BackgroundCerebrospinal fluid (CSF) biomarkers have been used to increase the evidence of underlying Alzheimer’s disease (AD) pathology in mild cognitive impairment (MCI). However, CSF biomarker-based classification often results in conflicting profiles with controversial prognostic value. Normalization of the CSF Aβ42 concentration to the level of total amyloid beta (Aβ), using the Aβ42/40 ratio, has been shown to improve the distinction between AD and non-AD dementia. Therefore, we evaluated whether the Aβ42/40 ratio would improve MCI categorization and more accurately predict progression to AD.MethodsOur baseline population consisted of 197 MCI patients, of which 144 had a follow-up ≥ 2 years, and comprised the longitudinal study group. To establish our own CSF Aβ42/40 ratio reference value, a group of 168 AD-dementia patients and 66 neurological controls was also included. CSF biomarker-based classification was operationalized according to the framework of the National Institute of Aging–Alzheimer Association criteria for MCI.ResultsWhen using the core CSF biomarkers (Aβ42, total Tau and phosphorylated Tau), 30% of the patients fell into the high-AD-likelihood (HL) group (both amyloid and neurodegeneration markers positive), 30% into the low-AD-likelihood group (all biomarkers negative), 28% into the suspected non-Alzheimer pathophysiology (SNAP) group (only neurodegeneration markers positive) and 12% into the isolated amyloid pathology group (only amyloid-positive). Replacing Aβ42 by the Aβ42/40 ratio resulted in a significant increase in the percentage of patients with amyloidosis (42–59%) and in the proportion of interpretable biological profiles (61–75%), due to a reduction by half in the number of SNAP cases and an increase in the proportion of the HL subgroup. Survival analysis showed that risk of progression to AD was highest in the HL group, and increased when the Aβ42/40 ratio, instead of Aβ42, combined with total Tau and phosphorylated Tau was used for biomarker-based categorization.ConclusionsOur results confirm the usefulness of the CSF Aβ42/40 ratio in the interpretation of CSF biomarker profiles in MCI patients, by increasing the proportion of conclusive profiles and enhancing their predictive value for underlying AD.Electronic supplementary materialThe online version of this article (10.1186/s13195-018-0362-2) contains supplementary material, which is available to authorized users.

The aim of this study was to investigate the accuracy of the Portuguese version of Addenbrooke's Cognitive Examination-Revised (ACE-R) in detecting and differentiating early stage subcortical vascular dementia (SVD) from early stage Alzheimer's disease (AD). Ninety-two subjects (18 SVD patients, 36 AD patients, and 38 healthy controls) were assessed using the ACE-R. Between-group's differences were evaluated using the Quade's rank analysis of covariance. The diagnostic accuracy and discriminatory ability of the ACE-R were examined via receiver operating characteristic (ROC) analysis. The ACE-R was able to successfully discriminate between patients and healthy subjects. The mean ACE-R total scores differed between SVD and AD patients; there were also significant differences in attention and orientation and in memory measures between the groups. An optimal cut-off of 72/73 was found for the detection of AD (sensitivity: 97%; specificity: 92%) and SVD (sensitivity: 100%; specificity: 92%).

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The purpose of this study is to analyze the utility of the Portuguese version of the Wechsler Memory Scale-3rd edition (WMS-III) with demented elderly people, namely its capacity to detect and discriminate between subcortical vascular dementia (SVD) and Alzheimer's disease (AD). We assessed early demented patients (SVD = 16; AD = 36) aged 65 or older who were compared to a control group (n = 40). Both clinical groups were adequately matched in terms of disease severity, overall cognitive functioning, depressive symptomatology, and pre-morbid intelligence. Between-group's differences were evaluated using the Quade's rank analysis of covariance. We also computed indexes and subtests optimal cut-off scores, and the corresponding sensitivity, specificity, and positive and negative predictive values, which were able to successfully discriminate between patients and healthy subjects. The SVD patients had a better overall memory performance than AD patients on the majority of the indexes and the delayed condition subtests of the WMS-III. The AD patients only showed a better performance on digit span subtest. Several measures discriminated patients from healthy subjects. This study suggests some recommendations for the diagnostic accuracy of the Portuguese version of WMS-III in dementia and about differential diagnosis between SVD and AD.

Background Colorectal cancer in pregnancy is a rare pathology with limited high-grade evidence available for guidance. The diagnosis of CRC in pregnant women is usually delayed, and once diagnosis is made, challenges exist as treatment options may be limited. Objective The study aims to highlight the importance of early investigation of symptomatic patients during pregnancy, as well as to update treatment and prognosis in CRC. Methods A literature search in PubMed database, including articles from 2006 to 2016 and cross-research articles with the initial research. Results Pregnancy can limit and contraindicate the utilization of standard diagnostic and therapeutic tools, which in particular can hamper the liberal use of colonoscopy and CT. Physical evaluation and abdominal US are first recommended; besides, MRI or CT may be used, only in indicated cases. Surgery is the main stay of treatment but radiotherapy and chemotherapy have significant role in posterior management of tumour. Conclusions Many studies are needed in order to achieve development in CRC pathogenesis during pregnancy as well as in treatment outcomes. The potential curative treatment of the disease should be the main aim of treatment when considering CRC in pregnancy. However, it is crucial to adapt the treatment to each patient, taking into account conscious decision on pregnancy further management.

Alpha-1 antitrypsin deficiency (AATD) is a rare genetic disorder characterised by reduced levels of circulating alpha-1 antitrypsin and an increased risk of lung and liver disease. Recent reviews of AATD have focused on diagnosis, epidemiology and clinical management; comprehensive reviews examining disease burden are lacking. Therefore, we conducted literature reviews to investigate the AATD disease burden for patients, caregivers and healthcare systems. Embase, PubMed and Cochrane libraries were searched for AATD publications from database inception to June 2021, in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Most published AATD studies were small and short in duration, with variations in populations, designs, measures and outcomes, complicating cross-study comparisons. AATD was associated with significant pulmonary and hepatic morbidity. COPD, emphysema and bronchiectasis were common lung morbidities, where smoking was a key risk factor. Fibrosis and steatosis were the most common liver complications reported in patients with a PiZ allele. Health status analyses suggested a poorer quality of life for AATD patients diagnosed with COPD versus those with non-AATD-associated COPD. The burden for caregivers included loss of personal time due to caring responsibilities, stress and anxiety. AATD was also associated with high direct medical costs and healthcare resource utilisation.

Background and purpose Creutzfeldt–Jakob disease (CJD) is a rare form of rapidly progressive neurodegenerative disorder. Seizures are uncommon in the early stage of CJD, increasing diagnostic difficulty. Methods An autopsy‐proven case of CJD presenting initially as an epilepsia partialis continua is reported, in which the initial workup was unremarkable. Retrospectively, the presence of nystagmus, which proved to be non‐epileptic, pointed to a cerebellar lesion before a diagnosis of clinically probable CJD was made. Results A 70‐year‐old man presented with a 3‐week history of intermittent rhythmic jerking tremors in his left limbs, interfering with his gait. Examination showed left body clonic movements. Electroencephalography revealed an ictal right centroparietal pattern of focal status epilepticus. Video‐oculography revealed right‐beating nystagmus (mean slow phase velocity [SPV] 3.4º/s) in the dark and left‐beating nystagmus (SPV 2.6º/s) in the light, left‐beating nystagmus after head shaking (SPV 4º/s) and during mastoid vibration (SPV 11º/s) and mildly hypoactive horizontal head impulses. Search for occult malignancy, serologies, cerebrospinal fluid analyses, anti‐onconeural antigen, auto‐immune panel and brain magnetic resonance imaging were unrevealing. Rapid neurological decline was observed. Three weeks later, cerebrospinal fluid was positive for 14.3.3 protein, electroencephalography showed generalized periodic sharp wave complexes and brain magnetic resonance imaging revealed diffusion restriction and T2/fluid‐attenuated inversion recovery hyperintensities in the cerebellum, basal ganglia, thalamus and cortex. He died 1 month later. Neuropathological study confirmed the diagnosis of CJD. Conclusion This case highlights that CJD should be considered in the differential diagnosis of new onset epilepsia partialis continua and that neuro‐ophthalmological examination can be helpful in pointing to early asymmetric cerebellar involvement.

Aim: Assess the budget impact of nationwide screening for diminished ovarian reserve (OR), via anti-Müllerian hormone (AMH) levels, to the Portugal National Health System (NHS). Patients & methods: The clinical journey was determined using literature and the family planning decision-making process/response using survey results. A panel of four local clinicians validated all assumptions/inputs. Results: Screening for OR led to an expected savings of € 9.4 million for the NHS, driven by a 24% reduction in medically assisted reproduction (MAR) use. When needed, referral for MAR was earlier and more women used first-line versus second-line techniques. The model estimated a 12% decrease in failure. Conclusion: This model shows AMH screening may allow more informed decisions, leading to a shorter fertility journey, more efficient use of treatments, and substantial cost-savings for the NHS.