John E. Lewis, PhD, and Lonnie A. Fravel, BA, BS

Introduction

Today worldwide, approximately 50 million people have Alzheimer’s disease and other forms of dementia,¹ about 10 million people have Parkinson’s disease,² and 2.5 million people have multiple sclerosis,³ which are the leading forms of neurodegenerative diseases. Alzheimer’s disease and related dementias are the sixth leading cause of death of Americans and a primary cause of institutionalization among the elderly.⁴ All of these diseases are marked by cognitive dysfunction and other functional impairments. Unfortunately, approved medications are highly ineffective and have costly untoward side effects. Thus, alternative approaches and treatments, such as dietary supplementation and nutrition, are needed to help those affected to have a better quality of life.

One alternative approach to addressing problems inherent with neurodegenerative disorders may be through the consumption of plasmalogens. Plasmalogens are a type of phospholipid present in almost all human tissues and in plasma lipoproteins in the cell membrane.⁵ They are thought to be antioxidative due to the presence of a double vinyl ether bond; however, that activity is not completely accepted, but they help to protect cell membranes and lipoproteins from reactive oxygen species.⁶

Plasmalogens are most abundant in the brain and heart,⁷ and these endogenously produced phospholipids can also be obtained from dietary sources, such as in scallop oil. In fact, several recent studies in Japan using plasmalogen-rich scallop oil were conducted in people with Alzheimer’s disease, mild cognitive impairment, and Parkinson’s disease showing significant improvement in cognitive function along with elevations in blood plasmalogen levels.⁷

Methods

Thus, we decided to test a unique extract of plasmalogen from scallop called Hokkaido Scallop Oil Plasmalogen (HSOP from Daiwa Pharmaceutical Co., Ltd.) in a sample of older adults from South Florida with either concerns about memory and cognition or some form of actual memory loss/cognitive dysfunction. Scallops from Hokkaido are known for their concentrated amount of plasmalogen relative to other sources and contain more desirable amounts of omega-3 fatty acids as well.

Assessments. Subjects were recruited to participate in a 90-day pilot program to determine if HSOP would have an effect on cognitive function according to the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). The Activities of Daily Living/Independent Activities of Daily Living (ADL/IADL) and the Center for Epidemiological Survey-Depression (CESD) forms were also included in the assessment, given their relevance to older people who have issues with activities and depressive symptoms or disorder.

The MMSE is used to assess mental status systematically and thoroughly. It is an 11-question measure that tests five areas of cognitive function: orientation, registration, attention and calculation, recall, and language with a maximum score of 30. A score of 23 or lower is indicative of cognitive impairment.

The MoCA assesses different cognitive domains: attention and concentration, executive functions, memory, language, visuoconstructional skills, conceptual thinking, calculations, and orientation. The maximal score is 30, and a score of 26 or above is considered normal.

The CESD total score is the sum of the 20 questions with a possible range of 0-60, and a score of 16 points or more is considered indicative of depression.

The IADL score is summed from 0-8 with 0 indicating total independence and 8 complete dependence.

The ADL score is summed from 0-7 with 0 indicating total independence and 7 complete dependence. One question for both IADL and ADL assesses if the subject experienced any significant decline in the previous six months, with possible answers being “no change,” “minimal decline,” and “significant decline.”

Subjects. Nine subjects agreed to participate in the pilot program and provided informed consent prior to starting. Subjects were provided with enough HSOP for the 90-day program, including instructions for taking the product, how to complete their intake diary, and what was expected of their participation. Subjects were randomly assigned to take either one 0.5 mg HSOP capsule per day (n=5) or two 0.5 mg HSOP capsules per day (n=4). Those taking one capsule per day were advised to take their capsule at a convenient time of the day with other dietary supplements or medications. Those taking two capsules per day were advised to take one in the morning and one in the evening.

Results

Demographics. Subjects were on average 76 years of age (SD=10.1) and included four men and five women. Six subjects were married and three subjects were widowed. Five subjects were white, non-Hispanic and four subjects were white, Hispanic. Four subjects primarily spoke English, and five subjects primarily spoke Spanish. One subject had completed the sixth grade, two subjects had completed high school, one subject had post-high school vocational training, two subjects had completed an associate degree, and three subjects were college graduates.

Clinical History. Five subjects had been diagnosed with some form of dementia (including possible Alzheimer’s); one subject had been diagnosed with Parkinson’s disease; one subject had been diagnosed with hydrocephalus; and two subjects had age-associated memory difficulties or concerns. Three subjects had also been diagnosed with depression, one with insomnia, one with aneurism, and one with diabetes. As expected, each subject was taking several different medications, and some subjects were also taking several dietary supplements, but no other plasmalogen product.

Subject Participation. Out of the nine subjects who agreed to participate in the program, seven completed the 90-day trial. The seven subjects who completed the trial reported a very high level of compliance with taking their daily dose of HSOP for the 90 days, and no one reported an adverse effect. Two subjects (husband and wife) dropped out about midway through the program due to an apparent worsening of the husband’s Parkinson’s condition, which also caused the wife to move out of their house and in with their daughter. Unfortunately, they refused repeated attempts to reestablish participation in the program.

The oldest participant in the program (95 years) was a severe case of Alzheimer’s, and he could not complete any of the outcome assessments (MMSE, MoCA, or CESD) at baseline or follow-up. His scores for the MMSE and MoCA were recorded as zero, and his score for the CESD was missing. However, according to his daughter, the primary caregiver, he took two 0.5 mg capsules of HSOP every day for the program and a couple of times showed awareness of his surroundings.

Changes on the MMSE. The average score of the MMSE at baseline was 19.1 (SD=9.7), and the average score at follow-up was 21.9 (SD=10.2), and the difference from baseline to follow-up was statistically significant (t(6)=-2.7, p=0.04). When splitting the group into those taking one HSOP capsule per day and those taking two HSOP capsules per day, no differences were noted for the change in the MMSE score from baseline to follow-up.

Changes on the MoCA. The average score of the MoCA at baseline was 15.9 (SD=8.6), and the average score at follow-up was 16.6 (SD=9.7), and the difference from baseline to follow-up was not statistically significant (t(6)=-0.9, p=0.44). When splitting the group into those taking one HSOP capsule per day and those taking two HSOP capsules per day, no differences were noted for the change in the MoCA score from baseline to follow-up.

Changes on the CESD. The average score of the CESD at baseline was 18.7 (SD=11.2), and the average score at follow-up was 10.0 (SD=8.4), and the difference from baseline to follow-up was not statistically significant (t(5)=1.6, p=0.16). When splitting the group into those taking one HSOP capsule per day and those taking two HSOP capsules per day, no differences were noted for the change in the CESD score from baseline to follow-up.

Changes on the IADL and ADL. The average score of the IADL at baseline was 4.7 (SD=3.8), and the average score at follow-up was 4.2 (SD=3.9), and the difference from baseline to follow-up on the IADL was not statistically significant (t(5)=1.0, p=0.36). The average score of the ADL at baseline was 1.5 (SD=2.5), and the average score at follow-up was 1.3 (SD=2.2), and the difference from baseline to follow-up on the ADL was also not statistically significant (t(5)=1.0, p=0.36).

Frequency of Changes on Outcome Measures. Finally, changes were calculated from baseline to follow-up for each of the outcome measures (see Tables 1a-1e). For the MMSE and the MoCA, a negative score reflects an improvement, a zero reflects no change, and a positive score reflects a decrease. For the CESD, IADL, and ADL, a negative score reflects a decrease, a zero reflects no change, and a positive score reflects improvement.

For the MMSE, five subjects improved, one subject remained the same, and one subject worsened. In particular, two subjects (a 77-year-old female with an aneurism 10 years ago and Alzheimer’s for the past year and an 86-year-old female with cognitive impairment and possible Alzheimer’s) both showed a 5-point improvement on the MMSE (20 to 25) going from moderate cognitive impairment to within the lower end of the normal cognitive range. Another subject (a 73-year-old male) with a history of hydrocephalus and memory-associated problems showed a 4-point improvement on the MMSE (23 to 27) going from mild cognitive impairment to within the normal cognitive range.

For the MoCA, three subjects improved, two subjects remained the same, and two subjects declined. In particular, one subject (a 62-year-old female with increasing forgetfulness and memory concerns) showed a 5-point improvement on the MoCA (25 to 30) going from mild cognitive impairment to normal cognitive function.

For the CESD, one subject worsened, and five subjects improved. In particular, three subjects showed impressive improvements in their depressive symptoms. A 73-year-old male with a history of hydrocephalus and memory associated problems showed a 12-point improvement on the CESD (16 to 4) going from mild depressive symptoms in the upper range to mild depressive symptoms in the lower range. An 80-year-old male with a recent diagnosis of Alzheimer’s showed an 11-point improvement on the CESD (20 to 9) going from moderate depressive symptoms to mild depressive symptoms in the lower range. A 77-year-old female with a long history of depression and associated memory problems showed a dramatic 31-point improvement on the CESD (35 to 4) going from severe depressive symptoms to mild depressive symptoms in the lower range.

For the IADL, five subjects remained the same, and one subject improved. For the ADL, five subjects remained the same, and one subject improved.

Relationship Between Age and Outcome Measures. To gain some insight into how much age of the subjects and the outcome measures were related with one another, correlation coefficients were calculated at baseline and follow-up for the MMSE, MoCA, CESD, IADL, and ADL. At baseline and as expected, age was inversely correlated with the MMSE (r=-0.88, p=0.002) and MoCA (r=-0.84, p=0.004). The MMSE and MoCA were linearly correlated with each other (r=0.86, p=0.003), and the MMSE (r=-0.93, p=0.002) and MoCA (r=-0.89, p=0.008) were inversely correlated with the ADL. No other correlations were significant. The correlations at follow-up showed a similar pattern to those at baseline.

Discussion

In summary, this 90-day pilot program of subjects with varying health issues related to memory loss or cognitive concerns, i.e., Alzheimer’s or another form of dementia, Parkinson’s, hydrocephalus, depression, and age-associated memory concerns, showed that HSOP demonstrated a significant improvement in the MMSE from baseline to follow-up.

Changes on the MMSE and MoCA of at least one point were clinically relevant for several subjects, including several subjects who went from the mild/moderate cognitive impairment range into the normal cognitive function range. Five subjects showed progress in depressive symptoms according to the CESD, and three subjects showed dramatic improvements in their scores. Changed scores in the IADL and ADL mostly demonstrated no difference from baseline to follow-up. Correlations among age and the outcome measures were typical and not of noteworthy discussion.

The two participants who dropped out apparently did so not because of the program or HSOP, but due to a worsening of the husband’s medical condition (Parkinson’s), which caused the wife to drop out as well. No subjects or caregivers reported any adverse effects. According to each daily diary, compliance was particularly good with taking one or two capsules per day for the 90-day period.

The results of this pilot program show that HSOP is safe to take and may provide some benefit to cognitive function and depressive symptoms according to the clinically relevant changes in the MMSE, MoCA, and CESD over a 90-day period. Given the lack of efficacy for treating people with age-associated memory and cognitive dysfunction, HSOP may provide a natural and safe alternative for those faced with such challenges.

References

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Originally published March 25, 2023

Author Affiliations

John E. Lewis, PhD, is affiliated with Morris Formulations, LLC, Miami, FL USA.
Lonnie A. Fravel, BA, BS, is affiliated with 7 Story Media, LLC, Ft. Lauderdale, FL USA.