Abstract: Cognitive decline constitutes an outcome phenomenon arising in terms of integral evolution of pathways determining viability of neuronal networks rather than of individual neuronal subsets. Indeed, synaptic integrity would promote a generalized preservation of pathways as predilected systems of neuroprotection against such system degeneration. One might view Alzheimer neurodegeneration as a characterization of system involvement that either initially determines evolution of cell death pathways or else primarily targets systems of interconnectivity between neuronal subgroups. It is in terms of both initiation and subsequent progression that differential systems of influence predetermine cascade pathways of development of neurodegenerative events as inherently integral events. Neurodegeneration, as pathways of promotion that are primarily concerned with initiating events and particularly Alzheimer disease, would possibly arise within a biologic context of brain aging. Genetic and sporadic predisposition would allow the further definition of characteristics of a disease process that initiates a heightened susceptibility primarily affecting also systems of interaction of hemodynamic dysregulation and glucose non-utilization. It is in the basic constitutional development of injury to neuronal networks that aging of the brain would possibly predetermine the further transformation of pathway events as Alzheimer neurodegeneration. The specific inter-relationships of brain aging with Alzheimer-type atrophy might involve particularly modes of initiation of damage to synapses as primarily network dysfunctionality. Alzheimer-type development of atrophy relates to regional phenomena that evolve as initiating events that further characterize biologic attributes of the synapse. Neuritogenesis is itself a product of characterized synapse maintenance or dysfunction that further develops in predetermined ways to induce injury as neuritic plaques and neurofibrillary tangles. It might be significant to consider cognitive decline as an outline evolving system that in Alzheimer brains would be further characterized as initial establishment of synaptic dysfunction. Primary determinants in development of Alzheimer`s disease would paradoxically characterize brain aging as a generic system of promotion of innumerable pathways of possible neuronal network injury. Potential development of predeterminants would allow the definition of attributes of neuronal networks beyond simple neuronal subsets and in terms particularly of modes of interaction of synapse and neurites as dystrophy and dysfunctionality phenomena.