Alzheimer's Disease: Potential Benefit of Isoflavones

Time to complete mazes is a test of planning. Subjects are asked to complete a set of 3 mazes. The time taken to complete the maze is inversely proportional to the cognitive function.

Time frame: 6 months

Participants are given 1 min to produce as many unique words as possible within a category (category fluency). More words per minute will correlates to better category fluency

Time frame: 6 months

Participants are given 1 min to produce as many words as possible starting with a given letter (letter fluency). More number of words per minute correlates to better phonemic fluency/verbal fluency

Time frame: 6 months

The Benton Visual Retention Test is an individually administered test for people aged from 8 years to adulthood that measures visual perception and visual memory. It can also be used to help identify possible learning disabilities among other afflictions that might affect an individual's memory. The individual examined is shown 10 designs, one at a time, and asked to reproduce each one as exactly as possible on plain paper from memory. The test is untimed, and the results are professionally scored by form, shape, pattern, and arrangement on the paper. For the 'test of number of errors' score is calculated based on the number and type of errors made for each design. The major categories for these errors are omissions, distortions, perseverations, rotations, misplacements, and size errors.These scores are then be compared to several sets of normative data available in the manual, each representing different demographic characteristics, and conclusions can be drawn by the examiner.

Time frame: 6 months

List of 15 semantically unrelated words is presented verbally to the participants once, after which they are asked to free recall as many words as possible. Subsequently, this presentation-test routine (learning trials) is repeated four more times. A total recall score is determined by adding the number of recalled items for the five learning trials. After presentation of a distractor list and a delay of approximately 20 minutes, participants are asked to freely recall items from the original word list. A delayed recall score is then derived from this test.

Time frame: 6 months

In the logical delayed memory test, participants are read a logically organized story. Approximately 20 minutes later, the participants are asked to recall the story from memory (Delayed Recall). The version used in this study uses only one story (Story A) read once to participants at each study visit. Possible scores for delayed recall trials range from 0 to 25, with higher scores reflecting more details recalled.

Time frame: 6 months

Trail Making Test-Version B (TMT B) \[113\], a measure of divided attention, the subject is asked to draw lines to connect consecutively numbered and lettered circles, alternating between the 2 sequences. The time needed to complete the task is recorded. More time taken to complete the test or higher score indicates lower executive function/higher impairment.

Time frame: 6 months

Selective attention was evaluated with the Stroop Color Word Interference Test. In the interference portion of this test, the subject identifies the color of ink in which words (red, green, or blue) are printed, requiring the subject to inhibit their natural tendency to read the word. A subject's score is the time taken to identify 50 stimulus items. The time taken to complete the maze is inversely proportional to the cognitive function.

Time frame: 6 months

The Benton Visual Retention Test (or simply Benton test or BVRT) is an individually administered test for people aged from 8 years to adulthood that measures visual perception and visual memory. It can also be used to help identify possible learning disabilities among other afflictions that might affect an individual's memory. The individual examined is shown 10 designs, one at a time, and asked to reproduce each one as exactly as possible on plain paper from memory. The test is untimed, and the results are professionally scored by form, shape, pattern, and arrangement on the paper. For the 'test of number of correct figures' score is calculated based on an all-or-nothing approach; points are awarded if the reproduction of the design matches the original.

Time frame: 6 months

Visual memory will be evaluated by complex figure delayed recall test. In this test , a two dimensional figure is shown to the subjects. After a delay of 30 min, they are asked to draw the same figure based on their memory. The Complex Figure Test assesses the subject's ability to remember a 2-dimensional figure presented briefly. The scoring system used includes scores related to location, accuracy and organization. Higher score correlates to better visual memory.

Time frame: 6 months

During the MMSE, a health professional asks a participant a series of questions designed to test memory, ability to solve simple problems and other thinking skills. The maximum MMSE score - 30 points. Score of 20 to 24 - mild dementia, 13 to 20 - moderate dementia, and \<12 indicates severe dementia. On average, the MMSE score of a person with Alzheimer's declines about 2 to 4 points each year.

Time frame: 6 months

Visual memory will be evaluated by Complex Figure copy test. The Complex Figure Test assesses the subject's ability to copy a 2-dimensional figure. The scoring system used include scores related to location, accuracy and organization. Higher score correlates to better visual memory.

Time frame: 6 months

The Grooved Pegboard is a dexterity test consisting of 25 holes with randomly positioned slots. Pegs with a key on one side must be rotated to match the hole before they can be inserted. Participants are instructed to place all pegs into the 25 holes, picking up one at a time, and using just one hand. They use their dominant hand. Time taken to finish the test inversely correlates to the cognitive ability.

Time frame: 6 months

The Grooved Pegboard is a dexterity test consisting of 25 holes with randomly positioned slots. Pegs with a key on one side must be rotated to match the hole before they can be inserted. Participants are instructed to place all pegs into the 25 holes, picking up one at a time, and using just one hand. They use their non-dominant hand. Time taken to finish the test inversely correlates to the cognitive ability.

Time frame: 6 months

Study partner is someone who has frequent contact with the subject (e.g. an average of 10 hours per week or more), and can accompany the subject to all clinic visits for the duration of the protocol. Study partner will report a short form GDS consisting of 15 questions. Out of 15 items, 10 indicate the presence of depression when answered positively, while the rest (question numbers 1, 5, 7, 11, 13) indicate depression when answered negatively. Scores of 0-4 are considered normal, depending on age, education, and complaints; Scores of 5-8 indicate mild depression; 9-11 indicate moderate depression; and Scores of 12-15 indicate severe depression. The Short Form is more easily used by physically ill and mildly to moderately demented patients who have short attention spans and/or feel easily fatigued. It takes about 5 to 7 minutes to complete.

Time frame: 6 months

Geriatric Depression Scale (GDS) has been tested and used extensively with the older population to measure depression. Subject will self-report a short form GDS consisting of 15 questions. Out of 15 items, 10 indicate the presence of depression when answered positively, while the rest (question numbers 1, 5, 7, 11, 13) indicate depression when answered negatively. Scores of 0-4 are considered normal, depending on age, education, and complaints; Scores of 5-8 indicate mild depression; 9-11 indicate moderate depression; and Scores of 12-15 indicate severe depression. The Short Form is more easily used by physically ill and mildly to moderately demented patients who have short attention spans and/or feel easily fatigued. It takes about 5 to 7 minutes to complete

Time frame: 6 months

Anger scale is one of the subscale of POMS. Tension scale has 12 items and scores ranges from 0-48. Higher score indicates more anger issues.

Time frame: 6 months

Confusion scale is one of the subscale of POMS. Confusion scale has 7 items and scores ranges from 0-28. Higher score indicates more severe outcomes.

Time frame: 6 months

Depression scale is one of the subscale of POMS. Depression scale has 15 items and scores ranges from 0-60. Higher score indicates more severe depression.

Time frame: 6 months

Fatigue scale is one of the subscale of POMS. Tension scale has 7 items and scores ranges from 0-28. Higher score indicates more fatigue.

Time frame: 6 months

Tension scale is one of the subscale of POMS. Tension scale has 9 items and scores ranges from 0-36. Higher score indicates more severe outcomes.

Time frame: 6 months

Vigor scale is one of the subscale of POMS. Vigor scale has 8 items and scores ranges from 0-32. Higher score indicates more severe outcomes.

Time frame: 6 months

The epsilon-4 allele of the apolipoprotein E gene (APOE4) has been consistently associated with a greater risk of Alzheimer's disease (AD) as well as an earlier onset of AD. Determination of apolipoprotein E (APOE) genotype was performed on a non-fasting blood sample collected at Baseline, using standard Polymerase chain reaction (PCR) and DNA sequencing techniques in a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory. DNA extracted from whole blood was amplified by PCR using specific primers for the ApoE gene and the DNA then sequenced and analyzed for genotype using the FinchTV program (Version 1.3; Geospiza, Inc.)

Time frame: Baseline

Population: Older adults with Alzheimer's disease

Estradiol assay will be performed on non-fasting blood samples collected at baseline using an enzyme immunoassay kit.

Time frame: At 3 month

Population: Estradiol analysis done by the same investigator as part of another project with different subjects (PMID: 9054783 linked in the citation), did not show any change in the estradiol levels. Based on that, investigators did not see the justification for running these analyses in the current study. No estradiol analyses were performed for this study.

Estradiol assay will be performed on non-fasting blood samples collected at baseline using an enzyme immunoassay kit.

Time frame: At 6 month

Population: Estradiol analysis done by the same investigator as part of another project with different subjects (PMID: 9054783 linked in the citation), did not show any change in the estradiol levels. Based on that, investigators did not see the justification for running these analyses in the current study. No estradiol analyses were performed for this study.

Estradiol assay will be performed on non-fasting blood samples collected at baseline using an enzyme immunoassay kit.

Time frame: baseline

Population: Estradiol analysis done by the same investigator as part of another project with different subjects (PMID: 9054783 linked in the citation), did not show any change in the estradiol levels. Based on that, investigators did not see the justification for running these analyses in the current study. No estradiol analyses were performed for this study.

Isoflavone assays will be performed on non-fasting blood samples collected at baseline. Novasoy capsules predominantly contain purified glycoside forms of isoflavones known genistein and diadzein. The plasma level of genistein and diadzine will be measured in the participants plasma.There is large inter-individual variations in the extent of intestinal metabolism, even when the quantity of isoflavone intake is standardized. Equol is a metabolite of isoflavones. Equol has high biological efficacy. Therefore, along with genistein and diadzein, plasma levels of equol will be measured to understand the isoflavone metabolism in the participants.

Time frame: baseline

Population: Data is unavailable for 2 subject from placebo group and 1 subjects from Novasoy group

Isoflavone assays will be performed on non-fasting blood samples collected at month 3. Novasoy capsules predominantly contain purified glycoside forms of isoflavones known genistein and diadzein. The plasma level of genistein and diadzine will be measured in the participants plasma.There is large inter-individual variations in the extent of intestinal metabolism, even when the quantity of isoflavone intake is standardized. Equol is a metabolite of isoflavones. Equol has high biological efficacy. Therefore, along with genistein and diadzein, plasma levels of equol will be measured to understand the isoflavone metabolism in the participants.

Time frame: At month 3

Population: Data is unavailable for 1 subject from each group

Isoflavone assays will be performed on non-fasting blood samples collected at month 6. Novasoy capsules predominantly contain purified glycoside forms of isoflavones known genistein and diadzein. The plasma level of genistein and diadzine will be measured in the participants plasma.There is large inter-individual variations in the extent of intestinal metabolism, even when the quantity of isoflavone intake is standardized. Equol is a metabolite of isoflavones. Equol has high biological efficacy. Therefore, along with genistein and diadzein, plasma levels of equol will be measured to understand the isoflavone metabolism in the participants.

Time frame: At month 6

Population: Data is unavailable for 1 subject from placebo group and 3 subjects from Novasoy group