MMSE Decline Research Articles

Ginkgo Biloba Extract and Long-Term Cognitive Decline: A 20-Year Follow-Up Population-Based Study

BackgroundNumerous studies have looked at the potential benefits of various nootropic drugs such as Ginkgo biloba extract (EGb761®; Tanakan®) and piracetam (Nootropyl®) on age-related cognitive decline often leading to inconclusive results due to small sample sizes or insufficient follow-up duration. The present study assesses the association between intake of EGb761® and cognitive function of elderly adults over a 20-year period.Methods and FindingsThe data were gathered from the prospective community-based cohort study ‘Paquid’. Within the study sample of 3612 non-demented participants aged 65 and over at baseline, three groups were compared: 589 subjects reporting use of EGb761® at at least one of the ten assessment visits, 149 subjects reporting use of piracetam at one of the assessment visits and 2874 subjects not reporting use of either EGb761® or piracetam. Decline on MMSE, verbal fluency and visual memory over the 20-year follow-up was analysed with a multivariate mixed linear effects model. A significant difference in MMSE decline over the 20-year follow-up was observed in the EGb761® and piracetam treatment groups compared to the ‘neither treatment’ group. These effects were in opposite directions: the EGb761® group declined less rapidly than the ‘neither treatment’ group, whereas the piracetam group declined more rapidly (β = −0.6). Regarding verbal fluency and visual memory, no difference was observed between the EGb761® group and the ‘neither treatment’ group (respectively, β = 0.21 and β = −0.03), whereas the piracetam group declined more rapidly (respectively, β = −1.40 and β = −0.44). When comparing the EGb761® and piracetam groups directly, a different decline was observed for the three tests (respectively β = −1.07, β = −1.61 and β = −0.41).ConclusionCognitive decline in a non-demented elderly population was lower in subjects who reported using EGb761® than in those who did not. This effect may be a specific medication effect of EGb761®, since it was not observed for another nootropic medication, piracetam.

Effects of education on the progression of early- versus late-stage mild cognitive impairment

Highly educated participants with normal cognition show lower incidence of Alzheimer's disease (AD) than poorly educated participants, whereas longitudinal studies involving AD have reported that higher education is associated with more rapid cognitive decline. We aimed to evaluate whether highly educated amnestic mild cognitive impairment (aMCI) participants show more rapid cognitive decline than those with lower levels of education. A total of 249 aMCI patients enrolled from 31 memory clinics using the standard assessment and diagnostic processes were followed with neuropsychological evaluation (duration 17.2 ± 8.8 months). According to baseline performances on memory tests, participants were divided into early-stage aMCI (-1.5 to -1.0 standard deviation (SD)) and late-stage aMCI (below -1.5 SD) groups. Risk of AD conversion and changes in neuropsychological performances according to the level of education were evaluated. Sixty-two patients converted to AD over a mean follow-up of 1.43 years. The risk of AD conversion was higher in late-stage aMCI than early-stage aMCI. Cox proportional hazard models showed that aMCI participants, and late-stage aMCI participants in particular, with higher levels of education had a higher risk of AD conversion than those with lower levels of education. Late-stage aMCI participants with higher education showed faster cognitive decline in language, memory, and Clinical Dementia Rating Sum of Boxes (CDR-SOB) scores. On the contrary, early-stage aMCI participants with higher education showed slower cognitive decline in MMSE and CDR-SOB scores. Our findings suggest that the protective effects of education against cognitive decline remain in early-stage aMCI and disappear in late-stage aMCI.

Leeftijd: een belangrijke factor voor cognitieve profielen van de ziekte van Alzheimer

Alzheimer’s disease (AD) in younger patients is associated with a higher prevalence of atypical symptoms. We examined neuropsychological performance according to age-at-onset. We assessed cognition in 172 patients with AD (81 early and 91 late onset) in five cognitive domains (memory, language, visuospatial functioning, executive functioning, attention). Dementia severity was assessed using MMSE and global cognitive decline using CAMCOG. Analyses of variance were performed with age-at-onset as between-subjects factor, and sex and education as covariates. Analysis was repeated after stratification for dementia severity (based on median MMSE). In early onset AD, age (mean±SD) was 60±4 years, 44 (54%) were female. In late onset AD, age was 72±5 years, 47 (52%) were female. Dementia severity and global cognitive decline did not differ between groups (early onset: MMSE: 20±5, CAMCOG: 69±15, late onset: MMSE: 21±5, CAMCOG: 70±15; p > 0.05). Early onset patients performed worse than late onset patients on visuospatial functioning (p < 0.01), executive functioning (p < 0.001) and attention (p < 0.01). Late onset patients performed worse on memory, although not significantly (p = 0.11). Stratification for dementia severity showed that in mildly demented early onset patients, memory function was remarkably preserved compared to late onset patients (p < 0.01). In moderate AD, differences in memory function disappeared, but early onset patients performed worse on visuospatial functioning (p < 0.01), executive functioning (p < 0.001) and attention (p < 0.01) than late onset patients. Adjustment for APOE left results unchanged. In conclusion, early onset AD presents with a different cognitive profile and the disease course seems differently. Relative sparing of memory function in early stages stresses the need to adequately test other cognitive domains.

Baseline Instrumental Activities of Daily Living and Incident Dementia

Sikkes et al.1 have written an important paper showing that individuals without dementia with impairment in at least one of nine instrumental activities of daily living (IADLs) at baseline had a significantly higher incidence of dementia at 12 months (24.4%) than individuals without IADL impairment at baseline (16.7%) (P = .04). Their 531 participants who were followed for 12 months were relatively young (mean age 69.6), so it was decided to duplicate their study from prospective data from the Wyong Hospital Memory Clinic, 100 km north of Sydney. From 415 individuals attending a memory clinic, community-dwelling individuals aged 60 and older who were free of dementia at baseline and had a Mini-Mental State Examination score (MMSE2) of 25 to 30 and a follow-up MMSE and Montreal Cognitive Assessment (MoCA), range 0 (worst) to 30 (best)3 at 12 months were selected in a consensus conference of a geriatrician (PJ) and a clinical nurse consultant (EH). Each individual's family rated IADLs on the Nottingham scale,4 which ranged from 0 (worst) to 22 (best). Twenty-two of 82 (27%) converted to dementia at 12 months, compared with Sikkes conversion rate of 20.8% at 24 months—the most likely reason for this difference was that mean age (79.1) was 9.5 years older than theirs (69.6). Stats Direct Version 2.7.8b (StatsDirect Ltd, Altrincham, UK) from November 2011 was used to compare converters and nonconverters. Mean age of the 22 converters at baseline was significantly higher that that of the 60 nonconverters (82.0 ± 5.8 vs 78.0 ± 6.8, P < .01), mean IADL score at baseline was significantly lower (13.1 ± 5.3 vs 16.1 ± 4.0, P = .0236), MMSE score at baseline was by definition lower (25.6 ± 0.73 vs 27.5 ± 1.50, P < .001), and MoCA score at baseline was lower (19.2 ± 3.5 vs 22.8 ± 3.9, P < .001). At 12 months, IADL (11.4 ± 5.6 vs 15.4 ± 4.5, P = .004), MMSE score (21.6 ± 4.5 vs 27.4 ± 1.6, P < .001), MoCA (16.8 ± 3.6 vs 22.8 ± 4.2, P < .001) remained significantly lower in converters. The Nottingham IADL covers seven of the nine IADL items that Sikkes used, excluding medications and finances. Women are more likely than men to perform five of the Nottingham IADL items unless the men live alone with no home care services: cleaning the kitchen, making a hot snack, washing small items of clothing, doing a full clothes wash, and doing housework. Although the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for dementia include a decline in social and occupational function, there is a surprising lack of research into IADLs as a predictor of incident dementia. This is an important topic for future research and ongoing studies are being conducted in three cohorts: Wyong Memory Clinic; general medical inpatients with delirium or subsyndromal delirium—a prospective randomized controlled trial, Central Coast Australia Delirium Intervention Study; and PhD study, PR DEFEAT DELIRIUM, in outpatients at high risk for incident delirium. One study5 with 255 community-dwelling individuals attending a memory clinic who were followed an average of 13 months has been published. The 11.4% of participants with antithyroid antibodies had similar outcomes at 12 months with respect to IADLs, decline in IADLs, MMSE and MoCA scores, and transfer to residential care. Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Author Contributions: Paul Regal designed the study, assessed patients, served on the consensus panel, analyzed the data, and wrote the article. Eileen Heatherington performed cognitive tests and was a panel member for consensus diagnosis of dementia. Sponsor's Role: No sponsor.

Efficacy and Cognitive Side Effects of Electroconvulsive Therapy (ECT) in Depressed Elderly Inpatients With Coexisting Mild Cognitive Impairment or Dementia

To study cognitive performance in depressed geriatric inpatients with or without preexisting cognitive impairment who received a first course of electroconvulsive therapy (ECT). Forty-four elderly inpatients with major depressive disorder (ICD-10 criteria) were included in a prospective consecutive case series of a university hospital. The patients were divided into 3 groups (no cognitive impairment [NCI], mild cognitive impairment [MCI], dementia) and rated for cognitive performance with the MMSE before first ECT, after sixth ECT, and 6 weeks and 6 months after ECT termination. Affective symptoms were rated by 21-item Hamilton Depression Rating Scale (HDRS-21) before and 6 weeks after ECT. Analysis of variance or Kruskal-Wallis tests on ECT-induced MMSE and HDRS-21 score changes were compared to baseline. Binary logistic regression was used for predictor analysis. The study was conducted from April 2004 to April 2008. After initial nonsignificant cognitive deterioration in all 3 groups, the NCI group improved cognitively 6 weeks (P = .018) and 6 months (P = .027) after ECT. The MCI group improved in cognition 6 months (P = .036) after ECT. In the dementia group, mean MMSE scores also improved numerically over the course of ECT without significance. Dementia patients with antidementia treatment improved in cognition to a clinically relevant extent after the sixth ECT. Dementia subjects without antidementia treatment deteriorated. After the sixth ECT, 70.0% of dementia patients (P = .004) presented a cognitive decline, and 68.8% of MCI patients (P < .001) presented a decline 6 weeks after ECT. Six months after ECT, one-third of the dementia patients (P < .036) still had a cognitive decline. Affective symptoms remitted after ECT in all 3 groups (P < .001). Pre-ECT cognitive deficits were the best predictor of MMSE decline (6 weeks after ECT, P = .007; 6 months after ECT, P = .055). ECT is effective and well tolerated in geriatric depressed inpatients regardless of preexisting cognitive impairment. Cognitive deficits were transient.

Cognitive Function and Antihypertensive Treatment in the Elderly: A 6-Year Follow-up Study

Both antihypertensive treatment and statins were proved to reduce mortality and morbidity from cardiovascular disease in the elderly. Yet their effect on cognitive functions of the elderly is unclear. In this study, 518 elderly were interviewed at their home six years ago. BP was measured and antihypertensive drug treatment and cognitive functions were evaluated. 318 of the original sample were re-examined (81% of the survivors). We evaluated the selective survival in relation to changes in BP, the specific drug usage and cognitive functioning. Beta blocker treatment increased the odds of survival but also the odds of decline in MMSE and memory scores. ACE-I treatment was also associated with decline in memory. Subjects treated with CCB had improved MMSE scores, memory, and performed better on tasks requiring concentration. Statins treatment in this study did not show any affect on cognitive functions. Although most subjects were treated by more than one antihypertensive drug, less than half were normalized at baseline and only one quarter at follow-up. Despite the low normalization rate, antihypertensive treatment regimen had been hardly changed during the six years follow-up. The use of statins, however, increased dramatically: from 6% at baseline to almost half at follow-up. According to our findings CCB emerges as the best option for reducing BP in elderly patients. It appeared to improve cognitive functions without hampering survival.

Regional variaton on the presentation of Alzheimer subjects in memory clinics within Europe: Data from the ICTUS study

To describe the European variation of Alzheimer disease (AD) patients regarding clinical and socio-demographic features, co-morbidities, drug treatment and psychosocial care. 1379 mild to moderate AD subjects of the ICTUS study recruited in academic memory clinics from 12 European countries were analyzed. The cohort was clustered into four geographical regions according to the WHO-classification of European countries. Clinical outcomes were MMSE, ADAScog, NPI, ADL / IADL, and Zarit caregiver burden, socio-demographic variables, drug-treatment, co-morbidities, living arrangements and care status. Northern patients showed the mildest severity of dementia (MMSE: 21.6 ± 3.7, p < 0.001) and the lowest rate of concomitant psychotropic drug treatment (24.3%, p < 0.001). They also appeared to be healthier than Europe's rest. Western subjects were diagnosed earlier (0.5 ± 0.9 month, p < 0.001) with dementia than the other European subjects, received the highest rate of formal care (45.0%, p < 0.001) and most frequently antidementia drugs (60.4%, p < 0.001). Southern subjects had the shortest education time (5.6 ± 4.0, p < 0.001) in Europe and the most severe cognitive decline in MMSE: 19.8 ± 4.0, p < 0.001 and ADAScog: 24.2 ± 9.6, p < 0.001. They received less antidementia drug treatment (37.6%; p < 0.001) than the others and lived more often together with their caregivers (74.4%, p < 0.001). Southern area had the highest caregiver burden (22.6 ± 15.2, p = 0.049).Eastern AD subjects received more concomitant psychopharmacological drugs (68.6%, p < 0.001) than the other Europeans. Their caregivers were more often different (18.6%, p < 0.001) from spouse or offspring. Caregiver burden was lower (18.7 ± 12.4, p = 0.049) than in other clusters. Nearly all subjects received only informal care (95.7%, p < 0.001). They were affected more by co-morbidities. The data show various differences in socio-demographic and clinical characteristics and management between AD patients from 4 European geographical regions. The presentation and management of AD in Europe appears to differ according European regions, probably affected by cultural factors and health politics. These data are important for the conductance of clinical trials as well as health policy makers.

3D maps localize caudate nucleus atrophy in 400 Alzheimer’s disease, mild cognitive impairment, and healthy elderly subjects

MRI research examining structural brain atrophy in Alzheimer's disease (AD) generally focuses on medial temporal and cortical structures, but amyloid and tau deposits also accumulate in the caudate. Here we mapped the 3D profile of caudate atrophy using a surface mapping approach in subjects with AD and mild cognitive impairment (MCI) to identify potential clinical and pathological correlates. 3D surface models of the caudate were automatically extracted from 400 baseline MRI scans (100 AD, 200 MCI, 100 healthy elderly). Compared to controls, caudate volumes were lower in MCI (2.64% left, 4.43% right) and AD (4.74% left, 8.47% right). Caudate atrophy was associated with age, sum-of-boxes and global Clinical Dementia Ratings, Delayed Logical Memory scores, MMSE decline 1 year later, and body mass index. Reduced right (but not left) volume was associated with MCI-to-AD conversion and CSF tau levels. Normal caudate asymmetry (with the right 3.9% larger than left) was lost in AD, suggesting preferential right caudate atrophy. Automated caudate maps may complement other MRI-derived measures of disease burden in AD.

Why Vitamin E Therapy Fails for Treatment of Alzheimer's Disease

ROS damage in the AD brain is widely reported at the levels of nucleic acids [1], protein [2] and lipids [3]. ROS damage is also associated with heart disease, cancer and aging. Consequently, numerous clinical trials of the lipid soluble anti-oxidant, vitamin E, have been conducted for prevention [4] and treatment [5] of age-related morbidity and mortality. The meta-analysis by Miller et al.[5] clearly shows that among 19 clinical trials, only the smaller trials show either an increase or a decrease in all-cause mortality and that the overall effect is near zero. By organizing these studies into a dose-response curve, a significant increase in all-cause mortality was observed for vitamin E doses above 400 IU/day. In an earlier trial of vitamin E treatment for AD at the high dose 2000 IU/day, there was no effect of vitamin E on mini-mental state of moderately severe AD patients, despite delays in nursing home placement [6]. In a trial of MCI patients, Petersen et al. [7] found that even early vitamin E treatment failed to improve cognition. These results prompted Lloret et al. [8] to introduce the novel concept of stratifying AD patients into vitamin E respondents and non-respondents, based on measures of plasma GSSG, the oxidized form of the common antioxidant glutathione (GSH). At the borderline detrimental dose of 800 IU/day [5], about half of the patients failed to respond to vitamin E with lower plasma GSSG; they showed a lower MMSE score after 6 months that suggested a 13% decline in cognitive performance [8]. The other half of the patients for whose GSSG decreased with vitamin E treatment did not significantly change their original MMSE score. Unfortunately, the study was not large enough to detect a decline in MMSE for treatment with placebo. Also provocative from Lloret et al.’s report was a strong negative correlation between GSSG and MMSE, but most of the effect was due to 4 of 19 AD patients with a 5–10% drop in GSSG in response to vitamin E.

High-throughput, Fully Automated Volumetry for Prediction of MMSE and CDR Decline in Mild Cognitive Impairment

Medial temporal lobe (MTL) atrophy is associated with increased risk for conversion to Alzheimer disease, but manual tracing techniques and even semiautomated techniques for volumetric assessment are not practical in the clinical setting. In addition, most studies that examined MTL atrophy in Alzheimer disease have focused only on the hippocampus. It is unknown the extent to which volumes of amygdala and temporal horn of the lateral ventricle predict subsequent clinical decline. This study examined whether measures of hippocampus, amygdala, and temporal horn volume predict clinical decline over the following 6-month period in patients with mild cognitive impairment (MCI). Fully automated volume measurements were performed in 269 MCI patients. Baseline volumes of the hippocampus, amygdala, and temporal horn were evaluated as predictors of change in Mini-mental State Examination and Clinical Dementia Rating Sum of Boxes over a 6-month interval. Fully automated measurements of baseline hippocampus and amygdala volumes correlated with baseline delayed recall scores. Patients with smaller baseline volumes of the hippocampus and amygdala or larger baseline volumes of the temporal horn had more rapid subsequent clinical decline on Mini-mental State Examination and Clinical Dementia Rating Sum of Boxes. Fully automated and rapid measurement of segmental MTL volumes may help clinicians predict clinical decline in MCI patients.

IC-P2-080: Brain structure change is associated with clinical decline of elderly controls: A longitudinal study using the ADNI dataset

Background: Automated segmentation and measurement of subregional brain volumes from MRI data has allowed high-throughput quantification of regional brain atrophy. Such measures predict subsequent clinical decline in patients with mild cognitive impairment (MCI). Quantitative analysis of brain structure change over time may be even more sensitive to the earliest effects of neurodegenerative disease, including that which may be present in elderly controls who have passed clinical screening. Methods: We examined whether longitudinal measures of brain change in healthy elderly controls is associated with decline on clinical and neuropsychological measures. We analyzed longitudinal MRI data from 70 control subjects of the Alzheimer’s Disease Neuroimaging Initiative (ADNI) who had 6and 12-month follow-up imaging at the time of the analysis. 6and 12-month subregional change was quantified with automated anatomical segmentation using FreeSurfer software and non-linear image registration. Subjects were sorted based upon the degree of change in the temporal horn of the lateral ventricle and dichotomized at the median, creating a group with a high-degree of anatomical change and a group with a low-degree of anatomical change. In addition, atrophy was analyzed as a continuous measure, plotting change in the temporal horn against 12-month change in MMSE. Results: Healthy elderly control subjects showing a high degree of anatomical change in bilateral temporal horn of the lateral ventricle declined more on MMSE over 12 months. This effect was significant both for 6-month change and for 12-month change in temporal horn volumes (each p .01, two-tailed). Average age of the high atrophy group (76.6 4.9) did not differ from the age of the low atrophy group (75.9 5.1). Correlation between change in temporal horn volume and MMSE decline was significant at p .02 for 6-month change and at p .005 for 12-month change. Conclusions: Change in temporal horn volume is associated with clinical decline of healthy elderly controls. Such changes may reflect processes of normal aging, but the rate of atrophy may rather suggest the presence of subclinical neurodegenerative disease. No patients converted to MCI or Alzheimer’s disease. Continued follow-up of the high atrophy cohort will determine whether such measures predict later clinical conversion.

Spatial patterns of brain atrophy in MCI patients, identified via high-dimensional pattern classification, predict subsequent cognitive decline

Spatial patterns of brain atrophy in mild cognitive impairment (MCI) and Alzheimer’s disease (AD) were measured via methods of computational neuroanatomy. These patterns were spatially complex and involved many brain regions. In addition to the hippocampus and the medial temporal lobe gray matter, a number of other regions displayed significant atrophy, including orbitofrontal and medial-prefrontal grey matter, cingulate (mainly posterior), insula, uncus, and temporal lobe white matter. Approximately 2/3 of the MCI group presented patterns of atrophy that overlapped with AD, whereas the remaining 1/3 overlapped with cognitively normal individuals, thereby indicating that some, but not all, MCI patients have significant and extensive brain atrophy in this cohort of MCI patients. Importantly, the group with AD-like patterns presented much higher rate of MMSE decline in follow-up visits; conversely, pattern classification provided relatively high classification accuracy (87%) of the individuals that presented relatively higher MMSE decline within a year from baseline. High-dimensional pattern classification, a nonlinear multivariate analysis, provided measures of structural abnormality that can potentially be useful for individual patient classification, as well as for predicting progression and examining multivariate relationships in group analyses.

Influence of Premorbid IQ and Education on Progression of Alzheimer’s Disease

Background: Lower education is associated with a higher risk of developing Alzheimer’s disease (AD). Years of education and measures of general intellectual function (IQ) are highly correlated. It is important to determine whether there is a relationship between education and AD outcomes that is independent of IQ. Objective: To test the hypothesis that premorbid IQ is a stronger predictor of cognitive decline, global progression, and overall survival, than education in patients with AD. Methods: The study included 478 probable AD patients (322 women and 156 men, mean age 74.5 years) followed in a large AD referral center for a mean of 3.2 years. Eligible participants had a baseline estimate of premorbid IQ using the American version of the Nelson Adult Reading Test (AMNART) and at least one follow-up visit with complete neuropsychological assessment. We used random effects linear regression analysis, and Cox proportional hazards analysis to determine whether or not education and/or premorbid IQ were independently associated with cognitive decline, global progression of AD, and survival. Results: When the baseline AMNART score was included in regression models along with education and other demographic variables, AMNART score, but not education, was associated with a higher baseline score and slower rate of decline in MMSE and ADAS-Cog scores, and the Clinical Dementia Rating sum of boxes score. Neither higher premorbid IQ nor higher education was associated with longer survival. Conclusions: We conclude that a baseline AMNART score is a better predictor of cognitive change in AD than education, but neither variable is associated with survival after diagnosis.

P2-241: Plasma testosterone levels and cognitive function in borderline hypogonadal older men

disease (cerebral, cardiac or peripheral arterial disease). These VRF were considered present according to history, medication used, examination or laboratory results at the first standardised evaluation. They were considered treated if they received, respectively, an antihypertensive, an oral antihyperglycemic or insulin, a statin or a fibrate, an antiplatelet or an anticoagulant. Preliminary Results: Among the first 406 patients included (approximately 57% of the whole cohort), 377 (92.1%) had at least one VRF. Only 121 (32.1%) had all their VRF treated (treated group). We compared them with the 83 (22%) who had none of their VRF treated (untreated group). Both groups were similar for age (73.1 years), sex distribution (62.6% women), educational level (76.5% lower level), baseline MMSE (21.7), final diagnosis (60.1% AD), acetyl-cholinesterase inhibitors utilization (67%), and follow-up length (3.5 years). MMSE evolution over time was compared between treated and untreated groups with a mixed model adjusted for age, sex, education, first MMSE, diagnosis and year of first visit. Overall, MMSE decline is significantly slower in the treated group (p 0.003, figure 1). For pure AD cases (n 128), a similar trend emerges but does not reach statistical significance (p 0.073, figure 2).

Motor subtype and cognitive decline in Parkinson’s disease, Parkinson’s disease with dementia, and dementia with Lewy bodies

Background: A previous cross sectional study found over-representation of a postural instability gait difficulty (PIGD) motor subtype in Parkinson’s disease patients with dementia (PDD) and dementia with Lewy bodies (DLB),...

Stability and predictability of the classification of mild cognitive impairment as assessed by episodic memory test performance over time

This study aimed to address the criteria and the stability of the classification of MCI. The Foresight Challenge cohort of 157 community-dwelling volunteers was assessed on 3 visits at 2-year intervals with episodic, semantic and working memory tests. Subjective memory complaints were assessed with the CAMDEX. Of the cohort, 2% had dementia and 31% were classified with MCI at visit 3, 43% with stable impairment from Time 1. Thirteen percent of those with objective memory impairment at Time 1 or 2 improved to control status by Time 3. Episodic memory tests were predictive for MCI at all timepoints, as were tests for praxis and Graded Naming, while at Time 3 spatial span lost predictive value, but processing speed became predictive. Decline in processing speed was seen in control and MCI groups, while memory performance and MMSE decline occurred only in the MCI group. The use of combined memory test scores gave better sensitivity to MCI than single tests. Subjective memory complaints were positive for 79% of the MCI group and 62.5% of controls. These findings would suggest consideration of modification of current MCI criteria. Our chief acknowledgement is to the individuals who volunteered to participate in the study. We acknowledge the support of Professor David Smith and Elizabeth King at OPTIMA and are grateful to the research nurses for administering the baseline screening tests. This work was supported by grants from the Medical Research Council, The Norman Collisson Foundation and The Clore Duffield Foundation.

Interim results of a Phase II study of resection and GliaSite brachytherapy for a single brain metastasis

Interim results of a Phase II study of resection and GliaSite brachytherapy for a single brain metastasis

Investigation of profile difference between Alzheimer’s disease patients declining at different rates: examination of baseline neuropsychological data

The rate of cognitive decline in AD has been noted to vary significantly among patients. The ability to predict the probable rate of decline early in the disease process would be of great practical importance. Attempts to analyze early cognitive deficits to find patterns associated with rapid decline have met with limited success. This paper utilized a large sample of patients with a diagnosis of probable AD evaluated longitudinally in ongoing research at the ADRC at Baylor College of Medicine and a statistical procedure of profile analysis to assess the initial data for a pattern associated with rapid decline. The findings indicated that despite initial equality of MMSE scores, patients showing rapid MMSE decline at one year displayed significantly more impaired performance on neuropsychological measures at diagnosis. Discussion includes discussion on the use of the MMSE for tracking general cognitive function and the difficulties of ascertaining stable profiles for prediction.

Effects of educational attainment and occupational status on cognitive and functional decline in persons with Alzheimer-type dementia.

Researchers have suggested that educational attainment and occupational status--indicators of cognitive and/or neurologic "reserve"--can help persons compensate for clinical manifestations of Alzheimer's disease (AD), such as the rates of cognitive and functional decline. The effects of educational attainment on rates of decline could be "direct" independent of occupational status), "indirect" (working through occupational status), or both. We used multilevel analysis for repeated measures to study the effects of educational attainment and occupational status on rates of decline in cognition (Mini-Mental State Examination, MMSE) and function (Cleveland Scale for Activities of Daily Living). Subjects included persons with "probable" or "possible" AD, drawn from our Alzheimer's Disease Research Center registry (N = 482 in the analysis of cognitive decline, and N = 450 in the analysis of functional decline). When controlling for year of birth, gender, ethnicity, and duration of illness, we found that there was an inverse relationship between number of years of education and rate of decline in MMSE, but effects of occupational status were not significant. This implies a "direct" effect of education on decline in MMSE, but no "indirect" effect through occupational status. Neither educational attainment nor occupational status affected rate of decline in functional ability. We conclude that education slows the rate of cognitive decline in persons with AD, but not through its impact on occupational status. Thus, the protective effects of reserve may be established early in life, before people enter the workforce.

Predictors of mortality in patients diagnosed with probable Alzheimer's disease.

We sought to identify factors associated with mortality in persons recently diagnosed with probable Alzheimer's disease (AD). Predicting mortality in AD in needed both in patient care and public health planning. Previous studies have identified several factors which contribute to mortality in AD, but few longitudinal studies of population-based cohorts exist. In a longitudinal follow-up study 327 patients with newly diagnosed probable AD (mean Mini-Mental State Examination [MMSE] score of 20) from a large, stable health maintenance organization were identified. Demographic characteristics, dementia severity, and comorbid conditions were identified at enrollment. Patients were followed longitudinally (median 3.3 years, total 898 person-years). Baseline characteristics were used to predict survival in univariate and multivariate models. Increased mortality was seen in patients with probable AD (9.0 deaths per 100 person-years) compared with the community population adjusted for age and gender (4.3 deaths per 100 person-years). On univariate analysis we found increased age, male gender, impairment on MMSE or Blessed dementia rating scale (DRS), rate of MMSE decline, wandering or agitation, vascular disease, and sensory impairment affecting the ability to read or hear to be moderately associated with decreased survival. After adjusting for age and gender in a multivariate model, Blessed DRS score and sensory impairment affecting the ability to read were independently associated with decreased survival. Short-term mortality is increased in patients newly diagnosed with probable AD. Measures of dementia severity, measures of general debility, and vascular disease are associated with increased mortality. Of these, general debility and sensory impairment were more strongly associated with shortened survival.