Amyloid Positron Emission Tomography and Subsequent Health Care Use Among Medicare Beneficiaries With Mild Cognitive Impairment or Dementia.

Importance: Results of amyloid positron emission tomography (PET) have been shown to change the management of patients with mild cognitive impairment (MCI) or dementia who meet Appropriate Use Criteria (AUC). Objective: To determine if amyloid PET is associated with reduced hospitalizations and emergency department (ED) visits over 12 months in patients with MCI or dementia. Design, Setting, and Participants: This nonrandomized controlled trial analyzed participants in the Imaging Dementia-Evidence for Amyloid Scanning (IDEAS) study, an open-label, multisite, longitudinal study that enrolled participants between February 2016 and December 2017 and followed up through December 2018. These participants were recruited at 595 clinical sites that provide specialty memory care across the US. Eligible participants were Medicare beneficiaries 65 years or older with a diagnosis of MCI or dementia within the past 24 months who met published AUC for amyloid PET. Each IDEAS study participant was matched to a control Medicare beneficiary who had not undergone amyloid PET. Data analysis was conducted on December 13, 2022. Exposure: Participants underwent amyloid PET at imaging centers. Main Outcomes and Measures: The primary end points were the proportions of patients with 12-month inpatient hospital admissions and ED visits. One of 4 secondary end points was the rate of hospitalizations and rate of ED visits in participants with positive vs negative amyloid PET results. Health care use was ascertained from Medicare claims data. Results: The 2 cohorts (IDEAS study participants and controls) each comprised 12 684 adults, including 6467 females (51.0%) with a median (IQR) age of 77 (73-81) years. Over 12 months, 24.0% of the IDEAS study participants were hospitalized, compared with 25.1% of the matched control cohort, for a relative reduction of -4.49% (97.5% CI, -9.09% to 0.34%). The 12-month ED visit rates were nearly identical between the 2 cohorts (44.8% in both IDEAS study and control cohorts) for a relative reduction of -0.12% (97.5% CI, -3.19% to 3.05%). Both outcomes fell short of the prespecified effect size of 10% or greater relative reduction. Overall, 1467 of 6848 participants (21.4%) with positive amyloid PET scans were hospitalized within 12 months compared with 1081 of 4209 participants (25.7%) with negative amyloid PET scans (adjusted odds ratio, 0.83; 95% CI, 0.78-0.89). Conclusions and Relevance: Results of this nonrandomized controlled trial showed that use of amyloid PET was not associated with a significant reduction in 12-month hospitalizations or ED visits. Rates of hospitalization were lower in patients with positive vs negative amyloid PET results.

Continuity of care (COC) and amyloid-ß PET scan: the CARE-IDEAS study.

BACKGROUND: High continuity of care (COC) is associated with better clinical outcomes among older adults. The impact of amyloid-ß PET scan on COC among adults with mild cognitive impairment (MCI) or dementia of uncertain etiology is unknown. METHODS: We linked data from the CARE-IDEAS study, which assessed the impact of amyloid-ß PET scans on outcomes in Medicare beneficiaries with MCI or dementia of uncertain etiology and their care partners, to Medicare claims (2015-2018). We calculated a participant-level COC index using the Bice-Boxerman formula and claims from all ambulatory evaluation and management visits during the year prior to and following the amyloid-ß PET scan. We compared baseline characteristics by scan result (elevated or non-elevated) using standardized differences. To evaluate changes in COC, we used multiple regression models adjusting for sociodemographics, cognitive function, general health status, and the Charlson Comorbidity Index. RESULTS: Among the 1171 cohort members included in our analytic population, the mean age (SD) was 75.2 (5.4) years, 61.5% were male and 93.9% were non-Hispanic white. Over two-thirds (68.1%) had an elevated amyloid-ß PET scan. Mean COC for all patients was 0.154 (SD = 0.102; range = 0-0.73) prior to the scan and 0.158 (SD = 0.105; range = 0-1.0) in the year following the scan. Following the scan, the mean COC index score increased (95% CI) by 0.005 (-0.008, 0.019) points more for elevated relative to not elevated scan recipients, but this change was not statistically significant. There was no association between scan result (elevated vs. not elevated) or any other patient covariates and changes in COC score after the scan. CONCLUSION: COC did not meaningfully change following receipt of amyloid-ß PET scan in a population of Medicare beneficiaries with MCI or dementia of uncertain etiology. Future work examining how care continuity varies across marginalized populations with cognitive impairment is needed.

Radiological assessment of dementia: the Italian inter-society consensus for a practical and clinically oriented guide to image acquisition, evaluation, and reporting.

BACKGROUND: Radiological evaluation of dementia is expected to increase more and more in routine practice due to both the primary role of neuroimaging in the diagnostic pathway and the increasing incidence of the disease. Despite this, radiologists often do not follow a disease-oriented approach to image interpretation, for several reasons, leading to reports of limited value to clinicians. In our work, through an intersocietal consensus on the main mandatory knowledge about dementia, we proposed a disease-oriented protocol to optimize and standardize the acquisition/evaluation/interpretation and reporting of radiological images. Our main purpose is to provide a practical guideline for the radiologist to help increase the effectiveness of interdisciplinary dialogue and diagnostic accuracy in daily practice. RESULTS: We defined key clinical and imaging features of the dementias (A), recommended MRI protocol (B), proposed a disease-oriented imaging evaluation and interpretation (C) and report (D) with a glimpse to future avenues (E). The proposed radiological practice is to systematically evaluate and score atrophy, white matter changes, microbleeds, small vessel disease, consider the use of quantitative measures using commercial software tools critically, and adopt a structured disease-oriented report. In the expanding field of cognitive disorders, the only effective assessment approach is the standardized disease-oriented one, which includes a multidisciplinary integration of the clinical picture, MRI, CSF and blood biomarkers and nuclear medicine.

Positron Emission Tomography-Based Assessment of Cognitive Impairment and Dementias, Critical Role of Fluorodeoxyglucose in such Settings.

Positron emission tomography (PET) has been a key component in the diagnostic armamentarium for assessing neurodegenerative diseases such as Alzheimer or Parkinson disease. PET imaging has been useful for diagnosing these disorders, identifying their pathophysiology, and following their treatment. Further, PET imaging has been extensively used for both clinical and research purposes, particularly for helping with potential therapeutic approaches for managing neurodegenerative diseases. This article will review the current literature regarding PET imaging in patients with neurodegenerative disorders. This includes an evaluation of the most commonly used tracer fluorodeoxyglucose that measures cerebral glucose metabolism, tracers that assess neurotransmitter systems, and tracers designed to reveal disease-specific pathophysiological processes. With the continuing development of an expanding variety of radiopharmaceuticals, PET imaging will likely play a prominent role in future research and clinical applications for neurodegenerative diseases.

Epidemiologic Trends, Social Determinants, and Brain Health: The Role of Life Course Inequalities.

Brain health as expressed in our mental health and occurrence of specific disorders such as dementia and stroke is vitally important to quality of life, functional independence, and risk of institutionalization. Maintaining brain health is, therefore, a societal imperative, and public health challenge, from prevention of acquisition of brain disorders, through protection and risk reduction to supporting those with such disorders through effective societal and system approaches. To identify possible mechanisms that explain the differential effect of potentially modifiable risk factors, and factors that may mitigate risk, a life course approach is needed. This is key to understanding how poor health can accumulate from the earliest life stages. It also allows us to integrate and investigate key material, behavioral, and psychological factors that generate health inequalities within and across communities and societies. This review provides a narrative on how brain health is intimately linked to wider health determinants, thus importance for clinicians and societies alike. There is compelling evidence accumulated from research over decades that socioeconomic status, higher education, and healthy lifestyle extend life and compress major morbidities into later life. Brain health is part of this, but collective action has been limited, partly because of the separation of disciplines and focus on highly reductionist approaches in that clinicians and associated research have focused more on mitigation and early detection of specific diseases. However, clinicians could be part of the drive for better brain health for all society to support life courses that have more protection and less risk. There is evidence of change in such risks for conditions such as stroke and dementia across generations. The evidence points to the importance of starting with parental health and life course inequalities as a central focus.

Assessment of Racial/Ethnic Disparities in Timeliness and Comprehensiveness of Dementia Diagnosis in California.

Importance: The US aging population is rapidly becoming more racially and ethnically diverse. Early diagnosis of dementia is a health care priority. Objective: To examine the associations between race/ethnicity and timeliness of dementia diagnosis and comprehensiveness of diagnostic evaluation. Design, Setting, and Participants: This retrospective cross-sectional study used 2013-2015 California Medicare fee-for-service data to examine the associations of race/ethnicity, individual factors, and contextual factors with the timeliness and comprehensiveness of dementia diagnosis. Data from 10 472 unique beneficiaries were analyzed. The sample was selected on the basis of the following criteria: presence of 1 or more claims; no diagnoses of dementia or mild cognitive impairment in 2013 to 2014; continuous enrollment in Medicare Parts A and B; Asian, Black, Hispanic, or White race/ethnicity; and incident diagnoses of dementia or mild cognitive impairment in January through June 2015. Data analyses were conducted from November 1, 2019, through November 10, 2020. Main Outcomes and Measures: Timeliness of diagnosis, defined as incident diagnosis of mild cognitive impairment vs dementia, and comprehensiveness of diagnostic evaluation, defined as presence of the following services in claims within 6 months before or after the incident diagnosis date: specialist evaluation, laboratory testing, and neuroimaging studies. Results: The sample comprised 10 472 unique Medicare beneficiaries with incident diagnoses of dementia or mild cognitive impairment (6504 women [62.1%]; mean [SD] age, 82.9 [8.0] years) and included 993 individuals who identified as Asian (9.5%), 407 as Black (3.9%), 1255 as Hispanic (12.0%), and 7817 as White (74.6%). Compared with White beneficiaries, those who identified as Asian (odds ratio, 0.46; 95% CI, 0.38-0.56), Black (odds ratio, 0.73; 95% CI, 0.56-0.94), or Hispanic (odds ratio, 0.62; 95% CI, 0.52-0.72) were less likely to receive a timely diagnosis. Asian beneficiaries (incidence rate ratio, 0.81; 95% CI, 0.74-0.87) also received fewer diagnostic evaluation elements. These associations remained significant after adjusting for age, sex, comorbidity burden, neighborhood disadvantage, and rurality. Conclusions and Relevance: These findings highlight substantial disparities in the timeliness and comprehensiveness of dementia diagnosis. Public health interventions are needed to achieve equitable care for people living with dementia across all racial/ethnic groups.

Evaluating 2-[18F]FDG-PET in differential diagnosis of dementia using a data-driven decision model.

2-[18F]fluoro-2-deoxy-d-glucose positron emission tomography (2-[18F]FDG-PET) has an emerging supportive role in dementia diagnostic as distinctive metabolic patterns are specific for Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD). Previous studies have demonstrated that a data-driven decision model based on the disease state index (DSI) classifier supports clinicians in the differential diagnosis of dementia by using different combinations of diagnostic tests and biomarkers. Until now, this model has not included 2-[18F]FDG-PET data. The objective of the study was to evaluate 2-[18F]FDG-PET biomarkers combined with commonly used diagnostic tests in the differential diagnosis of dementia using the DSI classifier. We included data from 259 subjects diagnosed with AD, DLB, FTD, vascular dementia (VaD), and subjective cognitive decline from two independent study cohorts. We also evaluated three 2-[18F]FDG-PET biomarkers (anterior vs. posterior index (API-PET), occipital vs. temporal index, and cingulate island sign) to improve the classification accuracy for both FTD and DLB. We found that the addition of 2-[18F]FDG-PET biomarkers to cognitive tests, CSF and MRI biomarkers considerably improved the classification accuracy for all pairwise comparisons of DLB (balanced accuracies: DLB vs. AD from 64% to 77%; DLB vs. FTD from 71% to 92%; and DLB vs. VaD from 71% to 84%). The two 2-[18F]FDG-PET biomarkers, API-PET and occipital vs. temporal index, improved the accuracy for FTD and DLB, especially as compared to AD. Moreover, different combinations of diagnostic tests were valuable to differentiate specific subtypes of dementia. In conclusion, this study demonstrated that the addition of 2-[18F]FDG-PET to commonly used diagnostic tests provided complementary information that may help clinicians in diagnosing patients, particularly for differentiating between patients with FTD, DLB, and AD.

Assessing Neural Compensation With Visuospatial Working Memory Load Using Near-Infrared Imaging.

Alzheimer's disease is characterized by the progressive deterioration of cognitive abilities particularly working memory while mild cognitive impairment (MCI) represents its prodrome. It is generally believed that neural compensation is intact in MCI but absent in Alzheimer's disease. This study investigated the effects of increasing task load as a means to induce neural compensation through a novel visual working memory (VSWM) task using functional near-infrared spectroscopy (fNIRS). The bilateral prefrontal cortex (PFC) was explored due to its relevance in VSWM and neural compensation. A total of 31 healthy controls (HC), 12 patients with MCI and 18 patients with mild Alzheimer's disease (mAD) were recruited. Although all groups showed sensitivity in terms of behavioral performance (i.e. score) towards increasing task load (level 1 to 3), only in MCI load effect on cortical response (as measured by fNIRS) was significant. At lower task load, bilateral PFC activation did not differ between MCI and HC. Neural compensation in the form of hyperactivation was only noticeable in MCI with a moderate task load. Lack of hyperactivation in mAD, coupled with significantly poorer task performance across task loads, suggested the inability to compensate due to a greater degree of neurodegeneration. Our findings provided an insight into the interaction of cognitive load theory and neural compensatory mechanisms. The experiment results demonstrated the feasibility of inducing neural compensation with the proposed VSWM task at the right amount of cognitive load. This may provide a promising avenue to develop an effective cognitive training and rehabilitation for dementia population.

Financial Management Skills in Aging, MCI and Dementia: Cross Sectional Relationship to 18F-Florbetapir PET Cortical ß-amyloid Deposition.

BACKGROUND: There is a need to more fully characterize financial capacity losses in the preclinical and prodromal stages of Alzheimer's disease (AD) and their pathological substrates. OBJECTIVES: To test the association between financial skills and cortical ß-amyloid deposition in aging and subjects at risk for AD. DESIGN: Cross-sectional analyses of data from the Alzheimer's Disease Neuroimaging Initiative (ADNI-3) study conducted across 50 plus sites in the US and Canada. SETTING: Multicenter biomarker study. PARTICIPANTS: 243 subjects (144 cognitively normal, 79 mild cognitive impairment [MCI], 20 mild AD). MEASUREMENTS: 18F-Florbetapir brain PET scans to measure global cortical ß-amyloid deposition (SUVr) and the Financial Capacity Instrument Short Form (FCI-SF) to evaluate an individual's financial skills in monetary calculation, financial concepts, checkbook/register usage, and bank statement usage. There are five sub scores and a total score (range of 0-74) with higher scores indicating better financial skill. RESULTS: FCI-SF total score was significantly worse in MCI [Cohen's d= 0.9 (95%CI: 0.6-1.2)] and AD subjects [Cohen's d=3.1(CI: 2.5-3.7)] compared to normals. Domain scores and completion times also showed significant difference. Across all subjects, higher cortical ß-amyloid SUVr was significantly associated with worse FCI-SF total score after co-varying for age, education, and cognitive score [Cohen's f2=0.751(CI: 0.5-1.1)]. In cognitively normal subjects, after covarying for age, gender, and education, higher ß -amyloid PET SUVr was associated with longer task completion time [Cohen's f2=0.198(CI: 0.06-0.37)]. CONCLUSION: Using a multicenter study sample, we document that financial capacity is impaired in the prodromal and mild stages of AD and that such impairments are, in part, associated with the extent of cortical ß-amyloid deposition. In normal aging, ß-amyloid deposition is associated with slowing of financial tasks. These data confirm and extend prior research highlighting the utility of financial capacity assessments in at risk samples.

Association of Amyloid Positron Emission Tomography With Subsequent Change in Clinical Management Among Medicare Beneficiaries With Mild Cognitive Impairment or Dementia.

Importance: Amyloid positron emission tomography (PET) detects amyloid plaques in the brain, a core neuropathological feature of Alzheimer disease. Objective: To determine if amyloid PET is associated with subsequent changes in the management of patients with mild cognitive impairment (MCI) or dementia of uncertain etiology. Design, Setting, and Participants: The Imaging Dementia-Evidence for Amyloid Scanning (IDEAS) study was a single-group, multisite longitudinal study that assessed the association between amyloid PET and subsequent changes in clinical management for Medicare beneficiaries with MCI or dementia. Participants were required to meet published appropriate use criteria stating that etiology of cognitive impairment was unknown, Alzheimer disease was a diagnostic consideration, and knowledge of PET results was expected to change diagnosis and management. A total of 946 dementia specialists at 595 US sites enrolled 16 008 patients between February 2016 and September 2017. Patients were followed up through January 2018. Dementia specialists documented their diagnosis and management plan before PET and again 90 (±30) days after PET. Exposures: Participants underwent amyloid PET at 343 imaging centers. Main Outcomes and Measures: The primary end point was change in management between the pre- and post-PET visits, as assessed by a composite outcome that included Alzheimer disease drug therapy, other drug therapy, and counseling about safety and future planning. The study was powered to detect a 30% or greater change in the MCI and dementia groups. One of 2 secondary end points is reported: the proportion of changes in diagnosis (from Alzheimer disease to non-Alzheimer disease and vice versa) between pre- and post-PET visits. Results: Among 16 008 registered participants, 11 409 (71.3%) completed study procedures and were included in the analysis (median age, 75 years [interquartile range, 71-80]; 50.9% women; 60.5% with MCI). Amyloid PET results were positive in 3817 patients with MCI (55.3%) and 3154 patients with dementia (70.1%). The composite end point changed in 4159 of 6905 patients with MCI (60.2% [95% CI, 59.1%-61.4%]) and 2859 of 4504 patients with dementia (63.5% [95% CI, 62.1%-64.9%]), significantly exceeding the 30% threshold in each group (P < .001, 1-sided). The etiologic diagnosis changed from Alzheimer disease to non-Alzheimer disease in 2860 of 11 409 patients (25.1% [95% CI, 24.3%-25.9%]) and from non-Alzheimer disease to Alzheimer disease in 1201 of 11 409 (10.5% [95% CI, 10.0%-11.1%]). Conclusions and Relevance: Among Medicare beneficiaries with MCI or dementia of uncertain etiology evaluated by dementia specialists, the use of amyloid PET was associated with changes in clinical management within 90 days. Further research is needed to determine whether amyloid PET is associated with improved clinical outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT02420756.

Infrequent false positive [18F]flutemetamol PET signal is resolved by combined histological assessment of neuritic and diffuse plaques.

BACKGROUND: The performance of [18F]flutemetamol amyloid PET against histopathological standards of truth was the subject of our recent article in Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring (2017;9:25-34). MAIN BODY: This viewpoint article addresses infrequently observed discordance between visual [18F]flutemetamol PET image readings and histopathology based solely on neuritic plaque assessment by CERAD criteria, which is resolved by assessing both neuritic and diffuse plaques and/or brain atrophy. CONCLUSION: [18F]flutemetamol PET signal corresponds predominantly to neuritic plaque pathology but is also influenced by the presence of diffuse plaques. This could allow for detection of diffuse amyloid deposits in the early stages of AD dementia, particularly in the striatum where diffuse amyloid is most commonly observed.

Automated assessment of FDG-PET for differential diagnosis in patients with neurodegenerative disorders.

PURPOSE: To review literature until November 2015 and reach a consensus on whether automatic semi-quantification of brain FDG-PET is useful in the clinical setting for neurodegenerative disorders. METHODS: A literature search was conducted in Medline, Embase, and Google Scholar. Papers were selected with a lower limit of 30 patients (no limits with autopsy confirmation). Consensus recommendations were developed through a Delphi procedure, based on the expertise of panelists, who were also informed about the availability and quality of evidence, assessed by an independent methodology team. RESULTS: Critical outcomes were available in nine among the 17 papers initially selected. Only three papers performed a direct comparison between visual and automated assessment and quantified the incremental value provided by the latter. Sensitivity between visual and automatic analysis is similar but automatic assessment generally improves specificity and marginally accuracy. Also, automated assessment increases diagnostic confidence. As expected, performance of visual analysis is reported to depend on the expertise of readers. CONCLUSIONS: Tools for semi-quantitative evaluation are recommended to assist the nuclear medicine physician in reporting brain FDG-PET pattern in neurodegenerative conditions. However, heterogeneity, complexity, and drawbacks of these tools should be known by users to avoid misinterpretation. Head-to-head comparisons and an effort to harmonize procedures are encouraged.

Dementia among Older Persons in Jamaica: Prevalence and Policy Implications / La demencia entre las personas de edad en Jamaica: prevalencia e implicaciones para la implementación de políticas

ABSTRACT Objective: To determine the prevalence of dementia and dementia types in Jamaica. Methods: An embedded case-control design was used to investigate dementia within the ageing population. Cases (Mini-Mental State Examination [MMSE] scores of < 20) and controls (MMSE scores of > 20) were evaluated using DSM-IVprotocol and magnetic resonance imaging. Prevalences (crude and age-adjusted) were calculated and distribution of dementia by type described. Results: Dementia prevalence was 5.9%. Alzheimer's pattern dementia accounted for 61.8% and vascular dementia 32.4%. However, vascular disease was prominent in 45.5% of the Alzheimer's cases. Female gender and increasing age were associated with higher rates of dementia. Dementia was 38 times more likely in participants with MMSE scores below 20. Conclusion: This first nationally representative study indicated that dementia rates in Jamaica were comparable with regional and global estimates. Regardless of the dementia type, vascular change was pervasive and suggested that synergistic efforts should be made to address underlying contributory factors. Cardiovascular and cerebrovascular risk reduction should be deliberately pursued as integral adjuncts to dementia risk reduction.

RESUMEN Objetivo: Determinar la prevalencia de los tipos de demencia y demencia en Jamaica. Métodos: Se utilizó un diseño de caso-control incrustado para investigar la demencia dentro de la población en proceso de envejecimiento. Los casos (puntuación < 20 en el Mini Examen del Estado Mental [MEEM]) y los controles (puntuación > 20 en el MEEM) fueron evaluados usando el protocolo DSM-IVy la imagen por resonancia magnética. Se calcularon prevalencias (crudas y ajustadas por edad) y se describió la distribución de la demencia por tipo. Resultados: La prevalencia de demencia fue de 5.9%. El Alzheimer representó el 61.8% y la demencia vascular 32.4%. Sin embargo, la enfermedad vascular fue prominente en el 45.5% de los casos de Alzheimer. El género femenino y la edad creciente se asociaron con tasas más altas de demencia. La demencia fue 38 veces más probable en los participantes con puntuaciones de MEEM por debajo de 20. Conclusión: Este primer estudio nacionalmente representativo indicó que las tasas de demencia en Jamaica eran comparables con los estimados regionales y globales. Independientemente del tipo de demencia, el cambio vascular fue generalizado y sugirió que se hicieran esfuerzos sinérgicos para abordar los factores contribuyentes subyacentes. Debe buscarse deliberadamente la reducción del riesgo cardiovascular y cerebrovascular como adjuntos integrantes de la reducción del riesgo de demencia.

Cognitive impairment in hemodialysis patients: Implementation of cut-off values for the Montreal Cognitive Assessment (MoCA)-test for feasible screening.

OBJECTIVE: Reliable identification of cognitive impairment in hemodialysis patients is of utmost importance, as it is associated with poor outcomes including dialysis withdrawal and death. High prevalence of cognitive impairment has been demonstrated in several studies using brief screening instruments or neuropsychological test batteries. However, the relevance of cognitive impairment as well as the accuracy of screening procedures have never been studied in this patient population. METHODS: 151 chronic hemodialysis patients (mean age 65.78 ± 14.88 years, 73,5% male) underwent cognitive testing under standardized conditions by the Montreal Cognitive Assessment (MoCA) and, in a second step, the Clinical Dementia Rating scale (CDR), an international standard to measure the severity of dementia. For calculating MoCA cut-off values on the basis of the CDR global score, receiver operator characteristics (ROC) analysis and c-statistic were applied. RESULTS: 49.0% of patients were categorized as 0.5 in the CDR global with memory being the predominantly affected domain (47.7% of patients scored ≥ 0.5). Youden's Index led to a threshold of 23.5 points for the MoCA test for optimal differentiation between cognitively normal (CDR global < 0.5) and impaired patients (CDR global ≥ 0.5) based on a sensitivity of approximately 99% and a specificity of approximately 74%. CONCLUSION: Interference of cognitive impairment with patients' independence and daily life was shown using the CDR for the first time in hemodialysis patients. A MoCA score of 23.5 points turned out as optimal threshold to differentiate between patients with and without functional impairment in the CDR, thereby paving the way for implementation of the MoCA test as a quick and thus highly feasible screening instrument for periodic testing in clinical routine.

Clinical Use and Utility of Amyloid Imaging.

Currently, 3 amyloid PET tracers are approved and commercially available for clinical use. They allow for the accurate in vivo detection of amyloid plaques, one hallmark of Alzheimer disease. Here, we review the current knowledge on the clinical use and utility of amyloid imaging. Appropriate use criteria for the clinical application of amyloid imaging are established, and most currently available data point to their validity. Visual amyloid image analysis is highly standardized. Disclosure of amyloid imaging results is desired by many cognitively impaired subjects and seems to be safe once appropriate education is delivered to the disclosing clinicians. Regarding clinical utility, increasing evidence points to a change in diagnosis via amyloid imaging in about 30% of cases, to an increase in diagnostic confidence in about 60% of cases, to a change in patient management in about 60% of cases, and specifically to a change in medication in about 40% of cases. Also, amyloid imaging results seem to have a relevant impact on caregivers. Further, initial simulation studies point to a potential positive effect on patient outcome and to cost effectiveness of amyloid imaging. These features, however, will require confirmation in prospective clinical trials. More work is also required to determine the clinical utility of amyloid imaging specifically in subjects with mild cognitive impairment and in comparison with or in conjunction with other Alzheimer disease biomarkers. In summary, the clinical use of amyloid imaging is being studied, and the currently available data point to a relevant clinical utility of this imaging technique. Ongoing research will determine whether this accurate and noninvasive approach to amyloid plaque load detection will translate into a benefit to cognitively impaired subjects.

The Role of Neuroimaging in the Assessment of the Cognitively Impaired Elderly.

This article reviews the current diagnostic tools that are available for structural, functional, and molecular imaging of the brain, summarizing some of the key findings that have been reported in individuals diagnosed with Alzheimer disease, mild cognitive impairment, prodromal AD, or other prevalent dementias. Given recent advances in the development of amyloid PET tracers, current guidelines for the use of amyloid PET imaging in patients with cognitive complaints are reviewed. In addition, data addressing the potential value of amyloid PET imaging in the clinical setting are highlighted.

Validation of the Total Cerebrovascular Disease Burden Scale in a Community Sample.

BACKGROUND: A total cerebrovascular disease (CeVD) burden scale was previously constructed and an inverse association of CeVD burden and cognition was found. However, the generalizability of the CeVD scale has not been examined. OBJECTIVE: The objective was to validate the previously constructed total CeVD burden scale by establishing its association with cognitive function and dementia diagnosis in a community sample. METHODS: Eligible participants were assessed on an extensive neuropsychological battery and underwent MRI scans. The total CeVD scale, comprising markers of both small- and large-vessel diseases, was derived according to previously described criteria. Association of total CeVD burden with global and domain-based cognitive performance and dementia diagnostic utility of the scale was established. RESULTS: A total of 863 participants were included in the analysis. A stepwise association of CeVD burden score with global and domain-specific cognitive function was found. Per score increase on the total CeVD burden scale was associated with 3.6 (95% CI = 2.1-6.4) times higher odds of dementia compared to dementia-free. DISCUSSION: The total CeVD burden scale is associated with cognition and dementia in a community sample. Longitudinal studies are required to establish the predictive ability of this scale.

Regional cerebral blood flow single photon emission computed tomography for detection of Frontotemporal dementia in people with suspected dementia.

BACKGROUND: In the UK, dementia affects 5% of the population aged over 65 years and 25% of those over 85 years. Frontotemporal dementia (FTD) represents one subtype and is thought to account for up to 16% of all degenerative dementias. Although the core of the diagnostic process in dementia rests firmly on clinical and cognitive assessments, a wide range of investigations are available to aid diagnosis.Regional cerebral blood flow (rCBF) single-photon emission computed tomography (SPECT) is an established clinical tool that uses an intravenously injected radiolabelled tracer to map blood flow in the brain. In FTD the characteristic pattern seen is hypoperfusion of the frontal and anterior temporal lobes. This pattern of blood flow is different to patterns seen in other subtypes of dementia and so can be used to differentiate FTD.It has been proposed that a diagnosis of FTD, (particularly early stage), should be made not only on the basis of clinical criteria but using a combination of other diagnostic findings, including rCBF SPECT. However, more extensive testing comes at a financial cost, and with a potential risk to patient safety and comfort. OBJECTIVES: To determine the diagnostic accuracy of rCBF SPECT for diagnosing FTD in populations with suspected dementia in secondary/tertiary healthcare settings and in the differential diagnosis of FTD from other dementia subtypes. SEARCH METHODS: Our search strategy used two concepts: (a) the index test and (b) the condition of interest. We searched citation databases, including MEDLINE (Ovid SP), EMBASE (Ovid SP), BIOSIS (Ovid SP), Web of Science Core Collection (ISI Web of Science), PsycINFO (Ovid SP), CINAHL (EBSCOhost) and LILACS (Bireme), using structured search strategies appropriate for each database. In addition we searched specialised sources of diagnostic test accuracy studies and reviews including: MEDION (Universities of Maastricht and Leuven), DARE (Database of Abstracts of Reviews of Effects) and HTA (Health Technology Assessment) database.We requested a search of the Cochrane Register of Diagnostic Test Accuracy Studies and used the related articles feature in PubMed to search for additional studies. We tracked key studies in citation databases such as Science Citation Index and Scopus to ascertain any further relevant studies. We identified 'grey' literature, mainly in the form of conference abstracts, through the Web of Science Core Collection, including Conference Proceedings Citation Index and Embase. The most recent search for this review was run on the 1 June 2013.Following title and abstract screening of the search results, full-text papers were obtained for each potentially eligible study. These papers were then independently evaluated for inclusion or exclusion. SELECTION CRITERIA: We included both case-control and cohort (delayed verification of diagnosis) studies. Where studies used a case-control design we included all participants who had a clinical diagnosis of FTD or other dementia subtype using standard clinical diagnostic criteria. For cohort studies, we included studies where all participants with suspected dementia were administered rCBF SPECT at baseline. We excluded studies of participants from selected populations (e.g. post-stroke) and studies of participants with a secondary cause of cognitive impairment. DATA COLLECTION AND ANALYSIS: Two review authors extracted information on study characteristics and data for the assessment of methodological quality and the investigation of heterogeneity. We assessed the methodological quality of each study using the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies) tool. We produced a narrative summary describing numbers of studies that were found to have high/low/unclear risk of bias as well as concerns regarding applicability. To produce 2 x 2 tables, we dichotomised the rCBF SPECT results (scan positive or negative for FTD) and cross-tabulated them against the results for the reference standard. These tables were then used to calculate the sensitivity and specificity of the index test. Meta-analysis was not performed due to the considerable between-study variation in clinical and methodological characteristics. MAIN RESULTS: Eleven studies (1117 participants) met our inclusion criteria. These consisted of six case-control studies, two retrospective cohort studies and three prospective cohort studies. Three studies used single-headed camera SPECT while the remaining eight used multiple-headed camera SPECT. Study design and methods varied widely. Overall, participant selection was not well described and the studies were judged as having either high or unclear risk of bias. Often the threshold used to define a positive SPECT result was not predefined and the results were reported with knowledge of the reference standard. Concerns regarding applicability of the studies to the review question were generally low across all three domains (participant selection, index test and reference standard).Sensitivities and specificities for differentiating FTD from non-FTD ranged from 0.73 to 1.00 and from 0.80 to 1.00, respectively, for the three multiple-headed camera studies. Sensitivities were lower for the two single-headed camera studies; one reported a sensitivity and specificity of 0.40 (95% confidence interval (CI) 0.05 to 0.85) and 0.95 (95% CI 0.90 to 0.98), respectively, and the other a sensitivity and specificity of 0.36 (95% CI 0.24 to 0.50) and 0.92 (95% CI 0.88 to 0.95), respectively.Eight of the 11 studies which used SPECT to differentiate FTD from Alzheimer's disease used multiple-headed camera SPECT. Of these studies, five used a case-control design and reported sensitivities of between 0.52 and 1.00, and specificities of between 0.41 and 0.86. The remaining three studies used a cohort design and reported sensitivities of between 0.73 and 1.00, and specificities of between 0.94 and 1.00. The three studies that used single-headed camera SPECT reported sensitivities of between 0.40 and 0.80, and specificities of between 0.61 and 0.97. AUTHORS' CONCLUSIONS: At present, we would not recommend the routine use of rCBF SPECT in clinical practice because there is insufficient evidence from the available literature to support this.Further research into the use of rCBF SPECT for differentiating FTD from other dementias is required. In particular, protocols should be standardised, study populations should be well described, the threshold for 'abnormal' scans predefined and clear details given on how scans are analysed. More prospective cohort studies that verify the presence or absence of FTD during a period of follow up should be undertaken.