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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Psychotic symptoms are an important and increasingly recognized aspect of Alzheimer's disease (AD). They have been shown to contribute to faster disease progression in clinic-based, demographically homogenous samples with high educational attainment.Objective: We studied the association between baseline psychotic symptoms and disease progression among individuals with incident AD or 'at risk' of developing AD, from a demographically heterogenous, community-based cohort with minimal educational attainment.Methods: 212 participants received the Columbia University Scale of Psychopathology in Alzheimer's Disease scale. Participants had psychotic symptoms with any of: visual illusions, delusions, hallucinations, or agitation/aggression. Disease progression was measured yearly and defined by meeting cognitive (≤10 on the Folstein MMSE) or functional endpoints (≥10 on the Blessed Dementia Rating Scale or ≥4 on the Dependence Scale).Results: The mean age was 85 years old. The cohort was 78.3% female, 75.9% Hispanic, and had a mean 6.96 years of education. Within the follow-up period (mean: 3.69 years), 24 met the cognitive endpoint, 59 met the functional endpoint, and 132 met the cutoff for dependence. The presence of at least one psychotic symptom was initially associated with an increased risk of reaching the functional endpoint (HR 3.12, 95% CI 1.67-5.86, p < 0.001) and the endpoint of dependence (HR = 1.498, 95% CI 1.05-2.13, p = 0.03). However, these associations were attenuated and non-significant when adjusted for baseline functional status. Psychotic symptoms were not associated with the cognitive endpoint.Conclusion: Psychotic symptoms may predict functional decline in patients of non-Caucasian ethnicity and with lower educational attainment. [ABSTRACT FROM AUTHOR]

Alzheimer's disease causes both cognitive and non-cognitive symptoms. There is increasing evidence that the presentation and course of Alzheimer's disease is highly heterogenous. This heterogeneity presents challenges to patients, their families, and clinicians due to the difficulty in prognosticating future symptoms and functional impairment. Behavioral and psychiatric symptoms are emerging as a significant contributor to this clinical heterogeneity. These symptoms have been linked to multiple areas of neurodegeneration, which may suggest that they are representative of network-wide dysfunction in the brain. However, current diagnostic criteria for Alzheimer's disease focus exclusively on the cognitive aspects of disease. Behavioral and psychiatric symptoms have been found in multiple studies to be related to disease severity and to contribute to disease progression over time. A better understanding of how behavioral and psychiatric symptoms relate to cognitive aspects of Alzheimer's disease would help to refine the models of disease and hopefully lead to improved ability to develop therapeutic options for this devastating disease. [ABSTRACT FROM AUTHOR]

Background: Routine healthcare visits offer the opportunity to screen older adults for cognitive changes that accompany the earliest clinical stages of Alzheimer's disease (AD) including Mild Cognitive Impairment (MCI) and Subjective Cognitive Decline (SCD). It is well‐established that women are at increased risk for AD and that many women see their gynecologist as their primary care doctor. Given this unique relationship, the Women's Preventive Services Initiative and the American College of Obstetrics and Gynecology now advocate for integrated care of women at all ages. Memory screening of older women should be paramount in this effort. Research is needed to determine which screening tools are most effective and practical. Here we assess the feasibility and utility of a subjective memory screener at the well‐woman visit. Method: Women aged 60 and above completed a 5‐item screener at their well‐woman visit at the Columbia University Integrated Women's Health Center (Table 1). Women who endorsed any item were considered to have a positive screen and were given the option to pursue clinical evaluation for memory concerns through the Division of Aging and Dementia. Result: Only 8 of 354 women declined to complete the screener. Of the completed screeners, 16% (n = 56) were positive. The most frequently endorsed item was difficulty with memory or thinking compared to others the same age (8%, n = 28) (See Table 1). 44% (n = 24) of women with positive screens pursued referral, and six have been seen to date. One woman was diagnosed with MCI. Clinical impressions of the remainder were unremarkable. All six cases had family history of dementia or memory problems. Conclusion: The well‐woman visit provides a key opportunity to routinely screen older women for early indicators of AD and treatable causes of cognitive impairment. Preliminary results support the feasibility and value of such screening as part of a comprehensive well‐woman program. Early identification of women experiencing SCD will enable investigation into the cause of their memory concerns, and longitudinal monitoring of cognitive change. Future work should evaluate the added value of an objective cognitive screen to complement SCD screening and identify women who may benefit from further evaluation. [ABSTRACT FROM AUTHOR]

Background: At present, no research criteria exist for the diagnosis of prodromal behavioral variant frontotemporal dementia (bvFTD). Leveraging data from carriers of pathogenic genetic mutations as a proxy for frontotemporal lobar degeneration pathology, we sought to develop and test a proposed set of research criteria for prodromal bvFTD, termed "Mild Behavioral and/or Cognitive Impairment in bvFTD" (MBCI‐FTD). Method: Participants included 68 carriers of a pathogenic mutation in microtubule‐associated protein tau (MAPT), or progranulin (GRN), or a repeat expansion in chromosome 9 open reading frame 72 (C9orf72), with mild behavioral and/or cognitive changes. Based on extensive clinical workup, the prodromal mutation carrier group was divided into a Development Group (N=22) and a Test Group (N=46). The Development Group was selected to be the subset of the prodromal mutation carriers for whom we had longitudinal evidence of conversion to a bvFTD phenotype, and were used to develop the criteria. The Test Group was the remainder of the prodromal mutation carriers (e.g., single visits only) and was used to validate the criteria. Familial non‐carriers were included as controls (N=165). Result: Frequencies of behavioral and neuropsychiatric features, neuropsychological deficits, and social cognitive dysfunction in prodromal mutation carriers and non‐carrier controls were assessed. Based on sensitivity and specificity analyses, seven core features were identified: apathy without moderate‐severe dysphoria, behavioral disinhibition, irritability/agitation, reduced empathy/sympathy, repetitive behaviors (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 behavioral 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 Development Group of prodromal mutation carriers, and 41% of the Test Group, with a false positive rate of <10%. Conclusion: We present the first diagnostic criteria for prodromal bvFTD. Future research should prioritize establishing generalizability to non‐genetic cases, and testing the specificity of these criteria against psychiatric, neurologic and other neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Background: Frontotemporal dementia (FTD) can present with significant phenotypic heterogeneity. Most cases of sporadic FTD do not present for diagnosis until functional impairment is evident, making it difficult to identify and characterize the earliest features of FTD. Focusing on participants from families with known FTD‐causing pathogenic mutations allows for the characterization of the earliest features of FTD in genetic carriers. Method: The ARTFL and LEFFTDS consortia (AG063911, AG045390, NS092089, AG016976) are joint, multi‐center cohort studies of patients with FTLD, including symptomatic and asymptomatic family members. For this study, a subset of ARTFL/LEFFTDS participants from families with known genetic mutations were selected if they were determined by a study physician to have (a) a phenotype of Mild Behavioral / Cognitive Impairment (MBI/MCI) and CDR®+NACC‐FTLD = 0.5 (44 participants, 19 C9orf72, 12 GRN, 13 MAPT mutations), or (b) CDR®+NACC‐FTLD = 1 (33 participants, 16 C9orf72, 10 GRN, 7 MAPT mutations). We examined the NACC Uniform Data Set (UDS) B9F form, bvFTD criteria. Pearson chi‐squared tests compared the frequency of identified bvFTD features between MBI/MCI and bvFTD participants. Result: The most common bvFTD diagnostic criteria features questionably or definitely present in the 44 MBI/MCI participants were Apathy and Disinhibition, both at 30% (Within the early FTLD group: Apathy at 70% and Disinhibition at 72%). Neuropsychological testing deficits consistent with bvFTD were present in 27% (72%), and loss of empathy in 25% (72%). Impaired daily functioning was next at 16% (81%), Ritualistic behaviors were observed in 7%, (36%) and Hyperorality in 5% (33%). Chi‐squared tests revealed significant differences between the two groups for all features, with the largest numerical and statistical difference in impaired daily functioning. Conclusion: Apathy and Disinhibition were the most common neuropsychiatric symptoms noted in FLTD MBI/MCI. Development of impairments in daily functioning best distinguished the MBI/MCI and FTLD groups. This may be related to the requirement of functional impairment for the diagnosis of dementia. The relative frequency of different features in early dementia of genetic FTLD is similar to that reported in sporadic bvFTD. As more longitudinal data is collected, within‐subject assessment of the development of features in genetic bvFTD over time will be instructive. [ABSTRACT FROM AUTHOR]