ABSTRACT
Wildtype Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 337
17.8 Implementation in R . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 338
17.8.1 Common Parameter for Histology in the Wildtype
Group . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 338
17.8.2 Age-Specific Parameters for Histology in the Wildtype
Group . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 343
17.9 Concluding Remarks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 344
Alzheimer’s disease (AD), the most common cause of dementia, is an irreversible age-related condition resulting in an increase in dependency on care providers for basic functioning. Clinical symptoms of sporadic AD manifest mostly in the elderly population (at least 65 years) and include progressive deterioration of specific cognitive functions such as memory, speech, motor skills and perception (McKhann et al., 1984). A proper diagnosis of AD suffers from the lack of diagnostic tools that can accurately distinguish AD from other causes of cognitive impairment especially at an early stage of the disease (Blennow, 2004; Chetelat and Baron, 2003; Galvin and Sadowsky, 2012). Moreover, AD results in multiple pathological changes in the brain, which do not manifest the same way in all patients. The most common AD-related pathological changes in the brain include amyloid-beta protein plague deposition (Masters et al., 1985; Hardy and Selkoe, 2002), neurofibrillary tangle (hyperphosphorylated tau) formation, and neuro-degeneration (Hol et al., 2003; Serrano-Pozo et al., 2011). How these changes influence the progression of AD is unfortunately not clearly understood since the onset of clinical symptoms of AD occurs much later than the onset of the pathological changes associated with the disease (Agronin, M.E., 2007). Considering the fact that there is no known cure for AD, an early diagnosis of the disease would therefore be preferable in order to allow for the introduction of treatments that may delay the progression of the disease such as a lifestyle intervention or novel therapeutic management of the patients.
