非痴呆老年人认知功能的差异性:从成功老化到轻度认知损伤

目的：对非痴呆的自诉记忆力减退的老年人,就其总体认知水平而言可能存在相对同源的不同亚型进行初步探讨。方法：对34例调查者进行临床记忆量表等17种神经心理测验,将结果进行Q型聚类分析。结果：15例调查者被诊断为轻度认知损伤,占44％;聚类分析产生6类新样本。结论：在正常老化与早期阿尔茨海默病这一过渡期内,老年人的认知状态是不均质的,其中既有成功老化,也有一般老化,尤其是还存在着具有痴呆发病危险性的认知损伤。     

Mild cognitive impairment and preclinical Alzheimer's disease

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is characterized by a gradual decline of numerous cognitive processes, culminating in dementia. Mild cognitive impairment (MCI) is a relatively broad clinical condition involving a slight memory deficit, which in many cases represents a transitional state between normal cognition and AD. Much research is currently being conducted on MCI, since any therapy that is effective at treating this early manifestation of dementia may provide an opportunity for managing the disease while patient function is relatively preserved. Current research seeks to develop disease-modifying treatments that intervene in the pathobiologic processes involved in MCI and AD. Another goal of current research is to develop antecedent biomarkers that can be used to detect AD prior to the appearance of symptoms and before substantial and irreversible brain damage occurs.     

老年轻度认知功能损害的脑诱发电位变化及其发展为痴呆的预测因素

目的检测老年轻度认知功能损害（MCI）患者的脑诱发电位变化，探索其发展为痴呆的脑诱发电位预测因素。方法前瞻性对照研究。对象为患轻度认知功能损害的老年人（MCI组）和认知功能正常的老年人（NC组）两组。结果23例MCI和29例NC完成了基线脑诱发电位检查。与NC组相比，MCI组的听觉脑干反应波V绝对波幅和P300的P3靶波幅降低有统计学意义（P〈0．01）。多元逐步判别分析显示听觉脑干反应波V绝对波幅和P300的P3靶波幅的判别具有统计学意义（P〈0．01），两组判别总正确率为75％，但Logislic回归分析未发现脑诱发电位指标对MCI是否发展为痴呆有显著性预测作用。结论脑诱发电位检测有助于了解MCI的脑电生理变化，听觉脑干反应波V绝对波幅和P300的P3靶波幅的降低对MCI具有诊断价值。本研究未证实4种检测的脑诱发电位指标对预测MCI发展为痴呆有统计学意义。     

Mild cognitive impairment: epidemiology and dementia risk in an elderly Italian population

OBJECTIVES: To investigate prevalence and incidence of mild cognitive impairment (MCI) and its risk of progression to dementia in an elderly Italian population.
DESIGN: Longitudinal.
SETTING: Population-based cohort aged 65 and older resident in an Italian municipality.
PARTICIPANTS: A total of 1,016 subjects underwent baseline evaluation in 1999/2000. In 2003/04, information about cognitive outcome was collected for 745 participants who were free of dementia at baseline.
MEASUREMENTS: MCI (classified as with or without impairment of the memory domain), dementia, Alzheimer's dementia (AD), and vascular dementia (VaD) diagnosed according to current international criteria.
RESULTS: Overall prevalence of MCI was 7.7% (95% confidence interval (CI)=6.1–9.7 %) and was greater with older age and poor education. During 4 years of follow-up, 155 incident MCI cases were diagnosed, with an incidence rate of 76.8 (95% CI=66.8–88.4) per 1,000 person-years. Approximately half of prevalent and incident MCI cases had memory impairment. Compared with normal cognition, multivariable-adjusted risk for progression from MCI with memory impairment to dementia was 4.78 (95% CI=2.78–8.07) for any dementia, 5.92 (95% CI=3.20–10.91) for AD, and 1.61 (95% CI=0.37–7.00) for VaD. No association with dementia risk was found for MCI without memory impairment. Approximately one-third of MCI cases with memory impairment did not progress to dementia.
CONCLUSION: MCI occurs often in this elderly Italian cohort and is associated with greater risk of AD, but only when the impairment involves the memory domain. However, a substantial proportion of MCI cases with memory impairment do not progress to dementia.     

Prospects of genetic research of mild cognitive impairment

Mild cognitive impairment (MCI) is a common problem in the elderly. Genetic research may yield valuable clues to improve the diagnostic and prognostic tools for MCI. As the majority of patients progress into Alzheimer's disease (AD) and other forms of dementia, the genetics of MCI cannot be separated from the genetics of AD and dementia in general. Follow-up studies of carriers of mutations underlying AD may yield valuable clues for the development of new diagnostic tools for MCI. In particular, large-scale studies of carriers of the apolipoprotein E 4 allele may still be of interest. Our knowledge of the genes involved in MCI is still very limited. In addition, we need powerful and carefully designed candidate gene studies aiming to discover new genes involved in the risk and progression of MCI. Although the genetics of MCI will be difficult to disentangle, there is ample opportunity to improve research of the genes involved.     

Early detection of Alzheimer's disease using neuroimaging

Neuroimaging is being increasingly used to complement clinical assessments in the early detection of Alzheimer's disease (AD). Structural magnetic resonance imaging (MRI) and metabolic positron emission tomography (FDG-PET) are the most clinically used and promising modalities to detect brain abnormalities in individuals who might be at risk for AD but who have not yet developed symptoms. The knowledge of established risk factors for AD enabled investigators to develop enrichment strategies for longitudinal imaging studies to reduce the sample sizes and study duration. The present review focuses on the results obtained by MRI and FDG-PET studies that examined the preclinical AD stages in several at risk populations: (1) individuals from families with autosomal dominant early-onset AD (FAD), (2) patients with mild cognitive impairment (MCI), particularly in memory, who are at very high risk for declining to AD with an estimated decline rate of 10-30% per year, (3) normal young and middle-age subjects carriers of known susceptibility genes for late-onset AD such as the Apolipoprotein E (ApoE) E4 allele, and (4) as age is the main risk factor for AD, normal elderly individuals followed to the onset of MCI and AD. Overall, these studies show that the use of imaging for the early detection of AD is successful even in the earlier stages of disease when clinical symptoms are not fully expressed and the regional brain damage may be limited.     

简易认知量表和8条目痴呆筛查问卷在高龄老年人群早期认知功能下降筛查中的应用

目的探讨简易认知量表（Mini-Cog）和8条目痴呆筛查问卷（8-item ascertain dementia, AD8）对80岁以上老年人群早期轻度认知功能障碍（mild cognitive impairment, MCI）的筛查价值。 方法选取杭州市某福利中心的2014年10月前已入住的908名高龄老年人进行Mini-Cog和AD8筛查,随访5年后对仍然健在且能配合完成检查者进行二次认知功能评估。计算Mini-Cog和AD8初筛的敏感度和特异度,并分析随访5年后AD8的ROC曲线结果以及两种量表的一致性检验结果。 结果908例高龄老年人中523例确诊为痴呆（不计入后续筛查及随访调查）,余385例筛查结果显示：Mini-Cog、AD8诊断MCI的敏感度分别为54.88%、57.32%,特异度分别为85.52%、86.43%。随访5年后仍健在且接受二次评估的老年人共167名,其中认知功能正常106例（54例出现认知功能下降）,MCI 61例（36例出现认知功能进一步下降）。对于随访5年的认知功能正常者及MCI者,AD8诊断的AUC分别为0.572（95%CI=0.486-0.658）、0.723（95%CI=0.611-0.835）,Mini-Cog和AD8（以得分>3为分界线）诊断的一致性Kappa值分别为0.105、0.018和0.225、0.524。 结论AD8和Mini-Cog均具有一定的MCI评估效能,尤其适用于养老机构及社区高龄老年群体的认知功能筛查。     

MRI and CSF studies in the early diagnosis of Alzheimer's disease

The main goal of our studies has been to use MRI, FDG-PET, and CSF biomarkers to identify in cognitively normal elderly (NL) subjects and in patients with mild cognitive impairment (MCI), the earliest clinically detectable evidence for brain changes due to Alzheimer's disease (AD). A second goal has been to describe the cross-sectional and longitudinal interrelationships amongst anatomical, CSF and cognition measures in these patient groups. It is now well known that MRI-determined hippocampal atrophy predicts the conversion from MCI to AD. In our summarized studies, we show that the conversion of NL subjects to MCI can also be predicted by reduced entorhinal cortex (EC) glucose metabolism, and by the rate of medial temporal lobe atrophy as determined by a semi-automated regional boundary shift analysis (BSA-R). However, whilst atrophy rates are predictive under research conditions, they are not specific for AD and cannot be used as primary evidence for AD. Consequently, we will also review our effort to improve the diagnostic specificity by evaluating the use of CSF biomarkers and to evaluate their performance in combination with neuroimaging. Neuropathology studies of normal ageing and MCI identify the hippocampal formation as an early locus of neuronal damage, tau protein pathology, elevated isoprostane levels, and deposition of amyloid beta 1-42 (Abeta42). Many CSF studies of MCI and AD report elevated T-tau levels (a marker of neuronal damage) and reduced Abeta42 levels (possibly due to increased plaque sequestration). However, CSF T-tau and Abeta42 level elevations may not be specific to AD. Elevated isoprostane levels are also reported in AD and MCI but these too are not specific for AD. Importantly, it has been recently observed that CSF levels of P-tau, tau hyperphosphorylated at threonine 231 (P-tau231) are uniquely elevated in AD and elevations found in MCI are useful in predicting the conversion to AD. In our current MCI studies, we are examining the hypothesis that elevations in P-tau231 are accurate and specific indicators of AD-related changes in brain and cognition. In cross-section and longitudinally, our results show that evaluations of the P-tau231 level are highly correlated with reductions in the MRI hippocampal volume and by using CSF and MRI measures together one improves the separation of NL and MCI. The data suggests that by combining MRI and CSF measures, an early (sensitive) and more specific diagnosis of AD is at hand. Numerous studies show that neither T-tau nor P-tauX (X refers to all hyper-phosphorylation site assays) levels are sensitive to the longitudinal progression of AD. The explanation for the failure to observe longitudinal changes is not known. One possibility is that brain-derived proteins are diluted in the CSF compartment. We recently used MRI to estimate ventricular CSF volume and demonstrated that an MRI-based adjustment for CSF volume dilution enables detection of a diagnostically useful longitudinal P-tau231 elevation. Curiously, our most recent data show that the CSF isoprostane level does show significant longitudinal elevations in MCI in the absence of dilution correction. In summary, we conclude that the combined use of MRI and CSF incrementally contributes to the early diagnosis of AD and to monitor the course of AD. The interim results also suggest that a panel of CSF biomarkers can provide measures both sensitive to longitudinal change as well as measures that lend specificity to the AD diagnosis.     

Hypertension, cognitive decline and dementia

Dementia is one of the most common neurological disorders in the elderly. Aging is associated with a large increase in the prevalence and incidence of degenerative (Alzheimer's disease) and vascular dementia, leading to a devastating loss of independence. In view of increasing longevity of populations worldwide, prevention and treatment of dementia has turned into a major public health challenge. In the past decade, longitudinal studies have shown a close association between high blood pressure in middle age, cognitive decline and dementia, including Alzheimer's disease, in the late life. Pathophysiologically, a summation of cerebrovascular damage, white matter changes and pre-existing asymptomatic Alzheimer's brain lesions may lead to dementia, even when each type of lesion individually is not sufficiently severe to cause it. Longitudinal studies assessing the beneficial role of antihypertensive drugs on cognitive decline and dementia have produced promising results. There are few randomised placebo controlled studies, although some of these have produced positive results. Results of three recent meta-analyses are inconsistent, possibly due to methodological issues. Further long-term randomised trials, designed especially to assess a link between antihypertensive therapy and cognitive decline or dementia are therefore needed.     

Stroke and cognition

Several studies confirm cognitive impairment and dementia to be increased after stroke in the elderly. Although not necessarily involving memory deficits, the frequency of cognitive impairments may occur in up to 30% of stroke survivors at 3 months. This impairment may be confounded by preexisting cognitive decline or dementia. By contrast, cognitive changes and dementia are widely recognized in familial forms of stroke, such as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Several factors, including type of stroke, recurrent episodes, the site and laterality of the lesion(s), volume of cerebral infarction, medial temporal lobe atrophy, and coexistent neurodegenerative pathology predict the degree of impairment. Aphasia, diabetes mellitus, atrial fibrillation, and depression are listed among other biologic factors that further exacerbate cognition and affect long-term survival. There is no clear consensus whether genetic factors, such as the apolipoprotein E ε4 allele or angiotensin converting enzyme gene polymorphisms, modify cognitive changes or stroke outcome. Although several neurotransmitter systems may be affected in post-stroke dementia, the amelioration of cholinergic function is a worthy target.     

Classifying late-onset dementia with MRI: Is arteriosclerotic brain degeneration the most common cause of Alzheimer’s syndrome?

Our aim was to use early magnetic resonance imaging (MRI) to investigate the causes of cognitive decline in elderly people with mild cognitive impairment (MCI). Baseline structural and flow quantification MR sequences, and clinical and neuropsychological follow-up for at least two years, were performed on 62 elderly subjects with MCI. Of these subjects, 17 progressed to dementia, and 15 of these progressed to dementia of the Alzheimer type (DAT). Conversion to clinically diagnosed DAT was related to six distinct MR profiles, including one profile suggesting severe AD (20% of these converters) and five profiles suggesting severe cerebrovascular dysfunction. Two profiles suggested arteriosclerotic brain degeneration, one profile suggested severe venous windkessel dysfunction, and two suggested marked cerebral hypoperfusion associated with very low craniospinal compliance or marked brain atrophy. As compared with vascular MR type converters, AD MR type converters showed high executive and mobility predementia performances. Severe whole anteromesial temporal atrophy and predominantly left brain atrophy on visual MR analysis was only observed in AD MR type converters. In conclusion, these observations enhance the pathogenic complexity of the Alzheimer syndrome, and suggest that the role of arteriosclerotic brain degeneration in late life dementia is underestimated.     

Injury-related hospitalisation in community-dwelling older people across the cognitive spectrum: A population based study

ObjectivesTo describe the injury profile, hospitalisation rates and health outcomes for older people with cognitive impairment and to determine whether these differ from those with normal cognition.MethodsParticipants were 867 community-dwelling 70–90 year olds enrolled in the population-based longitudinal Sydney Memory and Ageing Study (MAS). Participant’s cognitive status was classified as normal, mild cognitive impairment (MCI) and dementia at baseline, then 2, 4 and 6 years’ follow-up. MAS records were linked to hospital and death records to identify injury-related hospitalisations for the 2-year period following each assessment.ResultsThere were 335 injury-related hospitalisations for participants; 222 (25.6%) participants had at least one injury-related hospitalisation. The injury-related hospitalisation rate for participants with MCI (63.0 [95%CI 51.6–74.4] per 1000 person-years) was higher than for people with normal cognition (39.3 [95%CI 32.4–46.1] per 1000 person-years) but lower than people with dementia (137.1 [95%CI 87.2–186.9] per 1000 person-years).Upper limb fractures (22.1%) were the most common injuries for participants with normal cognition, and non-fracture head injuries for participants with MCI and dementia (25.9% and 23.3% respectively). Participants with dementia had a higher proportion of hip fractures (20.0%, p = 0.0483) than participants with normal cognition. There was no difference in 30-day mortality between participants with normal cognition, MCI and dementia (3.9%, 1.7%, 3.3% respectively).ConclusionOlder people with objectively defined MCI are at higher risk of injury-related hospitalisation than their cognitively intact peers, but lower risk than people with dementia. Falls-risk screening and fall prevention initiatives may be indicated for older people with MCI.     

Atrial fibrillation and risk of dementia in non-demented elderly subjects with and without mild cognitive impairment (MCI)

MCI is regarded as a precursor of dementia, but not all patients with MCI actually develop dementia. As Alzheimer and vascular dementia (AD and VD, respectively) are thought to share many common etiopathogenetic mechanisms, we investigated whether the vascular risk factor atrial fibrillation affect the risk of conversion to dementia for different MCI subtypes diagnosed according to international criteria. One-hundred-eighty elderly outpatients with MCI and 431 elderly outpatients with a normal cognition were followed-up for a mean of 3 and 4 years, respectively. The risk of conversion to dementia associated with atrial fibrillation was studied in both samples using a Cox proportional-hazards model adjusted for sociodemographic and medical variables. Overall conversion rate to dementia was 10.5 (8.0-13.8) per 100 person-years in the MCI group and 2.2 (1.5-3.1) per 100 person-years in the normal cognition group. Atrial fibrillation was significantly associated with conversion to dementia (hazard ratio=HR=4.63, 95% confidence interval=Cl=1.72-12.46) in the MCI group, but not in the cognitively normal group (HR=1.10, 95% Cl=0.40-3.03). Current diagnostic criteria for MCI subtypes define heterogeneous populations, but atrial fibrillation can be useful in identifying people with increased risk of conversion to dementia.     

Hippocampal disconnection contributes to memory dysfunction in individuals at risk for Alzheimer's disease

The concept of amnestic mild cognitive impairment (MCI) describes older people who show a decline predominantly in memory function, but who do not meet criteria for dementia. Because such individuals are at high risk for developing Alzheimer's disease, they are of great interest for understanding the prodromal stages of the disease process. The mechanism underlying memory dysfunction in people with MCI is not fully understood. The present study uses quantitative, high-resolution structural MRI techniques to investigate, in vivo, the anatomical substrate of memory dysfunction associated with MCI. Changes in brain structures were assessed with two imaging techniques: (i) whole-brain, voxel-based morphometry to determine regions of reduced white matter volume and (ii) sensitive volumetric segmentation of the entorhinal cortex and hippocampus, gray matter regions that are critically important for memory function. In participants with amnestic MCI, compared with age-matched controls, results showed a significant decrease in white matter volume in the region of the parahippocampal gyrus that includes the perforant path. There was also significant atrophy in both the entorhinal cortex and the hippocampus. Regression models demonstrated that both hippocampal volume and parahippocampal white matter volume were significant predictors of declarative memory performance. These results suggest that, in addition to hippocampal atrophy, disruption of parahippocampal white matter fibers contributes to memory decline in elderly individuals with MCI by partially disconnecting the hippocampus from incoming sensory information.     

Imaging cerebral atrophy: normal ageing to Alzheimer's disease

CONTEXT: With ageing populations, the prevalence of dementia, especially Alzheimer's disease, is set to soar. Alzheimer's disease is associated with progressive cerebral atrophy, which can be seen on MRI with high resolution. Longitudinal MRI could track disease progression and detect neurodegenerative diseases earlier to allow prompt and specific treatment. Such use of MRI requires accurate understanding of how brain changes in normal ageing differ from those in dementia. STARTING POINT: Recently, Henry Rusinek and colleagues, in a 6-year longitudinal MRI study of initially healthy elderly subjects, showed that an increased rate of atrophy in the medial temporal lobe predicted future cognitive decline with a specificity of 91% and sensitivity of 89% (Radiology 2003; 229: 691-96). WHERE NEXT? As understanding of neurodegenerative diseases increases, specific disease-modifying treatments might become available. Serial MRI could help to determine the efficacy of such treatments, which would be expected to slow the rate of atrophy towards that of normal ageing, and might also detect the onset of neurodegeneration. The amount and pattern of excess atrophy might help to predict the underlying pathological process, allowing specific therapies to be started. As the precision of imaging improves, the ability to distinguish healthy ageing from degenerative dementia should improve.     

Italian Project on Epidemiology of Alzheimer's disease (I.PR.E.A.): study design and methodology of cross-sectional survey

BACKGROUND AND AIMS: The purpose of this paper is to describe the design and diagnostic procedures of the multicenter community-based prospective Italian Project on the Epidemiology of Alzheimer's disease (I.PR.E.A.). The study is aimed at estimating the prevalence and incidence of Alzheimer's disease (AD) in the preclinical phase, examining the natural history of cognitive decline without dementia (mainly AD) in the Italian population, and identifying risk factors or health determinants related or associated with various health outcomes. METHODS: Both cross-sectional and longitudinal phases will be performed in 4800 elderly subjects aged 65-84 years. The sample will be selected from the registries of 12 Italian rural and urban municipalities, with an interval of one year between examinations. The study population will undergo several screening examinations, including personal and informant interviews by means of a structured ad hoc questionnaire, physical and neurological examination, laboratory tests, genetic markers and a neuropsychological battery. Neuroimaging screening will also be carried out in a subgroup of subjects positive for cognitive impairment without dementia. The longitudinal phase will include all subjects who, during the cross-sectional survey, are identified as affected by cognitive impairment without dementia, and will aim at assessing the incidence and natural history of cognitive impairment without dementia and the degree of disease progression from the earliest stage. This is the first systematic prospective study on the preclinical phase of AD in Italy.     

Novel image–novel location object recognition task sensitive to age-related cognitive decline in nondemented elderly

Traditional tests used in the clinic to identify dementia, such as the mini-mental state examination (MMSE), are useful to identify severe cognitive impairments but might be less sensitive to detect more subtle age-related cognitive changes. Previously, the novel image–novel location (NINL) object recognition test was shown to be sensitive to detect effects of apolipoprotein E4, a risk factor for developing age-related cognitive decline and Alzheimer’s disease, in nondemented elderly. In the present longitudinal study, performance on the MMSE and the NINL tests were compared over a 4-year period. Individual NINL scores over this period were highly correlated. In addition, while MMSE scores did not change over the 4-year period, NINL scores did. In a final testing session of a subset of the participants, NINL scores correlated with logical memory and word recall lists, cognitive tasks used to detect dementia in the clinic, as well as clinical dementia rating scales. These results support that the NINL might be a valuable tool to assess age-related cognitive decline.     

Role of cardiovascular risk factors (CRF) in the patients with mild cognitive impairment (MCI)

Few therapeutic options are available nowadays to improve the prognosis of patients with Alzheimer's disease (AD). There are rather several evidences in literature that controlling vascular risk factors may be an effective intervention for modifying the course of this disease. The aim of our study was to investigate the role of CRF in 50 patients with MCI according to Petersens's criteria, and to evaluate their influence on cognitive and behavioral features of the disease and on the development of dementia. Statistical analysis of the data showed that the 60% of the patients with MCI and CRF developed dementia, while 40% maintained the same cognitive conditions at the end of the study. Only 32% of the subjects without cardiovascular comorbidities developed dementia. The results of the study suggest that CRF play a key role in cognitive decline of patients with MCI. Patients with MCI and CRF showed not only worse cognitive performances, but also behavioral disorders, depression and functional disability. Patients with CRF had higher conversion rate to AD than the other group, with a mean disease-free period 3 months shorter than the control group.     

Physical activity, physical function, and incident dementia in elderly men: the Honolulu-Asia Aging Study

BACKGROUND: Although evidence is accumulating for a protective effect of late life physical activity on the risk of dementia, the findings are inconsistent, especially in men. We examined the association of late life physical activity and the modifying effect of physical function with future risk of dementia in a well-characterized cohort of elderly men participating in the Honolulu-Asia Aging Study (HAAS). METHODS: Physical activity by self-report and performance-based physical function was assessed in 2263 men aged 71-92 years without dementia at the baseline examination of the HAAS in 1991-1993. Follow-up for incident dementia occurred at repeat examinations conducted in 1994-1996 and 1997-1999. Analyses were based on Cox proportional hazards models with adjustment for potential confounders, including age, baseline cognitive function, education, and apolipoprotein E genotype. RESULTS: There were 173 incident cases of dementia with a mean follow-up of 6.1 years. Although the incidence of dementia tended to decline with increasing physical activity and function, there was a significant interaction between the latter two factors on dementia risk (p =.022). For men with low physical function, high levels of physical activity were associated with half the risk of dementia versus men who were the least active (hazard ratio [HR], 0.50; 95% confidence interval [CI], 0.28-0.89), with a moderate level of physical activity also providing a protective effect (HR, 0.57; 95% CI, 0.32-0.99). Risk of dementia and Alzheimer's disease declined significantly with increasing physical activity. Findings persisted after age and risk factor adjustment. Similar associations were absent in men with moderate and high physical function. CONCLUSIONS: In elderly men with poor physical function, increasing general physical activity may potentially confer a protective effect or delay the onset for dementia.     

Complex activities of daily living in mild cognitive impairment: conceptual and diagnostic issues

BACKGROUND: The impact of cognitive impairment on activities of daily living (ADL) is being used as a major criterion for differentiating between mild cognitive impairment (MCI) and dementia. The concept of an ADL threshold that separates MCI from dementia, however, appears to be improbable for several reasons. OBJECTIVES: To determine whether complex ADL are impaired in patients with MCI; to examine the usefulness of the assessment of ADL impairment for the diagnosis of MCI; to explore whether both cognitive testing and assessment of impaired ADL are significant predictors of the diagnosis according to the diagnostic gold standard of MCI. DESIGN: Cross-sectional study. SETTING: University-based outpatient clinic. SUBJECTS: A total of 45 elderly MCI patients diagnosed according to research diagnostic criteria and 30 age-matched cognitively unimpaired controls. METHODS: Clinical assessment - Alzheimer's disease Assessment scale, cognitive subscale (ADAS-cog) for the assessment of cognitive functions, Alzheimer's disease Cooperative Study scale for ADL in MCI (ADCS-MCI-ADL) for the assessment of impairments of complex ADL. Statistical evaluation - Mann-Whitney U tests for significant differences on measures of cognition and everyday functioning. Non-parametric correlations for associations between ADL and cognitive ability. Receiver operator curve (ROC) analyses to identify optimal cut-off scores on the ADCS-MCI-ADL and ADAS-cog scales to differentiate between MCI patients and controls. Binary logistic regression analyses to predict the diagnosis of MCI on the basis of the above-mentioned instruments. RESULTS: Patients scored significantly higher than controls on the ADAS-cog scale and significantly lower on the ADCS-MCI-ADL scale. There was a significant negative correlation of the above-mentioned scales in MCI patients (r = -0.46, P < 0.01). Both instruments discriminated well between patients and controls (ADCS-MCI-ADL: optimal cut-off 52 points, sensitivity 0.89, specificity 0.97; ADAS-cog: optimal cut-off 10 points, sensitivity 0.78, specificity 1.0). With regard to the linear predictor in the logistic regression built, both instruments were strong predictors of the diagnosis according to the diagnostic gold standard (ADCS-MCI-ADL: P = 0.002; ADAS-cog: P = 0.041). CONCLUSION: Impairment of ADL is already present in MCI. Therefore, intact ADL cannot be used as a criterion to define the syndrome of MCI and to distinguish it from mild dementia. The assessment of complex ADL is probably useful for the diagnosis of MCI.