To expand the differential diagnosis of headache and ophthalmoparesis by describing a case report in which anti-GQ1b was demonstrated to be the cause.
Anti-GQ1b antibody syndrome refers to a clinical ...spectrum of conditions that share common mechanisms and overlapping manifestations, including the Miller-Fisher syndrome, pharyngeal-cervical-brachial weakness, and Bickerstaff brainstem encephalitis. Rare atypical cases presenting as acute ophthalmoparesis (AO) without ataxia or areflexia have been described. Headache is a rare condition in these disorders.
A 49-year-old woman with no history of headaches began experiencing an acute severe bilateral throbbing headache associated with nausea and photophobia. Five days later, she developed constant binocular horizontal diplopia.
Bilateral paresis of both sixth nerves was noted. Her ocular fundi, tendon reflexes, and other findings of the physical exam were normal. In addition, both a brain MRI performed with gadolinium and a lumbar puncture yielded normal results. Serum anti-GQ1b IgG was found to be positive. Her symptoms resolved completely following treatment with immunoglobulins (0.4 g/kg/day for 5 days).
This is the first reported case of AO related to anti-GQ1b antibodies presenting with headache as its initial symptom. The presence of anti-GQ1b antibodies should be determined in patients with headache and AO of unknown origin. Immunoglobulins could hasten the resolution of symptoms in these patients.
The global growing rates of cognitive decline and dementia, together with the absence of curative therapies for these conditions, support the interest in researching potential primary prevention ...interventions, with particular focus on dietary habits. The aim was to assess the association between polyphenol intake and 6-year change in cognitive function in the ‘Seguimiento Universidad de Navarra’ (SUN) Project, a Spanish prospective cohort study. Changes (final – initial) in cognitive function were evaluated in a subsample of 806 participants (mean age 66 (sd 5) years, 69·7 % male) of the SUN Project using the validated Spanish Telephone Interview for Cognitive Status-modified score. Polyphenol intake was derived from a validated semi-quantitative FFQ and matching food composition data from the Phenol-Explorer database. Multivariable linear regression models were used to evaluate the association between total polyphenol intake, polyphenol subclasses and cognitive changes. No significant association between total polyphenol intake and changes in cognitive function was found. However, a higher intake of lignans (β
Quintile (Q) 5 v. Q1 0·81; 95 % CI 0·12, 1·51; P
trend = 0·020) and stilbenes (β
Q5 v. Q1 0·82; 95 % CI 0·15, 1·49; P
trend = 0·028) was associated with more favourable changes in cognitive function over time, particularly with respect to immediate memory and language domains. Olive oil and nuts were the major sources of variability in lignan intake, and wine in stilbene intake. The results suggest that lignan and stilbene intake was associated with improvements in cognitive function.
Addenbrooke's Cognitive Examination III (ACE-III) is a screening test that was recently validated for diagnosing dementia. Since it assesses attention, language, memory, fluency, and visuospatial ...function separately, it may also be useful for general neuropsychological assessments. The aim of this study was to analyze the tool's ability to detect early stages of Alzheimer's disease and to examine the correlation between ACE-III scores and scores on standardized neuropsychological tests.
Our study included 200 participants categorized as follows: 25 healthy controls, 48 individuals with subjective memory complaints, 47 patients with amnestic mild cognitive impairment and 47 mild Alzheimer's disease, and 33 patients with other neurodegenerative diseases.
The ACE-III memory and language domains were highly correlated with the neuropsychological tests specific to those domains (Pearson correlation coefficient of 0.806 for total delayed recall on the Free and Cued Selective Reminding Test vs. 0.744 on the Boston Naming Test). ACE-III scores discriminated between controls and patients with amnestic mild cognitive impairment (AUC: 0.906), and between controls and patients with mild Alzheimer's disease (AUC: 0.978).
Our results suggest that ACE-III is a useful neuropsychological test for assessing the cognitive domains of attention, language, memory, and visuospatial function. It also enables detection of Alzheimer's disease in early stages.
Plasma biomarkers for Alzheimer's disease (AD) are a promising tool that may help in early diagnosis. However, their levels may be influenced by physiological parameters and comorbidities that should ...be considered before they can be used at the population level. For this purpose, we assessed the influences of different comorbidities on AD plasma markers in 208 cognitively unimpaired subjects. We analyzed both plasma and cerebrospinal fluid levels of Aβ40, Aβ42, and p-tau181 using the fully automated Lumipulse platform. The relationships between the different plasma markers and physiological variables were studied using linear regression models. The mean differences in plasma markers according to comorbidity groups were also studied. The glomerular filtration rate showed an influence on plasma Aβ40 and Aβ42 levels but not on the Aβ42/Aβ40 ratio. The amyloid ratio was significantly lower in diabetic and hypertensive subjects, and the mean p-tau181 levels were higher in hypertensive subjects. The glomerular filtration rate may have an inverse relationship on plasma Aβ40 and Aβ42 levels but not on the amyloid ratio, suggesting that the latter is a more stable marker to use in the general population. Cardiovascular risk factors might have a long-term effect on the amyloid ratio and plasma levels of p-tau181.
Abstract
Background
The arrival of new disease-modifying treatments for Alzheimer’s disease (AD) requires the identification of subjects at risk in a simple, inexpensive, and non-invasive way. With ...tools allowing an adequate screening, it would be possible to optimize the use of these treatments. Plasma markers of AD are very promising, but it is necessary to prove that alterations in their levels are related to alterations in gold standard markers such as cerebrospinal fluid or PET imaging. With this research, we want to evaluate the performance of plasma Aβ40, Aβ42, and p-tau181 to detect the pathological changes in CSF using the automated Lumipulse platform.
Methods
Both plasma and CSF Aβ40, Aβ42, and p-tau181 have been evaluated in a group of 208 cognitively unimpaired subjects with a 30.3% of
ApoE
4 carriers. We have correlated plasma and CSF values of each biomarker. Then, we have also assessed the differences in plasma marker values according to amyloid status (A − / +), AD status (considering AD + subjects to those A + plus Tau +), and ATN group defined by CSF. Finally, ROC curves have been performed, and the area under the curve has been measured using amyloid status and AD status as an outcome and different combinations of plasma markers as predictors.
Results
Aβ42, amyloid ratio, p-tau181, and p-tau181/Aβ42 ratio correlated significantly between plasma and CSF. For these markers, the levels were significantly different in the A + / − , AD + / − , and ATN groups. Amyloid ratio predicts amyloid and AD pathology in CSF with an AUC of 0.89.
Conclusions
Plasma biomarkers of AD using the automated Lumipulse platform show good diagnostic performance in detecting Alzheimer’s pathology in cognitively unimpaired subjects.
Subjective cognitive decline (SCD) may represent a preclinical stage of Alzheimer's disease (AD). Predicting progression of SCD patients is of great importance in AD-related research but remains a ...challenge.
To develop and implement an ensemble machine learning (ML) algorithm to identify SCD subjects at risk of conversion to mild cognitive impairment (MCI) or AD.
Ninety-nine SCD patients were included. Thirty-two progressed to MCI/AD, while 67 remained stable. To minimize the effect of class imbalance, both classes were balanced, and sensitivity was taken as evaluation metric. Bagging and boosting ML models were developed by using socio-demographic and clinical information, Mini-Mental State Examination and Geriatric Depression Scale (GDS) scores (feature-set 1a); socio-demographic characteristics and neuropsychological tests scores (feature-set 1b) and regional magnetic resonance imaging grey matter volumes (feature-set 2). The most relevant variables were combined to find the best model.
Good prediction performances were obtained with feature-sets 1a and 2. The most relevant variables (variable importance exceeding 20%) were: Age, GDS, and grey matter volumes measured in four cortical regions of interests. Their combination provided the optimal classification performance (highest sensitivity and specificity) ensemble ML model, Extreme Gradient Boosting with over-sampling of the minority class, with performance metrics: sensitivity = 1.00, specificity = 0.92 and area-under-the-curve = 0.96. The median values based on fifty random train/test splits were sensitivity = 0.83 (interquartile range (IQR) = 0.17), specificity = 0.77 (IQR = 0.23) and area-under-the-curve = 0.75 (IQR = 0.11).
A high-performance algorithm that could be translatable into practice was able to predict SCD conversion to MCI/AD by using only six predictive variables.
Plasma biomarkers of Alzheimer's disease (AD) constitute a non-invasive tool for diagnosing and classifying subjects. They change even in preclinical stages, but it is necessary to understand their ...properties so they can be helpful in a clinical context.
With this work we want to study the evolution of p-tau231 plasma levels in the preclinical stages of AD and its relationship with both cognitive and imaging parameters.
We evaluated plasma phosphorylated (p)-tau231 levels in 146 cognitively unimpaired subjects in sequential visits. We performed a Linear Mixed-effects Model to analyze their rate of change. We also correlated their baseline levels with cognitive tests and structural and functional image values. ATN status was defined based on cerebrospinal fluid biomarkers.
Plasma p-tau231 showed a significant rate of change over time. It correlated negatively with memory tests only in amyloid-positive subjects. No significant correlations were found with any imaging measures.
Increases in plasma p-tau231 can be detected at one-year intervals in cognitively healthy subjects. It could constitute a sensitive marker for detecting early signs of neuronal network impairment by amyloid.
The optimal cut-off for Alzheimer's disease (AD) CSF biomarkers remains controversial.
To analyze the performance of cut-off points standardized by three methods: one that optimized the agreement ...between 11C-Pittsburgh compound B PET (a-PET) and CSF biomarkers (Aβ1-42, pTau, tTau, and Aβ1-42/Aβ1-40 ratio) in our population, called PET-driven; an unbiased cut-off using data from a healthy research cohort, called data-driven, and that provided by the manufacturer. We also compare changes in ATN classification.
CSF biomarkers measured by the LUMIPULSE G600II platform and qualitative visualization of amyloid positron emission tomography (a-PET) were performed in all the patients. We established a cut-off for each single biomarker and Aβ1-42/Aβ1-40 ratio that optimized their agreement with a-PET using ROC curves. Sensitivity, Specificity, and Overall Percent of Agreement are assessed using a-PET or clinical diagnosis as gold standard for every cut-off. Also, we established a data-driven cut-off from our cognitively unimpaired cohort. We then analyzed changes in ATN classification.
One hundred and ten patients were recruited. Sixty-six (60%) were a-PET positive. PET-driven cut-offs were: pTau > 57, tTau > 362.62, Aβ1-42/Aβ1-40 < 0.069. For a single biomarker, pTau showed the highest accuracy (AUC 0.926). New PET-driven cut-offs classified patients similarly to manufacturer cut-offs (only two patients changed). However, 20 patients (18%) changed when data-driven cut-offs were used.
We established our sample's best CSF biomarkers cut-offs using a-PET as the gold standard. These cut-offs categorize better symptomatic subjects than data-driven in ATN classification, but they are very similar to the manufacturer's.
