By 2050, nearly 14 million individuals in the US will be living with Alzheimer’s disease (AD), up from 5 million in 2013 (Hebert, Weuve, Scherr, & Evans, 2013). AD is the most common cause of dementia, resulting in the loss of cognitive functions such as memory, reasoning, language, and cognitive, social, physical, and emotional control, to the extent that losses interfere with activities of daily living and necessitate continuous monitoring and care (Reisberg et al., 1987). AD and other dementias mainly affect elders; after age 65, probability of onset of AD approximately doubles every 5 years(Cummings & Cole, 2002). At the same time, a large and especially tragic AD cohort develops the disease at a younger age because genetic factors (and many environmental factors) amplify risks of early onset (Chartier-Harlin et al., 1991; Picard, Pasquier, Martinaud, Hannequin, & Godefroy, 2011). AD is a progressive disease in which symptoms emerge following a long pre-clinical period, with the pathology progressively growing in the brain over the course of many years. Although current AD treatments may slow the progression towards dementia, increased resilience is modest and short-lived; no current treatment stops or reverses disease progression (Group et al., 2007; Reines et al., 2004; Thal et al., 2005). The majority of individuals with AD are cared for by family and friends; in 2012, 15.4 million US citizens provided 17.5 billion hours of unpaid care, at great personal and emotional cost (Thies, Bleiler, & Alzheimer's, 2013).
Neuroimaging studies have shown that signature markers of AD are initially expressed in subcortical neuromodulatory nuclei (Braak & Braak, 1998) then advance to be initially expressed in the “default network” (DN), the highest-level cortical areas that control our most-complex and abstract cognitive operations (Buckner, Andrews-Hanna, & Schacter, 2008). Studies have also shown that these most-susceptible cortical areas are progressively disconnected in aging on the path to AD (Buckner et al., 2005; Greicius, Srivastava, Reiss, & Menon, 2004; Liu et al., 2012; Rombouts, Barkhof, Goekoop, Stam, & Scheltens, 2005; Sorg et al., 2007). With their progressive deactivation, there is sharp reduction in activity-stimulated blood flow, known to presage frank pathology(Hachinski et al., 1975; Jobst et al., 1992). Those changes in perfusion dynamics—and the parallel decline in the expression of a primary regulator of immune responses in brain tissues, noradrenaline (NE) (Heneka et al., 2010; Raskind, Peskind, Halter, & Jimerson, 1984; Rossor, Iversen, Reynolds, Mountjoy, & Roth, 1984)—compromises the immune system’s scavenging of debris from slowly-plastically-degrading brain tissues. Because a disconnected, inactive DN is slowly undergoing plastic simplification (Arendt et al., 1997), it is a particularly rich source of cellular debris including prions and other amyloid-attracting brain matter—arising in now-immunologically-compromised brain tissues.
The pathological processes that lead to AD begin years before its diagnosis. More than half of 70-year-olds express AD pathology, when only 7% are diagnosed with the disease (Kantarci et al., 2011). The long pre-clinical phase of AD provides a key opportunity for disease-delaying (potentially, disease-preventing) therapies.
I apply 17 forms (modules) of targeted brain plasticity-based exercises delivered in about 1,200 short training blocks, designed to increase the feed-forward powers of all of the brain systems, and to directly, intensively exercise that highest-order brain machinery. Subjective reports of daily living and congnitive assessment measuing the effectivenss of traning are embedded in the training.