Cholinesterase Inhibitors May Not Benefit Mild Cognitive Impairment and Mild Alzheimer Disease Dementia Introduction: We investigated whether cholinesterase inhibitors (ChEIs) benefit cognitive outcomes in mild cognitive impairment due to Alzheimer disease (MCI-AD) and in mild AD dementia (ADdem). Methods: Data from 2242 individuals, clinically diagnosed with MCI-AD [Clinical Dementia Rating (CDR), 0 or 0.5] or with mild ADdem (CDR, 0.5 or 1), were available from the National Alzheimer’s Coordinating Center’s (NACC) Uniform Data Set (UDS). General linear mixed models were used to examine the annual change in the CDR Sum of Boxes (CDR-SB) and in neuropsychological performance. We compared slopes before and after ChEI initiation among ChEI users, and also compared the change in scores of ChEI users versus nonusers. Results: Thirty-four percent of 944 MCI-AD and 72% of 1298 ADdem participants were ChEI users. Cognitive decline was greater after ChEI initiation in MCI-AD and ADdem groups (eg, MCI-AD, CDR-SB: 0.03 points/y before initiation; 0.61 points/y after initiation, P<0.0001). Both MCI-AD and ADdem groups had faster decline after ChEI initiation than nonusers (eg, MCI-AD, CDR-SB: 0.61 points/y, ChEI users; 0.24 points/y, nonusers, P<0.0001). Discussion: This study suggests that ChEI use may not improve the cognitive course in MCI-AD and mild ADdem.

Alzheimer’s Environmental and Genetic Risk Scores are Differentially Associated With General Cognitive Ability and Dementia Severity Purpose: We investigated the association of the Australian National University Alzheimer’s Disease Risk Index (ANU-ADRI) and an Alzheimer disease (AD) genetic risk score (GRS) with cognitive performance. Methods: The ANU-ADRI (composed of 12 risk factors for AD) and GRS (composed of 25 AD risk loci) were computed in 1061 community-dwelling older adults. Participants were assessed on 11 cognitive tests and activities of daily living. Structural equation modeling was used to evaluate the association of the ANU-ADRI and GRS with: (1) general cognitive ability (g), (2) dementia-related variance in cognitive performance (δ), and (3) verbal ability (VA), episodic memory (EM), executive function (EF), and processing speed (PS). Results: A worse ANU-ADRI score was associated with poorer performance in “g” [β (SE)=−0.40 (0.02), P<0.001], δ [−0.40 (0.04), P<0.001], and each cognitive domain [VA=−0.29 (0.04), P<0.001; EM=−0.34 (0.03), P<0.001; EF=−0.38 (0.03), P<0.001; and PS=−0.40 (0.03), P<0.001]. A worse GRS was associated with poorer performance in δ [−0.08 (0.03), P=0.041] and EM [−0.10 (0.03), P=0.035]. Conclusions: The ANU-ADRI was broadly associated with worse cognitive performance, including general ability and dementia severity, validating its further use in early dementia risk assessment.

Which MCI Patients Should be Included in Prodromal Alzheimer Disease Clinical Trials? Background: Prodromal Alzheimer disease (AD) clinical trials enroll patients with mild cognitive impairment (MCI) meeting biomarker criteria, but specific enrollment criteria vary among trials. Methods: We used data from AD Neuroimaging Initiative (ADNI) MCI participants to assess AD biomarker eligibility, variation in trial outcome measures, and statistical power. Results: Most (65%) participants meet eligibility criteria based on low cerebrospinal fluid amyloid beta (Aβ). Relative to trials enrolling exclusively based on low cerebrospinal fluid Aβ, trials including participants with a high ratio of phosphorylated tau to Aβ would include an additional 15% of participants. Fewer (34% to 62%) participants met criteria for Aβ and tau. Differences in clinical and demographic characteristics of modeled trial samples were minimal. Those with low Aβ and high tau showed the greatest change over time on outcome measures. Conclusions: Eligibility rates for prodromal trials vary depending on the specific biomarker criteria, though differences in demographics and the variation associated with outcome measures are minimal. Broadening inclusion criteria beyond amyloid alone may facilitate recruitment but include patients showing slower progression over time. Biomarker criteria selection should be informed by the goal of enrolling individuals most likely to utilize and benefit from the intervention under investigation in a particular setting.

Long-term Changes in 18F-Flutemetamol Uptake in Nondemented Older Adults Purpose: Longitudinal studies into the variability of 18F-Flutemetamol uptake are lacking. Methods/Patients: Therefore, the current study examined change in 18F-Flutemetamol uptake in 19 nondemented older adults (65 to 82 y old) who were either cognitively intact or had Mild Cognitive Impairment (MCI) who were scanned twice across 3.6 years. Results: Baseline and follow-up composite SUVRs were significantly correlated (0.96, P<0.001). Significant increases in the composite SUVR from baseline to follow-up were observed (P=0.002). For the total sample, the average difference over this time period when using the composite SUVR was 6.8%. Similar results were seen in subsets of the total sample (MCI vs. cognitively intact, amyloid positive vs. negative). Finally, a Reliable Change Index that exceeded ±0.046 SUVR units would indicate a significant change of 18F-Flutemetamol. Conclusions: The current results extend the limited literature on longitudinal variability of 18F-Flutemetamol uptake across 3.6 years, which should give clinicians and researchers more confidence in the stability of this amyloid imaging agent in longer therapeutic and prevention trials in cognitive decline in MCI and Alzheimer disease.

An Algorithm to Characterize a Dementia Population by Disease Subtype Purpose: Identification of Alzheimer disease and related dementias (ADRD) subtypes is important for pharmacologic treatment and care planning, yet inaccuracies in dementia diagnoses make ADRD subtypes hard to identify and characterize. The objectives of this study were to (1) develop a method to categorize ADRD cases by subtype and (2) characterize and compare the ADRD subtype populations by demographic and other characteristics. Methods: We identified cases of ADRD occurring during 2008 to 2014 from the OptumLabs Database using diagnosis codes and antidementia medication fills. We developed a categorization algorithm that made use of temporal sequencing of diagnoses and provider type. Results: We identified 36,838 individuals with ADRD. After application of our algorithm, the largest proportion of cases were nonspecific dementia (41.2%), followed by individuals with antidementia medication but no ADRD diagnosis (15.6%). Individuals with Alzheimer disease formed 10.2% of cases. Individuals with vascular dementia had the greatest burden of comorbid disease. Initial documentation of dementia occurred primarily in the office setting (35.1%). Discussion: Our algorithm identified 6 dementia subtypes and three additional categories representing unique diagnostic patterns in the data. Differences and similarities between groups provided support for the approach and offered unique insight into ADRD subtype characteristics.

Olfactory Impairment and Hippocampal Volume in a Chinese MCI Clinical Sample Purpose: The aim of this study was to evaluate the relationship between olfactory function and hippocampal volume in patients with mild cognitive impairment (MCI). Methods: We enrolled a total of 31 MCI patients and 9 normal control subjects. All participants underwent 3.0 T-magnetic resonance imaging scanning. The scan results were processed using GE ADW4.6 processing software and V0xar 3D workstation to acquire the hippocampal volume. The University of Pennsylvania Smell Identification Test (UPSIT) was used to evaluate the olfactory function of MCI patients. The correlations of UPSIT score with hippocampal volume and hippocampal head volume were evaluated by Pearson correlation coefficient analysis. Results: MCI patients had significantly smaller left (2.78±0.50 vs. 3.19±0.31 cm3) and right (2.97±0.42 vs. 3.31±0.25 cm3) hippocampal volumes compared with normal controls (P<0.05). In addition, patients with olfactory dysfunction had smaller volumes of the hippocampus (left hippocampal volume, 2.57±0.39 vs. 3.23±0.40 cm3; right hippocampal volume, 2.86±0.43 vs. 3.22±0.30 cm3) and hippocampal head (left hippocampal head volume, 1.18±0.16 vs. 1.53±0.25 cm3; right hippocampal head volume, 1.25±0.22 vs. 1.54±0.22 cm3) compared with those with normal olfactory function (P<0.05). No significant difference in the hippocampal body volume and hippocampal tail volume was found between MCI patients with olfactory loss and those with normal olfactory function. The UPSIT score was significantly positively correlated with left hippocampal volume (r=0.55, P<0.05), right hippocampal volume (r=0.42, P<0.05), left hippocampal head volume (r=0.53, P<0.05), and right hippocampal head volume (r=0.45, P<0.05). Conclusions: Olfactory function correlates well with hippocampal volume among patients with MCI.

Differences in Awareness of Disease Between Young-onset and Late-onset Dementia Introduction: Awareness of disease is the ability to acknowledge changes caused by deficits related to the disease process. We aimed to investigate whether there are differences in awareness of disease between young-onset dementia (YOD) and late-onset dementia (LOD) and examined how awareness interacts with cognitive and clinical variables. Materials and Methods: Using a cross-sectional design, 49 people with YOD and 83 with LOD and their caregivers were included. We assessed awareness of disease, cognition, functionality, stage of dementia, mood, neuropsychiatric symptoms, and caregivers’ quality of life (QoL) and burden. Results: We found that people with YOD were more aware of the disease than people with LOD (P<0.005). Multivariate linear regression revealed that higher impairment in functional level was associated with unawareness in both groups (YOD=P<0.001; LOD=P<0.001). In the YOD group, preserved awareness was related to worse self-reported QoL (P<0.05), whereas, in LOD, deficits in awareness were related to caregivers’ worst perceptions about people with dementia QoL (P<0.001). Conclusions: The findings highlight the distinct nature of awareness between YOD and LOD. The YOD group had higher levels of disease awareness compared with the LOD group, even though the first group had a greater impairment in functionality.

Prevalence of Mild Cognitive Impairment Among Older People in Kazakhstan and Potential Risk Factors: A Cross-sectional Study Background: There have been no epidemiological studies of mild cognitive impairment (MCI) in Central Asia. Objective: The objective of this study was to describe the prevalence of, and risk factors for, MCI in an urban population in Kazakhstan. Methods: Adults aged 60 years and over were randomly selected from registers of 15 polyclinics in Almaty. Of 790 eligible people, 668 agreed to participate (response rate 85%). Subjects were screened using the Montreal Cognitive Assessment (MoCA). Those who scored 26 or lower on the MoCA were assessed by a multidisciplinary team and a diagnosis of normal cognition, MCI or dementia was made. Results: The median MoCA score was 22 and the prevalence of MCI was 30%. MoCA scores were lower, and MCI prevalence was higher, among those with less education and those with older age. There was no difference in MoCA scores or MCI prevalence by sex or ethnic group (Kazakh or Russian). High blood pressure, older age, and lower education were associated with increased odds of MCI in crude analyses but only age and education remained statistically significant in an adjusted logistic regression model. Conclusions: The prevalence of MCI in Kazakhstan is high. Higher levels of education may lead to lower prevalence of MCI in the future.

Dementia Reported Missing: Use of an Online Search Engine to Track Outcomes in Persons With Dementia Reported Missing Background: Persons with dementia (PWD) reported missing are known to be at high risk for mortality. Analysis of online search engines’ reports of missing PWD may show patterns in the data of this relatively common event and the broad patterns relevant to mortality risk factors. Methods: We searched Google news for PWD reported missing for 2015. Demographics, personal details, and outcomes were recorded. Results: Of 673 cases, 67 were found deceased, 525 alive, and the remainder had unknown outcomes. Mortality did not differ significantly by race/ethnicity for cases with known outcomes, but cases with unknown outcomes were significantly overrepresented among non-Caucasians (P<0.001; analysis of variance). Duration missing predicted mortality (P<0.001; χ2), and mortality was lower if a photograph was provided (P<0.05; χ2). Five states had no reports and some appeared to have fewer reports that would be expected based on estimates of dementia prevalence. Conclusions: Duration missing was the strongest predictor of mortality. Likelihood of mortality was not predicted by use of missing person alerts, and this may be a consequence of inconsistent reporting and follow-up of cases across states. Prevalence and mortality may likewise be underestimated because of the variability in usage and reporting of relevant search terms and definitions. Online resources and social media can provide information about trends and outcomes related to missing persons with dementia, but greater consistency is needed in definitions, searching, and reporting.

Cognitive Complaints in Nondemented Parkinson’s Disease Patients and Their Close Contacts do not Predict Worse Cognitive Outcome Objectives: The main purpose of this study was to investigate 4 methods of eliciting subjective cognitive complaints (SCCs) in Parkinson’s disease (PD) patients without dementia and determine the relationship between their SCC and cognitive performance. Design: This study was a retrospective analysis of a prospective cohort study. Setting: Six North American movement disorder clinics. Measurements: SCCs were elicited through a modified Neurobehavioral Inventory administered to patients and close contacts, a general complaint question, and Movement Disorders Society Unified Parkinson's Disease Rating Scale item question 1.1 administered to patients. Clinical evaluation, formal neuropsychological testing and Disability Assessment for Dementia were conducted in Ontario state. Agreement between SCCs eliciting methods was calculated. Associations between SCC, cognitive testing, and mild cognitive impairment (MCI) were assessed. Results: Of 139 participating nondemented PD patients, 42% had PD-MCI at baseline. Agreement between SCC eliciting methods was low. Neither patient-reported nor close contact-reported SCCs were associated with impaired baseline cognitive testing or PD-MCI nor were they associated with cognitive decline over time. In PD patients with normal baseline cognition, 26% of patients with 1-year follow-up and 20% of patients with 2-year follow-up met MCI criteria. Conclusions: Agreement between SCC eliciting methods is poor and no SCC method was associated with cognitive testing or decline over time. With no clear superior method for eliciting SCCs, clinicians should consider performing regular screening.