Virtual delivery of improvisational movement and social engagement interventions in the IMOVE trial during the COVID-19 pandemic.

Background: IMOVE evaluated the contributions of movement and social engagement to quality of life, brain network connectivity, and motor and social-emotional functioning in people with early-stage Alzheimer's disease participating with a caregiver. In response to COVID-19 restrictions, a pilot study was conducted to assess integrity of key elements of the intervention and feasibility of virtual intervention delivery. Methods: Participants in the parent study were randomized to one of 4 study conditions (Movement Group [MG], Movement Alone [MA], Social Group [SG], or Usual Care [UC; control]). To test virtual adaptations of each condition, groups of three participant-caregiver dyads (6 individuals) who had completed the parent trial participated in virtual adaptation classes. We adopted an engineering-inspired, rapid refinement model to optimize virtual interventions on the dimensions of social connectedness, fun, and physical exertion. After completing one iteration, participants gave feedback and adjustments were made to the intervention. This process was repeated until no further adjustments were needed. Results: The MA arm easily transitioned to virtual format. The virtual MG intervention required the most iterations, with participants reporting needs for additional technology support, higher level of physical exertion, and stronger social connection. The virtual SG intervention reported good social connection, but needed additional technology instruction and measures to promote equal participation. Conclusions: Our pilot study results underscore the feasibility of delivering remote social and/or dance interventions for older adults and provide a useful road map for other research teams interested in increasing their reach by adapting in-person group behavioral interventions for remote delivery.

Maintenance of white matter integrity in a rat model of radiation-induced cognitive impairment.

Radiation therapy is used widely to treat primary and metastatic brain tumors, but also can lead to delayed neurological complications. Since maintenance of myelin integrity is important for cognitive function, the present study used a rat model that demonstrates spatial learning and memory impairment 12 months following fractionated whole-brain irradiation (WBI) at middle age to investigate WBI-induced myelin changes. In this model, 12-month Fischer 344 x Brown Norway rats received 9 fractions of 5 Gy delivered over 4.5 weeks (WBI rats); Sham-IR rats received anesthesia only. Twelve months later, the brains were collected and measures of white matter integrity were quantified. Qualitative observation did not reveal white matter necrosis one year post-WBI. In addition, the size of major forebrain commissures, the number of oligodendrocytes, the size and number of myelinated axons, and the thickness of myelin sheaths did not differ between the two groups. In summary, both the gross morphology and the structural integrity of myelin were preserved one year following fractionated WBI in a rodent model of radiation-induced cognitive impairment. Imaging studies with advanced techniques including diffusion tensor imaging may be required to elucidate the neurobiological changes associated with the cognitive impairment in this model.

Caloric restriction and age affect synaptic proteins in hippocampal CA3 and spatial learning ability.

Caloric restriction (CR) is a daily reduction of total caloric intake without a decrease in micronutrients or disproportionate reduction of any one dietary component. CR can increase lifespan reliably in a wide range of species and appears to counteract some aspects of the aging process throughout the body. The effects on the brain are less clear, but moderate CR seems to attenuate age-related cognitive decline. Thus, we determined the effects of age and CR on key synaptic proteins in the CA3 region of the hippocampus and whether these changes were correlated with differences in behavior on a hippocampal-dependent learning and memory task. We observed an overall, age-related decline in the NR1, N2A and N2B subunits of the N-methyl-d-aspartate (NMDA)-type and the GluR1 and GluR2 subunits of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA)-type ionotropic glutamate receptors. Interestingly, we found that CR initially lowers the glutamate receptor subunit levels as compared to young AL animals, and then stabilizes the levels across lifespan. Synaptophysin, a presynaptic vesicle protein, showed a similar pattern. We also found that both CR and ad libitum (AL) fed animals exhibited age-related cognitive decline on the Morris water maze task. However, AL animals declined between young and middle age, and between middle age and old, whereas CR rats only declined between young and middle age. Thus, the decrease in key synaptic proteins in CA3 and cognitive decline occurring across lifespan are stabilized by CR. This age-related decrease and CR-induced stabilization are likely to affect CA3 synaptic plasticity and, as a result, hippocampal function.

Effects of aging and caloric restriction on dentate gyrus synapses and glutamate receptor subunits.

Caloric restriction (CR) attenuates aging-related degenerative processes throughout the body. It is less clear, however, whether CR has a similar effect in the brain, particularly in the hippocampus, an area important for learning and memory processes that often are compromised in aging. In order to evaluate the effect of CR on synapses across lifespan, we quantified synapses stereologically in the middle molecular layer of the dentate gyrus (DG) of young, middle aged and old Fischer 344 x Brown Norway rats fed ad libitum (AL) or a CR diet from 4 months of age. The results indicate that synapses are maintained across lifespan in both AL and CR rats. In light of this stability, we addressed whether aging and CR influence neurotransmitter receptor levels by measuring subunits of NMDA (NR1, NR2A and NR2B) and AMPA (GluR1, GluR2) receptors in the DG of a second cohort of AL and CR rats across lifespan. The results reveal that the NR1 and GluR1 subunits decline with age in AL, but not CR rats. The absence of an aging-related decline in these subunits in CR rats, however, does not arise from increased levels in old CR rats. Instead, it is due to subunit decreases in young CR rats to levels that are sustained in CR rats throughout lifespan, but that are reached in AL rats only in old age.

Caloric restriction eliminates the aging-related decline in NMDA and AMPA receptor subunits in the rat hippocampus and induces homeostasis.

Caloric restriction (CR) extends life span and ameliorates the aging-related decline in hippocampal-dependent cognitive function. In the present study, we compared subunit levels of NMDA and AMPA types of the glutamate receptor and quantified total synapses and multiple spine bouton (MSB) synapses in hippocampal CA1 from young (10 months), middle-aged (18 months), and old (29 months) Fischer 344xBrown Norway rats that were ad libitum (AL) fed or caloric restricted (CR) from 4 months of age. Each of these parameters has been reported to be a potential contributor to hippocampal function. Western blot analysis revealed that NMDA and AMPA receptor subunits in AL animals decrease between young and middle age to levels that are present at old age. Interestingly, young CR animals have significantly lower levels of glutamate receptor subunits than young AL animals and those lower levels are maintained across life span. In contrast, stereological quantification indicated that total synapses and MSB synapses are stable across life span in both AL and CR rats. These results indicate significant aging-related losses of hippocampal glutamate receptor subunits in AL rats that are consistent with altered synaptic function. CR eliminates that aging-related decline by inducing stable NMDA and AMPA receptor subunit levels.

Insulin-like growth factor-1 does not ameliorate the age-related decline in presumptive inhibitory synapses in layer 2 of rat sensorimotor cortex.

Four old (29 months) Brown Norway x Fischer 344 (BN x F344) rats received intracerebroventricular infusion of insulin-like growth factor-1 (IGF-1) and four middle-aged (18 months) and four old (29 months) rats received infusion of saline for 28 days. Sensorimotor cortex containing layer 2 was blocked and processed for electron microscopy. Thin (700 A) and semithin (1 microm) sections were collected from the same anatomical space for quantification of synapses and neurons, respectively, using the physical disector. Numerical density (Nv) of presumptive inhibitory synapses in layer 2 of sensorimotor cortex has been reported to decline with age Poe et al., 2001; Brunso-Bechtold et al. [Brain Res. 872 (2000) 125]. Infusion of IGF-1 did not affect the density of synapses or neurons when old IGF-1 animals were compared with old saline animals.