Velez‐Uribe, Idaly

Abstract Background Research on gender and ethnic differences in white matter tracts yields mixed results. Although men show larger global corpus callosum (CC) in absolute values, women have demonstrated larger splenium and isthmus. Additionally, men have shown greater white matter and fractional anisotropy (FA) in multiple regions than women. This study investigates sex and ethnic differences in the corpus callosum and transcallosal white matter tissue microstructure of older individuals with normal cognition and memory disorders. Method 191 participants (Female n = 120; Hispanics n = 115; Non‐Hispanics n = 76; Age mean = 71.07; SD = 7.75) were included in the sample from the 1Florida ADRC with cognitively normal ( n = 75), MCI ( n = 88), and dementia ( n = 28) diagnoses. Corpus callosum volumes were collected using a Siemens Skyra 3T MRI scanner and were divided into anterior, mid‐anterior, central, mid‐posterior, and posterior regions. Also, MRI‐based free water diffusion tensor imaging (FW‐DTI) measured FW‐corrected FA (fwcFA) to assess and compare the integrity of transcallosal tract templates (TCATT) across motor, temporal, parietal, and occipital regions across males and females and ethnic groups. Result Univariate ANCOVAs controlling for age and clinical diagnosis were performed; females had larger normalized CC volumes in the posterior, F (1, 184) = 8.92, p = .003, η p 2 = .046, mid‐anterior, F (1,184)= 5.68, p = .018, η p 2 = .030, and anterior, F (1,184)= 14.54, p < .001, η p 2 = .073, regions, which all survived FDR corrections, with no ethnic differences observed. For transcallosal tracts, females had higher fwcFA in the inferior temporal gyrus, η p 2 Hispanics had higher fwcFA in the premotor cortex, η p 2 η p 2 Conclusion Sex and ethnicity influence white matter changes during aging independently of age and cognitive diagnosis. However, the effect explained by these demographic variables was very small, suggesting the influence of additional factors.

Abstract Background Population aging is expected to increase the burden of Alzheimer's disease (AD) and related dementias (ADRD), yet up to 45% of ADRD risk may be modified. Disparities in ADRD burden among Hispanic/Latino and Black/African Americans suggests that socioeconomic deprivation and medical comorbidities may influence AD risk. The relationship between these factors, symptomatic age of onset, and neuropathologic findings in AD remains unclear. This study aims to investigate these associations in an ethnoracially diverse, neuropathologically diagnosed AD case series. Understanding these risk factors may help develop more effective AD risk reduction strategies. Method We queried the Florida Autopsied Multi‐Ethnic (FLAME) cohort database for neuropathologically‐diagnosed AD cases with available age onset of cognitive symptoms, who self‐identified as Hispanic/Latino ( n = 75) or Black/African American ( n = 22). Cases were matched to non‐Hispanic White decedents ( n = 101) by sex and year of birth. Medical records at the time of brain donation were retrospectively reviewed, assessing completeness for demographics, clinical characteristics, and medical comorbidities (Table 1). Result The table shows a comparative analysis stratified by young‐onset AD (YOAD, onset <65 years) and late‐onset AD (LOAD, onset ≥65 years). YOAD cases had a significantly higher level of education compared to LOAD ( p = 0.003). No differences were observed in sex , APOE ε4 carriership, or Area Deprivation Index between YOAD and LOAD. However, YOAD cases had a longer disease duration and were more likely to present with atypical clinical features compared to LOAD (both p <0.001). YOAD cases also showed a faster rate of decline on MMSE compared to LOAD ( p = 0.002), higher frequency of depression ( p = 0.018), and lower frequency of stroke/TIA ( p = 0.025). YOAD cases also had lower brain weight ( p = 0.041), less cerebrovascular disease burden ( p = 0.003) and higher neurofibrillary tangle density in association cortices ( p <0.001) compared to LOAD cases. Conclusion Socioeconomic deprivation and most medical comorbidities were not associated with AD symptomatic onset. Despite having higher education levels and lower cerebrovascular burden, YOAD decedents experienced faster cognitive decline but a longer disease course, with more frequent atypical clinical presentations and depression compared to LOAD. Further discussion will address the topographic distribution of tangle and plaque pathology.

Abstract Background The locus coeruleus (LC) degenerates early in Alzheimer's disease (AD), with profound volume and neuronal loss. The loss of noradrenergic LC projection neurons results in alterations in attention, memory, and arousal, and constitutes the first site of neurofibrillary tangle accumulation preceding the onset of cognitive symptoms. We sought to investigate the relationship between LC neuronal density and clinical heterogeneity in a neuropathologically‐diagnosed series of AD cases. Methods The FLorida Autopsied Multi‐Ethnic (FLAME) cohort database was queried for neuropathologically‐diagnosed AD cases with a clinical diagnosis of AD dementia or an atypical, non‐amnestic clinical syndrome (e.g., corticobasal syndrome, posterior cortical atrophy). AD cases were selected based on high AD neuropathologic change (ADNC) and lack of frontotemporal lobar degeneration or hippocampal sclerosis, resulting in 591 AD cases and an additional 74 none‐low ADNC controls. Databased clinical diagnosis for AD cases was classified as amnestic or non‐amnestic. Hematoxylin & eosin‐stained slides were digitized and neuronal density was quantified using an in‐house developed macro on 900µmx900µm region of interest using Aperio technology (Leica Biosystems). LC level was classified using neuroanatomic landmarks as rostral, middle, or caudal. Results Control cases had greater neuronal density in the LC compared to AD cases at all three levels, p <0.05. In AD cases, we observed an association between age and neuronal density. Examining these differences along the rostrocaudal‐axis, we found that a younger age at symptomatic onset was associated with lower LC neuronal density in the rostral (correlation coefficient: 0.48; p <0.001) and middle LC (correlation coefficient: 0.28; p <0.001), no association between age at onset and neuronal density was observed at the caudal level. Stratifying our analysis by clinical syndrome, we found fewer neurons in the rostral and middle LC in non‐amnestic AD compared to amnestic AD ( p = 0.006 and 0.029 respectively, Table 1). No significant differences between amnestic and non‐amnestic cases were observed in the caudal LC. Conclusions The locus coeruleus, especially the rostral and middle levels, are especially vulnerable in young‐onset and atypical forms of AD. The loss of noradrenergic neuromodulation may contribute to the atypical symptomatology.