Journal of Alzheimer's Disease Reports

Controlled naturalistic driving for examining impacts of cognitive impairment on driving safety is rare.

Evaluating the safety among drivers with mild cognitive impairment based on near collision incidents using naturalistic driving, and investigating its correlation with cognitive measures.

Frequency of near collisions of 44 cognitively impaired [Age = 75.1(±6.7), MMSE = 25.5(±2.5)] and 19 control group drivers [Age = 72.5(±7.8), MMSE = 29.3(±0.8)] were obtained from two weeks of recorded driving. Survival time free of predicted collision based on a previously established near-collision to collision estimate ratio of 11 : 1, for 140 hours of driving exposure was calculated. Participants were also tested using Mini-Mental Status Examination (MMSE), Trail A, and Trail B. Spearman correlation and Cox survival analysis were conducted.

Near collision frequency per driving hour was correlated with MMSE (r = –0.258, p = 0.041). Survival analyses showed that cognitively impaired drivers might be prone to higher probability of having collision (p = 0.056) with a hazard ratio of 5.78 (p = 0.092). When all participants were combined, there was a significant difference (p < 0.017) in all the three cognitive measures between drivers with and without predicted collision, which were not significant within patient or control group alone (p > 0.186). Cox regression analysis showed MMSE as the only significant factor (p < 0.025) for survival time of predicted collision, but not age, gender, or driving experience.

The association between driving critical events and cognitive measures suggests that some drivers with mild cognitive impairment might have an elevated driving collision risk compared to control drivers. Standard clinical cognitive measures may be reasonable predictors.

Studies on prevalence or the therapy of dementia are rare or non-existent in Russia.

The purpose of this study was to analyze the prescription patterns of antidementia therapy in Russia in 2018.

This retrospective cross-sectional study was based on the IQVIA Russia LRx database, which covers approximately 11% of all patients enrolled in federal or regional reimbursement state healthcare programs. We descriptively analyzed the proportions of patients treated with antidementia drugs, antipsychotics, antidepressants, and benzodiazepines.

A total of 12,051 dementia patients were available for analysis. Of those, 6,394 patients had a vascular dementia (VaD) diagnosis, while 3,413 were diagnosed with dementia in other diseases (DOD), 1,128 with Alzheimer’s disease (AD), and 1,116 with unspecified dementia (UD). The therapy with the highest patient proportion was antipsychotics, with 74% of VaD patients, 73% of UD patients, and 47% of DOD patients receiving these drugs. The proportion of patients treated with antidementia drugs was 68% in AZ, 56% in VaD, 45% in UD, and only 9% in DOD. Antidepressants were a relatively rare therapy in dementia patients (between 4% and 12%), and 30% of DOD patients received benzodiazepines, while the proportions of patients receiving this therapy class in other dementias was low (7–10%). Most patients were treated with old-generation drugs.

The proportion of older drugs prescribed in Russia is higher than in Western Europe, which may likely be due to their low prices, resulting in a higher chance for successful health insurance reimbursement claims.

Diffusion tensor imaging (DTI) estimates the microstructural alterations of the brain, as a magnetic resonance imaging (MRI)-based neuroimaging technique. Prior DTI studies reported decreased structural integrity of the superficial white matter (SWM) in the brain diseases.

This study aimed to determine the diffusion characteristics of SWM in Alzheimer’s disease (AD) and mild cognitive impairment (MCI) using tractography and region of interest (ROI) approaches.

The diffusion MRI data were downloaded from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database on 24 patients with AD, 24 with MCI, and 24 normal control (NC) subjects. DTI processing was performed using DSI Studio software. First, for ROI-based analysis, The superficial white matter was divided into right and left frontal, parietal, temporal, insula, limbic and occipital regions by the Talairach Atlas, Then, for tractography-based analysis, the tractography of each of these regions was performed with 100000 seeds. Finally, the average diffusion values were extracted from voxels within the ROIs and tracts.

Both tractography and ROI analyses showed a significant difference in radial, axial and mean diffusivity values between the three groups (p < 0.05) across most of the SWM. Furthermore, The Mini-Mental State Examination was significantly correlated with radial, axial, and mean diffusivity values in parietal and temporal lobes SWM in the AD group (p < 0.05).

DTI provided information indicating microstructural changes in the SWM of patients with AD and MCI. Therefore, assessment of the SWM using DTI may be helpful for the clinical diagnosis of patients with AD and MCI.

Previous modelling found that fitness and aortic stiffness both independently predicted spatial working memory (SWM) performance in older people. There is also evidence that greater engagement in moderate intensity exercise contributes to better cognitive performance, potentially working through improving fitness and aortic stiffness.

To investigate the effect of exercise on the previously established relationships between fitness, aortic stiffness, and SWM, and whether these associations differ between older adults of higher and lower fitness.

One hundred and two residents of independent living facilities, aged 60–90 (M = 77.5, SD = 6.9) participated in the study. Measures included computerized cognitive assessment, the Six-Minute Walk fitness test, the CHAMPS physical activity questionnaire, and aortic pulse wave analysis. Multiple structural equation models were used to test hypotheses.

Overall, exercise levels had a small additional effect in predicting SWM, working exclusively through fitness, although this was only true for those of lower than average fitness. Additionally, it was found that while fitness was the most important factor in predicting SWM in those of lower fitness, aortic stiffness was the strongest predictor in those of higher fitness.

Fitness and aortic stiffness are strong predictors of cognition in older people, and greater engagement in exercise predicted better cognition in those who were of lower fitness. Fitter older people may benefit more from interventions which target aortic stiffness in order to preserve cognitive performance as they age, while those who are less fit may benefit most from improving fitness first, including through increased physical activity.

The Neuropsychiatric Inventory (NPI) is a widely used scale for the assessment of the behavioral and psychological symptoms of dementia (BPSD). We previously developed a novel dementia scale, the ABC dementia scale, in the TRIAD1412 trial and we compared the BPSD domain scores with the NPI scores. We, therefore, considered that we should investigate the quality of the NPI items using statistical approaches.

We investigated the statistical characteristics of the 12 questions or items in the Japanese version of the NPI using the item response theory. This theory is the standard approach for the development of a new assessment scale and we used it to evaluate the quality of the items in the NPI.

First, we performed factor analysis with Promax rotation to identify latent constructs in the data from 312 patients obtained in TRIAD1412. Second, following the result of the factor analysis, we divided the 12 items into domains and then investigated the characteristics of the sub-syndromes in each domain using item response category characteristic curves.

We found three latent constructs or domains: “hyperactivity,” “psychosis and apathy,” and “affect” (Cronbach’s α= 0.68) in the 12 items. Further, the items on euphoria, apathy, and appetite and eating abnormalities did not provide sufficient information to estimate BPSD severity.

The NPI item characteristics indicate that while the scale can distinguish whether patients have severe BPSD or not, it cannot estimate the degree of severity in a suspected case with a mild or unknown level of BPSD.

Brain amyloid is a neuropathological hallmark of Alzheimer’s disease (AD). By visualizing brain amyloid, positron emission tomography (PET) may influence the diagnostic assessment and management of patients with cognitive impairment.

As part of a Japanese post-approval study to measure the safety of [¹⁸F]flutemetamol PET, the association of amyloid PET results with changes in diagnosis and diagnostic confidence was assessed.

Fifty-seven subjects were imaged for amyloid PET using [¹⁸F]flutemetamol at a single Japanese memory clinic. The cognitive diagnosis and referring physician’s confidence in the diagnosis were recorded before and after availability of PET results. Imaging started approximately 90 minutes after [¹⁸F]flutemetamol administration with approximately 185 MBq injected. PET images were acquired for 30 minutes.

Amyloid PET imaging led to change in diagnosis in 15/44 clinical subjects (34%). Mean diagnostic confidence increased by approximately 20%, from 73% pre-scan to 93% post-scan, and this rise was fairly consistent across the main patient subgroups (mild cognitive impairment, AD, and non-AD) irrespective of the pre-scan diagnosis and scan result.

The study examined the utility of amyloid PET imaging in a Japanese clinical cohort and highlighted the use of an etiological diagnosis in the presence of the amyloid scan. [¹⁸F]Flutemetamol PET led to a change in diagnosis in over 30% of cases and to an increase in diagnostic confidence by approximately 20% consistent with other reports.

Preclinical studies, clinical trials, and reviews suggest increasing 3’,5’-cyclic adenosine monophosphate (cAMP) and 3’,5’-cyclic guanosine monophosphate (cGMP) with phosphodiesterase inhibitors is disease-modifying in Alzheimer’s disease (AD). cAMP/protein kinase A (PKA) and cGMP/protein kinase G (PKG) signaling are disrupted in AD. cAMP/PKA and cGMP/PKG activate cAMP response element binding protein (CREB). CREB binds mitochondrial and nuclear DNA, inducing synaptogenesis, memory, and neuronal survival gene (e.g., brain-derived neurotrophic factor) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α). cAMP/PKA and cGMP/PKG activate Sirtuin-1, which activates PGC1α. PGC1α induces mitochondrial biogenesis and antioxidant genes (e.g.,Nrf2) and represses BACE1. cAMP and cGMP inhibit BACE1-inducing NFκB and tau-phosphorylating GSK3β.

We review efficacy-testing clinical trials, epidemiology, and meta-analyses to critically investigate whether phosphodiesteraseinhibitors prevent or treat AD.

Caffeine and cilostazol may lower AD risk. Denbufylline and sildenafil clinical trials are promising but preliminary and inconclusive. PF-04447943 and BI 409,306 are ineffective. Vinpocetine, cilostazol, and nicergoline trials are mixed. Deprenyl/selegiline trials show only short-term benefits. Broad-spectrum phosphodiesterase inhibitor propentofylline has been shown in five phase III trials to improve cognition, dementia severity, activities of daily living, and global assessment in mild-to-moderate AD patients on multiple scales, including the ADAS-Cogand the CIBIC-Plus in an 18-month phase III clinical trial. However, two books claimed based on a MedScape article an 18-month phase III trial failed, so propentofylline was discontinued. Now, propentofylline is used to treat canine cognitive dysfunction, which, like AD, involves age-associated wild-type Aβ deposition.

Phosphodiesterase inhibitors may prevent and treat AD.

Alzheimer’s disease (AD) is a chronic condition that progresses over time. While several therapeutic approaches have been developed, none have substantially altered disease progression. One explanation is that the disease is multi factorial.

Using the Affirmativ Health Personal Therapeutic Program (PTPr), we sought to determine whether a comprehensive and personalized program could improve cognitive and metabolic function in individuals diagnosed with subjective cognitive impairment, mild cognitive impairment, and early stage AD.

35 individuals submitted blood samples and Montreal Cognitive Assessment (MoCA) scores, and answered intake questions. Individuals and caregivers participated in a four-day immersion program, which included Personal Therapeutic Plans (PTP), consultations with clinical practitioners, and explanations of the PTPr and PTP. Participants had follow-up by telemonitoring, with repeat blood sample analysis, updates regarding lifestyle choices, current medications and supplements, and MoCA testing at least once between 3 and 12 months after the PTPr.

By comparing baseline to follow-up testing, we determined several risk factor scores, including blood glucose and insulin levels, and levels of vitamins B12, D3, and E, improved either in the entire participant pool or specifically in individuals with measures outside the normal range for specific factors. MoCA scores were stabilized in the entire participant pool and significantly improved in individuals scoring 24 or less at baseline.

Our findings provide evidence that a comprehensive and personalized approach designed to mitigate AD risk factors can improve risk factor scores and stabilize cognitive function, warranting more extensive and placebo-controlled clinical studies.

Diabetes has been shown as a risk factor for cognitive impairments. However, it is still not clear about the time course of developing abnormal cognition in those with diabetes especially if the morbidity accelerates the cognitive deterioration process.

To study how diabetes is related to the abnormal cognition development.

A retrospective analysis was performed using data collected by the National Alzheimer’s Coordinating Center. Incidence, prevalence, and age at onset (AAO) of either mild cognitive impairment (MCI) or dementia were compared between participants with and without diabetes.

During a follow-up period of more than 10 years, the diabetic group had a higher incidence and prevalence of MCI or dementia than the non-diabetic group. However, the AAO of either MCI or dementia was independent of the diagnosis of diabetes.

Although diabetic patients have a higher incidence and prevalence of abnormal cognition than those without diabetes, diabetes does not accelerate the cognitive deterioration process.

The presence of cell cycle markers in postmortem Alzheimer’s disease (AD) brains suggest a potential role of cell cycle activation in AD. It was shown that cell cycle activation in postmitotic neurons in mice produces Aβ and tau pathologies from endogenous mouse proteins in the absence of AβPP or tau mutations.

In this study, we examined the microglial and astrocytic responses in these mice since neuroinflammation is another key pathological feature in AD.

Our neuronal cell cycle re-entry (NCCR) mouse model are bitransgenic mice heterozygous for both Camk2a-tTA and TRE-SV40T. Using this tet-off system, we triggered NCCR in our animals via neuronal expression of SV40T starting at 1 month of age. TRE-SV40T Tg mice were used as SV40T transgene controls. The animals were examined at following time points: 2, 3, 4, 6, and 12 months of age. The microglia and astrocyte responses in our mice were determined by image analysis and stereology on brain sections immunofluorescently labeled using the following antibodies: Iba1, CD45, CD68, MHCII, and GFAP. Cellular senescent marker p16 was also used in this study.

Our NCCR mice demonstrate early and persistent activation of microglia and astrocytes. Additionally, proinflammatory and senescent microglia phenotype and brain leukocyte infiltration is present at 12 months of age.

In the absence of FAD gene mutations, our NCCR mice simultaneously display many of the pathological changes associated with AD, such as ectopic neuronal cell cycle re-entry, Aβ and tau pathologies, neuroinflammation, and neurodegeneration. These animals represent a promising alternative AD mouse model.

Soluble oligomeric amyloid-β (Aβ), rather than Aβ plaques, seems to be the culprit in Alzheimer’s disease (AD). Accordingly, a new concept vaccine of small cyclic peptide conjugates, selectively targeting oligomeric Aβ, has been developed.

Study the therapeutic potential of this new vaccine in a mouse model for AD.

J20 mice, overexpressing human amyloid precursor protein, were validated for an AD-like phenotype. Then, J20 mice were vaccinated at 2, 3, and 4 months of age and AD phenotype was evaluated at 6, 9, and 12 months of age; or at 9, 10, and 11 months with evaluation at 12 months. Effects on Aβ pathology were studied by plaque load (immunohistochemistry; 6E10) and antibody titers against Aβ (ELISA). AD behavioral phenotype was evaluated by performance in a battery of cognitive tests.

J20 mice displayed age-related Aβ plaque development and an AD-like behavioral phenotype. A consistent antibody response to the cyclic peptides was, however, not extended to Aβ, leaving plaque load unaffected. Nevertheless, immunization at young ages prevented working- and short-term spatial memory loss, but deteriorated long-term spatial learning and memory, at 12 months of age. Immunization at later ages did not affect any measured parameter.

J20 mice provide a relevant model for AD to study potential anti-Aβ treatment. Early vaccination prevented short-term memory loss at later ages, but deteriorated long-term spatial memory, however without affecting Aβ pathology. Later vaccination had no effects, but optimal timing may require further investigation.

Although aging is the strongest risk factor for the development of Alzheimer’s disease (AD), it remains uncertain if the blood DNA methylation clock, which reflects the effect of biological aging on DNA methylation (DNAme) status of blood cells, may be used as a surrogate biomarker for AD pathology in the central nervous system (CNS).

We aimed to develop a practical model to predict for A/T/N-based AD biomarkers as the prediction targets using the aging acceleration of blood cells.

We obtained data of North American ADNI study participants (n = 317) whose blood DNA methylation microarray (Illumina HumanMethylation EPIC Beadchips) and cerebrospinal fluid (CSF) AD biomarkers (Aβ, t-tau, and p-tau) were recorded simultaneously. Methylation clock was calculated to conduct machine learning, in order to predict binary statuses (+ or –) for A (corresponding to the lowered CSF Aβ), T (the elevated CSF p-tau), or N (the elevated CSF t-tau). The predictive performance of the models was evaluated by area under curve (AUC) in the test subset within ADNI.

Among the 317 included samples, 194 (61.2%) were A+, 247 (77.9%) were T+, and 104 (32.8%) were N+. The degree of blood aging acceleration showed weak positive correlation with the CSF Aβ levels, even after adjustment with APOE genotype and other covariates. However, the contribution of aging acceleration to improve the predictive performance of models was not significant for any of A+, T+, or N+.

Our exploratory attempts could not demonstrate the substantial utility of the peripheral blood cells’ methylation clock as a predictor for A/T/N-based CSF biomarkers of AD, and further additional work should be conducted to determine whether the blood DNAme signatures including methylation clock have substantial utility in detecting underlying amyloid, tau or neurodegeneration pathology of AD.

Persons with Alzheimer’s disease and related dementias (ADRD) frequently experience sleep–wake (circadian) cycle disturbances that lead them to remain awake at night, causing stress and fatigue for families and caregivers. Light therapy shows promise as a nonpharmacological treatment for regulating sleep in this population.

We investigated the long-term impact of a circadian-effective lighting intervention on sleep, mood, and behavior problems in persons with ADRD.

This 25-week clinical trial administered an all-day lighting intervention to 47 patients with ADRD in 9 senior-care facilities, employing wrist-worn actigraphy measures and standardized measures of sleep quality, mood, and behavior.

The intervention significantly improved Pittsburgh Sleep Quality Index scores, from an estimated mean±SEM of 11.89±0.53 at baseline to 5.36±0.63 at the end of the intervention. Additional improvements were noted for sleep efficiency data from actigraph measurements. The intervention significantly reduced Cornell Scale for Depression in Dementia scores (mean±SEM of 11.36±0.74 at baseline and 4.18±0.88 at the end of the intervention) and Cohen-Mansfield Agitation Inventory scores (mean±SEM of 47.10±1.98 at baseline and 35.33±2.23 at the end of the intervention).

A regular circadian-effective daytime lighting intervention can improve sleep at night and reduce depression and agitation in patients with dementia living in controlled environments. More importantly, the positive effects of the tailored lighting intervention on these outcomes appear to be cumulative over time.

Processing speed, which can be assessed using the Symbol Digit Modalities Test (SDMT), is central to many brain functions. Processing speed declines with advanced age but substantial impairments are indicative of brain injury or disease.

The purpose of this study was to provide SDMT normative data for older community-dwelling individuals in the U.S. and Australia.

The ASPREE trial recruited 19,114 relatively healthy older men and women in Australia and the U.S. from the general community. All participants were without a diagnosis of dementia and with a Modified Mini-Mental State examination score of 78 or more at enrolment. The SDMT was administered at baseline as part of a neuropsychological test battery.

The median age of participants was 74 years (range 65–99), and 56% were women. The median years of education was 12. Ethno-racial differences in SDMT performance were observed and normative data were thus presented separately for 16,289 white Australians, 1,082 white Americans, 891 African-Americans, and 316 Hispanic/Latinos. There were consistent positive associations found between SDMT and education level, and negative associations between SDMT and age. Mean scores for women were consistently higher than men with the exception of Hispanic/Latinos aged ≥70 years.

This study provides comprehensive SDMT normative data for whites (Australian and U.S.), Hispanic/Latinos, and African-Americans, according to gender, age, and education level. These norms can be used clinically as reference standards to screen for cognitive impairments in older individuals.

Alzheimer’s disease (AD) is a prevalent neurodegenerative disease. Treatments are necessary to target people at high risk for AD. Inflammation, particularly tumor necrosis factor alpha (TNFα), appears to be an important marker associated with the development of AD pathophysiology. Consuming a high-fat diet induces tissue expression of TNFα.

This study investigates the relationship between nutrition, circulating inflammation, and cognition in African American women (age: M = 59.5 (±8.20) [42–73] years) at risk for developing AD.

Participants were split into high-fat and low-fat groups based on total dietary fat consumption self-reported on the Lower Mississippi Delta Nutrition Intervention Research Initiative Food Frequency Questionnaire (Delta NIRI FFQ).

A high-fat diet was associated with increased blood serum TNFα (p = 0.02) compared to the low-fat diet. In addition, global cognition scores were 9.0% better in those who consumed a higher fat diet (p = 0.04). No significant differences across groups were noted for executive function, dual-tasking, and visuospatial performance.

These results indicate that there may be multiple biological pathways involved in AD development, suggesting the need for more holistic approaches to mitigate AD-development risk.

It has been studied that nutrition can influence Alzheimer’s disease (AD) onset and progression. Some studies on rodents using intraventricular streptozotocin (STZ) injection showed that this toxin changes cerebral glucose metabolism and insulin signaling pathways.

The aim of the present study was to evaluate whether a nutritional formulation could reduce cognitive impairment in STZ-induced animals.

The rats were randomly divided into two groups: sham and STZ. The STZ group received a single bilateral STZ-ICV injection (1 mg/kg). The sham group received a bilateral ICV injection of 0.9% saline solution. The animals were treated with AZ1 formulation (Instanth^® NEO, Prodiet Medical Nutrition) (1 g/kg, PO) or its vehicle (saline solution) for 30 days, once a day starting one day after the stereotaxic surgery (n = 6–10). The rats were evaluated using the open field test to evaluate locomotor activity at day 27 after surgery. Cognitive performance was evaluated at day 28 using the object recognition test and the spatial version of the Y-maze test. At day 30, the rats were anesthetized with chloral hydrate (400 mg/kg, i.p) and euthanized in order to evaluate IBA1 in the hippocampus. The differences were analyzed using one-way ANOVA with Bonferroni’s or Kruskal Wallis with Dunn’s post-hoc test.

STZ-lesioned rats present memory impairment besides the increased microglial activation. The treatment with AZ1 formulation reversed the memory impairment observed in the object recognition test and Y-maze and also reduced IBA1 in CA1 and DG.

The cause of Alzheimer’s disease (AD) is poorly understood. Neurotropic microbes, particularly herpesviruses, might set off chronic neuroinflammation. Amyloid-β (Aβ) has antimicrobial properties and could represent a brain defense against infection.

We searched for protein sequence alignment between herpes simplex virus type I (HSV-1) HSV-2, and Aβ.

Protein data bank (pdb) structures for Aβ, HSV-1, and HSV-2 were searched on the RCSB Protein Data Bank. The protein structures were superimposed and aligned on PYMOL v 2.3.4.

For HSV-1 and Aβ, amino acid residues ser549 – his569 of HSV-1 aligned closely with residues asp7 - asn27 of Aβ. For HSV-2 and Aβ, amino acid residues of HSV-2 aligned less closely than those of HSV-1 with residues of Aβ.

Conjugating and binding to the same alpha helix in the HSV-1 protease, Aβ could be marking HSV-1 for attack by the immune system, providing a rapid inherited immune response to a destructive neurotropic virus that would otherwise require the more time-consuming involvement of T-cells, B-cells, and the adaptive immune system. But older people do not respond to viral infections as well as younger individuals. When HSV-1 infection advances in an old person, more and more amyloid is produced, forming an adhesive web. As the brain tries to hold the pathologic process in check, neuroinflammation increases and spreads. Progressive neurodegeneration and cognitive decline are the outcome.

Dementia is a spectrum of neurological diseases characterized by memory impairment and cognitive decline with the pathogenesis and effective management remaining elusive. Several studies have identified a correlation between anemia and Alzheimer’s disease and related dementias (ADRD); however, anemia subtypes and association with ADRD have yet to be studied conclusively.

To study an association between ADRD and anemia of chronic inflammation.

We conducted a retrospective case-control study of the patients, diagnosed with ADRD at Brookdale Hospital. Pair-wise comparisons between means of controls and cases in terms of iron studies and laboratory results were performed using a Mann–Whitney U test. Pair-wise comparisons between anemia subgroups (moderate and severe) were performed using a Two Sample proportion Z-Test, where for each couple of normally distributed population.

There was a total of 4,517 (1,274 ADRD group; 3,243 Control group) patients. There was significant difference in hemoglobin 10.15 versus 11.04 [p-value <0.001]. Iron studies showed a significant difference in ferritin 395±488.18 versus 263±1023.4 [p < 0.001], total iron binding capacity 225±84.08 versus 266±82.30 [p < 0.001] and serum iron level 64±39.34 versus 53±41.83 [p < 0.001]. Folic acid and vitamin B12 levels were normal in both groups. Severe and moderate anemia in the ADRD group were respectively 6.2% [95% CI: 4.2–8.4] and 13% [95% CI: 9.8–16.2] higher. Overall, incidence of moderate-to-severe anemia was found to be 19% higher in ADRD group [95% CI: 15.8–22.1].

We demonstrated an association between ADRD and anemia of chronic inflammation independent of age, renal function, and HgbA1C levels.

High magnesium intake has been associated with a decreased risk of dementia. In contrast, other research has found that both low and high serum magnesium levels were associated with an increased risk of Alzheimer’s disease and mixed dementia. Hence, presently the role of magnesium levels in dementia is unclear.

To investigate a possible association between serum magnesium concentrations and dementia in a large population-based sample.

Maccabi Healthcare Service in Israel provides healthcare to over 2 million citizens. Maccabi maintains a registry with approximately 26,000 diagnosed dementia patients. We focused on patients of both sexes with Alzheimer’s disease or mixed dementia aged 65 or older, excluding patients with clinical diagnoses that could affect serum magnesium level, or with other causes of cognitive decline. Our control group consisted of patients of the same age and sex without dementia.

No significant differences were found in mean, mode, and median magnesium levels between the dementia and control groups. However, there were marginally but significantly more cases with low magnesium levels among dementia patients than among controls: A total of 9.4% of tests done in patients with dementia and 7.81% done in non-dementia subjects were hypomagnesemic (p <  0.00001).

Despite similar means and medians of serum magnesium in dementia and controls, the proportion of lower than normal magnesium test results was slightly higher among dementia patients. It is possible that patients with dementia have more episodes of hypomagnesemia than controls, despite similar overall mean levels of magnesium.

Awareness of functional status may underlie specific profiles and differences related to stage severity in individuals with Alzheimer’s disease (AD).

This study aimed to assess self-reported experiences of awareness of functional activity in people with mild and moderate AD.

This is a mixed methods approach. The qualitative part was conducted through semi-structured interviews concerning the experiences and awareness of deficits in 38 older adults with mild or moderate AD. The quantitative approach included a comparison between groups with regard to concerns of awareness and clinic and demographic data.

Impairment on awareness of disease and awareness of functional deficits was observed even in the mild stages of AD. There was also a noticeable progression of impairments of both kinds of awareness from mild to moderate stage of disease. The majority of participants with mild and moderate AD were partially aware of their functional deficits. Both groups of participants reported some negative impact; however, they were not able to entirely describe their functional status. Also, deficits to recognize the need for help with hygiene and general tasks were observed. Significant differences were found in awareness of need for help with general tasks and awareness of need for help with hygiene tasks.

People with mild and moderate AD may describe their aware of the disease better than specific functional deficits, and most of them can provide some reports concerning to the impact of the disease.

Memory tests focused on binding may be more sensitive to diagnose Alzheimer’s disease (AD) at an early phase. TMA-93 examines relational binding by images.

Evaluate the reliability (internal consistency and inter-rater and test-retest reliability) and feasibility of the TMA-93 in a clinic setting with low-educated individuals and limited face-to-face time per patient.

The study was undertaken in a neurology outpatient clinic of a hospital in Southern Spain. The internal consistency of the TMA-93 was estimated in 35 patients with amnestic mild cognitive impairment (aMCI) and 40 healthy controls (HCs). The inter-rater reliability (by two raters) and feasibility (by recording the percentage of participants who completed the test, and by timing the administration time) were evaluated in HCs (n = 16), aMCI patients (n = 18), and mild dementia patients (n = 15). The test-retest reliability for the TMA-93 total score was studied in 51 HCs tested by the same examiner 2–4 months apart. The internal consistency was estimated by Cronbach’s alpha. The inter-rater and test-retest reliability was quantified by the intraclass correlation coefficient (ICC). The administration time was compared by diagnosis.

The internal consistency was “optimal” (Cronbach’s alpha = 0.936). The test-retest reliability was “good” [ICC = 0.802 (CI 95%  = 0.653–0.887)]. The inter-rater reliability was “optimal” [ICC = 0.999, (CI 95%  = 0.999–1)]. All participants completed the test. The administration time ranged from less than 3 min in HCs to 6 min in aMCI patients, and 7 min in mild dementia patients.

Good feasibility and reliability support using the TMA-93 for examining visual relational binding, particularly in the context of low-educational attainment and limited time per patient.

There are no studies on how the same psychosocial dementia care program is adapted to both in-home and residential care settings.

To evaluate the time investment required by professionals to implement a psychosocial dementia care program to manage neuropsychiatric symptoms.

A prospective observational study design was used. The program consisted of 1) a one-day training course, 2) three interdisciplinary discussion meetings in five months, and 3) a web-based tool for the continued assessment of neuropsychiatric symptoms. Care professionals implemented the intervention in in-home (19 in-home care management agencies and 14 multiple in-home service providers) and residential care settings (19 group homes and eight nursing homes) in Japan from October 2019 to February 2020. The level of neuropsychiatric symptoms for the participants was evaluated using the Neuropsychiatric Inventory (NPI: 0–144). The time investment was reported by participating professionals. A total of 125 persons with dementia were included at baseline.

Neuropsychiatric symptoms were significantly decreased at the final follow-up in all types of providers (Cohen’s d_rm = 0.44–0.61). The mean (SD) time required for the five-month implementation was 417.9 (219.8) minutes. There was a mean (SD) decrease of 8.6 (14.0) points in the total NPI score among the 103 persons with completed interventions. The time investment was significantly lower in in-home care management agencies than in group homes, and lower in follow-ups than at baseline assessment.

The program implementation may incur a substantial time investment regardless of setting. An additional benefit scheme to reward the time investment would be helpful to encourage implementation until the follow-ups.

Cognitive aging is a dynamic process in late life with significant heterogeneity across individuals.

To review the evidence for latent classes of cognitive trajectories and to identify the associated predictors and outcomes.

A systematic search was performed in MEDLINE and EMBASE for articles that identified two or more cognitive trajectories in adults. The study was conducted following the PRISMA statement.

Thirty-seven studies were included, ranging from 219 to 9,704 participants, with a mean age of 60 to 93.4 years. Most studies (n = 30) identified distinct cognitive trajectories using latent class growth analysis. The trajectory profile commonly consisted of three to four classes with progressively decreasing baseline and increasing rate of decline—a ‘stable-high’ class characterized as maintenance of cognitive function at high level, a ‘minor-decline’ class or ‘stable-medium’ class that declines gradually over time, and a ‘rapid-decline’ class with the steepest downward slope. Generally, membership of better classes was predicted by younger age, being female, more years of education, better health, healthier lifestyle, higher social engagement and lack of genetic risk variants. Some factors (e.g., education) were found to be associated with cognitive function over time only within individual classes.

Cognitive aging in late life is a dynamic process with significant inter-individual variability. However, it remains unclear whether similar patterns of cognitive aging are observed across all cognitive domains. Further research into unique factors which promote the maintenance of high-cognitive function is needed to help inform public policy.

Brain insulin resistance and deficiency are well-recognized abnormalities in Alzheimer’s disease (AD) and likely mediators of impaired energy metabolism. Since apolipoprotein E (APOE) is a major risk factor for late-onset AD, it was of interest to examine its potential contribution to altered insulin-linked signaling networks in the brain.

The main goal was to evaluate the independent and interactive contributions of AD severity and APOE ɛ4 dose on brain expression of insulin-related polypeptides and inflammatory mediators of metabolic dysfunction.

Postmortem fresh frozen frontal lobe tissue from banked cases with known APOE genotypes and different AD Braak stages were used to measure insulin network polypeptide immunoreactivity with a commercial multiplex enzyme-linked immunosorbent assay (ELISA).

Significant AD Braak stage and APOE genotype-related abnormalities in insulin, C-peptide, gastric inhibitory polypeptide (GIP), glucaton-like peptide-1 (GLP-1), leptin, ghrelin, glucagon, resistin, and plasminogen activator inhibitor-1 (PAI-1) were detected. The main factors inhibiting polypeptide expression and promoting neuro-inflammatory responses included AD Braak stage and APOE ɛ4/ɛ4 rather than ɛ3/ɛ4.

This study demonstrates an expanded role for impaired expression of insulin-related network polypeptides as well as neuroinflammatory mediators of brain insulin resistance in AD pathogenesis and progression. In addition, the findings show that APOE has independent and additive effects on these aberrations in brain polypeptide expression, but the impact is decidedly greater for APOE ɛ4/ɛ4 than ɛ3/ɛ4.

Alzheimer’s disease (AD) is the 6th leading cause of death in the United States and has no cure or progression prevention. The Cognitive Reserve (CR) theory poses that constant brain activity earlier in life later helps to deter pathological changes in the brain, delaying the onset of disease symptoms.

To determine the reliability and validity of the Cognitive Reserve Index questionnaire (CRIq) in AD patients.

Primary data collection was done using the CRIq to quantify CR in 90 participants. Correlations and multivariable linear regressions were used to assess reliability and validity.

Reliability was tested in 34 participants. A Pearson correlation coefficient of 0.89 (p < 0.001) indicated a strong positive correlation. Validity was tested in 33 participants. A Pearson correlation coefficient of 0.30 (p = 0.10) indicated an insignificant weak positive correlation.

The CRIq was found reliable. Gaining a better understanding of how CR tools can be used in various cognitive populations will help with the establishment of a research tool that is universally accepted as a true CR measure.

Recent evidence suggests that the accumulation of iron, specifically ferrous Fe²⁺, may play a role in the development and progression of neurodegeneration in Alzheimer’s disease (AD) through the production of oxidative stress.

To localize and characterize iron deposition and oxidation state in AD, we analyzed human hippocampal autopsy samples from four subjects with advanced AD that have been previously characterized with correlative MRI-histology.

We perform scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), and electron energy loss spectroscopy (EELS) in the higher resolution transmission electron microscope on the surface and cross-sections of specific iron-rich regions of interest.

Specific previously analyzed regions were visualized using SEM and confirmed to be iron-rich deposits using EDS. Subsequent analysis using focused ion beam cross-sectioning and SEM characterized the iron deposition throughout the 3-D volumes, confirming the presence of iron throughout the deposits, and in two out of four specimens demonstrating colocalization with zinc. Analysis of traditional histology slides showed the analyzed deposits overlapped both with amyloid and tau deposition. Following higher resolution analysis of a single iron deposit using scanning transmission electron microscope (STEM), we demonstrated the potential of monochromated STEM-EELS to discern the relative oxidation state of iron within a deposit.

These findings suggest that iron is present in the AD hippocampus and can be visualized and characterized using combined MRI and EM techniques. An altered relative oxidation state may suggest a direct link between iron and oxidative stress in AD. These methods thus could potentially measure an altered relative oxidation state that could suggest a direct link between iron and oxidative stress in AD. Furthermore, we have demonstrated the ability to analyze metal deposition alongside commonly used histological markers of AD pathology, paving the way for future insights into the molecular interactions between Aβ, tau, iron, and other putative metals, such as zinc.