Differential Diagnosis Of Alzheimer's Disease Research Articles

PET Imaging in Alzheimer Disease: Pathology and Research Insights for Technologists.

Alzheimer disease (AD) is the sixth leading cause of death in the United States and is projected to affect over 13 million people by the year 2060. Although there is currently no cure for AD, disease-modifying treatments that target amyloid plaques have recently been approved for use. The advent of PET tracers that can reliably detect the presence of cortical amyloid plaques and tau pathologies has allowed researchers and clinicians to identify individuals who have pathologic markers of AD before the onset of cognitive decline. Although these tracers have been widely used in research settings for some time, they are now on the verge of being used to aid clinicians in the differential diagnosis of AD. As the use of these tracers increases, technologists will need to be educated on the best practices and potential problems they may encounter in their clinical populations. This article will review the available tracers for amyloid and tau PET scans and educate technologists about the most important practices and procedures that can be implemented to ensure patient safety and the capture of high-quality scans.

Practical use of DAT SPECT imaging in diagnosing dementia with Lewy bodies: a US perspective of current guidelines and future directions.

Diagnosing Dementia with Lewy Bodies (DLB) remains a challenge in clinical practice. The use of 123I-ioflupane (DaTscan™) SPECT imaging, which detects reduced dopamine transporter (DAT) uptake-a key biomarker in DLB diagnosis-could improve diagnostic accuracy. However, DAT imaging is underutilized despite its potential, contributing to delays and suboptimal patient management. This review evaluates DLB diagnostic practices and challenges faced within the U.S. by synthesizing information from current literature, consensus guidelines, expert opinions, and recent updates on DaTscan FDA filings. It contrasts DAT SPECT with alternative biomarkers, provides recommendations for when DAT SPECT imaging may be indicated and discusses the potential of emerging biomarkers in enhancing diagnostic approaches. The radiopharmaceutical 123I-ioflupane for SPECT imaging was initially approved in Europe (2000) and later in the US (2011) for Parkinsonism/Essential Tremor. Its application was extended in 2022 to include the diagnosis of DLB. DaTscan's diagnostic efficacy for DLB, with its sensitivity, specificity, and predictive values, confirms its clinical utility. However, US implementation faces challenges such as insurance barriers, costs, access issues, and regional availability disparities. 123I-ioflupane SPECT Imaging is indicated for DLB diagnosis and differential diagnosis of Alzheimer's Disease, particularly in uncertain cases. Addressing diagnostic obstacles and enhancing physician-patient education could improve and expedite DLB diagnosis. Collaborative efforts among neurologists, geriatric psychiatrists, psychologists, and memory clinic staff are key to increasing diagnostic accuracy and care in DLB management.

Effects of the Fasting-Postprandial State on Arterial Spin Labeling MRI-Based Cerebral Perfusion Quantification in Alzheimer's Disease.

The fasting-postprandial state remains an underrecognized confounding factor for quantifying cerebral blood flow (CBF) in the cognitive assessment and differential diagnosis of Alzheimer's disease (AD). To investigate the effects of fasting-postprandial state on arterial spin labeling (ASL)-based CBF in AD patients. Prospective. Ninety-two subjects (mean age = 62.5 ± 6.4 years; females 29.3%), including 30 with AD, 32 with mild cognitive impairment (MCI), and 30 healthy controls (HCs). Differential diagnostic models were developed with a 4:1 training to testing set ratio. 3-T, T1-weighted imaging using gradient echo and pseudocontinuous ASL imaging using turbo spin echo. Two ASL scans were acquired to quantify fasting state and postprandial state regional CBFs based on an automated anatomical labeling atlas. Two-way ANOVA was used to assess the effects of fasting/postprandial state and disease state (AD, MCI, and HC) on regional CBF. Pearson's correlation analysis was conducted between regional CBF and cognitive scores (Mini-Mental State Examination [MMSE] and Montreal Cognitive Assessment [MoCA]). The diagnostic performances of the fasting state, postprandial state, and mixed state (random mixing of the fasting and postprandial state CBF) in differential diagnosis of AD were conducted using support vector machine and logistic regression models. Two-way ANOVA, Pearson's correlation, and area under the curve (AUC) of diagnostic model were performed. P values <0.05 indicated statistical significance. Fasting-state CBF was correlated with cognitive scores in more brain regions (17 vs. 4 [MMSE] and 15 vs. 9 [MoCA]) and had higher absolute correlation coefficients than postprandial-state CBF. In the differential diagnosis of AD patients from MCI patients and HCs, fasting-state CBF outperformed mixed-state CBF, which itself outperformed postprandial-state CBF. Compared with postprandial CBF, fasting-state CBF performed better in terms of cognitive score correlations and in differentiating AD patients from MCI patients and HCs. 2 TECHNICAL EFFICACY: Stage 3.

Potential Utility of Plasma Biomarker Panels in Differential Diagnosis of Alzheimer's Disease.

Blood tests are in need, in the clinical diagnosis of Alzheimer's disease (AD) as minimally invasive and less expensive alternatives to cerebrospinal fluid and neuroimaging methods. On these lines, single molecule array (Simoa) analysis of amyloid-β (Aβ42), total tau (t-tau), phospho-tau (p-tau 181), and neurofilament L (NfL) in the plasma samples of AD subjects, healthy controls (HC), and non-AD subjects was conducted. Findings from this study suggest that a panel of multiple plasma biomarkers (NfL, Aβ42, t-tau, and p-tau 181) combined with the clinical assessments could support differential diagnosis of AD and other dementias from healthy controls.

A comparative transcranial magnetic stimulation study: Assessing cortical excitability and plasticity in Alzheimer's disease, dementia with Lewy bodies and Frontotemporal dementia.

Here, we aimed to investigate the roles of long-term potentiation-like (LTP-like) plasticity using intermittent theta burst (iTBS) protocol and resting motor threshold (rMT) in the differential diagnosis of Alzheimer's disease (AD), diffuse dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD). We enrolled 21 subjects with AD, 28 subjects with DLB, 14 subjects with FTD, and 33 elderly subjects with normal cognitive functions into the study. We recorded rMT and percentage amplitude change of motor evoked potentials (MEPs) after the iTBS protocol in each group. In patients with AD and DLB, the percentage amplitude change of MEPs, and rMTs were significantly lower than in healthy subjects. However, no significant difference was observed in individuals with FTD. Our findings showed that transcranial magnetic stimulation measures, particularly rMTs and LTP-like plasticity, may be potential biomarkers to distinguish between different dementia subtypes. Impaired motor cortical excitability and synaptic plasticity were more prominent in AD and DLB than in FTD. This aligns with the evidence that cortical motor networks are usually spared in FTDs in early-to-middle stages.

Differentiation Between Alzheimer̓s Disease and Old Age Depression: Overview and Conception of a Questionnaire for Relatives

Differential diagnosis of Alzheimer's disease and major depression in the elderly is difficult because of overlapping and similar symptoms. A questionnaire for relatives may facilitate the diagnostic burden in clinical practice. Based on a selection of clinical criteria, an expert survey, and statistical analysis of the expert survey, a questionnaire for relatives was designed. 18 out of 48 suggested clinical criteria were assessed by neuropsychologists as suitable for the differential diagnosis and were summarized in a questionnaire for relatives (ADAD). First results of the validation of the questionnaire gave an indication of the suitability of the clinical criteria. The ADAD questionnaire could be simply implemented in clinical practice to differentiate between symptoms of Alzheimer's disease and major depression, but it needs to be evaluated in a larger group of patients.

Mastermind of the Alzheimer’s blood‐based biomarkers: development of cutoffs and a visualization tool for use in clinical practice

AbstractBackgroundPhosphorylated (P‐)tau, amyloid‐beta (Abeta)1‐42/1‐40, glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) are the current key Alzheimer’s disease (AD) blood‐based biomarkers. Interpreting results of the four biomarkers simultaneously in a clinical context is challenging. A decision algorithm could aid in the interpretation, tailored to clinically relevant questions: 1) identify positive amyloid status among preclinical and prodromal AD stages, 2) discriminate AD‐dementia from frontotemporal dementia (FTD), 3) discriminate AD‐dementia from dementia with Lewy bodies (DLB). We aimed to develop such an interpretation tool.MethodWe included 1199 participants from the Amsterdam Dementia Cohort (table 1) with subjective cognitive decline (SCD), mild cognitive impairment (MCI), AD‐dementia, FTD (mixed pathologies) or DLB. Plasma P‐tau181, Abeta1‐42/1‐40, GFAP and NfL were measured with Simoa. NfL levels were adjusted for age (method: https://doi.org/10.1002/acn3.51676). We used LASSO regression with bootstrap (1000 iterations) to identify which plasma markers robustly contribute to the prediction of the outcomes of our clinically relevant questions. When a marker was selected in &gt;95% of the iterations in at least one of the clinical scenarios, we qualified it as a contributing marker. Subsequently, we constructed UpSet plots applying Youden’s cutoffs as interpretation tool for the plasma results.ResultP‐tau181, GFAP and NfL were selected as contributing biomarkers. Abeta1‐42/1‐40 was not selected. The panel of P‐tau181, GFAP and NfL had an AUC = 83% (95%CI: 76‐90%) to identify amyloid positivity in SCD+MCI, AUC = 87% (95%CI: 79‐94%) to differentiate AD‐dementia from FTD, and AUC = 73% (95%CI: 62‐84%) to differentiate AD‐dementia from DLB. The UpSet plots show the simultaneous interpretation of P‐tau181, GFAP and NfL results for each clinically relevant question (figure 1): e.g., when all three biomarkers are abnormal in participants with SCD+MCI, there is 83% agreement with an abnormal PET or CSF amyloid status, and when all three plasma markers are normal, there is 88% agreement with a normal amyloid status.ConclusionThe combination of P‐tau181, GFAP and NfL in plasma could support decision making in different clinical contexts. UpSet plots enable easy interpretation of a combination of the markers, and could serve as a tool to support both detection and differential diagnosis of Alzheimer’s disease.

The role of visual rating and automated brain volumetry in early detection and differential diagnosis of Alzheimer's disease.

Medial temporal lobe atrophy (MTA) is a diagnostic marker for mild cognitive impairment (MCI) and Alzheimer's disease (AD), but the accuracy of quantitative MTA (QMTA) in diagnosing early AD is unclear. This study aimed to investigate the accuracy of QMTA and its related components (inferior lateral ventricle [ILV] and hippocampus) with MTA in the early diagnosis of MCI and AD. This study included four groups: normal (NC), MCI stable (MCIs), MCI converted to AD (MCIs), and mild AD (M-AD) groups. Magnetic resonance image analysis software was used to quantify the hippocampus, ILV, and QMTA. MTA was rated by two experienced neurologists. Receiver operating characteristic area under the curve (AUC) analysis was performed to compare their capability in differentiating AD from NC and MCI, and optimal thresholds were determined using the Youden index. QMTA distinguished M-AD from NC and MCI with higher diagnostic accuracy than MTA, hippocampus, and ILV (AUCNC = 0.976, AUCMCI = 0.836, AUCMCIs = 0.894, AUCMCIc = 0.730). The diagnostic accuracy of QMTA was superior to that of MTA, the hippocampus, and ILV in differentiating MCI from AD. The diagnostic accuracy of QMTA was found to remain the best across age, sex, and pathological subgroups analyzed. The sensitivity (92.45%) and specificity (90.64%) were higher in this study when a cutoff value of 0.635 was chosen for QMTA. QMTA may be a better choice than the MTA scale or the associated quantitative components alone in identifying AD patients and MCI individuals with higher progression risk.

Executive function deficits and medial temporal lobe atrophy in late-life depression and Alzheimer's disease: a comparative study.

Alzheimer's disease (AD) and late-life depression (LLD) frequently exhibit executive function deficits (EFD) and medial temporal lobe atrophy (MTA) as shared characteristics. The objective of this research was to examine the utility of the Trail Making Test (TMT) and the MTA scale in distinguishing between LLD and AD. A study of 100 patients, 50 with AD and 50 with LLD, was conducted using a cross-sectional design. The individuals were subjected to clinical evaluations to assess their level of depression and overall cognitive abilities, which included the Geriatric Depression Scale (GDS), Mini-Mental State Examination (MMSE), and Montreal Cognitive Assessment (MoCA). We evaluated executive function deficits (EFD) through the use of the TMT, which includes both TMT-A and TMT-B. MTA was measured using magnetic resonance imaging. To evaluate the ability of TMT and MTA scale to distinguish between the two groups, a receiver operating characteristic (ROC) curve was utilized. To investigate the connections between MTA and neuropsychological measures, a correlation analysis was performed. AD patients exhibited notably reduced MMSE, MoCA, and GDS scores, as well as an increased MTA total scores, time spent on TMT-A, and TMT-B compared to LLD patients (p < 0.05). TMT-A and TMT-B both exhibited excellent discriminatory power between AD and LLD, achieving area under curve (AUC) values of 92.2 and 94.2%, respectively. In AD patients, there was a negative correlation between MMSE and MoCA scores and MTA scores, while in LLD patients, there was a positive correlation between time spent on TMT-A and GDS scores and MTA scores. AD patients experience more severe EFD and MTA than LLD patients. The differential diagnosis of AD and LLD can be aided by the useful tool known as TMT. It is important to acknowledge that TMT is capable of capturing only a fraction of the executive function, thus necessitating a cautious interpretation of research findings.

Biochimie du liquide cérébrospinal

AbstractBasic biochemical analysis of cerebrospinal fluid (CSF) is limited to the dosages of proteins (proteinorrhachia) and glucose (glycorrhachia), always completed with cytological and bacteriological examination of CSF and with notation of its aspect. They form the basic examination of CSF for the diagnosis of infectious meningitidis or sub-arachnoid haemorrhage. A number of other biochemical analyses were developed with electrophoresis, the study of immunoglobulins, and application of index for transudation or intrathecal synthesis, also isoelectric focalisation searching for oligoclonal bands characteristic of multiple sclerosis as well as the development of biomarkers of inflammatory neurological diseases and in particular neurodegenerative diseases. Tau and phosphorylated-tau proteins help in the differential diagnosis of Alzheimer’s disease. The elevation of angiotensin-converting enzyme activity in CSF helps in the diagnosis of neurosarcoidosis. Neurotransmitters allow the study of paediatric neurological diseases with abnormal movements.

Differentiation of Alzheimer's Disease from Frontotemporal Dementia and Mild Cognitive Impairment Based on Arterial Spin Labeling Magnetic Resonance Imaging: A Pilot Cross-Sectional Study from PUMCH Dementia Cohort.

Arterial spin labeling (ASL) is helpful in early diagnosis and differential diagnosis of Alzheimer's disease (AD), with advantages including no exposure to radioactivity, no injection of a contrast agent, more accessible, and relatively less expensive. To establish the perfusion pattern of different dementia in Chinese population and evaluate the effectiveness of ASL in differentiating AD from cognitive unimpaired (CU), mild cognitive impairment (MCI), and frontotemporal dementia (FTD). Four groups of participants were enrolled, including AD, FTD, MCI, and CU based on clinical diagnosis from PUMCH dementia cohort. ASL image was collected using 3D spiral fast spin echo-based pseudo-continuous ASL pulse sequence with background suppression and a high resolution T1-weighted scan covering the whole brain. Data processing was performed using Dr. Brain Platform to get cerebral blood flow (ml/100g/min) in every region of interest cortices. Participants included 66 AD, 26 FTD, 21 MCI, and 21 CU. Statistically, widespread hypoperfusion neocortices, most significantly in temporal-parietal-occipital cortices, but not hippocampus and subcortical nucleus were found in AD. Hypoperfusion in parietal lobe was most significantly associated with cognitive decline in AD. Hypoperfusion in parietal lobe was found in MCI and extended to adjacent temporal, occipital and posterior cingulate cortices in AD. Significant reduced perfusion in frontal and temporal cortices, including subcortical nucleus and anterior cingulate cortex were found in FTD. Hypoperfusion regions were relatively symmetrical in AD and left predominant especially in FTD. Specific patterns of ASL hypoperfusion were helpful in differentiating AD from CU, MCI, and FTD.

Visinin-like protein 1 levels in blood and CSF as emerging markers for Alzheimer’s and other neurodegenerative diseases

BackgroundVisinin-like protein 1 (VILIP-1) belongs to the group of emerging biomarkers with the potential to support the early diagnosis of Alzheimer’s disease (AD). However, studies investigating the differential diagnostic potential in cerebrospinal fluid (CSF) are rare and are not available for blood.MethodsWe set up a novel, sensitive single molecule array (Simoa) assay for the detection of VILIP-1 in CSF and serum. In total, paired CSF and serum samples from 234 patients were investigated: 73 AD, 18 behavioral variant frontotemporal dementia (bvFTD), 26 parkinsonian syndromes, 20 amyotrophic lateral sclerosis (ALS), 22 Creutzfeldt-Jakob disease (CJD), and 75 non-neurodegenerative control (Con) patients. The differential diagnostic potential of CSF and serum VILIP-1 was assessed using the receiver operating characteristic curve analysis and findings were compared to core AD biomarkers.ResultsCSF and serum VILIP-1 levels correlated weakly (r=0.32 (CI: 0.20–0.43), p<0.0001). VILIP-1 concentrations in CSF and serum were elevated in AD compared to Con (p<0.0001 and p<0.01) and CJD (p<0.0001 for CSF and serum), and an increase in CSF was observed already in early AD stages (p<0.0001). In the discrimination of AD versus Con, we could demonstrate a strong diagnostic potential for CSF VILIP-1 alone (area under the curve (AUC): 0.87), CSF VILIP-1/CSF Abeta 1-42 (AUC: 0.98), and serum VILIP-1/CSF Abeta 1-42 ratio (AUC: 0.89).ConclusionsWe here report on the successful establishment of a novel Simoa assay for VILIP-1 and illustrate the potential of CSF and serum VILIP-1 in the differential diagnosis of AD with highest levels in CJD.

Classification accuracy of blood-based and neurophysiological markers in the differential diagnosis of Alzheimer’s disease and frontotemporal lobar degeneration

BackgroundIn the last decade, non-invasive blood-based and neurophysiological biomarkers have shown great potential for the discrimination of several neurodegenerative disorders. However, in the clinical workup of patients with cognitive impairment, it will be highly unlikely that any biomarker will achieve the highest potential predictive accuracy on its own, owing to the multifactorial nature of Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD).MethodsIn this retrospective study, performed on 202 participants, we analysed plasma neurofilament light (NfL), glial fibrillary acidic protein (GFAP), and tau phosphorylated at amino acid 181 (p-Tau181) concentrations, as well as amyloid β42 to 40 ratio (Aβ1–42/1–40) ratio, using the ultrasensitive single-molecule array (Simoa) technique, and neurophysiological measures obtained by transcranial magnetic stimulation (TMS), including short-interval intracortical inhibition (SICI), intracortical facilitation (ICF), long-interval intracortical inhibition (LICI), and short-latency afferent inhibition (SAI). We assessed the diagnostic accuracy of combinations of both plasma and neurophysiological biomarkers in the differential diagnosis between healthy ageing, AD, and FTLD.ResultsWe observed significant differences in plasma NfL, GFAP, and p-Tau181 levels between the groups, but not for the Aβ1–42/Aβ1–40 ratio. For the evaluation of diagnostic accuracy, we adopted a two-step process which reflects the clinical judgement on clinical grounds. In the first step, the best single biomarker to classify “cases” vs “controls” was NfL (AUC 0.94, p < 0.001), whilst in the second step, the best single biomarker to classify AD vs FTLD was SAI (AUC 0.96, p < 0.001). The combination of multiple biomarkers significantly increased diagnostic accuracy. The best model for classifying “cases” vs “controls” included the predictors p-Tau181, GFAP, NfL, SICI, ICF, and SAI, resulting in an AUC of 0.99 (p < 0.001). For the second step, classifying AD from FTD, the best model included the combination of Aβ1–42/Aβ1–40 ratio, p-Tau181, SICI, ICF, and SAI, resulting in an AUC of 0.98 (p < 0.001).ConclusionsThe combined assessment of plasma and neurophysiological measures may greatly improve the differential diagnosis of AD and FTLD.

Differential Diagnosis of Alzheimer Disease vs. Mild Cognitive Impairment Based on Left Temporal Lateral Lobe Hypomethabolism on 18F-FDG PET/CT and Automated Classifiers.

Purpose: We evaluate the ability of Artificial Intelligence with automatic classification methods applied to semi-quantitative data from brain 18F-FDG PET/CT to improve the differential diagnosis between Alzheimer Disease (AD) and Mild Cognitive Impairment (MCI). Procedures: We retrospectively analyzed a total of 150 consecutive patients who underwent diagnostic evaluation for suspected AD (n = 67) or MCI (n = 83). All patients received brain 18F-FDG PET/CT according to the international guidelines, and images were analyzed both Qualitatively (QL) and Quantitatively (QN), the latter by a fully automated post-processing software that produced a z score metabolic map of 25 anatomically different cortical regions. A subset of n = 122 cases with a confirmed diagnosis of AD (n = 53) or MDI (n = 69) by 18–24-month clinical follow-up was finally included in the study. Univariate analysis and three automated classification models (classification tree –ClT-, ridge classifier –RC- and linear Support Vector Machine –lSVM-) were considered to estimate the ability of the z scores to discriminate between AD and MCI cases in. Results: The univariate analysis returned 14 areas where the z scores were significantly different between AD and MCI groups, and the classification accuracy ranged between 74.59% and 76.23%, with ClT and RC providing the best results. The best classification strategy consisted of one single split with a cut-off value of ≈ −2.0 on the z score from temporal lateral left area: cases below this threshold were classified as AD and those above the threshold as MCI. Conclusions: Our findings confirm the usefulness of brain 18F-FDG PET/CT QL and QN analyses in differentiating AD from MCI. Moreover, the combined use of automated classifications models can improve the diagnostic process since its use allows identification of a specific hypometabolic area involved in AD cases in respect to MCI. This data improves the traditional 18F-FDG PET/CT image interpretation and the diagnostic assessment of cognitive disorders.

Review on the roles of specific cell-derived exosomes in Alzheimer's disease.

Alzheimer's disease (AD) is the sixth leading cause of death worldwide and cannot be effectively cured or prevented; thus, early diagnosis, and intervention are important. The importance of exosomes, membrane-bound extracellular vesicles produced in the endosome of eukaryotic cells, in the development, diagnosis, and treatment of AD has been recognized; however, their specific functions remain controversial and even unclear. With the development of exosome extraction, isolation, and characterization, many studies have focused on exosomes derived from different cells and body fluids. In this study, we summarized the roles of exosomes derived from different body fluids and cells, such as neuron, glial, stem, and endothelial cells, in the development, diagnosis, monitoring, and treatment of AD. We also emphasize the necessity to focus on exosomes from biological fluids and specific cells that are less invasive to target. Moreover, aside from the concentrations of classic and novel biomarkers in exosomes, the size and number of exosomes may also influence early and differential diagnosis of AD.

Cerebrospinal Fluid Biomarkers for Early and Differential Diagnosis of Alzheimer's Disease

Cerebrospinal Fluid Biomarkers for Early and Differential Diagnosis of Alzheimer's Disease

ALZHEIMER'S DISEASE: ETIOLOGY, DIAGNOSIS, STAGES OF THE COURSE AND PREVENTION

Numerous scientific studies show that Alzheimer’s disease (AD) is the most common neurodegenerative disease [1]. Despite the huge amount of knowledge accumulated over the past two decades about the biological basis of the disease, its etiology remains unknown. The main initial symptom of AD is memory loss. As the disease progresses, there take place dementia, changes in personality and behavior. During the final stages, patients are not able to perform even the simplest tasks, and they are completely dependent on caregivers. The diagnosis of AD is based on the recommendations of the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for AD [1, 2]. Differential diagnosis of AD should be established with vascular dementia, dementia with Lewy bodies, and other diseases that cause dementia. Patient care is very important as well as the treatment of other AD symptoms and coexistent diseases.

Clinical application of CSF biomarkers for Alzheimer's disease: From rationale to ratios.

Biomarker testing is recommended for the accurate and timely diagnosis of Alzheimer's disease (AD). Using illustrative case narratives we consider how cerebrospinal fluid (CSF) biomarker tests may be used in different presentations of cognitive impairment to facilitate timely and differential diagnosis, improving diagnostic accuracy, providing prognostic information, and guiding personalized management in diverse scenarios. Evidence shows that (1) CSF ratios are superior to amyloid beta (Aβ)1‐42 alone; (2) concordance of CSF ratios to amyloid positron emission tomography (PET) is better than Aβ1‐42 alone; and (3) phosphorylated tau (p‐tau)/Aβ1‐42 ratio is superior to p‐tau alone. CSF biomarkers are recommended for the exclusion of AD as the underlying cause of cognitive impairment, diagnosis of AD at an early stage, differential diagnosis of AD in individuals presenting with other neuropsychiatric symptoms, accurate diagnosis of AD in an atypical presentation, and for clinical trial enrichment.Highlights Cerebrospinal fluid (CSF) Alzheimer's disease (AD) biomarker testing may be underused outside specialist centers.CSF biomarkers improve diagnostic accuracy, guiding personalized management of AD.CSF ratios (amyloid beta [Aβ]1‐42/Aβ1‐40 and phosphorylated tau/Aβ1‐42) perform better than single markers.CSF ratios produce fewer false‐negative and false‐positive results than individual markers.CSF biomarkers should be included in diagnostic work‐up of AD and mild cognitive impairment due to AD.

Clinical features that differentiate young‐onset AD from young‐onset FTLD: An examination of the NACC UDS 3.0 and FTLD Module

AbstractBackgroundClinicopathologic studies reported that the NACC Uniform Dataset (UDS) 2.0 core measures do not adequately differentiate patients who ultimately died of Frontotemporal Lobar Degeneration (FTLD) from Alzheimer’s disease (AD). The FTLD Module (FTLD‐MOD) assesses core features of behavioral variant FTD (bvFTD) and primary progressive aphasia (PPA). Initial investigations suggest that the FTLD‐MOD improves discrimination between biomarker‐supported bvFTD and typical late‐onset AD, and that clinically diagnosed PPA participants performed worse than bvFTD on all FTLD‐MOD language tasks. However, the utility of these measures in the differential diagnosis of AD vs. major FTLD syndromes in young‐onset cases remains underexplored.MethodWe examined participants with age‐of‐onset &lt; 65 years in the ARTFL‐LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD) consortium and the Longitudinal Early Onset AD Study (LEADS). 115 bvFTD, 53 semantic variant PPA (svPPA), 29 non‐fluent variant PPA (nfvPPA) and 124 early‐onset AD (eoAD) cases completed the UDS3 and FLTD‐MOD. Linear regression analyses measured group differences in FLTD‐MOD raw scores and UDS3 neuropsychological z‐scores after accounting for group differences in demographic variables and global severity ratings. Alpha was 0.05 with Bonferroni corrections.ResultsParticipants with eoAD demonstrated the most impaired scores on tasks of attention, working memory, and processing speed, including Digit Span Backward (z=‐1.87) and Trails A (z=‐3.82). They also demonstrated difficulty on FTLD‐MOD language tasks with a working memory requirement (sentence repetition raw=3.68/5) and, as expected, memory (story delayed recall z=‐2.4z). svPPA performed the worst on FTLD‐MOD and UDS3 tasks assessing semantic memory, especially naming (all p’s ≤ 0.03). nfvPPA performed worst on sentence reading, sentence repetition, and letter fluency (all p’s ≤ 0.02). Consistent with previous work, these measures differentiate between bvFTD and PPA variants. However, relative to eoAD, bvFTD was equivalent (Trails B: bvFTDz=‐3.8, eoADz=‐3.82; p=0.12) or outperformed (sentence repetition: bvFTD=4.22/5, eoAD=3.68/5; p&lt;0.001) the eoAD group on all tasks.ConclusionsWe undertook this analysis to compare performance of the major young‐onset sporadic AD and FTLD clinical syndromes in the ALLFTD and LEADS studies. Results demonstrate relatively distinct cognitive profiles among eoAD, svPPA, and nfvPPA, but not in bvFTD. Future analyses will include FTLD‐MOD behavioral symptom questionnaires to assess their utility in differentiating bvFTD.

The use of a new diagnostic method in patients for the differential diagnosis of Alzheimer’s disease (AD)

The use of a new diagnostic method in patients for the differential diagnosis of Alzheimer’s disease (AD)