Patient description: A 35-year-old woman presents with history of acne and mild hirsutism. The primary evaluation revealed elevated testosterone levels. She recently noticed gradual enlargement of her hands and feet and recognized that her ring is getting small for her finger. There is some irregularity in her menstrual cycle as well as some nipple discharge. She also has positive history for snoring and headache. The physical examination revealed subtle facial features of acromegaly and prognathism. Visual fields are normal by confrontation. Hirsutism, soft tissue thickening and diaphoresis of the hands and feet are noted. Laboratory evaluation in the fasting state reveals IGF-1 of 968 ng/mL and random GH of 19.7 ng/mL. MRI reveals a macroadenoma with no invasion. She is on stable doses of octreotide LAR since her diagnosis was confirmed. She is married and has 2 children. She is using IUD as her contraceptive method.

Clinical trial eligibility criteria: eligible ages (years): 65.0-90.0,  Vitamin D Deficiency Cognitive Decline for this study are: 1) Age 65-90; 2) Low Vitamin D status, defined by a serum 25-OHD <20 ng/ml, as measured by competitive immunoassay at the Screening visit; 3) Fluent in either English or Spanish; 4) Willingness to be randomized to high-dose vs. standard dose vitamin D; 5) Education adjusted scores between 12-30 on the Montreal Cognitive Assessment (MOCA) at baseline; 6) A consensus clinical diagnosis of No Cognitive Impairment, Mild Cognitive Impairment, or mild AD dementia In order to be included in the No Cognitive Impairment (NC) subgroup, an individual must show no significant cognitive impairment on the baseline neuropsychological tests. Diagnoses are made by a comprehensive case conference review, including investigators from both sites, resulting in a consensus diagnosis made according to current research criteria. We will also require a minimum MOCA score of 23 or above for those with education >12 y, or MOCA >20 (uncorrected score) for those with education <12 years. These subjects are expected to mostly have CDR global scores of 0, but we will not CDR=0.5, as long as Peterson (Petersen, Journal of Internal Medicine 2004) for MCI (amnestic or non-amnestic) are not met and the CDR-Sum of Boxes is <1.0. Similarly, we will not elderly with subjective memory complaints from the NC group In order to be included in the Mild Cognitive Impairment (MCI) subgroup, a participant will need to meet research for amnestic MCI, either single-domain or multiple-domain (McKhann et al, Neurology 1984). Thus, participants with amnestic MCI will have standardized memory scores >1.5 SDs below average, and if cognitive scores in other cognitive domains are also >1.5 SDs below average they will be classified as multiple-domain amnestic MCI. All MCI participants will be required to have a global CDR=0.5. In addition, we will require a minimum MOCA score of >20 for those with education >12 y, or MOCA >17 (uncorrected score) for those with education <12 years In order to be included in the Mild AD dementia subgroup, a participant will need to meet research for probable or possible AD (McKhann et al, Neurology 1984). A global CDR score of 1 will be required (mild dementia). In addition, we will require a minimum MOCA score of >15 at entry for those with education >12 y, or MOCA >12 (uncorrected score) for those with education <12 y. AD therapies will be allowed (e.g. donepezil, memantine) as long as doses have been stable for >6 weeks, and no changes in doses or CNS active medications are planned while participating in this trial  (for all participants) are: 1) Lacks adequate vision, hearing, or literacy to complete the required psychometric tests (e.g. severe bilateral deafness despite use of hearing aids, or visual acuity poorer than 20/100 in both eyes); 2) Hepatic insufficiency, defined by either albumin <3.3 g/dL or by a value >2X the upper limit of normal (ULN) in either alanine aminotransaminase (ALT/SGPT) or bilirubin, or >3X the ULN for aspartate aminotransaminase (AST/SGOT); 3) Renal insufficiency, defined by either serum creatinine >1.7 mg/dL or glomerular filtration rate <40 mL/min/1.73 m2; (calculated per CKD-EPI formula). 4) Hypercalcemia, defined by serum calcium level >2 standard deviations above the mean. Corrected Calcium mg/dL = [0.8*(4.0g/dL Patients Albumin g/dL)] + Serum Calcium mg/dL (X of 8.6-10.5 is in normal range; formula accurate only if Albumin is in 3.2-4.6 range). 5) Current serious or unstable medical illnesses including cardiovascular (e.g. unstable ischemic cardiovascular disease), hepatic, renal, gastroenterologic, respiratory, endocrinologic, neurologic, psychiatric, immunologic, or hematologic disease and other conditions that, in the investigator's opinion, could interfere with the participant being able to safely take high-dose vitamin D for the 3.5 year study duration; or has a life expectancy of <4 years; 6) History of recurrent renal stones; 7) Unable to undergo MRI scanning (e.g. pacemaker, metallic implants, severe claustrophobia); 8) Subjects with a history of osteoporosis will be excluded if the Screening serum 25-OHD level is < 12 ng/ml. 9) History of chronic psychiatric illness (e.g. schizophrenia, bipolar disorder), any episode of major depression within last 2 years, or current GDS > 6, any recent suicide attempts or suicidal ideation; 10) history within the last 5 years of a serious infectious disease affecting the brain (including neurosyphilis, meningitis, or encephalitis), or head trauma resulting in protracted loss of consciousness (>10 minutes) or any persistent cognitive deficit; 11) History of chronic alcohol or drug abuse/dependence as defined by DSM-IV, within the past 5 years; 12) History within the last 5 years of a primary or recurrent malignant disease with the exceptions of resected cutaneous squamous cell carcinoma in situ, basal cell carcinoma, cervical carcinoma in situ, or non-metastatic prostate cancer with a normal prostate-specific antigen post-treatment; 13) Does not have good venous access, such that multiple blood draws would be precluded; 14) Regular use of any of these CNS active medications: benzodiazepines, antipsychotics, narcotics, cholinesterase inhibitors, memantine or anti-epileptic drugs. Stable doses of SSRIs or SNRI anti-depressants will be allowed, and included persons will be discouraged to change the doses of any potentially CNS active medication throughout the 3.5-year study. 15) Those who plan to change their dosage of any vitamin supplement during the duration of the study may be discontinued from the clinical trial. Changes in vitamin supplement dosing (e.g. vitamin B12) will only be allowed if a specific deficiency has been found. If participants are taking vitamin D supplementation (e.g. in a daily multi-vitamin) at the time of screening, they should continue on this same dose of vitamin supplementation throughout the duration of the randomized clinical trial. 16) Current participation in any clinical trial involving experimental AD therapies (anti-amyloid, anti-tau, etc.). 17) Female subjects who are pregnant or plan to become pregnant during participation in this trial. 18) Inability to swallow oral capsules We will not subjects with stable coronary artery disease or vascular risk factors such as diabetes or hypertension, who otherwise meet our inclusion/exclusion criteria. We will allow of participants with prior TIA or prior history of one stroke, but will those with past history of multiple strokes. We will allow participants with up to two incidental infarcts on structural MRI, because the presence of cerebrovascular disease is very common in any representative sample of U.S. elderly persons, and may be an important contributor to dementia and age-associated cognitive decline. We will not those with severe white matter (WM) hyperintensities, for similar reasons