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1.
Transl Neurodegener ; 12(1): 5, 2023 Jan 30.
Article in English | MEDLINE | ID: mdl-36717892

ABSTRACT

The impact of coronavirus disease 2019 (COVID-19) pandemic on patients with neurodegenerative diseases and the specific neurological manifestations of COVID-19 have aroused great interest. However, there are still many issues of concern to be clarified. Therefore, we review the current literature on the complex relationship between COVID-19 and neurodegenerative diseases with an emphasis on Parkinson's disease (PD) and Alzheimer's disease (AD). We summarize the impact of COVID-19 infection on symptom severity, disease progression, and mortality rate of PD and AD, and discuss whether COVID-19 infection could trigger PD and AD. In addition, the susceptibility to and the prognosis of COVID-19 in PD patients and AD patients are also included. In order to achieve better management of PD and AD patients, modifications of care strategies, specific drug therapies, and vaccines during the pandemic are also listed. At last, mechanisms underlying the link of COVID-19 with PD and AD are reviewed.


Subject(s)
Alzheimer Disease , COVID-19 , Neurodegenerative Diseases , Parkinson Disease , Humans , Alzheimer Disease/diagnosis , Alzheimer Disease/epidemiology , Alzheimer Disease/therapy , Parkinson Disease/diagnosis , Parkinson Disease/epidemiology , Parkinson Disease/therapy , Disease Progression
2.
Curr Opin Psychiatry ; 36(2): 126-133, 2023 Mar 01.
Article in English | MEDLINE | ID: mdl-36705011

ABSTRACT

PURPOSE OF REVIEW: Young-onset dementia (YOD) refers to a dementia for which symptom onset occurs below the age of 65. This review summarizes the recent literature in this area, focusing on updates in epidemiology, diagnosis and service provision. RECENT FINDINGS: In the last year, internationally, the prevalence of YOD was reported as 119 per 100 000, but this may vary according to population types. Although the commonest causes of YOD are Alzheimer's disease (AD) and frontotemporal dementia (FTD), there is increasing recognition that YOD is diagnostically and phenotypically broader than AD and FTD. YOD may be due to many other diseases (e.g. Huntington's disease, vascular dementia) whereas accumulation of the same protein (e.g. amyloid protein) may lead to different phenotypes of Alzheimer's disease (such as posterior cortical atrophy and behavioural-variant/frontal-variant AD). This heterogeneity of phenotypic presentation is also seen in YOD due to known genetic mutations. Biomarkers such as plasma and cerebrospinal fluid proteins, neuroimaging and genetics have shown promise in the early identification of YOD as well as providing further understanding behind the overlap between psychiatric and neurodegenerative conditions occurring in younger people. The management of YOD needs to consider age-specific issues for younger people with dementia and their family networks together with better integration with other health services such as aged, disability and improved access to services and financial assistance. SUMMARY: These findings emphasize the need for early identification and appropriate age-specific and person-centred management for people with young-onset dementia.


Subject(s)
Alzheimer Disease , Frontotemporal Dementia , Humans , Alzheimer Disease/diagnosis , Frontotemporal Dementia/diagnosis , Age of Onset
3.
Curr Opin Psychiatry ; 36(2): 119-125, 2023 Mar 01.
Article in English | MEDLINE | ID: mdl-36705010

ABSTRACT

PURPOSE OF REVIEW: Dementia is a syndrome with several possible pathologies. To date, definitive methods for diagnosis and treatment of sub-types of dementia have not been established. Emerging evidence suggests that exosomes can provide important information for the diagnosis and treatment of several subtypes of dementia. This article reviews recent studies on the application of exosomes in dementia. RECENT FINDINGS: Exosomes are involved in the pathogenesis of Alzheimer's disease (AD) and Parkinson's disease (PD) through transporting toxic proteins such as amyloid beta (Aß), tau, and α-synuclein. Exosomal microRNAs (miR) and proteins reflect the disease state, and therefore, exosomes can be used as diagnostic markers for diseases such as AD, PD, Huntington's disease (HD), vascular dementia (VaD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD). Mesenchymal stem cell (MSC)-derived exosomes have been shown to ameliorate disease pathology, and improve cognitive function in AD, PD, and VAD. SUMMARY: Recent studies have shown that exosomes could be novel diagnostic agents for dementia because they contain molecules that could be potential biomarker candidates indicative of the type and stage of dementia. Therapeutic application of exosomes in dementia has revealed that exosomes only, or exosomes loaded with an active pharmaceutical ingredient (API), ameliorate disease phenotype of dementia. Further work is needed to exploit this potential.


Subject(s)
Alzheimer Disease , Exosomes , Lewy Body Disease , Parkinson Disease , Humans , Lewy Body Disease/diagnosis , Lewy Body Disease/therapy , Lewy Body Disease/metabolism , Amyloid beta-Peptides/metabolism , Exosomes/metabolism , Exosomes/pathology , Alzheimer Disease/diagnosis , Alzheimer Disease/therapy , Alzheimer Disease/metabolism , Parkinson Disease/diagnosis , Parkinson Disease/therapy , Parkinson Disease/metabolism , tau Proteins/metabolism , Biomarkers/metabolism
4.
JAMA Netw Open ; 6(1): e2252387, 2023 Jan 03.
Article in English | MEDLINE | ID: mdl-36692879

ABSTRACT

Importance: Previous research has suggested an association of kidney function with risk of Alzheimer disease (AD) or other dementias and dementia-related blood biomarkers, but a distinct association remains unclear. Objective: To evaluate the association of kidney function with risk of diagnosis of incident AD or dementia within 17 years and with the blood biomarkers neurofilament light (NfL), phosphorylated tau181 (p-tau181), and glial fibrillary acidic protein (GFAP). Design, Setting, and Participants: In this prospective, population-based cohort study and nested case-control study, 9940 participants in Germany were enrolled between 2000 and 2002 by their general practitioners and followed up for up to 17 years. Participants were included if information on dementia status and creatinine/cystatin C measurements were available. A subsample of participants additionally had measurements of NfL, p-tau181, and GFAP obtained from blood samples. Statistical analysis was performed from January 3 to November 25, 2022. Exposures: Impaired kidney function, based on estimated glomerular filtration rate less than 60 mL/min/1.73 m2 according to the 2021 Chronic Kidney Disease Epidemiology Collaboration creatinine-cystatin C equation. Main Outcomes and Measures: All-cause dementia, AD, and vascular dementia diagnosis, as well as log-transformed levels of NfL, p-tau181, and GFAP in blood. Results: Of 6256 participants (3402 women [54.4%]; mean [SD] age at baseline, 61.7 [6.6] years), 510 received an all-cause dementia diagnosis within 17 years of baseline. The dementia-related blood biomarker nested case-control sample included 766 participants. After adjusting for age and sex, impaired kidney function at baseline was not associated with a higher risk of all-cause dementia (hazard ratio [HR], 0.95; 95% CI, 0.69-1.29), AD (HR, 0.94; 95% CI, 0.55-1.63), or vascular dementia diagnosis (HR, 1.06; 95% CI, 0.65-1.70) within 17 years. In the cross-sectional analysis, after adjusting for age and sex, impaired kidney function was significantly associated with NfL and p-tau181 levels in blood (NfL: ß = 0.47 and P < .001; p-tau181: ß = 0.21 and P = .003). After adjusting for age and sex, significant associations with GFAP levels were evident only among men (men: ß = 0.31 and P = .006; women: ß = -0.12 and P = .11). Conclusions and Relevance: In this population-based study of community-dwelling adults, reduced kidney function was associated with increased levels of dementia-related blood biomarkers but not increased dementia risk. Kidney function might influence the accuracy of dementia-related blood biomarkers and should be considered in clinical translation.


Subject(s)
Alzheimer Disease , Dementia, Vascular , Male , Adult , Humans , Female , Child , Alzheimer Disease/diagnosis , Alzheimer Disease/epidemiology , Cystatin C , Cohort Studies , Prospective Studies , Cross-Sectional Studies , Case-Control Studies , Creatinine , tau Proteins , Biomarkers , Kidney
5.
Int J Mol Sci ; 24(2)2023 Jan 05.
Article in English | MEDLINE | ID: mdl-36674580

ABSTRACT

There is a paucity of empirical research on the use of non-pharmacological interventions to both treat and curb the spread of Alzheimer's disease (AD) across the globe. This paper examines the biochemical and clinical outlook and the social implications of the condition in relation to psychological aspects that may indicate a direction for further interventions. There is a scarcity of research on the effectiveness of using various psychological aspects of AD, a disease characterized by a process of transition from health and independence to a dependent state with a progressive loss of memory and functional skills. The paper investigates the biochemical and psychological aspects of AD and their significance for improving quality of life for patients with this disease. Psychological interventions based on, among other factors, biochemical studies, are conducted to improve the emotional wellbeing of AD patients and may assist in slowing down the progression of the disease. To date, however, no effective methods of AD treatment have been established.


Subject(s)
Alzheimer Disease , Humans , Alzheimer Disease/diagnosis , Alzheimer Disease/therapy , Alzheimer Disease/psychology , Quality of Life
6.
Int J Environ Res Public Health ; 20(2)2023 Jan 10.
Article in English | MEDLINE | ID: mdl-36674027

ABSTRACT

In developing countries, there is more concern for Alzheimer's disease (AD) by public health professionals due to its catastrophic effects on the elderly. Early detection of this disease helps in starting the therapy soon and slows down the progression of the disease. Imaging techniques are considered to be the best solutions for its detection. Brain imaging was initially used to diagnose AD. Different techniques for identifying protein accumulation in the nervous system, a sign of Alzheimer's disease, are identified by MRI imaging. Although they were initially attributed to cortical dysfunction, visual system impairments in Alzheimer's patients were also found in the early 1970s. Several non-invasive approaches reported for screening, prevention, and therapy were unsuccessful. It is vitally necessary to develop new diagnostic methods in order to accurately identify patients who are in the early stages of this disease. It would be wonderful to have a quick, non-invasive, affordable, and easily scalable Alzheimer's disease screening. Researchers may be able to identify biomarkers for Alzheimer's disease and understand more about its aetiology with imaging and data processing. This study clarifies the need for medical image processing and analysis strategies which aid in the non-invasive diagnosis of AD.


Subject(s)
Alzheimer Disease , Humans , Aged , Alzheimer Disease/diagnosis , Magnetic Resonance Imaging/methods , Brain
7.
Trials ; 24(1): 33, 2023 Jan 17.
Article in English | MEDLINE | ID: mdl-36650552

ABSTRACT

BACKGROUND: Capturing changes in health and wellbeing within randomised controlled trials (RCTs) can be complex. The precision and accuracy of outcome scales to measure change is crucial, and therefore, consideration needs to be given to potential measurement errors when collecting these outcomes. Many RCTs use multiple researchers to collect data, which has the potential to introduce variation in measurements. This study aimed to identify if there was a measurable effect of using different researchers to collect repeated assessments of quality of life (QoL) at different time points. METHODS: A previously conducted study assessing the impact of reminiscence therapy on participants with dementia and carer (PwD-carer) dyads, 'REMCARE' (Reminiscence groups for people with dementia and their family caregivers), provided the platform for this exploratory secondary analysis. Data was categorised into two broad groups: those where the same researcher attended all assessments and those where different researchers undertook the assessments. ANCOVA (analysis of covariance) models used in the original REMCARE analysis with the addition of the 'researcher-continuity' variable were run on two QoL measures, the QoL-AD (Quality of Life in Alzheimer's Disease) and QCPR (Quality of the Caregiving Relationship). RESULTS: Three hundred thirty PwD-carer dyads were included in the analysis. For the PwD, a statistically significant effect was found on the researcher continuity variable for the QoL-AD and QCPR outcome measures at follow-up 1 but not at follow-up 2 signifying an impact of researcher attendance at the first follow-up but not follow-up 2. For the carer data, analyses revealed no statistically significant effects at follow-up 1; however, the QoL-AD measure at follow-up 2 was found to be statistically significant. CONCLUSIONS: These exploratory results indicate the possible impact of researcher continuity on QoL outcomes in dementia studies. Further research is required to explore this further and establish causality. If demonstrated, this would have implications for the planning of future empirical studies in dementia, in order to reduce this potential source of bias.


Subject(s)
Alzheimer Disease , Dementia , Humans , Dementia/diagnosis , Dementia/therapy , Quality of Life , Memory , Outcome Assessment, Health Care , Alzheimer Disease/diagnosis , Alzheimer Disease/therapy , Caregivers , Randomized Controlled Trials as Topic
8.
Comput Biol Med ; 153: 106518, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36641934

ABSTRACT

Alzheimer's disease (AD) is a common cognitive disorder. Recently, many computer-aided diagnostic techniques have been used for AD prediction utilizing deep learning technology, among which graph neural networks have received increasing attention owing to their ability to model sample relationships on large population graphs. Most of the existing graph-based methods predict diseases according to a single model, which makes it difficult to select an appropriate node embedding algorithm for a certain classification task. Moreover, integrating data from different patterns into a unified model to improve the quality of disease diagnosis remains a challenge. Hence, in this study, we aimed to develop a multi-model fusion framework for AD prediction. A spectral graph attention model was used to aggregate intra- and inter-cluster node embeddings of normal and diseased populations, whereafter, a bilinear aggregation model was applied as an auxiliary model to enhance the abnormality degree in different categories of populations, and finally, an adaptive fusion module was designed to dynamically fuse the results of both models and enhance AD prediction. Compared to other comparison methods, the model proposed in this study provides the best results.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Humans , Alzheimer Disease/diagnosis , Algorithms , Neural Networks, Computer
10.
J Prev Alzheimers Dis ; 10(1): 41-49, 2023.
Article in English | MEDLINE | ID: mdl-36641609

ABSTRACT

BACKGROUND: Screening procedures for early Alzheimer's disease (AD) trials seek to efficiently identify participants who fulfill clinical and biomarker criteria for AD and enrich for those most likely to experience significant clinical progression during the study. Episodic memory performance is often assessed in screening, but the utility of different memory tests for optimizing screening efficiency and/or rates of clinical progression remains uncertain. OBJECTIVES: Cross-study comparisons of the effects of inclusion criteria based on performance on the Free and Cued Selective Reminding Test (FCSRT) or the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) on screen-failure rates for episodic memory and ß-amyloid (Aß) positivity (by CSF or PET) and on subsequent rates of clinical disease progression in randomized participants across three clinical trials in early (prodromal-to-mild) AD. DESIGN: Secondary analyses of cross-sectional and longitudinal clinical trial data. SETTING: Multi-center international clinical trials. PARTICIPANTS: Individuals with prodromal-to-mild AD screened and/or randomized in clinical trials for crenezumab (CREAD, CREAD2) or semorinemab (Tauriel). Cross-sectional analyses of screening data for episodic memory impairment included participants from CREAD2 (n=2897) and Tauriel (n=887) and for Aß positivity included participants from CREAD (n=1138), CREAD2 (n=1119), and Tauriel (n=483). Longitudinal analyses of rates of clinical progression included participants from CREAD (n=779), CREAD2 (n=773), and Tauriel (n=331). MEASUREMENTS: Cross-sectional analyses examined eligibility rates per cutoffs defined for the FCSRT (CREAD, CREAD2) or RBANS (Tauriel) and per Aß positivity using CSF and/or PET biomarkers. Longitudinal analyses examined rates of clinical progression on the Clinical Dementia Rating-Sum of Boxes (CDR-SB), the 13-item version of the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog13), and Alzheimer's Disease Cooperative Study-Activities of Daily Living Scale (ADCS-ADL). RESULTS: Lower rates of study eligibility per episodic memory criteria were seen with the FCSRT (CREAD2) relative to the RBANS (Tauriel), but similar rates of eligibility per Aß positivity criteria were seen amongst participants with episodic memory impairment per the cutoffs used on either assessment. Similar rates of clinical decline over 18 months on the CDR-SB, ADAS-Cog13, and ADCS-ADL were observed in study populations enriched using the FCSRT (CREAD, CREAD2) or the RBANS (Tauriel). CONCLUSIONS: Cutoffs for episodic memory impairment on the FCSRT used in the CREAD and CREAD2 studies are more stringent than those on the RBANS used in the Tauriel study, resulting in lower rates of eligibility. However, given that study enrichment with either test yields similar rates of Aß positivity and clinical progression, considerations beyond these factors may drive the decision of which assessment to use for screening in early AD clinical trials.


Subject(s)
Alzheimer Disease , Memory, Episodic , Humans , Alzheimer Disease/diagnosis , Alzheimer Disease/drug therapy , Alzheimer Disease/psychology , Cross-Sectional Studies , Activities of Daily Living , Neuropsychological Tests , Disease Progression , Biomarkers
11.
J Prev Alzheimers Dis ; 10(1): 9-18, 2023.
Article in English | MEDLINE | ID: mdl-36641605

ABSTRACT

BACKGROUND: Consensus is lacking on what constitutes a meaningful score change for individual patients on clinical outcome assessments (COAs) that are commonly used in clinical trials of Alzheimer's disease. Such thresholds are one important approach to help contextualize trial results and demonstrate meaningful treatment benefit. OBJECTIVES: To estimate meaningful within-patient change thresholds for the Clinical Dementia Rating Scale - Sum of Boxes (CDR-SB), Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog), and the Mini-Mental State Examination (MMSE) among participants with mild cognitive impairment (MCI). DESIGN: Retrospective anchor- and distribution-based analyses of data from the ADC-008 (NCT00000173) study were used to estimate thresholds for meaningful within-patient change on the target measures. SETTING: Analyses were conducted using data from ADC-008 a Phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group study among participants with the amnestic subtype of MCI, which was conducted by the Alzheimer's Disease Cooperative Study (ADCS) between March 1999 and January 2004 in the United States and Canada. PARTICIPANTS: Analyses were based on 769 eligible participants who completed the baseline assessment from 69 ADCS sites in the United States and Canada. MEASUREMENTS: The target outcome measures for this analysis included the CDR-SB, the ADAS-Cog, and the MMSE. The anchor measures for this analysis included the Global Deterioration Scale and the MCI-Clinical Global Impression of Change. RESULTS: Focusing on the 12-month time point, within-patient increases of 1-2.5 points in the CDR-SB and increases of 2-5 points on the 11-item ADAS-Cog and 13-item ADAS-Cog, on average, reflect minimal-to-moderate levels of deterioration, respectively. CONCLUSIONS: These thresholds may be useful to aid the interpretation of Alzheimer's disease clinical trial data by illustrating meaningful within-patient progression over the course of a clinical trial via supplementary progressor analyses, which may in turn be informative for treatment decisions. Estimates generated via these methods are specifically intended to evaluate within-patient change and are not intended to assess the magnitude and meaningfulness of differences between group-level changes over time.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Humans , Alzheimer Disease/complications , Alzheimer Disease/diagnosis , Alzheimer Disease/drug therapy , Retrospective Studies , Cognitive Dysfunction/complications , Cognitive Dysfunction/diagnosis , Outcome Assessment, Health Care , Mental Status and Dementia Tests
12.
Adv Clin Chem ; 112: 249-281, 2023.
Article in English | MEDLINE | ID: mdl-36642485

ABSTRACT

Alzheimer's disease (AD) characterization has progressed from being indexed using clinical symptomatology followed by neuropathological examination at autopsy to in vivo signatures using cerebrospinal fluid (CSF) biomarkers and positron emission tomography. The core AD biomarkers reflect amyloid-ß plaques (A), tau pathology (T) and neurodegeneration (N), following the ATN schedule, and are now being introduced into clinical routine practice. This is an important development, as disease-modifying treatments are now emerging. Further, there are now reproducible data on CSF biomarkers which reflect synaptic pathology, neuroinflammation and common co-pathologies. In addition, the development of ultrasensitive techniques has enabled the core CSF biomarkers of AD pathophysiology to be translated to blood (e.g., phosphorylated tau, amyloid-ß and neurofilament light). In this chapter, we review where we stand with both core and novel CSF biomarkers, as well as the explosion of data on blood biomarkers. Also, we discuss potential applications in research aiming to better understand the disease, as well as possible use in routine clinical practice and therapeutic trials.


Subject(s)
Alzheimer Disease , Humans , Alzheimer Disease/diagnosis , tau Proteins/cerebrospinal fluid , Amyloid beta-Peptides , Biomarkers , Peptide Fragments
13.
JAMA Netw Open ; 6(1): e2250921, 2023 Jan 03.
Article in English | MEDLINE | ID: mdl-36637820

ABSTRACT

Importance: Individuals who are amyloid-positive with subjective cognitive decline and clinical features increasing the likelihood of preclinical Alzheimer disease (SCD+) are at higher risk of developing dementia. Some individuals with SCD+ undergo amyloid-positron emission tomography (PET) as part of research studies and frequently wish to know their amyloid status; however, the disclosure of a positive amyloid-PET result might have psychological risks. Objective: To assess the psychological outcomes of the amyloid-PET result disclosure in individuals with SCD+ and explore which variables are associated with a safer disclosure in individuals who are amyloid positive. Design, Setting, and Participants: This prospective, multicenter study was conducted as part of The Amyloid Imaging to Prevent Alzheimer Disease Diagnostic and Patient Management Study (AMYPAD-DPMS) (recruitment period: from April 2018 to October 2020). The setting was 5 European memory clinics, and participants included patients with SCD+ who underwent amyloid-PET. Statistical analysis was performed from July to October 2022. Exposures: Disclosure of amyloid-PET result. Main Outcomes and Measures: Psychological outcomes were defined as (1) disclosure related distress, assessed using the Impact of Event Scale-Revised (IES-R; scores of at least 33 indicate probable presence of posttraumatic stress disorder [PTSD]); and (2) anxiety and depression, assessed using the Hospital Anxiety and Depression scale (HADS; scores of at least 15 indicate probable presence of severe mood disorder symptoms). Results: After disclosure, 27 patients with amyloid-positive SCD+ (median [IQR] age, 70 [66-74] years; gender: 14 men [52%]; median [IQR] education: 15 [13 to 17] years, median [IQR] Mini-Mental State Examination [MMSE] score, 29 [28 to 30]) had higher median (IQR) IES-R total score (10 [2 to 14] vs 0 [0 to 2]; P < .001), IES-R avoidance (0.00 [0.00 to 0.69] vs 0.00 [0.00 to 0.00]; P < .001), IES-R intrusions (0.50 [0.13 to 0.75] vs 0.00 [0.00 to 0.25]; P < .001), and IES-R hyperarousal (0.33 [0.00 to 0.67] vs 0.00 [0.00 to 0.00]; P < .001) scores than the 78 patients who were amyloid-negative (median [IQR], age, 67 [64 to 74] years, 45 men [58%], median [IQR] education: 15 [12 to 17] years, median [IQR] MMSE score: 29 [28 to 30]). There were no observed differences between amyloid-positive and amyloid-negative patients in the median (IQR) HADS Anxiety (-1.0 [-3.0 to 1.8] vs -2.0 [-4.8 to 1.0]; P = .06) and Depression (-1.0 [-2.0 to 0.0] vs -1.0 [-3.0 to 0.0]; P = .46) deltas (score after disclosure - scores at baseline). In patients with amyloid-positive SCD+, despite the small sample size, higher education was associated with lower disclosure-related distress (ρ = -0.43; P = .02) whereas the presence of study partner was associated with higher disclosure-related distress (W = 7.5; P = .03). No participants with amyloid-positive SCD+ showed probable presence of PTSD or severe anxiety or depression symptoms at follow-up. Conclusions and Relevance: The disclosure of a positive amyloid-PET result to patients with SCD+ was associated with a bigger psychological change, yet such change did not reach the threshold for clinical concern.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Male , Humans , Adult , Aged , Alzheimer Disease/diagnosis , Brain/metabolism , Amyloid beta-Peptides/metabolism , Prospective Studies , Disclosure , Positron-Emission Tomography , Cognitive Dysfunction/diagnostic imaging
14.
PLoS One ; 18(1): e0280178, 2023.
Article in English | MEDLINE | ID: mdl-36634049

ABSTRACT

Cognitive screening is often a first step to document cognitive status of patients suspected having Alzheimer's disease (AD). Unfortunately, screening neuropsychological tests are often insensitivity in the detection. The goal of this study was to develop a simple and sensitive screening neuropsychological test to facilitate early detection of AD. This study recruited 761 elderly individuals suspected of having AD and presenting various cognitive statuses (mean age: 77.69 ± 8.45 years; proportion of females: 65%; cognitively unimpaired, CU, n = 133; mild cognitive impairment, MCI, n = 231; dementia of Alzheimer's type, DAT, n = 397). This study developed a novel screening neuropsychological test incorporating assessments of the core memory deficits typical of early AD and an interview on memory function with an informant. The proposed History-based Artificial Intelligence-Show Chwan Assessment of Cognition (HAI-SAC) was assessed in terms of psychometric properties, test time, and discriminative ability. The results were compared with those obtained using other common screening tests, including Cognitive Abilities Screening Instrument (CASI), Montreal Cognitive Assessment (MoCA), and an extracted Mini-Mental State Examination score from CASI. HAI-SAC demonstrated acceptable internal consistency. Factor analysis revealed two factors: memory (semantic and contextual) and cognition-related information from informants. The assessment performance of HAI-SAC was strongly correlated with that of the common screening neuropsychological tests addressed in this study. HAI-SAC outperformed the other tests in differentiating CU individuals from patients with MCI (sensitivity: 0.87; specificity: 0.58; area under the curve [AUC]: 0.78) or DAT (sensitivity: 0.99; specificity: 0.89; AUC: 0.98). Performance of HAI-SAC on differentiating MCI from DAT was on par with performances of other tests (sensitivity: 0.78; specificity: 0.84; AUC: 0.87), while the test time was less than one quarter that of CASI and half that of MoCA. HAI-SAC is psychometrically sound, cost-effective, and sensitive in discriminating the cognitive status of AD.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Female , Humans , Aged , Aged, 80 and over , Alzheimer Disease/diagnosis , Alzheimer Disease/psychology , Artificial Intelligence , Copper , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/psychology , Neuropsychological Tests , Cognition , Sensitivity and Specificity
15.
Sci Eng Ethics ; 29(1): 2, 2023 Jan 10.
Article in English | MEDLINE | ID: mdl-36625928

ABSTRACT

Alzheimer's disease (AD), the devastating and most prevailing underlying cause for age-associated dementia, has no effective disease-modifying treatment. The last approved drug for the relief of AD symptoms was in 2003. The recent approval of sodium oligomannate (GV-971, 2019) in China and the human antibody aducanumab in the USA (ADUHELM, 2021) therefore represent significant breakthroughs, albeit ones that are fraught with controversy. Here, we explore potential scientific ethics issues associated with GV-971 and aducanumab's development and approval. While these issues may be belied by socioeconomic and political complexities in the heady business of commercial drug development, they are of fundamental importance to scientific integrity and ultimately, welfare of patients. We posit that the push for approval of both AD drugs based on incomplete research and unconvincing marginal effectiveness is ethically unsound. Regardless of how both these drugs shall perform in the market for the years to come, the scientific ethics issues and potentially questionable research practices should therefore be duly noted and lessons learned.


Subject(s)
Alzheimer Disease , Humans , Alzheimer Disease/drug therapy , Alzheimer Disease/complications , Alzheimer Disease/diagnosis , China
17.
Biomark Med ; 16(15): 1089-1100, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36625236

ABSTRACT

Background: Alzheimer's disease (AD) cannot currently be diagnosed by a blood test. One reason may be gender differences. Another may be the statistical methods used. The authors evaluate these possibilities. Objective: The authors applied serum lipidomics to find AD biomarkers in men and women. They hypothesized that AD biomarkers would differ between genders and that machine-learning algorithms would improve diagnostic performance. Methods: Serum lipids were analyzed by mass spectrometry for a training set of AD cases and controls and in a blinded test set. Statistical analyses considered gender differences. Results: Lipids best classifying AD subjects differed significantly between men and women. Robust statistical algorithms did not improve diagnostic performance. Conclusion: Poor performance of AD biomarkers appears to be due primarily to inherent variability in AD patients.


Alzheimer's disease (AD) cannot be diagnosed by a blood test or radiologic study. Newer laboratory methods using mass spectrometers have successfully identified molecules in blood that mark the presence of other diseases, but such approaches have failed to find diagnostic biomarkers for AD. Often, initial studies of serum from AD cases and controls have provided promising diagnostic biomarkers, but follow-up studies have not confirmed their usefulness. This study attempts to clarify why this is so by carrying out a serum lipid (fatty molecule) analysis using mass spectrometry (MS) in both an initial serum set of AD cases and matched controls and applying those results to AD diagnosis in a second, independent set of specimens. Sources of variability that could prevent the discovery of useful markers using MS analyses of serum include specimen integrity, variable MS results, problems with statistical methods that analyze MS data and inherent AD patient variability reflected in their sera. Specifically, this study asked if biological gender contributes to nonreproducibility. This approach employed state-of-the-art methods for specimen preparation and MS analysis. The authors used MS approaches that guarded against instrument bias or irreproducibility. Statistical analyses tested several methods of defining useful diagnostic AD marker models. As with previous reports, the authors found promising AD diagnostic serum lipid biomarkers in the first study but failed to replicate the results in the blinded confirmatory study. Results were significantly different for men and women but analyzing men and women separately did not improve AD diagnosis. Overall, the largest source of variability was AD patient variability. AD is complicated, often affecting people who have other medical problems and are on medications. Differences in disease occurrence, disease progression, symptoms and areas of the brain affected are reflected in a highly variable serum lipid composition that may obscure disease-specific, and hence diagnostic, AD biomarkers.


Subject(s)
Alzheimer Disease , Humans , Male , Female , Alzheimer Disease/diagnosis , Sex Factors , Mass Spectrometry/methods , Biomarkers , Lipids
18.
BMC Bioinformatics ; 24(1): 9, 2023 Jan 09.
Article in English | MEDLINE | ID: mdl-36624372

ABSTRACT

BACKGROUND: Feature selection is often used to identify the important features in a dataset but can produce unstable results when applied to high-dimensional data. The stability of feature selection can be improved with the use of feature selection ensembles, which aggregate the results of multiple base feature selectors. However, a threshold must be applied to the final aggregated feature set to separate the relevant features from the redundant ones. A fixed threshold, which is typically used, offers no guarantee that the final set of selected features contains only relevant features. This work examines a selection of data-driven thresholds to automatically identify the relevant features in an ensemble feature selector and evaluates their predictive accuracy and stability. Ensemble feature selection with data-driven thresholding is applied to two real-world studies of Alzheimer's disease. Alzheimer's disease is a progressive neurodegenerative disease with no known cure, that begins at least 2-3 decades before overt symptoms appear, presenting an opportunity for researchers to identify early biomarkers that might identify patients at risk of developing Alzheimer's disease. RESULTS: The ensemble feature selectors, combined with data-driven thresholds, produced more stable results, on the whole, than the equivalent individual feature selectors, showing an improvement in stability of up to 34%. The most successful data-driven thresholds were the robust rank aggregation threshold and the threshold algorithm threshold from the field of information retrieval. The features identified by applying these methods to datasets from Alzheimer's disease studies reflect current findings in the AD literature. CONCLUSIONS: Data-driven thresholds applied to ensemble feature selectors provide more stable, and therefore more reproducible, selections of features than individual feature selectors, without loss of performance. The use of a data-driven threshold eliminates the need to choose a fixed threshold a-priori and can select a more meaningful set of features. A reliable and compact set of features can produce more interpretable models by identifying the factors that are important in understanding a disease.


Subject(s)
Alzheimer Disease , Neurodegenerative Diseases , Humans , Alzheimer Disease/diagnosis , Biomarkers , Algorithms , Computational Biology/methods
19.
Semin Neurol ; 42(6): 742-751, 2022 12.
Article in English | MEDLINE | ID: mdl-36623535

ABSTRACT

Dementia is broadly defined by DSM-V as cognitive decline from a previous level that impacts the patient's functioning at work or play. This broad definition does not provide information about the underlying disease process, an aspect of clinical care that is of increasing importance, as therapeutic development inches closer to effective disease-modifying treatments. The most common neurodegenerative dementias include Alzheimer's disease, dementia with Lewy bodies, frontotemporal dementia, and Parkinson's disease dementia. Although rare, the prion diseases constitute an important group of dementias that should be routinely considered in the evaluation. Over the last two decades, advances in neuroimaging, biomarker development, and neurogenetics have not only led to a better understanding of the biology of these diseases, but they have improved our awareness of less common clinical subtypes of dementia. As such, to best define the disease process, the evaluation of a patient with cognitive decline requires attention to a myriad of disease aspects, such as the primary symptom at onset (memory, language, visual perception, praxis, etc.), the age at onset (younger or older than 65 years), the rate of disease progression (weeks to months or years), the cognitive and behavioral profile (neuropsychological assessment), and involvement of physical findings. We present here three cases that highlight the decision-making process in the evaluation of patients with atypical presentations of dementia.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Frontotemporal Dementia , Parkinson Disease , Prion Diseases , Humans , Aged , Parkinson Disease/diagnosis , Alzheimer Disease/diagnosis , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/etiology
20.
Cells ; 12(1)2022 Dec 28.
Article in English | MEDLINE | ID: mdl-36611925

ABSTRACT

Alzheimer's disease (AD), once considered a rare disease, is now the most common form of dementia in the elderly population. Current drugs (cholinesterase inhibitors and glutamate antagonists) are safe but of limited benefit to most patients, offering symptomatic relief without successful cure of the disease. Since the last several decades, there has been a great need for the development of a treatment that might cure the underlying causes of AD and thereby slow its progression in vulnerable individuals. That is why phase I, II, and III studies that act on several fronts, such as cognitive improvement, symptom reduction, and enhancing the basic biology of AD, are imperative to stop the disease. This review discusses current treatment strategies, summarizing the clinical features and pharmacological properties, along with molecular docking analyses of the existing medications.


Subject(s)
Alzheimer Disease , Humans , Aged , Alzheimer Disease/drug therapy , Alzheimer Disease/diagnosis , Molecular Docking Simulation , Cholinesterase Inhibitors/pharmacology , Cholinesterase Inhibitors/therapeutic use
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