Baseline Mini-Mental State Exam Research Articles

Postoperative Cognitive Decline in Patients Undergoing Major Gynecologic Oncology Surgery: A Pilot Prospective Study

ObjectivesPostoperative cognitive decline (POCD) is characterised by deficits in attention, memory, executive function, and information processing that persist beyond the early postoperative period. Its incidence ranges from 10%–25% after noncardiac surgery. Limited literature exists on POCD after gynecologic oncology surgery. Our primary objective was to identify the incidence of POCD among patients 55 years or older undergoing major gynecologic oncology surgery. MethodsThis mixed-methods, prospective, observational cohort study followed patients 55 years or older who underwent surgery for gynecologic malignancies between February and July 2022. Semi-structured interviews and the Mini-Mental State Exam (MMSE) were administered before surgery as well as 1 and 3 months after. Assessments were delivered virtually and in-person in the context of the COVID-19 pandemic. POCD was defined as ≥2-point decline from baseline MMSE score. ResultsTwenty-four patients participated; 19 completed the 1-month follow-up, and 15 completed the 3-month follow-up. The average age was 64 (range: 56–90). The mean preoperative MMSE score was 16.6 out of 17 (virtual) and 12.9 out of 13 (in-person). Two patients had a 1-point decline in their 1-month MMSE score; both recovered by 3 months. One patient had a 1-point decline in their 3-month MMSE score. Semi-structured interviews revealed common themes of “brain fog” at the 1-month follow-up and mild, persistent attention and word-finding deficits at 3 months postoperatively. ConclusionsThis study’s qualitative component captured subtle subjective findings suggestive of potential POCD. Larger studies are required, and a more extensive neuropsychological test battery may be required to elicit subtle findings not clearly reflected by MMSE scores.

Lateral temporal atrophy is a better predictor of baseline MMSE scores than hippocampal atrophy in Alzheimer’s disease: A retrospective cross-sectional study

Background: Mini-Mental State Exam (MMSE) is widely used for the cognitive assessment in Alzheimer’s disease (AD), but its interpretation could be affected by acute medical conditions, depression, or anxiety. Conversely, brain magnetic resonance imaging (MRI) is an independent diagnostic tool to evaluate specific cerebral pathology. Many studies have investigated the correlation between MRI visual scales such as hippocampal atrophy and baseline MMSE in AD patients. However, the correlation between a comprehensive MRI visual scale and baseline MMSE in people with AD remains less well known. Method: We retrospectively collected records of outpatients diagnosed with probable AD according to DSM -5 criteria. The comprehensive visual rating scale (CVRS) was used to semiquantitatively measure structural changes and vascular lesions. The relationship between MRI changes and baseline MMSE was evaluated using Bayesian model averaging (BMA). Results: A total of 65 patients, among whom 21 (32.31%) had early-onset AD, were included. Lateral temporal atrophy, level of education, and late age at onset were the strongest independent predictors of baseline MMSE. Furthermore, hippocampal atrophy was only correlated with delayed recall, while temporal atrophy was correlated with orientation, attention, language, and visual-spatial items of the MMSE. The cerebral atrophy and small vessel lesions scores of the late-onset AD group were significantly higher than those of the early-onset group, despite negligible differences in education and MMSE. Conclusion: Our study suggests lateral temporal atrophy correlates with baseline MMSE scores in people with AD better than the hippocampal atrophy. Age-related atrophy and silent small vessel disease lesions may have negligible impact on AD patients’ cognitive impairment.

Rate of cognitive decline before seizure diagnosis in individuals with dementia and seizures

AbstractBackgroundSeizures and epilepsy occur frequently in individuals diagnosed with dementia. While previous studies report highest incidence in advanced disease stages, emerging studies suggest subclinical seizures noted only on Magnetoencephalography or electroencephalography(EEG) occur frequently in early stages. Such recorded subclinical seizure activity is associated with a more rapid course of cognitive decline on longitudinal assessment. We thus hypothesized individuals with dementia who are diagnosed with seizures in any stage experience a rapid cognitive decline before they are diagnosed with seizures.MethodStudy design is a retrospective case‐control study, assessing clinical data from 24142 research subjects evaluated longitudinally from the National institute of health Alzheimer Coordination Center, years 2006‐2019. Seizures diagnosed during follow up were used as a predicting variable. Individuals with seizures on their first visit as well as individuals with unknown seizure status were excluded. Individuals with unknown APOE genotype and those without longitudinal data were also excluded. We assessed cognitive decline as an outcome using annual Mini Mental State Exam (MMSE) and Clinical Dementia Rating Sum of Boxes (CDR‐SB). We assessed the decline using a linear mixed effects models adjusting for other variables known to alter decline rate such as age at onset of symptoms, sex and ApoE4 genotype and included a random effect for time between visits within patients.ResultWe identified 205 and 4667 individuals with and without seizures respectively on follow up research visits. Patients with seizures had an younger mean age at symptom onset (65±11.3 vs 70±10.0), of similar sex (50.0% and 50.7% male) and remained longer on follow up (5±3 vs 3±2). Baseline MMSE and CDR‐SB was similar in both groups. Compared to subjects without seizures, those with seizures had a rapid annual decline in CDR‐SB (0.98, SE 0.24, 95% CI 0.51‐1.46, p<.0001) and MMSE (‐1.8, SE = .40, 95% CI ‐1.4 and ‐2.6, p<0.00001).ConclusionA rapid rate of decline can be observed in individuals with dementia prior to seizure diagnosis. Our study suggests undiagnosed seizures or seizures activity on EEG should be suspected in individuals who experience a rapid rate of cognitive decline.

Comparing Mini‐Mental Status Exam baseline data of cognitively normal individuals who declined to Alzheimer’s disease versus cognitively normal non‐decliners in the SIU Longitudinal cognitive aging study

AbstractBackgroundThe Mini‐Mental Status Exam (MMSE) is one of the most commonly used cognitive screening measures for diagnosing cognitive impairment in older adults. In the present study, we examined whether or not there were baseline differences in MMSE scores between cognitively normal individuals who developed Alzheimer’s disease over time (decliners) versus individuals who did not decline over time (non‐decliners).MethodWe included 67 participants who were administered the MMSE during a baseline assessment. All participants were enrolled in the SIU Longitudinal Cognitive Aging Study (SIU LCAS) as controls who were free of cognitive impairment at their baseline visits. Participants were divided into two groups (decliners versus non‐decliners). There were 25 participants in the decliner group and 39 participants in the non‐decliner group. Average age of decliners was 70.84, while average age of non‐decliners was 71.67. Average education of decliners was 15.76 years, while average education of non‐decliners was 16.49 years. The ratio of females to males was 4:1 among decliners and 1.6:1 among non‐decliners. A two‐sample t‐test was used to examine differences between the two groups with respect to their baseline MMSE scores.ResultThe decliner group (mean age = 70.8) was significantly younger than the non‐decliner group (mean age = 71.7). There were no significant differences between the two groups for education or gender distribution. 11 decliners had autopsy confirmed AD, while 14 decliners had AD diagnosis without autopsy. There were 5 individuals in the non‐decliner group with no evidence of AD pathology on autopsy. The decliner group had significantly lower baseline MMSE scores compared to the non‐decliner group (p < 0.05). MMSE scores for decliners compared to non‐decliners using WORLD backwards was 28.96 versus 29.44, respectively, and was 28.32 versus 28.85, respectively, when using serial 7’s.ConclusionThe results of the present study indicate that there are subtle differences in baseline MMSE scores (approximately 0.5 points) in older adults who decline to AD compared to older adults who remained cognitively normal. More studies with larger sample sizes, including more participants with brain autopsy, are needed to confirm these findings.

S-02-4: BLOOD PRESSURE, ANTIHYPERTENSIVES AND DEMENTIA, AN INDIVIDUAL PATIENT DATA META-ANALYSIS

Background: A large number of observational studies show links between hypertension or higher blood pressure (BP) in mid-life and an increased risk of later dementia. In late life, the evidence is more mixed with some studies indicating higher BP is associated with higher dementia risk and some finding U-shaped associations between BP and incident dementia in older age. The clinical trials of antihypertensives to lower BP have shown largely negative results when examining the relationship between antihypertensive use and incident dementia. However, the trials were designed to examine cardiovascular endpoints and several stopped early for cardiovascular benefit thus limiting their statistical power and ability to accrue dementia outcomes. To overcome some of these limitations a pooled individual patient data meta-analysis of five seminal double-blind placebo-controlled randomised trials was undertaken to better define the effects of BP lowering treatment for the prevention of dementia. Methods: The double-blind placebo-controlled randomised antihypertensive trials; Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation (ADVANCE), Hypertension in the Very Elderly Trial (HYVET), Perindopril Protection Against Recurrent Stroke Study (PROGRESS), Systolic Hypertension in the Elderly Program (SHEP), and SYSTolic Hypertension in EURope Trial (SYST-EUR) were merged into a single database. Multilevel logistic regression was used to evaluate the treatment effect on incident dementia. Effect modification was assessed for key population characteristics including age, baseline systolic BP, sex, baseline Mini-Mental State Exam (MMSE) score and presence of prior stroke. Results: All trials were balanced across randomised groups. The combined sample was n = 28,008 recruited from 20 countries. Mean baseline age was 69.1 (Standard Deviation 9.3). Median follow-up 4.3 years. Incident dementia occurred in 2.9% and 3.3% of those in active and placebo groups, respectively. Multilevel logistic regression reported an adjusted odds ratio 0.87 (95% confidence interval 0.75, 0.99) in favour of antihypertensive treatment reducing risk of incident dementia with a mean BP lowering of 10/4mmHg. Further multinomial regression taking account of death as a competing risk found similar results. There was no effect modification by age, sex, baseline systolic BP, baseline MMSE or prior stroke. Discussion: This is the first single-stage individual patient data meta-analysis from double-blind placebo-controlled clinical trials. It provides high-quality evidence to support the benefits of antihypertensive treatment in late-mid and later life to lower the risk of dementia. Questions remain as to the potential benefit from antihypertensive treatment commenced earlier in the life-course to reduce the long-term risk of dementia.

Polygenic risk scores for Alzheimer's disease predict MMSE decline in APOE4 carriers and noncarriers and the impact of sample overlap with GWAS summary statistics.

Heterogeneity in the progression of cognitive impairment, which is common in sporadic Alzheimer's disease (AD) trials, is especially challenging to predict in pre-symptomatic populations, and has a negative impact on clinical trial power. Heritability of AD extends beyond the APOE genotype, with multiple common genetic variants identified in large genome wide association studies (GWAS). Incorporating APOE and additional genetic variants into models has the potential to improve the prediction of disease progression. The limited volume of genetic cohorts in AD and the sample overlap in GWAS summary statistics poses some concern for polygenic risk score (PRS) overfitting. A PRS was calculated using genome-wide association study (GWAS) summary statistics for clinical AD diagnosis. PRS derived from this GWAS study was computed for participants drawn from two aging studies. Logistic regression models assessed the association between PRS and Mini Mental State Exam (MMSE) decline covarying for age, sex, education, APOE-ε4, and baseline MMSE score. Age and sex interactions with PRS were also assessed. Samples assumed to be used in the GWAS calculations were then removed from the test set and the impact to performance was analyzed. Participants in the training and test set showed similar baseline ages, years of education and baseline MMSE scores in the whole sample and after stratification by APOE4 carrier status. The PRS model was a significant predictor of MMSE decline, as well as in APOE4 carriers and noncarriers. Model performance was compared to the test set excluding the GWAS overlap samples and no significant difference was observed. The proposed model including PRS explains heterogeneity in cognitive decline above and beyond the APOE4 allele. Testing the model in a dataset excluding GWAS overlap samples did not result in a significant difference in performance and potential overfitting does not appear to be an impact. Utilization of demographic and genomic factors beyond APOE in PRS models could enhance clinical trial recruitment and stratification strategies for trial analyses, such that APOE4 carriers are selected for probable cognitive decline, in addition to APOE3 carriers that are high on polygenic risk.

NCOG-12. COGNITIVE FUNCTION (CF) & QUALITY OF LIFE (QOL) IN PATIENTS TREATED WITH PROCARBAZINE, CCNU, & VINCRISTINE (PCV) + RADIOTHERAPY (RT) VS. RT FOR ANAPLASTIC OLIGODENDROGLIOMA (AO) ON NRG RTOG TRIAL 9402

Abstract BACKGROUND PCV+RT substantially prolongs survival in AO patients, but long-term CF and QOL implications are unclear. We compared CF and QOL by treatment arm in RTOG 9402 participants and evaluated the impact that baseline characteristics had on CF, QOL, and survival. METHODS CF and QOL were evaluated using the Mini Mental State Exam (MMSE) and Brain-Quality of Life (B-QOL) scale at baseline and annually. Scores were analyzed between treatment arms at each time point for patients with ≥ 10 years of follow-up data. Shared parameter models evaluated MMSE and B-QOL scores and survival for all patients. RESULTS 42/148 (28.4%) participants in PCV+RT and 20/143 (14%) in RT alone arms survived ≥ 10 years. 35/42 and 39/42 (PCV+RT) and 18/20 and 17/20 (RT) participants completed baseline B-QOL and MMSE assessments, respectively. B-QOL scores did not differ between treatment groups at any time-point. Among 16 patients (10 PCV+RT, 6 RT) who completed year 10 MMSE evaluations, mean MMSE score at 10 years was higher in the RT arm (29.83 [95% CI 22.1, 30.0] vs. 26.50 [95% CI 29.4, 30.0], P= 0.04). Change in MMSE and B-QOL scores from baseline did not differ significantly between treatment groups at any time. In shared parameter models including all patients with baseline assessments, MMSE and B-QOL scores decreased over time (MMSE P= 0.0189, B-QOL P= 0.0005), but this did not differ by treatment group (MMSE P= 0.5727, B-QOL P= 0.3592). Younger age and higher KPS predicted better scores (MMSE P < 0.0001, P = 0.0002; B-QOL P = 0.0043, P = 0.0007). PCV+RT predicted better survival in both models. CONCLUSIONS PCV+RT improves survival in AO. Shared parameter models show decrease in MMSE and B-QOL over time. However, relative to RT alone, the addition of PCV did not impact change in CF and QOL over time.

Delirium in older patients undergoing aortic valve replacement: incidence, predictors, and cognitive prognosis

BackgroundTranscatheter aortic valve replacement is increasingly performed in frail older patients who were previously ineligible for a standard surgical procedure. The objectives of this study are to determine delirium incidence, predictors, and relationship with cognitive performance at 3-month follow-up in older patients undergoing aortic valve replacement (AVR).MethodsPatients (N = 93) aged 70 years and older, undergoing transcatheter (TAVR, N = 66) or surgical (SAVR, N = 27) aortic valve replacement in an academic medical center were enrolled in this prospective cohort study. Delirium was assessed using the Confusion Assessment Method (CAM) on postoperative days 1, 2, 3, and 7. Data on patients’ socio-demographics, functional status (including instrumental activities of daily living (IADL), and surgical risk scores (including Society of Thoracic Surgeons (STS) risk score), were collected at baseline. Cognitive status was assessed with the Mini-Mental Status Exam (MMSE) and the Clock Drawing Test (CDT) at baseline and 3 months after AVR.ResultsDelirium occurred in 21 (23%) patients, within the first three postoperative days in 95% (20/21) of the cases. Delirium incidence was lower in TAVR (13/66 = 20%) than SAVR (8/27 = 30%) patients, but this difference was not statistically significant (p = .298). Patients with delirium had lower baseline cognitive performance (median MMSE score 27.0 ± 3.0 vs 28.0 ± 3.0, p = .029), lower performance in IADL (7.0 vs 8.0, p = .038), and higher STS risk scores (4.7 ± 2.7 vs 2.9 ± 2.3, p = .020). In multivariate analyses, patients with intermediate (score > 3 to ≤8) and high (score > 8) STS risk scores had 4.3 (95%CI 1.2–15.1, p = .025) and 16.5 (95%CI 2.0–138.2, p = .010), respectively, higher odds of incident delirium compared to patients with low (score ≤ 3) STS risk scores. At 3-month follow-up (N = 77), patients with delirium still had lower MMSE score (27.0 ± 8.0 vs 28.0 ± 2.0, p = .007) but this difference did not remain significant once adjusting for baseline MMSE (β-coefficient 1.11, 95%CI [− 3.03–0.80], p = .248).ConclusionsDelirium occurred in about one in five older patients undergoing AVR, almost essentially within the first three postoperative days. Beside cognitive performance, STS risk score could enhance the identification of high-risk older patients to better target preventative interventions.

Effect of baseline cognitive impairment on association between predicted propofol effect site concentration and Bispectral index or sedation score

BackgroundThis study determined whether the relationship between predicted propofol effect site concentration (Ce) and observer’s assessment of alertness/sedation scale (OAA/S) or Bispectral Index (BIS) was similar comparing cognitively intact vs impaired patients undergoing hip fracture repair with spinal anesthesia and sedation.MethodsFollowing informed consent baseline mini-mental status exam (MMSE), Clinical Dementia Rating (CDR) and geriatric depression scale (GDS) were obtained. Intraoperatively OAA/S, BIS, and propofol (timing and exact amounts) administered were recorded. Cerebrospinal fluid was collected for Alzheimer’s (AD) biomarkers. Mean Ce level (AvgCe) during surgery was calculated using the area under the Ce measurement series from incision to closure, divided by surgical time. Average OAA/S (AvgOAA/S), and BIS (AvgBIS) were similarly calculated. Pearson correlations of AvgCe with AvgOAA/S and AvgBIS were calculated overall and by CDR. Nonparametric locally weighted scatterplot smoothing (LOWESS) fits of AvgOAA/S and AvgBIS on AvgCe were produced, stratified by CDR. Multivariable regression incorporating baseline cognitive measurements or AD biomarkers assessed AvgOAA/S or AvgBIS associations with AvgCe.ResultsIn 186 participants AvgBIS and AvgOAA/S correlated with AvgCe (Pearson ρ = − 0.72; p < 0.0001 and Pearson ρ = − 0.81; p < 0.0001, respectively), and remained unchanged across CDR levels. Association patterns of AvgOAA/S or AvgBIS on AvgCe guided by LOWESS fits and modeled through regression, were similar when stratified by CDR (p = 0.16). Multivariable modeling found no independent effect on AvgBIS or AvgOAA/S by MMSE, CDR, GDS, or AD biomarkers after accounting for AvgCe.ConclusionsWhen administering sedation in conjunction with spinal anesthesia, cognitive impairment does not affect the relationship between predicted propofol AvgCe and AvgOAA/S or AvgBIS.

Cognitive Impairment and Mortality in a Population-Based Parkinson's Disease Cohort.

Parkinson's disease (PD) is a heterogeneous disorder with variability in phenotype and progression. We describe characteristics of PD patients in the largest population-based cohort followed for progression to date, and evaluate clinical risk factors for cognitive impairment and mortality. We collected longitudinal data using the Unified Parkinson's Disease Rating Scale (UPDRS), Mini-Mental State Exam (MMSE), and Geriatric Depression Scale (GDS) in 242 new-onset PD patients followed for progression. We compared those who developed cognitive impairment (MMSE≤24) with those who did not, using t-tests, chi-square tests, and Cox proportional hazards regression. Mortality risk factors were assessed in all 360 patients enrolled at baseline. Thirty-four patients developed cognitive impairment during follow-up. Baseline characteristics predictive of faster time to cognitive impairment were older age at diagnosis, fewer years of education, and longer average sleep duration reported. The 197 patients who died were older at diagnosis, reported longer average sleep duration, had lower baseline MMSE scores, higher UPDRS-III scores, and a higher proportion were of the postural instability gait difficulty (PIGD) subtype. Patients with the tremor dominant (TD) subtype at baseline were less likely to develop cognitive impairment or die during follow-up. Progression of cognitive, depressive, and motor symptoms occurred in parallel. Motor symptom severity and subtype influence the incidence of cognitive impairment and mortality in PD, with the TD motor subtype being relatively protective. In addition, we newly found that longer average sleep duration at baseline predicts faster progression to cognitive impairment and mortality.

Depression and Risk of Alzheimer Dementia: A Longitudinal Analysis to Determine Predictors of Increased Risk among Older Adults with Depression

Older adults with depression are at increased risk of Alzheimer dementia, but predictors of increased risk remain incompletely understood. We aim to identify characteristics of older adults with depression most at risk of progressing to Alzheimer dementia. Identification of high-risk subgroups could facilitate future interventional strategies to reduce risk of Alzheimer dementia in older adults with depression. Using data from the National Alzheimer's Coordinating Center, 1,965 participants with clinically defined depression and mild cognitive impairment at baseline were followed until development of Alzheimer dementia or loss to follow-up. Seven hundred and eighty (39.7%) developed Alzheimer dementia over a median follow-up duration of 27 months. In survival analyses, age (hazard ratio [HR] 1.04, 95% 1.03-1.05), baseline Mini-Mental State Exam (HR 0.85, 95% confidence interval 0.83-0.87), amnestic subtype of mild cognitive impairment (HR 1.66, 95% 1.30-2.12), presence of APOE4 allele (HR 1.99, 1.69-2.36), and presence of active depression within the last two years (HR 1.44, 95% confidence interval 1.16-1.79) were all independently associated with increased risk of Alzheimer dementia. Six hundred and fifty-six (41.7%) participants with mild cognitive impairment and active depression within the last two years developed Alzheimer dementia compared to 120 (31.6%) of those with a more remote history of depression. Older adults with depression and mild cognitive impairment demonstrated a high rate of progression to Alzheimer dementia over a relatively short duration of follow-up. Individuals with a combination of mild cognitive impairment and recently active depression are a particularly high-risk subgroup.

Combining Polygenic Hazard Score With Volumetric MRI and Cognitive Measures Improves Prediction of Progression From Mild Cognitive Impairment to Alzheimer's Disease.

Improved prediction of progression to Alzheimer's Disease (AD) among older individuals with mild cognitive impairment (MCI) is of high clinical and societal importance. We recently developed a polygenic hazard score (PHS) that predicted age of AD onset above and beyond APOE. Here, we used data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) to further explore the potential clinical utility of PHS for predicting AD development in older adults with MCI. We examined the predictive value of PHS alone and in combination with baseline structural magnetic resonance imaging (MRI) data on performance on the Mini-Mental State Exam (MMSE). In survival analyses, PHS significantly predicted time to progression from MCI to AD over 120 months (p = 1.07e-5), and PHS was significantly more predictive than APOE alone (p = 0.015). Combining PHS with baseline brain atrophy score and/or MMSE score significantly improved prediction compared to models without PHS (three-factor model p = 4.28e-17). Prediction model accuracies, sensitivities and area under the curve were also improved by including PHS in the model, compared to only using atrophy score and MMSE. Further, using linear mixed-effect modeling, PHS improved the prediction of change in the Clinical Dementia Rating—Sum of Boxes (CDR-SB) score and MMSE over 36 months in patients with MCI at baseline, beyond both APOE and baseline levels of brain atrophy. These results illustrate the potential clinical utility of PHS for assessment of risk for AD progression among individuals with MCI both alone, or in conjunction with clinical measures of prodromal disease including measures of cognitive function and regional brain atrophy.

NEUROPSYCHIATRIC SYMPTOMS AND COGNITIVE DECLINE IN COGNITIVELY NORMAL ELDERLY: THE CACHE COUNTY STUDY OF AGING

NPS are well-replicated risk factors for cognitive and functional decline in prodromal Alzheimer's disease (AD) and there is stronge vidence that they have similar effects in cognitively older normal adults. We sought to examine these associations in the Cache County Study of Aging. A population-based sample of all residents > 65 years old in Cache County, Utah (USA) was evaluated with a multi-stage dementia screen and diagnoses adjudicated by a multidisciplinary geriatric specialty team. Participants were included in this analysis if the consensus diagnosis was cognitively normal, based on all available data. Assessments were performed 3–4 times 3–4 years apart. NPS were assessed with the Neuropsychiatric Inventory (NPI) and cognition with Mini-Mental State Exam (MMSE). MMSE trajectories were estimated with mixed-effects models, assessing the effect of baseline NPI domains scores and controlling for age, education, and gender. 470 cognitively normal participants (58% female) had mean(SD) age of 79 (7.8) years, 13.2 (3.0) years education, baseline MMSE of 27.3 (2.4), and baseline Clinical Dementia Rating Sum of Boxes of 0.54 (2.0). Baseline NPI scores were low with only 4.6% reporting depression and 4.0% reporting anxiety. Baseline NPI delusion and irritability scores were significantly associated with poorer cognition (lower MMSE). Similar results were observed if one coded NPI scores dichotomously as 0 vs. > 0. In this cognitively normal population-based sample, delusions and irritability were associated with poorer cognitive and functional outcomes most likely representing both non-AD and AD trajectories. These results will be contrasted and discussed in the context of findings from other large epidemiological cohorts demonstrating NPS-related progression in preclinical AD.

Effect of Vascular Risk Factors on the Progression of Mild Alzheimer's Disease and Lewy Body Dementia.

Vascular risk factors (VRF) are associated with an increased risk of neurodegenerative disease. To examine the association between VRF and cognitive decline in patients with Alzheimer's disease (AD) and Lewy body dementia (LBD). We included consecutive referrals with mild AD or LBD to dementia clinics in western Norway from 2005 to 2013. The Mini-Mental Status Exam (MMSE) and Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) were administered at baseline and then annually for up to five years. The VRF include diabetes mellitus, hypertension, hypercholesterolemia, overweight and smoking. Generalized Estimating Equations (GEE) were used to examine the potential association between VRF scores and the change in MMSE and CDR-SB scores, adjusting for age, sex, and the apolipoprotein ɛ4 allele (APOE4). A total of 200 patients were included (113 AD, 87 LBD) (mean age 76 years, mean baseline MMSE 24.0, mean follow-up time 3.5 years). Smoking was the only VRF significantly associated with a more rapid cognitive decline, however only in the AD group. Being overweight at baseline was associated with a slower cognitive decline. Moreover, hypertension at baseline predicted a slower decline in MMSE scores. In the LBD group diabetes mellitus was found to be associated with a slower increase in CDR-SB scores. With the exception of smoking, VRF at time of dementia diagnosis were not associated with a more rapid cognitive decline.

Associations of cumulative Pb exposure and longitudinal changes in Mini-Mental Status Exam scores, global cognition and domains of cognition: The VA Normative Aging Study

BackgroundLead (Pb) exposure has been associated with poorer cognitive function cross-sectionally in aging adults, however the association between cumulative Pb exposure and longitudinal changes in cognition is little characterized. MethodsIn a 1993–2007 subcohort of the VA Normative Aging Study (Mini-mental status exam (MMSE) n=741; global cognition summary score n=715), we used linear mixed effects models to test associations between cumulative Pb exposure (patella or tibia bone Pb) and repeated measures of cognition (MMSE, individual cognitive tests, and global cognition summary). Cox proportional hazard modeling assessed the risk of an MMSE score falling below 25. ResultsAmong men 51–98 at baseline, higher patella Pb concentration (IQR: 21μg/g) was associated with −0.13 lower baseline MMSE (95% CI: −0.25, −0.004) and faster longitudinal MMSE decline (−0.016 units/year, 95% CI: −0.032, −0.0004) over 15 years. Each IQR increase in patella Pb was associated with increased risk of a MMSE score below 25 (HR=1.21, 95% CI: 0.99, 1.49; p=0.07). There were no significant associations between Pb and global cognition (both baseline and longitudinal change). Patella Pb was associated with faster longitudinal decline in Word List Total Recall in the language domain (0.014 units/year, 95% CI: −0.026, −0.001) and Word List Delayed Recall in the memory domain (0.014 units/year, 95% CI: −0.027, −0.002). We found weaker associations with tibia Pb. ConclusionsCumulative Pb exposure is associated with faster declines in MMSE and Word List Total and Delayed Recall tests. These findings support the hypothesis that Pb exposure accelerates cognitive aging.

PS1 -125 Assessment of Function and Quality of Life in a Phase II Multi-Institutional Clinical Trial of Fractionated Simultaneous In-Field Boost Radiotherapy for Patients with 1-2 Brain Metastases

We examined functional outcomes and quality of life of whole brain radiotherapy (WBRT) with integrated fractionated stereotactic radiotherapy boost (FSRT) for brain metastases treatment. Methods Eighty seven people with 1-3 brain metastases were enrolled on this Phase II trial of WBRT (30Gy/10)+simultaneous FSRT, (60Gy/10). Results Mean (Min-Max) baseline KPS, Mini Mental Status Exam (MMSE) and FACT-BR quality of life were 83 (70-100), 28 (21-30) and 143 (98-153). Lower baseline MMSE (but not KPS or FACT-Br) was associated with worse survival after adjusting for age, number of metastases, primary and extra-cranial disease status. Crude rates of deterioration (&gt;10 points decrease from baseline for KPS and FACT-Br, MMSE fall to&lt;27) ranged from 26-38% for KPS, 32-59% for FACT-Br and 0-16%for MMSE depending on the time-point assessed with higher rates generally noted at earlier time points (&lt;6months post-treatment). Using a linear mixed models analysis, significant declines from baseline were noted for KPS and FACT-Br (largest effects at 6 weeks to 3 months) with no significant change in MMSE. Conclusions The effects on function and quality of life of this integrated treatment of WBRT+simultaneous FSRT were similar to other published series combining WBRT+SRS.

Reliability and Validity of a New Behavioral Scale to Measure Behavioral and Psychological Symptoms in Dementias (BPSD): Luthra's Behavioral Assessment and Intervention Response (LuBAIR) Scale

age, education, gender, and study visit. They were also matched on baseline Mini-Mental Status Exam (MMSE) and matched visit global Clinical Dementia Rating Scale (CDR). Images were processed as per the ADNI protocol. Results: Independent samples t-tests demonstrated significantly increased activity in the left temporal, left anterior insula and right anterior insular regions. The left temporal volume of interest (VOI) had 21 voxels, centered at Montreal Neurological Institute (MNI) coordinates x 1⁄440 , y1⁄40 , z1⁄4 34. The left insula VOI had 45 voxels centered at MNI coordinates x 1⁄4 30, y1⁄414, z1⁄410. The right insula VOI had 151 voxels centred at MNI coordinates x1⁄4 32, y1⁄426, z1⁄44. Conclusions: These regions (temporal lobe, insular cortices) are involved in sensory and emotional processing and have been previously implicated in neuroimaging studies of delusions in dementia. Future studies should attempt to replicate these findings in a larger sample of patients.

Latent classes of course in Alzheimer's disease and predictors: the Cache County Dementia Progression Study.

Several longitudinal studies of Alzheimer's disease (AD) report heterogeneity in progression. We sought to identify groups (classes) of progression trajectories in the population-based Cache County Dementia Progression Study (N = 328) and to identify baseline predictors of membership for each group. We used parallel-process growth mixture models to identify latent classes of trajectories on the basis of Mini-Mental State Exam (MMSE) and Clinical Dementia Rating sum of boxes scores over time. We then used bias-corrected multinomial logistic regression to model baseline predictors of latent class membership. We constructed receiver operating characteristic curves to demonstrate relative predictive utility of successive sets of predictors. We fit four latent classes; class 1 was the largest (72%) and had the slowest progression. Classes 2 (8%), 3 (11%), and 4 (8%) had more rapid worsening. In univariate analyses, longer dementia duration, presence of psychosis, and worse baseline MMSE and Clinical Dementia Rating sum of boxes were associated with membership in class 2, relative to class 1. Lower education was associated with membership in class 3. In the multivariate model, only MMSE remained a statistically significant predictor of class membership. Receiver operating characteristic areas under the curve were 0.98, 0.88, and 0.67, for classes 2, 3, and 4 relative to class 1. Heterogeneity in AD course can be usefully characterized using growth mixture models. The majority belonged to a class characterized by slower decline than is typically reported in clinical samples. Class membership could be predicted using baseline covariates. Further study may advance our prediction of AD course at the population level and in turn shed light on the pathophysiology of progression.

Modifying roles of glutathione S-transferase polymorphisms on the association between cumulative lead exposure and cognitive function

BackgroundGlutathione-S-transferase gene (GST) polymorphisms can result in variable ability of these enzymes to remove electrophilic substrates. We investigated whether the GSTP1 Val105 and GSTM1 deletion polymorphisms modify the lead-cognitive function association. MethodsWe used repeated measures analysis to compare the association between cumulative lead biomarkers—bone lead measured using K-shell X-Ray Fluorescence—and Mini-Mental State Exam (MMSE) score by GST variants, adjusted for covariates, among Normative Aging Study participants, a Boston-based prospective cohort of men. We had complete data for 698 men (providing 1292 observations) for GSTM1 analyses and 595 men (providing 1142 observations) for GSTP1 analyses. ResultsA 15μg/g higher tibia lead concentration (interquartile range of tibia lead) was associated with a 0.24 point decrement in MMSE score among GSTP1 Val105 variant carriers, which was significantly stronger than the association among men with only wild-type alleles (p=0.01). The association among GSTP1 Val105 carriers was comparable to that of 3 years of age in baseline MMSE scores. The association between tibia lead and MMSE score appeared progressively steeper in participants with increasingly more GSTP1 Val105 alleles. A modest association between tibia lead and lower MMSE score was seen among participants with the GSTM1 deletion polymorphism. Neither of the glutathione S-transferase variants was independently associated with cognitive function, nor with lead biomarker measures. The results pertaining to patella lead were similar to those observed for tibia lead. ConclusionOur results suggest that the GSTP1 Val105 polymorphism confers excess susceptibility to the cognitive effects of cumulative lead exposure.

Quantification of disease progression and dropout for Alzheimer’s disease

This research aimed to quantitatively describe the natural progression of Alzheimer's disease (AD) based on ADAScog scores in patients with mild-to-moderate AD. ADAS-cog data from 10 placebo-controlled clinical trials including more than 2,400 patients with up to 72 weeks of treatment were used. Different models describing the time course of ADAS-cog were evaluated. Patient characteristics potentially affect score changes were assessed. Furthermore, patient dropout patterns were characterized using parametric survival models. Covariate selection was performed to identify the risk factors associated with a higher dropout rate. ADAS-cog time course in mild-tomoderate AD patients receiving placebo was best described by a log-linear model, where the intercept represents the log-transformed ADAS-cog score at Week 10, the slope is the disease progression (i.e., natural increase of ADAS-cog score) on the log scale. Covariates influencing the intercept were baseline ADAS-cog score and baseline Mini Mental State Exam score. No covariates influenced the disease progression slope. A parametric log-normal model fit the dropout data best. Baseline ADAS-cog score and age were found to be significant predictors for dropout. AD disease and dropout models were both established. These models set up a quantitative basis for future clinical trial design and endpoint selection.