Showing papers by "Katherine P. Rankin published in 2021"

Psychosis in neurodegenerative disease: differential patterns of hallucination and delusion symptoms.

Abstract: 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.

Sex differences in the behavioral variant of frontotemporal dementia: A new window to executive and behavioral reserve

Abstract: Author(s): Illan-Gala, Ignacio; Casaletto, Kaitlin B; Borrego-Ecija, Sergi; Arenaza-Urquijo, Eider M; Wolf, Amy; Cobigo, Yann; Goh, Sheng Yang M; Staffaroni, Adam M; Alcolea, Daniel; Fortea, Juan; Blesa, Rafael; Clarimon, Jordi; Iulita, Maria Florencia; Brugulat-Serrat, Anna; Llado, Albert; Grinberg, Lea T; Possin, Katherine; Rankin, Katherine P; Kramer, Joel H; Rabinovici, Gil D; Boxer, Adam; Seeley, William W; Sturm, Virginia E; Gorno-Tempini, Maria Luisa; Miller, Bruce L; Sanchez-Valle, Raquel; Perry, David C; Lleo, Alberto; Rosen, Howard J | Abstract: IntroductionBiological sex is an increasingly recognized factor driving clinical and structural heterogeneity in Alzheimer's disease, but its role in the behavioral variant of frontotemporal dementia (bvFTD) is unknown.MethodsWe included 216 patients with bvFTD and 235 controls with magnetic resonance imaging (MRI) from a large multicenter cohort. We compared the clinical characteristics and cortical thickness between men and women with bvFTD and controls. We followed the residuals approach to study behavioral and cognitive reserve.ResultsAt diagnosis, women with bvFTD showed greater atrophy burden in the frontotemporal regions compared to men despite similar clinical characteristics. For a similar amount of atrophy, women demonstrated better-than-expected scores on executive function and fewer changes in apathy, sleep, and appetite than men.DiscussionOur findings suggest that women might have greater behavioral and executive reserve than men, and neurodegeneration must be more severe in women to produce symptoms similar in severity to those in men.

Measuring Behavior and Social Cognition in FTLD.

Abstract: Because changes to socioemotional cognition and behavior are an early and central symptom in many of the FTLD syndromes, an objective and standardized approach to patient identification and staging relies on availability of validated socioemotional measures. Such tests should reflect functioning in key selectively vulnerable brain networks central to socioemotional behavior, specifically the intrinsically connected networks underpinning salience (SN) and semantic appraisal (SAN). There have been many challenges to the development of appropriate tests for patients with the FTLD syndromes, including the difficulty of creating standardized evaluations for the highly idiosyncratic deficits caused by salience-driven attention impairments, the trade-off between behaviorally or psychophysiologically precise measures versus the need for easily administered measures that can scale to broader clinical contexts, and the complexities of measuring socioemotional behavior across linguistically and culturally diverse samples. A subset of available socioemotional tests are reviewed with respect to evidence for their ability to reflect structural and functional changes to the FTLD-specific SN and SAN networks, and their differential diagnostic utility in the neurodegenerative disease syndromes is discussed.

Reduced synchrony in alpha oscillations during life predicts post mortem neurofibrillary tangle density in early-onset and atypical Alzheimer's disease.

Abstract: Introduction Neurophysiological manifestations selectively associated with amyloid beta and tau depositions in Alzheimer's disease (AD) are useful network biomarkers to identify peptide specific pathological processes. The objective of this study was to validate the associations between reduced neuronal synchrony within alpha oscillations and neurofibrillary tangle (NFT) density in autopsy examination, in patients with AD. Methods In a well-characterized clinicopathological cohort of AD patients (n = 13), we quantified neuronal synchrony within alpha (8-12 Hz) and delta-theta (2-8 Hz) oscillations, using magnetoencephalography during the disease course, within six selected neocortical and hippocampal regions, including angular gyrus, superior temporal gurus, middle frontal gyrus, primary motor cortex, CA1, and subiculum, and correlated these with regional NFT density quantified at histopathological examination. Results Abnormal synchrony in alpha, but not in delta-theta, significantly predicted the NFT density at post mortem neuropathological examination. Discussion Reduced alpha synchrony is a sensitive neurophysiological index associated with pathological tau, and a potential network biomarker for clinical trials, to gauge the extent of network dysfunction and the degree of rescue in treatments targeting tau pathways in AD.

What Do We Mean by Behavioral Disinhibition in Frontotemporal Dementia

Abstract: Behavioral variant frontotemporal dementia, unlike other forms of dementia, is primarily characterized by changes in behavior, personality, and language, with disinhibition being one of its core symptoms. However, because there is no single definition that captures the totality of behavioral symptoms observed in these patients, disinhibition is an umbrella term used to encompass socially disruptive or morally unacceptable behaviors that may arise from distinct neural etiologies. This paper aims to review the current knowledge about behavioral disinhibition in this syndrome, considering the cultural factors related to our perception of behavior, the importance of phenomenological interpretation, neuroanatomy, the brain networks involved and, finally, a new neuroscientific theory that offers a conceptual framework for understanding the diverse components of behavioral disinhibition in this neurodegenerative disorder.

Salience driven attention is pivotal to understanding others' intentions.

Abstract: Interpreting others’ beliefs, desires and intentions is known as “theory of mind” (ToM), and is often evaluated using simplified measurement tools, which may not correctly reflect the brain circuit...

Empathy and its associations with age and sociodemographic characteristics in a large UK population sample.

Abstract: OBJECTIVES: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Detecting Alzheimer’s disease biomarkers with a brief tablet-based cognitive battery: sensitivity to Aβ and tau PET

Abstract: β-amyloid (Aβ) and tau positron emission tomography (PET) detect the pathological changes that define Alzheimer’s disease (AD) in living people. Cognitive measures sensitive to Aβ and tau burden may help streamline identification of cases for confirmatory AD biomarker testing. We examined the association of Brain Health Assessment (BHA) tablet-based cognitive measures with dichotomized Aβ -PET status using logistic regression models in individuals with mild cognitive impairment (MCI) or dementia (N = 140; 43 Aβ-, 97 Aβ+). We also investigated the relationship between the BHA tests and regional patterns of tau-PET signal using voxel-wise regression analyses in a subsample of 60 Aβ+ individuals with MCI or dementia. Favorites (associative memory), Match (executive functions and speed), and Everyday Cognition Scale scores were significantly associated with Aβ positivity (area under the curve [AUC] = 0.75 [95% CI 0.66–0.85]). We found significant associations with tau-PET signal in mesial temporal regions for Favorites, frontoparietal regions for Match, and occipitoparietal regions for Line Orientation (visuospatial skills) in a subsample of individuals with MCI and dementia. The BHA measures are significantly associated with both Aβ and regional tau in vivo imaging markers and could be used for the identification of patients with suspected AD pathology in clinical practice.

The Role of Spirituality in Conceptualizations of Health Maintenance and Healthy Aging Among Latin American Immigrants.

Abstract: Objectives We aimed to investigate ways in which spirituality was conceptualized in relationship to maintaining brain health and healthy aging in a cohort of older adults who immigrated to the United States from diverse regions of Latin America, in order to ultimately develop culturally-tailored brain health promotion approaches. Design We conducted a qualitative study using semi-structured interviews. Setting Participants were recruited from community centers and by a memory care center at a large academic medical center. Participants We interviewed 30 Spanish-speaking immigrants over age 60. Questions addressed perspectives about the brain, aging, and dementia. Interviews were coded for themes. Measurements Thematic analysis was used to analyze participants’ responses. Results We identified 5 themes: (1) expressing gratitude to God for mental and physical health, (2) putting the onus of life and death in God's hands, (3) using church as a place to socialize and build community as an approach to leading a healthy lifestyle, (4) using prayer as nourishment for the soul and the brain, and (5) gaining inner-peace and calm, and thus maintaining a healthy life, due to a connection with God. Conclusion The incorporation of customized spiritual interventions may be a mechanism by which to increase the effectiveness of brain health promotion efforts.

Social Behavior Observer Checklist: Patterns of Spontaneous Behaviors Differentiate Patients With Neurodegenerative Disease From Healthy Older Adults.

Abstract: Neurodegenerative disease syndromes often affect personality and interpersonal behavior in addition to cognition, but there are few structured observational measures of altered social demeanor validated for this population. We developed the Social Behavior Observer Checklist (SBOCL), a 3-min checklist tool, to facilitate identification of patterns of interpersonal behavior that are diagnostically relevant to different neurodegenerative syndromes. Research assistants without formal clinical training in dementia used the SBOCL to describe participants' behavior, including 125 healthy older adults and 357 patients diagnosed with one of five neurodegenerative disease syndromes: 135 behavioral variant frontotemporal dementia (bvFTD), 57 semantic variant primary progressive aphasia (svPPA), 51 non-fluent variant PPA (nfvPPA), 65 progressive supranuclear palsy (PSP), and 49 amyloid-positive Alzheimer's disease syndrome (AD), all of whom had concurrent 3D T1 MRI scans available for voxel-based morphometry analysis. SBOCL item interrater reliability ranged from moderate to very high, and score elevations showed syndrome-specific patterns. Subscale scores derived from a degree*frequency product of the items had excellent positive predictive value for identifying patients. Specifically, scores above 2 on the Disorganized subscale, and above 3 on the Reactive and Insensitive subscales, were not seen in any healthy controls but were found in many patients with bvFTD, svPPA, nfvPPA, PSP, and AD syndromes. Both the Disorganized and Reactive subscale scores showed significant linear relationships with frontal and temporal gray matter volume that generalized across syndromes. With these initial psychometric characteristics, the SBOCL may be a useful measure to help non-experts identify patients who are appropriate for additional specialized dementia evaluation, without adding time to patient encounters or requiring the presence of an informant.

Clinical, neuroimaging, and neuropathological characterization of a patient with Alzheimer's disease syndrome due to Pick's pathology.

Abstract: The most common neurodegenerative syndrome associated with Pick's disease pathology (PiD) is behavioral variant frontotemporal dementia (bvFTD), which features profound social behavioral changes. Rarely, PiD can manifest as an Alzheimer's disease (AD)-type dementia with early memory impairment. We describe a patient with AD-type dementia and pure PiD pathology who showed slowly progressive memory impairment, early social changes, and paucity of motor symptoms. Atrophy and PiD were found mainly in frontotemporal regions underlying social behavior. This report may help predict the pathology of patients with atypical AD, which will ultimately be critical for enrolling suitable subjects into disease-modifying clinical trials.

Genetic pleiotropy and the shared pathological features of corticobasal degeneration and progressive supranuclear palsy: a case report and a review of the literature.

Abstract: Though distinct pathological entities, corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) share multiple biochemical and genetic features suggesting overlapping pathophysiolog...

Right Anterior Temporal Degeneration, Emotions, and Loss of Nonverbal Semantics: Guidelines for Diagnosis of the Emotional Semantic Variant Frontotemporal Dementia

Abstract: Anterior temporal lobe (ATL) degeneration is caused by a pathological process that has a focal onset in the left or right hemisphere. Patients with left-lateralized ATL atrophy typically meet criteria for semantic variant primary progressive aphasia (PPA), a clinical syndrome characterized by loss of verbal semantic knowledge. There is less consensus regarding the symptoms that emerge when atrophy targets the right ATL (rATL), but previous studies have emphasized prosopagnosia as well as alterations in emotion, memory, behavior, and semantic knowledge, symptoms that often lead to a diagnosis of behavioral variant frontotemporal dementia (bvFTD). The goal of the present study was to characterize the cognitive and socioemotional deficits of patients with rATL degeneration in order to refine current conceptualizations of the rATL clinical syndrome. We identified individuals clinically diagnosed as bvFTD or PPA in our cohort of patients prospectively evaluated for FTD-spectrum disorders. We selected patients who also underwent structural MRI and a comprehensive, multidisciplinary evaluation (n = 478). Based on structural MRI atrophy index, individuals with predominant, rATL atrophy (n = 46) were identified and patients with co-occurrence of significant frontal atrophy were excluded. Nineteen patients with rATL degeneration had undergone autopsy. We used the clinical histories to identify early symptoms and examined the cognitive, socioemotional, genetic, and pathological profiles of patients with rATL degeneration. In patients with rATL degeneration, the most common early clinical symptoms were loss of empathy (27%), person-specific semantic knowledge (23%), and complex compulsions (18%). On socioemotional testing and informant-reported measures, patients exhibited diminished interpersonal warmth, empathy, and emotional theory of mind. Neuropsychological testing revealed deficits in identifying famous people and discriminating facial affect despite preserved face perception. FTLD-TDP was the most frequent pathological correlate of rATL degeneration (84%), followed by Pick’s type (10%), a subtype of FTLD-tau. Our results indicate that patients with early, rATL-predominant degeneration present with a behavioral syndrome that results from loss of empathy for others. The underlying mechanism is a progressive loss of semantic knowledge for concepts of social-emotional relevance. We herein refer to this syndrome as “emotional semantic variant frontotemporal dementia.” We propose novel diagnostic criteria for this rATL syndrome in order to facilitate early identification in clinical and research settings. This classification is relevant because, if appropriately diagnosed, these patients most often have FTLD-TDP Type-C pathology.