Broadening the reach of dementia risk-reduction initiatives: strategies from dissemination models.

BACKGROUND: Modifiable risk factors for dementia account for 40% of cases worldwide and exert impacts on risk across the life course. To have maximal public health impact, dementia risk-reduction initiatives need to reach a large and diverse audience, including people from a wide range of ages and socioeconomic backgrounds. Currently, dementia risk-reduction interventions primarily reach a narrow audience, consisting largely of highly educated older adults from high income countries. METHODS: In this commentary, we review established dissemination models to identify strategies that could be used to extend and broaden the reach of dementia risk-reduction initiatives. Three potential reach-broadening strategies can be identified from these models: engaging with distinct user groups; focusing on interpersonal communication; and utilising dissemination agents. RESULTS: Engaging with distinct user groups and utilising dissemination agents show promise for broadening the reach of dementia risk-reduction initiatives, while interpersonal communication has received limited attention in this context. Further evaluation of the impact of interpersonal communication may provide avenues to take advantage of this dissemination method. CONCLUSIONS: Based on the reviewed models and data from current risk-reduction initiatives, we suggest that utilising all three of these strategies may most effectively broaden the reach of dementia risk-reduction initiatives. This may promote risk reduction among a larger and more diverse audience, more equitably reducing the global impact of dementia.

Effects of TDP-43 overexpression on neuron proteome and morphology in vitro.

TDP-43 is pathologically and genetically with associated amyotrophic lateral sclerosis and frontotemporal lobar degeneration. These diseases are characterized by significant neurite defects, including cytoskeletal pathology. The involvement of TDP-43 in the degeneration of neurons in these diseases are not yet well understood, however accumulating evidence shows involvement in neurite outgrowth, remodelling and in regulation of many components of the neuronal cytoskeleton. In order to investigate how alterations to TDP-43 expression levels may exert effects on the neuronal cytoskeleton, primary cortical neurons from transgenic mice overexpressing one or two copies of human wildtype TDP-43 under the prion promoter were examined. Label-free quantitative proteomic analysis, followed by functional annotation clustering to identify protein families that clustered together within up- or down-regulated protein groups, revealed that actin-binding proteins were significantly more abundant in neurons overexpressing TDP-43 compared to wildtype neurons. Morphological analysis demonstrated that during early development neurons expressing one copy of human TDP-43 had an increased number of neurite branches and alterations to growth cone morphology, while no changes were observed in neurons expressing two copies of TDP-43. These developmental processes require specific expression and organization of the cytoskeleton. The results from these studies provide further insight into the normal function of TDP-43 and how alterations in TDP-43 expression may impact the cytoskeleton.