At the present time, there is increasing recognition and understanding of the mild cognitive impairment (MCI) entity as a stage which is a frequent precursor and harbinger of subsequently manifest Alzheimer's disease (AD) and, perhaps, other related conditions, such as vascular dementia (Gauthier et al., 2006). MCI has been defined in two disparate but generally compatible ways in the current literature (see Reisberg et al., 2008 (this issue), for a more complete historical overview of MCI). These two definitional approaches might be termed: (a) the clinical approach to MCI, and (b) the clinical plus psychometric approach to MCI.

Descriptions of dementia can be traced to antiquity. Prichard (1837) described four dementia stages and Kral (1962) described a “benign senescent forgetfulness” condition. The American Psychiatric Association's DSM-III (1980) identified an early dementia stage.

In 1982, the Clinical Dementia Rating (CDR) and the Global Deterioration Scale (GDS) were published, which identified dementia antecedents. The CDR 0.5 “questionable dementia” stage encompasses both mild dementia and earlier antecedents. GDS stage 3 described a predementia condition termed “mild cognitive decline” or, alternatively, beginning in 1988, “mild cognitive impairment” (MCI). This GDS stage 3 MCI condition is differentiated from both a preceding GDS stage 2, “subjective cognitive impairment” (SCI) stage and a subsequent GDS 4 stage of mild dementia.

GDS stage 3 MCI has been well characterized. For example, specific clinical concomitants, mental status and psychological assessment score ranges, behavioral and emotional changes, neuroimaging concomitants, neurological reflex changes, electrophysiological changes, motor and coordination changes, and changes in activities, accompanying GDS stage 3 MCI have been described.

Petersen and associates proposed a definition of MCI in 2001 which has been widely used (hereafter referred to as “Petersen's MCI”). Important differences between GDS stage 3 MCI and Petersen's MCI are that, because of denial, GDS stage 3 MCI does not require memory complaints. Also, GDS stage 3 MCI recognizes the occurrence of executive level functional deficits, which Petersen's MCI did not. Nevertheless, longitudinal and other studies indicate essential compatibility between GDS stage 3 MCI and Petersen's MCI duration and outcomes.

Mild cognitive impairment (MCI) is a classification reserved for nondemented elderly individuals at increased risk for future decline to dementia, compared to those with normal cognition. Cognitive tests, particularly those assessing verbal recall, have been found to be useful in the identification of elderly people with MCI. We argue that a variety of motor/psychomotor evaluations are also sensitive to MCI. Motor assessments described as complex correctly categorize normal versus MCI elderly with comparable accuracies to those obtained by cognitive tests. Unlike performance on verbally based cognitive measures, motor-test scores appear to be relatively independent of educational attainment, indicating that the use of certain motor tests may be particularly valuable in the identification of MCI among elderly with widely varying educational backgrounds.

Objective: This paper reviews the key lessons learned from the first published short-term, placebo-controlled trial of a cholinesterase inhibitor for treatment of mild cognitive impairment (MCI).

Methods: The study was a 24-week placebo-controlled trial designed to evaluate the efficacy and safety of donepezil HCl (donepezil) in the treatment of cognitive impairment in subjects with MCI. Primary outcome measures were the NYU Paragraphs Test and the ADCS Clinicians Global-Impression of Change in the intent-to-treat last-observation-carried-forward group.

Results: There was no benefit of donepezil treatment on primary outcome measures (NYU Paragraphs and ADCS CGI-C) in the ITT-LOCF group but positive findings were seen on NYU Paragraphs in the fully evaluable group and in certain secondary outcome measures across both groups.

Conclusions: The results highlight the need for the use of primary cognitive and functional measures that are reliable and sensitive to change in patients with MCI. Measures of episodic memory, psychomotor speed and complex attention were most sensitive in this study. Functional rating scales are needed that measure change in individual subjects' key areas of functional deficit, which typically involve executive aspects of instrumental ADLs. Tolerability can be increased by use of flexible dosing and efficacy is likely to be enhanced by increasing the length of the trial from six to 12 months and by enriching the sample with subjects more likely to decline during the trial.

A plethora of in vitro and in vivo studies have supported the neuroprotective role of estrogens and their impact on the neurotransmitter systems implicated in cognition. Recent hormonal replacement therapy (HRT) trials in non-demented postmenopausal women suggest a temporary positive effect (notably on verbal memory), and four meta-analyses converge to suggest a possible protective effect in relation to Alzheimer's disease (reducing risk by 29 to 44%). However, data from the only large randomized controlled trial published to date, the Women's Health Initiative Memory Study, did not confirm these observations and have even suggested an increase in dementia risk for women using HRT compared to controls. Apart from methodological differences, one key shortcoming of this trial has probably been the focus on late-onset (postmenopausal) hormonal changes, i.e. at a time when the neurodegenerative process has already begun and without taking into account individual lifetime exposure to hormone variability. Multifactorial models based on an exhaustive view of all hormonal events throughout the reproductive life (rather than on a specific exposure to a given steroid) together with other risk factors (notably genetic risk factors related to estrogen receptor polymorphisms) should be explored to clarify the role of hormonal risk factors, or protective factors for cognitive dysfunction and dementia.

Recent randomized control trials and meta-analyses of experimental studies indicate positive effects of non-pharmacological cognitive training on the cognitive function of healthy older adults. Furthermore, a large-scale randomized control trial with older adults, independent at entry, indicated that training delayed their cognitive and functional decline over a five-year follow-up. This supports cognitive training as a potentially efficient method to postpone cognitive decline in persons with mild cognitive impairment (MCI). Most of the research on the effect of cognitive training in MCI has reported increased performance following training on objective measures of memory whereas a minority reported no effect of training on objective cognitive measures. Interestingly, some of the studies that reported a positive effect of cognitive training in persons with MCI have observed large to moderate effect size. However, all of these studies have limited power and few have used long-term follow-ups or functional impact measures. Overall, this review highlights a need for a well-controlled randomized trial to assess the efficacy of cognitive training in MCI. It also raises a number of unresolved issues including proper outcome measures, issues of generalization and choice of intervention format.

Background: Matrix metalloproteinases (MMPs) are elevated in the brain tissue of patients with dementia and may play a role in the pathophysiology of dementia. MMP-9 and tissue inhibitors of MMPs (TIMPs) are elevated in postmortem brain tissue of patients with Alzheimer's disease (AD). In a previous study we showed that circulating levels of MMP-9 are elevated in AD patients. The aim of the present study was to examine circulating levels of MMP-1, MMP-2, MMP-9, TIMP-1 and TIMP-2 in the plasma of patients with mild cognitive impairment (MCI), AD, vascular dementia (VaD), dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD), to determine, whether plasma profiles of MMPs and TIMPs differ in various types of dementia.

Methods: Gelatinolytic activity (MMP-2 and MMP-9) was measured in all plasma samples by zymography. Levels of MMP-2, MMP-9, MMP-1 as well as TIMP-1 and TIMP-2 were measured by ELISA.

Results: We found constitutive expression of MMP-1, -2 and -9 as well as TIMP-1 and -2 in all the samples investigated. As shown previously, MMP-9 was significantly elevated in the plasma of AD patients (p = 0.004) as compared to controls and MCI patients. Plasma levels of TIMP-1 were significantly lower in VD samples as compared to all other groups. Levels of TIMP-2 were significantly lower in patients with FTD as compared to AD, VaD and MCI patients. There were no significant changes of MMP-1 and MMP-2 levels in the samples.

Conclusion: These findings suggest that circulating levels of MMP-9, TIMP-1 and TIMP-2 and changes in the MMP/TIMP balance in plasma differ in various types of dementia.

Objectives: The aim of the study was to assess the attitudes of clinicians to the diagnostic construct of mild cognitive impairment (MCI), their approach to relaying the diagnosis to patients and families, and recommended treatment and follow-up.

Method: An anonymous questionnaire was sent out to 503 members of the Australian Society for Geriatric Medicine (ASGM) and New Zealand Geriatrics Society (NZGS), of whom 163 replied.

Results: Most responders (83%) had diagnosed MCI. About 70% rated the importance of separating MCI from dementia, or MCI from normal cognition, as 4 or 5 on a scale from 1 (not very important) to 5 (very important). Most responders reported that they would inform their patients and families of a diagnosis of MCI, and used that term. A minority used the term “early Alzheimer's disease,” but 44% of NZGS members used other terms to relay the diagnosis compared to 13% of ASGM members. Follow-up was most often recommended at 6–12 months. Non-pharmacological treatment (such as mental stimulation strategies) was recommended most often, followed by no treatment.

Conclusions: The diagnostic entity of MCI appears to have a general acceptance among those who responded to the survey, and the term has gained use in clinical practice. Most clinicians are recommending follow-up, recognizing the high risk for progression. Treatment recommendations do not favor pharmaceuticals, reflecting the current evidence for lack of effect.

Background: Mild cognitive impairment (MCI) may be accompanied by extra pyramidal signs (EPS), which are related to the severity and type of cognitive impairment. We aimed to elucidate further the relationship between MCI and EPS, analyzing the correlation between the severity of EPS and cognitive functions, and the presence of EPS and neuro-psychiatric features.

Methods: Data were obtained from a longitudinal study of 150 MCI outpatients. Participants underwent a clinical assessment including the Unified Parkinson Disease Rating Scale, the Neuropsychiatric Inventory, the Tinetti Scale, and a standardized neuropsychological battery. Mild EPS could be defined as being present (MCI with mild EPS) using a subscale of UPDRS, based on three specific symptoms: bradykinesia, rigidity and tremor.

Results: The two groups, one with mild EPS (24%) and one without EPS (76%), differed in gait abnormalities and presence of extrapyramidal symptoms. Groups did not differ in terms of general cognitive functions evaluated using the Mini-mental State Examination, while subjects with MCI with mild EPS performed significantly worse than those with MCI without EPS in total global score and in non-memory items of the Alzheimer's Disease Assessment Scale. Moreover, severity of EPS was significantly correlated with low performance on executive functions and with high performance on episodic memory. The group with MCI with mild EPS were observed to have a greater prevalence of patients with anxiety, depression, apathy and sleep disturbances than in MCI without EPS.

Conclusion: MCI may be associated with mild parkinsonian signs, the severity of which are related to the severity of cognitive impairment, in particular of non-memory functions, and to a differential pattern of psycho-behavioral symptoms.

Background: A large proportion of patients with amnestic mild cognitive impairment (MCI) progress to Alzheimer's disease (AD), but the rate of conversion is highly variable, depending on selection and inclusion criteria. In the present prospective study, amnestic MCI criteria were applied in order to enrich the study population with prodromal AD patients.

Methods: A composite CERAD word list learning z-score of −1 was applied as a cut-off for memory performance at baseline. Competing causes of memory impairment other than prodromal AD were actively excluded. A cohort of 88 amnestic MCI patients was included; 75 were available for follow-up.

Results: After a mean delay of 19 months, 44% were found to have converted to AD, corresponding to an annualized conversion rate of 28%. The rate of new diagnoses other than stable MCI or AD was 6%. Baseline neuropsychological variables were not instrumental to predict progression.

Conclusion: Amnestic MCI patients, as identified by the present set of criteria, carry a high risk of median-term progression to AD.

Objective: The relationship of apolipoprotein E (APOE) genotype to lifetime cognitive decline was examined over 22 years in a large community-based population study.

Method: The sample for the present study was derived from follow-up of a probability sample of the adult household residents of East Baltimore. From the Baltimore cohort of the Epidemiologic Catchment Area Study, genotype data were collected on 818 participants at the study's fourth wave between 2003 and 2004. Participants were administered the Mini-mental State Examination (MMSE) at all four study waves. Three tests of verbal learning – immediate recall, delayed recall, and word recognition – were completed at waves 3 and 4. The 659 participants for whom genetic data were available had also completed cognitive testing at all time points. Test scores and changes in these scores were examined by APOE genotype group (x/x or 4/x) in younger and older subcohorts defined by age at wave 4 (< or ≥ age 65).

Results: Cross-sectional wave 4 scores on all four cognitive tasks were lower in APOEε4 carriers when compared to non-carriers. In longitudinal univariate models ε4 carriers in the younger cohort demonstrated a greater annual rate of decline on a delayed recall task and MMSE. After adjusting for covariates only the decline in the delayed recall task was significant.

Conclusion: We report an association between APOE genotype and decline in delayed recall and possibly MMSE over this extended time period limited to younger individuals. The lack of an association between APOE and decline in older individuals is likely to be the result of survival bias. Although a clear association exists between APOE genotype and cognitive decline or dementia in late life, these findings suggest that over the lifespan the relationship between APOE and cognitive decline is more complicated.

Background: The ability to remember to complete future intentions, prospective memory, often begins to fail in old age. The aim of the present study was to examine the sensitivity of a computer-based procedure using naturalistic stimuli to age-related increases in forgetting under conditions of high (increased visual and auditory noise) or low distraction.

Methods: Participants were tested in a virtual shopping precinct constructed from linked photographs, sounds, and video segments. Groups of 32 older and younger persons completed two concurrent memory tasks while moving along the street. In one task, participants were given errands to complete with an accessible checklist, in the other, they were required to remember to respond to three different targets that appeared repeatedly.

Results: The results confirmed previous findings that older adults have difficulty remembering future intentions, even on a self-paced task using naturalistic stimuli, and showed that this was accentuated in noisy environments.

Conclusions: Older persons have particular difficulty remembering in noisy environments, and results from testing in the clinic may underestimate the practical memory problems experienced by older adults with mild cognitive impairments. The findings provide encouragement for the construction of computer-generated environments to measure functional deficits in cognition.

Introduction: In this report, the results of a household survey were used to examine the prevalence of very mild and mild dementia in Chinese older persons in Hong Kong.

Methods: The study adopted a two-phase design. At Phase 1, 6100 subjects were screened using the Cantonese version of the Mini-mental State Examination (MMSE) and a short memory inventory. At Phase 2, 2073 subjects were screened positive and 737 were evaluated by psychiatrists. Clinical Dementia Rating (CDR) and cognitive assessment were used for diagnosis of dementia. Very mild dementia (VMD) was defined as a global CDR of 0.5, with memory and non-memory subscale scores of 0.5 or more. Mild dementia was classified for subjects with a CDR of 1.

Results: The overall prevalence of VMD and mild dementia for persons aged 70 years or above was 8.5% (95%CI: 7.4–9.6) and 8.9% (95%CI: 7.8–10.0) respectively. Among subjects with clinical dementia, 84.6% had mild (CDR1) dementia. Logistic regression analyses revealed that older age, lower educational level and significant cerebrovascular risk factors were risk factors for dementia, while regular physical exercise was a protective factor for dementia.

Conclusions: A sizable proportion of community-living subjects suffered from milder forms of dementia. They represent a high risk for early intervention to reduce potential physical and psychiatric morbidity.

Background: Although sleep problems are commonly reported among dementia caregivers, the nature and frequency of caregiver sleep disruptions, and their relationship to health status, has received little empirical attention to date.

Methods: The current study investigated the sleep situations of a sample of 60 spousal caregivers currently residing with a Alzheimer disease care recipient, including the frequency of nocturnal disruptions by the care recipient, and the reasons for these disruptions. In addition, exploratory correlations were computed between caregiver sleep variables and health outcomes.

Results: Some 63% of spousal caregivers reported sleep disruptions due to the nocturnal behavior of the recipients of their care. Poorer caregiver sleep quality was associated with higher frequency of nocturnal disruptions by the care recipient, the care recipient needing to use the bathroom, and wandering, higher caregiver depressive symptoms, and higher levels of caregiver role burden. The frequency of nocturnal disruptions was associated with poorer mental health status and a greater number of depressive symptoms.

Conclusions: Results suggest that nocturnal disruptions by the care recipient may have adverse health consequences for spousal caregivers, and that further study of the determinants of caregiver sleep quality and health outcomes are warranted.

Background: With the number of older drivers increasing, self-regulation of driving has been proposed as a viable means of balancing the autonomy of older adults against the sometimes competing demand of public safety. In this study, we investigate self-regulation of driving among a group of older adults with varying functional abilities.

Method: Participants in the study comprised 1,543 drivers aged 75 years or older. They completed an objective measure of visual attention from which crash risk was estimated, and self-report measures of driving avoidance, driving exposure, physical functioning, general health status, and vision. Crash records were obtained from the State Department of Public Safety.

Results: Overall, participants were most likely to avoid driving in bad weather followed by driving at night, driving on high traffic roads, driving in unfamiliar areas, and making left-hand turns across oncoming traffic. With the exception of driving at night, drivers at higher risk of crashes generally reported greater avoidance of these driving situations than lower risk drivers. However, across all driving situations a significant proportion of higher risk drivers did not restrict their driving. In general, self-regulation of driving did not result in reduced social engagement.

Conclusion: Some older drivers with visual attention impairments do not restrict their driving in difficult situations. There is a need for physicians and family members to discuss driving behaviors with older adults routinely to ensure their safety. The association between visual attention and driving restriction also has implications for interventions aimed at preserving mobility in the elderly.

Background: The relationship between self-stigma and self-esteem in patients with schizophrenia is receiving increased attention. However, studies to date have been limited to samples of persons under the age of 65.

Aim: To examine the relationship between self-stigma and self-esteem in people with schizophrenia in both younger and older age groups.

Methods: Face-to-face interviews were completed with 86 inpatients with schizophrenia in a psychiatric hospital (mean age = 54, 55% female). Self-esteem was assessed using Rosenberg's Self Esteem Scale. Self-stigma was assessed using an adapted version of the Internalized Stigma of Mental Health (ISMI) scale. Information regarding socio-demographic characteristics and psychiatric history and symptomatology was collected.

Results: Self-stigma was moderate with only 20–33% of the participants reporting high levels of stigmatization. Older participants reported lower levels of self-stigma than younger participants. A relatively strong association between self-stigma and self-esteem was found.

Conclusions: The findings point to the complexity of the association between self-stigma, self-esteem and age in people with schizophrenia. This study stresses the importance of clinicians taking the issue of self-stigma into consideration when treating young and old patients with schizophrenia.

Objective: This cross-sectional study examined the clinical significance and impact of subsyndromal depression in a sample of elderly people living in the community in Singapore.

Method: Data were analyzed from a population survey (the Singapore National Mental Health Survey of the Elderly). A total of 1092 respondents from a nationally representative multi-ethnic (Chinese, Malay and Indian) stratified random sample of older adults aged 60 and above were examined for depression using the Geriatric Mental State Examination (GMS). Diagnostic confidence levels of 3–5 indicated a DSM-IV diagnosis of syndromal depression, and 1–2 indicated subsyndromal depression. Other variables included sociodemographic characteristics, psychiatric and medical comorbidities, MMSE, health awareness, health and functional status.

Results: Subjects with subsyndromal depression were more likely to have poor socioeconomic status, cognitive impairment, anxiety, and measures of poor mental, physical and functional status compared with non-depressed subjects, and were similar to or worse than syndromal cases. In multivariate analyses that controlled for age, gender, ethnicity, education and several other sociodemographic factors, both subsyndromal and syndromal depression were significantly associated with higher numbers of medical comorbidities, diagnoses of comorbid dementia and anxiety, lower MMSE scores, self-reported mental health problem, functional disability and poor health status.

Conclusion: In this Asian population, subsydromal depression had the same clinical significance and health impact as syndromal depression, similar to findings in the West.

Concepts of personal autonomy and freedom have featured prominently in British social and political history. They are widely regarded as a very positive aspect of British culture. However, the presumption of mental capacity and the privileged status of autonomy over the promotion of well-being may on some occasions result in unnecessary suffering and neglect. Currently, individuals are presumed able to make autonomous decisions about their treatment. Their autonomy can only be challenged through a proactive process, in which the health professional must provide valid arguments for overriding it.