Mini-Mental State Examination Points Research Articles

Neuropsychological Predictors of Rapidly Progressing Patients with Alzheimer’s Disease

Background: Alzheimer disease (AD) has heterogeneous clinical manifestations. Different neuropsychological profiles in AD patients might be indicative of the diffusion of the pathological process and might be associated with differences in rates of disease progression. Methods: We studied 154 newly diagnosed AD patients (65.6% women; mean age: 73 years). Performance in memory, executive functions, praxis and language domains was categorized into mild, moderate and severe impairment. The time-dependent probability of losing 5 points on the Mini-Mental State Examination (MMSE) over 2 years was considered as disease progression and evaluated by survival analysis. Results: One fourth of the patients decreased by ≧5 MMSE points over the 2-year follow-up. Rapid disease progression was more frequent in more educated patients and in those with moderate severity of global cognitive impairment. In univariate analysis, more severe memory and executive functioning impairment were associated with higher probabilities of progression. The association with memory was explained by differences in executive function impairment that remained statistically significant in multivariate analyses. Conclusions: Patients with more severe executive functioning impairment have a worse prognosis over 2 years. This might be due to involvement of the prefrontal cortex by the pathological process of AD in patients with severe executive deficits.

Vitamin D and Risk of Cognitive Decline in Elderly Persons

To our knowledge, no prospective study has examined the association between vitamin D and cognitive decline or dementia. We determined whether low levels of serum 25-hydroxyvitamin D (25[OH]D) were associated with an increased risk of substantial cognitive decline in the InCHIANTI population-based study conducted in Italy between 1998 and 2006 with follow-up assessments every 3 years. A total of 858 adults 65 years or older completed interviews, cognitive assessments, and medical examinations and provided blood samples. Cognitive decline was assessed using the Mini-Mental State Examination (MMSE), and substantial decline was defined as 3 or more points. The Trail-Making Tests A and B were also used, and substantial decline was defined as the worst 10% of the distribution of decline or as discontinued testing. The multivariate adjusted relative risk (95% confidence interval [CI]) of substantial cognitive decline on the MMSE in participants who were severely serum 25(OH)D deficient (levels <25 nmol/L) in comparison with those with sufficient levels of 25(OH)D (>/=75 nmol/L) was 1.60 (95% CI, 1.19-2.00). Multivariate adjusted random-effects models demonstrated that the scores of participants who were severely 25(OH)D deficient declined by an additional 0.3 MMSE points per year more than those with sufficient levels of 25(OH)D. The relative risk for substantial decline on Trail-Making Test B was 1.31 (95% CI, 1.03-1.51) among those who were severely 25(OH)D deficient compared with those with sufficient levels of 25(OH)D. No significant association was observed for Trail-Making Test A. Low levels of vitamin D were associated with substantial cognitive decline in the elderly population studied over a 6-year period, which raises important new possibilities for treatment and prevention.

MMST zur Überlebensprognostik bei Demenz

Evaluation of the predictive power of the Mini-Mental State Examination (MMSE) for survival analyses of dementia patients. In an 8-year follow-up study for 145 dementia outpatients the survival and relative death risks (hazard ratios) were calculated with Kaplan Meier and Cox-regression analyses. Following Cox-regression the relative death risk increases by 36.2 % per severity level of dementia (mild / moderate / severe), p = 0.023. Per single MMSE point lost, the relative death risk rises by 4.1 % (p = 0.005). Kaplan Meier analysis supports the result. MMSE scores may in fact be used for dementia survival prognoses in counseling family and professional caregivers of dementia patients, but also for socioeconomic management of the increasing dementia burden for society.

CSF biomarkers predict rate of cognitive decline in Alzheimer disease

CSF biomarkers amyloid beta 1-42 (Abeta(42)), total tau (tau), and tau phosphorylated at threonine 181 (p-tau-181) are useful diagnostic markers for Alzheimer disease (AD). Less is known about these biomarkers as predictors for further cognitive decline in patients with AD. We hypothesized that high tau, especially in combination with relatively low p-tau-181, is a marker of rapid decline, since it has been associated with fast neuronal degeneration. A total of 151 patients with AD of whom we had baseline CSF were included from our memory clinic. All patients had at least 2 Mini-Mental State Examination (MMSE) scores, obtained no less than 1 year apart. Linear mixed models were used to assess associations between CSF biomarkers and the rate of cognitive decline as measured with the MMSE. CSF biomarkers were used in quintiles, random intercept and random slope with time were assumed, and the analyses were corrected for sex and age. The patients with AD (45% women, age 66 +/- 9 years, baseline MMSE 22 +/- 4) had a follow-up period of 2.0 (1.0-5.0) years. Linear mixed models revealed no relations between any CSF biomarker and baseline MMSE. However, CSF biomarkers did predict cognitive decline over time. A low p-tau-181/tau ratio was the strongest predictor with a dose-dependent effect (lowest vs highest quintile: 2.9 vs 1.3 MMSE points annual decline, p for trend <0.001). In addition, low Abeta(42), high tau, and high tau/Abeta(42)-ratio were associated with rapid cognitive decline (p < 0.05). At the time of diagnosis, a combination of high CSF tau without proportionally elevated p-tau-181 is associated with a faster rate of cognitive decline.

The stability of AQT processing speed, ADAS-Cog and MMSE during acetylcholinesterase inhibitor treatment in Alzheimer’s disease

To explore the longitudinal stability of measures of cognition during treatment with acetylcholinesterase inhibitors (AchEI) in patients with Alzheimer's disease (AD). Cognitive status was measured in a cohort of 60 patients at 6 months after initiation of treatment with AchEI (baseline) and after an additional 6 months of treatment (endpoint). A Quick Test of Cognitive Speed (AQT), Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), and MMSE were administered concurrently. Correlations (rho) between age and AQT processing speed were non-significant, but were significant for ADAS-Cog and Mini Mental State Examination (MMSE). AQT and ADAS-Cog means did not differ significantly between baseline and endpoint. There was a small, significant reduction in MMSE point scores. Measures of stability (Spearman's rho) were moderate-to-high for all tests. Means for subgroups did not differ as a function of medication type. AQT processing speed, ADAS-Cog, and MMSE measures proved stable during the second 6 months of treatment with AChEI.

Correction for age, education and other demographic variables in the use of the Mini Mental State Examination in Finland.

The population-based Helsinki Aging Study was comprised of three age groups: 75-, 80- and 85-year-olds. A random sample of 511 subjects completed the Mini Mental State Examination (MMSE) and were assessed on the Clinical Dementia Rating-scale (CDR). According to the CDR results 446 subjects were screened as non-demented. Of these subjects 30% scored below or at 24 MMSE points. Age, education and social group had a significant effect on the MMSE scores, even after excluding the demented cases. Together they explained 10% of the total variance within the MMSE. Social group correlated with education. The MMSE scores were corrected according to age and education. Adjustment of the originally used cutpoint of 24 resulted in cutpoints of 25 and 26 among the 75-year-olds, in the low and high education groups respectively; 23 and 26 in the 80-year-olds; 22 and 23 in the 85-year-olds.

Addenbrooke’s Cognitive Examination validation in Parkinson’s disease

There is a clear need for brief, sensitive and specific cognitive screening instruments in Parkinson's disease (PD). To study Addenbrooke's Cognitive Examination (ACE) validity for cognitive assessment of PD patient's using the Mattis Dementia Rating Scale (MDRS) as reference method. A specific scale for cognitive evaluation in PD, in this instance the Scales for Outcomes of Parkinson's disease-Cognition (SCOPA-COG), as well as a general use scale the Mini-mental state examination (MMSE) were also studied for further correlation. Forty-four PD patients were studied, of these 27 were males (61%), with a mean (SD) age of 69.5 (11.8) years, mean (SD) disease duration of 7.6 (6.4) years (range 1-25), mean (SD) total Unified Parkinson's Disease Rating Scale (UPDRS) score 37 (24) points, UPDRS III 16.5 (11.3) points. MDRS, ACE and SCOPA-COG scales were administered in random order. All patients remained in on-state during the study. Addenbrooke's Cognitive Examination correlated with SCOPA-COG (r = 0.93, P < 0.0001), and MDRS (r = 0.91 P < 0.0001) and also with MMSE (r = 0.84, P < 0.001). Area under the receiver-operating curve, taking MDRS as the reference test, was 0.97 [95% confidence interval (CI): 0.92-1.00] for ACE, 0.92 (95% CI: 0.83-1.00) for SCOPA-COG and 0.91 (95% CI: 0.83-1.00) for MMSE. Best cut-off value for ACE was 83 points [Sensitivity (Se) = 92%; Specificity (Sp) = 91%; Kappa concordance (K) = 0.79], 20 points for the SCOPA-COG (Se = 92%; Sp = 87%; K = 0.74) and 26 points for MMSE (Se = 61%; Sp = 100%; K = 0.69). Addenbrooke's Cognitive Examination appears to be a valid tool for dementia evaluation in PD, with a cut-off point which should probably be set at 83 points, displaying good correlation with both the scale specifically designed for cognitive deficits in PD namely SCOPA-COG, as well as with less specific tests such as MMSE.

Predictive Value of Rapid Decline in Mini Mental State Examination in Clinical Practice for Prognosis in Alzheimer’s Disease

Background: Given the poorer prognosis of Alzheimer’s disease (AD) patients with rapid cognitive decline (RCD), there is a need for a clinical assessment tool to detect these patients. Objective: To investigate if there is a Mini Mental State Examination (MMSE) threshold of decline during 6 months of follow-up which predicts a worse disease progression at the 2-year follow-up. Then, to propose a feasible definition of RCD for routine clinical practice. Methods: Data from 565 community-dwelling AD patients recruited in a multi-centre prospective observational study were assessed. All patients had MMSE scores between 10 and 26 at inclusion and were followed up 6-monthly using a standardised clinical assessment. Patients were classified as rapid and non-rapid decliners according to 2 MMSE decline thresholds tested: ≧3 points and ≧4 points for decline over the first 6 months of the study. Worse disease outcome was defined as attainment of 1 of 4 clinical end points 18 months later: institutionalisation, death, increased physical dependence or worsening of behavioural and psychological symptoms. Results: 135 patients (23.9%) lost ≧3 points during the first 6 months of follow-up in the MMSE score and 77 patients (13.6%) lost ≧4 points. Patients with moderate disease and a loss of ≧4 points showed a significantly increased risk of mortality (HR = 5.6, 95% CI 2.0–15.9) and institutionalisation (HR = 3.8, 95% CI 1.8–8.1) at the 2-year follow-up. The same MMSE threshold was associated with a higher risk of physical decline (HR = 1.6, 95% CI 1.2–2.3). Conclusion: The loss of ≧4 points in MMSE during the first 6 months of follow-up seems to be a predictor of worse clinical course, and thus it could be used to define the category of AD patients presenting a RCD.

Strategies to Reduce Site Differences in Multisite Studies: A Case Study of Alzheimer Disease Progression

The objectives of this study were to evaluate the magnitude and sources of site differences in a multisite study of rates of cognitive decline among patients with Alzheimer disease and to seek strategies to reduce the magnitude of site differences in this and future such studies. A total of 3,280 participants from 15 different sites was analyzed. For each participant, the average rate of change in the Mini-Mental State Examination (MMSE) was calculated. Participants who declined at least three MMSE points per year were classified "rapid decliners." Site differences in sociodemographic distributions and the percentage of rapid decliners were examined, and a signal detection approach was used to identify the main correlates of rapid decline. The percentage of rapid decliners for the 15 sites initially varied from 8%-40%. Two of the correlates of rapid decline were largely the result of different sampling protocols, namely baseline MMSE and elapsed time between the first and last MMSE. By selecting only those participants at each site with a baseline MMSE between 15 and 23, and limiting the follow-up time to a period of 11-24 months, the authors created greater homogeneity in the protocols across sites and reduced site variability of rapid decliners from 27%-50%. Results of single-site studies are often nonreproducible, and multisite studies that follow different protocols and do not take site differences into account may be misleading. This study indicates the importance of site differences and how relatively simple efforts to impose common sampling, measurement, and design criteria can reduce, if not totally remove, site differences.

Cerebrovascular Reactivity and Cognitive Decline in Patients With Alzheimer Disease

The aim of this study was to explore the possible contribution of alterations in cerebral hemodynamics to the evolution of cognitive impairment in patients with Alzheimer disease (AD). Fifty-three patients with AD were investigated. The evolution of cognitive decline over 12 months was evaluated by means of changes in Mini Mental State Examination (MMSE) and AD Assessment Scale for Cognition (ADAS-Cog) scores. Demographic characteristics, vascular risk profile, pharmacological treatment, and presence of white matter lesions were assessed at entry. Further, a basal evaluation of cerebrovascular reactivity to hypercapnia was measured with transcranial Doppler ultrasonography using the breath-holding index (BHI). Of all the variables considered, both MMSE and ADAS-Cog changes had the highest correlation with BHI, followed by age and diabetes. After subdividing both cognitive measures reductions into bigger and smaller-than-average decline (2 points for MMSE; 5 points for ADAS-Cog), multiple logistic regression indicated BHI as the sole significant predictor of cognitive decline. These results show an association between impaired cerebral microvessels functionality and unfavorable evolution of cognitive function in patients with AD. Further research is needed to fully establish whether altered cerebral hemodynamics may be considered an independent factor in sustaining cognitive decline progression or an effect of pathological processes involved in AD.

Cerebrospinal fluid markers and change in MMSE score over an 8-year follow-up period - the population study of women in Gothenburg, Sweden

Between 2010 and 2050, Alzheimer's disease (AD) willreach epidemic proportions, highlighting the importance of identifying appropriate preclinical markers for prevention. Biomarkers present in cerebrospinal fluid (CSF) may be useful for predicting progression from preclinical to clinical AD. We investigated the longitudinal relationship between cerebrospinal fluid markers - amyloid beta-42 (Abeta-42), tau, growth-associated protein-43 (GAP-43), and the CSF-to-serum albumin ratio (albumin ratio) - in relationship to dementia occurrence and change in Mini-Mental State Examination (MMSE) score over an 8-year follow-up period in a population-based sample of women. The MMSE and lumbar puncture were performed in 1992 on a representative sample of 84 women without dementia born in 1908, 1914, 1918, and 1922 (aged 70–84 years) as part of the Population Study of Women (PSW) in Göteborg, Sweden. Cerebrospinal fluid was analyzed for Abeta-42, GAP-43, tau protein, and the albumin ratio. Women were followed for 8 years after lumbar puncture for dementia occurrence and a repeat MMSE. Correlation and regression analyses and ANOVA were used to relate CSF markers, dementia, age, and change in MMSE score between 1992 and 2000. Women who developed dementia after 1992 (n=6) had a lower Abeta-42 (p=0.061) level, and higher tau (p=0.000) and GAP-43 (p=0.023) levels at baseline compared to women who did not become demented. Women who became demented also experienced a greater decline in MMSE score (p=0.000) between 1992 and 2000. Among 51 women who never developed dementia and who participated in the MMSE in 1992 and 2000, decline in MMSE score (range=3 to -8 points) was correlated with decreases in Abeta-42 (r=0.359, p=0.010). Of those experiencing a decline of at least 2 points in MMSE (n=14), mean Abeta-42 levels were lower compared to those who experienced no decline (p=0.025). In a multivariate linear regression model including all CSF markers and predicting change in MMSE, Abeta-42 was the sole predictor (R2=0.173, p=0.026). CSF Abeta-42 is a useful marker of cognitive decline as measured using the MMSE among elderly women without dementia, and CSF markers are useful predictors of dementia when measured at least one year prior to dementia onset.

Fall‐related brain injuries and the risk of dementia in elderly people: a population‐based study

Severe head injury in early adulthood may increase the risk of dementia in older age, but it is not known whether head injury in later life also increases the risk of dementia. A representative sample (82%) of persons aged 70 years or older with a Mini-Mental State Examination (MMSE) test score of > or =26 (n = 325) were followed-up for 9 years to record all their fall-related head injuries resulting in traumatic brain injury (TBI). At the end of the follow-up period, 152 persons (81% of the surviving population) were examined for clinical dementia, according to DSM-IV criteria. Eight persons sustained a TBI and 34 developed dementia. Brain injury was associated with younger age at detection of dementia even when adjusted for sex and educational status (low educational status significantly associated with dementia); age-specific hazard ratio (95% confidence interval) 2.80 (1.35-5.81). In a population scoring > or =28 points in the baseline MMSE an apolipoprotein E (ApoE) epsilon4 phenotype was also associated with younger age at the time of detecting dementia; 3.56 (1.35-9.34), and the effect of brain injury and ApoE epsilon4 phenotype was synergistic; 7.68 (2.32-25.3). We conclude that fall-related TBI predicts earlier onset of dementia and the effect is especially high amongst subjects who carry the ApoE epsilon4 allele.

Efficacy of rivastigmine in subjects with moderately severe Alzheimer's disease.

Cholinesterase (ChE) inhibitors are primarily used in the treatment of mild to moderate Alzheimer's disease (AD), but may also be effective in more severe disease. To evaluate the dual ChE inhibitor, rivastigmine, in more severe dementia. We retrospectively analysed pooled data from three randomised, placebo-controlled, double-blind, 6-month trials, involving 2126 AD subjects. Subjects were selected according to baseline Mini-Mental State Examination (MMSE) score to identify subjects with more severe cognitive impairment (10-12 MMSE points). One-hundred-and-seventeen subjects were included who had been treated with rivastigmine 6-12 mg/day or placebo. The AD Assessment Scale-Cognitive Subscale (ADAS-Cog), the MMSE, a six-item subscore of the Progressive Deterioration Scale (PDS) and the BEHAVE-AD assessed efficacy. Tolerability was assessed by recording adverse events (AEs) and the relative risk (RR) of discontinuation. This group of subjects responded well to rivastigmine. After 6 months, the mean ADAS-Cog score declined by 6.3 points in the placebo group and increased by 0.2 points in the rivastigmine group (observed cases; p<0.001). Clinical benefits were also observed with the MMSE, the six-item PDS score and items of the BEHAVE-AD. Rivastigmine showed the same pattern of AEs as in other studies, but the RR of dropping out due to AEs was lower than in subjects with milder AD. Current treatment guidelines do not recommend treating individuals with severe AD with ChE inhibitors. However, this retrospective analysis suggests that rivastigmine 6-12 mg/day may benefit subjects with more severe disease, as well as subjects with mild to moderate impairment.

COGNITIVE IMPAIRMENT AND INFECTIOUS BURDEN IN THE ELDERLY

Infectious agents have been suspected as contributing factors to dementia, especially in Alzheimer disease. We intended to test whether viral or bacterial seropositivity is associated with cognitive impairment among home-dwelling elderly. Viral burden (seropositivity for herpes simplex type 1 (HSVI), type 2 (HSV2), or cytomegalovirus (CMV), and bacterial burden (Chlamydia pneumoniae and Mycoplasma pneumoniae) were tested among 383 home-dwelling individuals with vascular disease (mainly coronary heart disease) in the ongoing DEBATE study (mean age 80 years). Mini-mental state examination (MMSE) and its changes were used to define cognitive impairment. At baseline, 0-1, 2, and 3 positive titers toward viruses were found in 48 (12.5 %), 229 (59.8 %), and 106 (27.7 %) individuals,respectively. MMSE points decreased with increasing viral burden (p = 0.03). At baseline,58 individuals (15.1 %) had cognitive impairment (MMSE < 24 points) which after adjustments was significantly associated with seropositivity for 3 viruses (risk ratio 2.5, 95%confidence interval 1.3 to 4.7). MMSE score decreased in 150 cases (43%) during 12-month follow-up. After adjustment for MMSE score at baseline and with 0-1 seropositivities as reference (1.0), the risk ratios were 1.8 (95 % confidence interval 0.9 to 3.6) and 2.3 (95% confidence interval 1.1 to 5.0) for 2 and 3 seropositivities, respectively. No significant associations were observed between bacterial burden and cognition. Viral burden of herpes virus and cytomegalovirus was associated with cognitive impairment in home-dwelling elderly. The association may offer a preventable cause of cognitive decline.

A longitudinal study of neuropsychological change in individuals with Parkinson's disease.

Neuropsychological changes in individuals with Parkinson's disease (PD) were studied longitudinally. Sixty-nine idiopathic PD patients, with Mini-Mental State Examination (MMSE) scores falling within normal range, and 37 elderly control participants were given neuropsychological tests twice approximately two years apart. The PD group performed poorer than the control group on Semantic Fluency, Letter Fluency, Modified Wisconsin Card Sorting Task, and Block Design at test time 1. Two years later, the PD group showed significant decline in Semantic and Letter Fluency. A subset of 12 PD patients declined in mental status by second testing (>4 MMSE points). Cox proportional-hazards models were used to see if any baseline measures were associated with relative risk of decline in mental status. In the final model, Repetition performance and Age were significantly associated with cognitive decline. Consistent with previous studies, executive function tasks were those most susceptible to disease progression.

A longitudinal study of neuropsychological change in individuals with Parkinson's disease.

Neuropsychological changes in individuals with Parkinson's disease (PD) were studied longitudinally. Sixty-nine idiopathic PD patients, with Mini-Mental State Examination (MMSE) scores falling within normal range, and 37 elderly control participants were given neuropsychological tests twice approximately two years apart. The PD group performed poorer than the control group on Semantic Fluency, Letter Fluency, Modified Wisconsin Card Sorting Task, and Block Design at test time 1. Two years later, the PD group showed significant decline in Semantic and Letter Fluency. A subset of 12 PD patients declined in mental status by second testing (> or =4 MMSE points). Cox proportional-hazards models were used to see if any baseline measures were associated with relative risk of decline in mental status. In the final model, Repetition performance and Age were significantly associated with cognitive decline. Consistent with previous studies, executive function tasks were those most susceptible to disease progression.

Impact of viral and bacterial burden on cognitive impairment in elderly persons with cardiovascular diseases.

Inflammation and infectious etiology have been implicated in the pathogenesis of dementia. We sought to investigate whether the seropositivity of common infections was associated with cognitive function. Viral burden (seropositivity for herpes simplex virus type 1 [HSV-1], herpes simplex virus type 2 [HSV-2], or cytomegalovirus [CMV]) and bacterial burden (Chlamydia pneumoniae and Mycoplasma pneumoniae) were related to cognitive status and its impairment among 383 home-dwelling elderly with cardiovascular diseases (mean age, 80 years). The Mini-Mental State Examination (MMSE) and its changes and the Clinical Dementia Rating (CDR) were used to define cognitive impairment. At baseline, 0 to 1, 2, and 3 positive titers toward viruses were found in 48 (12.5%), 229 (59.8%), and 106 individuals (27.7%), respectively. MMSE points decreased with increasing viral burden (P=0.03). At baseline, 58 individuals (15.1%) had cognitive impairment, which after adjustments was significantly associated with seropositivity for 3 viruses (hazard ratio, 2.5; 95% CI, 1.3 to 4.7). MMSE score decreased in 150 (43% of 348) during 12-month follow-up. After adjustment for MMSE score at baseline and with 0 to 1 seropositivities as reference (1.0), the hazard ratios were 1.8 (95% CI, 0.9 to 3.6) and 2.3 (95% CI, 1.1 to 5.0) for 2 and 3 seropositivities, respectively. The prevalence of possible or definite dementia according to CDR also increased with viral burden. No significant associations were observed between bacterial burden and cognition. Viral pathogen burden of HSV and CMV was associated with cognitive impairment in home-dwelling elderly persons with cardiovascular diseases. The results need to be tested in larger databases, but they may offer a preventable cause of cognitive decline.

Natural history of dementia associated with lacunar infarctions

Background: Lacunar stroke (VaD-L) is the most common stroke subtype associated with vascular dementia (VaD). Objective: To evaluate the rate of cognitive and behavioral changes in patients with probable VaD-L. Methods: We measured rates of change on the Mini-Mental State Examination (MMSE), Digit Span, Logical Memory, Controlled Oral Word Association Test, CERAD battery and the Neuropsychiatric Inventory (NPI) of 77 [age at entry 65.9±8.1 (mean±standard deviation) years] patients with probable VaD, periventricular white matter and basal ganglia lacunae, longitudinally studied for 25.7±11 months. Results: Mean number of follow-up visits was 2.6. Overall annual vascular event rate was 0.25. VaD-L in mildly and moderately impaired patients is characterized by progressive cognitive and behavioral decline. The rate of cognitive and behavioral progression depends on the occurrence of vascular episodes (VE) during the course of the illness [(−1.1) MMSE and (+4.0) NPI points annually without VE vs. (−2.0) and (+10.3) points following VE]. The rates of progression are a function of the severity of the cognitive and behavioral impairment. Impaired cognition is associated with impaired behavior. A subgroup of VaD-L patients runs a progressively deteriorating course despite the absence of clinically apparent new vascular episodes. Conclusion: VaD-L is characterized by cognitive and behavioral decline in 83% of the patients. The rate of decline is determined mainly by the severity of the cognitive and behavioral impairment at baseline and by the occurrence of new vascular episodes.

Prognostic factors in very old demented adults: a seven-year follow-up from a population-based survey in Stockholm.

To detect prognostic factors in very old demented subjects with Alzheimer's disease (AD), vascular dementia (VaD), and other types of dementia (OD). Follow-up clinical examinations of dementia patients from a population-based study after 3- and 7-year intervals. In an established population aged 75 years and older in Stockholm, Sweden, there were 133 cases of AD, 52 of VaD, and 38 of OD. Predictors of survival at 3- and 7-year follow-up examinations were evaluated by Cox proportional hazard models. Progression was measured as the annual rate of change in Mini-Mental State Examination (MMSE) scores. Linear models were used to evaluate predictors of progression. Older age, male gender, low education, comorbidity, and functional disability predicted shorter 7-year survival in the 223 prevalent dementia cases. Other factors, including type of dementia, dementia severity, and duration of the disease were not significant. The average rate of cognitive decline in the 81 mild to moderate demented subjects who survived 3 years was 2.4 MMSE points per year. Type of dementia (AD vs OD), higher baseline cognitive function, and greater functional disability predicted faster decline. Despite similar survival probability, predictors of death varied as a function of dementia type: Older age (for AD and VaD), comorbidity (for AD and OD), and functional dependency (for VaD). In AD, prognostic factors were similar to those described for the combined dementia groups, with the exception of an accelerated cognitive decline among women. Although methodological difficulties exist, it is possible to identify demented subjects with worse prognoses (shorter survival and faster cognitive decline) by using clinical and demographic data. Clinicians and healthcare planners should be aware of the potential usefulness of functional dependence as a prognostic indicator. Finally, the need for careful clinical examinations of demented subjects is stressed by the increased mortality found among those demented who are also affected by other chronic conditions.

Methodology, results and quality of clinical trials of tacrine in the treatment of Alzheimer's disease: a systematic review of the literature

To review systematically the methodology, results and quality of clinical trials of tacrine in the treatment of Alzheimer's disease (AD). Trials included were those conducted on AD patients, aged 40 years or over, assigned to tacrine- or placebo-based treatment. Studies were identified via the Cochrane Collaboration and MEDLINE databases. Trial-selection and data-extraction were carried out separately by two reviewers working independently. Any differences of opinion that arose were resolved by discussion. We identified 49 trials published in the period 1 January 1981 - 1 May 1997. Of these, 21 were randomized controlled trials, eight parallel-group and 13 cross-over type. In the random trials, tacrine dosage ranged from 25 to 200 mg/day, with a duration of 3-36 weeks. In all, 3555 patients with mild to moderate AD started treatment and 1149 failed to complete the course (mean 33.4% patients per trial). Over 80% of patient withdrawals were tacrine-related. Adverse events affected a mean of 59% patients per trial (range 34-90%), mainly in the form of cholinergic manifestations (mean 30.2%, range 5-62%) and transaminase elevations (mean 28.6%, range 0-53%). Adverse events were more frequent at doses of > or = 100 mg/day and disappeared on discontinuation of tacrine treatment. Just over 20% of patients given tacrine experienced improvements in cognitive function (3-4 points in Alzheimer's Disease Assessment Scale cognitive subscale and 2-3 points in Mini-Mental State Examination) and in functional ability at 3-6 months of treatment. No study gave a description of concealment of the randomization sequence or the success of the double-blind procedure. Tacrine shows a modest degree of efficacy among a small proportion of patients with mild to moderate AD, yet has important adverse effects which limit its clinical usefulness. It is not known which AD patient subgroup could benefit from the treatment. Information on the long-term effects of tacrine (over periods exceeding 7 months) and its effects on quality of life, patient institutionalization and mortality and patient burden on caregivers is inadequate.