Baseline Mini-Mental State Exam Research Articles

The effect of the addition of chemotherapy to radiotherapy on cognitive function in patients with low-grade glioma: Secondary analysis of RTOG 98-02.

2047 Background: The addition of PCV chemotherapy to radiotherapy (RT) for patients with WHO grade II glioma improves progression free survival (PFS) and overall survival (OS), for patients surviving at least 2 years (Shaw, J Clin Oncol 26: 2008). The effect of therapy intensification on cognitive function (CF) remains a concern in this population with substantial long term survival. Methods: 251patients with WHO grade II glioma and age > 40 with any extent of resection, or age < 40 with subtotal resection/biopsy were randomized to RT (54Gy) or RT + PCV. 111 patients with age < 40 and gross total resection were observed. CF was assessed by mini-mental status exam (MMSE)at baseline and years 1, 3, and 5 for patients without progression. Change in MMSE score from baseline of > 3 points was considered clinically significant. Results: Overall, very few patients experienced significant decline in MMSE score, with a median follow-up time of 9.7 years for alive patients. There were no significant differences in the proportion of patients experiencing MMSE decline between study arms at any time point. The table below summarizes MMSE change from baseline over time. Neither baseline MMSE score nor change in MMSE at year 1 significantly predicted for OS or PFS, but there was a trend towards worse OS for patients with MMSE loss of ≥ 2 points [HR 1.73, 95% CI (0.86, 3.47), p=0.12]. Conclusions: The MMSE is a relatively insensitive tool that has not been validated in patients receiving cranial RT, and subtle changes in CF may have been missed. However, the addition of PCV to RT for low grade glioma did not result in significantly higher rates of MMSE decline than RT alone or observation. There was a trend towards an MMSE decline of ≥ 2 points at year 1 predicting for worse OS. [Table: see text]

Incidence, Course, and Predictors of Apathy in Huntington's Disease: A Two-Year Prospective Study

This study examined the incidence and course of apathy in subjects with Huntington's disease (HD). Our results showed that at follow-up 14% of the subjects free of apathy at baseline had developed apathy. In these subjects, a lower baseline Mini-Mental State Exam score predicted incidence of apathy. Of the 34 subjects with apathy at baseline, 14 subjects were no longer apathetic at follow-up. Twenty subjects had persistent apathy, with a low baseline Symbol Digits Modalities Test as the only predictor. These results showed that apathy in HD is most closely linked to global and executive cognitive performance.

Depressive Symptoms and Risk for Dementia: A 9-Year Follow-Up of the Maastricht Aging Study

Depression relates to vascular disease and is a candidate risk factor for dementia. We assessed the risk associated with depressive symptoms for Alzheimer-type dementia and vascular dementia. Depressive symptoms (SCL-90 depression subscale) were assessed in 771 community-dwelling individuals age 55 years and older. Onset of dementia (N = 37) was recorded at serial assessments 3, 6, and 9 years after baseline. Depressive symptom scores predicted all-type dementia (OR = 1.06, 95% CI = 1.01-1.10), and vascular dementia (OR = 1.11; 95% CI = 1.03-1.19), but not Alzheimer-type dementia (OR = 1.04; 95% CI = 0.98-1.09). People scoring in the upper quartile of the SCL-90 depression scale (N = 180) were at increased risk for dementia (OR = 2.06, 95% CI = 1.01-4.22). Results were unchanged after co-varying for baseline mini-mental state exam and presence of vascular disease. Depressive symptoms increase the risk for later dementia in community-dwelling older adults.

Incidence, Course, and Predictors of Apathy in Huntington's Disease: A Two-Year Prospective Study

This study examined the incidence and course of apathy in subjects with Huntington's disease (HD). Our results showed that at follow-up 14% of the subjects free of apathy at baseline had developed apathy. In these subjects, a lower baseline Mini-Mental State Exam score predicted incidence of apathy. Of the 34 subjects with apathy at baseline, 14 subjects were no longer apathetic at follow-up. Twenty subjects had persistent apathy, with a low baseline Symbol Digits Modalities Test as the only predictor. These results showed that apathy in HD is most closely linked to global and executive cognitive performance.

Comparison of diagnostic power of cerebrospinal fluid Aß and Tau variables for Alzheimer's disease diagnosis: proposition of a simple decision tree

Background: Advanced glycations endproducts (AGE) are known to cause increased oxidant stress, inflammation, and neurotoxicity; serum levels are increased in diabetes and aging. We examined the relationship between levels of serum methylglyoxal (sMG), an AGE precursor, and cognitive decline in elderly. Methods: Subjects were 266 initially non-demented elderly who had complete data including at least two MMSEs. Tobit mixed regression models assessed the association of baseline MG with cognitive decline in the Mini Mental State Exam (MMSE) score over time, controlling for sociodemographic factors (age, sex, and years of education), and cardiovascular risk factors (diabetes and presence of anAPOE4 allele). sMGwas assessed by ELISA. Results: The sample averaged 83.5 years of age, 14.3 years of education, 36 months of follow up, and 0.93 nmol/ml of sMG. Average baseline MMSE of 28.2 reflected this cognitively normal sample. Seventy six percent of the sample was male since a major source of recruitment was the Mount Sinai affiliate James J. Peters Veterans Affairs Medical Center; 18% had diabetes and 20% carried an APOE4 allele. The fully adjusted model showed an annual decline of 0.33 MMSE points per unit increase in baseline sMG (p 1⁄4 0.015). Significance improved as additional risk factors were added to the model. The interactions of sMGwith diabetes, sex, age, and APOE4 genotype were not significant and did not substantially improve the model fit. In a small replication sample of 49 younger elderly (average age 70, education 14.6, 18 months of follow up, sMG1⁄4 0.91 nmol/ml, baselineMMSE 28.8, 53%males, 13% had diabetes, 9% carried an APOE4 allele), who had a broad neuropsychological battery, results were essentially identical: for the fully adjusted model: p 1⁄4 0.01 when using the MMSE as outcome measure and p 1⁄4 0.03 when using an overall cognition outcome measure. Conclusions: Higher levels of circulating MG were associated with a faster rate of cognitive decline, after adjusting for several sociodemographic and clinical characteristics. This relationship did not differ by sex, APOE4 genotype, or diabetes status suggesting its generality. Since subjects were cognitively normal at the beginning of the study, elevated circulating MG may be indicative of brain cell injury initiated before clinically evident cognitive compromise. Because levels of MG in blood correlate with those consumed with diet, lowering MG by AGE restricted diet has potential for preventing cognitive compromise.

Patterns of missing mini mental status exam (MMSE) in radiation therapy oncology group (RTOG) brain cancer trials.

The Mini Mental Status Exam (MMSE) instrument has been commonly used in the Radiation Therapy Oncology Group (RTOG) to assess mental status in brain cancer patients. Evaluating patient factors in relation to patterns of incomplete MMSE assessments can provide insight into predictors of missingness and optimal MMSE collection schedules in brain cancer clinical trials. This study examined eight RTOG brain cancer trials with ten treatment arms and 1,957 eligible patients. Patient data compliance patterns were categorized as: (1) evaluated at all time points (Complete), (2) not evaluated from a given time point or any subsequent time points but evaluated at all the previous time points (Monotone drop-out), (3) not evaluated at any time point (All missing), and (4) all other patterns (Mixed). Patient characteristics and reasons for missingness were summarized and compared among the missing pattern groups. Baseline MMSE scores and change scores after radiation therapy (RT) were compared between these groups, adjusting for differences in other characteristics. There were significant differences in frequency of missing patterns by age, treatment type, education, and Zubrod performance status (ZPS; P < 0.001). Ninety-two percent of patients were evaluated at least once: seven percent of patients were complete pattern, 49% were Monotone pattern, and 36% were mixed pattern. Patients who received RT only regimens were evaluated at a higher rate than patients who received RT + other treatments (49-64% vs. 27-45%). Institutional error and request to not be contacted were the most frequent known reasons for missing data, but most often, reasons for missing MMSE was unspecified. Differences in baseline mean MMSE scores by missing pattern (Complete, Monotone dropout, Mixed) were statistically significant (P < 0.001) but differences were small (<1.5 points) and significance did not persist after adjustment for age, ZPS, and other factors related to missingness. Post-RT change scores did not differ significantly by missing pattern. While baseline and change scores did not differ widely by missing pattern for available measurements, incomplete data was common and of unknown reason, and has potential to substantially bias conclusions. Higher compliance rates may be achievable by addressing institutional compliance with assessment schedules and patient refusal issues, and further exploration of how educational and health status barriers influence compliance with MMSE and other tools used in modern neurocognitive batteries.

Anosognosia Is a Significant Predictor of Apathy in Alzheimer’s Disease

Anosognosia and apathy are among the most common behavioral and psychological disorders of Alzheimer's disease and are significantly associated in cross-sectional studies. The aim for this study was to carry out for the first time a longitudinal assessment of this association with the aim of clarifying the predictive role between anosognosia and apathy in Alzheimer's disease. A consecutive series of 213 patients with probable Alzheimer's disease were assessed for the presence of apathy and anosognosia using a specific neuropsychiatry assessment. One hundred fifty four of the patients (72%) had a follow-up assessment between 1 and 4 years after the baseline evaluation. Patients with anosognosia at baseline had a significant increase in apathy scores during follow-up relative to patients without anosognosia at both assessments. Conversely, patients with or without apathy had an increase of similar magnitude in anosognosia scores. In conclusion, anosognosia is a significant predictor of apathy in Alzheimer's disease. This may be related to a specific pattern of progression of neuropathology and/or to poor adjustment of Alzheimer's disease patients with poor insight into their functional deficits.

Increased Risk for Falling Associated with Subtle Cognitive Impairment: Secondary Analysis of a Randomized Clinical Trial

Background/Aims: Having dementia increases patients’ risk for accidental falls. However, it is unknown if having mild cognitive deficits also elevates a person’s risk for falls. This study sought to clarify the relationship between subtle cognitive impairment, measured with a widely-used, clinic-based assessment, the Mini Mental State Exam (MMSE), and risk for falls. Methods: In a secondary analysis of the Kenosha County Falls Prevention Study, a randomized controlled trial targeting older adults at risk for falls, we examined the association between baseline MMSE and prospective rate of falls over 12 months in 172 subjects randomized to control group. Results: Using univariate analysis, the rate of falls increased with each unit decrease in MMSE score down to at least 22 (rate ratio 1.25, 95% confidence interval (CI) 1.09–1.45, p = 0.0026). Using stepwise multivariate regression, controlling for ability to perform activities of daily living, use of assistive device, current exercise, and arthritis, the association between MMSE score and falls rate persisted (rate ratio 1.20, 95% CI 1.03–1.40, p = 0.021). Conclusion: Minimal decrements on the MMSE were associated with elevations in rate of falls, suggesting that subtle cognitive deficits reflected in MMSE scores above a cut-off consistent with a diagnosis of dementia, can influence risk for falls.

Prognostic Value of Posteromedial Cortex Deactivation in Mild Cognitive Impairment

BackgroundNormal subjects deactivate specific brain regions, notably the posteromedial cortex (PMC), during many tasks. Recent cross-sectional functional magnetic resonance imaging (fMRI) data suggests that deactivation during memory tasks is impaired in Alzheimer's disease (AD). The goal of this study was to prospectively determine the prognostic significance of PMC deactivation in mild cognitive impairment (MCI).Methodology/Principal Findings75 subjects (34 MCI, 13 AD subjects and 28 controls) underwent baseline fMRI scanning during encoding of novel and familiar face-name pairs. MCI subjects were followed longitudinally to determine conversion to AD. Regression and analysis of covariance models were used to assess the effect of PMC activation/deactivation on conversion to dementia as well as in the longitudinal change in dementia measures. At longitudinal follow up of up to 3.5 years (mean 2.5±0.79 years), 11 MCI subjects converted to AD. The proportion of deactivators was significantly different across all groups: controls (79%), MCI-Nonconverters (73%), MCI-converters (45%), and AD (23%) (p<0.05). Mean PMC activation magnitude parameter estimates, at baseline, were negative in the control (−0.57±0.12) and MCI-Nonconverter (−0.33±0.14) groups, and positive in the MCI-Converter (0.37±0.40) and AD (0.92±0.30) groups. The effect of diagnosis on PMC deactivation remained significant after adjusting for age, education and baseline Mini-Mental State Exam (p<0.05). Baseline PMC activation magnitude was correlated with change in dementia ratings from baseline.ConclusionLoss of physiological functional deactivation in the PMC may have prognostic value in preclinical AD, and could aid in profiling subgroups of MCI subjects at greatest risk for progressive cognitive decline.

Wisconsin Comorbidity Assessment Scale (WCAS): A novel, comprehensive, performance-based assessment scale of geriatric syndromes and medical comorbidities in older cancer patients

19619 Background: Elderly patients with cancer have potential for multiple geriatric syndromes that influence treatment and outcomes. No single clinical assessment tool has targeted all the major geriatric syndromes and their interaction on cancer management and outcomes. We developed WCAS to evaluate cognitive and physical function, risk of falls and gait disorders, polypharmacy, and medical comorbidities. Methods: Eighteen newly diagnosed patients with breast cancer (age 55–82), were enrolled prior to cancer treatment. Cognitive function was evaluated with a comprehensive battery of neuropsychological tests targeting the domains of memory, executive function, attention, language, and praxis. Physical function skills were assessed with novel performance-based tasks (e.g., bed-making) and computerized assessments of balance, gait and risk of falls. Cancer treatment included surgery in all patients with variable use of adjuvant radiation and medical therapy. WCAS was administered at baseline and at month 6. Results: Ten subjects have completed both baseline and month 6 visits. Surgical treatment occurred at a mean of ten days after baseline assessment (SD 6.7). The mean (SD) of the age, years of education and baseline Mini Mental Status Exam (MMSE) was 66 years (7.3), 15.2 years (3.7) and 29.3 (1.1). From baseline to month six assessment performance on the WAIS Digit Symbol test, a measure of working memory and processing speed, declined (mean change −11.7, p&lt;0.01). Likewise, the performance on the WAIS letter number sequence test (mean change −1.3, p=0.09) and the MMSE (mean change −1.1, p=0.12) declined. Interestingly, four subjects with pre-existing hypothyroidism on replacement treatment showed a greater decline (p&lt;0.01) in memory than those without this common condition. Conclusions: Findings indicate that breast cancer diagnosis and therapy can be associated with significant decline in aspects of cognition in older adults with cancer. These changes can last at least 6 months and are more pronounced in those with hypothyroidism. Larger, longer term prospective studies utilizing WCAS are necessary to confirm our preliminary findings. No significant financial relationships to disclose.

O1-05-05: Predicting cognitive decline in non-demented elderly with MRI, DTI, and longitudinal single-voxel spectroscopic imaging

Background: It is important to predict cognitive decline in elderly individuals who may be at risk for Alzheimer’s disease (AD). Objective: To determine the regional patterns of gray and white matter change and metabolic changes in the brain that best predict cognitive decline. Methods: Sixty-two non-demented subjects (74.0 8.5 years old) were assessed with the Mini-mental status exam (MMSE) and the California Verbal Learning Test (CVLT) at baseline and follow-up 1.1 0.2 years later. Of the 62 subjects, 48 scored below (impaired) and 14 scored at or above (controls) the ageand education-adjusted norms on the CVLT. Predictors were structural and diffusion-tensor imaging (DTI) and single voxel H MRS imaging at baseline and 6 months later. The outcome measure was the 1-year change in a memory composite score derived from immediate recall trials 1-4 of the CVLT. Results: Stepwise linear regression models were used to determine the relationship between baseline MMSE scores and demographic information with subsequent cognitive decline. These models revealed group status (i.e., control vs. impaired; r 0.11, p 0.008) and educational level (r 0.11, p 0.02) to be significant predictors of decline. Imaging variables were then added to the models to determine the predictive “added value” of volumetric MRI, DTI and MRS imaging to cognitive testing. In one model, left temporal white matter (WM) volume (r 0.13, p 0.007), group status (r 0.22, p 0.002), and baseline MMSE (r 0.27, p 0.049) were significant predictors of cognitive decline. Another model revealed fractional anisotopry (FA) of the right posterior cingulum (r 0.21, p 0.007) and sex (r 0.39, p 0.02) to be significant predictors decline. A third model showed change in N-acetylaspartate (NAA)/creatine (Cr) ratio (r 0.27, p 0.0001) and educational level (r 0.40, p 0. 02) to be significant predictors of decline. Conclusions: Together these results suggest that temporal WM volume, posterior cingulum FA, and change in the posterior cingulate NAA/Cr ratio may add predictive value to neuropsychological testing for predicting cognitive decline.

Cognitive improvement by ginseng in Alzheimer's disease

Ginseng shows protective and trophic effects in neurodegenerative diseases in experimental models, and showed cognitive improvement in normal population. To investigate the efficacy of ginseng in patients with Alzheimer's disease, patients, who met NINDS-ADRDA criteria for AD were studied Subjects were randomly assigned to ginseng group and control group, and ginseng group was treated with Korean white ginseng powder (4.5 g/day) for 12 weeks. Efficacy variables included changes in mini-mental status exam (MMSE) and cognitive subscales of Alzheimer's disease assessment scale (ADAS-cog) at 4 weeks and 12 weeks. Baseline MMSE and ADAS scores showed no difference between the two groups. Results showed that ginseng improved ADAS-cog compared to the control group at 12 weeks (p<0.05). MMSE was also increased by ginseng treatment compared to the control at 12 weeks (p<0.01). This study suggests the symptomatic efficacy of ginseng in patients with Alzheimer's disease.

P2-208: Baseline assessment of EEG BIS-AD in longitudinal trial predicts subjects who later sought pharmacological cognitive therapy

BIS–AD, an EEG–derived index, was developed as a sensitive, simple–to–use biomarker for the early detection of dementia. Previous reports have demonstrated that BIS–AD correlates with metrics of cognitive function (e.g., Mini–Mental State Exam (MMSE), Alzheimer's Disease Assessment Scale (ADAScog)) in normal and demented subjects. This analysis evaluated BIS–AD in subjects in an ongoing longitudinal trial who were assessed at enrollment (i.e., unmedicated baseline), and before and after initial treatment with pharmacological cognitive enhancers. Following IRB approval, elderly subjects living independently in their community (age≥75; baseline MMSE ≥25) entered an ongoing longitudinal trial designed to explore early detection of dementia. EEG, MMSE and ADAScog were recorded every 3 months. Unpaired t–tests, paired t–tests, and Fisher's Exact Test were used to measure differences between groups or visits. P<0.05 was considered statistically significant. To date, 205 subjects have enrolled (format: mean +/– SD [range]; age: 80.5 +/ 3.7 [75–91]; MMSE: 28.9 +/– 1.1 [25–30] ; ADAScog: 7.4 +/– 3.3 [1–17]; BIS–AD: 94.8 +/– 3.2 [85–100]; Months in study: 9.4 +/– 8.0 [0–30].) Four subjects (2%) began pharmacological cognitive enhancing therapy (donepezil HCL (n=3) or mementine HCL (n=1)) during the study (14.3 +/– 6.2 [6–21] months after enrolling) . BIS–AD was lower (91.1 vs. 94.9, p=0.019) and MMSE (27.8 vs. 28.9, p=0.029) and ADAScog (13.6 vs 7.3, p=0.008) were worse at baseline in these 4 subjects who sought treatment compared to all others. In the 3 subjects monitored for more than 6 months prior to treatment, BIS–AD decreased from baseline prior to treatment (–2.3 +/– 0.90, p=0.049). At the visit following initial treatment, BIS–AD increased from pre–treatment in the 3 subjects with improved cognitive assessments (2.5 +/– 2.1 [0.5–4.6]), and decreased in the subject whose cognition worsened (–1.0 +/– DNE; p=0.25). BIS–AD was lower at baseline in subjects who later sought pharmacological cognitive therapy. Change in BIS–AD following treatment onset reflected the change in cognitive ability. BIS–AD might be useful for early detection of dementia, tracking the course of change of Alzheimer's disease, and evaluating the impact of potential therapies on the progression of the disease.

Pre-treatment cognitive functioning of older prostate cancer patients (PCa): Baseline data from a prospective study of androgen ablation and health status

8175 Background: Although higher endogenous testosterone levels and testosterone supplementation have been linked to better cognitive functioning and health status, few studies have investigated potential effects of androgen ablation on cognition and functional status. Methods: PCa pts >50 yrs initiating LHRH agonist therapy for > 2 yrs, who were not on chemotherapy, and had a baseline Mini-Mental State Exam (MMSE) > 21 were enrolled. Pts completed baseline functional measures (basic/instrumental activities of daily living (A/IADLs) and Berg Balance Score (BBS)) and underwent a comprehensive neuropsychological assessment including Delayed Verbal Learning (HVLT), Delayed Visual Memory (BVMT), Working Memory (LNS), Phonemic Fluency, and Semantic Fluency. Repeat assessments are planned at 6 and 24 mths following androgen ablation initiation. Results: To date, 20 pts completed a baseline evaluation and 11 have undergone 6-mth follow-up testing. Pt characteristics include 37% African-American with a mean age of 70 and mean education of 12 yrs. At baseline, there were no deficits in ADLs or IADLs. However, 47% were at risk for falls (<40/56 on BBS). No declines in function were found at 6-mths. At baseline, 26% of pts scored between 22–26 on the MMSE suggestive of cognitive impairment. Eight of the 20 initial pts (40%) were rated cognitively impaired based on scoring > 1.5 standard deviations below the mean on 2 or more neuropsychological tests. When comparing test scores standardized for age and education, these pts were significantly more impaired than the non-impaired group across the test battery: HVLT p = .005; BVMT p =.000; LNS p=.000; Phonemic Fluency p = .028; Semantic Fluency p =.019. At 6-mth follow-up, there were no significant declines of test scores in either group. Conclusions: 40% of older men with PCa exhibit neurocognitive deficits prior to starting treatment. Follow-up to determine whether pts with pre-treatment impairment are more vulnerable to the cognitive effects of androgen ablation (e.g. dementia) is ongoing. Comparison of studies investigating the cognitive effects of androgen ablation must take baseline functioning into account. No significant financial relationships to disclose.

EFFECTS OF EXERCISE TRAINING ON INDIVIDUALS WITH ALZHEIMER??S DISEASE AND RELATED DISORDERS

Recent studies suggest that physical activity can have a marked effect on the physical and mental health of older adults with dementia. Alzheimer's Disease (AD), and related cognitive impairments. PURPOSE This meta-analysis sought to analyze if exercise produces a positive effect size change on measures of cardiorespiratory fitness and muscle strength in older persons with AD and related cognitive disorders. This synthesis is two-fold: (1) to quantitatively determine the efficacy of physical activity interventions, and (2) to identify the most efficacious exercise paradigm used with this population. Method: A comprehensive literature search of published and unpublished abstracts and titles yielded 42 studies. Selection criteria for inclusion was satisfied when every aspect of the following information was included in the study: (1) subjects were aged 65 years or older and diagnosed with some type of cognitive impairment (i.e. dementia, AD, Mild Cognitive Impairment) or subjects with baseline Mini Mental State Exam scores below 24, (2) an exercise or physical intervention program, and (3) means, standard deviations, t-tests, or F-tests were reported. RESULTS Statistical analysis showed that treatment effect for cardiovascular and strength training were greater compared to other modes of exercise training. CONCLUSION Findings from this meta-analysis support those of previous research that shows promising evidence concerning the positive effects of physical activity on physical health of persons affected by dementia and related cognitive disorders. The extent to which persons with Alzheimer's disease and related cognitive impairments exhibit significant functional and cognitive benefits due to participation in an exercise program is still uncertain. Future research and techniques is needed to precisely determine the efficacy of exercise on individuals with Alzheimer's disease and related disorders.

Hippocampal Volume and Incident Dementia in Geriatric Depression

The authors investigated the role of baseline hippocampal volume on later clinical emergence of dementia in a group of older, non-demented depressed individuals. Subjects were 115 depressed, non-demented participants in a mental health clinical research center. All subjects were screened for dementia and agreed to have a magnetic resonance imaging (MRI) brain scan at baseline. Subjects were clinically evaluated by geriatric psychiatrists quarterly for up to 5 years and received annual neuropsychological testing. Bivariate analyses examined age, gender, race, educational level, baseline depression severity, age at depression onset, baseline Mini-Mental State Exam (MMSE), left and right hippocampal volume, and total cerebral volume. Age, baseline MMSE, total cerebral volume, and having a small left hippocampal volume were associated with later dementia and were included in subsequent survival analysis. Small left hippocampal volume was significantly associated with later dementia (hazard ratio=2.762). Small left hippocampal size on neuroimaging may be a marker for dementia in depressed patients who have not yet met criteria for a clinical diagnosis of a dementing disorder.

Importance of the mini-mental status examination in the treatment of patients with brain metastases: a report from the radiation therapy oncology group protocol 91-04

Purpose: Little information is available on the importance of pretreatment Mini-Mental Status Exam (MMSE) on long-term survival and neurologic function following treatment for unresectable brain metastases. This study examines the importance of the MMSE in predicting outcome in a group of patients treated with an accelerated fractionation regimen of 30 Gy in 10 daily fractions in 2 weeks. Materials and Methods: The Radiation Therapy Oncology Group (RTOG) accrued 445 patients to a Phase III comparison of accelerated hyperfractionated (AH) radiotherapy (1.6 Gy b.i.d.) to a total dose of 54.4 Gy vs. an accelerated fractionation (AF) of 30 Gy in 10 daily fractions from 1991 through 1995. All patients had histologic proof of malignancy at the primary site. Brain metastases were measurable by CT or MRI scan and all patients had a Karnofsky performance score (KPS) of at least 70 and a neurologic function classification of 1 or 2. Two hundred twenty-four patients were entered on the accelerated fractionated arm, and 182 were eligible for analysis (7 patients were judged ineligible, no MMSE information in 29, no survival data in 1, no forms submitted in 1). Results: Average age was 60 years; 58% were male and 25% had a single intracranial lesion on their pretherapy evaluation. KPS was 70 in 32%, 80 in 31%, 90 in 29%, and 100 in 14%. The average MMSE was 26.5, which is the lower quartile for normal in the U.S. population. The range of the MMSE scores was 11–30 with 30 being the maximum. A score of less than 23 indicates possible dementia, which occurred in 16% of the patients prior to treatment. The median time from diagnosis to treatment was 5 days (range, 0–158 days). The median survival was 4.2 months with a 95% confidence interval of 3.7–5.1 months. Thirty-seven percent of the patients were alive at 6 months, and 17% were alive at 1 year. The following variables were examined in a Cox proportional-hazards model to determine their prognostic value for overall survival: age, gender, KPS, baseline MMSE, time until MMSE below 23, time since diagnosis, number of brain metastases, and radiosurgery eligibility. In all Cox model analyses, age, KPS, baseline MMSE, time until MMSE below 23, and time since diagnosis were treated as continuous variables. Statistically significant factors for survival were pretreatment MMSE ( p = 0.0002), and KPS ( p = 0.02). Age was of borderline significance ( p = 0.065) as well as gender ( p = 0.074). A poorer outcome is associated with an increasing age, male gender, lower MMSE, and shorter time until MMSE below 23. Improvement in MMSE over time was assessed; 62 patients died prior to obtaining follow-up MMSE, and 30 patients had a baseline MMSE of 30 (the maximum), and, therefore, no improvement could be expected. Of the remaining 88, 48 (54.5%) demonstrated an improvement in their MMSE at any follow-up visit. Lack of decline of MMSE below 23 was seen in long-term survivors, with 81% at 6 months and 66% at 1 year of patients maintaining a MMSE above 23. Analysis of time until death from brain metastases demonstrated that decreasing baseline MMSE ( p = 0.003) and primary site (breast vs. lung vs. other p = 0.032) were highly associated with a terminal event. Conclusion: While gender and perhaps age remain significant predictors for survival, MMSE is also an important way of assessing a patient’s outcome. Accelerated fractionation used in the treatment of brain metastases (30 Gy in 10 fractions) appears to also be associated with an improvement in MMSE and a lack of decline of MMSE below 23 in long-term survivors.