Clinical variables contributing to the identification of biologically defined subgroups within cognitively unimpaired and mild cognitive impairment individuals.

BACKGROUND: A lack of consensus exists in linking demographic, behavioral, and cognitive characteristics to biological stages of dementia, defined by the ATN (amyloid, tau, neurodegeneration) classification incorporating amyloid, tau, and neuronal injury biomarkers. METHODS: Using a random forest classifier we investigated whether 27 demographic, behavioral, and cognitive characteristics allowed distinction between ATN-defined groups with the same cognitive profile. This was done separately for three cognitively unimpaired (CU) (112 A-T-N-; 46 A+T+N+/-; 65 A-T+/-N+/-) and three mild cognitive impairment (MCI) (128 A-T-N-; 223 A+T+N+/-; 94 A-T+/-N+/-) subgroups. RESULTS: Classification-balanced accuracy reached 39% for the CU and 52% for the MCI subgroups. Logical Delayed Recall (explaining 16% of the variance), followed by the Alzheimer's Disease Assessment Scale 13 (14%) and Everyday Cognition Informant (10%), were the most relevant characteristics for classification of the MCI subgroups. Race and ethnicity, marital status, and Everyday Cognition Patient were not relevant (0%). CONCLUSIONS: The demographic, behavioral, and cognitive measures used in our model were not informative in differentiating ATN-defined CU profiles. Measures of delayed memory, general cognition, and activities of daily living were the most informative in differentiating ATN-defined MCI profiles; however, these measures alone were not sufficient to reach high classification performance.

Small vessel disease burden and functional brain connectivity in mild cognitive impairment.

Background: The role of small vessel disease in the development of dementia is not yet completely understood. Functional brain connectivity has been shown to differ between individuals with and without cerebral small vessel disease. However, a comprehensive measure of small vessel disease quantifying the overall damage on the brain is not consistently used and studies using such measure in mild cognitive impairment individuals are missing. Method: Functional brain connectivity differences were analyzed between mild cognitive impairment individuals with absent or low (n = 34) and high (n = 34) small vessel disease burden using data from the Parelsnoer Institute, a Dutch multicenter study. Small vessel disease was characterized using an ordinal scale considering: lacunes, microbleeds, perivascular spaces in the basal ganglia, and white matter hyperintensities. Resting state functional MRI data using 3 Tesla scanners was analyzed with group-independent component analysis using the CONN toolbox. Results: Functional connectivity between areas of the cerebellum and between the cerebellum and the thalamus and caudate nucleus was higher in the absent or low small vessel disease group compared to the high small vessel disease group. Conclusion: These findings might suggest that functional connectivity of mild cognitive impairment individuals with low or absent small vessel disease burden is more intact than in mild cognitive impairment individuals with high small vessel disease. These brain areas are mainly responsible for motor, attentional and executive functions, domains which in previous studies were found to be mostly associated with small vessel disease markers. Our results support findings on the involvement of the cerebellum in cognitive functioning.

Effects of interventions on cerebral perfusion in the Alzheimer's disease spectrum: A systematic review.

Cerebral perfusion dysfunctions are seen in the early stages of Alzheimer's disease (AD). We systematically reviewed the literature to investigate the effect of pharmacological and non-pharmacological interventions on cerebral hemodynamics in randomized controlled trials involving AD patients or Mild Cognitive Impairment (MCI) due to AD. Studies involving other dementia types were excluded. Data was searched in April 2021 on MEDLINE, Embase, and Web of Science. Risk of bias was assessed using Cochrane Risk of Bias Tool. A meta-synthesis was performed separating results from MCI and AD studies. 31 studies were included and involved 310 MCI and 792 CE patients. The MCI studies (n = 8) included physical, cognitive, dietary, and pharmacological interventions. The AD studies (n = 23) included pharmacological, physical interventions, and phytotherapy. Cerebral perfusion was assessed with PET, ASL, Doppler, fNIRS, DSC-MRI, Xe-CT, and SPECT. Randomization and allocation concealment methods and subject characteristics such as AD-onset, education, and ethnicity were missing in several papers. Positive effects on hemodynamics were seen in 75 % of the MCI studies, and 52 % of the AD studies. Inserting cerebral perfusion outcome measures, together with established AD biomarkers, is fundamental to target all disease mechanisms and understand the role of cerebral perfusion in AD.

Short- and Long-Term Functional Connectivity Differences Associated with Alzheimer's Disease Progression.

INTRODUCTION: Progression of amnestic mild cognitive impairment (aMCI) to Alzheimer's disease (AD) is a clinical event with highly variable progression rates varying from 10-15% up to 30-34%. Functional connectivity (FC), the temporal similarity between spatially remote neurophysiological events, has previously been reported to differ between aMCI patients who progress to AD (pMCI) and those who do not (i.e., remain stable; sMCI). However, these reports had a short-term follow-up and do not provide insight into long-term AD progression. METHODS: Seventy-nine participants with a baseline and 78 with a 12-month, 51 with a 24-month, and 22 with a +48-month follow-up resting-state fMRI with aMCI diagnosis from the Alzheimer's Disease Neuroimaging Initiative database were included. FC was assessed using the CONN toolbox. Local correlation and group independent component analysis were utilized to compare regional functional coupling and between-network FC, respectively, between sMCI and pMCI groups. Two-sample t tests were used to test for statistically significant differences between groups, and paired t-tests were used to assess cognitive changes over time. RESULTS: All participants (i.e., 66 sMCI and 19 pMCI) had a baseline and a year follow-up fMRI scan. Progression from aMCI to AD occurred in 19 patients (10 at 12 months, 5 at 24 months, and 4 at >48 months), while 73 MCI patients remained cognitively stable (sMCI). The pMCI and sMCI cognitive profiles were different. More between-network FC than regional functional coupling differences were present between sMCI and pMCI patients. Activation in the salience network (SN) and the default mode network (DMN) was consistently different between sMCI and pMCI patients across time. DISCUSSION: sMCI and pMCI patients have different cognitive and FC profiles. Only pMCI patients showed cognitive differences across time. The DMN and SN showed local correlation and between-network FC differences between the sMCI and pMCI patient groups at multiple moments in time.

Functional connectivity differences in Alzheimer's disease and amnestic mild cognitive impairment associated with AT(N) classification and anosognosia.

Alzheimer's continuum biological profiles (A+T-N-, A+T+N-, A+T-N+, and A+T+N+) were established in the 2018 National Institute on Aging and Alzheimer's Association research framework for Alzheimer's disease (AD). We aim to assess the relation between AT(N) biomarker profiles and brain functional connectivity (FC) and assess the neural correlates of anosognosia. We assessed local functional coupling and between-network connectivity through between-group intrinsic local correlation and independent component analyses. The neural correlates of anosognosia were assessed via voxel-wise linear regression analysis in prodromal AD. Statistical significance for the FC analysis was set at p ≤ 0.05 false discovery rate (FDR)-corrected for cluster size. One hundred and twenty-one and 73 participants were included in the FC and the anosognosia analysis, respectively. The FC in the default mode network is greater in prodromal AD than AD with dementia (i.e., local correlation: T = 8.26, p-FDR < 0.001, k = 1179; independent component analysis: cerebellar network, T = 4.01, p-FDR = 0.0012, k = 493). The default mode network is persistently affected in the early stages of Alzheimer's biological continuum. The anterior cingulate cortex (T = 2.52, p-FDR = 0.043, k = 704) is associated with anosognosia in prodromal AD.

Factors Associated With Urgent-Start Peritoneal Dialysis Catheter Complications in ESRD.

INTRODUCTION: Urgent-start peritoneal dialysis (PD) in patients with newly diagnosed end-stage renal disease (ESRD) is a well-tolerated alternative to hemodialysis (HD). The primary aim of this study was to identify the demographic and clinical characteristics of ESRD patients, as well as the presurgical, surgical, and postsurgical factors associated with urgent-start PD complications. METHODS: A retrospective cross-sectional observational study was performed on 102 patients with ESRD who merited urgent-start PD from January 2015 to June 2019. The primary clinical outcome measures were catheter leakage, dysfunction, and peritonitis, whereas the secondary outcomes were catheter removal, repositioning, and death. Statistical inferences were made with the χ2 or Fisher's exact test and independent samples t tests. RESULTS: One hundred two subjects (65 men, 63.7%) 56.2 ± 15.1 years old were included in this study; 64 of the subjects had diabetes and hypertension (62.7%). Catheter leakage occurred in 8 patients (7.8%), catheter dysfunction in 27 patients (26.5%), and peritonitis in 14 patients (13.7%); meanwhile, catheter removal occurred in 6 patients (5.9%), catheter repositioning in 21 patients (20.6%), and death in 3 patients (2.9%). Peritonitis was associated with younger age (i.e., 47.0 ± 16.8 vs. 57.6 ± 14.4 years; P = 0.014; 95% confidence interval [CI]: 2.2-19.1; odds ratio [OR] 0.96; P = 0.018; 95% CI: 0.92-099), higher creatinine levels upon admission (i.e., 20.2 ± 9.8 vs. 14.1 ± 8.3; P = 0.014; 95% CI: -10.9 to -1.2), and heart failure (OR 4.79; P = 0.043; 95% CI: 1.05-21.88). Patients with abdominal hernia were 7.5 times more likely to have their catheter leak (OR 7.5; P = 0.036; 95% CI: 1.14-49.54). Catheter removal was associated with obesity (i.e., body mass index [BMI] of 31.6 ± 4.1 vs. 25.9 ± 4.9; P = 0.007; 95% CI: -9.8 to -1.6; OR 1.26; P = 0.013; 95% CI: 1.05-1.51) and Modification of Diet in Renal Disease glomerular filtration rate (MDRD-GFR) (i.e., 2.5 ± 0.6 vs. 3.7 ± 2.3; P = 0.003; 95% CI: 0.5-1.9). CONCLUSION: Peritonitis was associated with younger age, higher creatinine levels upon admission, and heart failure; meanwhile, catheter removal was linked to obesity and lower glomerular filtration rate. Compared with previous reports, our study included patients in which PD was initiated shortly after catheter insertion, making the intervention a true urgent-start PD. This study contributes to the existing urgent-start PD literature by providing evidence that urgent-start PD with catheter opening within 72 hours has limited complications, making it a relatively safe option.

Bioethical implications of end-of-life decision-making in patients with dementia: a tale of two societies.

End-of-life decision-making in patients with dementia is a complex topic. Belgium and the Netherlands have been at the forefront of legislative advancement and progressive societal changes concerning the perspectives toward physician-assisted death (PAD). Careful consideration of clinical and social aspects is essential during the end-of-life decision-making process in patients with dementia. Geriatric assent provides the physician, the patient and his family the opportunity to end life with dignity. Unbearable suffering, decisional competence, and awareness of memory deficits are among the clinical considerations that physicians should incorporate during the end-of-life decision-making process. However, as other societies introduce legislature granting the right of PAD, new social determinants should be considered; Mexico City is an example. Current perspectives regarding advance euthanasia directives (AED) and PAD in patients with dementia are evolving. A new perspective that hinges on the role of the family and geriatric assent should help culturally heterogeneous societies in the transition of their public health care policies regarding end-of-life choices.

Paraneoplastic opsoclonus-myoclonus syndrome secondary to melanoma metastasis form occult primary cancer.

INTRODUCTION: Opsoclonus-myoclonus syndrome (OMS) is an inflammatory neurological disorder, often requiring a prompt medical evaluation. Among the diverse etiologies associated with OMS are autoimmune, infectious, paraneoplastic, and systemic diseases, and drug intoxication. CLINICAL SUMMARY: The case of a 36-year-old female with a disabling holocranial headache, sudden loss of consciousness, aggressive behavior, vertigo, and a personal history of somatoform disorder and major depression is presented here. After hospital admission, the patient developed sudden stereotyped movements in all four extremities and oculogyric crises compatible with OMS. Cerebrospinal fluid analysis, viral and autoimmune assays, as well as blood, urine, and bronchial secretion cultures, drug metabolite urinalysis, and tumor markers were all negative. Furthermore, brain computed tomography (CT) and brain magnetic resonance imaging, along with thoraco-abdominopelvic CT and electroencephalography, were also all negative. The patient suffered type one respiratory insufficiency after 72 h of hospitalization, requiring an endotracheal tube. After 13 days the patient suffered cardiac arrest. Necropsy was performed reporting lymph nodes with a poorly differentiated malignant neoplastic lesion, HMB-45, melan-A, vimentin, and S-100 positive, compatible with melanoma metastasis from an occult primary cancer. DISCUSSION: While the incidence of melanoma of unknown primary is between 2.6 and 3.2%, with a median overall survival ranging between 24 and 127 months, when melanoma patients develop OMS their survival is markedly decreased. Although only 5 cases of paraneoplastic OMS secondary to melanoma have been reported in the literature, all had a poor prognosis, dying within 8 months of OMS onset.

Clinical Considerations in Physician-Assisted Death for Probable Alzheimer's Disease: Decision-Making Capacity, Anosognosia, and Suffering.

BACKGROUND: Requests for physician-assisted death (PAD) in patients with cognitive impairment are complex and require careful consideration. Of particular difficulty is determination of whether the request is voluntary and well considered. RESULTS: Euthanasia and physician-assisted suicide (PAS) are both legal in The Netherlands, Luxemburg, Colombia, and Canada. Euthanasia is legal in Belgium, while PAS is legal in Switzerland and Oregon, Washington, Montana, Vermont, and California (USA). Upon a PAD request, evaluation of the capacity to consent medical treatment is relevant for the decision-making process, while evaluation of testamentary capacity is appropriate before an advance euthanasia directive is written. Anosognosia assessment throughout the Alzheimer's disease continuum provides essential and relevant information regarding the voluntary and well-considered nature of the PAD request; meanwhile, early assessment of hypernosognosia or subjective cognitive decline assists in formulation of a clinical prognosis. Furthermore, the assessment of physical and psychological suffering should incorporate verbal and nonverbal cues as well as consideration of the psychosocial factors that might affect due care criteria. CONCLUSION: The clinical approach to a PAD request should consider the legal framework and the decision-making capacity, assess memory deficit awareness and the perception of suffering, and evaluate mental competency when considered pertinent.

Axillobifemoral bypass for total abdominal occlusion secondary to Takayasu's arteritis: A case report.

INTRODUCTION: Takayasu's arteritis (TA) is a rare disease that mainly affects large arteries. Approximately 20% of TA patients will require surgical intervention secondary to arterial complications such as intermittent claudication, persistent hypertension refractory to treatment, and heart failure. PRESENTATION OF CASE: The case of a 22-year-old female with TA of five years of evolution is presented. The patient deteriorated clinically after five years of corticosteroid and immunosuppressant management requiring surgical intervention with an axillobifemoral bypass for a total abdominal occlusion. Onset, pre-surgical and post-surgical Doppler ultrasonography as well as abdominal angiotomographies document and corroborate the patient's clinical and hemodynamic improvement. DISCUSSION: Very limited literature exists regarding surgical interventions for TA patients. While most reported cases present an endovascular surgical management. Open surgical procedures have lower rates of restenosis than endovascular management. Although endovascular management is less invasive than extra-anatomical axillobifemoral bypass, the patient was not a candidate for endovascular stent graft placement due to the increased risk for vascular injury and subsequent perforation. Approximately a fifth of TA patients are candidates for surgical intervention over time. CONCLUSION: Vascular surgery in TA cases becomes an option when the patient does not improve clinically after administration of medical treatment. Although endovascular management has fewer complications, the rate of restenosis is higher. Patients at risk of restenosis and who have increased perioperative vascular risk can benefit from open surgical procedures. Surgical management should be tailored to the patient's needs.

Functional Neural Correlates of Anosognosia in Mild Cognitive Impairment and Alzheimer's Disease: a Systematic Review.

Functional neuroimaging techniques (i.e. single photon emission computed tomography, positron emission tomography, and functional magnetic resonance imaging) have been used to assess the neural correlates of anosognosia in mild cognitive impairment (MCI) and Alzheimer's disease (AD). A systematic review of this literature was performed, following the Preferred Reporting Items for Systematic Reviews and Meta Analyses statement, on PubMed, EMBASE, and PsycINFO databases. Twenty-five articles met all inclusion criteria. Specifically, four brain connectivity and 21 brain perfusion, metabolism, and activation articles. Anosognosia is associated in MCI with frontal lobe and cortical midline regional dysfunction (reduced perfusion and activation), and with reduced parietotemporal metabolism. Reduced within and between network connectivity is observed in the default mode network regions of AD patients with anosognosia compared to AD patients without anosognosia and controls. During initial stages of cognitive decline in anosognosia, reduced indirect neural activity (i.e. perfusion, metabolism, and activation) is associated with the cortical midline regions, followed by the parietotemporal structures in later stages and culminating in frontotemporal dysfunction. Although the current evidence suggests differences in activation between AD or MCI patients with anosognosia and healthy controls, more evidence is needed exploring the differences between MCI and AD patients with and without anosognosia using resting state and task related paradigms.

Headache, Delirium or Encephalitis? A Case of Residual Mutism Secondary to Anti-NMDA Receptor Encephalitis.

Encephalitis is a heterogeneous syndrome that is diagnosed through clinical assessment and the assistance of laboratory, neuroimaging and electroencephalographic workup. Over the past 10 years, autoimmune encephalitis has been more frequently recognized; however, most reports come from highly specialized hospital settings. Anti-N-methyl-D-aspartate receptor (NDMAR) encephalitis has been associated with paraneoplastic encephalitis syndromes and was first recognized in 2005. We present the case of a 34-year-old male patient who debuted clinically with a headache associated with neuropsychiatric symptoms (i.e., visual and auditory hallucinations, anxiety, aggressiveness) and memory deficits, progressing to autonomic dysfunction (i.e., tachycardia and hypertension), seizures, and stupor with catatonic features. Initially, infectious, metabolic, and toxicological etiologies were excluded; followed by the assessment of immunological and paraneoplastic etiologies, yielding positive IgG levels for anti-NMDAR antibodies. The patient was treated successfully with systemic steroid therapy and therapeutic plasmapheresis, while mutism was the only sequela. Although large case series reporting on paraneoplastic and autoimmune anti-NMDAR encephalitis have been reported in the literature in recent years, this case is of particular importance due to the stepwise differential diagnosis and treatment management procedure that was used in a regional but not highly specialized hospital setting.

A Case of Acute Pemphigus Vulgaris Relapses Associated with Cocaine Use and Review of the Literature.

Pemphigus is a bullous autoimmune disease that affects the skin and mucous membranes. It is very difficult to establish the etiology and the triggering factors that influence reactivations in pemphigus vulgaris (PV). The case of a 33-year-old male with chronic history of intranasal cocaine consumption is presented in this report. We present the clinical case of the patient, followed for a total of 86 weeks, with ten relapses secondary to probable cocaine use. The patient was admitted to the emergency department after presenting polymorphic dermatosis characterized by blisters, vesicles, and excoriations extending from the oral cavity to the thorax, and to the inguinal and genital regions, affecting approximately 35 % of the body surface area with a score of 56 on the Pemphigus Skin Disorder Index. Skin biopsies were compatible with PV diagnosis. The patient had clinical improvement with a combination of methylprednisolone 500 mg intravenously (IV) and cyclophosphamide 500 mg IV every 15 days, along with prednisone 50 mg orally (PO) q24 h and mycophenolic acid 500 mg PO q6 h. Persistent cocaine use is highly likely to be the factor triggering lesion reactivation and responsible for the torpid evolution. We cannot definitively conclude whether the change from azathioprine to mycophenolic acid after the tenth relapse was the adjuvant medication responsible for the end of the consolidation phase and complete remission on therapy. This case study could potentially serve as a guide for management of patients who continuously persist with cocaine use, leading to a clinical picture refractory to multiple therapeutic schemes.

Invasive Pulmonary Adenocarcinoma with Lepidic Growth Pattern in a Pregnant Patient.

Among the differential diagnoses that should be considered in acute respiratory failure (ARF) are infectious processes, autoimmune diseases, interstitial pulmonary fibrosis, and pulmonary neoplasia. Timely diagnosis of lung neoplasia is complicated in the early stages. An opportune diagnosis, as well as the specific treatment, decrease mortality. ARF occurs 1 in 500 pregnancies and is most common during the postpartum period. Among the specific etiologies that cause ARF during pregnancy that must be considered are: (1) preeclampsia; (2) embolism of amniotic fluid; (3) peripartum cardiomyopathy; and (4) trophoblastic embolism. The case of a 36-year-old patient with a 33-week pregnancy and ARF is presented. The patient presented dyspnea while exerting moderate effort that progressed to orthopnea and type 1 respiratory insufficiency. Imaging studies showed bilateral alveolar infiltrates and predominantly right areas of consolidation. Blood cultures, a galactomannan assay and IgG antibodies against mycoplasma pneumoniae, were reported as negative. Autoimmune etiology was ruled out through an immunoassay. A percutaneous pulmonary biopsy was performed and an invasive pulmonary adenocarcinoma with lepidic growth pattern (i.e. lepidic pulmonary adenocarcinoma, LPA) result was reported. This etiology is rare and very difficult to recognize in acute respiratory failure cases. After infectious, autoimmune and interstitial lung fibrosis have been excluded the clinician must suspect of lung cancer in a patient with acute respiratory failure and chest imaging compatible with the presence of ground-glass nodular opacities, a solitary nodule or mass with bronchogram, and lung consolidation. In the presence of acute respiratory failure, the suspicion of pulmonary neoplasia in an adult of reproductive age must be timely. Failure to recognize this etiology can lead to fatal results.

Hippocampal Volumetry as a Biomarker for Dementia in People with Low Education.

BACKGROUND/AIMS: To evaluate the relationship between hippocampal volume and cognitive decline in patients with dementia due to probable Alzheimer's disease (AD), amnestic mild cognitive impairment (aMCI) and education, and the possible relationship between cognitive reserve and education in this population. METHODS: From February 2013 to October 2015, 76 patients (25 men, 51 women) were classified according to the NIA-AA diagnostic criteria. We used two 3.0-tesla MRI scanners and performed manual hippocampal volumetry. RESULTS: Twenty-six patients were found to have AD, 20 aMCI and 30 had normal aging (NA). The mean normalized hippocampal volume in age-, sex- and education (years)-matched subjects was 2.38 ± 0.51 cm3 in AD (p < 0.001), 2.91 ± 0.78 cm3 in aMCI (p = 0.019) and 3.07 ± 0.76 cm3 in NA. CONCLUSION: Psychometric test (MMSE and MoCA) scores had a good to strong positive correlation with statistically significant differences in the entire population and healthy subjects but not among dementia patients and lower educational level groups. The patients with low education had greater hippocampal volumes, which is in line with the cognitive reserve theory; lower-educated individuals can tolerate less neuropathology and will thus show less atrophy at a similar level of cognitive performance than higher-educated subjects.

Diagnosis and Treatment Options of Spinal Metastases.

Cancer patients with spinal metastases are a diagnostic and treatment challenge for the clinician. This challenge must be addressed through a multidisciplinary, multimodal, and individualized management. The presence of tumor cells in bone metastases results in homeostatic disruption between bone formation and remodeling. Bone destruction is a late event in the formation of lytic bone metastasis, starting when tumor cells proliferate; this in turn activates osteoclasts, seen as trabecular destruction in imaging studies. There may be excessive bone destruction and increased bone formation, which produce blastic lesions. Bone scintigraphy is currently the most widely used diagnostic method and is considered as the reference test for the diagnosis of spinal bone metastasis. However, we believe that in the near future positron emission tomography associated to computed tomography with 18F-NaF, or magnetic resonance using diffusion-weighted whole-body imaging with background body signal suppression, will replace bone scintigraphy due to their improved diagnostic accuracy. These new diagnostic tools will help prevent bone metastasis complications such as: intractable pain; spinal cord or cauda equina compression; hypercalcemia; pathological fractures; and spinal instability. With regards to the treatment, it can be uni- or multimodal, depending on the type and number of bone metastases. Among the types of treatment available for bone metastasis are chemotherapy, radiotherapy, and invasive procedures. The prognosis of patient survival depends on the histopathology of the primary tumor, the presence of bone metastasis, and the presence of neurological deficits.