The aim of this study was to develop a brief informant-based questionnaire, namely the Symptoms of Early Dementia-11 Questionnaire (SED-11Q), for the screening of early dementia. 459 elderly individuals participated, including 39 with mild cognitive impairment in the Clinical Dementia Rating scale (CDR) 0.5, 233 with mild dementia in CDR 1, 106 with moderate dementia in CDR 2, and 81 normal controls in CDR 0. Informants were required to fill out a 13-item questionnaire. Two items were excluded after analyzing sensitivities and specificities. The final version of the SED-11Q assesses memory, daily functioning, social communication, and personality changes. Receiver operator characteristic curves assessed the utility to discriminate between CDR 0 (no dementia) and CDR 1 (mild dementia). The statistically optimal cutoff value of 2/3, which indicated a sensitivity of 0.84 and a specificity of 0.90, can be applied in the clinical setting. In the community setting, a cutoff value of 3/4, which indicated a sensitivity of 0.76 and a specificity of 0.96, is recommended to avoid false positives. The SED-11Q reliably differentiated nondemented from demented individuals when completed by an informant, and thus is practical as a rapid screening tool in general practice, as well as in the community setting, to decide whether to seek further diagnostic confirmation.

White matter lesions (WMLs) are a common finding in patients with dementia. This study investigates the relationship between WMLs, hyperphosphorylated tau (P-tau) in cerebrospinal fluid (CSF) and apolipoprotein E (APOE) ε4 genotype in prodromal Alzheimer's disease (AD).Baseline levels of tau, P-tau and β-amyloid 1-42 in CSF, the presence of WMLs in the brain, and the APOE genotype were ascertained in 159 patients with mild cognitive impairment (MCI) and 38 cognitively healthy controls.After 5.7 years, 58 patients had developed AD. In this group, patients with normal levels of CSF P-tau had higher levels of WMLs in the parietal regions than those with pathological P-tau levels (p < 0.05). Also, patients without APOE ε4 alleles had more WMLs in the parietal lobes than those with at least one allele (p < 0.05). MCI patients with pathological P-tau levels and parietal WMLs showed a greater risk of developing AD than those with just one of the two pathological parameters.We suggest that WMLs in parietal lobes and tau pathology likely have independent but synergistic effects on the reduction of the cognitive reserve capacity of the brain. In patients with a more low-grade AD pathology, WMLs in the parietal lobes might increase the risk of developing dementia.

Objectives:

In certain health care facilities, the staff commonly wear uniforms for dementia care. Wearing uniforms are often believed to improve the well-being of institutionalized people with dementia (PwD) by facilitating orientation and preserving hygiene. However, when studied more thoroughly, it appears that their use counters to person centeredness. This study aims to investigate the impact of wearing uniforms on the quality of life (QoL) of institutionalized PwD.Method:A natural experimental design was operated in 4 special care units (SCUs) in France. Two SCUs served as an experimental group (caregivers wearing street clothes except when performing hands-on physical care; N = 13) and 2 served as a comparison group (caregivers wearing uniforms; N = 14). The QoL of PwD was measured using the QoL-Alzheimer's Disease scale, and focus groups were carried out with caregivers.

Results:

Overall and significantly enhanced QoL scores were observed for the experimental street clothing staff group when compared to the uniform group. Caregivers also reported subjective impressions of overall beneficial outcomes for PwD when the caregivers were not wearing uniforms and reported feeling more at ease when interacting with them.

Conclusion:

Results are discussed in terms of intergroup relationships, living and working conditions, and ethical issues.

OBJECTIVE:

To identify a neuroimaging signature predictive of brain amyloidosis as a screening tool to identify individuals with mild cognitive impairment (MCI) that are most likely to have high levels of brain amyloidosis or to be amyloid-free.

METHODS:

The prediction model cohort included 62 MCI subjects screened with structural magnetic resonance imaging (MRI) and (11) C-labeled Pittsburgh compound B positron emission tomography (PET). We identified an anatomical shape variation-based neuroimaging predictor of brain amyloidosis and defined a sMRI-based brain amyloidosis score (sMRI-BAS). Amyloid beta positivity (Aβ(+) ) predictive power of sMRI-BAS was validated on an independent cohort of 153 MCI patients with cerebrospinal fluid Aβ1-42 biomarker data but no amyloid PET scans. We compared the Aβ(+) predictive power of sMRI-BAS to those of apolipoprotein E (ApoE) genotype and hippocampal volume, the 2 most relevant candidate biomarkers for the prediction of brain amyloidosis.

RESULTS:

Anatomical shape variations predictive of brain amyloidosis in MCI embraced a characteristic spatial pattern known for high vulnerability to Alzheimer disease pathology, including the medial temporal lobe, temporal-parietal association cortices, posterior cingulate, precuneus, hippocampus, amygdala, caudate, and fornix/stria terminals. Aβ(+) prediction performance of sMRI-BAS and ApoE genotype jointly was significantly better than the performance of each predictor separately (area under the curve [AUC] = 0.88 vs AUC = 0.70 and AUC = 0.81, respectively) with >90% sensitivity and specificity at 20% false-positive rate and false-negative rate thresholds. Performance of hippocampal volume as an independent predictor of brain amyloidosis in MCI was only marginally better than random chance (AUC = 0.56).

INTERPRETATION:

As 1 of the first attempts to use an imaging technique that does not require amyloid-specific radioligands for identification of individuals with brain amyloidosis, our findings could lead to development of multidisciplinary/multimodality brain amyloidosis biomarkers that are reliable, minimally invasive, and widely available. ANN NEUROL 2013. © 2013 American Neurological Association.

N-truncated Aβ4-42 is highly abundant in Alzheimer disease (AD) brain and was the first Aβ peptide discovered in AD plaques. However, a possible role in AD aetiology has largely been neglected. In the present report, we demonstrate that Aβ4-42 rapidly forms aggregates possessing a high aggregation propensity in terms of monomer consumption and oligomer formation. Short-term treatment of primary cortical neurons indicated that Aβ4-42 is as toxic as pyroglutamate Aβ3-42 and Aβ1-42. In line with these findings, treatment of wildtype mice using intraventricular Aβ injection induced significant working memory deficits with Aβ4-42, pyroglutamate Aβ3-42 and Aβ1-42. Transgenic mice expressing Aβ4-42 (Tg4-42 transgenic line) developed a massive CA1 pyramidal neuron loss in the hippocampus. The hippocampus-specific expression of Aβ4-42 correlates well with age-dependent spatial reference memory deficits assessed by the Morris water maze test. Our findings indicate that N-truncated Aβ4-42 triggers acute and long-lasting behavioral deficits comparable to AD typical memory dysfunction.

For 20years the amyloid cascade hypothesis of Alzheimer disease (AD) has placed the amyloid-β peptide (Aβ), formed from the amyloid precursor protein (APP), centre stage in the process of neurodegeneration. However, no new therapeutic agents have reached the clinic through exploitation of the hypothesis. The APP metabolites, including Aβ, generated by its proteolytic processing, have distinct physiological functions. In particular, the cleaved intracellular domain of APP (AICD) regulates expression of several genes, including APP itself, the β-secretase BACE-1 and the Aβ-degrading enzyme, neprilysin and this transcriptional regulation involves direct promoter binding of AICD. Of the three major splice isoforms of APP (APP695, APP751, APP770), APP695 is the predominant neuronal form, from which Aβ and transcriptionally-active AICD are preferentially generated by selective processing through the amyloidogenic pathway. Despite intensive research, the normal functions of the APP isoforms remain an enigma. APP plays an important role in brain development, memory and synaptic plasticity and secreted forms of APP are neuroprotective. A fuller understanding of the physiological and pathological actions of APP and its metabolic and gene regulatory network could provide new therapeutic opportunities in neurodegeneration, including AD.

INTRODUCTION:

Rivastigmine, a treatment for mild to moderate Alzheimer disease (AD), is the first cholinesterase inhibitor to be available in the transdermal format. We aim to describe user experience and satisfaction with the rivastigmine patch, as well as any clinical changes perceived in patients.

METHODS:

Observational, cross-sectional, multicentre study with 239 investigators and 1851 informal caregivers of patients with mild to moderate AD. Patients were treated with transdermal rivastigmine patches for ≥ 6 months and had previously received high doses of oral rivastigmine.

RESULTS:

Mean caregiver age was 59.8±14.4 years and 70.9% were women. They spent 10.0±7.1hours per day providing care and 79.8% lived with the patient. Patch instructions were described as easy to follow by 97.1% of the caregivers and 92.1% of them rated patch application as easy or very easy. The most commonly cited disadvantage was adhesion problems (26.8%). Discontinuation of treatment was due to cutaneous reactions in most cases. Overall, 76.5% of the caregivers were satisfied or very satisfied with transdermal treatment and 77.4% considered that its interference with daily activities was minimal or null. The patch was preferred to oral treatment by 94.3% of caregivers. Clinical Global Impression of Change ratings improved according to 61.3% of the caregivers and 53% of the investigators. Few caregivers reported medication forgetfulness.

CONCLUSIONS:

Most caregivers of patients with mild to moderate AD preferred the transdermal format of rivastigmine to the oral format. Caregivers also reported overall satisfaction, ease of use, and reduced impact on daily activities for transdermal rivastigmine format, in addition to patient improvement compared to their condition under the previous treatment.

Donepezil, a member of the acetylcholinesterase inhibitor family, is approved for management of cognitive impairments as well as behavioral complications in patients with neurodegenerative Alzheimer's disease. Generally, donepezil is regarded as a safe medication in patients with Alzheimer's disease although there have been reports of several minor adverse events including gastrointestinal disturbances. Herein we describe a patient with Alzheimer's disease who demonstrated delirious behavior upon treatment with donepezil.

BACKGROUND::

Adherence to a Mediterranean diet has been associated with lower risk of various age-related diseases including dementia. Although narrative reviews have been published, no systematic review has synthesized studies on the association between Mediterranean diet adherence and cognitive function or dementia.

METHODS::

We conducted a systematic review of 11 electronic databases (including Medline) of published articles up to January 2012. Reference lists, selected journal contents, and relevant websites were also searched. Study selection, data extraction, and quality assessment were performed independently by two reviewers using predefined criteria. Studies were included if they examined the association between a Mediterranean diet adherence score and cognitive function or dementia.

RESULTS::

Twelve eligible papers (11 observational studies and one randomized controlled trial) were identified, describing seven unique cohorts. Despite methodological heterogeneity and limited statistical power in some studies, there was a reasonably consistent pattern of associations. Higher adherence to Mediterranean diet was associated with better cognitive function, lower rates of cognitive decline, and reduced risk of Alzheimer disease in nine out of 12 studies, whereas results for mild cognitive impairment were inconsistent.

CONCLUSIONS::

Published studies suggest that greater adherence to Mediterranean diet is associated with slower cognitive decline and lower risk of developing Alzheimer disease. Further studies would be useful to clarify the association with mild cognitive impairment and vascular dementia. Long-term randomized controlled trials promoting a Mediterranean diet may help establish whether improved adherence helps to prevent or delay the onset of Alzheimer disease and dementia.

Age-related functional alterations in the perforant path projection from the entorhinal cortex to the dentate gyrus (DG) of the hippocampus play a major role in age-related memory impairments, but little is known about the molecular mechanisms responsible for these changes. In a recent interesting study, Hara and colleagues (J Neurosci 2012;32:7336-7344) tested young and aged monkeys on the visual recognition memory test ''delayed nonmatching-to-sample''; then, electron microscopic immunocytochemistry was performed in the hippocampal DG to determine the subcellular localization of the GluA2 subunit of the glutamate a-amino-3-hydroxy-5-methyl-4- isoxazole-propionic acid receptor (AMPAR) and protein kinase Mζ (PKMζ), which promotes memory storage by regulating GluA2-containing AMPAR trafficking. The results obtained suggest that age-related deficits in visual recognition memory are coupled with impairment in PKMζ-dependent maintenance of GluA2 at the synapse. Together with previous evidences of the critical role of PKMζ in memory consolidation, these data render this enzyme an attractive potential therapeutic target for preventing or treating age-related memory decline, and support the view that the pharmacological manipulation of AMPAR trafficking in the synapses may provide new insights in the search of memory enhancers for aged individuals, including those affected by Alzheimer disease.