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Abstract INTRODUCTION Are reductions in the rate of decline from the new disease‐modifying treatments (DMTs) in early Alzheimer's disease (AD) meaningful? We examined whether such reductions may be reflected in changes in health‐related resource use. METHODS Patients with Clinical Dementia Rating (CDR) = 0.5 or 1 with a clinical diagnosis of mild cognitive impairment or AD, reflecting clinical trial populations. Health‐related resource use was reported using the Resource Use Inventory (RUI) including direct medical care, non‐medical care, unpaid informal care, and time use. RESULTS Faster decline in CDR–Sum of Boxes (CDR‐SB) from baseline was independently associated with higher likelihood and hours of informal care received, and lower likelihood of employment/volunteer work, but not with direct medical care. DISCUSSION Reductions in the rate of decline in CDR‐SB seen from DMTs significantly affect patients’ work capacity and need for informal care, indicators of economic impact meaningful to patients, families, and health systems. These measures are not readily captured in administrative data sets. Highlights Following a cohort of participants with MCI or mild dementia due to AD that mimics participants targeted for AD trials, this study showed slower decline in CDR‐SB have significant effects on patients’ work capacity and need for informal care, but not on their direct medical care utilization such as hospitalizations, ED use, and doctors’ visits. Capturing potential benefits in health‐related resource use may require direct measures of informal care and work/volunteer effort which are meaningful outcomes to patients, families and health systems. Caution is needed in our effort to assess benefits of recently developed disease modifying treatment in AD using electronic health records and administrative data from which utilization of direct medical care are routinely collected as these data sources may not capture the most apparent changes in resource utilization during early disease stages.

Background and objectivesApathy strongly affects function in Alzheimer’s disease and frontotemporal dementia, however its effect on function in Lewy Body Disease (LBD) has not been well-described. This study aims to (1) examine the prevalence and persistence of apathy in a large, national cohort of well-characterized patients with LBD, and (2) estimate the effect of apathy on function over time.MethodsStudy included 676 participants with mild cognitive impairment (MCI) or dementia in the National Alzheimer’s Coordinating Center Uniform Data Set. Participants were followed for an average of 3.4 ± 1.7 years and consistently had a primary diagnosis of LBD. Apathy was defined by clinician judgment, categorized into four mutually exclusive profiles: (1) never apathetic across all visits, (2) at least one but

Objective Cognitive dysfunction (CD) is detectable in approximately 40% of patients with SLE. Despite this high prevalence, there are no approved pharmacological treatment options for this detrimental condition. Preliminary murine studies show potential for targeting microglial activation as a treatment of SLE-CD, which may be ameliorated with centrally acting ACE inhibitor (cACEi) and angiotensin receptor blocker (cARB) use. The aim of this study is to determine if there is an association of cACEi/cARB use with cognitive function in a human SLE cohort.Methods The American College of Rheumatology neuropsychological battery was administered to patients with consecutive SLE at a single academic health centre at baseline, 6 and 12 months. Scores were compared with sex-matched and age-matched control subjects. Clinical and demographic data were gathered at each visit. The primary outcome was CD defined as dysfunction in two or more cognitive domains. The primary predictor was a total cumulative dose of cACEi/cARB in milligrams per kilogram, recorded as an equivalent ramipril dose. Odds of CD with respect to cACEi/cARB use were determined through generalised linear mixed modelling.Results A total of 300 patients, representing 676 visits, completed this study. One hundred sixteen (39%) met the criteria for CD. Fifty-three participants (18%) were treated with a cACEi or cARB. Mean cumulative dose was 236 mg/kg (calculated as equivalent ramipril dose). Cumulative cACEi/cARB dose was not protective against SLE-CD. Caucasian ethnicity, current employment status and azathioprine cumulative dose were each associated with reduced odds of SLE-CD. Increasing Fatigue Severity Scale score was associated with increased odds of CD.Conclusions In a single-centre SLE cohort, cACEi/cARB use was not associated with absence of CD. Many important confounders may have influenced the results of this retrospective study. A randomised trial is required to accurately determine if cACEi/cARB is a potential treatment for SLE-CD.

Abstract Prior research has demonstrated high levels of cognitive and physical functional impairments in World Trade Center (WTC) responders. A follow-up neuroimaging study identified changes to white matter connectivity within the cerebellum in responders with cognitive impairment (CI). In the first study to examine cerebellar cortical thickness in WTC responders with CI, we fielded a structural magnetic resonance imaging protocol. WTC responders (N = 99) participated in a structural magnetic resonance imaging (MRI) study, of whom 48 had CI. Participants with CI did not differ demographically or by intracranial volume when compared to cognitively unimpaired participants. MRIs were processed using the CERES imaging pipeline; bilateral cortical thickness in 12 cerebellar lobules was reported. Analyses were completed comparing mean cerebellar cortical thickness across groups. Lobules were examined to determine the location and functional correlates of reduced cerebellar cortical thickness. Multivariable-adjusted analyses accounted for the false discovery rate. Mean cerebellar cortical thickness was reduced by 0.17 mm in responders with CI. Decrements in cerebellar cortical thickness were symmetric and located in the Cerebellar Crus (I and II), and in Lobules IV, VI, VIIb, VIIIa, VIIIb, and IX. Cerebellar cortical thickness was associated with episodic memory, response speed, and tandem balance. WTC responders with CI had evidence of reduced cerebellar cortical thickness that was present across lobules in a pattern unique to this cohort.

Abstract Background The COVID-19 pandemic disrupted Alzheimer disease randomized clinical trials (RCTs), forcing investigators to make changes in the conduct of such trials while endeavoring to maintain their validity. Changing ongoing RCTs carries risks for biases and threats to validity. To understand the impact of exigent modifications due to COVID-19, we examined several scenarios in symptomatic and disease modification trials that could be made. Methods We identified both symptomatic and disease modification Alzheimer disease RCTs as exemplars of those that would be affected by the pandemic and considered the types of changes that sponsors could make to each. We modeled three scenarios for each of the types of trials using existing datasets, adjusting enrollment, follow-ups, and dropouts to examine the potential effects COVID-19-related changes. Simulations were performed that accounted for completion and dropout patterns using linear mixed effects models, modeling time as continuous and categorical. The statistical power of the scenarios was determined. Results Truncating both symptomatic and disease modification trials led to underpowered trials. By contrast, adapting the trials by extending the treatment period, temporarily stopping treatment, delaying outcomes assessments, and performing remote assessment allowed for increased statistical power nearly to the level originally planned. Discussion These analyses support the idea that disrupted trials under common scenarios are better continued and extended even in the face of dropouts, treatment disruptions, missing outcomes, and other exigencies and that adaptations can be made that maintain the trials’ validity. We suggest some adaptive methods to do this noting that some changes become under-powered to detect the original effect sizes and expected outcomes. These analyses provide insight to better plan trials that are resilient to unexpected changes to the medical, social, and political milieu.

Introduction Increasingly, older adults are turning to emergency departments (EDs) to address healthcare needs. To achieve these research demands, infrastructure is needed to both generate evidence of intervention impact and advance the development of implementation science, pragmatic trials evaluation and dissemination of findings from studies addressing the emergency care needs of older adults. The Geriatric Emergency Care Applied Research Network (https://gearnetwork.org) has been created in response to these scientific needs—to build a transdisciplinary infrastructure to support the research that will optimise emergency care for older adults and persons living with dementia.Methods and analysis In this paper, we describe our approach to developing the GEAR Network infrastructure, the scoping reviews to identify research and clinical gaps and its use of consensus-driven research priorities with a transdisciplinary taskforce of stakeholders that includes patients and care partners. We describe how priority topic areas are ascertained, the process of conducting scoping reviews with integrated academic librarians performing standardised searches and providing quality control on reviews, input and support from the taskforce and conducting a large-scale consensus workshop to prioritise future research topics. The GEAR Network approach provides a framework and systematic approach to develop a research agenda and support research in geriatric emergency care.Ethics and dissemination This is a systematic review of previously conducted research; accordingly, it does not constitute human subjects research needing ethics review. These reviews will be prepared as manuscripts and submitted for publication to peer-reviewed journals, and the results will be presented at conferences.Open Science Framework registered DOI: 10.17605/OSF.IO/6QRYX, 10.17605/OSF.IO/AKVZ8, 10.17605/OSF.IO/EPVR5, 10.17605/OSF.IO/VXPRS.

Abstract Introduction World Trade Center (WTC) responders who aided in the search and rescue efforts are now at midlife, and evidence has demonstrated that many are experiencing early-onset cognitive impairment and are at risk of developing dementia, such as Alzheimer’s disease (AD). According to the recent NIA-AA framework, AD is characterized by a neuropathological cascade commencing with β-amyloid deposition (A), followed by tauopathy (T) and neurodegeneration (N). However, the ATN model has not been replicated utilizing recently validated plasma-based biomarkers, and the role of the Aβ40 subtype in A is not well understood. This study examined plasma-based neuropathological markers of Aβ42 and Aβ40 for A, total tau for T, and NfL for N in a cohort of World Trade Center responders at midlife in order to determine the role for the two β-amyloid subtypes in the ATN model. Methods Ultrasensitive Simoa technology was utilized to measure neuropathology in plasma collected from a consecutive clinical sample (n =398). Generalized structural equation modeling was utilized for modeling linkages between pathological markers. Model fit was utilized to determine proposed directions of association. Results Our findings support the ATN neuropathological cascade model of AD and further identify an associative role for Aβ40 in A as playing a central role linking T to N. A strong correlation was found between CI and age, and it was found that women may be at increased risk of elevated T levels, with plasma NfL levels higher in responders with CI. Notably, our model reported associations between: Aβ42, CI and N; Aβ40, T and N; T and CI; Aβ42 and Aβ40. Conclusions The current ATN model of AD does not specify the subtype of β-amyloid to be considered, which may be overlooking the differential roles that these two subtypes serve in the pathogenesis of AD.

Abstract Objective This study examined whether World Trade Center (WTC) exposures and chronic posttraumatic stress disorder (PTSD) were associated with incidence of mild cognitive impairment (MCI) in a longitudinal analysis of a prospective cohort study of WTC responders. Methods Incidence of MCI was assessed in a clinical sample of WTC responders (N = 1800) who were cognitively intact at baseline assessment. Crude incidence rates were calculated and compared to population estimates using standardized incidence ratios. Multivariable analyses used Cox proportional‐hazards regression. Results Responders were 53.1 years old (SD = 7.9) at baseline. Among eligible cognitively intact responders, 255 (14.2%) developed MCI at follow‐up. Incidence of MCI was higher than expected based on expectations from prior published research. Incidence was higher among those with increased PTSD symptom severity, and prolonged exposure was a risk factor in apolipoprotein‐ε4 carriers. Conclusions PTSD and prolonged WTC exposures were associated with increased incidence of MCI in WTC responders, results that may portend future high rates of dementia in WTC‐exposed responders.

Abstract Introduction Chronic posttraumatic stress disorder (PTSD) is associated with poor memory and increased burden of various degenerative cerebral neuropathologies. The goal of this pilot study was to determine whether PTSD was associated with changes in plasma‐based neuropathological biomarkers of neurodegeneration among World Trade Center (WTC) responders. Methods Thirty‐four WTC responders had blood drawn and flash‐frozen within 15 minutes of retrieval. PTSD symptoms were assessed at that time. Age, sex, and WTC exposure duration were obtained from medical records. Plasma was assayed in duplicate using an ultra‐sensitive single‐molecule enzyme‐linked immunosorbent assay to examine the distribution of amyloid‐β (Aβ) 42/40 ratios, total Aβ, total tau, and neurofilament light (NfL). The comparison group was drawn from a bank of healthy controls collected and assayed at the same facility. Results The average age of WTC responders at blood draw was 53 years. Half were PTSD positive (PTSD+) as indicated by symptom severity. WTC responders had lower Aβ42/Aβ40 ratios but higher total tau and NfL levels in the plasma than healthy controls. PTSD+ status was associated with lower plasma Aβ load and higher Aβ42/Aβ40 ratios. Discussion Findings suggest that PTSD may be associated with alterations in plasma markers related to Aβ, tau, and NfL, highlighting the potential association between PTSD status and neurodegenerative neuropathology in WTC responders.

Background: More than half of the people with dementia live in lower-middle income countries (LMIC), yet we lack research and evidence-based knowledge to guide health promotion and prevention strategies for cognitive decline. In the Philippines, the prevalence of mild cognitive impairment (MCI) and cardiovascular risk factors among older persons are high, making this population at high risk for developing dementia. This protocol describes a cluster randomized controlled trial that aims to investigate the efficacy of a multicomponent intervention to maintain cognitive performance among high-risk population.Methods: This is a cluster-randomized, two-arm, single-blind trial of a multicomponent intervention that combines dance called INDAK (Improving Neurocognition through Dance and Kinesthetics), nutrition counseling, and vascular risk management. The intervention arm will receive 12 months (1-h, twice per week) of INDAK and every 3 months of nutrition counseling and intensive vascular risk management and monitoring. The control group will receive the usual vascular care advice and referral. A total of 605 (20–25 clusters per arm) community-dwelling Filipino older adults aged ≥ 60 years old with MCI will participate in the study and will be assessed at baseline, 6th- and 12th-month follow-up. The primary outcome is cognitive performance assessed by the Alzheimer's Disease Assessment Scale—Cognitive (ADAS-Cog), Mnemonic Similarity Tasks (MST), and executive function composite (EFC). Secondary outcomes are functional connectivity assessed through brain imaging, and measures of behavioral, functional level, and quality of life.Discussion: The study aims to provide scientific evidence on a public health intervention that is contextualized in a community setting to reduce dementia risk among older adults with MCI. This model can be an ecological, low-cost, and effective program, thereby conducive to widespread implementation in the Philippines as well as in other low-resource settings with similar public health challenges. The pilot phase was underway with eight villages (clusters), but temporarily interrupted by the pandemic. The full study is anticipated to start after community restrictions are eased.

Abstract Objective In community dwelling older adults, depression and anxiety symptoms can be associated with early cognitive decline. Symptoms of depression and anxiety are common in older adults prior to surgery. However, their significance is unknown. Our objective was to determine whether preoperative depression and anxiety symptoms are associated with postoperative cognitive decline (POCD) and in‐hospital delirium, in older surgical patients. Methods We conducted a secondary data analysis of postoperative cognitive dysfunction in a cohort study of patients 65 and older undergoing elective noncardiac surgery. We used the Hospital Anxiety and Depression Scale (HADS) to screen for depression and anxiety symptoms at a home visit prior to surgery and 3 months after surgery. Patients with a history of psychiatric (major depressive disorder, bipolar disorder, and schizophrenia) or neurologic disorder (Parkinson's disease and stroke) were excluded from the parent study. Results Out of the 167 patients, 9.6% (n = 16) reported significant depressive symptoms and 21.6% (n = 36) reported significant anxiety symptoms on preoperative screening. There was no association between preoperative or new‐onset postoperative depression and anxiety symptoms and the incidence of delirium or POCD three months after surgery. Patients with preoperative depressive symptoms had higher preoperative pain (scores 69 vs. 35.7, p = .002) and frailty (56 vs. 14.6, p

The US military veteran population receiving care through the Veterans Health Administration (VHA) is particularly susceptible to cognitive impairment and dementias such as Alzheimer's disease and related dementias due to demographic, clinical, and economic factors. In this report we summarize the prevalence of dementia among US veterans and risks associated with AD and related dementias. We discuss the likelihood that these risks may be increasing in those about to enter the age in which dementias are common. We propose that VHA, the largest integrated health care system in the US, has shown promise in managing health risks that impact dementia prevention and propose further system wide approaches to be assessed for effective dementia prevention and care delivery.

Cognitive dysfunction after surgery under general anesthesia is a well-recognized clinical phenomenon in the elderly. Physiological effects of various anesthetic agents have been studied at length. Very little is known about potential effects of anesthesia on brain structure. In this study we used Diffusion Tensor Imaging to compare the white matter microstructure of healthy control subjects under sevoflurane anesthesia with their awake state. Fractional Anisotropy, a white mater integrity index, transiently decreases throughout the brain during sevoflurane anesthesia and then returns back to baseline. Other DTI metrics such as mean diffusivity, axial diffusivity and radial diffusivity were increased under sevoflurane anesthesia. Although DTI metrics are age dependent, the transient changes due to sevoflurane were independent of age and sex. Volumetric analysis shows various white matter volumes decreased whereas some gray matter volumes increased during sevoflurane anesthesia. These results suggest that sevoflurane anesthesia has a significant, but transient, effect on white matter microstructure. In spite of the transient effects of sevoflurane anesthesia there were no measurable effects on brain white matter as determined by the DTI metrics at 2 days and 7 days following anesthesia. The role of white matter in the loss of consciousness under anesthesia will need to be studied and MRI studies with subjects under anesthesia will need to take these results into account.

Abstract Introduction The objective of this study was to investigate associations between dementia in World Trade Center (WTC) responders and in vivo volumetric measures of hippocampal subfield volumes in WTC responders at midlife. Methods A sample of 99 WTC responders was divided into dementia and unimpaired groups. Participants underwent structural T1‐weighted magnetic resonance imaging. Volumetric measures included the overall hippocampus and eight subfields. Regression models examined volumetric measure of interest adjusting for confounders including intracranial volume. Results Dementia was associated with smaller hippocampal volume and with reductions across hippocampal subfields. Smaller hippocampal subfield volumes were associated with longer cumulative time worked at the WTC. Domain‐specific cognitive performance was associated with lower volumetric measures across hippocampal subregions. Conclusions This is the first study to investigate hippocampal subfield volumes in a sample of WTC responders at midlife. Selective hippocampal subfield volume reductions suggested abnormal cognition that were associated with WTC exposure duration.

Abstract Introduction Understanding of the natural history of apathy and its impact on patient function is limited. This study examines, in a large, national sample of Alzheimer's disease (AD) patients with long follow‐ups: (1) prevalence, incidence, and persistence of apathy, and (2) impact of apathy on function across dementia severity. Methods A longitudinal study of 9823 well‐characterized AD patients in the National Alzheimer's Coordinating Center Uniform Data Set. Results Apathy was highly prevalent across disease severity with cumulative prevalence of 48%, 74%, and 82% in Clinical Dementia Rating (CDR) 0.5, 1.0, and 2.0, respectively. Persistence of apathy from clinician judgment varied from visit to visit at earlier disease stages but remained high at moderate dementia. Independent of cognition, persistent apathy was strongly associated with accelerated rate of functional decline. Discussion Findings point to important targets for the treatment and management of apathy, include functional outcomes, and study designs that account for variable persistence of the apathy syndrome.

Abstract Introduction Type 2 diabetes (T2D) is a risk factor for dementia. Ischemia due to vascular pathology is hypothesized to be an underlying mechanism for this association. Hyperbaric oxygen therapy (HBOT) is a treatment in which oxygen‐enriched air (up to 100%) is administered to patients in a chamber at a pressure above one atmosphere absolute. HBOT is approved for the treatment of T2D ischemic non‐healing wounds. Evidence from animal studies and small clinical trials suggests that HBOT improves hypoxic/ischemic brain injuries, consequently inducing brain angiogensis, leading to cognitive improvement. Methods We present the design of the first double‐blind, placebo‐controlled, clinical trial on brain and cognitive outcomes in elderly (n = 154) with T2D and mild cognitive impairment to compare the effects of HBOT versus sham (normal air with 1.1 ATA pressure in the first and last 5 minutes of the session). Eligible candidates are randomized with equal probability to HBOT and sham. Outcomes are assessed before and after treatment, and at 6‐ and 12‐month follow‐up. The primary cognitive outcome is global cognitive change, indexed by a composite sum of z‐scores of four executive functions and four episodic memory tests. The primary neurobiological outcome is cerebral blood flow (CBF; via arterial spin labeling magnetic resonance imaging [ASL‐MRI]) and cerebral glucose utilization via fluorodeoxyglucose positron emission tomography (FDG‐PET). Secondary outcome measures are specific cognitive domains (executive function and episodic memory) and functional measures (Clinical Dementia Rating sum of boxes, activities of daily living). Efficacy analyses will be performed for the intent‐to‐treat sample. Discussion Recent studies suggest that HBOT induces neuroplasticity and improves cognition in post‐stroke and traumatic brain injury patients. However, its effect on cognition, cerebral blood flow, and brain glucose utilization in T2D patients at high dementia risk is yet to be determined. If effective, this study may provide strong evidence for the brain and cognitive benefits of HBOT in this population.

Abstract Introduction This study examined cortical thickness (CTX) in World Trade Center (WTC) responders with cognitive impairment (CI). Methods WTC responders (N = 99) with/without CI, recruited from an epidemiologic study, completed a T1‐MPRAGE protocol. CTX was automatically computed in 34 regions of interest. Region‐based and surface‐based morphometry examined CTX in CI versus unimpaired responders. CTX was automatically computed in 34 regions of interest. Region‐based measures were also compared to published norms. Results Participants were 55.8 (SD = 0.52) years old; 48 had CI. Compared to unimpaired responders, global mean CTX was reduced in CI and across 21/34 cortical subregions. Surface‐based analyses revealed reduced CTX across frontal, temporal, and parietal lobes when adjusting for multiple comparisons. Both CI and unimpaired WTC groups had reduced CTX in the entorhinal and temporal cortices compared to published normative data. Discussion Results from the first structural magnetic resonance imaging study in WTC responders identified reduced CTX consistent with a neurodegenerative disease of unknown etiology.

The basic strategy for focusing exclusively on genetically identified targets for intervening in late life dementias was formulated 30 years ago. Three decades and billions of dollars later, all efforts at disease-modifying interventions have failed. Over that same period, evidence has accrued pointing to dementias as late-life clinical phenotypes that begin as midlife pathologies. Effective prevention therefore may need to begin in midlife, in order to succeed. No current interventions are sufficiently safe to justify their use in midlife dementia prevention trials. Observational studies could be informative in testing the proposal that amyloid imaging and APOEε4 genotype can predict those who are highly likely to develop Alzheimer’s disease and in whom higher risk interventions might be justifiable. A naturally occurring, diet-responsive cognitive decline syndrome occurs in canines that closely resembles human Alzheimer’s. Canine cognitive dysfunction could be useful in estimating how early intervention must begin in order to succeed. This model may also help identify and assess novel targets and strategies. New approaches to dementia prevention are urgently required, since none of the world’s economies can sustain the costs of caring for this epidemic of brain failure that is devastating half of the over 85-year-olds globally.

The long-term effects of blast exposure are a major health concern for combat veterans returning from the recent conflicts in Iraq and Afghanistan. We used an optimized diffusion tensor imaging tractography algorithm to assess white matter (WM) fractional anisotropy (FA) in blast-exposed Iraq and Afghanistan veterans (n = 40) scanned on average 3.7 years after deployment/trauma exposure. Veterans diagnosed with a blast-related mild traumatic brain injury (mTBI) were compared to combat veterans with blast exposure but no TBI diagnosis. Blast exposure was associated with decreased FA in several WM tracts. However, total blast exposure did not correlate well with neuropsychological testing performance and there were no differences in FA based on mTBI diagnosis. Yet, veterans with mTBI performed worse on every neurocognitive test administered. Multiple linear regression across all blast-exposed veterans using a six-factor prediction model indicated that the amount of blast exposure accounted for 11–15% of the variability in composite FA scores such that as blast exposure increased, FA decreased. Education accounted for 10% of the variability in composite FA scores and 25–32% of FA variability in the right cingulum, such that as level of education increased, FA increased. Total blast exposure, age, and education were significant predictors of FA in the left cingulum. We did not find any effect of post-traumatic stress disorder on cognition or composite FA. In summary, our findings suggest that greater total blast exposure is a contributing factor to poor WM integrity. While FA was not associated with neurocognitive performance, we hypothesize that FA changes in the cingulum in veterans with multiple combat exposures and no head trauma prior to deployment may represent a marker of vulnerability for future deficits. Future work needs to examine this longitudinally.

Background/Aims: Impaired motor function has been associated with cognitive impairment and dementia, but this relationship is poorly understood in elderly with type 2 diabetes (T2D). We thus investigated it in a large sample (n = 726) of cognitively normal elderly with T2D. Methods: In this cross-sectional study, hierarchical linear regressions assessed correlations of 3 motor measures (timed walk, grip strength, and self-reported motor difficulties) with episodic memory, attention/working memory, semantic categorization, executive function, and overall cognition controlling for demographics. Results: Longer timed walk and weaker grip strength were associated with poorer performance in all cognitive domains except episodic memory. Conclusions: Associations of motor and cognitive functions in T2D and non-T2D samples are consistent. A lack of association of motor function with episodic memory may suggest non-Alzheimer's disease-related underlying mechanisms.

To study the relationships of long-term trajectories of glycemic control with cognitive performance in cognitively normal elderly with type 2 diabetes (T2D).Subjects (n = 835) pertain to a diabetes registry (DR) established in 1998 with an average of 18 HbA1c measurements per subject, permitting identification of distinctive trajectory groups of HbA1c and examining their association with cognitive function in five domains: episodic memory, semantic categorization, attention/working memory, executive function, and overall cognition. Analyses of covariance compared cognitive function among the trajectory groups adjusting for sociodemographic, cardiovascular, diabetes-related covariates and depression.Subjects averaged 72.8 years of age. Six trajectories of HbA1c were identified, characterized by HbA1c level at entry into the DR (Higher/Lower), and trend over time (Stable/Decreasing/Increasing). Both groups with a trajectory of decreasing HbA1c levels had high HbA1c levels at entry into the DR (9.2%, 10.7%), and high, though decreasing, HbA1c levels over time. They had the worst cognitive performance, particularly in overall cognition (p

Although amnestic mild cognitive impairment (aMCI; often considered a prodromal phase of Alzheimer's disease, AD) is most recognized by its implications for decline in memory function, research suggests that deficits in attention are present early in aMCI and may be predictive of progression to AD. The present study used functional magnetic resonance imaging to examine differences in the brain during the attention network test between 8 individuals with aMCI and 8 neurologically healthy, demographically matched controls. While there were no significant behavioral differences between groups for the alerting and orienting functions, patients with aMCI showed more activity in neural regions typically associated with the networks subserving these functions (e.g., temporoparietal junction and posterior parietal regions, respectively). More importantly, there were both behavioral (i.e., greater conflict effect) and corresponding neural deficits in executive control (e.g., less activation in the prefrontal and anterior cingulate cortices). Although based on a small number of patients, our findings suggest that deficits of attention, especially the executive control of attention, may significantly contribute to the behavioral and cognitive deficits of aMCI.

Clock-drawing is a widely used bedside test of constructional ability, but it has never been systematically studied or standardized. We examined 87 clocks drawn by neurologically impaired patients and age-matched controls, and propose a set of criteria for scoring clocks. Patients with probable Alzheimer's disease and other dementias have gross impairments in clock-drawing. These deficits include poor spatial arrangement of numbers, incorrect numerical sequence, insertion of stray lines, and addition of extra numbers. In Alzheimer's disease, the total score on the clock-drawing test correlates with the score on the Modified “Mini-Mental State” Examination. Non-demented patients with Parkinson's disease showed only defects in the spatial organization of the numbers, and non-demented patients with other diseases perform as well as controls.

The aim of the study was to determine whether the clinical benefits of galantamine for patients with Alzheimer's disease lead to benefits for caregivers. Data were pooled from two concurrent, multi-centre, randomized, double-blind, placebo-controlled, 6-month trials. Time caregivers spent assisting with activities of daily living (ADL) and time patients could be left unsupervised each day were assessed using the Allocation of Caregiver Time Survey. In total, 825 patients with mild-to-moderate Alzheimer's disease were included. At endpoint, caregivers of galantamine-treated patients were more likely to report reductions (41% vs 37%), maintenance (19% vs 14%) or smaller increases (26% vs 34% reporting an increase >30 minutes) in time assisting with ADL compared with the placebo group (p = 0.026; Wilcoxon rank-sum test). The mean daily time difference was 32 minutes (p = 0.011). Among patients with moderate Alzheimer's disease, caregivers of galantamine-treated patients were even more likely to report reductions (46% vs 37%), maintenance (15% vs 6%) or smaller increases (25% vs 42% for increases >30 min) vs placebo (p = 0.004), with a mean daily time saving of 53 minutes (p = 0.021). Caregivers of galantamine-treated patients were more likely to report increases (22% vs 18%), maintenance (45% vs 43%) or smaller reductions (30% vs 37% for reductions >30 minutes) in time the patient could be left unsupervised compared with placebo (p = 0.027). Mean daily time saving was 27 minutes. Among patients with moderate Alzheimer's disease, the treatment effect was greater (p = 0.029), with caregivers in the galantamine group reporting the change in time left unsupervised as 68 minutes longer each day than caregivers of patients receiving placebo. The clinical benefits of galantamine for patients with Alzheimer's disease are also associated with benefits to caregiving. Copyright © 2003 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

For the second time in the past 3 years, the EU-US CTAD Task Force addressed challenges related to designing clinical trials for agitation in dementia, which is one of the most disruptive aspects of the condition for both patients and caregivers. Six recommendations emerged from the Task Force meeting: 1 - Operationalizing agitation criteria established by the IPA; 2 - Combining clinician- and caregiver-derived outcomes as primary outcome measures; 3 - Using global ratings to define clinically meaningful effects and power studies; 4 - Improving the accuracy of caregiver reports by better training and education of caregivers; 5 - Employing emerging technologies to collect near real-time behavioral data; and 6 - Utilizing innovative trial designs and increasing the use of biomarkers to maximize the productivity of clinical trials for neuropsychiatric symptoms., Competing Interests: JC owns the copyright of the NPI. Other authors have no conflicts of interest with this paper. The Task Force was partially funded by registration fees from industrial participants. These corporations placed no restrictions on this work.