ability to inhibit the concrete sense of each picture that allows access to a higher level of comprehension? (ability to abstract). These executive functions are sensitive to the effects of aging and educational level. The aim of our study was to evaluate the nature of the cognitive processes underlying the meaning of pictograms and to test the effect of aging and educational level. METHODS: We enrolled 19 older adults (60-69 years old) and 63 young adults (20-29 years old). Of these 63 young adults, 43 had a high educational level (Young-High participants), and 20 had a lower educational level (Young-Low participants). Each participant was asked the meaning of 20 pictograms and underwent an assessment of abstraction and logical abilities with WAIS-III test. RESULTS: Older adults had lower pictogram assessment scores and abstraction and logical abilities when compared with young adults. In both groups, abstraction and logical abilities were correlated with the interpretation of pictograms but only abstraction ability remains strongly correlated with pictogram comprehension in the older group after adjustment of sex, age and educational level. Consequently, the poorer performances of older adults to determine the meaning of pictograms could be explained by the decline of abstraction ability in elderly. CONCLUSIONS: Pictograms are not the universal communication system as we formerly thought. Age and educational level may influence the performance in determining the meaning of pictograms.

Region-specific hierarchy between atrophy, hypometabolism, and ß-amyloid (Aß) load in Alzheimer's disease dementia.

Gray matter atrophy, glucose hypometabolism, and ß-amyloid Aß deposition are well-described hallmarks of Alzheimer's disease, but their relationships are poorly understood. The present study aims to compare the local levels of these three alterations in humans with Alzheimer's disease. Structural magnetic resonance imaging, (18)F-fluorodeoxyglucose positron emission tomography (PET), and (18)F-florbetapir PET data from 34 amyloid-negative healthy controls and 20 demented patients with a high probability of Alzheimer's disease etiology (attested using neuroimaging biomarkers as recently recommended) were analyzed. For each patient and imaging modality, age-adjusted Z-score maps were computed, and direct between-modality voxelwise comparison and correlation analyses were performed. Significant differences in the levels of atrophy, hypometabolism, and Aß deposition were found in most brain areas, but the hierarchy differed across regions. A cluster analysis revealed distinct subsets of regions: (1) in the hippocampus, atrophy exceeded hypometabolism, whereas Aß load was minimal; (2) in posterior association areas, Aß deposition was predominant, together with high hypometabolism and lower but still significant atrophy; and (3) in frontal regions, Aß deposition was maximal, whereas structural and metabolic alterations were low. Atrophy and hypometabolism significantly correlated in the hippocampus and temporo-parietal cortex, whereas Aß load was not significantly related to either atrophy or hypometabolism. These findings provide direct evidence for regional variations in the hierarchy and relationships between Aß load, hypometabolism, and atrophy. Altogether, these variations probably reflect the differential involvement of region-specific pathological or protective mechanisms, such as the presence of neurofibrillary tangles, disconnection, as well as compensation processes.

Encephalopathy induced by levetiracetam in an elderly woman.

Levetiracetam is frequently used in the elderly considering its favorable pharmacological profile, efficacy, and good tolerance. We reported an encephalopathy with levetiracetam in an elderly subject who had no renal failure, no concomitant valproate medication, and no other additional co-morbidities. Levetiracetam should be discontinued when this condition is suspected.

Case report: benefits of quantitative polymerase chain reaction in the clinical management of herpes simplex virus 1 infection with prominent hepatitis and unusual secondary progression.

Herpes simplex virus (HSV) infection is rarely considered in the differential diagnosis of severe acute hepatitis and disseminated infection in immunocompetent adults. A case of disseminated HSV-1 infection in an 82-year-old woman initially presenting with neurological problems, signs of meningitis and prominent hepatitis was investigated. Initial diagnosis, monitoring, and follow-up were based on the application of molecular methods to cerebrospinal fluid, serum, and liver tissue samples from this patient. Following an initial full recovery, the patient presented delayed intracerebral haemorrhage and diffuse arthralgia. This atypical case, with delayed secondary progression, highlights the wide range of clinical features of HSV infection and the benefits of monitoring viral load by quantitative real-time polymerase chain reaction (PCR) during patient management.

Myasthenia gravis in the elderly: a rare cause of undernutrition.

Myasthenia gravis is not a frequent disease in the elderly. The diagnosis of this neuromuscular junction disease in the elderly is difficult because of comorbidities and the broad differential diagnosis. We report here the case of a 86-year-old woman referred to hospital for loss of weight and difficulties in feeding. She was cachectic and had been suffering from dysphagia for several weeks. One week later, her clinical state worsened with the appearance of ptosis and oropharyngeal dysfunction, disturbing eating and talking. Myasthenia gravis was suspected and confirmed by a positive acetylcholine receptor antibody titer. The clinical state of the patient unfortunately worsened, with acute respiratory insufficiency, causing death. Myasthenia gravis must be suspected in a context of dysphagia, swallowing difficulties and loss of weight. This diagnosis leads to specific and symptomatic treatment and allows neuromuscular blockade-inducing drugs to be avoided.

[Language disorders and neurodegenerative pathologies]. / Troubles du langage et pathologies neurodégénératives.

Language disorders in elderly people are not exclusively linked to the vascular pathology. There are many degenerative causes and the different clinical presentations and progression profiles must be known to clinicians. The detection of a language disorder during a "memory consultation" warrants an assessment by a speech therapist, in order to adapt the neuropsychological assessment and to decide on any complementary investigations.

Encephalopathy associated with autoimmune thyroid disease in patients with Graves' disease: clinical manifestations, follow-up, and outcomes.

BACKGROUND: The encephalopathy associated with autoimmune thyroid disease (EAATD) is characterized by neurological/psychiatric symptoms, high levels of anti-thyroid antibodies, increased cerebrospinal fluid protein concentration, non-specific electroencephalogram abnormalities, and responsiveness to the corticosteroid treatment in patients with an autoimmune thyroid disease. Almost all EAATD patients are affected by Hashimoto's thyroiditis (HT), although fourteen EAATD patients with Graves' disease (GD) have been also reported. METHODS: We have recorded and analyzed the clinical, biological, radiological, and electrophysiological findings and the data on the therapeutic management of all GD patients with EAATD reported so far as well as the clinical outcomes in those followed-up in the long term. RESULTS: Twelve of the fourteen patients with EAATD and GD were women. The majority of GD patients with EAATD presented with mild hyperthyroidism at EAATD onset or shortly before it. Active anti-thyroid autoimmunity was detected in all cases. Most of the patients dramatically responded to corticosteroids. The long term clinical outcome was benign but EAATD can relapse, especially at the time of corticosteroid dose tapering or withdrawal. GD and HT patients with EAATD present with a similar clinical, biological, radiological, and electrophysiological picture and require an unaffected EAATD management. CONCLUSIONS: GD and HT equally represent the possible background condition for the development of EAATD, which should be considered in the differential diagnosis of all patients with encephalopathy of unknown origin and an autoimmune thyroid disease, regardless of the nature of the underlying autoimmune thyroid disease.

Preserved subcortical volumes and cortical thickness in women with sexual abuse-related PTSD.

Posttraumatic stress disorder (PTSD) has been frequently associated with volumetric reductions of grey matter structures (e.g. hippocampus and anterior cingulate), but these results remain controversial, especially in female non-combat-related samples. The present study aimed at exploring whole-brain structures in women with sexual abuse-related PTSD on the basis of cortical and subcortical structure comparisons to a matched pair sample that was well-controlled. Seventeen young women who had experienced sexual abuse and who had a diagnosis of chronic PTSD based on the Clinician Administered PTSD Scale for DSM-IV and 17 healthy controls individually matched for age and years of education were consecutively recruited. Both groups underwent structural magnetic resonance imaging and psychiatric assessment of the main disorders according to Axis I of DSM-IV. The resulting scans were analyzed using automated cortical and subcortical volumetric quantifications. Compared with controls, PTSD subjects displayed normal global and regional brain volumes and cortical thicknesses. Our results indicate preserved subcortical volumes and cortical thickness in a sample of female survivors of sexual abuse with PTSD. The authors discuss potential differences between neural mechanisms of sexual abuse-related PTSD and war-related PTSD.

[Vitamin D and cognition in the elderly]. / Vitamine D et cognition chez le sujet âgé

The understanding of the role of vitamin D in maintaining good health has considerably increased in the recent years. There is a growing evidence that vitamin D has not only a beneficial effect to prevent osteoporosis and the risk of falls in the elderly, but also may reduce incidence of cancers, infections, autoimmune, cardiovascular and neurologic diseases, and psychiatric disorders. Laboratory studies yield a biological plausibility for a positive contribution of vitamin D to brain functions: vitamin D receptor and 1,α-hydroxylase, the terminal calcitriol-activating enzyme, are widely distributed in both the fetal and adult brain. Vitamin D may be involved in neuroprotection, control of proinflammatory cytokine induced cognitive dysfunction and synthesis of calcium-binding proteins and neurotransmitter acetylcholine. However, the observational studies conducted in humans are still inconclusive, given the various tests of the cognitive functions that have been used, the performance of the studies either in patients or in healthy subjects, and different designs and/or confounding factors. The role of the vitamin D receptor in the pathophysiology of cognitive decline, incidence of Alzheimer's disease or vascular dementia and/or cognitive decline with respect to previous plasma 25OHD concentration, and the effect on cognition of vitamin D supplementation should be explored in further studies.

[Decision making in the elderly: which tools for its evaluation by the clinician?]. / La prise de décision chez le sujet âgé : quels outils d'évaluation pour le clinicien ?

Numerous decision-making situations occur in the activities of daily living. The consequences of the decision-making capacity disturbances may have a great impact on the patient's autonomy, financial management, and his or her reaction to a diagnosis as well as the ability to accept a therapeutic option or give informed consent. Decision-making is a complex and multi-dimensional process and brings into play attention, memory and executive functions, which are processed in the prefrontal cortex, particularly vulnerable in aging. A better comprehension of the mechanisms of decision-making, and of the resulting social consequences of their dysfunction may improve autonomy of the elderly. Unfortunately, we still lack appropriate tools to explore decision-making in routine practice.

Topography of syllable change-detection electrophysiological indices in children and adults with reading disabilities.

INTRODUCTION: Developmental dyslexia (DD) is a frequent language-based learning disorder. The predominant etiological view postulates that reading problems originate from a phonological impairment. METHOD: We studied mismatch negativity (MMN) and Late Discriminative Negativity (LDN) to syllables change in both children (n=12; 8-12 years) and young adults (n=15; 14-23 years) with DD compared with controls. RESULTS/DISCUSSION: The present study confirmed abnormal automatic discrimination of syllable changes in both children and adults with developmental dyslexia. MMN topographic, amplitude and latency group differences were evidenced, suggesting different brain mechanisms involved in elementary auditory stimulus change-detection in DD, especially in the left hemisphere. The LDN results demonstrated that the auditory disorder of temporal processing in DD children becomes more serious at late stages of information processing and that the apparent cerebral hypo reactivity to speech changes in DD actually may correspond to additional processes. The age-related differences observed in both MMN and LDN topographies, amplitudes and latency between subjects with DD and controls could indicate different developmental courses in the neural representation of basic speech sounds in good and poor readers, with a tendency to normalization with increasing age. CONCLUSION: Our results showing atypical electrophysiological concomitants of speech auditory perception in DD strongly support the hypothesis of deviant cortical organization in DD.