Pre-dementia Stage Research Articles

New potential biomarkers of Alzheimer's disease: markers of endothelial dysfunction and neuroinflammation.

Alzheimer's disease (AD) is the most common cause of dementia in the elderly. The aim of the work wasObjective: to determine the relationship between laboratory biomarkers in blood plasma and cerebrospinal fluid (CSF) in patients with AD and indicators of neuropsychological testing.Patients and methods. 52 patients with AD were examined, in which the concentration of 90 potential biomarkers were measured in blood plasma and CSF. Neuropsychological assessment included the Mini-Mental State Exam (MMSE), Frontal Assessment Battery (FAB), Montreal Cognitive Assessment (MoCA), and etc.Results and discussion. Correlations of different strength between the values of biomarkers in blood plasma and CSF and the results of neuropsychological assessment were revealed. A correlation was found between the soluble cell adhesion molecule (sICAM-1) in blood plasma and the largest number of neuropsychological tests sensitive to dementia stages (MoCA, MMSE, FAB) in patients with AD at the dementia stage. A correlation was found between the concentration of growth/differentiation factor 15 and interferon γ in blood plasma and FAB scores in patients with AD. The levels of granulocyte colony-stimulating factor (G-CSF) in CSF were associated with the dementia stage in AD, and the interleukin-1 receptor antagonist (IL-1RA) levels, on the contrary, with stages preceding the development of dementia in AD.Conclusion. sICAM-1 level in blood plasma, which is a marker of endothelial dysfunction, may be an indicator of the severity of the vascular neurodegenerative process in AD at the dementia stage. G-CSF in the CSF is associated with the dementia stage in AD, and IL-1RA – with the pre-dementia stage of AD, which determines the prospect of their further study as diagnostic markers.

Clinical and basic science review of Alzheimer's disease

The purpose of this study is to provide a brief overview of Alzheimer's disease and a definition of moderate disability that includes (MCI). This paper focuses on the medical and cardiovascular properties of Alzheimer's disease and Parkinson's. This article also covers the recent advances in the use of biomarkers to diagnose Alzheimer's disease, as well as existing efforts to find new therapies. Alzheimer's disease (AD), the most common form of dementia, affects 50 lakh Indians aged 65 and over, or one in nine. A Clinical and Research Science Review of Alzheimer's Disease. There has been significant progress in identifying pre-dementia stages of Alzheimer's disease, such as MCI, as well as developing diagnosis and therapeutic procedures for treating Alzheimer's disease. Our ability to find a cure for Alzheimer's disease will be determined by our ability to find the right genetic markers for early diagnosis and clinical intervention in patients at risk, as well as a greater understanding of the cellular and molecular processes that go wrong. After the National Institutes of Health (NIA) recognised urgent need to develop clinically useful neuroimaging and other biomarkers for the early detection of Alzheimer's disease, the Alzheimer's Disease Neuroimaging Initiative (ADNI) was established in 2004.

Plasma biomarkers for Alzheimer\u2019s Disease in relation to neuropathology and cognitive change

Plasma biomarkers related to amyloid, tau, and neurodegeneration (ATN) show great promise for identifying these pathological features of Alzheimer’s Disease (AD) as shown by recent clinical studies and selected autopsy studies. We have evaluated ATN plasma biomarkers in a series of 312 well-characterized longitudinally followed research subjects with plasma available within 5 years or less before autopsy and examined these biomarkers in relation to a spectrum of AD and related pathologies. Plasma Aβ42, Aβ40, total Tau, P-tau181, P-tau231 and neurofilament light (NfL) were measured using Single molecule array (Simoa) assays. Neuropathological findings were assessed using standard research protocols. Comparing plasma biomarkers with pathology diagnoses and ratings, we found that P-tau181 (AUC = 0.856) and P-tau231 (AUC = 0.773) showed the strongest overall sensitivity and specificity for AD neuropathological change (ADNC). Plasma P-tau231 showed increases at earlier ADNC stages than other biomarkers. Plasma Aβ42/40 was decreased in relation to amyloid and AD pathology, with modest diagnostic accuracy (AUC = 0.601). NfL was increased in non-AD cases and in a subset of those with ADNC. Plasma biomarkers did not show changes in Lewy body disease (LBD), hippocampal sclerosis of aging (HS) or limbic-predominant age-related TDP-43 encephalopathy (LATE) unless ADNC was present. Higher levels of P-tau181, 231 and NfL predicted faster cognitive decline, as early as 10 years prior to autopsy, even among people with normal cognition or mild cognitive impairment. These results support plasma P-tau181 and 231 as diagnostic biomarkers related to ADNC that also can help to predict future cognitive decline, even in predementia stages. Although NfL was not consistently increased in plasma in AD and shows increases in several neurological disorders, it had utility to predict cognitive decline. Plasma Aβ42/40 as measured in this study was a relatively weak predictor of amyloid pathology, and different assay methods may be needed to improve on this. Additional plasma biomarkers are needed to detect the presence and impact of LBD and LATE pathology.

Association of Plasma Oligomerized Amyloid-β and Cerebral White Matter Lesions in a Health Screening Population.

Cerebral white matter lesions (WML) are related to a higher risk of vascular and Alzheimer's dementia. Moreover, oligomerized amyloid-β (OAβ) can be measured from blood for dementia screening. We aimed to investigate the relationship of plasma OAβ levels with clinical and radiological variables in a health screening population. WML, other volumetric parameters of magnetic resonance images, cognitive assessment, and plasma OAβ level were evaluated. Ninety-two participants were analyzed. The majority of participants' clinical dementia rating was 0 or 0.5 (96.7%). White matter hyperintensities (WMH) increased with age, but OAβ levels did not (r2 = 0.19, p < 0.001, r2 = 0.03, p = 0.10, respectively). No volumetric data, including cortical thickness/hippocampal volume, showed any significant correlation with OAβ. Log-WMH volume was positively correlated with OAβ (r = 0.24, p = 0.02), and this association was significant in the periventricular area. White matter signal abnormalities from 3D-T1 images were also correlated with the OAβ in the periventricular area (p = 0.039). Multivariate linear regression showed that log-WMH values were independently associated with OAβ (B = 0.879 (95% confidence interval 0.098 -1.660, p = 0.028)). Higher tertiles of WMH showed higher OAβ levels than lower tertiles showed (p = 0.044). Using a cutoff of 0.78 ng/mL, the high OAβ group had a larger WMH volume, especially in the periventricular area, than the low OAβ group (p = 0.036). Both WML and plasma OAβ levels can be early markers for neurodegeneration in the healthcare population. The lesions, especially in the periventricular area, might be related to amyloid pathogenesis, which strengthens the importance of WML in the predementia stage.

Matrix metalloproteinase 10 is linked to the risk of progression to dementia of the Alzheimer's type.

Alzheimer's disease has a long asymptomatic phase that offers a substantial time window for intervention. Using this window of opportunity will require early diagnostic and prognostic biomarkers to detect Alzheimer's disease pathology at predementia stages, thus allowing identification of patients who will most probably progress to dementia of the Alzheimer's type and benefit from specific disease-modifying therapies. Consequently, we searched for CSF proteins associated with disease progression along with the clinical disease staging. We measured the levels of 184 proteins in CSF samples from 556 subjective cognitive decline and mild cognitive impairment patients from three independent memory clinic longitudinal studies (Spanish ACE, n = 410; German DCN, n = 93; German Mannheim, n = 53). We evaluated the association between protein levels and clinical stage, and the effect of protein levels on the progression from mild cognitive impairment to dementia of the Alzheimer's type. Mild cognitive impairment subjects with increased CSF level of matrix metalloproteinase 10 (MMP-10) showed a higher probability of progressing to dementia of the Alzheimer's type and a faster cognitive decline. CSF MMP-10 increased the prediction accuracy of CSF amyloid-β 42 (Aβ42), phospho-tau 181 (P-tau181) and total tau (T-tau) for conversion to dementia of the Alzheimer's type. Including MMP-10 to the [A/T/(N)] scheme improved considerably the prognostic value in mild cognitive impairment patients with abnormal Aβ42, but normal P-tau181 and T-tau, and in mild cognitive impairment patients with abnormal Aβ42, P-tau181 and T-tau. MMP-10 was correlated with age in subjects with normal Aβ42, P-tau181 and T-tau levels. Our findings support the use of CSF MMP-10 as a prognostic marker for dementia of the Alzheimer's type and its inclusion in the [A/T/(N)] scheme to incorporate pathologic aspects beyond amyloid and tau. CSF level of MMP-10 may reflect ageing and neuroinflammation.

3-D CNN-Based Multichannel Contrastive Learning for Alzheimer’s Disease Automatic Diagnosis

Alzheimer’s disease (AD) is a common progressive neurodegenerative disease in the elderly. Mild cognitive impairment (MCI) is the symptomatic predementia stage of AD. Accurately distinguishing AD and MCI patients from normal people is the first step of the disease diagnosis. Several studies have demonstrated the potential of deep learning in the automatic diagnosis of AD and MCI using T1-weighted magnetic resonance imaging (MRI) images. In this article, we proposed an automatic classification method of AD versus normal control (NC) and MCI versus NC based on MRI images. This method used the 3-D convolutional neural network and took the whole 3-D MRI image as the input, which can obtain image information to the greatest extent. In addition, the multichannel contrastive learning strategy based on multiple data transformation methods (e.g., add noise) can combine the supervised classification loss with the unsupervised contrastive loss, which can further improve the classification accuracy and generalization ability of the network. To verify the effectiveness of our method, a large number of experiments were implemented on the ADNI dataset. The results show that our method can achieve excellent performance in accurate diagnosis of AD and MCI; the multichannel contrastive learning strategy can greatly improve the classification accuracy (AD versus NC: 4.19%; MCI versus NC: 4.57%) and generalization ability of the network.

Motoric Cognitive Risk Syndrome: Prevalence and Cognitive Performance. A cross-sectional study

Motoric Cognitive Risk Syndrome (MCR) is a predementia stage where slow gait speed and subjective memory complaints are present. The purpose of this study was to estimate the prevalence of MCR and assess its relationship with sociodemographic factors and chronic conditions. This is a secondary analysis of the SABE Colombia study conducted in 2015. The analytic sample consisted of 17·577 participants. After determining MCR prevalence, logistic regression was performed to examine the correlates of MCR. The prevalence of MCR was 10·71 %. The median age was 71 years and women composed 74·63 % of the MCR group. After adjusting for confounding variables MCR was associated with increasing age (OR 1·69, CI 1·43 - 1·92), no or low education (OR 1·99, CI 1·67- 2·37), MMSE (OR 0·93, CI 0·91 - 0·95) and chronic conditions such as mental disorders (OR 1·36, CI 1·11-1·67), history of myocardial infarction (OR 1·24, CI 1·04 - 1·47), hypertension (OR 1·23, CI 1·08 - 1·40) and diabetes (OR 1.18, CI 1.01 - 1.37). This study found a prevalence of 10·71 % of MCR in Colombian older adults. Additionally, MCR was associated with chronic conditions and sociodemographic factors identified in prior studies. These results increase the awareness of a novel predementia stage whose identification can be performed by clinicians in the outpatient clinic, minimizing the cost of a full neuropsychologic evaluation performed in a memory clinic. Funded by the Administrative Department of Science, Technology and Innovation (Colciencias) and the Ministry of Health and Social Protection of Colombia.

Motoric Cognitive Risk Syndrome: Prevalence and Cognitive Performance

Cognitive decline and dementia have a significant impact older adult. Motor Cognitive Risk Syndrome (MCRS) is a pre-dementia stage where slow gait speed and subjective memory complaints are present. MCRS increases the risk of frailty, dementia, disability, falls and overall mortality. We used data from the SABE Colombia study (Health, Well-Being, and Aging) conducted in 2015 in adults aged 60 years and older. After adjusting for confounding variables MCRS was associated with MMSE (OR 0.90, CI 0.82-0.99), pre-frail (OR 9.1, CI 3.26-25.47) and frail (OR 21.38, CI 6.30-72.57). This study found a prevalence of 5.45% of MCRS in Colombian older adults. We found an associations between cognitive performance (MMSE), frailty and MCRS. Our results increase the awareness of a pre-dementia stages different to Mild Cognitive Impairment (MCI), as these individuals are at greater risk than those with MCI to develop dementia.

Conceptual framework for the definition of preclinical and prodromal frontotemporal dementia.

The presymptomatic stages of frontotemporal dementia (FTD) are still poorly defined and encompass a long accrual of progressive biological (preclinical) and then clinical (prodromal) changes, antedating the onset of dementia. The heterogeneity of clinical presentations and the different neuropathological phenotypes have prevented a prior clear description of either preclinical or prodromal FTD. Recent advances in therapeutic approaches, at least in monogenic disease, demand a proper definition of these predementia stages. It has become clear that a consensus lexicon is needed to comprehensively describe the stages that anticipate dementia. The goal of the present work is to review existing literature on the preclinical and prodromal phases of FTD, providing recommendations to address the unmet questions, therefore laying out a strategy for operationalizing and better characterizing these presymptomatic disease stages.

Trajectories of self‐rated concerns in individuals developing cognitive decline

AbstractBackgroundSubjective perception of cognitive decline is identified as an important marker related to the risk of progression to Alzheimer's disease. However, loss of awareness has also been observed in predementia stages, potentially reducing the validity of the subjective experience. The aim of this study was to characterize the trajectories of complaints in cognitively normal (CN) individuals who later developed cognitive decline, as well as investigate differences in demographics, brain pathology and clinical progression between individuals aware and unaware of these changes.MethodWe included participants (CN at baseline) from the Harvard Aging Brain Study. Linear Mixed effect models were used to compute individual longitudinal changes of memory complaints (7 questions questionnaire) and cognition (Preclinical Alzheimer’s Cognitive Composite, PACC5). Participants who demonstrated a statistically significant PACC5 decline over time were divided into two groups: an Unaware (N=36) group defined as individuals with statistically significantly decreasing or displaying low (&lt;2.5/7) complaints, and a Heightened (N=14) group defined as individuals with significantly increasing or displaying high (&gt;2.5/7) complaints (Fig 1). Participants who did not decline in memory were assigned to the Stable group (N=248). Kaplan‐Meier survival analysis was performed to determine the rate of progression from CN to clinically impaired (MCI or dementia diagnosis) across groups.ResultNo group differences were found for gender, education, depressive symptoms or Apolipoprotein E4‐carrier status (Tab 1). Unaware participants were significantly older than the Stable group (p&lt;0.001). The Heightened and Unaware groups demonstrated equivalent amyloid burden, which was significantly greater than the Stable group (p&lt;0.01). The survival analysis revealed significant differences between all groups (p&lt;0.001,Fig 2). Heightened participants had the fastest rate of clinical progression, followed by the Unaware group.ConclusionParticipants with heightened awareness demonstrated the fastest rate of progression from cognitively normal to MCI or dementia. Importantly, among the individuals with a subsequent cognitive decline, a number of individuals (72%) were unaware of their decline. These individuals had the same demographic profile and amyloid burden as the individuals with heightened awareness. Future research will investigate the mechanisms of self‐awareness and potential dysfunction of systems underlying the loss of awareness, as it can be essential for the preservation of individual autonomy.

Cortical thinning and white matter abnormalities relate to longitudinal neuropsychiatric symptoms differentially in predementia and dementia stages

AbstractBackgroundSubjects with cognitive impairment and dementia often suffer from neuropsychiatric symptoms (NPS). Recent studies reported the association between brain structural damages and NPS. However, little is known about how domains of NPS map to region‐specific multimodal macro‐ and micro‐structural brain changes and whether the patterns vary across different cognitive stages. Importantly, most existing evidence is cross‐sectional. Here, we sought to investigate how baseline cortical thickness (CTh) and white matter (WM) microstructure influenced longitudinal progression of NPS in predementia and dementia.MethodLongitudinal neuropsychiatric inventory (NPI) total severity and subsyndrome scores (Hyperactivity, Psychosis, Affective, Apathy) over 5 years were reported in 334 memory‐clinic patients (187 cognitive impairment no dementia (CIND) and 147 dementia). All participants underwent T1‐weighted structural and diffusion MRI at baseline. A free‐water (FW) imaging method was applied to derive individual‐level WM‐FW and tissue‐compartment maps from diffusion‐MRI. The grey matter (GM) CTh was derived using Freesurfer. We examined the association of baseline WM‐FW, WM‐tissue or GM‐CTh with baseline/longitudinal NPI (total severity and sub‐syndrome) using general linear models.ResultIn CIND, higher total NPI severity was associated with widespread WM‐FW increases (fronto‐parietal projection, temporal and callosal fibres) and more focal tissue fractional‐anisotropy (FAt) reductions (fronto‐parietal/callosal fibres) cross‐sectionally (Fig‐1). Specifically, such WM‐measures were associated with affective and hyperactive sub‐syndromes, but not with psychosis and apathy. No NPI‐cortical thickness association was detected in CIND. By contrast, in dementia, GM‐CTh in frontal executive and default mode and central sensory networks, but not WM‐alteration, was related to higher total NPI severity (Fig‐2). Also, GM‐CTh was associated with apathy and psychosis, but not with affective and hyperactive sub‐syndromes.Furthermore, baseline WM‐measures were associated with longitudinal changes in total NPI severity (Fig‐3) and affective and hyperactive in CIND. By contrast, no association was found between GM‐CTh and longitudinal NPI (total and subsyndromes) in dementia.ConclusionThis study demonstrated that WM‐abnormalities, which were early marker of disease, were related to NPS in CIND, while GM‐CTh was associated with NPS in dementia. Early identification and interventions should be developed for timely management of affective and hyperactive disorders, followed up by close monitoring of the progression of cerebral structural disruptions.

Cerebrospinal fluid and blood biomarkers in the diagnostic assays of Alzheimer’s disease

The anti-amyloid-β (anti-Aβ) fibrils and soluble oligomers antibody aducanumab were approved to effectively slow down the progression of Alzheimer’s disease (AD) at higher doses in 2019, reaffirming the therapeutic effects of targeting the core pathology of AD. A timely and accurate diagnosis in the prodromal or pre-dementia stage of AD is essential for patient recruitment, stratification, and monitoring of treatment effects. AD core biomarkers amyloid-β (Aβ1−42), total tau (t-tau), and phosphorylated tau (p-tau) have been clinically validated to reflect AD-type pathological changes through cerebrospinal fluid (CSF) measurement or positron-emission tomography (PET) and found to have high diagnostic performance for AD identification in the stage of mild cognitive impairment. The development of ultrasensitive immunoassay technology enables AD pathological proteins such as tau and neurofilament light (NFL) to be measured in blood samples. However, combined biomarker detection or targeting multiple biomarkers in immunoassays will increase detection sensitivity and specificity and improve diagnostic accuracy. This review summarizes and analyzes the performance of current detection methods for early diagnosis of AD, and provides a concept of detection method based on multiple biomarkers instead of a single target, which may become a potential tool for early diagnosis of AD in the future.

Interest of cerebrospinal fluid biomarkers for prodromal Alzheimer's disease diagnosis: About 4 cases

Alzheimer's disease (AD) is the main cause of dementias. It is characterized neuropathologically by senile plaques, mainly made up of beta-amyloid peptide aggregates (especially in its AB42 form) and neurofibrillary degeneration (DNF), the main constituent of which is the Tau protein, in its hyperphosphorylated form. The prodromal phase of AD in its typical form is manifested by impairment of episodic memory, without major repercussions on autonomy. Biologically, the accumulation of the Tau protein precedes the first symptoms from 10 to 15 years. Biomarkers of AD in the cerebrospinal fluid (CSF) accessible during the patient's lifetime can testify to Alzheimer's disease. Indeed, the current stake of the diagnosis of AD, is at the pre-dementia stage, in the perspective of the development of drugs likely to act on the etiology of the disease.

Can specific nutrients, foods, or dietary patterns modulate cognitive function in (older) adults? Latest evidence from randomized controlled trials.

Epidemiological findings and results of randomized clinical trials in the last two decades have identified diet as a modifiable risk factor for cognitive decline, a predementia stage that is increasing worldwide as population ages. The literature on this critical association is expanding, making this review relevant and timely. Data from 15 trials and several systematic reviews/meta-analyses indicate that, in healthy older adults, isolated nutrients or antioxidant-rich foods usually fail to improve cognition. However, studies targeting populations at risk of cognitive decline tend to have positive results. There is ample epidemiological evidence of cognitive benefit from plant-based dietary patterns (i.e., Mediterranean diet), but more clinical trials are needed. Long-term multicomponent trials, simultaneously targeting several risk factors in patients with early dementia stages, offer promising evidence. A long-term multinutrient intervention in patients at risk for dementia appears as a sound preventive strategy. This review summarizes the latest evidence on nutrients, foods, and dietary patterns as tools to improve cognition and promote brain health. Dietary changes are important to help delay cognitive decline, particularly in populations more at risk. Large-scale strategies based on healthy diets combined with other health-promoting lifestyle changes should be a public health priority.

Personalized prediction of progression in pre-dementia patients based on individual biomarker profile: A development and validation study.

The prognosis of patients at the pre-dementia stage is difficult to define. The aim of this study is to develop and validate a biomarker-based continuous model for predicting the individual cognitive level at any future moment. In addition to personalized prognosis, such a model could reduce trial sample size requirements by allowing inclusion of a homogenous patient population. Disease-progression modeling of longitudinal cognitive scores of pre-dementia patients (baseline Clinical Dementia Rating ≤ 0.5) was used to derive a biomarker profile that was predictive of patient's cognitive progression along the dementia continuum. The biomarker profile model was developed and validated in the MEMENTO cohort and externally validated in the Alzheimer's Disease Neuroimaging Initiative. Of nine candidate biomarkers in the development analysis, three cerebrospinal fluid and two magnetic resonance imaging measures were selected to form the final biomarker profile. The model-based prognosis of individual future cognitive deficit was shown to significantly improve when incorporating biomarker information on top of cognition and demographic data. In trial power calculations, adjusting the primary analysis for the baseline biomarker profile reduced sample size requirements by ≈10%. Compared to conventional cognitive cut-offs, inclusion criteria based on biomarker-profile cut-offs resulted in up to 28% reduced sample size requirements due to increased homogeneity in progression patterns. The biomarker profile allows prediction of personalized trajectories of future cognitive progression. This enables accurate personalized prognosis in clinical care and better selection of patient populations for clinical trials. A web-based application for prediction of patients' future cognitive progression is available online.

Sex differences in psychotropic and analgesic drug use before and after initiating treatment with acetylcholinesterase inhibitors.

Background/aimsThe aim was to explore the impact of sex on prevalence, patterns and trends in the prescription of psychotropics and analgesics in users of acetylcholinesterase inhibitors (AChEIs), before and after AChEI initiation, compared to the general population.MethodsA prospective study applying data from the Norwegian Prescription Database (NorPD) in the period 2004–2016. Prescription of antidepressants, antipsychotics, analgesics including opioids, benzodiazepines and z-hypnotics in persistent AChEI users was studied in a follow-up period from four years before to two years after AChEI initiation in men and women of four age groups: 37–64, 65–72, 73–80 and 81–88 years.ResultsUse of antidepressants, antipsychotics and weaker analgesics increased in both sexes during the follow-up period in 11.764 persistent AChEI users. Women with pre-dementia and dementia stages of AD showed a prescription pattern with more use of psychotropics and opioids than men, except for antipsychotics.ConclusionFemale sex showed to have a significant influence on the prescriptions of psychotropics and analgesics in AD patients in a pre-dementia and dementia stage. The exception is for antipsychotics, that men used more than women. The prescription pattern showed a higher extent of polypharmacy of psychotropics and/or opioids in women than in men. The total prescription pattern of analgesics could indicate an undertreatment of pain in pre-dementia and dementia stages, most pronounced in men.

Familiarity in Mild Cognitive Impairment as a Function of Patients' Clinical Outcome 4 Years Later.

The current study addresses the nature of memory difficulties in amnestic mild cognitive impairment (aMCI). Whereas recollection is consistently found to be impaired in aMCI, the results on familiarity are divergent. One potential factor that could explain this divergence in findings relates to the heterogeneity of aMCI patients, so that only those aMCI patients who develop Alzheimer disease (AD) may present with impaired familiarity. The present study aimed at testing this hypothesis. A group of 45 aMCI patients and a group of 26 healthy older adults performed a verbal recognition memory test with the Remember/Know paradigm to assess recollection and familiarity processes. All participants were followed for 4 years with clinical and neuropsychological testing. At the end of follow-up, 22 aMCI patients progressed to AD and 23 aMCI patients remained stable. Initial memory performance was compared between the 3 groups. Whereas recollection was severely diminished in all aMCI patients, familiarity accuracy (and consequently global recognition accuracy) was found to be impaired only in aMCI patients who subsequently developed AD. These findings suggest that the enrichment of the aMCI population with predementia stage patients may modulate the likelihood to observe familiarity deficits, and impaired global recognition accuracy may accompany incipient AD.

Acute Exercise and Cognitive Function in Alzheimer's Disease.

Many studies have shown the impact of acute aerobic exercises (AAE) on cognition in healthy adults or at a pre-dementia stage. Few studies, however, have explored the positive effects of AAE in moderate Alzheimer's disease (ADM) patients. Evaluating the effect of AAE on cognitive functions in ADM patients. Overall, 79 (age: 69.62±0.99) ADM patients were recruited. Participants were divided into three groups according to the task: aerobic exercises done alone or combined with cognitive games presented on a screen, and a control group who performed a reading task. The aerobic exercise protocol consisted of a 20-min cycling exercise of moderate intensity, corresponding to 60%of the individual target maximal heart rate recorded in a 6-minute walking test. The participants' cognition was monitored before and after the intervention using the Tower of Hanoi, Digit Span, and Stroop tasks. After the exercise, the participants' attention in both the physical and combined groups improved for the Stroop, the forward and backward Digit Span tasks, as well as the time taken to solve the Tower of Hanoi, although no significant differences were found in the number of moves taken in the latter. By contrast, the control group did not show any significant improvement for most of the cognitive tasks after the reading session. Current evidence suggests that AAE may help to improve cognitive functions in ADM patients. This improvement is enhanced when the exercise is combined with cognitive games. Safe and progressive types of exercises should be promoted among ADM patients.

Serum and cerebrospinal fluid Neutrophil gelatinase-associated lipocalin (NGAL) levels as biomarkers for the conversion from mild cognitive impairment to Alzheimer's disease dementia

Neutrophil gelatinase-associated lipocalin (NGAL) is an acute phase protein that has been reported as a potential marker for pre-dementia stages of Alzheimer's disease (AD). Longitudinal studies for its association with the conversion of mild cognitive impairment to AD is still lacking. This study included n = 268 study participants with subjective cognitive decline (SCD) (n=82), mild cognitive impairment (MCI) (n=98) and AD dementia (n=88) at baseline and two-year follow-up clinical assessments. Serum and cerebrospinal fluid (CSF)NGAL, CSF amyloid beta1-42, total-Tau, and phospho-Tau levels were measured with ELISA analysis. CSF NGAL levels were significantly lower in MCI participants compared to people with SCD at baseline. Lower baseline CSF NGAL levels predicted MCI converters to AD dementia vs. non-converters after 2-years follow-up. A positive correlation between CSF NGAL and amyloid beta1-42 was found particularly in MCI participants at baseline. NGAL in CSF holds potential to be used as a predictive marker for the conversion of MCI to AD dementia and may reflect pathophysiological processes of prodromal AD neuropathology.

Severity and treatment of cognitive impairment

With an increase in life expectancy in the population, the proportion of people with cognitive impairment (CI) increases. Modern neurology focuses on the milder forms of CI: moderate, mild, and subjective CI, which are more promising in terms of successful treatment and slowing down their progression. Age is the leading risk factor for CI, the prevalence of which in the general population of people aged over 65 years reaches 10–15%. The primary role in CI development is played by Alzheimer's disease, cerebrovascular diseases, mixed vascular-neurodegenerative process, and other types of neurodegenerative diseases, and all of them share some pathophysiological mechanisms. Correction of vascular risk factors plays a leading role in the treatment of pre-dementia stages of CI. The possibilities of using nimodipine in the therapy of CI are analyzed.