The Ketogenic Diet in the Treatment of Alzheimer's Disease

Inclusion Criteria:

1. Subject is between the ages of 50 - 85;

2. Subject must have completed the sixth grade of primary school (or its equivalent)and capable of completing the cognitive ability assessments and other tests asstipulated in the protocol;

3. Meeting the diagnostic criteria for probable AD dementia of the National Instituteon Aging and the Alzheimer's Association (NIA-AA) (2011);

4. Having experienced memory decline for at least 12 months and a slow progressivetrend;

5. Subject with mild to moderate disease severity, specifically those who meet thefollowing criteria at the screening visit and baseline: 11 points ≤ Mini-MentalState Examination (MMSE) total score < 26 points (for subjects with primary schooleducation, 11 points ≤ MMSE total score ≤ 22 points); 1 point ≤ Clinical DementiaRating Scale (CDR) total score ≤ 2 points;

6. Total score on the Hachinski Ischemic Scale (HIS) ≤ 4 points;

7. Total score on the Hamilton Depression Scale (HAMD, 17-item version) ≤ 17 points;

8. At the screening visit or within the past 6 months, subject must undergo a brainmagnetic resonance imaging (MRI) plain scan and oblique coronal hippocampal scan:

①Showing high likelihood of AD (Visual Rating Scale of Medial Temporal Lobe Atrophy [MTA Scale] grade: Grade 1 or higher is considered abnormal);

②No infarct lesions in key areas such as the thalamus, hippocampus, entorhinalcortex, parahippocampal cortex, angular gyrus, cortex, and other subcortical graymatter nuclei;

③The grade on the Brain White Matter Lesion Rating Scale (Fazekas Scale) ≤ 2. If thepatient can provide the results of the brain MRI oblique coronal hippocampal scanthat meet the protocol requirements within 6 months prior to the screening visit, itcan be used as the basis for enrollment and does not need to be repeated. If theresearcher is unable to determine whether the subject's condition has changed,additional brain MRI plain scan and oblique coronal hippocampal scan can beconducted prior to enrollment.

9. Female patients must be postmenopausal women (postmenopause ≥ 24 weeks), haveundergone surgical sterilization, or fertile women who agree to take effectivecontraceptive measures during the study. Fertile women or patients with apostmenopausal period shorter than 24 weeks must undergo a urine pregnancy testduring the screening period, and the result must be negative;

10. Subjects are required to be receiving stable and regular anti-dementia drugtreatment for more than 1 month at the first screening;

11. The subject should have a stable and reliable caregiver who can provide care for atleast 4 days per week, with at least 4 hours per day. The caregiver will assist thesubject throughout the study and must accompany the subject to each study visit,ensuring sufficient interaction and communication with the subject to facilitate theresearcher in completing the relevant scale evaluations.

12. Prior to the screening visit examination, the subject must sign a written informedconsent form. If the subject cannot sign due to limited cognitive ability or otherreasons, the signature may be left blank, and the rationale must be stated. Thelegal guardian should provide the reason, sign the name, date, and time in thereason description area, and also sign the name, date, and time in the legalguardian column.

Exclusion Criteria:

1. Dementia caused by other factors: vascular dementia, central nervous systeminfections (such as AIDS, syphilis, etc.), Creutzfeldt-Jakob disease, Huntington'sdisease and Parkinson's disease, Lewy body dementia, traumatic brain injurydementia, other physical and chemical factors (such as drug poisoning, alcoholpoisoning, carbon monoxide poisoning, etc.), significant somatic diseases (such ashepatic encephalopathy, pulmonary encephalopathy, etc.), intracranialspace-occupying lesions (such as subdural hematoma, brain tumors), endocrine systemdisorders (such as thyroid diseases, parathyroid diseases) and dementia caused byvitamin deficiency or any other known causes;

2. Fasting blood glucose > 7.0 mmol/L or patients previously diagnosed with diabetes;

3. Having suffered from neurological diseases other than Alzheimer's disease, includingcerebrovascular diseases, neurodegenerative diseases, central nervous systeminfections, demyelinating diseases, movement disorders, epilepsy, spinal corddiseases, peripheral neuropathy, autonomic nervous system diseases, neuromuscularjunction and muscle diseases;

4. Patients diagnosed with psychiatric conditions according to the Diagnostic andStatistical Manual of Mental Disorders, Fifth Edition (DSM-5), includingschizophrenia or other mental illnesses, bipolar disorder, moderate to severedepression or delirium;

5. Abnormal laboratory tests at screening visit and baseline: including liver functiontests (alanine aminotransferase [ALT], aspartate aminotransferase [AST]) exceedingtwice the upper limit of normal; and renal function (creatinine [Cr]) exceeding 1.5times the upper limit of normal. Slight exceedances that are not clinicallysignificance, as judged by the investigator, may not be excluded;

6. Fasting triglycerides ≥ 5.7 mmol/L or total cholesterol ≥ 10.34 mmol/L at thescreening visit and baseline;

7. Presence any of the following infections at the screening visit: Positive human immunodeficiency virus antibody (HIV Ab); Positive Treponema pallidumantibody (TP Ab);

8. Other active and poorly controlled systemic severe bacterial, viral, fungal orparasitic infections (excluding fungal nail infections) that the investigator deemsunsuitable for participation in this clinical study, such as sepsis, pyemia,bacteremia, and pneumonia caused by novel coronavirus infection;

9. Gastrointestinal diseases that could affect the absorption or metabolism of theinvestigational product as judged by the investigator, within 2 months before thescreening visit;

10. Having undergone major surgeries deemed unsuitable for enrollment by theinvestigator within 6 months before the screening visit or those planning to undergomajor surgeries during the study period (The definition of major surgeries refers toGrade 3 and Grade 4 surgeries as outlined in the "Administrative Measures forGrading of Surgeries in Medical Institutions (Trial)" implemented on December 6, 2022);

11. Patients who have suffered from malignant tumors within 3 years prior to thescreening visit (excluding basal cell carcinoma of the skin that has been radicallycured, squamous cell carcinoma of the skin and/or carcinoma in situ that has beenradically resected);

12. Having a history of alcohol or drug abuse within 1 year prior to the screeningvisit;

13. Known allergy to any components of the investigational product in this study;

14. Having uncorrectable visual or auditory impairments or any other conditions thatwould affect the assessment of the scale;

15. Lactating women;

16. Contraindications to JT821:

Absolute contraindications:

1. Type 1 diabetes

2. Primary carnitine deficiency (Laboratory tests: Hypoglycemia with low ketone levels,elevated creatine kinase (CK), etc.)

3. Carnitine palmitoyltransferase (CPT) I and II deficiency (Laboratory tests:Hypoglycemia with low ketone levels, elevated transaminases, CK, elevated bloodammonia, tandem mass spectrometry for measurement of blood acylcarnitine profile,etc.)

4. Carnitine translocase deficiency (Laboratory tests: Hypoglycemia with low ketonelevels, elevated transaminases, CK, elevated blood ammonia, tandem mass spectrometryfor measurement of blood acylcarnitine profile, etc.)

5. β-Oxidation disorders (Laboratory tests: Blood glucose, electrolytes, blood lipids,coagulation, liver function, kidney function)

6. Medium-chain acyl dehydrogenase deficiency (MCAD) (Laboratory tests: Hypoglycemiawith low ketone levels, elevated transaminases, CK, elevated blood ammonia,metabolic acidosis, tandem mass spectrometry for measurement of blood acylcarnitineprofile, etc.)

7. Long-chain acyl dehydrogenase deficiency (LCAD) (Laboratory tests: Hypoglycemia withlow ketone levels, elevated transaminases, CK, elevated creatine kinase isoenzyme (CK-MB) and lactate dehydrogenase (LDH), tandem mass spectrometry for measurement ofblood acylcarnitine profile)

8. Short-chain acyl dehydrogenase deficiency (SCAD) (Laboratory tests: Tandem massspectrometry for measurement of blood acylcarnitine profile, determination of SCADenzyme activity)

9. Long-chain 3-hydroxyacyl-CoA deficiency (Laboratory tests: Hypoglycemia with lowketone levels, elevated transaminases, CK, elevated CK-MB and LDH, analysis of bloodacylcarnitine profile, etc.)

10. Medium-chain 3-hydroxyacyl-CoA deficiency (Laboratory tests: Hypoglycemia with lowketone levels, elevated transaminases, CK, elevated CK-MB and LDH, analysis of bloodacylcarnitine profile, etc.)

11. Pyruvate carboxylase deficiency (Laboratory tests: Hypoglycemia with low ketonelevels, elevated transaminases, CK, elevated CK-MB and LDH, analysis of bloodacylcarnitine profile, etc.)

12. Porphyria (Laboratory tests: Sunlight test of urinary porphobilinogen) Relativecontraindications: (Fasting blood glucose < 2.8 mmol/L, blood ketone > 0.5 mmol/L)Patients who cannot maintain adequate nutrition (17) Any other situations that theinvestigator considers unsuitable for participating in this study; (18)Currentlyparticipating in other drug/device clinical trials.