Neuropsychological criteria for mild cognitive impairment (MCI) more accurately predict progression to Alzheimer’s disease (AD) and are more strongly associated with AD biomarkers and neuroimaging profiles than ADNI criteria. However, research to date has been conducted in relatively healthy samples with few comorbidities. Given that history of traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) are risk factors for AD and common in Veterans, we compared neuropsychological, typical (Petersen/Winblad), and ADNI criteria for MCI in Vietnam-era Veterans with histories of TBI or PTSD.

267 Veterans (mean age = 69.8) from the DOD-ADNI study were evaluated for MCI using neuropsychological, typical, and ADNI criteria. Linear regressions adjusting for age and education assessed associations between MCI status and AD biomarker levels (cerebrospinal fluid [CSF] p-tau181, t-tau, and Aβ42) by diagnostic criteria. Logistic regressions adjusting for age and education assessed the effects of TBI severity and PTSD symptom severity simultaneously on MCI classification by each criteria.

Agreement between criteria was poor. Neuropsychological criteria identified more Veterans with MCI than typical or ADNI criteria, and were associated with higher CSF p-tau181 and t-tau. Typical and ADNI criteria were not associated with CSF biomarkers. PTSD symptom severity predicted MCI diagnosis by neuropsychological and ADNI criteria. History of moderate/severe TBI predicted MCI by typical and ADNI criteria.

MCI diagnosis using sensitive neuropsychological criteria is more strongly associated with AD biomarkers than conventional diagnostic methods. MCI diagnostics in Veterans would benefit from incorporation of comprehensive neuropsychological methods and consideration of the impact of PTSD.

In Alzheimer’s disease (AD), angiotensin II receptor blockers (ARBs) could reduce cerebrovascular dysfunction, while angiotensin-converting enzyme inhibitors (ACEis) might increase brain amyloid-β by suppressing effects of the angiotensin-converting enzyme 1, an amyloid-β-degrading enzyme. However, ACEis could benefit patients with AD by reducing the amyloidogenic processing of the amyloid precursor protein, by central cholinergic and anti-inflammatory mechanisms, and by peripheral modulation of glucose homeostasis. We aimed to investigate whether the ACE insertion/deletion polymorphism is associated with clinical changes in patients with AD, while considering apolipoprotein E (APOE)-ϵ4 carrier status and blood pressure response to angiotensin modulators.

Consecutive outpatients with late-onset AD were screened with cognitive tests and anthropometric measurements, while their caregivers were queried for functional and caregiver burden scores. Prospective pharmacogenetic associations were estimated for 1 year, taking APOE-ϵ4 carrier status and genotypes of the ACE insertion/deletion polymorphism into account, along with treatment with ACEis or ARBs.

For 193 patients (67.4% women, 53.4% APOE-ϵ4 carriers), the ACE insertion/deletion polymorphism was in Hardy–Weinberg equilibrium (p = 0.281), while arterial hypertension was prevalent in 80.3% (n = 124 used an ACEi, n = 21 used an ARB). ARBs benefitted mostly APOE-ϵ4 carriers concerning caregiver burden variations, cognitive and functional decline. ACEis benefitted APOE-ϵ4 non-carriers concerning cognitive and functional decline due to improved blood pressure control in addition to possible central mechanisms. The ACE insertion/deletion polymorphism led to variable response to angiotensin modulators concerning neurological outcomes and blood pressure variations.

Angiotensin modulators may be disease-modifiers in AD, while genetic stratification of samples is recommended in clinical studies.

Brain reserve, cognitive reserve, and education are thought to protect against late-life cognitive decline, but these variables have not been directly compared to one another in the same model, using future cognitive and functional decline as outcomes. We sought to determine whether the influence of these protective factors on executive function (EF) and daily function decline was dependent upon Alzheimer’s disease (AD) pathology severity, as measured by the total tau to beta-amyloid (T-τ/Aβ1-42) ratio in cerebrospinal fluid (CSF).

Participants were 1201 older adult volunteers in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) study. Brain reserve was defined using a composite index of structural brain volumes (total brain matter, hippocampus, and white matter hyperintensity). Cognitive reserve was defined as the variance in episodic memory performance not explained by brain integrity and demographics.

At higher levels of T-τ/Aβ1-42, brain and cognitive reserve predicted slower decline in EF. Only brain reserve attenuated decline at lower levels of T-τ/Aβ1-42. Education had no independent association with cognitive decline.

These results point to a hierarchy of protection against aging- and disease-associated cognitive decline. When pathology is low, only structural brain integrity predicts rate of future EF decline. The ability of cognitive reserve to predict future EF decline becomes stronger as CSF biomarker evidence of AD increases. Although education is typically thought of as a proxy for cognitive reserve, it did not show any protective effects on cognition after accounting for brain integrity and the residual cognitive reserve index.

While declarative learning is dependent on the hippocampus, procedural learning and repetition priming can operate independently from the hippocampus, making them potential targets for behavioral interventions that utilize non-declarative memory systems to compensate for the declarative learning deficits associated with hippocampal insult. Few studies have assessed procedural learning and repetition priming in individuals with amnestic mild cognitive impairment (aMCI).

This study offers an overview across declarative, conceptual repetition priming, and procedural learning tasks by providing between-group effect sizes and Bayes Factors (BFs) comparing individuals with aMCI and controls. Seventy-six individuals with aMCI and 83 cognitively unimpaired controls were assessed. We hypothesized to see the largest differences between individuals with aMCI and controls on declarative learning, followed by conceptual repetition priming, with the smallest differences on procedural learning.

Consistent with our hypotheses, we found large differences between groups with supporting BFs on declarative learning. For conceptual repetition priming, we found a small-to-moderate between-group effect size and a non-conclusive BF somewhat in favor of a difference between groups. We found more variable but overall trivial differences on procedural learning tasks, with inconclusive BFs, in line with expectations.

The current results suggest that conceptual repetition priming does not remain intact in individuals with aMCI while procedural learning may remain intact. While additional studies are needed, our results contribute to the evidence-base that suggests that procedural learning may remain spared in aMCI and helps inform behavioral interventions that aim to utilize procedural learning in this population.

Traditional naming tests are unsuitable to assess naming impairment in diverse populations, given the influence of culture, language, and education on naming performance. Our goal was therefore to develop and validate a new test to assess naming impairment in diverse populations: the Naming Assessment in Multicultural Europe (NAME).

We carried out a multistage pilot study. First, we generated a list of 149 potentially suitable items – e.g. from published cross-linguistic word lists and other naming tests – and selected those with a homogeneous age of acquisition and word frequency across languages. We selected three to four colored photographs for each of the 73 remaining items; 194 controls selected the most suitable photographs. Thirteen items were removed after a pilot study in 15 diverse healthy controls. The final 60-item test was validated in 39 controls and 137 diverse memory clinic patients with subjective cognitive impairment, neurological/neurodegenerative disease or psychiatric disorders in the Netherlands and Turkey (mean age: 67, SD: 11). Patients were from 15 different countries; the majority completed primary education or less (53%).

The NAME showed excellent reliability (Spearman–Brown coefficient: 0.95; Kuder–Richardson coefficient: 0.94) and robust correlations with other language tests (ρ = .35–.73). Patients with AD/mixed dementia obtained lower scores on most (48/60) NAME items, with an area under the curve of 0.88. NAME scores were correlated with age and education, but not with acculturation or sex.

The NAME is a promising tool to assess naming impairment in culturally, educationally, and linguistically diverse individuals.

Anticholinergic medications block cholinergic transmission. The central effects of anticholinergic drugs can be particularly marked in patients with dementia. Furthermore, anticholinergics antagonise the effects of cholinesterase inhibitors, the main dementia treatment.

This study aimed to assess anticholinergic drug prescribing among dementia patients before and after admission to UK acute hospitals.

352 patients with dementia were included from 17 hospitals in the UK. All were admitted to surgical, medical or Care of the Elderly wards in 2019. Information about patients’ prescriptions were recorded on a standardised form. An evidence-based online calculator was used to calculate the anticholinergic drug burden of each patient. The correlation between two subgroups upon admission and discharge was tested with Spearman’s Rank Correlation.

Table 1 shows patient demographics. On admission, 37.8% of patients had an anticholinergic burden score ≥1 and 5.68% ≥3. At discharge, 43.2% of patients had an anticholinergic burden score ≥1 and 9.1% ≥3. The increase was statistically significant (rho 0.688; p=2.2x10-16). The most common group of anticholinergic medications prescribed at discharge were psychotropics (see Figure 1). Among patients prescribed cholinesterase inhibitors, 44.9% were also taking anticholinergic medications.

This multicentre cross-sectional study found that people with dementia are frequently prescribed anticholinergic drugs, even if also taking cholinesterase inhibitors, and are significantly more likely to be discharged with a higher anticholinergic drug burden than on admission to hospital.

This project was planned and executed by the authors on behalf of SPARC (Student Psychiatry Audit and Research Collaborative). We thank the National Student Association of Medical Research for allowing us use of the Enketo platform. Judith Harrison was su

Story memory tasks are among the most commonly used memory tests; however, research suggests they may be less sensitive to memory decline and have a weaker association with hippocampal volumes than list learning tasks. To examine its utility, we compared story memory to other memory tests on impairment rates and association with hippocampal volumes.

Archival records from 1617 older adults (Mage = 74.41, range = 65–93) who completed the Wechsler Memory Scale – 4th edition (WMS-IV) Logical Memory (LM), Hopkins Verbal Learning Test – Revised (HVLT-R), and Brief Visuospatial Memory Test – Revised (BVMT-R) as part of a clinical neuropsychological evaluation were reviewed. Scores >1.5 SD below age-adjusted means were considered impaired, and frequency distributions were used to examine impairment rates. A subset of participants (n = 179) had magnetic resonance imaging (MRI) data that underwent image quality assessment. Partial correlations and linear regression analyses, accounting for age, education, and total intracranial volume (TIV), examined associations between memory raw scores and hippocampal volumes.

For delayed recall, nearly half of the sample was impaired on HVLT-R (48.8%) and BVMT-R (46.1%), whereas a little more than a third was impaired on LM (35.7%). Better performance on all three measures was related to larger hippocampal volumes (r’s =. 26–.43, p’s < .001). Individually adding memory scores to regression models predicting hippocampal volumes improved the model fit for all measures.

Despite findings suggesting that story memory is less sensitive to memory dysfunction, it was not differentially associated with hippocampal volumes compared to other memory measures. Results support assessing memory using different formats and modalities in older adults.

Cynical hostility (CH), a specific dimension of hostility that consists of a mistrust of others, has been suggested as a high-risk trait for dementia. However, the influence of CH on the incidence of Alzheimer's disease (AD) remains poorly understood. This study investigated whether late-life CH is associated with AD risk and structural neuroimaging markers of AD.

In community-dwelling older adults from the French ESPRIT cohort (n = 1388), incident dementia rate according to CH level was monitored during an 8-year follow-up and analyzed using Cox proportional hazards regression models. Brain magnetic resonance imaging volumes were measured at baseline (n = 508). Using automated segmentation procedures (Freesurfer 6.0), the authors assessed brain grey and white volumes on all magnetic resonance imaging scans. They also measured white matter hyperintensities volumes using semi-automated procedures. Mean volumes according to the level of CH were compared using ANOVA.

Eighty-four participants developed dementia (32 with AD). After controlling for potential confounders, high CH was predictive of AD (HR 2.74; 95% CI 1.10–6.85; p = 0.030) and all dementia types are taken together (HR 2.30; 95% CI 1.10–4.80; p = 0.027). High CH was associated with white matter alterations, particularly smaller anterior corpus callosum volume (p < 0.01) after False Discovery Rate correction, but not with grey matter volumes.

High CH in late life is associated with cerebral white matter alterations, designated as early markers of dementia, and higher AD risk. Identifying lifestyle and biological determinants related to CH could provide clues on AD physiopathology and avenues for prevention strategies.

The objective of the present study was to explore the level of intestinal endotoxemia (IETM) in the model of Alzheimer disease's rats which were established by D-galactose and aluminum trichloride (AlCl3).

Adult Wistar rats were subjected to 90 days of intraperitoneal injection with D-galactose and AlCl3 to establish the Alzheimer disease's model. After the administration, the study and memory ability of the Alzheimer disease's rats were observed by Morris water maze; The level of Lipopolysaccharide (LPS) in the sera of Alzheimer disease's rats was determined by tachypleus amebocyte lysate method; The level of tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1) in the sera of Alzheimer disease's rats were determined by radioimmunity method;

Compared with the normal control, the level of LPS, TNF-α and IL-1 in the sera of Alzheimer disease's rats were markedly increased (P< 0.01).

The model of Alzheimer disease's rats which were established by D-galactose and AlCl3 is accompanied IETM.

The objective of the present study was to explore the intestinal endotoxemia (IETM) in the cell apoptosis of Alzheimer disease's rats which were established by D-galactose and aluminum trichloride (AlCl3).

Adult wistar rats were subjected to 90 days of intraperitoneal injection with D-galactose and AlCl3 to establish the Alzheimer disease's model. After the administration, the study and memory ability of the Alzheimer disease's rats were observed by Morris water maze; The level of Lipopolysaccharide (LPS) in the sera of Alzheimer disease's rats was determined by tachypleus amebocyte lysate method; The level of tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1) in the sera of Alzheimer disease's rats were determined by radioimmunity method; The apoptotic neuron was detected by TdT-mediated dUTP Nick End Labeling (TUNEL).

Compared with the normal control, the level of LPS, TNF-αin the sera and PD in the brine of Alzheimer disease's rats were markedly increased (P< 0.01).

The level of LPS, TNF-αin the sera and PD in the brine of Alzheimer disease's rats were markedly increased, IETM maybe an important reason of the apoptotic in Alzheimer disease.

Studies investigating psychiatric disorders as Alzheimer's disease (AD) risk factors have yielded heterogeneous findings. Differences in time windows between the exposure and outcome could be one explanation. We examined whether (1) mental and behavioral disorders in general or (2) specific mental and behavioral disorder categories increase the risk of AD and (3) how the width of the time window between the exposure and outcome affects the results.

A nationwide nested case-control study of all Finnish clinically verified AD cases, alive in 2005 and their age, sex and region of residence matched controls (n of case-control pairs 27,948). History of hospital-treated mental and behavioral disorders was available since 1972.

Altogether 6.9% (n = 1932) of the AD cases and 6.4% (n = 1784) of controls had a history of any mental and behavioral disorder. Having any mental and behavioral disorder (adjusted OR = 1.07, 95% CI = 1.00–1.16) or depression/other mood disorder (adjusted OR = 1.17, 95% CI = 1.05–1.30) were associated with higher risk of AD with 5-year time window but not with 10-year time window (adjusted OR, 95% CI 0.99, 0.91–1.08 for any disorder and 1.08, 0.96–1.23 for depression).

The associations between mental and behavioral disorders and AD were modest and dependent on the time window. Therefore, some of the disorders may represent misdiagnosed prodromal symptoms of AD, which underlines the importance of proper differential diagnostics among older persons. These findings also highlight the importance of appropriate time window in psychiatric and neuroepidemiology research.

The Apolipoprotein (APOE) ε4 allele increases the risk for mild cognitive impairment (MCI) and dementia, but not all carriers develop MCI/dementia. The purpose of this exploratory study was to determine if early and subtle preclinical signs of cognitive dysfunction and medial temporal lobe atrophy are observed in cognitively intact ε4 carriers who subsequently develop MCI.

Twenty-nine healthy, cognitively intact ε4 carriers (ε3/ε4 heterozygotes; ages 65–85) underwent neuropsychological testing and MRI-based measurements of medial temporal volumes over a 5-year follow-up interval; data were converted to z-scores based on a non-carrier group consisting of 17 ε3/ε3 homozygotes.

At follow-up, 11 ε4 carriers (38%) converted to a diagnosis of MCI. At study entry, the MCI converters had significantly lower scores on the Mini-Mental State Examination, Rey Auditory Verbal Learning Test (RAVLT) Trials 1–5, and RAVLT Immediate Recall compared to non-converters. MCI converters also had smaller MRI volumes in the left subiculum than non-converters. Follow-up logistic regressions revealed that left subiculum volumes and RAVLT Trials 1–5 scores were significant predictors of MCI conversion.

Results from this exploratory study suggest that ε4 carriers who convert to MCI exhibit subtle cognitive and volumetric differences years prior to diagnosis.

The Visual Cognitive Assessment Test (VCAT) is a language-neutral cognitive screening tool designed for use in culturally diverse populations without the need for translations or adaptations. While it has been established to be language-neutral, the VCAT’s construct validity has not been investigated.

471 participants were recruited, comprising 233 healthy comparisons, 117 mild cognitive impairment (MCI), and 121 mild Alzheimer’s disease (AD) patients. VCAT and domain-specific neuropsychological tests were administered in the same sitting. Construct validity was assessed by analyzing domain-specific associations between the VCAT and well-established cognitive assessments. Reliability (internal consistency) was measured by Cronbach’s alpha. Diagnostic ability (area under the curve) and recommended cutoffs were determined by receiver operating characteristic (ROC) analysis.

The VCAT and its subdomains demonstrated good construct validity in terms of both convergent and divergent validity and good internal consistency (α = .74). ROC analysis found that the VCAT was on par with the Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) at distinguishing between healthy comparisons, MCI, and mild AD. Consistent with previous studies, VCAT scores were not affected by language of administration or ethnicity in our cohort. Findings suggest the following cutoffs: Dementia 0–19, MCI 20–24, Normal 25–30.

This study established the construct validity of the VCAT, which is vital to ensure its subdomains effectively measure the cognitive processes they were designed to. The VCAT is capable of detecting early cognitive impairments and allows for meaningful cross-cultural comparisons, especially useful for international collaborations and clinical trials, and for clinical use in diverse multiethnic populations.

Misplacing objects is often reported as a clinically important symptom in dementia. Here we explored misplacing objects in relation to dementia type and stage in an online sample of individuals with dementia and their caregivers.

Participants were recruited from www.dementiaguide.com, a web-based tracker for common dementia symptoms. Users provided information about symptoms that they selected as important for monitoring. We analysed cross-sectional data from respondents who tracked at least three symptoms, which allowed for staging dementia severity.

Of 2,775 users with three-plus symptoms, 787 (28%) identified misplacing objects for symptom tracking. Misplacing objects was monitored by users across all stages of dementia, but was more prevalent in mild and severe dementia. Three common clinical subtypes of misplacing were investigated: lost & found (forgetting the location of items), hidden away (hiding items so others would not find them), and odd places (putting items in usual spots). Of the 787, 96% targeted lost & found, the most frequent type. Odd places (targeted in 56%) significantly increased with dementia severity (p < 0.001). Misplacing objects was most strongly associated with the symptoms of interaction with strangers (OR 4.60, 95% CI: 3.20-6.62), reading (3.68: 2.86-4.73), shopping (3.55: 2.73-4.61) and travel/vacationing (3.31: 2.54-4.31).

Misplacing objects was most often selected for tracking in mild and severe stages of dementia. As disease advances, misplacing more often reflects odd placement of objects rather than their simple loss. Misplacing objects may be a clinically important therapeutic target for improving patients’ quality of life and lessening caregiver burden.

The efficacy and tolerability of idalopirdine, a selective 5-hydroxytryptamine6 receptor antagonist, in patients with Alzheimer’s disease (AD) is uncertain. A systematic review and meta-analysis of randomized controlled trials (RCTs) testing idalopirdine for patients with AD was performed.

We included RCTs of idalopirdine for patients with AD and used Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog) scores as a primary measure.

Four RCTs with 2,803 patients with AD were included. There was no significant difference in ADAS-cog between the idalopirdine and placebo groups [mean difference (MD) = −0.41, P = 0.32, I2 = 62%]. However, significant heterogeneity remained. Sensitivity analysis revealed that idalopirdine was more effective than placebo for ADAS-cog in the high dose and moderate AD subgroups (high dose subgroup: MD = −2.15, P = 0.005, moderate AD subgroup: MD = −2.15, P = 0.005). Moreover, meta-regression analysis showed that idalopirdine effect size for ADAS-cog was associated with mean dose (coefficient, −0.0289), ADAS-cog at baseline (coefficient, −0.9519), and proportion of male participants (coefficient, 0.2214). For safety outcomes, idalopirdine was associated with a higher incidence of at least one adverse event and increased γ-glutamyltransferase, alanine aminotransferase, aspartate aminotransferase, and vomiting than placebo. There were no significant differences in other secondary outcomes between both treatments.

Idalopirdine is not effective for AD patients and is associated with a risk of elevated liver enzymes and vomiting. Although idalopirdine might be more effective at high doses and in moderate AD subgroups, the effect size is small and may be limited.