A number of studies have compared Alzheimer’s disease (AD), the commonest form of dementia, based on their age of onset, i.e. before the age of 65 years (early-onset AD, EO-AD) to those developing after 65 years of age (late-onset AD, LO-AD), but the differences are not clear. We performed a systematic review and meta-analysis to compare clinical characteristics between EO-AD and LO-AD.

Medline, Embase, PsycINFO, and CINAHL databases were systematically searched for studies comparing time to diagnosis, cognitive scores, annual cognitive decline, activities of daily living (ADLs), neuropsychiatric symptoms (NPS), quality of life (QoL), and survival time for EO-AD and LO-AD patients.

Forty-two studies were included (EO-AD participants n = 5,544; LO-AD participants n = 16,042). An inverse variance method with random effects models was used to calculate overall effect estimates for each outcome. People with EO-AD had significantly poorer baseline cognitive performance and faster cognitive decline but longer survival times than people with LO-AD. There was no evidence that EO-AD patients differ from people with LO-AD in terms of symptom onset to diagnosis time, ADLs, and NPS. There were insufficient data to estimate overall effects of differences in QoL in EO-AD compared to LO-AD.

Our findings suggest that EO-AD differs from LO-AD in baseline cognition, cognitive decline, and survival time but otherwise has similar clinical characteristics to LO-AD. Larger studies using standardized questionnaires focusing on the clinical presentations are needed to better understand the impact of age of onset in AD.

Among people with dementia, poor nutritional status has been associated with worse cognitive and functional decline, but few studies have examined its association with neuropsychiatric symptoms (NPS). We examined this topic in a population-based sample of persons with dementia.

Longitudinal, observational cohort study.

Community.

Two hundred ninety-two persons with dementia (71.9% Alzheimer’s disease, 56.2% women) were followed up to 6 years.

We used a modified Mini-Nutritional Assessment (mMNA) and the Neuropsychiatric Inventory (NPI) to evaluate nutritional status and NPS, respectively. Individual linear mixed effects models examined the associations between time-varying mMNA total score or clinical categories (malnourishment, risk for malnourishment, or well-nourished) and NPI total score (excluding appetite domain) or NPI individual domain or cluster (e.g. psychosis) scores. Covariates tested were dementia onset age, type, and duration, medical comorbidities, sex, apolipoprotein E (APOE) genotype, and education.

Compared to the well-nourished, those at risk for malnourishment and those malnourished had higher total NPI scores [b (95% CI) = 1.76 (0.04, 3.48) or 3.20 (0.62, 5.78), respectively], controlling for significant covariates. Higher mMNA total score (better nutritional status) was associated with lower total NPI [b (95% CI) = −0.58 (−0.86, −0.29)] and lower domain scores for psychosis [b (95% CI) = −0.08 (−0.16, .004)], depression [b (95% CI = −0.11 (−0.16, −0.05], and apathy [b (95% CI = −0.19 (−0.28, −0.11)].

Worse nutritional status is associated with more severe NPS. Dietary or behavioral interventions to prevent malnutrition may be beneficial for persons with dementia.

This paper used data from the Apathy in Dementia Methylphenidate Trial 2 (NCT02346201) to conduct a planned cost consequence analysis to investigate whether treatment of apathy with methylphenidate is economically attractive.

A total of 167 patients with clinically significant apathy randomized to either methylphenidate or placebo were included. The Resource Utilization in Dementia Lite instrument assessed resource utilization for the past 30 days and the EuroQol five dimension five level questionnaire assessed health utility at baseline, 3 months, and 6 months. Resources were converted to costs using standard sources and reported in 2021 USD. A repeated measures analysis of variance compared change in costs and utility over time between the treatment and placebo groups. A binary logistic regression was used to assess cost predictors.

Costs were not significantly different between groups whether the cost of methylphenidate was excluded (F(2,330) = 0.626, ηp2 = 0.004, p = 0.535) or included (F(2,330) = 0.629, ηp2 = 0.004, p = 0.534). Utility improved with methylphenidate treatment as there was a group by time interaction (F(2,330) = 7.525, ηp2 = 0.044, p < 0.001).

Results from this study indicated that there was no evidence for a difference in resource utilization costs between methylphenidate and placebo treatment. However, utility improved significantly over the 6-month follow-up period. These results can aid in decision-making to improve quality of life in patients with Alzheimer’s disease while considering the burden on the healthcare system.

Alzheimer’s disease (AD) has prolonged asymptomatic or mild symptomatic periods. Given that there is an increase in treatment options and that early intervention could modify the disease course, it is desirable to devise biological indices that may differentiate AD and nonAD at mild cognitive impairment (MCI) stage.

Based on two well-acknowledged observations of background slowing (attenuation in alpha power and enhancement in theta and delta powers) and early involvement of posterior cingulate cortex (PCC, a neural hub of default-mode network), this study devised novel neural markers, namely, spectral ratios of alpha1 to delta and alpha1 to theta in the PCC.

We analysed 46 MCI patients, with 22 ADMCI and 24 nonADMCI who were matched in age, education, and global cognitive capability. Concordant with the prediction, the regional spectral ratios were lower in the ADMCI group, suggesting its clinical application potential.

Previous research has verified that neural markers derived from clinical electroencephalography may be informative in differentiating AD from other neurological conditions. We believe that the spectral ratios in the neural hubs that show early pathological changes can enrich the instrumental assessment of brain dysfunctions at the MCI (or pre-clinical) stage.

To perform a meta-analysis of clinical studies on the differences in treatment or research decision-making capacity among patients with Mild Cognitive Impairment (MCI), Alzheimer’s disease (AD), and healthy comparisons (HCs).

A systematic search was conducted on Medline/Pubmed, CINAHL, PsycINFO, Web of Science, and Scopus. Standardized mean differences and random-effects model were used in all cases.

The United States, France, Japan, and China.

Four hundred and ten patients with MCI, 149 with AD, and 368 HCs were included.

The studies we included in the analysis assessed decisional capacity to consent by the MacArthur Competence Assessment Tool for Treatment (MAcCAT-T), MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR), Capacity to Consent to Treatment Instrument (CCTI), and University of California Brief Assessment of Capacity to Consent (UBACC).

We identified 109 potentially eligible studies from 1672 records, and 7 papers were included in the meta-analysis. The meta-analysis showed that there was significant impairment in a decision-making capacity in MCI patients compared to the HCs group in terms of Understanding (SMD = −1.04, 95% CI: −1.31 to −0.77, P < 0.001; I2 = 52%, P = 0.07), Appreciation (SMD = −0.51, 95% CI: −0.66 to −0.36, P < 0.001; I2 = 0%, P = 0.97), and Reasoning (SMD = −0.62, 95% CI: −0.77, −0.47, P < 0.001; I2=0%, P =0.46). MCI patients scored significantly higher in Understanding (SMD = 1.50, 95% CI: 0.91, 2.09, P = 0.01, I2 = 78%, P = 0.00001) compared to patients affected by AD.

Patients affected by MCI are at higher risk of impaired capacity to consent to treatment and research compared to HCs, despite being at lower risk compared to patients affected by AD. Clinicians and researchers need to carefully evaluate decisional capacity in MCI patients providing informed consent.

Alzheimer’s Disease (AD), characterized by deficits in memory and cognition and by behavioral impairment, is a progressive neurodegenerative disorder that influences more than 47 million people worldwide. Currently, no available drug is able to stop AD progression. Therefore, novel therapeutic strategies need to be investigated.

We analyzed the RNA sequencing data (RNA-seq) derived from the Gene Expression Omnibus (GEO) database to identify the differentially expressed mRNAs in AD. The AD mouse model Tg2576 was used to verify the effects of IGF-2. The Morris Water Maze was administered to test the role of IGF-2 in memory consolidation. In addition, we quantified cell apoptosis by the TUNEL assay. The levels of amyloid plaques and the levels of Aβ40 and Aβ42 in the hippocampus were also determined by immunohistochemistry and ELISA, respectively.

RNA-seq analysis revealed that IGF-2 was remarkably reduced in AD. The expression of the upstream genes PI3K and AKT and the downstream gene CREB in the PI3K signaling pathway was significantly increased in the hippocampus of Tg2576 mice cells treated with IGF-2. The Morris water maze test showed that IGF-2 improved memory consolidation in Tg2576 mice. The activity of caspase-3 was decreased in Tg2576 mice treated with IGF-2. Amyloid plaques in the hippocampus were reduced, and the levels of Aβ40 and Aβ42 were decreased. The above effects of IGF-2 on AD were blocked when the PI3K signaling pathway inhibitor wortmannin was added.

IGF-2 attenuates memory decline, oxidative stress, cell apoptosis and amyloid plaques in the AD mouse model Tg2576 by activating the PI3K/AKT/CREB signaling pathway.

It may be assumed that increased public awareness of dementia due to Alzheimer's disease (AD) together with the availability of efficacious treatment will result in diagnostic evaluation at earlier stages of cognitive decline and diagnosis of dementia due to AD at earlier stages.

All persons that were examined at a university based memory clinic, in Germany, between 1985 and 2009 were included.

In the 3,951 persons identified, linear regression analysis revealed a positive association between Mini Mental State Examination (MMSE) score and year of initial examination (yearIE) (β = 0.266; p < 0.001). In the 1,821 patients diagnosed with dementia due to AD, a positive association between MMSE score and yearIE (β = 0.230; p < 0.001) was revealed. MMSE scores were higher (β = 0.195; p < 0.001) after the introduction of cholinesterase inhibitors in Germany in 1997.

Diagnostic evaluation of individuals occurred at progressively earlier stages of cognitive decline. Dementia due to AD was diagnosed at progressively earlier stages, and this trend was associated with the availability of efficacious treatment. This is the first study on changes in patient referral and diagnosis based on a continuous 25 years period.

Caregiver burden is a complex and multidimensional construct. Although previous studies have explored numerous factors associated with caregiver burden, these factors have not been identified with a large population-based sample in a theory-based multidimensional way. This study explores multidimensional determinants associated with family caregiver burden to determine the main contributors of caregiver burden in Alzheimer's disease (AD) using a large community dataset.

A retrospective secondary data analysis was conducted on 1,133 patients with AD and 1,133 primary caregivers who were registered in a metropolitan city dementia center in South Korea. The patient data included socio-demographic and disease profiles. The caregiver data consisted of socio-demographic and caregiving profiles.

The study results identified that dementia-related factors were the most significant factors, representing 25.6% of caregiver burden and were followed by caregiving-related factors explaining caregiver burden significantly. Behavioral problems and instrumental activities of daily living (IADL) dependency of the patient, spousal relationship, hours of caregiving, and the number of diseases associated with the caregiver were found to be significant individual variables.

It is vital to develop a service and support program with a greater emphasis on the behavioral problems and IADL deficiency of patients with AD as well as on improving the competence ability of caregivers to deal with such difficulties.

The assessment of visuospatial abilities is usually performed by drawing tasks. In patients with very low formal education, the use of these tasks might be biased by their cultural background. The Stick Design Test was developed for the assessment of this population. We aim to expand the test psychometric properties by assessing its construct, criterion-related and ecological validity in older adults with low formal education.

Healthy older adults (n = 63) and Alzheimer's disease patients (n = 92) performed the Stick Design Test, Mini-Mental State Examination, Digit Span Forward and the Clock Drawing Test. Their caregivers answered Personal Care and Instrumental Activities of Daily Living). Construct validity was assessed by factor analysis, convergent correlations (with the Clock Drawing Test), and divergent correlations (with Digit Span Forward); criterion-related validity by receiver operating characteristic curve analysis and binary logistic regression; and Ecological validity by correlations with ADL.

The test factor structure was composed by one component (R2 = 64%). Significant correlations with the Clock Drawing Test and Digit Span Forward were found, and the relationship was stronger with the first measure. The test was less associated with formal education than the Clock Drawing Test. It classified about 76% of the participants correctly and had and additive effect with the Mini-Mental State Examination (84% of correct classification). The test also correlated significantly with measures of ADL, suggesting ecological validity.

The Stick Design Test shows evidence of construct, criterion-related and ecological validity. It is an interesting alternative to drawing tasks for the assessment of visuospatial abilities.