Prevalence and classification of mild cognitive impairment in the Cardiovascular Health Study Cognition Study: part 1

OBJECTIVE: To examine the prevalence of mild cognitive impairment (MCI) and its diagnostic classification in the Cardiovascular Health Study (CHS) Cognition Study. DESIGN: The CHS Cognition Study is an ancillary study of the CHS that was conducted to determine the presence of MCI and dementia in the CHS cohort. SETTING: Multicenter population study. PATIENTS: We examined 3608 participants in the CHS who had undergone detailed neurological, neuropsychological, neuroradiological, and psychiatric testing to identify dementia and MCI. MAIN OUTCOME MEASURES: The prevalence of MCI was determined for the whole cohort, and specific subtypes of MCI were examined in detail only at the Pittsburgh, Pa, center (n = 927). Mild cognitive impairment was classified as either MCI amnestic-type or MCI multiple cognitive deficits-type. RESULTS: The overall prevalence of MCI was 19% (465 of 2470 participants); prevalence increased with age from 19% in participants younger than 75 years to 29% in those older than 85 years. The overall prevalence of MCI at the Pittsburgh center was 22% (130 of 599 participants); prevalence of the MCI amnesic-type was 6% and of the MCI multiple cognitive deficits-type was 16%. CONCLUSIONS: Twenty-two percent of the participants aged 75 years or older had MCI. Mild cognitive impairment is a heterogeneous syndrome, where the MCI amnestic-type is less frequent than the MCI multiple cognitive deficits-type. Most of the participants with MCI had comorbid conditions that may affect their cognitive functions.     

Risk factors for dementia in the cardiovascular health cognition study

BACKGROUND: The Cardiovascular Health Cognition Study has evaluated the determinants of dementia among 3,608 participants that had a magnetic resonance imaging (MRI) of the brain in 1991 and were followed to 1998-1999. METHODS: There were 480 incident dementia cases, 330 (69%) were classified as Alzheimer's disease (AD). RESULTS: In univariate analysis, low scores on the Modified Mini-Mental State Examination (3MSE) and on the Digit Symbol Substitution Test as well as declines in scores over time prior to the development of dementia were significant predictors of dementia. A high ventricular grade on the MRI (atrophy) as well as high white matter grade, a number of brain infarcts on the MRI were all determinants of dementia. Apolipoprotein E epsilon4 (Apo(E-4)) was also a powerful predictor of dementia. In a multivariate Cox proportional hazards model controlling for race, gender and grade, the hazard ratios for age (1.1), 3MSE score (0.9), ventricular size (1.4), white matter grade (1.8), presence of large infarcts >3 mm (1.3) and Apo(E-4) (2.1) were significant predictors of dementia. The combination of an Apo(E-4) genotype, 3MSE score <90, > or =5 ventricular grade, > or =3 white matter grade at the time of the MRI were associated with a 17-fold increased risk (95% CI: 8.6-34.9) of dementia as compared to individuals with none of the above attributes. CONCLUSIONS: Measures of cognition, Apo(E-4) and MRI of the brain are strong predictors of both dementia and of AD.     

Cystatin C as a marker of cognitive function in elders: findings from the health ABC study

We determined whether serum cystatin C, a novel measure of kidney function that colocalizes with brain beta-amyloid, is associated with cognition among 3,030 elders. Those with high cystatin C (n = 445; 15%) had worse baseline scores on Modified Mini-Mental State Examination or Digit Symbol Substitution Test (p or=1.0 standard deviation) was greatest among those with high cystatin C (Modified Mini-Mental State Examination: 38 vs 25%; adjusted odds ratio, 1.92; 95% confidence interval, 1.37-2.69; Digit Symbol Substitution: 38 vs 26%; odds ratio, 1.54; 95% confidence interval, 1.10-2.15).     

The effect of apolipoprotein E epsilon4 in the relationships of smoking and drinking to cognitive function

OBJECTIVES: To investigate the joint effect of the apolipoprotein E epsilon4 (APOE epsilon4), smoking and drinking on cognitive performance in a population-based longitudinal study of elderly men. DESIGN AND SETTING: The NHLBI Twin Study, a longitudinal cardiovascular study of World War II, white, male veterans. PARTICIPANTS: A total of 589 male participants in the third cardiovascular examination of this panel and aged 59-69 when assessed for cognitive function. OUTCOME MEASURES: Cognitive function assessed by the Mini-Mental State Examination, the Digit Symbol Substitution Test, the Benton Visual Retention Test, APOE epsilon4 allele frequency and cardiovascular disease (CVD) health status. RESULTS: For the sample as a whole, after adjustment for age, education and CVD, smoking was significantly associated with poor cognitive function (odds ratio (OR) = 2.0, 95% confidence interval (CI) 1.2-3.2, in current smokers compared with never smokers), whereas light drinking (one or fewer drinks per day) showed a protective effect (OR = 0.6, 95% CI 0.4-0.9 compared with abstainers). Stratification by APOE epsilon4 indicated that the protective effect of light drinking was stronger and the harmful effect of smoking was weaker among APOE epsilon4 carriers than among noncarriers. CONCLUSIONS: These data suggest a possible mediating effect of the APOE epsilon4 allele in the relation of smoking and drinking to cognitive function in the elderly.     

Greater responsiveness to donepezil in Alzheimer patients with higher levels of acetylcholinesterase based on attention task scores and a donepezil PET study

The aim of the study was to predict donepezil responders among patients with Alzheimer disease (AD) based on cognitive tests and positron emission tomography. The Mini-Mental State Examination, Digit Symbol subtest (DigSm) of Wechsler Adult Intelligence Scale Revised, and Trail-Making Test A were administered for 80 patients with AD to assess global function, attention, and executive function, respectively. The same tests and the Clinical Global Impression (CGI) scale were conducted after treatment with oral donepezil (5 mg/d) for 6 months (study 1). [C]-Donepezil positron emission tomography examinations were conducted before and after treatment for 30 randomly selected patients. The distribution volume (DV), which indicates the density of donepezil-binding sites, was calculated using Logan graphical analysis (study 2). In study 1, 35 patients were identified as responders based on the CGI and Mini-Mental State Examination changes. These patients had higher baseline DigSm scores compared with nonresponders. In study 2, 15 patients were responders. DigSm correlated with DV at baseline. DV at baseline and %DV change in responders were higher than in nonresponders, and these variables correlated with ΔDigSm and CGI scores. Higher baseline attention may predict responsiveness to donepezil in patients with AD, and higher acetylcholinesterase levels result in a greater clinical effect.     

A clinical memory battery for screening for amnestic mild cognitive impairment in an elderly chinese population

Amnestic mild cognitive impairment (MCI) might be more likely to progress to Alzheimer’s disease than single non-memory MCI and multiple domain MCI. After excluding those who did not conform to the inclusion criteria of amnestic MCI or healthy controls, a neuropsychologic battery that included the Mini-Mental State Examination, Clinical Dementia Rating, Chinese version of the Montreal Cognitive Assessment, Instrumental Activities of Daily Living scale and Auditory Verbal Learning Test was performed on 150 amnestic MCI and 150 normal control patients. The Chinese version of the Montreal Cognitive Assessment was measured for its test-retest reliability, sensitivity and specificity. Blood was collected for apolipoprotein E (APOE) genotyping. Compared with the control group, the amnestic MCI group performed significantly worse on all neuropsychological tests, and non-APOE-??4 carriers in the amnestic MCI group performed better than APOE-??4 carriers in the amnestic MCI group. The set of neuropsychological tests in our study could distinguish amnestic MCI participants from normal elderly participants accurately. APOE did have a role in amnestic MCI patients, but the magnitude and mechanism of its influence are not fully understood.     

Congestive heart failure and cognitive functioning amongst older adults.

BACKGROUND: Congestive heart failure is associated with decline in quality of life and, possibly, cognitive functions such as memory and attention. AIMS: The present study was designed to investigate the presence of cognitive impairment amongst patients with congestive heart failure (CHF). We hypothesised that CHF patients would have lower scores than elderly controls on general measures of cognitive functioning. METHODS AND RESULTS: We examined a sample of 50 consecutive patients admitted to hospital with CHF functional class III/IV and a convenience sample of 30 older adults assessed at the outpatient service of geriatric medicine of a teaching hospital in S?o Paulo, Brazil. All subjects were interviewed with the Cambridge Examination for Mental Disorders of the Elderly (CAMDEX), as well as the neuropsychological battery of the CAMDEX (CAMCOG), Mini-Mental State Examination (MMSE), Trail Making A and B, Digit Span, Digit Symbol, and Letter Cancellation Test. All CHF patients had left ventricular ejection fraction (EF) below 45% and all controls above 65%. The cognitive performance of CHF patients was significantly worse than controls for all cognitive assessments. Twenty-seven of 50 CHF patients had a MMSE total score lower than 24, compared with only 10/30 controls (p=0.073). Similarly, 36/49 and 9/30 CHF subjects and controls respectively had CAMCOG scores below 80 (p<0.001). Cognitive scores were significantly associated with EF, which was the most robust predictor of cognitive impairment according to the CAMCOG in a logistic regression model. CONCLUSION: Our results indicate that CHF is associated with significant levels of cognitive impairment and show that mental performance is, at least partly, a consequence of EF. Physicians should be prepared to assess the mental state of patients, as poor cognitive functioning may interfere with treatment compliance and management plan.     

Rapid cognitive screening in multiple sclerosis accomplished by the Free Recall and Recognition Test

This study sought to investigate the feasibility of the Free Recall and Recognition Test (FRRT) as a practical screening tool for cognitive impairment in multiple sclerosis (MS). Persons with MS (n = 227) were consecutively recruited and assessed with four cognitive tests; FRRT, Symbol Digit Modalities Test (SDMT), Paced Auditory Serial Addition Test (PASAT), and the Mini-Mental State Examination (MMSE). Disease severity was assessed by the Expanded Disability Status Scale (EDSS). The FRRT, which was completed by 99% of the cohort in approximately 5 minutes per assessment, correlated significantly with the other cognitive tests, as well as with the disease severity rating. A cut-off of 4 for the FRRT recall rendered 90% sensitivity and 25% specificity, and a cut-off of 4.2 for the FRRT recognition resulted in 70% sensitivity and 51% specificity. We conclude that the FRRT proved feasible as a practical screening tool for cognitive impairment in MS within a clinical setting.     

Depressive symptoms, vascular disease, and mild cognitive impairment: findings from the Cardiovascular Health Study

CONTEXT: Depressive symptoms are common in patients with dementia and may be associated with increased risk of developing dementia. It has been hypothesized that depressive symptoms and dementia may be attributable to underlying vascular disease in some older persons. OBJECTIVES: To test the hypotheses (1) that depressive symptoms are associated with increased risk of developing mild cognitive impairment (MCI), a preclinical state that often precedes dementia, and (2) that the association between depressive symptoms and MCI is attributable to underlying vascular disease. DESIGN: Prospective, population-based, longitudinal study. SETTING: Random sample of adults 65 years or older recruited from 4 US communities. PARTICIPANTS: Subjects were 2220 participants in the Cardiovascular Health Study Cognition Study with high cognitive function at baseline. Depressive symptoms were measured at baseline using the 10-item Center for Epidemiological Studies Depression Scale and were classified as none (0-2 points), low (3-7 points), and moderate or high (>/=8 points). Vascular disease measures at baseline included confirmed history of stroke, transient ischemic attack, diabetes mellitus, or hypertension; carotid artery stenosis; ankle-arm blood pressure index; and small or large infarcts or white matter disease on cerebral magnetic resonance imaging. Mild cognitive impairment was diagnosed after 6 years of follow-up based on the consensus of a team of dementia experts using standard clinical criteria. MAIN OUTCOME MEASURE: Diagnosis of MCI. RESULTS: Depressive symptoms at baseline were associated with increased risk of MCI (10.0%, 13.3%, and 19.7% for those with no, low, and moderate or high depressive symptoms, respectively). This association was diminished only slightly by adjustment for vascular disease measures and demographics. Vascular disease measures also were associated with increased risk of MCI, and these associations were not diminished by adjustment for depressive symptoms or demographics. CONCLUSION: Depressive symptoms were associated with increased risk of MCI, and this association was independent of underlying vascular disease.     

Gender differences in tea, coffee, and cognitive decline in the elderly: the Cardiovascular Health Study

Although caffeine can enhance cognitive function acutely, long-term effects of consumption of caffeine-containing beverages such as tea and coffee are uncertain. Data on 4,809 participants aged 65 and older from the Cardiovascular Health Study (CHS) were used to examine the relationship of consumption of tea and coffee, assessed by food frequency questionnaire, on change in cognitive function by gender. Cognitive performance was assessed using serial Modified Mini-Mental State (3MS) examinations, which were administered annually up to 9 times. Linear mixed models were used to estimate rates of change in standard 3MS scores and scores modeled using item response theory (IRT). Models were adjusted for age, education, smoking status, clinic site, diabetes, hypertension, stroke, coronary heart disease, depression score, and APOE genotype. Over the median 7.9 years of follow-up, participants who did not consume tea or coffee declined annually an average of 1.30 points (women) and 1.11 points (men) on standard 3MS scores. In fully adjusted models using either standard or IRT 3MS scores, we found modestly reduced rates of cognitive decline for some, but not all, levels of coffee and tea consumption for women, with no consistent effect for men. Caffeine consumption was also associated with attenuation in cognitive decline in women. Dose-response relationships were not linear. These longitudinal analyses suggest a somewhat attenuated rate of cognitive decline among tea and coffee consumers compared to non-consumers in women but not in men. Whether this association is causal or due to unmeasured confounding requires further study.     

Heritability of cognitive performance in aging twins. The National Heart, Lung, and Blood Institute Twin Study

The genetic contribution to performance on scales designed to measure mild to moderate decrements in cognitive functioning in a population at risk is unknown. In the present analysis, 134 monozygotic and 133 dizygotic male twin pairs (mean age, 63 years) were given three cognitive tests: the Mini-Mental State examination, the Iowa Screening Battery for Mental Decline, and, for comparison, the Digit Symbol Substitution Test from the Wechsler Adult Intelligence Scale. The primary objective of the analysis was to test for a significant heritable component to performance on these measures. A secondary objective was to determine the extent to which shared variance with significant confounders such as education, age, and depression affects the outcome of the heritability analysis. Results indicate that performance on tests intended to measure cognitive decline in the elderly does have a significant genetic component and that these estimates tend to increase after adjustment for covariates. Heritability estimates adjusted for covariates were 30% for the Iowa Screening score, 60% for the Mini-Mental State score, and 67% for the Digit Symbol Substitution score.     

Serum lipoprotein levels, statin use, and cognitive function in older women

BACKGROUND: Few strategies are available for the prevention of cognitive impairment in elderly persons. Serum lipoprotein levels may be important predictors of cognitive function, and drugs that lower cholesterol may be effective for the prevention of cognitive impairment. OBJECTIVE: To determine whether serum lipoprotein levels, the 4-year change in serum lipoprotein levels, and the use of statin drugs are associated with cognition in older women without dementia. DESIGN, SETTING, AND PARTICIPANTS: An observational study of 1037 postmenopausal women with coronary heart disease enrolled in the Heart and Estrogen/progestin Replacement Study (participants at 10 of 20 centers). MAIN OUTCOME MEASURE: The Modified Mini-Mental State Examination was administered at the end of the study after 4 years of follow-up. Women whose score was less than 84 points (>1.5 SDs below the mean) were classified as having cognitive impairment. Lipoprotein levels (total, high-density lipoprotein, and low-density lipoprotein [LDL] cholesterol and triglycerides) were measured at baseline and at the end of the study; statin use was documented at each visit. RESULTS: Compared with women in the lower quartiles, women in the highest LDL cholesterol quartile at cognitive testing had worse mean plus minus SD Modified Mini-Mental State Examination scores (93.7 plus minus 6.0 vs 91.9 plus minus 7.6; P =.002) and an increased likelihood of cognitive impairment (adjusted odds ratio, 1.76; 95% confidence interval, 1.04-2.97). A reduction in the LDL cholesterol level during the 4 years tended to be associated with a lower odds of impairment (adjusted odds ratio, 0.61; 95% confidence interval, 0.36-1.03) compared with women whose levels increased. Higher total and LDL cholesterol levels, corrected for lipoprotein(a) levels, were also associated with a worse Modified Mini-Mental State Examination score and a higher likelihood of impairment, whereas high-density lipoprotein cholesterol and triglyceride levels were not associated with cognition. Compared with nonusers, statin users had higher mean plus minus SD Modified Mini-Mental State Examination scores (92.7 plus minus 7.1 vs 93.7 plus minus 6.1; P =.02) and a trend for a lower likelihood of cognitive impairment (odds ratio, 0.67; 95% confidence interval, 0.42-1.05), findings that seemed to be independent of lipid levels. CONCLUSIONS: High LDL and total cholesterol levels are associated with cognitive impairment, and lowering these lipoprotein levels may be a strategy for preventing impairment. The association between statin use and better cognitive function in women without dementia requires further study.     

Development and assessment of a composite score for memory in the Alzheimer’s Disease Neuroimaging Initiative (ADNI)

We sought to develop and evaluate a composite memory score from the neuropsychological battery used in the Alzheimer’s Disease (AD) Neuroimaging Initiative (ADNI). We used modern psychometric approaches to analyze longitudinal Rey Auditory Verbal Learning Test (RAVLT, 2 versions), AD Assessment Schedule - Cognition (ADAS-Cog, 3 versions), Mini-Mental State Examination (MMSE), and Logical Memory data to develop ADNI-Mem, a composite memory score. We compared RAVLT and ADAS-Cog versions, and compared ADNI-Mem to RAVLT recall sum scores, four ADAS-Cog-derived scores, the MMSE, and the Clinical Dementia Rating Sum of Boxes. We evaluated rates of decline in normal cognition, mild cognitive impairment (MCI), and AD, ability to predict conversion from MCI to AD, strength of association with selected imaging parameters, and ability to differentiate rates of decline between participants with and without AD cerebrospinal fluid (CSF) signatures. The second version of the RAVLT was harder than the first. The ADAS-Cog versions were of similar difficulty. ADNI-Mem was slightly better at detecting change than total RAVLT recall scores. It was as good as or better than all of the other scores at predicting conversion from MCI to AD. It was associated with all our selected imaging parameters for people with MCI and AD. Participants with MCI with an AD CSF signature had somewhat more rapid decline than did those without. This paper illustrates appropriate methods for addressing the different versions of word lists, and demonstrates the additional power to be gleaned with a psychometrically sound composite memory score.     

Diabetes, glucose control, and 9-year cognitive decline among older adults without dementia

OBJECTIVES To determine if prevalent and incident diabetes mellitus (DM) increase risk of cognitive decline and if, among elderly adults with DM, poor glucose control is related to worse cognitive performance. DESIGN Prospective cohort study. SETTING Health, Aging, and Body Composition Study at 2 community clinics. PARTICIPANTS A total of 3069 elderly adults (mean age, 74.2 years; 42% black; 52% female). MAIN OUTCOME MEASURES Participants completed the Modified Mini-Mental State Examination (3MS) and Digit Symbol Substitution Test (DSST) at baseline and selected intervals over 10 years. Diabetes mellitus status was determined at baseline and during follow-up visits. Glycosylated hemoglobin A1c level was measured at years 1 (baseline), 4, 6, and 10 from fasting whole blood. RESULTS At baseline, 717 participants (23.4%) had prevalent DM and 2352 (76.6%) were without DM, 159 of whom developed incident DM during follow-up. Participants with prevalent DM had lower baseline test scores than participants without DM (3MS: 88.8 vs 90.9; DSST: 32.5 vs 36.3, respectively; t?=?6.09; P?=?.001 for both tests). Results from mixed-effects models showed a similar pattern for 9-year decline (3MS: -6.0- vs -4.5-point decline; t?=?2.66; P?=?.008; DSST: -7.9- vs -5.7-point decline; t?=?3.69; P?=?.001, respectively). Participants with incident DM tended to have baseline and 9-year decline scores between the other 2 groups but were not statistically different from the group without DM. Multivariate adjustment for demographics and medical comorbidities produced similar results. Among participants with prevalent DM, glycosylated hemoglobin A1c level was associated with lower average mean cognitive scores (3MS: F?=?8.2; P for overall?=?.003; DSST: F?=?3.4; P for overall?=?.04), even after multivariate adjustment. CONCLUSION Among well-functioning older adults, DM and poor glucose control among those with DM are associated with worse cognitive function and greater decline. This suggests that severity of DM may contribute to accelerated cognitive aging.     

Depressive symptoms and cognitive decline in nondemented elderly women: a prospective study

BACKGROUND: The association between depressive disorders and subsequent cognitive decline is controversial. We tested the hypothesis that elderly women (aged 65 years and older) without dementia but with depressive symptoms have worse cognitive function and greater cognitive decline than women with few or no symptoms. METHODS: As part of an ongoing prospective study, we evaluated 5781 elderly, mostly white, community-dwelling women. Women completed the Geriatric Depression Scale short form. Three cognitive tests--Trails B, Digit Symbol, and a modified Mini-Mental State Examination--were administered at baseline and approximately 4 years later. Baseline, follow-up, and change scores for the cognitive tests were analyzed by analysis of covariance and Kruskal-Wallis analysis; the odds of cognitive deterioration (> or =3-point decline on the modified Mini-Mental State Examination) were determined by logistic regression. RESULTS: At baseline, 211 (3.6%) of the women had 6 or more depressive symptoms. Only 16 (7.6%) of these women were receiving antidepressant medication. Increasing symptoms of depression were associated with worse performance at baseline and follow-up on all 3 tests of cognitive function (P<.001 for all comparisons). For example, the baseline Digit Symbol score (mean +/- SD) was 45.5 +/- 10.7 among women with 0 to 2 symptoms of depression, 40.3 +/- 10.7 for women with 3 to 5 symptoms, and 39.0 +/- 11.3 for women with 6 or more symptoms. After adjusting for the baseline score, cognitive change scores were also inversely associated with the number of depressive symptoms (P<.001 for all comparisons). Odds ratios for cognitive deterioration using 0 to 2 symptoms as the reference were 1.6 (95% confidence interval, 1.3-2.1) for 3 to 5 symptoms and 2.3 (95% confidence interval, 1.6-3.3) for 6 or more symptoms. Results were similar after being adjusted for education, age, health status, exercise, alcohol use, functional status, and clinic site. CONCLUSIONS: Depressive symptoms in older women are associated with both poor cognitive function and subsequent cognitive decline. Mechanisms underlying the association between these 2 common conditions need further exploration.     

Effects of Lacunar Infarctions on Cognitive Impairment in Patients with Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy

Background and Purpose

Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited microangiopathy caused by mutations in the Notch3 gene. Although previous studies have shown an association between lacunar infarction and cognitive impairment, the relationship between MRI parameters and cognition remains unclear. In this study we investigated the influence of MRI parameters on cognitive impairment in CADASIL.

Methods

We applied a prospective protocol to 40 patients. MRI analysis included the normalized volume of white-matter hyperintensities (nWMHs), number of lacunes, and number of cerebral microbleeds. Cognition was assessed with the aid of psychometric tests [Mini-Mental State Examination (MMSE), Alzheimer''s Disease Assessment Scale-cognition (ADAS-cog), Trail-Making Test, and Stroop interference (Stroop IF)].

Results

A multivariate regression analysis revealed that the total number of lacunes influenced the performance in the MMSE, ADAS-cog, and Stroop IF, while nWMHs had a strong univariate association with ADAS-cog and Stroop IF scores. However, this association disappeared in the multivariate analysis.

Conclusions

These findings demonstrate that the number of lacunes is the main predictive factor of cognitive impairment in CADASIL.     

Cerebral ventricular changes associated with transitions between normal cognitive function, mild cognitive impairment, and dementia

Expansion of the cerebral ventricles may occur at an accelerated rate in subjects with dementia, but the time course of expansion during transitions between normal cognitive function, mild cognitive impairment (MCI), and dementia is not well understood. Furthermore, the effects of cardiovascular risk factors on rate of ventricular expansion are unclear. We used a fully automated segmentation technique to measure change rate in lateral ventricle-to-brain ratio (VBR) on 145 longitudinal pairs of magnetic resonance images of subjects in the Cardiovascular Health Study Cognition Study from the Pittsburgh Center. A multivariate model analyzed VBR change rate, accounting for dementia statuses at both imaging times (normal, MCI, or dementia), age, sex, education, race, magnetic resonance-defined infarcts, Center for Epidemiology Studies Depression Scale, baseline ventricular volume, and cardiovascular risk factors. VBR change was faster in subjects who were demented or transitioned from MCI to dementia, compared with subjects normal at both images and subjects who transitioned from normal to MCI or dementia. Patients with diabetes had faster VBR change. Ventricular expansion may accelerate late in the progression from normal cognitive function to dementia, and may be modulated by diabetes.     

Association of low serum anticholinergic levels and cognitive impairment in elderly presurgical patients

Low-dose scopolamine, given as presurgery medication, resulted in low levels of serum anticholinergic activity and caused measurable cognitive impairment in 18 psychiatrically healthy elderly patients. The degree of impairment was directly related to serum anticholinergic activity levels and, in the small subgroup of patients scheduled for spinal anesthesia, to CSF anticholinergic activity. Two of the mental status tests used, the Rey Auditory-Verbal Learning Test and the Saskatoon Delirium Checklist, were sensitive enough to detect these mild drug-induced changes, while two other tests, the Mini-Mental State and the Symbol Digit Modalities Test, were not.     

Subjective memory complaints in an elderly sample: a cross-sectional study

BACKGROUND: Community based studies show that neurological or psychiatric symptoms are very frequent among the elderly population, with poor memory complaints being the most common. However, the relationship between poor memory complaints and objective memory performance is unclear. We designed this study to evaluate whether subjective memory complaints (SMC) are associated with objective cognitive performance or depression amongst the elderly Brazilian generation. METHODS: A cross-sectional study was carried out in 114 patients who were 50+, with or without SMC having no obvious cognitive impairment at its baseline (this was screened by the Mini-Mental State Examination with cut-off values adapted according to the subjects' educational background). Subjects were assessed regarding memory difficulty complaints, demographic data and underwent a neuropsychological assessment made up of nine cognitive tests (Rey Auditory Verbal Learning Test, Visual Reproduction Test, Logic Memory--History A, Free and Cued Selective Reminding Test, Stroop Test, Digit Span, Digit Symbol, Trail Making Test, fluency tests: naming animals and fruits) and the Geriatric Depression Scale. RESULTS: Twenty-one percent of the subjects had subjective memory complaints. The scores in the cognitive assessment of subjects with SMC did not differ from the scores of subjects without SMC. However, patients with subjective memory complaints had lower scores in the fluency test--category animals and the Geriatric Depression Scale. CONCLUSIONS: These results support the finding from other cross-sectional studies showing that subjective memory complaints are associated with depressive symptoms rather than objective cognitive performance.     

Hormone replacement therapy and reduced cognitive decline in older women: the Cache County Study.

OBJECTIVE: To examine the association between postmenopausal hormone replacement therapy (HRT) and the trajectory of global cognitive change with age. METHODS: The Modified Mini-Mental State Examination (MMSE) was administered to a population sample of 2,073 nondemented, community-dwelling female residents of Cache County, UT, aged 65 and older. Current and past HRT and other medications at a baseline interview and at follow-up 3 years later were assessed. Between interviews, a telephone Women's Health Questionnaire was administered to assess initial exposure, duration, and recency of HRT. Generalized estimating equation marginal models were used to evaluate the cross-sectional and longitudinal relations of HRT and modified MMSE score. Also assessed were effects with multivitamins and calcium supplements as exposures likely to reflect a "healthy lifestyle" among HRT users. Model covariates included the presence of APOE epsilon4 alleles, age, education, concurrent depression, several chronic diseases, and self-perceived general health. RESULTS: Age, lower education, depression, and APOE epsilon4 were all associated with lower baseline modified MMSE scores. With these covariates in the model, lifetime HRT use was associated with better baseline modified MMSE scores and a slower rate of decline. Stratification by APOE genotype did not alter these effects. Apparent benefits with HRT were attenuated but remained significant after elimination of scores from participants with incident dementia. A significant interaction between age and HRT indicated the strongest effects in women aged 85 and older. Measures of age at initial use of HRT, duration, and recency of exposure did not improve the models. No effects were seen with the "healthy lifestyle" control exposures. CONCLUSIONS: In a population cohort of older women, lifetime HRT exposure was associated with improved global cognition and attenuated decline over a 3-year interval. Improvements were greatest in the oldest old.