Asunto(s)
Apolipoproteína E4/genética , Corteza Cerebral/diagnóstico por imagen , Disfunción Cognitiva/diagnóstico por imagen , Proteína HMGB1/metabolismo , Anciano , Estudios de Casos y Controles , Corteza Cerebral/patología , Disfunción Cognitiva/genética , Disfunción Cognitiva/metabolismo , Escolaridad , Femenino , Humanos , Inflamación/metabolismo , Masculino , Persona de Mediana Edad , Tamaño de los ÓrganosRESUMEN
BACKGROUND: Young-onset cognitive disorders (YOCD) often manifests with complex and atypical presentations due to underlying heterogenous pathologies. Therefore, a biomarker-based evaluation will allow for timely diagnosis and definitive management. OBJECTIVE: Here, we evaluated the safety and usefulness of cerebrospinal fluid (CSF) sampling through lumbar puncture (LP) in YOCD patients in a tertiary clinical setting. METHODS: Patients with mild cognitive impairment (MCI) and mild dementia with age of onset between 45-64 years were evaluated. Patients underwent magnetic resonance imaging and their medial temporal lobe atrophy (MTA) was rated. LP side-effects and the impact of the CSF findings on diagnosis and management were analyzed. RESULTS: 142 patients (53 (37.32%) MCI, 51 (35.92%) dementia of the Alzheimer's disease [DAT] type, and 38 (26.76%) non-AD type dementia) who underwent LP between 2015 to 2021 were analyzed. Using post-LP results and MTA ratings, 74 (52.11%) patients met the AT(N) criteria for AD. 56 (39.44%) patients (28 out of 53 (50.0%) MCI, 12 out of 51 (21.43%) DAT, and 16 out of 38 (28.57%) non-AD dementia) had a change in diagnosis following LP. 13 (9.15%) patients developed side-effects post-LP (11 (84.62%) patients had headache, 1 (7.69%) patient had backache, and 1 (7.69%) patient had headache and backache). 32 (22.54%) patients had a change in management post-LP, 24 (75.0%) had medication changes, 10 (31.30%) had referrals to other specialists, and 3 (9.40%) was referred for clinical trial with disease modifying interventions. CONCLUSION: LP is well-tolerated in YOCD and can bring about relevant clinical decisions with regards to the diagnosis and management of this complex clinical condition.
Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Demencia , Humanos , Enfermedad de Alzheimer/diagnóstico , Péptidos beta-Amiloides/líquido cefalorraquídeo , Atrofia , Biomarcadores/líquido cefalorraquídeo , Cognición , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/patología , Disfunción Cognitiva/terapia , Demencia/diagnóstico , Progresión de la Enfermedad , Cefalea , Punción Espinal/efectos adversosRESUMEN
BACKGROUND: Lipid biomarkers have potential neuroprotective effects in Parkinson's disease (PD) and there is limited evidence in the field. OBJECTIVE: This study aims to investigate the association between comprehensive blood lipid biomarkers and PD. METHODS: A total of 205 PD patients and 102 non-PD subjects were included from Early Parkinson's disease Longitudinal Singapore (PALS) cohort. We investigated 6 serum lipid biomarkers including total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A1 (Apo A1), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (Apo B). PD patients were further classified into mild cognitive impairment (MCI) and normal cognition (NC) subgroups. We conducted a cross-sectionals study to examine the association between lipids and PD and further explored the relationship between lipids and PD-MCI. RESULTS: PD patients had significantly lower level of lipid panel including TC, TG, HDL-C, Apo A1, LDL-C, and Apo B (all pâ<â0.05). TC, TG, Apo A1, and Apo B levels were independent protective factors (pâ<â0.05) for PD in the logistic regression model. PD-MCI group had significantly higher mean TC, TG, and Apo A1 levels compared to PD-NC group. Higher TC, TG, and Apo A1 levels were independent risk factors (pâ<â0.05) for PD-MCI. CONCLUSION: We demonstrated that PD patients had significantly lower levels of lipid biomarkers while PD-MCI patients had higher levels of TC, TG, and Apo A1. TC, TG, and Apo A1 may be useful biomarkers for PD-MCI.
Asunto(s)
Disfunción Cognitiva , Enfermedad de Parkinson , Apolipoproteína A-I , Apolipoproteínas B , Biomarcadores , HDL-Colesterol , LDL-Colesterol , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/etiología , Humanos , Lípidos , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/diagnóstico , TriglicéridosRESUMEN
We examined amyloid-tau-neurodegeneration biomarker effects on cognition in a Southeast-Asian cohort of 84 sporadic young-onset dementia (YOD; age-at-onset <65 years) patients. They were stratified into A+N+, A- N+, and A- N- profiles via cerebrospinal fluid amyloid-ß1-42 (A), phosphorylated-tau (T), MRI medial temporal atrophy (neurodegeneration- N), and confluent white matter hyperintensities cerebrovascular disease (CVD). A, T, and CVD effects on longitudinal Mini-Mental State Examination (MMSE) were evaluated. A+N+ patients demonstrated steeper MMSE decline than A- N+ (ßâ=â1.53; pâ=â0.036; CI 0.15:2.92) and A- N- (ßâ=â4.68; pâ=â0.001; CI 1.98:7.38) over a mean follow-up of 1.24 years. Within A- N+, T- CVD+ patients showed greater MMSE decline compared to T+CVD- patients (ßâ=â- 2.37; pâ=â0.030; CI - 4.41:- 0.39). A+ results in significant cognitive decline, while CVD influences longitudinal cognition in the A- sub-group.
Asunto(s)
Enfermedad de Alzheimer , Amiloidosis , Enfermedades Cardiovasculares , Disfunción Cognitiva , Demencia , Humanos , Enfermedad de Alzheimer/psicología , Amiloide , Péptidos beta-Amiloides , Biomarcadores , Cognición , Disfunción Cognitiva/diagnóstico por imagen , Demencia/diagnóstico por imagen , Proteínas tau , Persona de Mediana Edad , Edad de InicioRESUMEN
BACKGROUND: Non-amyloid mechanisms behind neurodegeneration and cognition impairment are unclear. Cerebrovascular disease (CVD) may play an important role in suspected non-Alzheimer's pathophysiology (SNAP), especially in Asia. OBJECTIVE: To examine the association between CVD and medial temporal lobe atrophy (MTA) in amyloid-ß negative patients with mild amnestic type dementia. METHODS: Thirty-six mild dementia patients with complete neuropsychological, cerebrospinal fluid (CSF) biomarker, and neuroimaging information were included. Only patients with clinically significant MTA were recruited. Patients were categorized based on their CSF Aß levels. Neuroimaging and neuropsychological variables were analyzed. RESULTS: Despite comparable MTA between Aß positive and negative patients, Aß-negative patients had significantly greater white matter hyperintensities (WMH; Total Fazekas Rating) than their Aß-positive counterparts (6.42 versus 4.19, pâ=â0.03). A larger proportion of Aß-negative patients also had severe and confluent WMH. Regression analyses controlling for baseline characteristics yielded consistent results. CONCLUSION: Our findings demonstrate that MTA is associated with greater CVD burden among Aß-negative patients with amnestic type dementia. CVD may be an important mechanism behind hippocampal atrophy. This has implications on clinical management strategies, where measures to reduce CVD may slow neurodegeneration and disease progression.
Asunto(s)
Amnesia/patología , Atrofia/patología , Demencia/patología , Lóbulo Temporal/patología , Sustancia Blanca/patología , Anciano , Amnesia/líquido cefalorraquídeo , Amnesia/diagnóstico por imagen , Amnesia/psicología , Péptidos beta-Amiloides/líquido cefalorraquídeo , Atrofia/líquido cefalorraquídeo , Atrofia/diagnóstico por imagen , Atrofia/psicología , Demencia/líquido cefalorraquídeo , Demencia/diagnóstico por imagen , Demencia/psicología , Progresión de la Enfermedad , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Neuroimagen , Pruebas Neuropsicológicas , Lóbulo Temporal/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagenRESUMEN
Individuals with mild cognitive impairment (MCI) exhibit varying serial position effect (SPE) performances. The relationship between SPE performance in word list recall and clinical, genetic, and neuroimaging features of MCI requires elucidation. 119 MCI and 68 cognitively normal (CN) participants underwent cognitive assessment, apolipoprotein E (ApoE) genotyping, and volumetric MRI brain scans processed via voxel-based morphometry. A 10-word recall task was used to assess SPE performance in relation to recency and primacy recall. MCI participants were classified as having Good SPE performance (high primacy and recency, Good SPE) or Poor SPE performance (low primacy only, LP-SPE; low recency only, LR-SPE; or both low, Low SPE). Poor SPE participants had reduced grey matter (GM) volumes and increased white matter hyperintensities (WMH) volumes. Participants with LP-SPE demonstrated reduced hippocampal GM volumes and were more likely to be ApoE ε4 carriers. LR-SPE was associated with higher WMH volumes. Presence of both greater WMH volumes and ApoE ε4 resulted in Low SPE. LP-SPE MCI participants had features typical of Alzheimer's disease. LR-SPE MCI was associated with increased WMH volumes, likely representing vascular pathology. SPE profiles are associated with distinct clinical patterns of MCI pathophysiology and could have potential as a clinical marker.