Multiple-domain Mild Cognitive Impairment Research Articles

Everyday functioning in mild cognitive impairment and its relationship with executive cognition

Elderly persons with mild cognitive impairment (MCI) are at increased risk of dementia and functional impairments. The present study investigated the contribution of three domains of executive cognition to everyday functioning among persons with MCI. 124 MCI patients and 68 cognitively normal elderly participants were administered a cognitive screening battery. These tests were used to divide patients into four subgroups (amnestic single domain, amnestic multiple domain, non-amnestic single domain, and non-amnestic multiple domain). Subjects were then administered 18 executive function tests that assess planning/problem-solving, working memory, and judgment. Performance of everyday activities and everyday cognition was rated with two informant-reported measures. All MCI subtypes had more difficulties in everyday activities than cognitively normal elderly participants. Multiple domain MCI patients had more functional impairments than single domain MCI patients. Contrary to our expectations, only one executive function component, working memory, contributed significantly to functional status after controlling for demographic, health-related and other cognitive factors. Functional abilities are compromised in all MCI subtypes. Working memory may be associated with functional impairments, but general cognitive measures account for more unique variance.

Functional Abilities in Older Adults with Mild Cognitive Impairment

Background: A classification scheme and general set of criteria for diagnosing mild cognitive impairment (MCI) were recently proposed by a multidisciplinary group of experts who met at an international symposium on MCI. One of the proposed criteria included preserved basic activities of daily living and minimal impairment in complex instrumental activities of daily living (IADLs). Objective: To investigate whether older adults with MCI classified according to the subtypes identified by the Working Group (i.e. amnestic, single non-memory domain, and multiple domain with or without a memory component) differed from cognitively intact older adults on a variety of measures indexing IADLs and to examine how well measures of IADL predict concurrent MCI status. Methods: Two hundred and fifty community-dwelling older adults, ranging in age from 66 to 92, completed self-report measures of IADLs (Lawton and Brody IADL Scale, Scales of Independent Behaviour-Revised – SIB-R) and a measure of everyday problem solving indexing IADLs (Everyday Problems Test – EPT). Ratings of participants’ IADL functioning were also obtained from informants (e.g. spouse, adult child and friend). Results: Older adults with multiple-domain MCI demonstrated poorer IADL functioning than older adults with no cognitive impairment on the EPT and the SIB-R (both self- and informant-report versions). The multiple-domain MCI participants also demonstrated poorer IADLs than MCI participants with impairments in a single cognitive domain on the self-reported SIB-R and EPT. The single-domain MCI groups demonstrated poorer IADLs than older adults without cognitive impairment on the informant-reported SIB-R and EPT. No significant group differences were found on the Lawton and Brody IADL Scale. Using the EPT and SIB-R as predictors in a multinomial regression analysis, MCI group status was reliably predicted, but the classification rate was poor. Conclusion: Individuals with MCI demonstrated poorer IADL functioning compared to cognitively intact older adults. However, the changes in IADL functioning observed in MCI may be too subtle to be detected by certain measures, such as the Lawton and Brody IADL Scale.

Impact of Vascular Risk Factors and Diseases on Cognition in Persons with Mild Cognitive Impairment

Background/Aim: To investigate the impact of vascular burden (assessed by the number of vascular risk factors and diseases) on the cognition of persons with amnestic mild cognitive impairment (aMCI). Methods: This study included 145 participants; 68 meeting criteria for amnesic single-domain or multiple-domain MCI and 77 matched controls. Four cognitive domains were assessed: executive functions, processing speed, episodic memory and general cognitive functioning. Results: A larger vascular burden among aMCI is correlated with lower performance in the executive domain. In addition, persons with aMCI with high vascular burden were more frequently of the multiple domain subtype, whereas persons with no vascular burden were more frequently of the single domain subtype. Conclusion: Our findings suggest that the combined effect of multiple vascular risk factors and diseases increases the amount of executive impairment in persons with aMCI. Vascular burden may play an important role in the heterogeneity of aMCI by impairing cognitive functions other than memory.

Structural MRI biomarkers for preclinical and mild Alzheimer's disease

Noninvasive MRI biomarkers for Alzheimer's disease (AD) may enable earlier clinical diagnosis and the monitoring of therapeutic effectiveness. To assess potential neuroimaging biomarkers, the Alzheimer's Disease Neuroimaging Initiative is following normal controls (NC) and individuals with mild cognitive impairment (MCI) or AD. We applied high-throughput image analyses procedures to these data to demonstrate the feasibility of detecting subtle structural changes in prodromal AD. Raw DICOM scans (139 NC, 175 MCI, and 84 AD) were downloaded for analysis. Volumetric segmentation and cortical surface reconstruction produced continuous cortical surface maps and region-of-interest (ROI) measures. The MCI cohort was subdivided into single- (SMCI) and multiple-domain MCI (MMCI) based on neuropsychological performance. Repeated measures analyses of covariance were used to examine group and hemispheric effects while controlling for age, sex, and, for volumetric measures, intracranial vault. ROI analyses showed group differences for ventricular, temporal, posterior and rostral anterior cingulate, posterior parietal, and frontal regions. SMCI and NC differed within temporal, rostral posterior cingulate, inferior parietal, precuneus, and caudal midfrontal regions. With MMCI and AD, greater differences were evident in these regions and additional frontal and retrosplenial cortices; evidence for non-AD pathology in MMCI also was suggested. Mesial temporal right-dominant asymmetries were evident and did not interact with diagnosis. Our findings demonstrate that high-throughput methods provide numerous measures to detect subtle effects of prodromal AD, suggesting early and later stages of the preclinical state in this cross-sectional sample. These methods will enable a more complete longitudinal characterization and allow us to identify changes that are predictive of conversion to AD.

Characteristic Profiles of Instrumental Activities of Daily Living in Different Subtypes of Mild Cognitive Impairment

Background/Aims: The purposes of this study were to describe restrictions in instrumental activities of daily living (IADL) in mild cognitive impairment (MCI) and to assess different patterns of IADL in each MCI subtype. Methods: A total of 566 participants, those not cognitively impaired (NCI; n = 311) and MCI patients (n = 255), 60–94 years old (71.25 ± 6.00), were examined. Neuropsychological tests were administered to participants, and each MCI patient was classified into one of four subtypes. They completed the Barthel ADL and Seoul-IADL (S-IADL) for ADL measures. Results: There was a significant difference between NCI and MCI in terms of total S-IADL scores. ANOVA and a post hoc Dunnett analysis revealed that MCI patients performed significantly worse on four out of a total 15 items (i.e. telephone, transportation, finances and household appliances). ANCOVA showed a significant difference in S-IADL-MCI (4 of 15 items) between NCI and amnestic MCI-multiple domains after adjusting for age, gender, education and Geriatric Depression Scale (F = 4.257, d.f. = 1,556, p = 0.002). Conclusion: These findings suggest that scorings of specific IADL items are different in MCI subjects, and these items can possibly help in the identification of MCI subtypes, especially amnestic MCI-multiple domains.

Odor Identification and Self-reported Olfactory Functioning in Patients with Subtypes of Mild Cognitive Impairment

Olfactory dysfunction is a very early symptom of Alzheimer's disease (AD), and olfactory dysfunction has also been found in mild cognitive impairment (MCI). The goal of the present study was to compare odor identification ability and self-reported olfactory functioning in patients with different types of MCI. We included 104 elderly participants classified into two groups: patients with mild cognitive impairment (MCI) and elderly controls (EC). Based on their performance in neuropsychological testing the study population was divided into four groups of participants based on cognitive features: amnestic MCI single domain (11), amnestic MCI multiple domain (19), non-amnestic MCI single domain (21) and non-amnestic MCI multiple domain (13), respectively. The MCI patients were compared to 40 elderly controls (EC) controls with no cognitive deficit. Comparison for odor identification revealed a significant difference between amnestic MCI multiple domain patients and the EC group. No other group comparison was significant. Statistical analyses for self-reported olfactory functioning revealed no significant group differences between any subgroup of MCI patients and the control group. Correlational analyses indicated that odor identification ability was related to cognition whereas no relationship was found for self-reported olfactory functioning. The present study showed that amnestic MCI patients with additional deficits in other cognitive domains have a specific odor identification impairment. Together with cognitive testing, olfactory testing may more accurately help predict whether or not a patient with MCI will convert to AD in the near future.

Deterioro cognitivo leve: características neuropsicológicas de los distintos subtipos

To evaluate the frequency of mild cognitive impairment (MCI) subtypes and their neuropsychological characteristics in our population, and estimate the change in this frequency according to the extension of the neuropsychological examination. Patients with diagnostic of MCI were included from 01/01/2003 to 31/12/2007. MCI was classified as MCI-amnestic type (MCI-AT), MCI-multiple domain type (MCI-MDT) and MCI-single domain non amnestic (MCI-MNOA). A neuropsychological test was considered abnormal if its result was equal or less than 1.5 standard deviations from what expected for age and educational level. The cohort was divided in short evaluation (less than 14 test, from 2003-2005) and basic-extended evaluation (equal or more than 14 test, from 2006-2007). Out of 204 patients included, 51 (26%) were classified as MCI-AT, 11 (5,4%) as MCI-MNOA and 142 (69,9%) as MCI-MDT. A higher educational level was associated with an increase in the number of MCI-MDT. The longer the evaluation, the greater was the proportion of MCI-MDT and MCI-MNOA and the lower the proportion of MCI-AT, without statistical significance. The most frequent MCI subtype was MCI-MDT. A more extended evaluation would allow a better classification of MCI subtypes and increase the number of MCI-MDT and MCI-MNOA at the expense of MCI-AT.

Mild behavioral impairment: A prodromal stage of dementia.

Mild cognitive impairment (MCI) was defined by Petersen et al. (1999) as progressive memory loss, a prodrome of Alzheimer’s disease. MCI is a well-established entity that can be both a diagnosis in medical practice and a valid target of Alzheimer’s prevention therapy. More recently MCI has expanded to include other cognitive domains with other potential causes: amnestic MCI, multiple domains MCI, and single domain non-amnestic MCI. Behavioral symptoms in MCI are associated with a higher risk of dementia, but their association with dementia risk in patients without MCI is unknown. The objective of our paper was to address the question of whether aging patients with behavioral symptoms with or without cognitive impairment represent a population at risk for dementia. Mild Behavioral Impairment (MBI) defines a late life syndrome with prominent psychiatric and related behavioral symptoms in the absence of major cognitive symptoms. MBI also appears to be a transitional state between normal aging and dementia. MBI may carry a higher risk for dementia than MCI. A subgroup of MBI patients is likely to exhibit symptoms of a frontotemporal dementia (FTD) prodrome. We proposed 4 subtypes of patients at risk for dementia: amnestic MCI (which is said to progress preferentially to Alzheimer’s disease), multiple domain MCI (which may represent normal aging or may progress to vascular cognitive impairment or a neurodegenerative disorder), single domain non-amnestic MCI, and MBI (which may progress to frontotemporal dementia, Lewy Body dementia or Alzheimer’s disease). We concluded that MBI is a counterpart of MCI as a transitional state between normal aging and dementia. These findings have implications for early detection, prevention, and treatment of patients with late-life dementia.

Impairment in Emotion Recognition Abilities in Patients With Mild Cognitive Impairment, Early and Moderate Alzheimer Disease Compared With Healthy Comparison Subjects

To investigate emotion discrimination abilities in healthy comparison subjects, patients with mild cognitive impairment (MCI), early and moderate Alzheimer disease (AD). Prospective study design. Outpatient memory clinic, Department of Psychiatry, Innsbruck, Austria. One hundred forty-one subjects older than 60 years were included in the study. Thirty-five subjects were classified as healthy comparison subjects, 51 subjects as MCI (21 subjects with amnestic MCI single domain, 31 subjects with amnestic MCI multiple domain), 32 subjects with early AD and 23 subjects with moderate AD. All subjects were tested on an extensive neuropsychological test battery including the Penn Emotion Recognition Tests and depression symptoms were assessed additionally. Healthy subjects and patients with MCI, early and moderate AD differed significantly in the recognition of all emotions and neutral faces combined. When separated by emotion, the authors found significant differences in emotion recognition between the diagnostic groups for happy, sad, fearful, and neutral faces. Compared with comparison subjects, amnestic MCI patients single domain did not differ significantly in their emotion recognition abilities, but amnestic MCI multiple domain patients were already impaired in the recognition of overall emotions, sad, fearful, and neutral faces and the deficits increased with the severity of AD. Depression had a significant influence on the recognition of overall emotion and neutral faces and increased the probability of misinterpreting neutral faces as sad leading to a negative bias. Diminished abilities for emotion discrimination are already present in patients with MCI and further decreased with AD progression.

Mild cognitive impairment and subjective cognitive impairment

Mild cognitive impairment and subjective cognitive impairment

Cognitive impairment in incident, untreated Parkinson disease

Little is known regarding the cognitive impairment in subjects with early, drug-naïve Parkinson disease (PD). The aim of this study was to explore the proportion with mild cognitive impairment (MCI) and subtypes in an incidence cohort of untreated PD in Southern and Western Norway. A total of 196 non-demented, drug-naive patients who were recruited after an extensive search of all new cases of PD in the area and 201 healthy control subjects completed a battery of neuropsychological tests of verbal memory, visuospatial, and attentional-executive functioning. Subjects were classified as MCI if the age- and education-corrected z-score was falling 1.5 standard deviations below the mean for at least one of the cognitive domains. The PD group was more impaired on all neuropsychological tests than controls, but the effect sizes were small. The largest effect size was found for verbal memory. A total of 18.9% of the patients with PD were classified as MCI, with a relative risk of 2.1 (1.2-3.6) in PD compared to the control group. Patients with PD with and without MCI did not differ significantly regarding demographic and motor features. Among PD-MCI patients, nearly two-thirds had a non-amnestic MCI subtype, and one third had an amnestic MCI subtype. The findings demonstrate a twofold increase in the proportion with cognitive impairment in subjects with early, untreated Parkinson disease (PD) compared to controls. This has implications for diagnosis and management of PD. AD = Alzheimer disease; aMCI-MD = amnestic multiple-domain MCI; aMCI-SD = amnestic single-domain MCI; CVLT-2 = California Verbal Learning Test II; IQCode = Informant Questionnaire on Cognitive decline in the elderly; MADRS = Montgomery and Aasberg Depression Rating Scale; MCI = mild cognitive impairment; MMSE = Mini-Mental State Examination; naMCI-MD = non-amnestic multiple-domain MCI; naMCI-SD = non-amnestic single-domain MCI; PD = Parkinson disease; RR = relative risks; UPDRS = Unified Parkinson's Disease Rating Scale; VOSP = Visual Object and Space Perception Battery.

P3-134: Assessment of Japanese- and English-language equivalence of the cognitive abilities screening instrument (CASI) among Japanese-Americans in two large epidemiological studies

memory, the Neuropsychological Assessment Battery (NAB) List Learning (LL) test (Stern & White, 2003) is a promising tool for the assessment of older adults due to its relative simplicity, excellent psychometric validation, equivalent forms, and extensive normative data in older individuals. This study examined the diagnostic utility of the NAB LL test in differentiating cognitively normal, MCI, and AD participants. Methods: Extant data from the Boston University Alzheimer’s Disease Center Registry was retrospectively analyzed for 153 participants (57-94 years, 74 8 years; 61% women) diagnosed by a consensus team as cognitively normal (n 98), amnestic MCI (single or multiple domain; n 29), or AD (n 26). Diagnoses were made independent of NAB LL performance. To determine classification accuracy, receiver operating characteristics analyses were conducted for seven NAB LL variables (List A Immediate Recall, List B Immediate Recall, Short Delay Recall, Long Delay Recall, Percent Retention, and Recognition Hits and False Alarms). In addition, ordinal multiple regression was used to create a model to predict group membership based on a combination of the NAB LL variables. Results: The sensitivities and specificities of the NAB LL test variables were good to excellent, yielding positive likelihood ratios ranging from 1.8 to 30.2 (Mdn 4.2). The ordinal regression produced a model that predicted group membership with an overall accuracy of 85%. The model was most accurate at classifying controls (97%), followed by AD (74%) and MCI (52%), which indicates that it can very accurately rule out the latter two diagnoses. Conclusions: Both the regression-based model and the individual NAB LL variables were highly accurate in differentiating cognitively normal controls, MCI, and AD groups. Compared to published data, the classification accuracy statistics presented here appear to match or exceed those reported for other common list learning tests (e.g., HVLT-R, CERAD, CVLT) in this population.

Characteristic profiles of instrumental activities of daily living in Chinese older persons with mild cognitive impairment.

Increasing evidence suggests that performance of the instrumental activities of daily living (IADL) can be impaired at the mild cognitive impairment (MCI) stage. Our study aimed at investigating the profiles of functional impairment in Chinese subjects with MCI. Subjects with MCI were categorized into single-domain amnestic MCI (a-MCI) (n=54) and multiple-domain amnestic MCI (md-MCI) (n=93) groups. Their functional scores of Disability Assessment of Dementia (DAD) were compared with those of cognitively normal elderly controls (NC) (n=78) and those with mild Alzheimer's disease (AD) (n=85). Subjects with md-MCI had intermediate performance in IADL between the NC and those with mild AD. Subjects with a-MCI had functional scores similar to those of normal controls. Age, education, and global cognitive test scores were not associated with functional scores in MCI subjects. Our results demonstrated that Chinese older persons with md-MCI had impairment in IADL, as compared to NC and subjects with a-MCI. This finding suggests that assessment of IADL should be incorporated in the clinical evaluation of MCI.

Mini-mental State Examination performance in mild cognitive impairment subtypes

Diagnosis of mild cognitive impairment (MCI) and its subtypes requires a detailed diagnostic assessment and so may be missed at routine primary-care appointments, since the ordinary dementia screening tests lack sensitivity owing to ceiling effects, especially in highly educated subjects. The study was undertaken using a cross-sectional assessment of 112 elderly subjects (mean age 67.96+/-5.77 years, and mean education level of 12.8+/-5.7 years) with a semi-structured interview and a neuropsychological battery. MCI patients did not differ from controls on total MMSE scores (p=0.212). Nevertheless, MCI patients showed worse performance than controls on the verbal memory task (p=0.012), and "drawing a pentagon" (p=0.03). Amnestic MCI patients performed worse only on the "three-word recall" task (p=0.013); non-amnestic MCI patients performed worse on the "three-stage command" task (p=0.001); and multiple-domain MCI patients performed worse on the "drawing a pentagon" task (p=0.001) and had a trend toward performing poorly on the 'three word recall' task (p=0.06). The analysis of MMSE subtest scores, in addition to MMSE total scores, may increase the sensitivity of the MMSE test in screening for MCI and its subtypes.

Spatial navigation deficit in amnestic mild cognitive impairment

Patients with Alzheimer's disease (AD) frequently have difficulties with spatial orientation in their day-to-day life. Although AD is typically preceded by amnestic mild cognitive impairment (MCI), spatial navigation has not yet been studied in MCI. Sixty-five patients were divided into five groups: probable AD (n = 21); MCI, further classified as amnestic MCI single domain (n = 11); amnestic MCI multiple domain (n = 18), or nonamnestic MCI (n = 7), and subjective memory complaints (n = 8). These patients, together with a group of healthy control subjects (n = 26), were tested by using a four-subtests task that required them to locate an invisible goal inside a circular arena. Each subtest began with an overhead view of the arena showed on a computer monitor. This was followed by a real navigation inside of the actual space, an enclosed arena 2.9 m in diameter. Depending on the subtest, the subjects could use the starting position and/or cues on the wall for navigation. The subtests thus were focused on allocentric and egocentric navigation. The AD group and amnestic MCI multiple-domain group were impaired in all subtests. The amnestic MCI single-domain group was impaired significantly in subtests focused on allocentric orientation and at the beginning of the real space egocentric subtest, suggesting impaired memory for allocentric and real space configurations. Our results suggest that spatial navigation impairment occurs early in the development of AD and can be used for monitoring of the disease progression or for evaluation of presymptomiatic AD.

Deficits in Facial Emotion Processing in Mild Cognitive Impairment

Background: Patients with Alzheimer disease consistently demonstrate impaired performance on tests of facial emotion processing. However, it remains unclear how early in the neurodegenerative process these deficits emerge. Methods: We approached this question by examining facial emotional processing in a ‘pre-dementia’ condition, amnestic mild cognitive impairment (MCI). Nine single-domain amnestic MCI subjects, 14 multiple-domain amnestic MCI subjects (MCI-MD), and 68 normal control subjects were assessed with the Florida Affect Battery. Results: After adjustment for age and gender, analyses of performance across the facial affect processing subtests of the Florida Affect Battery demonstrated intact performance in the single-domain MCI group but significantly impaired performance in the MCI-MD group, particularly on a test of facial affect discrimination. Within the MCI-MD group, men performed disproportionately worse than women. Performance on facial affect discriminations in the MCI-MD group correlated most robustly with performance on tests of frontal/executive function. Conclusion: These data suggest that facial emotion processing can be impaired in MCI prior to the more marked cognitive deficits seen with clinically diagnosed Alzheimer disease.

Mild cognitive impairment

To empirically validate the expanded concept of mild cognitive impairment (MCI), which differentiates between four clinical subtypes-amnestic MCI-single domain, amnestic MCI-multiple domains, nonamnestic MCI-single domain, and nonamnestic MCI-multiple domains-and to examine the prevalence, course, and outcome of these four clinical MCI subtypes. We studied a community sample of 980 dementia-free individuals aged 75 years or older who participated in the Leipzig Longitudinal Study of the Aged (LEILA 75+). All participants were examined by neuropsychological testing based on 6 years of observation. The diagnoses of the four clinical MCI subtypes were made according to the original and to slightly modified criteria by Petersen et al. (2001) (both with a cutoff of 1.0 SD and with a cutoff of 1.5 SD). The complete range of outcome types (dementia, death, improvement, stable diagnosis, unstable diagnosis) was described for all subtypes. The relative predictive power of stable MCI for dementia onset was determined. MCI-single domain is more frequent than MCI-multiple domains, and the nonamnestic MCI type is as frequent as the amnestic MCI type. The "MCI modified, 1.0 SD" criteria have the highest relative predictive power for the development of dementia (sensitivity = 74%, specificity = 73%). Alzheimer disease (AD) was the most common type of dementia at follow-up in all but one MCI subtype. Participants with nonamnestic MCI-multiple domains were more likely to progress to a non-AD dementia. It has been assumed that each MCI subtype is associated with an increased risk for a particular type of dementia. We can only partially agree with this.

Pathologic and Nicotinic Receptor Binding Differences Between Mild Cognitive Impairment, Alzheimer Disease, and Normal Aging

Neurochemical and pathologic studies show that mild cognitive impairment (MCI) is frequently a transitional state between normal aging and Alzheimer disease (AD). Neuropathologic sample sizes have been limited because relatively few individuals with MCI die before dementia develops. Decreased neocortical nicotinic receptor binding is characteristic of AD but has not been investigated in subjects with MCI. To assess nicotinic receptor binding and pathologic differences in control subjects with no dementia (ND) and in subjects with clinically and pathologically described MCI or Alzheimer disease. This was a clinicopathologic analysis. Subjects with ND had no demonstrable cognitive or functional impairment. Subjects with MCI met Petersen clinical criteria for single- or multiple-domain amnestic MCI and died before the disorder progressed to AD. Subjects with AD met National Institute for Neurological Diseases and Stroke/Alzheimer's Disease and Related Disorders Association clinical criteria for AD. All subjects underwent a complete diagnostic and semiquantitative neuropathologic examination. Data were examined after both clinical and histopathologic classification of subjects. Sun Health Research Institute Brain Donation Program, and Arizona Alzheimer Disease Center. Twenty-one control subjects with ND, 8 subjects with MCI, and 70 subjects with AD, prospectively followed up to autopsy. Nicotinic acetylcholine receptor binding value, total tangle density, total plaque density, and Braak stage. At the last examination before death, subjects with AD were significantly younger, less educated, and more cognitively and globally impaired compared with subjects with ND. When categorized by clinical diagnosis, MCI was always intermediate between ND and AD. On the whole, MCI was pathologically intermediate between ND and AD for senile plaque density, neurofibrillary tangle density, and Braak stage, but some subjects with MCI lacked neuritic plaques entirely. Binding for nicotinic acetylcholine receptors did not differ between the ND and MCI groups, but it was significantly less in the AD group. Most MCI may be considered a transitional state between ND and AD clinically and neuropathologically, but in some MCI cases there is lack of neuritic plaques, and, therefore, it cannot be considered early AD. Nicotinic receptor binding seems to be lost during the transition from MCI to AD.

Subtype of Mild Cognitive Impairment and Progression to Dementia and Death

Background: Mild cognitive impairment (MCI) represents a common cognitive state between normal cognitive aging and dementia. There is limited information about the heterogeneity of MCI and how this heterogeneity may influence the clinical course of MCI. We determined the longitudinal course of subtypes of MCI and assessed the rate of progression to dementia and to death. Methods: As part of the Alzheimer’s Disease Research Centers of California, we studied 327 patients with MCI (250 with amnestic MCI, 34 with single nonmemory MCI, and 43 with multiple domain MCI) who were followed longitudinally. We determined if subtype of MCI was independently associated with time to dementia diagnosis and time to death using Cox proportional hazard models, and type of dementia using Fisher’s exact test. Results: Mean age of the patients with MCI was 72.9 ± 9.3 years and mean Mini-Mental State Examination score was 25.7 ± 4.3. After a mean follow-up of 3.1 years, 199 (65%) progressed to dementia and 80 (24%) died. After multivariate adjustment, compared to those with amnestic MCI, patients with single nonmemory or multiple subtype MCI were less likely to receive a diagnosis of dementia (HR = 0.60; 95% CI 0.35–1.05 and HR = 0.71; 95% CI 0.44–1.14) but more likely to die (HR = 2.57; 95% CI 1.13–5.84 and HR = 1.73; 95% CI 0.72–4.18), but these results were of borderline statistical significance. There were significant differences in the type of dementia diagnosed across MCI subtypes (p = 0.006). Among the patients who progressed to Alzheimer’s disease, 76% had prior amnestic MCI; of the patients who progressed to vascular dementia, 50% had prior amnestic MCI; all patients who progressed to a frontal dementia syndrome had single nonmemory MCI previously. Conclusions: The majority of patients with MCI progressed to dementia and a significant proportion died. Subtype of MCI may influence rates of progression to death and to dementia and has a major influence on subsequent type of dementia diagnosis.

P2-179: MMSE performance in mild cognitive impairment subtypes

Mild Cognitive Impairment (MCI) is a major risk factor for Alzheimer's disease and other dementias. Subtle aspects of cognitive dysfunction may be depicted through brief cognitive assessment, which may help identify at–risk individuals. However, due to ceiling effects such cases are often misclassified when assessed by dementia screening tests. We propose that the interpretation of subtest performance on screening tools such as the Mini–Mental State Examination, in addition to the evaluation of total scores, can increase the sensitivity to the identification of MCI. To assess whether scores on total MMSE and on MMSE subtests are influenced by different MCI subtypes. 112 elderly individuals (mean age: 67.96 ± 5.77; 25.2% male; mean education level: 12.8 ± 5.17) were assessed in a tertiary memory clinic for memory deficit complaints. Fifty nine individuals had no evidence of dementing disorders and were considered normal controls. Fifty three were diagnosed as MCI according to Petersen et al (1999) criteria. As formal education was significantly higher in control than MCI patients on ANOVA tests (p= 0.008), General Linear Model was used to evaluate the difference of performance at total MMSE scores and its sub items between controls and MCI subjects, using as covariate “Years of Education”. There was no significant statistical difference on total MMSE scores (p= 0.212). However, subjects with MCI performed significantly worse than controls in the memory subtest (3 word recall) (p= 0.03), as well as amnestic MCI patients (p=0.017); multiple domain MCI performed worse on total language (p= 0.015) and drawing sub item (p= 0.002); non–amnestic MCI performed worse on three–stage command task (p= 0.003). Despite MCI and controls subjects did not significantly differ in total MMSE scores. The former individuals performed worse on particular MMSE subitems, depending on the MCI subtype, and reflecting the predominantly affected cognitive domains. Therefore, the careful observation of the performance on MMSE subtests, more than the interpretation of overall results, might be useful to help discriminate those subjects who might warrant extensive cognitive assessment in order to identify high risk individuals to develop Alzheimer's disease and other forms of dementia.