Tragic Optimism as a Buffer Against COVID-19 Suffering and the Psychometric Properties of a Brief Version of the Life Attitudes Scale.

The Life Attitudes Scale (LAS) was designed to measure tragic optimism (TO)-a distinct type of optimism that could generate hopeless hope even in dire situations according to existential positive psychology (PP 2.0). This study explains why only a faith-based TO could serve as a buffer against suffering at the Nazi death camps as well as the global coronavirus disease 2019 (COVID-19) pandemic. In study 1, the results showed that the factorial structure of a 15-item LAS-Brief (LAS-B), which is a short measure of TO, replicated the original structure of the 32-item long version. The five factors (i.e., affirmation, acceptance, courage, faith, and self-transcendence) provided a good data model fit statistics for LAS-B; the measure had adequate-to-strong internal and latent construct reliability estimates. In study 2, the buffering effect of TO on the association between suffering experiences during COVID-19 and life satisfaction in adults was examined. The results of the studies were consistent with our hypothesis that TO as measured by LAS-B serves as a buffer against the impact of COVID-19 suffering on life satisfaction.

Mediating Effect of Personal Meaning in the Prediction of Life Satisfaction and Mental Health Problems Based on Coronavirus Suffering.

Research Problem: The onset of the COVID-19 pandemic has triggered a multi-faceted crisis worldwide. Researchers and health authorities in various parts of the world echoed the dire condition of the public's mental health. This study sought to examine the mediating effect of personal meaning on the association between coronavirus (COVID-19)-related suffering, mental health problems, and life satisfaction. Participants included 231 adults (mean age = 46.65 ± 13.98; 68% female) and completed measures of suffering related to COVID-19, meaning, life satisfaction, and mental health problems online. Results: Findings from mediation analysis showed that suffering had significant associations with personal meaning, mental health, and well-being. Furthermore, personal meaning was significantly associated with adults' mental health and well-being and mediated the negative effect of suffering on mental health and well-being. Discussion: Overall, results from this study indicate that personal meaning is an important promotive factor that may help to understand the negative effect of coronavirus-related suffering on mental health and well-being amid the public health crisis.

Measuring total mercury due to small-scale gold mining activities to determine community vulnerability in Cihonje, Central Java, Indonesia.

This research is comparative study of gold mining and non-gold mining areas, using four community vulnerability indicators. Vulnerability indicators are exposure degree, contamination rate, chronic, and acute toxicity. Each indicator used different samples, such as wastewater from gold mining process, river water from Tajum river, human hair samples, and health questionnaire. This research used cold vapor atomic absorption spectrometry to determine total mercury concentration. The result showed that concentration of total mercury was 2,420 times than the maximum content of mercury permitted in wastewater based on the Indonesian regulation. Moreover, the mercury concentration in river water reached 685 ng/l, exceeding the quality threshold standards of the World Health Organization (WHO). The mercury concentration in hair samples obtained from the people living in the research location was considered to identify the health quality level of the people or as a chronic toxicity indicator. The highest mercury concentration--i.e. 17 ng/mg, was found in the gold mining respondents. Therefore, based on the total mercury concentration in the four indicators, the community in the gold mining area were more vulnerable to mercury than communities in non-gold mining areas. It was concluded that the community in gold mining area was more vulnerable to mercury contamination than the community in non-gold mining area.

Agitation in Alzheimer's disease is a manifestation of frontal lobe dysfunction.

OBJECTIVES: (1) To investigate the prevalence and characteristics of agitation in patients with Alzheimer's disease (AD) and other forms of dementia; (2) to explore the association between agitation and other clinical variables, including disease severity, functional impairment and other neuropsychiatric symptoms, and (3) to determine the predictors of agitation. METHODS: Data for 427 men and women with dementia from outpatient clinics of the University of California, Los Angeles Alzheimer's Disease Center were analyzed. There were 277 patients with AD, 43 with vascular dementia, 47 with mixed dementia, 45 with frontotemporal dementia and 15 with dementia with Lewy bodies. Patients were evaluated with the Mini-Mental State Examination (MMSE), Neuropsychiatric Inventory (NPI), Functional Activities Questionnaire (FAQ), neuropsychological tests and the Caregiver Appraisal instrument. SPSS10 was utilized for statistical analysis. RESULTS: There was no difference in agitation subscale scores among patients with dementia of various etiologies. In patients with AD, there was increased prevalence of agitation with increasing dementia severity. Agitation contributed substantially to caregiver burden and impact. There was a significant correlation between the FAQ and the NPI agitation subscale score after adjusting for MMSE scores. Delusion, disinhibition and irritability subscale scores in AD patients were correlated with agitation across disease severity. Subscale scores of frontally mediated behaviors including irritability, delusions and disinhibition predicted most of the variance in agitation levels. CONCLUSION: Agitation is common in AD and other dementias and has a marked impact on caregivers. It is related to dementia severity and to specific types of associated psychopathology implicating frontal lobe dysfunction. The present study is the largest and most comprehensive assessment of agitation reported. The data suggest that agitation in AD is a frontal lobe syndrome. Frontal lobe dysfunction may predispose AD patients to agitation by exaggerating behavioral responses to many types of coexisting psychopathology or environmental provocations.

A transcultural study of agitation in dementia.

Agitation is one of the most troublesome behaviors in demented patients. It is etiologically heterogeneous and has varied associated behaviors. To explore the transcultural differences in the manifestation of agitation, we evaluated 50 consecutive Alzheimer's disease (AD) patients in three countries (Taiwan, Italy, and the United States) using the Neuropsychiatric Inventory (NPI) and the Mini-Mental State Examination (MMSE). In a focused analysis, only patients with composite NPI scores > 2 for agitation were selected, with similar levels of disease severity as measured by the MMSE, from the three groups (n = 15 per group) to evaluate culturally specific correlates of agitation. Agitated Taiwanese had significantly more hallucinations than either Italian or American patients. Agitated Italian patients had significantly more apathy than both Taiwanese and American patients. Cultural factors may influence the manifestation of agitation more than a common underlying neuropathology. Management strategies targeting unique behavioral instigators of agitation may be specific for different ethnic groups.

Probabilistic approaches for atlasing normal and disease-specific brain variability.

The extreme variability in the structural conformation of the human brain poses significant challenges for the creation of population-based atlases. The ability to statistically and visually compare and contrast brain image data from multiple individuals is essential to understanding normal variability within a particular population as well as differentiating normal from diseased populations. This paper introduces the application of probabilistic atlases that describe specific subpopulations, measures their variability and characterizes the structural differences between them. Utilizing data from structural MRI, we have built atlases with defined coordinate systems creating a framework for mapping data from functional, histological and other studies of the same population. This paper describes the basic approach and a brief description of the underlying mathematical constructs that enable the calculation of probabilistic atlases and examples of their results from several different normal and diseased populations.

Neuropsychiatric aspects of Huntington's disease.

OBJECTIVE: Neuropsychiatric symptoms are common in Huntington's disease and have been considered its presenting manifestation. Research characterising these symptoms in Huntington's disease is variable, however, encumbered by limitations within and across studies. Gaining a better understanding of neuropsychiatric symptoms is essential, as these symptoms have implications for disease management, prognosis, and quality of life for patients and caregivers. METHOD: Fifty two patients with Huntington's disease were administered standardised measures of cognition, psychiatric symptoms, and motor abnormalities. Patient caregivers were administered the neuropsychiatric inventory. RESULTS: Ninety eight per cent of the patients exhibited neuropsychiatric symptoms, the most prevalent being dysphoria, agitation, irritability, apathy, and anxiety. Symptoms ranged from mild to severe and were unrelated to dementia and chorea. CONCLUSIONS: Neuropsychiatric symptoms are prevalent in Huntington's disease and are relatively independent of cognitive and motor aspects of the disease. Hypothesised links between neuropsychiatric symptoms of Huntington's disease and frontal-striatal circuitry were explored. Findings indicate that dimensional measures of neuropsychiatric symptoms are essential to capture the full range of pathology in Huntington's disease and are vital to include in a comprehensive assessment of the disease.

Differential diagnosis of dementia: clinical examination and laboratory assessment.

Recent breakthroughs in putative disease-modifying interventions for Alzheimer's disease (AD) underscore the urgency of making the earliest possible diagnosis. In the absence of a convenient and reliable laboratory test for AD, the clinical assessment is still the cornerstone of the diagnostic approach. This article provides a basis for conducting an assessment within the realities of a busy clinical practice for patients complaining of cognitive decline. The assessment will enable the clinician to diagnose the earliest manifestation of AD.

Behavioral disorders and caregivers' reaction in Taiwanese patients with Alzheimer's disease.

OBJECTIVES: To evaluate the applicability of the Chinese version of the Neuropsychiatric Inventory Scale (NPI), and to explore the neuropsychiatric manifestations of Taiwanese patients with Alzheimer's disease (AD) and caregiver distress. METHOD: The Mini-Mental State Examination (MMSE) was administered to 95 patients with AD, and their caregivers were interviewed with the NPI. To assess the test-retest reliability of the Chinese version of the NPI, 86 caregivers underwent a second NPI 3 weeks later. RESULTS: The Cronbach's alpha coefficient of the Chinese version of the NPI was .76. The test-retest reliabilities of frequency, severity, and caregiver burden scores were significantly correlated; overall correlations were .85 for frequency (p < .001), .82 for severity (p < .001), and .79 (p < .001) for distress. Factor analysis was carried out, and three groups, "mood and psychosis," "psychomotor regulation," and "social engagement," were found. Aberrant motor behavior was the most frequently recorded behavior; euphoria was the least. There was no significant correlation between the patient's MMSE and the caregiver distress score, except for aberrant motor activity (r = -.23, p = .03). The symptoms most frequently reported to be severely distressing to caregivers were aberrant motor activity, anxiety, agitation, and delusions. CONCLUSIONS: These results indicate that the NPI is a reliable tool to assess behavioral disturbance and caregiver distress in Taiwanese AD patients. These findings also confirm the high prevalence of psychopathology among AD patients and the marked distress produced by many of these behaviors.

Orbitofrontal and anterior cingulate cortex neurofibrillary tangle burden is associated with agitation in Alzheimer disease.

Few studies evaluate neuropathological correlates of behavioral changes in Alzheimer disease (AD). We identified 31 autopsy patients with a diagnosis of definite AD. Behavioral changes were assessed with the Neuropsychiatric Inventory. Brain sections were collected from bilateral orbitofrontal and left anterior cingulate, superior temporal, inferior parietal, occipital, and hippocampal cortices for quantification of neurofibrillary tangles (NFTs) and diffuse and neuritic plaques. Sections from frontal, cingulate, and hippocampal cortices were reviewed for the presence of Lewy bodies (LBs). Hypothesis-driven correlational analyses were performed by the bootstrap method. Subgroup analyses contrasted a group with high scores of one specific behavior to a group with low scores after equating groups for other behaviors. NFT burden in the left orbitofrontal cortex across all 31 patients significantly correlated with agitation scores (r = 0.41, p < 0.015) and NFTs correlated significantly (r = 0.66, p = 0.004) with higher agitation scores in the subgroup analysis. Left anterior cingulate NFTs, although not within our hypotheses, also showed a significant relationship to agitation within the subgroups (r = 0.76, p = 0.0003; Bonferroni p = 0.02). Seven patients, including three in the agitation subgroup, had cortical LBs. Aberrant motor behavior and NFT density in the left orbitofrontal cortex showed a significant relationship for the entire group (r = 0.38, p < 0.03) and for subgroups (r = 0.49, p = 0.04), whereas apathy and left anterior cingulate NFTs showed a significant relationship only for the entire group (r = 0.25, p < or = 0.01). These observations suggest that agitation and aberrant motor behavior are correlates of greater NFT pathology in the orbitofrontal cortex in AD, whereas increasing apathy may relate to greater NFT burden in the anterior cingulate.

Cognitive and metabolic responses to metrifonate therapy in Alzheimer disease.

OBJECTIVE: The objective of this study was to identify the relation between the cognitive benefit seen with the cholinesterase inhibitor metrifonate and changes in brain metabolism as visualized with [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET). BACKGROUND: The regional metabolic correlates of treatment with cholinesterase inhibitors are poorly understood. METHODS: Six patients with mild to moderate Alzheimer disease (AD) were evaluated before and after treatment with the long-lasting cholinesterase inhibitor metrifonate. Patients were given 60 or 80 mg of metrifonate per day (based on weight) for 6 to 12 weeks. Clinical evaluations included the cognitive portion of the Alzheimer's Disease Assessment Scale (ADAS-cog), the Mini-Mental State Examination (MMSE), and the Neuropsychiatric Inventory. Imaging was carried out using FDG-PET. The PET studies, registered to a probabilistic anatomic atlas, were normalized across the group's mean intensity levels and subjected to voxel-by-voxel subtraction of the posttreatment minus pretreatment studies. Subvolume thresholding corrected random lobar noise to produce a three-dimensional functional significance map. RESULTS: The criteria for cognitive improvement with treatment were met for the MMSE (>2 points improvement from baseline), and the drawing subscale of the ADAS-cog was significantly improved with treatment. The three-dimensional significance map revealed a significant metabolic increase of the dorsolateral frontoparietal network on the left and bilateral temporal cortex with metrifonate treatment. CONCLUSION: The clinical benefits observed in AD with cholinesterase inhibitor therapy are associated with a metabolic increase of heteromodal cognitive and medial temporal networks.

Cortical change in Alzheimer's disease detected with a disease-specific population-based brain atlas.

We report the first detailed population-based maps of cortical gray matter loss in Alzheimer's disease (AD), revealing prominent features of early structural change. New computational approaches were used to: (i) distinguish variations in gray matter distribution from variations in gyral patterns; (ii) encode these variations in a brain atlas (n = 46); (iii) create detailed maps localizing gray matter differences across groups. High resolution 3D magnetic resonance imaging (MRI) volumes were acquired from 26 subjects with mild to moderate AD (age 75.8+/-1.7 years, MMSE score 20.0+/-0.9) and 20 normal elderly controls (72.4+/-1.3 years) matched for age, sex, handedness and educational level. Image data were aligned into a standardized coordinate space specifically developed for an elderly population. Eighty-four anatomical models per brain, based on parametric surface meshes, were created for all 46 subjects. Structures modeled included: cortical surfaces, all major superficial and deep cortical sulci, callosal and hippocampal surfaces, 14 ventricular regions and 36 gyral boundaries. An elastic warping approach, driven by anatomical features, was then used to measure gyral pattern variations. Measures of gray matter distribution were made in corresponding regions of cortex across all 46 subjects. Statistical variations in cortical patterning, asymmetry, gray matter distribution and average gray matter loss were then encoded locally across the cortex. Maps of group differences were generated. Average maps revealed complex profiles of gray matter loss in disease. Greatest deficits (20-30% loss, P<0.001-0.0001) were mapped in the temporo-parietal cortices. The sensorimotor and occipital cortices were comparatively spared (0-5% loss, P>0.05). Gray matter loss was greater in the left hemisphere, with different patterns in the heteromodal and idiotypic cortex. Gyral pattern variability also differed in cortical regions appearing at different embryonic phases. 3D mapping revealed profiles of structural deficits consistent with the cognitive, metabolic and histological changes in early AD. These deficits can therefore be (i) charted in a living population and (ii) compared across individuals and groups, facilitating longitudinal, genetic and interventional studies of dementia.

Orbital and dorsolateral frontal perfusion defect associated with behavioral response to cholinesterase inhibitor therapy in Alzheimer's disease.

The authors retrospectively explored the behavioral and functional imaging profile of Alzheimer's disease (AD) patients who respond to cholinesterase inhibitor therapy by using the Neuropsychiatric Inventory (NPI) and baseline [99mTc]HMPAO SPECT. Thirty AD patients were divided into three groups (Responders, Nonresponders, and Unchanged) based on their behavioral response to donepezil. Responders had significantly (P < or = 0.01) more pretreatment irritability, disinhibition (P < or = 0.05), and euphoria (P = 0.05) than Nonresponders and significantly lower lateral orbital frontal (P < 0.00001) and dorsolateral frontal (P < or = 0.0005) perfusion bilaterally. A pretreatment orbitofrontal syndrome may predict behavioral response to cholinesterase inhibitor therapy in AD.

Cerebral correlates of psychotic symptoms in Alzheimer's disease.

BACKGROUND: Psychotic symptoms are produced by distributed neuronal dysfunction. Abnormalities of reality testing and false inference implicate frontal lobe abnormalities. OBJECTIVES: To identify the functional imaging profile of patients with Alzheimer's disease manifesting psychotic symptoms as measured by single photon emission computed tomography (SPECT). METHODS: Twenty patients with Alzheimer's disease who had SPECT and clinical evaluations were divided into two equal groups with similar mini mental status examination (MMSE), age, sex, and the range of behaviours documented by the neuropsychiatric inventory (NPI), except delusions and hallucinations. SPECT studies, registered to a probabilistic anatomical atlas, were normalised across the combined group mean intensity level, and subjected to a voxel by voxel subtraction of the non-psychotic minus psychotic groups. Subvolume thresholding (SVT) corrected random lobar noise to produce a three dimensional functional significance map. RESULTS: The significance map showed lower regional perfusion in the right and left dorsolateral frontal, left anterior cingulate, and left ventral striatal regions along with the left pulvinar and dorsolateral parietal cortex, in the psychotic versus non-psychotic group. CONCLUSION: Patients with Alzheimer's disease who manifest psychosis may have disproportionate dysfunction of frontal lobes and related subcortical and parietal structures.

Left frontotemporal hypoperfusion is associated with aggression in patients with dementia.

BACKGROUND: Aggressive behavior is common in patients with dementia. Temporolimbic and prefrontal cortical lesions can produce pathological aggression; however, involvement of these structures has not been established in aggressive patients with dementia. OBJECTIVE: To study the relation between regional brain perfusion and aggressive behavior in patients with dementia. METHODS: We compared the pattern of regional cerebral perfusion determined with technetium Tc 99m-labeled hexamethylpropelene amineoxime single photon emission computed tomography in 2 groups of 10 patients with dementia with and without aggression, that were comparable for demographic factors, severity of cognitive impairments, and other behavioral symptoms as measured by the Neuropsychiatric Inventory. RESULTS: Patients with aggression revealed significant (P<.001) hypoperfusion in the left anterior temporal cortex; additional bilateral dorsofrontal and right parietal cortex were also found to be significantly hypoperfused. CONCLUSION: These results indicated an association between aggression and decreased perfusion in the left anterior temporal cortex. Arch Neurol. 2000.

Cerebral metabolic and cognitive decline in persons at genetic risk for Alzheimer's disease.

The major known genetic risk for Alzheimer's disease (AD), apolipoprotein E-4 (APOE-4), is associated with lowered parietal, temporal, and posterior cingulate cerebral glucose metabolism in patients with a clinical diagnosis of AD. To determine cognitive and metabolic decline patterns according to genetic risk, we investigated cerebral metabolic rates by using positron emission tomography in middle-aged and older nondemented persons with normal memory performance. A single copy of the APOE-4 allele was associated with lowered inferior parietal, lateral temporal, and posterior cingulate metabolism, which predicted cognitive decline after 2 years of longitudinal follow-up. For the 20 nondemented subjects followed longitudinally, memory performance scores did not decline significantly, but cortical metabolic rates did. In APOE-4 carriers, a 4% left posterior cingulate metabolic decline was observed, and inferior parietal and lateral temporal regions demonstrated the greatest magnitude (5%) of metabolic decline after 2 years. These results indicate that the combination of cerebral metabolic rates and genetic risk factors provides a means for preclinical AD detection that will assist in response monitoring during experimental treatments.

Analyzing functional brain images in a probabilistic atlas: a validation of subvolume thresholding.

PURPOSE: The development of structural probabilistic brain atlases provides the framework for new analytic methods capable of combining anatomic information with the statistical mapping of functional brain data. Approaches for statistical mapping that utilize information about the anatomic variability and registration errors of a population within the Talairach atlas space will enhance our understanding of the interplay between human brain structure and function. METHOD: We present a subvolume thresholding (SVT) method for analyzing positron emission tomography (PET) and single photon emission CT data and determining separately the statistical significance of the effects of motor stimulation on brain perfusion. Incorporation of a priori anatomical information into the functional SVT model is achieved by selecting a proper anatomically partitioned probabilistic atlas for the data. We use a general Gaussian random field model to account for the intrinsic differences in intensity distribution across brain regions related to the physiology of brain activation, attenuation effects, dead time, and other corrections in PET imaging and data reconstruction. RESULTS: H2(15)O PET scans were acquired from six normal subjects under two different activation paradigms: left-hand and right-hand finger-tracking task with visual stimulus. Regional region-of-interest and local (voxel) group differences between the left and right motor tasks were obtained using nonparametric stochastic variance estimates. As expected from our simple finger movement paradigm, significant activation (z = 6.7) was identified in the left motor cortex for the right movement task and significant activation (z = 6.3) for the left movement task in the right motor cortex. CONCLUSION: We propose, test, and validate a probabilistic SVT method for mapping statistical variability between groups in subtraction paradigm studies of functional brain data. This method incorporates knowledge of, and controls for, anatomic variability contained in modern human brain probabilistic atlases in functional statistical mapping of the brain.

Mathematical/computational challenges in creating deformable and probabilistic atlases of the human brain.

Striking variations in brain structure, especially in the gyral patterns of the human cortex, present fundamental challenges in human brain mapping. Probabilistic brain atlases, which encode information on structural and functional variability in large human populations, are powerful research tools with broad applications. Knowledge-based imaging algorithms can also leverage atlased information on anatomic variation. Applications include automated image labeling, pathology detection in individuals or groups, and investigating how regional anatomy is altered in disease, and with age, gender, handedness and other clinical or genetic factors. In this report, we illustrate some of the mathematical challenges involved in constructing population-based brain atlases. A disease-specific atlas is constructed to represent the human brain in Alzheimer's disease (AD). Specialized strategies are developed for population-based averaging of anatomy. Sets of high-dimensional elastic mappings, based on the principles of continuum mechanics, reconfigure the anatomy of a large number of subjects in an anatomic image database. These mappings generate a local encoding of anatomic variability and are used to create a crisp anatomical image template with highly resolved structures in their mean spatial location. Specialized approaches are also developed to average cortical topography. Since cortical patterns are altered in a variety of diseases, gyral pattern matching is used to encode the magnitude and principal directions of local cortical variation. In the resulting cortical templates, subtle features emerge. Regional asymmetries appear that are not apparent in individual anatomies. Population-based maps of cortical variation reveal a mosaic of variability patterns that segregate sharply according to functional specialization and cytoarchitectonic boundaries.

The spectrum of behavioral responses to cholinesterase inhibitor therapy in Alzheimer disease.

BACKGROUND: Behavioral abnormalities are common in Alzheimer disease (AD); cholinergic treatment reduces the behavioral disturbances of some patients with AD. Characterizing the pretreatment profile of patients who are likely to respond to cholinergic therapy will aid the efficient use of clinical resources. OBJECTIVE: To determine the baseline behavioral profile for 86 patients with AD treated with the cholinesterase inhibitor donepezil hydrochloride. METHODS: Open-label retrospective study of treatment-related behavioral assessments. Based on previous double-blind placebo-controlled experience using the Neuropsychiatric Inventory (NPI), patients were divided into responder (> or =4-point total NPI score decrease, indicating improvement), unchanged (+/-3-point total NPI score change), or nonresponder (> or =4-point total NPI score increase, indicating worsening) groups. The Mini-Mental State Examination assessed cognitive response. RESULTS: Behavioral improvement was seen in 35 patients (41%), worsening in 24 (28%), and no change in 27 (31%). Comparison of profiles in behavioral responders vs nonresponders revealed significantly worse delusions (P = .04), agitation (P = .04), depression (P = .006), anxiety (P = .02), apathy (P = .003), disinhibition (P = .02), and irritability (P<.001) at baseline in responders. Five behaviors changed significantly from baseline, improving for the responders and worsening for the nonresponders: delusions (P = .003 for nonresponders, P = .004 for responders), agitation (P = .01), anxiety (P = .006 for nonresponders, P = .004 for responders), disinhibition (P = .02 for nonresponders, P = .05 for responders), and irritability (P = .003 for nonresponders, P = .001 for responders). The behavioral changes were dose dependent. Cognition did not change significantly with donepezil treatment within any group. CONCLUSIONS: Donepezil has psychotropic properties, and pretreatment behaviors help predict patients' responses to treatment.