Erratum to: Association between Modifiable Risk Factors and Levels of Blood-Based Biomarkers of Alzheimer's and Related Dementias in the Look AHEAD Cohort.

[This corrects the article DOI: 10.14283/jarlife.2024.1.].

Association between Modifiable Risk Factors and Levels of Blood-Based Biomarkers of Alzheimer's and Related Dementias in the Look AHEAD Cohort.

Background: Emerging evidence suggests that a number of factors can influence blood-based biomarker levels for Alzheimer's disease (AD) and Alzheimer's related dementias (ADRD). We examined the associations that demographic and clinical characteristics have with AD/ADRD blood-based biomarker levels in an observational continuation of a clinical trial cohort of older individuals with type 2 diabetes and overweight or obesity. Methods: Participants aged 45-76 years were randomized to a 10-year Intensive Lifestyle Intervention (ILI) or a diabetes support and education (DSE) condition. Stored baseline and end of intervention (8-13 years later) plasma samples were analyzed with the Quanterix Simoa HD-X Analyzer. Changes in Aß42, Aß40, Aß42/Aß40, ptau181, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were evaluated in relation to randomization status, demographic, and clinical characteristics. Results: In a sample of 779 participants from the Look AHEAD cohort, we found significant associations between blood-based biomarkers for AD/ADRD and 15 of 18 demographic (age, gender, race and ethnicity, education) and clinical characteristics (APOE, depression, alcohol use, smoking, body mass index, HbA1c, diabetes duration, diabetes treatment, estimated glomerular filtration rate, hypertension, and history of cardiovascular disease) . Conclusions: Blood-based biomarkers of AD/ADRD are influenced by common demographic and clinical characteristics. These factors should be considered carefully when interpreting these AD/ADRD blood biomarker values for clinical or research purposes.

Seizure focus affects regional language networks assessed by fMRI.

OBJECTIVE: To investigate the degree of language dominance in patients with left and right hemisphere seizure foci compared to normal volunteers using a fMRI reading comprehension task. METHODS: Fifty patients with complex partial epilepsy, aged 8 to 56 years and 33 normal volunteers, aged 7 to 34 had fMRI (1.5 T) and neuropsychological testing. Participants silently named an object described by a sentence compared to a visual control. Data were analyzed with region of interest (ROI) analysis based on t maps for inferior frontal gyrus (IFG), midfrontal gyrus (MFG), and Wernicke area (WA). Regional asymmetry indices (AIs) were calculated [(L - R)/(L + R)]; AI > 0.20 was deemed left dominant and AI < 0.20 as atypical language. RESULTS: Left hemisphere focus patients had a higher likelihood of atypical language than right hemisphere focus patients (21% vs 0%, chi2 < 0.002). Left hemisphere focus patients, excluding those with atypical language, had lower regional AI in IFG, MFG, and WA than controls. Right hemisphere focus patients were all left language dominant and had a lower AI than controls in WA and MFG, but not for IFG. AI in MFG and WA were similar between left hemisphere focus/left language patients and right hemisphere focus patients. Patients activated more voxels than healthy volunteers. Lower AIs were attributable to greater activation in right homologous regions. Less activation in the right-side WA correlated with better verbal memory performance in right focus/left hemisphere-dominant patients, whereas less strongly lateralized activation in IFG correlated better with Verbal IQ in left focus/left hemisphere-dominant patients. CONCLUSIONS: Patients had lower asymmetry indices than healthy controls, reflecting increased recruitment of homologous right hemisphere areas for language processing. Greater right hemisphere activation may reflect greater cognitive effort in patient populations, the effect of epilepsy, or its treatment. Regional activation patterns reflect adaptive efforts at recruiting more widespread language processing networks that are differentially affected based on hemisphere of seizure focus.

fMRI identifies regional specialization of neural networks for reading in young children.

BACKGROUND: fMRI allows mapping of neural networks underlying cognitive networks during development, but few studies have systematically examined children 7 and younger, in whom language networks may be more diffusely organized than in adults. OBJECTIVE: To identify neural networks during early reading consolidation in young children. METHODS: The authors studied 16 normal, right-handed, native English-speaking children with a mean age of 7.2 years (range 5.8 to 7.9) with fMRI reading paradigms adjusted for reading level. Data were acquired with the echoplanar imaging BOLD technique at 1.5 T. Group data were analyzed with statistical parametric mapping (SPM-99); individual data sets were analyzed with a region of interest approach from individual study t maps (t = 4). The number of activated pixels in brain regions was determined and an asymmetry index (AI) ([L-R]/[L+R]) calculated for each region. RESULTS: In group analysis the authors found prominent activation in left inferior temporal occipital junction and left fusiform gyrus (Brodmann area [BA] 37), middle temporal gyrus (BA 21, 22), middle frontal gyrus (BA 44, 45), and the supplementary motor area. Activation was strongly lateralized in middle frontal gyrus and Wernicke areas (AI 0.54, 0.62). Fourteen subjects had left-sided language lateralization, one was bilateral, and one had poor activation. CONCLUSIONS: The neural networks that process reading are strongly lateralized and regionally specific by age 6 to 7 years. Neural networks in early readers are similar to those in adults.

Auditory comprehension of language in young children: neural networks identified with fMRI.

OBJECTIVE: The organization of neuronal systems that process language in young children is poorly understood. The authors used fMRI to identify brain regions underlying auditory comprehension in healthy young children. METHODS: Fifteen right-handed children (mean age 6.8 years) underwent fMRI at 1.5-T using blood oxygen level dependent echoplanar imaging. They listened to stories with a reverse speech control condition. Group data were analyzed with statistical parametric mapping. Individual subject data were analyzed with a region of interest approach based on t-maps. An asymmetry index (AI = [(L-R)/(L+R)]) was calculated for each region. RESULTS: Group analysis showed significant activation in the left middle temporal gyrus (Brodmann area [BA] 21) and left superior temporal gyrus (BA 22) along the superior temporal sulcus extending back to the angular gyrus (BA 39). Individual maps showed lateralized activation in temporal regions (AI > 0.49 +/- 0.39). There was minimal activation in the frontal lobe. There were no significant correlations between age and regional AI. CONCLUSION: Networks for auditory language processing are regionally localized and lateralized by age 5. These data may provide a means to interpret language fMRI studies performed in preparation for brain surgery, and may be employed to investigate the effect of chronic disease states, such as epilepsy, on language organization during critical periods for plasticity.