ApoE4 is not a mere risk factor for AD, on the contrary, ApoE4 is an integral component of the pathogenesis of the disease. ApoE4 creates its own specific etiology and pathogenesis and thus creates a distinct disease. The end stage of AD, type-APOE4 then merges with the final common pathway of AD.
There is no treatment for end stage AD with dementia.
In my opinion, AD in carriers of APOE4 should be viewed as a 4 stage disease.
Latent stage: Asymptomatic deterioration of cerebral microcirculation. This stage goes on for decades. It can only be diagnosed with PET scans of brain.
Prodromal Stage: Some accumlation of beta-amyloid on PET scans. Some impairment of cerebral microcirculation on PET scans. Slight impairment of memory, good executive function.
Mild Cognitive Impairment (MCI).
In my opinion, Latent stage and prodromal stage should be treated to prevent conversion to MCI and Dementia.
Treatment plan for Latent and Prodromal stage:
Lifestyle: Physical activity, low calorie diet, low intake saturated fats, high intake poly unsaturated fats; Avoid alcohol, tobacco, head trauma.
Treat elevated cholesterol with Simvastatin (Zocor.)
Treat elevated blood pressure angiotensin II suppression with drug that crosses BBB.
Lower mTOR1 with weekly (intermittent) rapamycin.
Avoid Overweight, Obesity, type 2 Diabetes.