Increasing the prepartum dose of rumen-protected choline: Effects on milk production and metabolism in high-producing Holstein dairy cows

ABSTRACT: Peripartum rumen-protected choline (RPC) supplementation is beneficial for cow health and production, yet the optimal dose is unknown. In vivo and in vitro supplementation of choline modulates hepatic lipid, glucose, and methyl donor metabolism. The objective of this experiment was to determine the effects of increasing the dose of prepartum RPC supplementation on milk production and blood biomarkers. Pregnant multiparous Holstein cows (n = 116) were randomly assigned to one of 4 prepartum choline treatments that were fed from −21 d relative to calving (DRTC) until calving. From calving until +21 DRTC, cows were fed diets targeting 0 g/d choline ion (control, CTL) or the recommended dose (15 g/d choline ion; RD) of the same RPC product that they were fed prepartum. The resulting treatments targeted: (1) 0 g/d pre- and postpartum [0.0 ± 0.000 choline ion, percent of dry matter (%DM); CTL]; (2) 15 g/d pre- and postpartum of choline ion from an established product (prepartum: 0.10 ± 0.004 choline ion, %DM; postpartum: 0.05 ± 0.004 choline ion, %DM; ReaShure, Balchem Corp.; RPC1RD▸RD); (3) 15 g/d pre- and postpartum of choline ion from a concentrated RPC prototype (prepartum: 0.09 ± 0.004 choline ion, %DM; postpartum: 0.05 ± 0.003 choline ion, %DM; RPC2, Balchem Corp.; RPC2RD▸RD); or (4) 22 g/d prepartum and 15 g/d postpartum from RPC2 [prepartum: 0.13 ± 0.005 choline ion, %DM; postpartum: 0.05 ± 0.003 choline ion, %DM; high prepartum dose (HD), RPC2HD▸RD]. Treatments were mixed into a total mixed ration, and cows had ad libitum access via a roughage intake control system (Hokofarm Group). From calving to +21 DRTC, all cows were fed a common base diet and treatments were mixed into the total mixed ration (supplementation period, SP). Thereafter, all cows were fed a common diet (0 g/d choline ion) until +100 DRTC (postsupplementation period, postSP). Milk yield was recorded daily and composition analyzed weekly. Blood samples were obtained via tail vessel upon enrollment, approximately every other day from −7 to +21 DRTC, and at +56 and +100 DRTC. Feeding any RPC treatment reduced prepartum dry matter intake compared with CTL. During the SP, no evidence for a treatment effect on energy-corrected milk (ECM) yield was found, but during the postSP, RPC1RD▸RD and RPC2RD▸RD treatments tended to increase ECM, protein, and fat yields. During the postSP, the RPC1RD▸RD and RPC2RD▸RD treatments tended to increase, and RPC2HD▸RD increased, the de novo proportion of total milk fatty acids. During the early lactation SP, RPC2HD▸RD tended to increase plasma fatty acids and β-hydroxybutyrate concentrations, and RPC1RD▸RD and RPC2RD▸RD reduced blood urea nitrogen concentrations compared with CTL. The RPC2HD▸RD treatment reduced early lactation serum lipopolysaccharide binding protein compared with CTL. Overall, peripartum RPC supplementation at the recommended dose tended to increase ECM yield postSP, but no evidence was seen of an additional benefit on milk production with an increased prepartum dose of choline ion. The effects of RPC on metabolic and inflammatory biomarkers support the potential for RPC supplementation to affect transition cow metabolism and health and may support the production gains observed

Frequency of LATE neuropathologic change across the spectrum of Alzheimer’s disease neuropathology: combined data from 13 community-based or population-based autopsy cohorts

Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) and Alzheimer’s disease neuropathologic change (ADNC) are each associated with substantial cognitive impairment in aging populations. However, the prevalence of LATE-NC across the full range of ADNC remains uncertain. To address this knowledge gap, neuropathologic, genetic, and clinical data were compiled from 13 high-quality community- and population-based longitudinal studies. Participants were recruited from United States (8 cohorts, including one focusing on Japanese–American men), United Kingdom (2 cohorts), Brazil, Austria, and Finland. The total number of participants included was 6196, and the average age of death was 88.1 years. Not all data were available on each individual and there were differences between the cohorts in study designs and the amount of missing data. Among those with known cognitive status before death (n = 5665), 43.0% were cognitively normal, 14.9% had MCI, and 42.4% had dementia—broadly consistent with epidemiologic data in this age group. Approximately 99% of participants (n = 6125) had available CERAD neuritic amyloid plaque score data. In this subsample, 39.4% had autopsy-confirmed LATE-NC of any stage. Among brains with “frequent” neuritic amyloid plaques, 54.9% had comorbid LATE-NC, whereas in brains with no detected neuritic amyloid plaques, 27.0% had LATE-NC. Data on LATE-NC stages were available for 3803 participants, of which 25% had LATE-NC stage > 1 (associated with cognitive impairment). In the subset of individuals with Thal Aβ phase = 0 (lacking detectable Aβ plaques), the brains with LATE-NC had relatively more severe primary age-related tauopathy (PART). A total of 3267 participants had available clinical data relevant to frontotemporal dementia (FTD), and none were given the clinical diagnosis of definite FTD nor the pathological diagnosis of frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP). In the 10 cohorts with detailed neurocognitive assessments proximal to death, cognition tended to be worse with LATE-NC across the full spectrum of ADNC severity. This study provided a credible estimate of the current prevalence of LATE-NC in advanced age. LATE-NC was seen in almost 40% of participants and often, but not always, coexisted with Alzheimer’s disease neuropathology