Living With Frontotemporal Degeneration: Diagnostic Journey, Symptom Experiences, and Disease Impact.

Frontotemporal degeneration (FTD) is an umbrella term encompassing a range of rare neurodegenerative disorders that cause progressive declines in cognition, behavior, and personality. Hearing directly from individuals living with FTD and their care partners is critical in optimizing care, identifying meaningful clinical trial endpoints, and improving research recruitment and retention. The current paper presents a subset of data from the FTD Insights Survey, chronicling the diagnostic journey, symptoms, and the impact of FTD on distress, quality of life, and independence, in the mild to moderate stages of the disease. Survey respondents included 219 individuals diagnosed with FTD and 437 current care partners, representing a range of FTD diagnoses. Around half of survey respondents reported seeing three or more doctors before an FTD diagnosis was given, and a range of prior diagnoses were noted. Most frequently endorsed symptoms tended to be consistent with clinical characteristics of the specific diagnosis, though there was significant variability in symptoms reported within diagnostic categories as well as considerable overlap in symptoms between diagnostic categories. Cognitive and language symptoms of FTD were generally most distressing to the person diagnosed, and a loss of independence was endorsed as affecting quality of life. The distinct perspectives of diagnosed persons and care partners regarding disease impact differed notably for bvFTD/Pick's disease. Participating independently in a range of activities, within the home, outside the home, and with other people, were reported as challenging for people living with FTD, underscoring the degree to which the lives of these individuals are affected even at the mild and moderate stages of disease. Overall, by heeding the perspectives of those living with FTD, we can begin to design more meaningful research studies, provide better care, and develop therapies that improve quality of life.

Demographic and Symptom Correlates of Initial Idiopathic Psychiatric Diagnosis in Frontotemporal Dementia.

INTRODUCTION: This study aims to measure frequency and correlates of initial idiopathic psychiatric diagnosis in a cohort of 147 patients with Frontotemporal Dementia (FTD)-spectrum disorders. METHODS: Participants were evaluated at the National Institutes of Health in Bethesda, Maryland. Initial participant diagnoses were determined by chart review and patient and informant interviews. Logistic regression was used to assess the relationships between diagnosis and age of symptom onset, gender, education, family history of psychiatric illness, and family history of dementia. Additional exploratory analyses investigated patients' first symptom type. RESULTS: 25% (n=43) of all the patients reviewed were initially misdiagnosed with an idiopathic psychiatric illness, which is less than half the commonly cited 50% rate.3 Depression was the most common misdiagnosis (46.5%). Family history of dementia, family history of mental illness and an exploratory analysis of behavioral first symptoms suggested significant association with a greater likelihood of initial idiopathic psychiatric diagnosis in FTD patients. DISCUSSION: This data confirms patterns of initial idiopathic psychiatric diagnosis in FTD and elucidates potential factors underlying misdiagnosis. Potential implications for patient outcomes, caregiver burden and healthcare costs are discussed.

Proposed research criteria for prodromal behavioural variant frontotemporal dementia.

At present, no research criteria exist for the diagnosis of prodromal behavioural variant frontotemporal dementia (bvFTD), though early detection is of high research importance. Thus, we sought to develop and validate a proposed set of research criteria for prodromal bvFTD, termed 'mild behavioural and/or cognitive impairment in bvFTD' (MBCI-FTD). Participants included 72 participants deemed to have prodromal bvFTD; this comprised 55 carriers of a pathogenic mutation known to cause frontotemporal lobar degeneration, and 17 individuals with autopsy-confirmed frontotemporal lobar degeneration. All had mild behavioural and/or cognitive changes, as judged by an evaluating clinician. Based on extensive clinical workup, the prodromal bvFTD group was divided into a Development Group (n = 22) and a Validation Group (n = 50). The Development Group was selected to be the subset of the prodromal bvFTD group for whom we had the strongest longitudinal evidence of conversion to bvFTD, and was used to develop the MBCI-FTD criteria. The Validation Group was the remainder of the prodromal bvFTD group and was used as a separate sample on which to validate the criteria. Familial non-carriers were included as healthy controls (n = 165). The frequencies of behavioural and neuropsychiatric features, neuropsychological deficits, and social cognitive dysfunction in the prodromal bvFTD Development Group and healthy controls were assessed. Based on sensitivity and specificity analyses, seven core features were identified: apathy without moderate-severe dysphoria, behavioural disinhibition, irritability/agitation, reduced empathy/sympathy, repetitive behaviours (simple and/or complex), joviality/gregariousness, and appetite changes/hyperorality. Supportive features include a neuropsychological profile of impaired executive function or naming with intact orientation and visuospatial skills, reduced insight for cognitive or behavioural changes, and poor social cognition. Three core features or two core features plus one supportive feature are required for the diagnosis of possible MBCI-FTD; probable MBCI-FTD requires imaging or biomarker evidence, or a pathogenic genetic mutation. The proposed MBCI-FTD criteria correctly classified 95% of the prodromal bvFTD Development Group, and 74% of the prodromal bvFTD Validation Group, with a false positive rate of <10% in healthy controls. Finally, the MBCI-FTD criteria were tested on a cohort of individuals with prodromal Alzheimer's disease, and the false positive rate of diagnosis was 11-16%. Future research will need to refine the sensitivity and specificity of these criteria, and incorporate emerging biomarker evidence.

Examining the Role of Aging Perceptions in Subjective Cognitive Decline.

OBJECTIVE: While subjective cognitive decline (SCD) is gaining ground as a "preclinical" risk state for Alzheimer disease, its utility depends on our understanding of the factors linked to SCD. Rarely examined sociocultural factors including perceptions of aging may relate to the subjective experience of cognitive aging. Identifying such associations will help to refine the utility of SCD as an early marker of AD while setting the stage for addressing modifiable factors contributing to SCD. METHODS: The study consisted of N=136 participants (68% female; 73% White; 22% Black race, age mean =74.72; education mean =16.01). Questionnaires assessed SCD, depressive symptoms, and age perceptions (essentialist aging beliefs, subjective age, age group identification, and explicit/implicit age stereotypes). Cognitive functioning was measured with a semantic interference and learning task. RESULTS: SCD was correlated with essentialist aging beliefs, age identification, and depressive symptoms [ rrange =0.18 to 0.22, Prange =0.009 to 0.02, confidence interval (CI) range =0.00-0.39]. Essentialist aging beliefs were correlated with subjective age and age group identification ( rrange =0.22 to 0.42, Prange <0.001 to 0.003, CI range =0.08-0.57). Both age group identification and essentialism were correlated with depressive symptoms ( rrange =0.22, Prange =0.009 to 0.01, CI range =0.04-0.39). In the adjusted regression model including depressive symptoms, age perceptions, and SCD, only SCD was associated with cognition ( b =-0.31, P <0.001). CONCLUSION: Although correlated with SCD, perceptions of aging do not explain the relationship between SCD and performance on a sensitive cognitive test among older adults.

Towards Defining the Neuroanatomical Basis of Late-Onset Psychiatric Symptoms.

Psychiatric symptoms, including changes in emotional processing, are a common feature of many neurodegenerative disorders, such as Alzheimer's disease, dementia with Lewy Bodies, frontotemporal dementia, and Huntington's disease. However, the neuroanatomical basis of emotional symptoms is not well defined; this stands in contrast to the relatively well-understood neuroanatomical correlates of cognitive and motor symptoms in neurodegenerative disorders. Furthermore, psychiatric diagnostic categories, as defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM) and International Statistical Classification of Diseases and Related Health Problems (ICD), may have limited applicability in patients with late-onset psychiatric symptoms in the context of neurodegenerative disorders. In this clinical review, we suggest that early-onset and late-onset psychiatric symptoms have distinct etiologies, and that late-onset changes in emotional processing are likely underpinned by neurodegenerative disease. Furthermore, we suggest that an improved understanding of the neuroanatomical correlates of emotional changes in neurodegenerative disease may facilitate diagnosis and future treatment development. Finally, we propose a novel clinical approach, in a preliminary attempt to incorporate late-onset emotional symptoms alongside cognitive and motor symptoms into a clinical "algorithm," with a focus on the neuroanatomy implicated when particular combinations of emotional, cognitive, and motor features are present. We anticipate that this clinical approach will assist with the diagnosis of neurodegenerative disorders, and our proposed schema represents a move towards integrating neurologic and psychiatric classification systems.

The contribution of behavioral features to caregiver burden in FTLD spectrum disorders.

INTRODUCTION: Caregivers of patients with frontotemporal lobar degeneration (FTLD) spectrum disorders experience tremendous burden, which has been associated with the neuropsychiatric and behavioral features of the disorders. METHODS: In a sample of 558 participants with FTLD spectrum disorders, we performed multiple-variable regressions to identify the behavioral features that were most strongly associated with caregiver burden, as measured by the Zarit Burden Interview, at each stage of disease. RESULTS: Apathy and disinhibition, as rated by both clinicians and caregivers, as well as clinician-rated psychosis, showed the strongest associations with caregiver burden, a pattern that was consistent when participants were separated cross-sectionally by disease stage. In addition, behavioral features appeared to contribute most to caregiver burden in patients with early dementia. DISCUSSION: Caregivers should be provided with early education on the management of the behavioral features of FTLD spectrum disorders. Interventions targeting apathy, disinhibition, and psychosis may be most useful to reduce caregiver burden.

A Comparison of Quit Outcomes for Men and Women in a Smoking Cessation Program Offering Personalized Nicotine Replacement Therapy and Counseling in Primary Care Clinics.

INTRODUCTION: Women may have greater difficulty achieving long-term abstinence following a quit attempt compared to men. We sought to determine whether there were differences in treatment characteristics or outcome between female and male primary care patients enrolled in a smoking cessation program providing personalized nicotine replacement therapy (NRT) with counseling support. AIMS AND METHODS: The sample included 27 601 Ontarians (53% female, 47% male) who enrolled in the Smoking Treatment for Ontario Patients program between 2016 and 2018. Dose, type, and duration of NRT supplied were personalized to need. Thirty-day point prevalence tobacco smoking abstinence was self-reported via online or telephone survey at 6 months after enrollment. RESULTS: Both female and male participants received a median of 8 weeks of NRT. Types of NRT received were similar, with 80% of both female and male participants receiving patch and short-acting NRT. The total cumulative dose was somewhat higher for men (1373 mg vs. 1265 mg, p < .001); but when calculated as dose per day, per cigarette smoked at baseline, the dose was slightly higher among women (1.6 mg vs. 1.5 mg, p < .001). Quit rates at 6 months were lower for women versus men (24% vs. 27%; adjusted OR = 0.84 [95% CI = 0.78 to 0.90], p < .001). There were no significant interactions between gender and dose, type, or duration of NRT supplied. CONCLUSIONS: Women were slightly less likely to quit than men, despite receiving similar treatment. There was no evidence that women benefitted more or less from variations in dose, type, or duration of NRT supplied. IMPLICATIONS: Women who received personalized NRT with counseling support in a primary care setting had lower quit success than men. Although the absolute difference in quit outcome was small, the public health impact may be large given the burden of disease associated with continued smoking. NRT supplied was similar for women and men, and there was no evidence upon which to suggest tailoring the dose, duration, or type, based on gender alone. Further research to identify the underlying biological and social factors responsible for reduced quit success will help identify ways to optimize treatment for women.

Verbal Adynamia and Conceptualization in Partial Rhombencephalosynapsis and Corpus Callosum Dysgenesis.

Verbal adynamia is characterized by markedly reduced spontaneous speech that is not attributable to a core language deficit such as impaired naming, reading, repetition, or comprehension. In some cases, verbal adynamia is severe enough to be considered dynamic aphasia. We report the case of a 40-year-old, left-handed, male native English speaker who presented with partial rhombencephalosynapsis, corpus callosum dysgenesis, and a language profile that is consistent with verbal adynamia, or subclinical dynamic aphasia, possibly underpinned by difficulties selecting and generating ideas for expression. This case is only the second investigation of dynamic aphasia in an individual with a congenital brain malformation. It is also the first detailed neuropsychological report of an adult with partial rhombencephalosynapsis and corpus callosum dysgenesis, and the only known case of superior intellectual abilities in this context.

Subthalamic deep brain stimulation identifies frontal networks supporting initiation, inhibition and strategy use in Parkinson's disease.

Initiation and inhibition are executive functions whose disruption in Parkinson's disease impacts substantially on everyday activities. Management of Parkinson's disease with subthalamic deep brain stimulation (DBS) modifies initiation and inhibition, with prior work suggesting that these effects may be mediated via the connectivity of the subthalamic nucleus (STN) with the frontal cortex. Here, we employed high-resolution structural neuroimaging to investigate the variability in initiation, inhibition and strategy use in a cohort of twenty-five (ten females, mean age 62.5, mean Hoehn and Yahr stage 2.5) participants undertaking subthalamic DBS for Parkinson's disease. Neuropsychological assessment of initiation and inhibition was performed preoperatively and at six months postoperatively. We first reconstructed the preoperative connectivity of the STN with a frontal network of anterior and superior medial cortical regions. We then modelled the postoperative site of subthalamic stimulation and reconstructed the connectivity of the stimulation field within this same network. We found that, at both pre- and postoperative intervals, inter-individual variability in inhibition and initiation were strongly associated with structural network connectivity. Measures of subcortical atrophy and local stimulation effects did not play a significant role. Preoperatively, we replicated prior work, including a role for the right inferior frontal gyrus in inhibition and strategy use, as well as the left inferior frontal gyrus in tasks requiring selection under conditions of maintained inhibition. Postoperatively, greater connectivity of the stimulation field with right anterior cortical regions was associated with greater rule violations and suppression errors, supporting prior work implicating right-hemispheric STN stimulation in disinhibition. Our findings suggest that, in Parkinson's disease, connectivity of the frontal cortex with the STN is an important mediator of individual variability in initiation and inhibition,. Personalised information on brain network architecture could guide individualised brain circuit manipulation to minimise neuropsychological disruption after STN-DBS.

Idea Formulation for Spoken Language Production: The Interface of Cognition and Language.

BACKGROUND: Language and communication are fundamental to the human experience, and, traditionally, spoken language is studied as an isolated skill. However, before propositional language (i.e., spontaneous, voluntary, novel speech) can be produced, propositional content or 'ideas' must be formulated. OBJECTIVE: This review highlights the role of broader cognitive processes, particularly 'executive attention', in the formulation of propositional content (i.e., 'ideas') for propositional language production. CONCLUSIONS: Several key lines of evidence converge to suggest that the formulation of ideas for propositional language production draws on executive attentional processes. Larger-scale clinical research has demonstrated a link between attentional processes and language, while detailed case studies of neurological patients have elucidated specific idea formulation mechanisms relating to the generation, selection and sequencing of ideas for expression. Furthermore, executive attentional processes have been implicated in the generation of ideas for propositional language production. Finally, neuroimaging studies suggest that a widely distributed network of brain regions, including parts of the prefrontal and parietal cortices, supports propositional language production. IMPLICATIONS: Theoretically driven experimental research studies investigating mechanisms involved in the formulation of ideas are lacking. We suggest that novel experimental approaches are needed to define the contribution of executive attentional processes to idea formulation, from which comprehensive models of spoken language production can be developed. Clinically, propositional language impairments should be considered in the context of broader executive attentional deficits.

Best practices in active and student-centered learning in physiology classes.

This review article includes our analysis of the literature and our own experiences in using various types of active learning as best practices for evidence-based teaching in physiology. We have evaluated what physiology students should be expected to learn and what are specific challenges to enhancing their learning of physiology principles. We also consider how the instructor should design his or her teaching to improve buy-in from both students and other faculty members. We include a discussion of how the readers can evaluate their teaching approaches for their successes in enhancing student learning of physiology. Thus we have addressed pedagogical improvements specific to student learning of physiology, with additional suggestions from cognitive psychology approaches that can improve physiology teaching and learning.

Review and evaluation of online tobacco dependence treatment training programs for health care practitioners.

BACKGROUND: Training health care professionals is associated with increased capacity to deliver evidence-based smoking cessation interventions and increased quit rates among their patients. Online training programs hold promise to provide training but questions remain regarding the quality and usability of available programs. OBJECTIVE: The aim was to assess the quality of English-language online courses in tobacco dependence treatment using a validated instrument. METHODS: An environmental scan was conducted using the Google search engine to identify available online tobacco dependence treatment courses. The identified courses were then evaluated using the Peer Review Rubric for Online Learning, which was selected based on its ability to evaluate instructional design. It also has clear and concise criteria descriptions to ensure uniformity of evaluations by trained experts. RESULTS: A total of 39 courses were identified, of which 24 unique courses were assessed based on their accessibility and functionality during the period of evaluation. Overall, the course ratings indicated that 17 of 24 courses evaluated failed to meet minimal quality standards and none of the courses evaluated could be ranked as superior. However, many excelled in providing effective navigation, course rationale, and content. Many were weak in the use of instructional design elements, such as teaching effectiveness, learning strategies, instructor's role, and assessment and evaluation. Evaluation results and suggestions for improvement were shared with course administrators. CONCLUSIONS: Based on the courses evaluated in this review, course developers are encouraged to employ best practices in instructional design, such as cohesiveness of material, linearity of design, practice exercises, problem solving, and ongoing evaluation to improve existing courses and in the design of new online learning opportunities.

0.9% saline induced hyperchloremic acidosis.

In the acute care setting, the type and amount of fluid administered has a significant impact on patient outcomes. In particular, 0.9% saline infusions are known to cause or exacerbate hyperchloremia. The studies presented evaluate possible complications from 0.9% saline infusions. These studies compared administration of 0.9% saline with lactated ringer or plasmalyte in the acute care setting. In each trial, the patients who were randomized to receive 0.9% saline infusions had a more severe acidosis from increased serum chloride levels. From the available data, chloride-restrictive intravenous fluid such as plasmalyte appears to reduce acid-base disturbances and improve patient outcomes.

Specificity of Processing α-glucosidase I is guided by the substrate conformation: crystallographic and in silico studies.

BACKGROUND: The enzyme "GluI" is key to the synthesis of critical glycoproteins in the cell. RESULTS: We have determined the structure of GluI, and modeled binding with its unique sugar substrate. CONCLUSION: The specificity of this interaction derives from a unique conformation of the substrate. SIGNIFICANCE: Understanding the mechanism of the enzyme is of basic importance and relevant to potential development of antiviral inhibitors. Processing α-glucosidase I (GluI) is a key member of the eukaryotic N-glycosylation processing pathway, selectively catalyzing the first glycoprotein trimming step in the endoplasmic reticulum. Inhibition of GluI activity impacts the infectivity of enveloped viruses; however, despite interest in this protein from a structural, enzymatic, and therapeutic standpoint, little is known about its structure and enzymatic mechanism in catalysis of the unique glycan substrate Glc3Man9GlcNAc2. The first structural model of eukaryotic GluI is here presented at 2-Å resolution. Two catalytic residues are proposed, mutations of which result in catalytically inactive, properly folded protein. Using Autodocking methods with the known substrate and inhibitors as ligands, including a novel inhibitor characterized in this work, the active site of GluI was mapped. From these results, a model of substrate binding has been formulated, which is most likely conserved in mammalian GluI.

Changes in Digital Speech Measures in Asymptomatic Carriers of Pathogenic Variants Associated With Frontotemporal Degeneration.

BACKGROUND AND OBJECTIVES: Clinical trials developing therapeutics for frontotemporal degeneration (FTD) focus on pathogenic variant carriers at preclinical stages. Objective, quantitative clinical assessment tools are needed to track stability and delayed disease onset. Natural speech can serve as an accessible, cost-effective assessment tool. We aimed to identify early changes in the natural speech of FTD pathogenic variant carriers before they become symptomatic. METHODS: In this cohort study, speech samples of picture descriptions were collected longitudinally from healthy participants in observational studies at the University of Pennsylvania and Columbia University between 2007 and 2020. Participants were asymptomatic but at risk for familial FTD. Status as "carrier" or "noncarrier" was based on screening for known pathogenic variants in the participant's family. Thirty previously validated digital speech measures derived from automatic speech processing pipelines were selected a priori based on previous studies in patients with FTD and compared between asymptomatic carriers and noncarriers cross-sectionally and longitudinally. RESULTS: A total of 105 participants, all asymptomatic, included 41 carriers: 12 men [30%], mean age 43 ± 13 years; education, 16 ± 2 years; MMSE 29 ± 1; and 64 noncarriers: 27 men [42%]; mean age, 48 ± 14 years; education, 15 ± 3 years; MMSE 29 ± 1. We identified 4 speech measures that differed between carriers and noncarriers at baseline: mean speech segment duration (mean difference -0.28 seconds, 95% CI -0.55 to -0.02, p = 0.04); word frequency (mean difference 0.07, 95% CI 0.008-0.14, p = 0.03); word ambiguity (mean difference 0.02, 95% CI 0.0008-0.05, p = 0.04); and interjection count per 100 words (mean difference 0.33, 95% CI 0.07-0.59, p = 0.01). Three speech measures deteriorated over time in carriers only: particle count per 100 words per month (ß = -0.02, 95% CI -0.03 to -0.004, p = 0.009); total narrative production time in seconds per month (ß = -0.24, 95% CI -0.37 to -0.12, p < 0.001); and total number of words per month (ß = -0.48, 95% CI -0.78 to -0.19, p = 0.002) including in 3 carriers who later converted to symptomatic disease. DISCUSSION: Using automatic processing pipelines, we identified early changes in the natural speech of FTD pathogenic variant carriers in the presymptomatic stage. These findings highlight the potential utility of natural speech as a digital clinical outcome assessment tool in FTD, where objective and quantifiable measures for abnormal behavior and language are lacking.

COPUS-TA: An "Entry-Level" Peer Observation Tool to Support Teaching Assistant Professional Pedagogical Development.

When coordinating teams of teaching assistants (TAs) in our courses, it can be time and resource prohibitive to provide mentorship for individual professional development of their teaching. Peer observation of teaching is a useful and effective approach for professional development and for forming a community of practice that TAs can engage in. However, structured peer observation can require substantial training - which may make it infeasible for large teams of TAs with variable teaching expertise and limited contract hours. This article describes the development of an observation protocol, adapted for the TA context, from the Classroom Observation Protocol for Undergraduate STEM (COPUS; by Smith et al. 2013). We have used this successfully, with very minimal training (15-min discussion plus one practice observation). I include the modified form (COPUS-TA) for practical and immediate use in supporting the development of TAs' teaching skills.

Better Writing, Brick by Brick: a Student-Centered Writing Exercise Using LEGO.

Supporting student development of clear science communication skills is critically important and incredibly challenging. In this activity, to help students understand the importance of clear written communication, students work in pairs with LEGO bricks. One student with a completed LEGO structure describes a small LEGO construction, directing a second student to build it, sight unseen. This exercise serves three aims. First, it acts as an icebreaker in the beginning of this writing-intensive course; second, it prompts thinking about the features of clear communication; and finally, it highlights challenges in written communication. The exercise is followed by a short debrief and an in-class writing assignment. Most students found the exercise to be enjoyable and useful and advised including it in future course offerings. With modifications, it also runs well in an online format, and is easily adaptable to many other course contexts.

Verbal and nonverbal fluency in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a multi-system disorder that commonly affects cognition and behaviour. Verbal fluency impairments are consistently reported in ALS patients, and we aimed to investigate whether this deficit extends beyond the verbal domain. We further aimed to determine whether deficits are underpinned by a primary intrinsic response generation impairment (i.e., a global reduction across tasks), potentially related to apathy, or an inability to maintain responding over time (i.e., a 'drop off' pattern). Twenty-two ALS patients and 21 demographically-matched controls completed verbal and nonverbal fluency tasks (phonemic/semantic word fluency, design fluency, gesture fluency and ideational fluency), requiring the generation of responses over a specified time period. Fluency performance was analysed in terms of the overall number of novel items produced, as well as the number of items produced in the first 'initiation' and the remaining 'maintenance' time periods. ALS patients' overall performance was not globally reduced across tasks. Patients were impaired only on meaningful gesture fluency, which requires the generation of gestures that communicate meaning (e.g., waving). On phonemic fluency, ALS patients showed a 'drop off' pattern of performance, where they had difficulty maintaining responding over time, but this pattern was not evident on the other fluency tasks. Apathy did not appear to be related to fluency performance. The selective meaningful gesture fluency deficit, in the context of preserved meaningless gesture fluency, highlights that the retrieval of action knowledge may be weakened in early ALS.

Mirror movements and callosal dysgenesis in a family with a DCC mutation: Neuropsychological and neuroimaging outcomes.

Corpus callosum dysgenesis is a congenital abnormality whereby the corpus callosum fails to develop normally, and has been associated with a range of neuropsychological outcomes. One specific finding in some individuals with corpus callosum dysgenesis is "congenital mirror movement disorder", which is the presence of involuntary movements on one side of the body that mimic voluntary movements of the other side. Mirror movements have also been associated with mutations in the deleted in colorectal carcinoma (DCC) gene. The current study aims to comprehensively document the neuropsychological outcomes and neuroanatomical mapping of a family (a mother, daughter and son) with known DCC mutations. All three family members experience mirror movements, and the son additionally has partial agenesis of the corpus callosum (pACC). All family members underwent extensive neuropsychological testing, spanning general intellectual functioning, memory, language, literacy, numeracy, psychomotor speed, visuospatial perception, praxis and motor functioning, executive functioning, attention, verbal/nonverbal fluency, and social cognition. The mother and daughter had impaired memory for faces, and reduced spontaneous speech, and the daughter demonstrated scattered impairments in attention and executive functioning, but their neuropsychological abilities were largely within normal limits. By contrast, the son showed areas of significant impairment across multiple domains including reduced psychomotor speed, fine motor dexterity and general intellectual functioning, and he was profoundly impaired across areas of executive functioning and attention. Reductions in his verbal/non-verbal fluency, with relatively intact core language, resembled dynamic frontal aphasia. His relative strengths included aspects of memory and he demonstrated largely sound theory of mind. Neuroimaging revealed an asymmetric sigmoid bundle in the son, connecting, via the callosal remnant, the left frontal cortex with contralateral parieto-occipital cortex. Overall, this study documents a range of neuropsychological and neuroanatomical outcomes within one family with DCC mutations and mirror movements, including one with more severe consequences and pACC.

Association of Subjective Cognitive Decline With Progression to Dementia in a Cognitively Unimpaired Multiracial Community Sample.

BACKGROUND AND OBJECTIVES: This prospective study seeks to examine the utility of subjective cognitive decline (SCD) as a marker of future progression to dementia in a community-based cohort of non-Latinx White, non-Latinx Black, and Latinx individuals. Debate surrounds the utility of SCD, the subjective perception of decline in one's cognition before such impairment is evident in traditional neuropsychological assessments, as an early indicator of impending Alzheimer disease. Unfortunately, most studies examining SCD have been conducted in non-Latinx White samples and commonly exclude groups of individuals shown to be most vulnerable to dementia. METHODS: Participants were enrolled into this cohort study from the Washington Heights-Inwood Columbia Aging Project if they were cognitively unimpaired, had baseline measurement of SCD, and self-identified as non-Latinx White, non-Latinx Black, or Latinx. SCD was measured as a continuous sum of 10 items assessing cognitive complaints. Competing risk models tested the main effects of baseline SCD on progression to dementia. Models were adjusted for age, sex/gender, years of education, medical comorbidity burden, enrollment cohort, and baseline memory test performance with death jointly modelled as a function of race/ethnicity. RESULTS: A total of 4,043 (1,063 non-Latinx White, 1,267 non-Latinx Black, and 1,713 Latinx) participants were selected for this study with a mean age of 75 years, 67% women, and with a mean follow-up of 5 years. Higher baseline SCD was associated with increased rates of incident dementia over time in the full sample (hazard ratio [HR] 1.085, CI 1.047-1.125, p < 0.001) and within Latinx (HR 1.084, CI 1.039-1.130, p < 0.001) and non-Latinx Black individuals (HR 1.099, CI 1.012-1.194, p = 0.024). DISCUSSION: Overall results of this study support SCD as a prodromal marker of dementia in a multiracial community sample, and in Latinx and non-Latinx Black individuals in particular. Because models examining the risk of dementia were adjusted for baseline memory test performance, the results support the idea that SCD, a subjective reflection of one's own current cognitive functioning, contributes information above and beyond standard memory testing. Current findings highlight the importance of carefully evaluating any memory concerns raised by older adults during routine visits and underscore the potential utility of screening older adults for SCD.