Effect of Acetylcholinesterase Inhibitors on Bone Metabolism

1. Diagnosis of cognitive impairment, including clinical assessment, radiographic or laboratory biomarker assessment

2. Willing to initiate treatment for cognitive impairment

3. A) For females: either age > 55 years, or Age < 55 years and at least 12 months since last menstrual period B) For males, age > 50 years

4. Geriatric Depression Scale score < 6

5. English-speaking

1. Currently on acetylcholinesterase inhibitor or memantine

2. History of bradycardia, heart block, long QT, unexplained syncope, or other contraindication for donepezil; subject with ECG showing HR < 50, PR interval > 200 ms, QTc > 440 ms in men or > 460 ms in women, or evidence of atrioventricular block

3. Currently on osteoporosis medication (e.g., bisphosphonate, SERM, denosumab, teriparatide, abaloparatide, romozosumab, calcitonin)

4. Use of bisphosphonate within last 5 years

5. Use within last 6 months of estrogens or testosterone, androgen deprivation therapy or aromatase inhibitors, antiepileptic, heparin therapy, thiazolidinediones

6. History of disorders associated with secondary osteoporosis: collagen vascular diseases, malabsorption, inflammatory bowel disease, severe liver disease/cirrhosis, hyperthyroidism (endogenous or exogenous)

7. History of fracture of the humerus, wrist, or vertebra due to fall from standing height or less

8. History of hip fracture, hip replacement, or non-ambulatory

9. Long-term use (>6 months) of corticosteroids

10. History of Parkinson's, HIV, Huntington's disease

11. History of solid organ transplantation

12. History of bariatric surgery or intending to lose weight by bariatric surgery or weight loss medication (e.g. GLP-1 agonist) in the next 12-months

13. Severe kidney impairment (eGFR < 30 ml/min),

14. Active malignancy currently undergoing chemotherapeutic, surgical, or radiation therapy, except non-melanomatous skin cancer

15. 1-year mortality > 25%, measured by ePrognosis calculator

16. Planning to move out of the area in the next 12-months

17. Planning surgery in the next 12-months