Dysarthria as a Presenting Symptom With Rapidly Progressive Imaging Features in Sporadic Creutzfeldt-Jakob Disease: A Case Report.

Sporadic Creutzfeldt-Jakob disease (sCJD) is a rare and fatal neurodegenerative disorder belonging to a group of diseases known as prion disease. Characterized by the formation of abnormal prion proteins in the brain, these conditions lead to tissue damage and vacuolation, giving the brain a sponge-like appearance. sCJD represents the most prevalent form of CJD, accounting for roughly 85% of all CJD cases. We report a case with unusual clinical manifestations. The patient experienced progressive neurological symptoms and MRI progression.

APOEɛ4 Status and Plasma p-tau181 Levels May Influence Memory and Executive Function Decline in Older Adults Without Dementia.

BACKGROUND: Elevated tau phosphorylation has been linked to the Apolipoprotein E (APOE) ɛ4 allele, which is considered one of the most significant genes related to Alzheimer's disease (AD). However, it is uncertain whether the impact of increased plasma tau phosphorylated at threonine 181 (p-tau181) on memory and executive function decline would be greater among APOEɛ4 carriers. OBJECTIVE: To investigate the effects of plasma p-tau181 and APOEɛ4 on memory and executive function. METHODS: The longitudinal analysis included 608 older adults without dementia (aged 72±7 years; 47% female; follow-up period of 1.59±1.47 years) from the ADNI dataset, including 180 individuals with normal cognition and 429 individuals with mild cognitive impairment. Linear mixed-effects models were utilized to assess the contributions of APOEɛ4 status and plasma p-tau181 to longitudinal changes in memory composite score and executive function composite score. RESULTS: At baseline, the APOEɛ4+/Tau+ group exhibited poorer performance in memory composite score and executive function composite score, and an elevated load of cerebrospinal fluid Aß and tau pathologies. To further understand longitudinal changes, we compared groups directly based on plasma p-tau181 and APOEɛ4 status (four groups: APOEɛ4-/Tau-, APOEɛ4-/Tau+, APOEɛ4+/Tau-, APOEɛ4+/Tau+). Both the memory composite score and executive function composite score showed a significantly greater decline in the APOEɛ4+/Tau+ group than in all other groups. CONCLUSIONS: Our findings indicate that there is an interaction between plasma p-tau181 levels and APOEɛ4 status, which contributes to the longitudinal changes of memory and executive function in older adults without dementia.

APOE ε4 status and plasma p-tau181 interact to influence cognitive performance among non-demented older adults.

OBJECTIVE: In this study, we aimed to investigate the relationships among plasma p-tau181, APOE ε4, and cognitive performance in non-demented elderly individuals. METHODS: We used individuals (n = 630) with cognitive normal (CN, n = 182) and mild cognitive impairment (MCI, n = 448). Multiple linear regression models were performed to test the effects of APOE ε4 × plasma p-tau181 interaction on MMSE, CDR-SOB, ADAS-cog13, and RAVLT immediate recall. All models adjusted for age, sex, and education. RESULTS: In total, our study comprised 630 samples including 364 APOE ε4 non-carriers and 266 APOE ε4 carriers. In APOE ε4 carriers, plasma p-tau181 was significantly associated with MMSE (B = -0.04, p = 0.003), ADAS-Cog13 (B [unstandardized coefficient] = 0.21, p < 0.001), CDR-SB (B = 0.02, p = 0.003) and RAVLT immediate recall ((B = -0.17, p = 0.035). After correcting for Aß status and diagnosis, the interaction between APOE ε4 and plasma p-tau181 was significant or marginally significant associations for RAVLT immediate recall (p = 0.076), MMSE (p = 0.011), CDR (p = 0.008), and ADAS-Cog13 (p < 0.001). CONCLUSIONS: Our findings suggested that plasma p-tau181 levels predicted cognitive performance among non-demented older adults, but only in the APOE ε4 carriers.

Association of obstructive sleep apnea with cognitive decline and age among non-demented older adults.

We aimed to investigate whether obstructive sleep apnea (OSA) status affects the relationship between cognitive decline and age among non-demented elderly people. A total of 1422 participants (493 normal cognition and 929 amnestic mild cognitive impairment) were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. Based on the self-reported medical history of OSA, participants were categorized into two groups (OSA- and OSA +). Multiple linear regression models were performed to assess the effect of the OSA * Age interaction on MMSE, ADAS-cog11 and RAVLT immediate recall in non-demented group and in APOE ε4 carriers/non-carriers adjusting for gender and educational attainment. In the present study, the OSA + group demonstrated significant cognitive decline versus the OSA- group. In addition, in APOE ε4- group, our findings showed a significant OSA * age interaction for ADAS-cog11 and RVALT immediate recall, but not MMSE. No significant interaction was observed in the APOE ε4+ individuals. In conclusion, our findings implicate that OSA status may affect the association of age with cognitive impairment among non-demented older people.

APOE ε4 is associated with higher levels of CSF SNAP-25 in prodromal Alzheimer's disease.

The underlying mechanism of apolipoprotein E ε4 (APOE ε4) in the pathogenesis of Alzheimer's disease (AD) remains elusive. We hypothesize that synaptic function is differentially affected by APOE isoforms. Levels of CSF SNAP-25 were compared between APOE ε4 carriers and noncarriers in 55 participants with normal cognition, 75 patients with mild cognitive impairment (MCI), and 16 patients with mild AD dementia. We investigated relationships between SNAP-25 levels and age, gender, education, CSF Aß42, and tau protein. We found that levels of SNAP-25 in CSF were substantially greater in APOE ε4 carriers compared to noncarriers with MCI. There was no significant difference in SNAP-25 levels between APOE ε4 carriers and noncarriers with normal cognition or AD. CSF SNAP-25 levels were associated with MMSE and CSF Aß and tau levels. In summary, APOE ε4 may affect CSF SNAP levels in MCI patients, suggesting an important role of APOE ε4 in synaptic dysfunction leading to AD.