Objective Physical Function in the Alzheimer's Disease Continuum: Association with Cerebrospinal Fluid Biomarkers in the ALBION Study.

Cognitive and physical decline, both indicators of aging, seem to be associated with each other. The aim of the present study was to investigate whether physical function parameters (walking time and handgrip strength) are related to cerebrospinal fluid (CSF) biomarkers (amyloid-beta Aß42, Tau, PhTau) in individuals in the Alzheimer's disease (AD) continuum. The sample was drawn from the Aiginition Longitudinal Biomarker Investigation of Neurodegeneration study, comprising 163 individuals aged 40-75 years: 112 cognitively normal (CN) and 51 with mild cognitive impairment (MCI). Physical function parameters were measured at baseline, a lumbar puncture was performed the same day and CSF biomarkers were analyzed using automated methods. The association between walking time, handgrip strength and CSF biomarkers was evaluated by linear correlation, followed by multivariate linear regression models adjusted for age, sex, education and APOEe4 genotype. Walking time was inversely related to CSF Aß42 (lower CSF values correspond to increased brain deposition) in all participants (p < 0.05). Subgroup analysis showed that this association was stronger in individuals with MCI and participants older than 60 years old, a result which remained statistically significant after adjustment for the aforementioned confounding factors. These findings may open new perspectives regarding the role of mobility in the AD continuum.

Initial Data and a Clinical Diagnosis Transition for the Aiginition Longitudinal Biomarker Investigation of Neurodegeneration (ALBION) Study.

Background and Objectives: This article presents data from the ongoing Aiginition Longitudinal Biomarker Investigation of Neurodegeneration study (ALBION) regarding baseline clinical characterizations and CSF biomarker profiles, as well as preliminary longitudinal data on clinical progression. Materials and Methods: As of March 2022, 138 participants who either were cognitively normal (CN, n = 99) or had a diagnosis of mild cognitive impairment (MCI, n = 39) had been recruited at the specialist cognitive disorders outpatient clinic at Aiginition Hospital. Clinical characteristics at baseline were provided. These patients were followed annually to determine progression from CN to MCI or even dementia. CSF biomarker data (amyloid ß1-42, phosphorylated tau at threonine 181, and total tau) collected using automated Elecsys® assays (Roche Diagnostics) were available for 74 patients. These patients were further sorted based on the AT(N) classification model, as determined by CSF Aß42 (A), CSF pTau (T), and CSF tTau (N). Results: Of the 49 CN patients with CSF biomarker data, 21 (43%) were classified as exhibiting "Alzheimer's pathologic change" (A+Τ− (Ν)−) and 6 (12%) as having "Alzheimer's disease" (A+T−(N)+, A+T+(N)−, or A+T+(N)+). Of the 25 MCI patients, 8 (32%) displayed "Alzheimer's pathologic change", and 6 (24%) had "Alzheimer's disease". A total of 66 individuals had a mean follow-up of 2.1 years (SD = 0.9, min = 0.8, max = 3.9), and 15 of those individuals (22%) showed a clinical progression (defined as a worsening clinical classification, i.e., from CN to MCI or dementia or from MCI to dementia). Overall, participants with the "AD continuum" AT(N) biomarker profile (i.e., A+T−(N)−, A+T−(N)+, A+T+(N)−, and A+T+(N)+) were more likely to clinically progress (p = 0.04). Conclusions: A CSF "AD continuum" AT(N) biomarker profile is associated with an increased risk of future clinical decline in CN or MCI subjects.

Cerebral Amyloidosis in Individuals with Subjective Cognitive Decline: From Genetic Predisposition to Actual Cerebrospinal Fluid Measurements.

The possible relationship between Subjective Cognitive Decline (SCD) and dementia needs further investigation. In the present study, we explored the association between specific biomarkers of Alzheimer's Disease (AD), amyloid-beta 42 (Aß42) and Tau with the odds of SCD using data from two ongoing studies. In total, 849 cognitively normal (CN) individuals were included in our analyses. Among the participants, 107 had available results regarding cerebrospinal fluid (CSF) Aß42 and Tau, while 742 had available genetic data to construct polygenic risk scores (PRSs) reflecting their genetic predisposition for CSF Aß42 and plasma total Tau levels. The associations between AD biomarkers and SCD were tested using logistic regression models adjusted for possible confounders such as age, sex, education, depression, and baseline cognitive test scores. Abnormal values of CSF Aß42 were related to 2.5-fold higher odds of SCD, while higher polygenic loading for Aß42 was associated with 1.6-fold higher odds of SCD. CSF Tau, as well as polygenic loading for total Tau, were not associated with SCD. Thus, only cerebral amyloidosis appears to be related to SCD status, either in the form of polygenic risk or actual CSF measurements. The temporal sequence of amyloidosis being followed by tauopathy may partially explain our findings.

Long COVID-19 Symptoms in People with Dementia or Mild Cognitive Impairment.

What is the impact of long COVID-19 on people with mild cognitive impairment (MCI) or dementia? Self-reported questionnaire was used for the report of long COVID-19 symptoms. People with MCI or dementia or their caregivers regarding patients' health were recruited COVID-19 throughout from the Athens Alzheimer's Association. We included 72 participants. Thirty had the diagnosis of MCI and 39 had dementia. Most symptoms lasted for 3-4 weeks. The majority of patients reported having all the symptoms, with fatigue being the major disturbance. The diagnosis and the management of long COVID-19 symptoms requires a more holistic and comprehensive approach.

A Candidate microRNA Profile for Early Diagnosis of Sporadic Alzheimer's Disease.

Background: Late-onset or sporadic Alzheimer's disease (sAD) is a neurodegenerative disease leading to cognitive impairment and memory loss. The underlying pathological changes take place several years prior to the appearance of the first clinical symptoms, however, the early diagnosis of sAD remains obscure. Objective: To identify changes in circulating microRNA (miR) expression in an effort to detect early biomarkers of underlying sAD pathology. Methods: A set of candidate miRs, earlier detected in biofluids from subjects at early stage of sAD, was linked to the proposed tau-driven adverse outcome pathway for memory loss. The relative expression of the selected miRs in serum of 12 cases (mild cognitive impairment, MCI) and 27 cognitively normal subjects, recruited within the ongoing Aiginition Longitudinal Biomarker Investigation Of Neurodegeneration (ALBION) study, was measured by RT-qPCR. Data on the protein levels of amyloid-ß (Aß42) and total/phosphorylated tau (t-tau/p-tau), in cerebrospinal fluid (CSF), and the cognitive z-scores of the participants were also retrieved. Results: Each doubling in relative expression of 13 miRs in serum changed the odds of either having MCI (versus control), or having pathological Aß42 or pathological Aß42 and tau (versus normal) proteins in their CSF, or was associated with the global composite z-score. Conclusion: These candidate human circulating miRs may be of great importance in early diagnosis of sAD. There is an urgent need for confirming these proposed early predictive biomarkers for sAD, contributing not only to societal but also to economic benefits.

The Effect of Prolonged Lockdown Due to COVID-19 on Greek Demented Patients of Different Stages and on Their Caregivers.

BACKGROUND: The impact of the new coronavirus disease (COVID-19) is deteriorating as time passes and the virus keeps spreading, with people with dementia and their caregivers being affected significantly. OBJECTIVE: The aim of this study was to examine the effect of prolonged isolation because of the COVID-19 pandemic on people with dementia and their caregivers. METHODS: Caregivers answered online questions regarding their own physical and psychological burden, and of the person they take care of. Participants were mostly members of online seminars of the Athens Alzheimer's Association. Questions referred to their own burden, the overall decline of the persons they take care of, and changes in specific domains as well. Further, participants were asked about any changes between the two major lockdown periods. Analysis was performed including the total sample and then, by three different stages of dementia. RESULTS: A total of 339 caregivers took part in the study. Results indicated significant decline, both in an overall aspect of the people with dementia, and in specific domains (mostly communication and mood). Regarding the caregivers, they reported having significantly increased physical and psychological burden, and also, noticing an overall change between the two lockdown periods in their own burden. Analysis by dementia-stage group indicated that significant decline occurred both in the middle-stage and the late-stage group. CONCLUSION: An urgency for further support of both the people with neurodegenerative disorders and their caregivers is needed. Collaboration among care workers, online programs, governmental support, and day-care centers should be planned to ensure continuity of care for those in need during the pandemic.