IntroductionThere is a growing body of evidence that subtle deficits in instrumental activities of daily living (IADL) may be present in mild cognitive impairment (MCI). However, it is not clear if there are IADL domains that are consistently affected across patients with MCI. In this systematic review, therefore, we aimed to summarize research results regarding the performance of MCI patients in specific IADL (sub)domains compared with persons who are cognitively normal and/or patients with dementia.MethodsThe databases PsycINFO, PubMed and Web of Science were searched for relevant literature in December 2013. Publications from 1999 onward were considered for inclusion. Altogether, 497 articles were retrieved. Reference lists of selected articles were searched for potentially relevant articles. After screening the abstracts of these 497 articles, 37 articles were included in this review.ResultsIn 35 studies, IADL deficits (such as problems with medication intake, telephone use, keeping appointments, finding things at home and using everyday technology) were documented in patients with MCI. Financial capacity in patients with MCI was affected in the majority of studies. Effect sizes for group differences between patients with MCI and healthy controls were predominantly moderate to large. Performance-based instruments showed slight advantages (in terms of effect sizes) in detecting group differences in IADL functioning between patients with MCI, patients with Alzheimer’s disease and healthy controls.ConclusionIADL requiring higher neuropsychological functioning seem to be most severely affected in patients with MCI. A reliable identification of such deficits is necessary, as patients with MCI with IADL deficits seem to have a higher risk of converting to dementia than patients with MCI without IADL deficits. The use of assessment tools specifically designed and validated for patients with MCI is therefore strongly recommended. Furthermore, the development of performance-based assessment instruments should be intensified, as they allow a valid and reliable assessment of subtle IADL deficits in MCI, even if a proxy is not available. Another important point to consider when designing new scales is the inclusion of technology-associated IADL. Novel instruments for clinical practice should be time-efficient and easy to administer.
IntroductionThe objective of this study was to describe the longitudinal cognitive outcome in Alzheimer's disease (AD) and analyze factors that affect the outcome, including the impact of different cholinesterase inhibitors (ChEI).MethodsIn an open, three-year, nonrandomized, prospective, multicenter study, 843 patients were treated with donepezil, rivastigmine, or galantamine in a routine clinical setting. At baseline and every six months, patients were assessed using several rating scales, including the Mini-Mental State Examination (MMSE) and the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and the dose of ChEI was recorded. Sociodemographic and clinical characteristics were investigated. The relationships of these predictors with longitudinal cognitive ability were analyzed using mixed-effects models.ResultsSlower long-term cognitive decline was associated with a higher cognitive ability at baseline or a lower level of education. The improvement in cognitive response after six months of ChEI therapy and a more positive longitudinal outcome were related to a higher mean dose of ChEI, nonsteroidal anti-inflammatory drug (NSAID)/acetylsalicylic acid usage, male gender, older age, and absence of the apolipoprotein E (APOE) ε4 allele. More severe cognitive impairment at baseline also predicted an improved response to ChEI treatment after six months. The type of ChEI agent did not influence the short-term response or the long-term outcome.ConclusionsIn this three-year AD study performed in a routine clinical practice, the response to ChEI treatment and longitudinal cognitive outcome were better in males, older individuals, non-carriers of the APOE ε4 allele, patients treated with NSAIDs/acetylsalicylic acid, and those receiving a higher dose of ChEI, regardless of the drug agent.
The rate of functional but not cognitive decline was a strong risk factor for NHP. The results could be used to identify the care recipients that might risk early NHP to ensure that these individuals receive a sufficient level of assistance. Furthermore, higher doses of ChEI might postpone institutionalization in AD.
BackgroundWhether age at onset influences Alzheimer’s disease (AD) progression and the effectiveness of cholinesterase inhibitor (ChEI) therapy is not clear. We aimed to compare longitudinal cognitive and global outcomes in ChEI-treated patients with early-onset Alzheimer’s disease (EOAD) versus late-onset Alzheimer’s disease (LOAD) in clinical practice.MethodsThis 3-year, prospective, observational, multicentre study included 1017 participants with mild to moderate AD; 143 had EOAD (age at onset < 65 years) and 874 had LOAD (age at onset ≥ 65 years). At baseline and semi-annually, patients were assessed using cognitive, global and activities of daily living (ADL) scales, and the dose of ChEI was recorded. Potential predictors of decline were analysed using mixed-effects models.ResultsSix-month response to ChEI therapy and long-term prognosis in cognitive and global performance were similar between the age-at-onset groups. However, deterioration was significantly faster when using the Alzheimer’s Disease Assessment Scale–Cognitive subscale (ADAS-Cog) over 3 years in participants with EOAD than in those with LOAD; hence, prediction models for the mean ADAS-Cog trajectories are presented. The younger cohort had a larger proportion of homozygote apolipoprotein E (APOE) ε4 allele carriers than the older cohort; however, APOE genotype was not a significant predictor of cognitive impairment in the multivariate models. A slower rate of cognitive progression was related to initiation of ChEIs at an earlier stage of AD, higher ChEI dose and fewer years of education in both groups. In LOAD, male sex, better instrumental ADL ability and no antipsychotic drug use were additional protective characteristics. The older patients received a lower ChEI dose than the younger individuals during most of the study period.ConclusionsAlthough the participants with EOAD showed a faster decline in ADAS-Cog, had a longer duration of AD before diagnosis, and had a higher frequency of two APOE ε4 alleles than those with LOAD, the cognitive and global responses to ChEI treatment and the longitudinal outcomes after 3 years were similar between the age-at-onset groups. A higher mean dose of ChEI and better cognitive status at the start of therapy were independent protective factors in both groups, stressing the importance of early treatment in adequate doses for all patients with AD.
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