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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

Although executive dysfunction is the characteristic cognitive marker of behavioral variant frontotemporal dementia (bvFTD), episodic memory deficits are relatively common, and may be present even during the prodromal disease phase. In a cohort of mutation carriers with mild behavioral and/or cognitive symptoms consistent with prodromal bvFTD, we aimed to investigate patterns of performance on an abbreviated list learning task, with a particular focus on recognition memory. We further aimed to characterize the cognitive prodromes associated with the three major genetic causes of frontotemporal dementia, as emerging evidence suggests there may be subtle differences in cognitive profiles among carriers of different genetic mutations. Participants included 57 carriers of a pathogenic mutation in microtubule-associated protein tau (MAPT, N=23), or progranulin (GRN, N=15), or a or a hexanucleotide repeat expansion in chromosome 9 open reading frame 72 (C9orf72, N=19), with mild cognitive and/or behavioral symptoms consistent with prodromal bvFTD. Familial non-carriers were included as controls (N=143). All participants completed a comprehensive neuropsychological examination, including an abbreviated list learning test assessing episodic memory recall and recognition. MAPT mutation carriers performed worse than non-carriers in terms of list recall, and had difficulty discriminating targets from distractors on the recognition memory task, primarily due to the endorsement of distractors as targets. MAPT mutation carriers also showed nonverbal episodic memory and semantic memory dysfunction (object naming). GRN mutation carriers were variable in performance and overall the most dysexecutive. Slowed psychomotor speed was evident in C9orf72 repeat expansion carriers. Identifying the earliest cognitive indicators of bvFTD is of critical clinical and research importance. List learning may be a sensitive cognitive marker for incipient dementia in MAPT and potentially a subset of GRN carriers. Our results highlight that distinct cognitive profiles may be evident in carriers of the three disease-causing genes during the prodromal disease stage.

Background: Dependence has been proposed as a holistic, transparent, and meaningful representation of dementia disease severity to quantify and stage disease progression. Modeling clusters in dependence trajectories can help understand changes over time in the course of dementia and related cost of care. Method: 199 initially community‐living patients with probable AD in early stages of the disease were recruited to the Predictors 2 Study from three academic medical centers in the US. Patients were followed for up to 10 years and had at least two Dependence Scale (DS) recorded. Non‐parametric K‐means cluster analysis for longitudinal data (KmL) was used to identify dependence clusters. Medicare expenditures (1999‐2010) were compared between clusters at 6‐month intervals and cumulatively over 5 years. Result: KmL identified two distinct DS clusters: (A) high initial dependence, faster decline, and (B) low initial dependence, slower decline. At baseline, DS score in cluster A was on average 2.25 points higher than in cluster B (p

Extreme longevity is associated with resilience to Alzheimer’s disease. A major goal of centenarian studies is therefore to identify factors associated with maintaining cognitive function throughout life. Over the past year, two studies of centenarians and their offspring (age 60-110+ years) have pivoted from in-home assessments of cognitive and physical function to hybridized, Zoom-based assessments including comprehensive cognitive testing, blood pressure, grip strength, and accelerometry and biological sample collections. Protocols were optimized for accessibility for individuals with limited technology experience (e.g., investigator remotely controls all functions of the participant’s tablet) and sensory impairments (e.g., integration of wireless headphones) and include high-sensitivity data collection (e.g., sensor-based wearables and digital recording of cognitive test responses). Advantages of virtual administration included the ability to accommodate fatigue through multi-day assessment and to include geographically-isolated individuals. Disadvantages included participant burden due to equipment setup and inability to collect certain measures virtually (e.g., carotid ultrasounds).

Subjective cognitive decline may reflect a dementia prodrome or modifiable risk factor such as sleep disturbance. What is the association between sleep and subjective cognitive decline? Cross-sectional design, from two studies of older adults: the WHICAP in the USA and the HELIAD in Greece. A total of 1,576 WHICAP and 1,456 HELIAD participants, without mild cognitive impairment, dementia or severe depression/anxiety, were included. Participants were mostly women, with 12 (WHICAP) and 8 (HELIAD) mean years of education. Sleep problems were estimated using the Sleep Scale from the Medical Outcomes Study. Subjective cognitive decline was assessed using a structured complaint questionnaire that queries for subjective memory and other cognitive symptoms. Multinomial or logistic regression models were used to examine whether sleep problems were associated with complaints about general cognition, memory, naming, orientation and calculations. Age, sex, education, sleep medication, use of medications affecting cognition, co-morbidities, depression and anxiety were used as co-variates. Objective cognition was also estimated by summarizing neuropsychological performance into composite z-scores. Sleep problems were associated with two or more complaints: WHICAP: β = 1.93 (95% confidence interval: 1.59–2.34), p ≤ .0001; HELIAD: β = 1.48 (95% confidence interval: 1.20–1.83), p ≤ .0001. Sleep problems were associated with complaints in all the cognitive subcategories, except orientation for the WHICAP. The associations were noted regardless of objective cognition. At any given level of objective cognition, sleep disturbance is accompanied by subjective cognitive impairment. The replicability in two ethnically, genetically and culturally different cohorts adds validity to our results. The results have implications for the correlates, and potential aetiology of subjective cognitive decline, which should be considered in the assessment and treatment of older adults with cognitive complaints.

Objectives: To examine how misidentification of dementia affects estimation of Medicare costs in a largely minority cohort of participants for whom accurate in‐person diagnoses are available. Design: Prospective cohort study. Setting: Washington Heights‐Inwood Columbia Aging Project, a multiethnic, population‐based, prospective study of cognitive aging of Medicare beneficiaries aged 65 and older. Participants: Individuals clinically diagnosed with dementia (n=495) and individuals clinically diagnosed without dementia (n=1,701). Measurements: Medicare claims‐identified dementia was defined according to the presence of any International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes for Alzheimer's disease and related dementias in all available claims during the study period. Participant characteristics associated with claims misidentification of dementia were estimated using logistic regression. Effects of dementia misidentification on Medicare expenditures were estimated using generalized linear models. Results: Medicare claims correctly identified 250 of the 495 (51%) dementia cases and 1,565 of the 1,701 (92%) nondementia cases. Sensitivity of claims‐identified dementia was 0.51, and specificity was 0.92. Average annual Medicare expenditures were $14,721 for a beneficiary with a clinical diagnosis of dementia, and $18,208 for a beneficiary with claim‐identified dementia, suggesting an overestimation of $3,487 per person per year when Medicare claims were used to identify dementia. Total annual expenditures for all beneficiaries with claims‐identified dementia were $258,707 lower than that for all those who were clinically diagnosed, suggesting an overall underestimation of total Medicare expenditures if Medicare claims were used to identify dementia. Different types of misidentification have different effects on dementia‐related cost estimates. Average annual expenditures per person were highest for false positives. Conclusion: Misidentification of dementia in Medicare claims is common. Using claims to identify dementia may result in significantly biased estimates of the cost of dementia.

Objective: Financial Capacity (FC) is not a unidimensional construct, and therefore it cannot be assumed that all elements of FC decline with aging. Indeed, aspects of FC that rely on crystallized knowledge could be expected to improve rather than decline with age. The current study sought to thoroughly investigate the cognitive correlates of FC dimensions in older adults (OAs). Method: The sample included 31 healthy older adults (Dementia Rating Scale mean score = 140.9 (2.56); 73.51% female, 70.6% Caucasian) with an average age of 67.9 (SD = 5.28) and 16.12 (SD = 2.07) years of education. Financial items from the Financial Competency Assessment Inventory (FCAI) were used to measure overall FC and its five dimensions - Everyday Financial Abilities (EFA), Financial Judgement (FJ), Estate management (EM), Financial Cognition (FC), need for Support Resources (SR). Cognition was measured using a comprehensive battery of tests measuring aspects of crystallized (vocabulary, financial literacy) and fluid (inhibition, working memory) abilities. Results: After adjusting for multiple associations, vocabulary was associated with EFA, FJ and FC, whereas inhibition was related to FJ and EM. Overall FC was associated with both vocabulary (r = .67, p < .001) and inhibition (r = .61, p < .001). Financial literacy was not associated with any dimension, but written arithmetic was correlated with EFA, FC and FJ, and oral arithmetic with EM. Conclusions: In OAs, we present partial evidence for the multidimensional nature of FC as different cognitive abilities uniquely relate to specific FC dimensions. However, the influence of crystallized versus fluid abilities is not clear cut, as a few FC dimensions correlated with both of these abilities. Thus, whereas some FC dimensions such as EFA may be preserved or may improve with age, others such as FJ may decline, and still others such as EM may not show a clear pattern. Longitudinal studies or case-control matched studies will help shed light on the trajectories of FC dimensions.

BACKGROUND: Few studies have examined patterns of health care utilization and costs during the period around incident dementia. METHODS: Participants were drawn from the Washington Heights-Inwood Columbia Aging Project, a multiethnic, population-based, prospective study of cognitive aging of Medicare beneficiaries in a geographically defined area of northern Manhattan. Medicare utilization and expenditure were examined in individuals with clinically diagnosed dementia from 2 years before until 2 years after the initial diagnosis. A sample of non-demented individuals who were matched on socio-demographic and clinical characteristics at study enrollment was used as controls. Multivariable regression analysis estimated effects on Medicare utilization and expenditures associated with incident dementia. RESULTS: During the 2 years before incident dementia, rates of inpatient admissions and outpatient visits were similar between dementia patients and non-demented controls, but use of home health and skilled nursing care and durable medical equipment were already higher in dementia patients. Results showed a small but significant excess increase associated with incident dementia in inpatient admissions but not in other areas of care. In the 2 years before incident dementia, total Medicare expenditures were already higher in dementia patients than in non-demented controls. But we found no excess increases in Medicare expenditures associated with incident dementia. CONCLUSIONS: Demand for medical care already is increasing and costs are higher at the time of incident dementia. There was a small but significant excess risk of inpatient admission associated with incident dementia.

OBJECTIVES: The aim of this study is to examine the relative contribution of functional impairment and cognitive deficits on risk of hospitalization and costs. METHODS: A prospective cohort of Medicare beneficiaries aged 65 and older who participated in the Washington Heights-Inwood Columbia Aging Project (WHICAP) were followed approximately every 18 months for over 10 years (1805 never diagnosed with dementia during study period, 221 diagnosed with dementia at enrollment). Hospitalization and Medicare expenditures data (1999-2010) were obtained from Medicare claims. Multivariate analyses were conducted to examine (1) risk of all-cause hospitalizations, (2) hospitalizations from ambulatory care sensitive (ACSs) conditions, (3) hospital length of stay (LOS), and (4) Medicare expenditures. Propensity score matching methods were used to reduce observed differences between demented and non-demented groups at study enrollment. Analyses took into account repeated observations within each individual. RESULTS: Compared to propensity-matched individuals without dementia, individuals with dementia had significantly higher risk for all-cause hospitalization, longer LOS, and higher Medicare expenditures. Functional and cognitive deficits were significantly associated with higher risks for hospitalizations, hospital LOS, and Medicare expenditures. Functional and cognitive deficits were associated with higher risks of for some ACS but not all admissions. CONCLUSIONS: These results allow us to differentiate the impact of functional and cognitive deficits on hospitalizations. To develop strategies to reduce hospitalizations and expenditures, better understanding of which types of hospitalizations and which disease characteristics impact these outcomes will be critical.

OBJECTIVES: A high body mass index (BMI) in middle-age or a decrease in BMI at late-age has been considered a predictor for the development of Alzheimer's disease (AD). However, little is known about the BMI change close to or after AD onset. METHODS: BMI of participants from three cohorts, the Washington Heights and Inwood Columbia Aging Project (WHICAP; population-based) and the Predictors Study (clinic-based), and National Alzheimer's Coordinating Center (NACC; clinic-based) were analyzed longitudinally. We used generalized estimating equations to test whether there were significant changes of BMI over time, adjusting for age, sex, education, race, and research center. Stratification analyses were run to determine whether BMI changes depended on baseline BMI status. RESULTS: BMI declined over time up to AD clinical onset, with an annual decrease of 0.21 (p=0.02) in WHICAP and 0.18 (p=0.04) kg/m2 in NACC. After clinical onset of AD, there was no significant decrease of BMI. BMI even increased (b=0.11, p=0.004) among prevalent AD participants in NACC. During the prodromal period, BMI decreased over time in overweight (BMI>/=25 and /=30) NACC participants. After AD onset, BMI tended to increase in underweight/normal weight (BMI

The amyloid cascade hypothesis suggests that aberrant metabolism of the amyloid precursor glycoprotein, and subsequent accumulation of soluble oligomers β-amyloid 40 (Aβ40) and 42 (Aβ42), is the primary trigger for the development of Alzheimer disease (AD). The Tg2576 mouse model of AD has shown that plasma Aβ levels decrease as brain Aβ levels increase, generating interest in the suitability of plasma Aβ level as a risk biomarker for AD. Indeed, we have reported that elevated plasma Aβ42 at baseline and decreasing levels over time predict conversion to AD, and other studies support these findings. The current study sought to specify existing work by investigating the extent to which plasma Aβ levels (1) can be linked to specific cognitive changes that constitute conversion to AD and (2) may be relevant for cognition independent of dementia.

OBJECTIVE: To determine whether APOE epsilon 4 predicts rate of cognitive change in incident and prevalent Alzheimer disease (AD). METHODS: Individuals were recruited from two longitudinal cohort studies-the Washington Heights and Inwood Columbia Aging Project (WHICAP; population-based) and the Predictors Study (clinic-based)--and were followed for an average of 4 years. Three samples of participants diagnosed with AD, with diverse demographic characteristics and baseline cognitive functioning, were studied: 1) 199 (48%) of the incident WHICAP cases; 2) 215 (54%) of the prevalent WHICAP cases; and 3) 156 (71%) of the individuals diagnosed with AD in the Predictors Study. Generalized estimating equations were used to test whether rate of cognitive change, measured using a composite cognitive score in WHICAP and the Mini-Mental State Examination in Predictors, varied as a function of epsilon 4 status in each sample. RESULTS: The presence of at least one epsilon 4 allele was associated with faster cognitive decline in the incident population-based AD group (p = 0.01). Parallel results were produced for the two prevalent dementia samples only when adjusting for disease severity or excluding the most impaired participants from the analyses. CONCLUSION: APOE epsilon 4 may influence rate of cognitive decline most significantly in the earliest stages of Alzheimer disease.

Background: Although the motor and non-motor features of essential tremor (ET) have been characterized in detail, it is not known whether ET patients suffer psychologically and whether those who are close to them consider them to be suffering in this way. Methods: Fifty ET patients and 50 “close others” (COs), identified by patients “as someone who knows you well and sees you often” and who can “provide a different perspective on your well-being”, reported their own depressive symptoms, daily stress, and perceptions of patient psychological suffering and patient overall suffering with validated scales. ET patients’ tremor severity, duration, disability, cognition, and number of medications were also assessed. Results: ET patients reported levels of psychological suffering within the range documented in arthritis and dementia patients from previous studies, and COs perceived significantly more psychological suffering in patients than patients reported themselves. Regression models, controlling for tremor severity, duration, and disability revealed that patients’ greater psychological suffering was associated with greater patient depression. The greater perceptions of COs of patient psychological and overall suffering were associated with greater CO depression and daily stress. Sensitivity analysis showed that patients’ cognitive status or number of medications did not affect the results. Discussion: Multidisciplinary teams caring for ET patients should look beyond simple clinical ET indicators. They should be aware of patient experiences and perceptions of COs of psychological and overall suffering. This will help guide the development of evidence-based, supportive interventions that improve communication about the needs of ET patients and those who are close to them.