In 2011, the National Institute on Aging and Alzheimer's Association created separate diagnostic recommendations for the preclinical, mild cognitive impairment, and dementia stages of Alzheimer's ...disease. Scientific progress in the interim led to an initiative by the National Institute on Aging and Alzheimer's Association to update and unify the 2011 guidelines. This unifying update is labeled a “research framework” because its intended use is for observational and interventional research, not routine clinical care. In the National Institute on Aging and Alzheimer's Association Research Framework, Alzheimer's disease (AD) is defined by its underlying pathologic processes that can be documented by postmortem examination or in vivo by biomarkers. The diagnosis is not based on the clinical consequences of the disease (i.e., symptoms/signs) in this research framework, which shifts the definition of AD in living people from a syndromal to a biological construct. The research framework focuses on the diagnosis of AD with biomarkers in living persons. Biomarkers are grouped into those of β amyloid deposition, pathologic tau, and neurodegeneration AT(N). This ATN classification system groups different biomarkers (imaging and biofluids) by the pathologic process each measures. The AT(N) system is flexible in that new biomarkers can be added to the three existing AT(N) groups, and new biomarker groups beyond AT(N) can be added when they become available. We focus on AD as a continuum, and cognitive staging may be accomplished using continuous measures. However, we also outline two different categorical cognitive schemes for staging the severity of cognitive impairment: a scheme using three traditional syndromal categories and a six-stage numeric scheme. It is important to stress that this framework seeks to create a common language with which investigators can generate and test hypotheses about the interactions among different pathologic processes (denoted by biomarkers) and cognitive symptoms. We appreciate the concern that this biomarker-based research framework has the potential to be misused. Therefore, we emphasize, first, it is premature and inappropriate to use this research framework in general medical practice. Second, this research framework should not be used to restrict alternative approaches to hypothesis testing that do not use biomarkers. There will be situations where biomarkers are not available or requiring them would be counterproductive to the specific research goals (discussed in more detail later in the document). Thus, biomarker-based research should not be considered a template for all research into age-related cognitive impairment and dementia; rather, it should be applied when it is fit for the purpose of the specific research goals of a study. Importantly, this framework should be examined in diverse populations. Although it is possible that β-amyloid plaques and neurofibrillary tau deposits are not causal in AD pathogenesis, it is these abnormal protein deposits that define AD as a unique neurodegenerative disease among different disorders that can lead to dementia. We envision that defining AD as a biological construct will enable a more accurate characterization and understanding of the sequence of events that lead to cognitive impairment that is associated with AD, as well as the multifactorial etiology of dementia. This approach also will enable a more precise approach to interventional trials where specific pathways can be targeted in the disease process and in the appropriate people.
Empathy is fundamental to social cognition, driving prosocial behaviour and mental health but associations with aging and other socio-demographic characteristics are unclear. We therefore aimed to ...characterise associations of these characteristics with two main self-reported components of empathy, namely empathic-concern (feeling compassion) and perspective-taking (understanding others' perspective).
We asked participants in an internet-based survey of UK-dwelling adults aged ≥18 years to complete the Interpersonal Reactivity Index subscales measuring empathic concern and perspective taking, and sociodemographic and personality questionnaires. We weighted the sample to be UK population representative and employed multivariable weighted linear regression models.
In 30,033 respondents, mean empathic concern score was 3.86 (95% confidence interval 3.85, 3.88) and perspective taking was 3.57 (3.56. 3.59); the correlation between these sub-scores was 0.45 (p < 0.001). Empathic concern and perspective taking followed an inverse-u shape trajectory in women with peak between 40 and 50 years whereas in men, perspective taking declines with age but empathic concern increases. In fully adjusted models, greater empathic concern was associated with female gender, non-white ethnicity, having more education, working in health, social-care, or childcare professions, and having higher neuroticism, extroversion, openness to experience and agreeableness traits. Perspective taking was associated with younger age, female gender, more education, employment in health or social-care, neuroticism, openness, and agreeableness.
Empathic compassion and understanding are distinct dimensions of empathy with differential demographic associations. Perspective taking may decline due to cognitive inflexibility with older age whereas empathic concern increases in older men suggesting it is socially-driven.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Although psychosis is a defining feature of Lewy body disease, psychotic symptoms occur in a subset of patients with every major neurodegenerative disease. Few studies, however, have compared ...disease-related rates of psychosis prevalence in a large autopsy-based cohort, and it remains unclear how diseases differ with respect to the nature or content of the psychosis. We conducted a retrospective chart review of 372 patients with autopsy-confirmed neurodegenerative pathology: 111 with Alzheimer's disease, 59 with Lewy body disease and concomitant Alzheimer's disease, 133 with frontotemporal lobar degeneration (FTLD) with tau inclusions (including progressive supranuclear palsy, corticobasal degeneration or Pick's disease), and 69 with FTLD and TDP inclusions (FTLD-TDP, including types A-C). Psychosis content was classified by subtype, and the frequency of each subtype was compared among pathological diagnoses using logistic regression. A total of 111 of 372 patients had psychosis. Compared to other groups, patients with Lewy body disease/Alzheimer's disease pathology were significantly more likely to have hallucinations and were more likely to have more than one subtype of hallucination. Patients with Braak Parkinson stage 5-6 Lewy body disease were significantly more likely than those with no Lewy body disease to have visual hallucinations of misperception, peripheral hallucinations, hallucinations that moved, hallucinations of people/animals/objects, as well as delusions regarding a place and delusions of misidentification. The feeling of a presence occurred significantly more frequently in patients with Lewy body disease/Alzheimer's disease than all other pathologies. Patients with FTLD-TDP were significantly more likely to have delusions, and for the delusions to occur in the first 3 years of the disease, when compared to patients with Alzheimer's disease and FTLD-tau, though rates were not significantly greater than patients with Lewy body disease/Alzheimer's disease. Paranoia occurred more frequently in the FTLD-TDP and Lewy body disease/Alzheimer's disease categories compared to patients with Alzheimer's disease or FTLD-tau. Patients with FTLD-TDP pathology had delusions of misidentification as frequently as patients with Lewy body disease/Alzheimer's disease, and were significantly more likely to have self-elevating delusions such as grandiosity and erotomania compared to patients with other pathologies including FTLD-tau. These data show that the nature and content of psychosis can provide meaningful information about the underlying neurodegenerative pathology, emphasizing the importance of characterizing patients' psychoses for prediction of the neuropathological diagnosis, regardless of a patient's clinical syndrome.
We used linear and multivariate models to examine the associations between geography, biodiversity, per capita economic output, national spending on conservation, governance, and cultural traits in ...55 countries. Cultural traits and social metrics of modernization correlated positively with national spending on conservation. The global distribution of this spending culture was poorly aligned with the distribution of biodiversity. Specifically, biodiversity was greater in the tropics where cultures tended to spend relatively less on conservation and tended to have higher collectivism, formalized and hierarchical leadership, and weaker governance. Consequently, nations lacking social traits frequently associated with modernization, environmentalism, and conservation spending have the largest component of Earth's biodiversity. This has significant implications for setting policies and priorities for resource management given that biological diversity is rapidly disappearing and cultural traits change slowly. Therefore, we suggest natural resource management adapt to and use characteristics of existing social organization rather than wait for or promote social values associated with conservation spending. Supporting biocultural traditions, engaging leaders to increase conservation commitments, cross-national efforts that complement attributes of cultures, and avoiding interference with nature may work best to conserve nature in collective and hierarchical societies. Spending in modernized nations may be a symbolic response to a symptom of economic development and environmental degradation, and here conservation actions need to ensure that biodiversity is not being lost. Utilizamos modelos lineales y multivariados para examinar las relaciones entre la geografía, la biodiversidad, la producción per cápita y económica, el gasto nacional en conservación, la governanza y las características culturales en 55 países. Las características culturales y las medidas sociales de la modernización tuvieron una correlación positiva con el gasto nacional en conservación. La distribución global de esta cultura de gasto tuvo una alineación mínima con la distribución de la biodiversidad. En específico, la biodiversidad fue mayor en los trópicos en donde las culturas tuvieron la tendencia a gastar relativamente menos en la conservación y tuvieron la tendencia a tener un colectivismo mayor, liderazgo formalizado y jerárquico y gobiernos más débiles. En consecuencia, los países carentes de características sociales asociadas frecuentemente con la modernización, el ambientalismo y el gasto de conservación tienen el mayor componente de biodiversidad de la Tierra. Esto tiene implicaciones significativas para establecer políticas y prioridades para el manejo dado que la diversidad biológica está desapareciendo rápidamente y las características culturales cambian lentamente. Por esto, sugerimos que el manejo de recursos naturales se adapte y use las características de las organizaciones sociales existentes en lugar de esperar o promover valores sociales asociados con el gasto de conservación. Apoyar las tradiciones bioculturales, involucrar a los líderes para incrementar los compromisos de conservación, realizar esfuerzos internacionales que complementen los atributos de las culturas y evitar la interferencia con la naturaleza puede funcionar mejor para conservar la naturaleza en sociedades colectivas y jerárquicas. El gasto en los países modernizados puede ser una respuesta simbólica al síntoma del desarrollo económico y la degradación ambiental, y es aquí donde la conservación tiene que asegurar que no se está perdiendo la biodiversidad.
Executive functioning is widely targeted when human cognition is assessed, but there is little consensus on how it should be operationalized and measured. Recognizing the difficulties associated with ...establishing standard operational definitions of executive functioning, the National Institute of Neurological Disorders and Stroke entered into a contract with the University of California-San Francisco to develop psychometrically robust executive measurement tools that would be accepted by the neurology clinical trials and clinical research communities. This effort, entitled Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research (EXAMINER), resulted in a series of tasks targeting working memory, inhibition, set shifting, fluency, insight, planning, social cognition and behavior. We describe battery conceptualization and development, data collection, scale construction based on item response theory, and lay the foundation for studying the battery's utility and validity for specific assessment and research goals.
Summary Background Individuals with schizophrenia have functionally significant deficits in automatic and controlled social cognition, but no currently available pharmacologic treatments reduce these ...deficits. The neuropeptide oxytocin has multiple prosocial effects when administered intranasally in humans and there is growing interest in its therapeutic potential in schizophrenia. Methods We administered 40 IU of oxytocin and saline placebo intranasally to 29 male subjects with schizophrenia and 31 age-matched, healthy controls in a randomized, double-blind, placebo-controlled, cross-over study. Social cognition was assessed with The Awareness of Social Inference Test (TASIT) and the Reading the Mind in the Eyes Test (RMET). We examined the effects of oxytocin administration on automatic social cognition (the ability to rapidly interpret and understand emotional cues from the voice, face, and body); controlled social cognition (the ability to comprehend indirectly expressed emotions, thoughts, and intentions through complex deliberations over longer time periods); and a control task (the ability to comprehend truthful dialog and perform general task procedures) in individuals with and without schizophrenia using mixed factorial analysis of variance models. Results Patients with schizophrenia showed significant impairments in automatic and controlled social cognition compared to healthy controls, and administration of oxytocin significantly improved their controlled, but not automatic, social cognition, F (1, 58) = 8.75; p = 0.004. Conversely, oxytocin administration had limited effects on social cognition in healthy participants. Patients and controls performed equally well and there were no effects of oxytocin administration on the control task. Discussion Intact social cognitive abilities are associated with better functional outcomes in individuals with schizophrenia. Our data highlight the potentially complex effects of oxytocin on some but not all aspects of social cognition, and support the exploration of intranasal oxytocin as a potential adjunct treatment to improve controlled social cognition in schizophrenia.
IMPORTANCE: Neurodegenerative diseases can cause dysfunction of neural structures involved in judgment, executive function, emotional processing, sexual behavior, violence, and self-awareness. Such ...dysfunctions can lead to antisocial and criminal behavior that appears for the first time in the adult or middle-aged individual or even later in life. OBJECTIVE: To investigate the frequency and type of criminal behavior among patients with a diagnosed dementing disorder. DESIGN, SETTING, AND PARTICIPANTS: We conducted a retrospective medical record review of 2397 patients who were seen at the University of California, San Francisco, Memory and Aging Center between 1999 and 2012, including 545 patients with Alzheimer disease (AD), 171 patients with behavioral variant of frontotemporal dementia (bvFTD), 89 patients with semantic variant of primary progressive aphasia, and 30 patients with Huntington disease. Patient notes containing specific keywords denoting criminal behavior were reviewed. Data were stratified by criminal behavior type and diagnostic groups. MAIN OUTCOMES AND MEASURES: Frequencies of criminal behavior and χ2 statistics were calculated. RESULTS: Of the 2397 patients studied, 204 (8.5%) had a history of criminal behavior that emerged during their illness. Of the major diagnostic groups, 42 of 545 patients (7.7%) with AD, 64 of 171 patients (37.4%) with bvFTD, 24 of 89 patients (27.0%) with semantic variant of primary progressive aphasia, and 6 of 30 patients (20%) with Huntington disease exhibited criminal behavior. A total of 14% of patients with bvFTD were statistically significantly more likely to present with criminal behavior compared with 2% of patients with AD (P < .001) and 6.4% were statistically significantly more likely to exhibit violence compared with 2% of patients with AD (P = .003). Common manifestations of criminal behavior in the bvFTD group included theft, traffic violations, sexual advances, trespassing, and public urination in contrast with those in the AD group, who commonly committed traffic violations, often related to cognitive impairment. CONCLUSIONS AND RELEVANCE: Criminal behavior is more common in patients with bvFTD and semantic variant of primary progressive aphasia than in those with AD and is more likely to be an early manifestation of the disorder. Judicial evaluations of criminality in the demented individual might require different criteria than the classic “insanity defense” used in the American legal system; these individuals should be treated differently by the law. The appearance of new-onset criminal behavior in an adult should elicit a search for frontal and anterior temporal brain disease and for dementing disorders.
Empathy is a complex social behaviour mediated by a network of brain structures. Recently, several functional imaging studies have investigated the neural basis of empathy, but few corroborative ...human lesion studies exist. Severe empathy loss is a common feature of frontotemporal lobar degeneration (FTLD), and is also seen in other neurodegenerative diseases. In this study, the neuroanatomic basis of empathy was investigated in 123 patients with FTLD, Alzheimer's disease, corticobasal degeneration and progressive supranuclear palsy using the Interpersonal Reactivity Index (IRI). IRI Empathic Concern and Perspective taking scores were correlated with structural MRI brain volume using voxel-based morphometry. Voxels in the right temporal pole, the right fusiform gyrus, the right caudate and right subcallosal gyrus correlated significantly with total empathy score (P < 0.05 after whole-brain correction for multiple comparisons). Empathy score correlated positively with the volume of right temporal structures in semantic dementia, and with subcallosal gyrus volume in frontotemporal dementia. These findings are consistent with previous research suggesting that a primarily right frontotemporal network of brain regions is involved in emotion processing, and highlights the roles of the right temporal pole and inferior frontal/striatal regions in regulating complex social interactions. This is the first large-scale lesion study to investigate the neural basis of empathy using correlational analytic methods. The results suggest that the right anterior temporal and medial frontal regions are essential for real-life empathic behaviour.
Large-scale brain networks are integral to the coordination of human behaviour, and their anatomy provides insights into the clinical presentation and progression of neurodegenerative illnesses such ...as Alzheimer's disease, which targets the default mode network, and behavioural variant frontotemporal dementia, which targets a more anterior salience network. Although the default mode network is recruited when healthy subjects deliberate about 'personal' moral dilemmas, patients with Alzheimer's disease give normal responses to these dilemmas whereas patients with behavioural variant frontotemporal dementia give abnormal responses to these dilemmas. We hypothesized that this apparent discrepancy between activation- and patient-based studies of moral reasoning might reflect a modulatory role for the salience network in regulating default mode network activation. Using functional magnetic resonance imaging to characterize network activity of patients with behavioural variant frontotemporal dementia and healthy control subjects, we present four converging lines of evidence supporting a causal influence from the salience network to the default mode network during moral reasoning. First, as previously reported, the default mode network is recruited when healthy subjects deliberate about 'personal' moral dilemmas, but patients with behavioural variant frontotemporal dementia producing atrophy in the salience network give abnormally utilitarian responses to these dilemmas. Second, patients with behavioural variant frontotemporal dementia have reduced recruitment of the default mode network compared with healthy control subjects when deliberating about these dilemmas. Third, a Granger causality analysis of functional neuroimaging data from healthy control subjects demonstrates directed functional connectivity from nodes of the salience network to nodes of the default mode network during moral reasoning. Fourth, this Granger causal influence is diminished in patients with behavioural variant frontotemporal dementia. These findings are consistent with a broader model in which the salience network modulates the activity of other large-scale networks, and suggest a revision to a previously proposed 'dual-process' account of moral reasoning. These findings also characterize network interactions underlying abnormal moral reasoning in frontotemporal dementia, which may serve as a model for the aberrant judgement and interpersonal behaviour observed in this disease and in other disorders of social function. More broadly, these findings link recent work on the dynamic interrelationships between large-scale brain networks to observable impairments in dementia syndromes, which may shed light on how diseases that target one network also alter the function of interrelated networks.
Background: Loss of insight is a core diagnostic criterion for frontotemporal dementia (FTD), whereas failure to recognise cognitive deficits and unawareness of disease (anosognosia) are well ...established findings in Alzheimer’s disease (AD). However, self awareness of personality has not been quantified in these patient groups. Methods: Twenty two patients (12 with frontal variant FTD; 10 with early AD) and 11 older adult normal controls completed self report questionnaires (the Interpersonal Adjectives Scales) describing their current personality. First degree relative informants completed two questionnaires, one describing the subject’s current personality, the other retrospectively describing the subject’s personality before disease onset. Differences between subject and informant reports of current personality were used to measure the accuracy of self awareness. Results: Discriminant function analysis showed significant differences in self awareness among the three groups, with those in the FTD group showing the greatest magnitude of error in the largest number of personality dimensions (dominance, submissiveness, cold heartedness, introversion, and ingenuousness). Despite personality changes over time, patients with AD showed accurate self awareness in all personality dimensions except submissiveness and extraversion. Normal controls showed a pattern of underestimating positive qualities, whereas patients with FTD exaggerated positive qualities and minimised negative qualities. For the personality facets showing impaired insight, the self reports of patients with FTD and AD most closely matched their premorbid personalities, suggesting a failure to update their self image after disease onset. Conclusions: This study operationalises research criteria for loss of insight in FTD.
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