Blood Biomarkers of Alzheimer's Disease and Cognition: A Literature Review.

Recent advances in blood-based biomarkers of Alzheimer's Disease (AD) show great promise for clinical applications, offering a less invasive alternative to current cerebrospinal fluid (CSF) measures. However, the relationships between these biomarkers and specific cognitive functions, as well as their utility in predicting longitudinal cognitive decline, are not yet fully understood. This descriptive review surveys the literature from 2018 to 2023, focusing on the associations of amyloid-ß (Aß), Total Tau (t-Tau), Phosphorylated Tau (p-Tau), Neurofilament Light (NfL), and Glial Fibrillary Acidic Protein (GFAP) with cognitive measures. The reviewed studies are heterogeneous, varying in design and population (cognitively unimpaired, cognitively impaired, or mixed populations), and show results that are sometimes conflicting. Generally, cognition positively correlates with Aß levels, especially when evaluated through the Aß42/Aß40 ratio. In contrast, t-Tau, p-Tau, Nfl, and GFAP levels typically show a negative correlation with cognitive performance. While p-Tau measures generally exhibit stronger associations with cognitive functions compared to other biomarkers, no single blood marker has emerged as being predominantly linked to a specific cognitive domain. These findings contribute to our understanding of the complex relationship between blood biomarkers and cognitive performance and underscore their potential utility in clinical assessments of cognition.

Risk of cognitive decline progression is associated to increased blood-brain-barrier permeability: A longitudinal study in a memory unit clinical cohort.

INTRODUCTION: This study examined the relationship between blood-brain-barrier permeability (BBBp), measured by cerebrospinal fluid/serum albumin ratio (QAlb), and cognitive decline progression in a clinical cohort. METHODS: This prospective observational study included 334 participants from the BIODEGMAR cohort. Cognitive decline progression was defined as an increase in Global Deterioration Scale and/or Clinical Dementia Rating scores. Associations between BBBp, demographics, and clinical factors were explored. RESULTS: Male sex, diabetes mellitus, and cerebrovascular burden were associated with increased log-QAlb. Vascular cognitive impairment patients had the highest log-QAlb levels. Among the 273 participants with valid follow-up data, 154 (56.4%) showed cognitive decline progression. An 8% increase in the hazard of clinical worsening was observed for each 10% increase in log-QAlb. DISCUSSION: These results suggest that increased BBBp in individuals with cognitive decline may contribute to clinical worsening, pointing to potential targeted therapies. QAlb could be a useful biomarker for identifying patients with a worse prognosis.

NEURONORMA Cognitive Battery Associations with Cerebrospinal Fluid Amyloid-ß and Tau Levels in the Continuum of Alzheimer's Disease.

BACKGROUND: Neuropsychological assessments are essential to define the cognitive profile and contribute to the diagnosis of Alzheimer's disease (AD). The progress in knowledge about the pathophysiological process of the disease has allowed conceptualizing AD through biomarkers as a biological continuum that encompasses different clinical stages. OBJECTIVE: To explore the association between cerebrospinal fluid (CSF) biomarkers of AD and cognition using the NEURONORMA battery, in a sample of cognitively unimpaired (CU), mild cognitive impaired (MCI), and mild dementia of the Alzheimer type (DAT) subjects, and to characterize the cognitive profiles in MCI subjects classified by A/T/N system. METHODS: 42 CU, 35 MCI, and 35 mild DAT were assessed using the NEURONORMA battery. Core AD biomarkers [amyloid-ß42 (Aß42) peptide, total tau (t-tau), and phosphorylated tau 181 (p-tau181)] proteins were measured in CSF. Correlation coefficients, multivariate regression, and effect sizes were calculated. We explored the age- and education-adjusted cognitive profiles by A/T/N variants within the MCI group. RESULTS: Cognitive outcomes were directly associated with CSF Aß42 and inversely with CSF tau measures. We found differences in both biomarkers and cognitive outcomes comparing all pairs except for CSF measures between cognitively impaired groups. The highest effect size was in memory tasks and biomarkers ratios. Lower performances were in memory and executive domains in MCI subjects with AD pathology (A+T+N±) compared to those with normal levels of AD biomarkers (A- T- N). CONCLUSION: This study provides further evidence of the validity of Spanish NEURONORMA cognitive battery to characterize cognitive impairment in the AD pathological continuum.

Plasma and CSF biomarkers in a memory clinic: Head-to-head comparison of phosphorylated tau immunoassays.

INTRODUCTION: Direct comparisons of the main blood phosphorylated tau immunoassays in memory clinic populations are needed to understand possible differences. METHODS: In the BIODEGMAR study, 197 participants presenting with cognitive complaints were classified into an Alzheimer's disease (AD) or a non-AD cerebrospinal fluid (CSF) profile group, according to their amyloid beta 42/ phosphorylated tau (Aß42/p-tau) ratio. We performed a head-to-head comparison of nine plasma and nine CSF tau immunoassays and determined their accuracy to discriminate abnormal CSF Aß42/p-tau ratio. RESULTS: All studied plasma tau biomarkers were significantly higher in the AD CSF profile group compared to the non-AD CSF profile group and significantly discriminated abnormal CSF Aß42/p-tau ratio. For plasma p-tau biomarkers, the higher discrimination accuracy was shown by Janssen p-tau217 (r = 0.76; area under the curve [AUC] = 0.96), ADx p-tau181 (r = 0.73; AUC = 0.94), and Lilly p-tau217 (r = 0.73; AUC = 0.94). DISCUSSION: Several plasma p-tau biomarkers can be used in a specialized memory clinic as a stand-alone biomarker to detect biologically-defined AD. HIGHLIGHTS: Patients with an Alzheimer's disease cerebrospinal fluid (AD CSF) profile have higher plasma phosphorylated tau (p-tau) levels than the non-AD CSF profile group. All plasma p-tau biomarkers significantly discriminate patients with an AD CSF profile from the non-AD CSF profile group. Janssen p-tau217, ADx p-tau181, and Lilly p-tau217 in plasma show the highest accuracy to detect biologically defined AD. Janssen p-tau217, ADx p-tau181, Lilly p-tau217, Lilly p-tau181, and UGot p-tau231 in plasma show performances that are comparable to their CSF counterparts.

Effects of COVID-19 Pandemic Confinement in Patients With Cognitive Impairment.

Introduction: State of emergency caused by COVID-19 pandemic and subsequent lockdown hit Spain on 14th March 2020 and lasted until 21st June 2020. Social isolation measures were applied. Medical attention was focused on COVID-19. Primary and social care were mainly performed by telephone. This exceptional situation may affect especially vulnerable patients such as people living with dementia. Our aim was to describe the influence of restrictive measures on patients living with mild cognitive decline and dementia evaluating SARS-CoV2 infection, changes in routines, cognitive decline stage, neuropsychiatric symptoms, delirium, falls, caregiver stress, and access to sanitary care. Materials and Methods: We gathered MCI and dementia patients with clinical follow-up before and after confinement from DegMar registry (Hospital del Mar). A telephone ad-hoc questionnaire was administered. Global status was assessed using CDR scale. Changes in neuropsychiatric symptoms were assessed by Neuropsychiatric Inventory (NPI) and retrospective interview for pre-confinement base characteristics. Results: We contacted a total of 60 patients, age 75.4 years ± 5,192. 53.3% were women. Alzheimer's Disease (41.7%) and Mild Cognitive Impairment (25%) were the most prevalent diagnosis. Remaining cases included different dementia disorders. A total of 10% of patients had been diagnosed with SARS-CoV-2. During confinement 70% of patients abandoned previous daily activities, 60% had cognitive worsening reported by relatives/caretakers, 15% presented delirium episodes, and 13% suffered increased incidence of falls. Caregivers reported an increased burden in 41% cases and burnout in 11% cases. 16% reported difficulties accessing medical care, 33% received medical phone assistance, 20% needed emergency care and 21% had changes in psychopharmacological therapies. Neuropsychiatric profile globally worsened (p < 0.000), also in particular items like agitation (p = 0.003), depression (p < 0.000), anxiety (p < 0.000) and changes in appetite (p = 0.004). Conclusion: SARS-CoV2-related lockdown resulted in an important effect over social and cognitive spheres and worsening of neuropsychiatric traits in patients living with mild cognitive decline and dementia. Although the uncertainty regarding the evolution of the pandemic makes strategy difficult, we need to reach patients and caregivers and develop adequate strategies to reinforce and adapt social and health care.

Clinical management of patients with advanced Parkinson's disease treated with continuous intestinal infusion of levodopa/carbidopa.

Patients with Parkinson's disease often have a good initial response to dopaminergic therapy but later usually develop motor fluctuations and dyskinesia. In these patients, continuous infusion of levodopa-carbidopa intestinal gel (LCIG) allows for maintaining adequate dopamine levels and for improving motor and nonmotor symptoms, as well as quality of life and autonomy. Adequate candidate selection and follow-up are crucial for treatment success. Management should be multidisciplinary, and patient and caregiver education is a priority. This expert consensus document has been developed by a team of neurologists, gastroenterologists and nurses who have a vast experience in LCIG therapy, with an intention to provide knowledge and tools to facilitate patient management throughout all phases of LCIG treatment process.

Efficacy of long-term continuous subcutaneous apomorphine infusion in advanced Parkinson's disease with motor fluctuations: a multicenter study.

Continuous subcutaneous apomorphine infusion (CSAI) is, at present, an alternative option for advanced Parkinson's disease (PD) with motor fluctuations. We studied the evolution of patients with PD and severe motor fluctuations long-term treated with CSAI. We reviewed data from 82 patients with PD (mean age, 67 +/- 11.07; disease duration, 14.39 +/- 5.7 years) and severe motor fluctuations referred to 35 tertiary hospitals in Spain. These patients were long-term treated (for at least 3 months) with CSAI and tolerated the procedure without serious side effects. We compared the baseline data of these 82 patients (before CSAI) with those obtained from the last follow-up visit of each patient. The mean follow-up of CSAI was 19.93 +/- 16.3 months. Mean daily dose of CSAI was 72.00 +/- 21.38 mg run over 14.05 +/- 1.81 hours. We found a statistically significant reduction in off-hours, according to self-scoring diaries (6.64 +/- 3.09 vs. 1.36 +/- 1.42 hours/day, P < 0.0001), total and motor UPDRS scores (P < 0.0001), dyskinesia severity (P < 0.0006), and equivalent dose of antiparkinsonian therapy (1,405 +/- 536.7 vs. 800.1 +/- 472.9 mg of levodopa equivalent units P < 0.0001). CSAI is an effective option for patients with PD and severe fluctuations, poorly controlled by conventional oral drug treatment.