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.

Mutations in the colony stimulating factor 1 receptor (CSF1R) gene cause hereditary diffuse leukoencephalopathy with spheroids.

Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is an autosomal-dominant central nervous system white-matter disease with variable clinical presentations, including personality and behavioral changes, dementia, depression, parkinsonism, seizures and other phenotypes. We combined genome-wide linkage analysis with exome sequencing and identified 14 different mutations affecting the tyrosine kinase domain of the colony stimulating factor 1 receptor (encoded by CSF1R) in 14 families with HDLS. In one kindred, we confirmed the de novo occurrence of the mutation. Follow-up sequencing identified an additional CSF1R mutation in an individual diagnosed with corticobasal syndrome. In vitro, CSF-1 stimulation resulted in rapid autophosphorylation of selected tyrosine residues in the kinase domain of wild-type but not mutant CSF1R, suggesting that HDLS may result from partial loss of CSF1R function. As CSF1R is a crucial mediator of microglial proliferation and differentiation in the brain, our findings suggest an important role for microglial dysfunction in HDLS pathogenesis.

The SPONASTRIME dysplasia: familial short-limb dwarfism with saddle nose, spinal alterations and metaphyseal striation. Report of 4 siblings.

We report clinical, anthropometric and radiological findings in 4 siblings with a new type of skeletal dysplasia. 4 normally intelligent girls exhibit dwarfism between -3.4 and -4.6 standard deviations with accentuated shortening of the lower limbs, moderate deformity of the vertebral bodies, mildly striated metaphyses, saddle nose, frontal bossing, and relatively large head. The family pedigree suggests autosomal recessive inheritance. We propose the designation of SPONASTRIME dysplasia, derived from spondylar and nasal alterations with striation of the metaphyses.

Photographic art and dealing with death

Recently, we were faced with a request from a student photographer who wanted to take pictures of bodies donated to our institute and used for dissection courses for medical students or for scientific purposes. Students are expressly forbidden to take pictures in the dissection hall; however, we allowed this student photographer to do her diploma work in our institute. The reason why she was proposing such a topic was that her brother died young and her parents donated his body to science. To overcome this loss of a loved one, she wanted to know what happens to the donated bodies. She followed the procedure of embalming and different dissections that took place during the summer semester and she took pictures throughout. The outcome of this work was a very nice photographic document, called 'dissection', a book with many pictures but no figure legends. The image document shows the different steps in the preparation and preservation of bodies and the work of an anatomist in the dissection hall. As we impose rules on our students, we had also to give directives in the use of the photographs taken, especially for a photographer who will use the most prominent pictures for exhibitions, i.e. that the pictures do not show names or are used for publication on the internet, or show identification numbers of cadavers, or give indication ofn the institution and are relatively anonymous. This story tells how one can deal with death and at the same time advance one's personal career. The author represents the Swiss Anatomical Society SGAHE and is supported by the Swiss Academy of Science, ScNat.

Growing up with bilateral hippocampal atrophy: from childhood to teenage.

The respective roles of the medial temporal lobe (MTL) structures in memory are controversial. Some authors put forward a modular account according to which episodic memory and recollection-based processes are crucially dependent on the hippocampal formation whereas semantic acquisition and familiarity-based processes rely on the adjacent parahippocampal gyri. Others defend a unitary view. We report the case of VJ, a boy with developmental amnesia of most likely perinatal onset diagnosed at the age of 8. Magnetic resonance imaging (MRI), including quantitative volumetric measurements of the hippocampal formation and of the entorhinal, perirhinal, and temporopolar cortices, showed severe, bilateral atrophy of the hippocampal formation, fornix and mammillary bodies; by contrast, the perirhinal cortex was within normal range and the entorhinal and temporopolar cortex remained within two standard deviations (SDs) from controls' mean. We examined the development of his semantic knowledge from childhood to teenage as well as his recognition and cued recall memory abilities. On tasks tapping semantic memory, VJ increased his raw scores across years at the same rate as children from large standardisation samples, except for one task; he achieved average performance, consistent with his socio-educational background. He performed within normal range on 74% of recognition tests and achieved average to above average scores on 42% of them despite very severe impairment on 82% of episodic recall tasks. Both faces and landscapes-scenes gave rise to above average scores when tested with coloured stimuli. Cued recall, although impaired, was largely superior to free recall. This case supports a modular account of the MTL with episodic, but not semantic memory depending on the hippocampal formation. Furthermore, the overall pattern of findings is consistent with evidence from both brain-damaged and neuroimaging studies indicating that recollection requires intact hippocampal formation and familiarity relies, at least partly, on the adjacent temporal lobe cortex.

Cytochemical and immunocytochemical characterization of nuclear bodies during hibernation.

Brown adipose tissue and liver of hibernating, arousing and euthermic individuals of the dormouse Muscardinus avellanarius were studies using ultrastructural cytochemistry and immunocytochemistry with the aim to investigate possible fine structural modifications of the cell nucleus during the seasonal cycle. The general morphology of brown adipocyte and hepatocyte nuclei was similar in the three experimental groups. However, three nuclear structural constituents were identified only in hibernating individuals: coiled bodies (CBs) and amorphous bodies (ABs) were observed in hepatocytes and, together with bundles of nucleoplasmic fibrils (NF), were present in brown adipocytes of hibernating dormice. In arousing animals only some structural constituents suggestive of poorly structured CBs were found. The latter showed the same immunocytochemical features as CBs of hibernating individuals, suggesting that they are disappearing CBs. A possible involvement of CBs in storing and/or processing RNA which must be rapidly and abundantly released upon arousal is discussed. ABs similarly to CBs contain RNA and nucleoplasmic ribonucleoproteins (RNPs) and could also be involved in mRNA pathways. NF do not contain nucleic acids or RNPs and seem to be composed of protein-aceous material; their functional role in the nuclear metabolism of hibernating brown adipocytes remains unclear.

Rapidly fatal poisoning with an insecticide containing rotenone.

Introduction: Rotenone is a botanical pesticide derived from extracts of Derris roots, which is traditionally used as piscicide, but also as an industrial insecticide for home gardens. Its mechanism of action is potent inhibition of mitochondrial respiratory chain by uncoupling oxidative phosphorylation by blocking electron transport at complex-I. Despite its classification as mild to moderately toxic to humans (estimated LD50, 300-500 mg/kg), there is a striking variety of acute toxicity of rotenone depending on the formulation (solvents). Human fatalities with rotenone-containing insecticides have been rarely reported, and a rapid deterioration within a few hours of the ingestion has been described previously in one case. Case report: A 49-year-old Tamil man with a history of asthma, ingested 250 mL of an insecticide containing 1.24% of rotenone (3.125 g, 52.1-62.5 mg/kg) in a suicide attempt at home. The product was not labeled as toxic. One hour later, he vomited repeatedly and emergency services were alerted. He was found unconscious with irregular respiration and was intubated. On arrival at the emergency department, he was comatose (GCS 3) with fixed and dilated pupils, and absent corneal reflexes. Physical examination revealed hemodynamic instability with hypotension (55/30 mmHg) and bradycardia (52 bpm). Significant laboratory findings were lactic acidosis (pH 6.97, lactate 17 mmol/L) and hypokalemia (2 mmol/L). Cranial computed tomography (CT) showed early cerebral edema. A single dose of activated charcoal was given. Intravenous hydration, ephedrine, repeated boli of dobutamine, and a perfusor with 90 micrograms/h norepinephine stabilized blood pressure temporarily. Atropine had a minimal effect on heart rate (58 bpm). Intravenous lipid emulsion was considered (log Pow 4.1), but there was a rapid deterioration with refractory hypotension and acute circulatory failure. The patient died 5h after ingestion of the insecticide. No autopsy was performed. Quantitative analysis of serum performed by high-resolution/accurate mass-mass spectrometry and liquid chromatography (LC-HR/AM-MS): 560 ng/mL rotenone. Other substances were excluded by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS/MS). Conclusion: The clinical course was characterized by early severe symptoms and a rapidly fatal evolution, compatible with inhibition of mitochondrial energy supply. Although rotenone is classified as mild to moderately toxic, physicians must be aware that suicidal ingestion of emulsified concentrates may be rapidly fatal. (n=3): stridor, cyanosis, cough (one each). Local swelling after chewing or swallowing soap developed at the earliest after 20 minutes and persisted beyond 24 hours in some cases. Treatment with antihistamines and/or steroids relieved the symptoms in 9 cases. Conclusion: Bar soap ingestion by seniors carries a risk of severe local reactions. Half the patients developed symptoms, predominantly swellings of tongue and/or lips (38%). Cognitive impairment, particularly in the cases of dementia (37%), may increase the risk of unintentional ingestion. Chewing and intraoral retention of soap leads to prolonged contact with the mucosal membranes. Age-associated physiological changes of oral mucosa probably promote the irritant effects of the surfactants. Medical treatment with antihistamines and corticosteroids usually leads to rapid decline of symptoms. Without treatment, there may be a risk of airway obstruction.

Distribution and genesis of the RFRP-producing neurons in the rat brain: comparison with melanin-concentrating hormone- and hypocretin-containing neurons.

Prepro-RFRP-containing neurons have recently been described in the mammalian brain. These neurons are only found in the tuberal hypothalamus. In this work, we have provided a detailed analysis of the distribution of cells expressing the RFRP mRNA, and found them in seven anatomical structures of the tuberal hypothalamus. No co-expression with melanin-concentrating hormone (MCH) or hypocretin (Hcrt), that are also described in neurons of the tuberal hypothalamus, was observed. Using the BrdU method, we found that all RFRP cell bodies are generated between E13 and E14. Thus, RFRP neurons form a specific cell population with a complex distribution pattern in the tuberal hypothalamus. However, they are generated in one peak. These observations are discussed with data concerning the distribution and genesis of the MCH and Hcrt cell populations that are also distributed in the tuberal hypothalamus.

3-M syndrome associated with growth hormone deficiency: 18 year follow-up of a patient.

3-M syndrome is a rare autosomal recessive disorder that causes short stature, unusual facial features and skeletal abnormalities. Mutations in the CUL7, OBSL1 and CCDC8 genes could be responsible for 3-M syndrome.Here we describe the growth and evolution of dismorphic features of an Italian boy with 3-M syndrome and growth hormone deficiency (GHD) from birth until adulthood. He was born full term with a very low birth weight (2400 g=-3.36 standard deviation score, SDS) and length (40.0 cm =-6.53 SDS). At birth he presented with a broad, fleshy nose with anteverted nostrils, thick and patulous lips, a square chin, curvilinear shaped eyebrows without synophrys, short thorax and long slender bones. Then, during childhood tall vertebral bodies, hip dislocation, transverse chest groove, winged scapulae and hyperextensible joints became more evident and the diagnosis of 3-M syndrome was made; this was also confirmed by the finding of a homozygous deletion in exon 18 of the CUL7 gene, which has not been previously described.The patient also exhibited severe GHD (GH <5 ng/ml) and from the age of 18 months was treated with rhGH. Notwithstanding the early start of therapy and good compliance, his growth rate was always very low, except for the first two years of treatment and he achieved a final height of 132 cm (-6.42 SDS).

The role of palliative care in patients with neurological diseases.

Palliative care aims to improve the quality of life of patients and their families affected by life-threatening illness. This approach applies to a large and growing proportion of neurological disorders, most prominently stroke and dementia. Challenges in the palliative care of patients with incurable neurological diseases include the broad spectrum of the rate of symptom progression, a lack of reliable prognostic markers, scarcity of evidence for efficacy of symptomatic treatments, and a high prevalence of difficulties with communication, cognitive impairment and behavioural disturbances. A genuinely multidisciplinary approach to neurological palliative care is, therefore, required. However, palliative care is not an integral part of neurological training in most countries. This Perspectives article aims to underscore the importance of integrating palliative care into daily clinical practice. The basic principles and challenges of neurological palliative care are also outlined in the light of relevant literature.

Insights into shallow magmatic processes in large silicic magma bodies: the trace element record in the Fish Canyon magma body, Colorado

Highly evolved rhyolite glass plus near-solidus mineral assemblages in voluminous, dacitic, crystal-rich ignimbrites provide an opportunity to evaluate the late magmatic evolution of granodiorite batholiths. This study reports laser-ablation ICP-MS analyses of trace element concentrations in feldspars, hornblende, biotite, titanite, zircon, magnetite, and interstitial glass of the crystal-rich Fish Canyon Tuff. The high-silica rhyolite glass is characterized by relatively high concentrations of feldspar-compatible elements (e.g., 100 ppm Sr and 500 ppm Ba) and low concentrations of Y (< 7 ppm) and HREE (&SIM; 1 ppm Yb), hence high LREE/HREE (Ce/Yb > 40) compared to many well-studied high-silica rhyolite glasses and whole-rock compositions. Most minerals record some trace element heterogeneities, with, in particular, one large hornblende phenocryst showing four- to six-fold core-to-rim increases in Sr and Ba coupled with a decrease in Sc. The depletions of Y and HREE in the Fish Canyon glass relative to the whole-rock composition (concentrations in glass &SIM; 30% of those in whole rocks) reflect late crystallization of phases wherein these elements were compatible. As garnet is not stable at the low-P conditions at which the Fish Canyon magma crystallized, we show that a combination of modally abundant hornblende (&SIM; 4%) + titanite (&SIM; 0.5-1%) and the highly polymerized nature of the rhyolitic liquid led to Y and HREE depletions in melt. Relatively high Sr and Ba contents in glass and rimward Sr and Ba increases in euhedral, concentrically zoned hornblende suggest partial feldspar dissolution and a late release of these elements to the melt as hornblende was crystallizing, in agreement with textural evidence for feldspar (and quartz) resorption. Both observations are consistent with thermal rejuvenation of the magma body prior to eruption, during which the proportion of melt increased via feldspar and quartz dissolution, even as hydrous and accessory phases were crystallizing. Sr/Y in Fish Canyon glass (13-18) is lower than the typical ``adakitic'' value (> 40), confirming that high Sr/Y is a reliable indicator of high-pressure magma generation and/or differentiation wherein garnet is implicated.

Wandering, verbally and physically abusive behaviour and their relation with pain in nursing homes residents

Backgrounds:¦Behavioural and psychological symptoms of dementia (BPSD) include, among others, hallucinations, delusions, depression, euphoria, agitation, aggression, sexual desinhibition, sleep disturbances, and apathy (1). To our knowledge, surprisingly few studies looked into the possible association between pain and BPSD in nursing home residents. Given this dearth of studies, we wondered whether or not there is an association, in nursing home residents, between pain and BPSD, in particular wandering as well as verbally and physically abusive behaviour, and whether or not this possible association changes with the degree of cognitive impairment.¦Method:¦All nursing home residents in the three Swiss cantons Aargau, Basel-City, and Solothurn (corresponding to 13.5%¦of the total Swiss population) receive a Resident Assessment Instrument Minimum Data Set (RAI-MDS)¦assessment within the first two weeks upon entry. This yielded a total sample of 16'430 nursing home residents considering that the residents' assessment took place between 1997 and 2007 and that we only took into account the admission RAI-MDS assessment. Only residents for whom data on pain was recorded were included in the study (n = 16'183).¦Results:¦Wandering correlated significantly with pain although the effect size was small (Spearman correlation coefficient = 0.052; p = 0.000), a result very similar to that found for VAB (Spearman correlation coefficient = 0.034; p = 0.000) and PAB (Spearman correlation coefficient = 0.043; p = 0.000). Likewise, using linear regression analyses, pain was very significantly associated with any of the three BPSD considered, but it predicted astonishingly little of the¦variance observed (wandering: B = 0.036; p = 0.000; R2 = 0.002; VAB: B = 0.021; p = 0.000; R2 = 0.001 PAB: B = 0.012; p = 0.000; R2 = 0.001). The interaction of pain and cognition had a significant effect on the three BPSD, suggesting that cognition was a moderator of the relationship between pain and all three behaviours.¦Conclusion:¦Wandering behaviours, VAB and PAB seem to be predicted by many factors. Although pain predicts only a small part of variance of these behaviours, it still remains important to recognise and treat pain in order to reduce these behaviours at least a little both in intensity and frequency. Given the dearth of studies and their somewhat contradictory results, further studies ought to investigate the role, the type and localisation of pain might play on the expression of different BPSD or how residents suffering from dementia perceive pain.

Theory of mind and cognitive processes in aging and Alzheimer type dementia: a systematic review.

OBJECTIVES: Theory of mind (ToM) performance in aging and dementia of the Alzheimer type (DAT) has been a growing interest of researchers and recently, theoretical trends in ToM development have led to a focus on determining the cognitive skills involved in ToM performance. The aim of the present review is to answer three main questions: How is ToM assessed in aging and DAT? How does ToM performance evolve in aging and DAT? Do cognitive processes influence ToM performance in aging and DAT? METHOD: A systematic review was conducted to provide a targeted overview of recent studies relating ToM performance with cognitive processes in aging and DAT. RESULTS: RESULTS suggest a decrease in ToM performance, more pronounced in complex ToM tasks. Moreover, the review points up the strong involvement of executive functions, especially inhibition, and reasoning skills in ToM task achievement. CONCLUSION: Current data suggest that the structure of ToM tasks itself could lead to poor performance, especially in populations with reduced cognitive abilities.

Small vascular and Alzheimer disease-related pathologic determinants of dementia in the oldest-old.

The relative contributions of Alzheimer disease (AD) and vascular lesion burden to the occurrence of cognitive decline are more difficult to define in the oldest-old than they are in younger cohorts. To address this issue, we examined 93 prospectively documented autopsy cases from 90 to 103 years with various degrees of AD lesions, lacunes, and microvascular pathology. Cognitive assessment was performed prospectively using the Clinical Dementia Rating scale. Neuropathologic evaluation included the Braak neurofibrillary tangle (NFT) and β-amyloid (Aβ) protein deposition staging and bilateral semiquantitative assessment of vascular lesions. Statistics included regression models and receiver operating characteristic analyses. Braak NFTs, Aβ deposition, and cortical microinfarcts (CMIs) predicted 30% of Clinical Dementia Rating variability and 49% of the presence of dementia. Braak NFT and CMI thresholds yielded 0.82 sensitivity, 0.91 specificity, and 0.84 correct classification rates for dementia. Using these threshold values, we could distinguish 3 groups of demented cases and propose criteria for neuropathologic definition of mixed dementia, pure vascular dementia, and AD in very old age. Braak NFT staging and severity of CMI allow for defining most of demented cases in the oldest-old. Most importantly, single cutoff scores for these variables that could be used in the future to formulate neuropathologic criteria for mixed dementia in this age group were identified.

Personality changes in patients with beginning Alzheimer disease

Objective: To investigate personality traits in patients with Alzheimer disease, compared with mentally healthy control subjects. We compared both current personality characteristics using structured interviews as well as current and previous personality traits as assessed by proxies.Method: Fifty-four patients with mild Alzheimer disease and 64 control subjects described their personality traits using the Structured Interview for the Five-Factor Model. Family members filled in the Revised NEO Personality Inventory, Form R, to evaluate their proxies' current personality traits, compared with 5 years before the estimated beginning of Alzheimer disease or 5 years before the control subjects.Results: After controlling for age, the Alzheimer disease group presented significantly higher scores than normal control subjects on current neuroticism, and significantly lower scores on current extraversion, openness, and conscientiousness, while no significant difference was observed on agreeableness. A similar profile, though less accentuated, was observed when considering personality traits as the patients' proxies remembered them. Diachronic personality assessment showed again significant differences between the 2 groups for the same 4 domains, with important personality changes only for the Alzheimer disease group.Conclusions: Group comparison and retrospective personality evaluation are convergent. Significant personality changes follow a specific trend in patients with Alzheimer disease and contrast with the stability generally observed in mentally healthy people in their personality profile throughout their lives. Whether or not the personality assessment 5 years before the current status corresponds to an early sign of Alzheimer disease or real premorbid personality differences in people who later develop Alzheimer disease requires longitudinal studies.