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Alzheimer’s Disease Not Merely Results of Brain Pathology, Purpose of Life Matters

For decades, abnormal proteins called amyloid and tau were widely accepted as the cause of Alzheimer’s disease. These theories dominated the field of science and led people to believe that removal of the abnormal plaque formed by the proteins, could cure Alzheimer’s disease.

Clinical trials on Aducanumab as a beta-amyloid antibody did reduce beba-amyloid load in the brain. However, patients’ clinical cognitive impairment did not reduce correspondingly. It leads to the conclusion that Alzheimer’s disease is not merely the results of brain pathological changes, preventive actions seem to be the most advisable strategies for the management.

Pathologies Are Not Determinants of Cognitive Decline

According to the publication on two clinical-pathologic studies on a total of 856 deceased participants,  the common pathologic changes only accounted for less than a third of the cognitive decline. Much remains unexplained.

There were also many examples demonstrating the mismatch between the severity of pathologic burden and the degree of cognitive impairment.

For instance, a research on 28 elderly subjects indicated that 9 of them, about 32 percent, were not demented when evaluated just prior to their death, but the postmortem neuropathology tests demonstrated extensive cortical plaques, including senile plaque and neurofibrillary tangles.

A postmortem examination on 137 residents whose average age was 85.5 years old, the results showed that only 55 percent of them demonstrated Alzheimer’s disease pathological characteristics. Nonetheless, 79 percent of the residents were demented during their late life.

In a Nun study on 130 women of 76-102 years old, only 42 percent of the participants demonstrated cognitive impairment among those with Alzheimer’s disease lesions in their brain.

In another study on 296 deceased subjects without cognitive impairment, post-mortem evaluation found that nearly every brain had neurofibrillary pathology and over 70 percent had amyloid accumulation.

These findings stimulated a demand to understand the basis of this pathology—cognition gap and the broader picture of Alzheimer’s disease.

As human beings are a holistic body with physical, mental, and spiritual components, there is an emerging trend in studying the mental and spirituality aspects in the disease course and prevention of AD.

Purpose of Life and Alleviating Alzheimer’s

A surprising mental factor—purpose of life, is found to be related to Alzheimer’s disease.

Purpose of life is a psychological tendency to derive meaning from Life’s experiences, it is about cultivating an understanding of what is important in life and developing principles to guide one’s actions especially when life gets tough.

A  longitudinal study on 246 subjects from the Rush Memory and Aging Project showed that the purpose of life can modify the global Alzheimer’s disease pathologic changes and cognition. That means, the higher levels of purpose in life tend to exhibit better cognitive function, despite the pathologic changes of Alzheimer’s disease. Furthermore, the purpose of life could alleviate the pathologic changes and cognitive decline of Alzheimer’s disease, and the protective effect persisted after controlling potentially influential variables.

Another research performed on more than 900 community-dwelling older persons found that a person with a high score on the purpose of life was approximately 2.4 times more likely to remain free of Alzheimer’s disease than a person with a low score (Figure 1), and exhibit a lower cognitive decline (Figure 2). The results concluded that greater purpose in life is associated with a reduced risk of Alzheimer’s disease.

Figure 1 Cumulative hazard of Alzheimer disease for participants with high vs low purpose in life scores.
(Source:Patricia A. Boyle, Aron S. Buchman, Lisa L. Barnes, David A. Bennett. Effect of a Purpose in Life on Risk of Incident Alzheimer Disease and Mild Cognitive Impairment in Community-Dwelling Older Persons. Arch Gen Psychiatry. 2010 Mar; 67(3):304–310.)
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Figure 2 Decline in global cognition for participants with high vs low scores on the purpose in life measure. (Source: Patricia A. Boyle, Aron S. Buchman, Lisa L. Barnes, David A. Bennett. Effect of a Purpose in Life on Risk of Incident Alzheimer Disease and Mild Cognitive Impairment in Community-Dwelling Older Persons. Arch Gen Psychiatry. 2010 Mar; 67(3): 304–310.)

Attaining High Purpose of Life

The ability to attain a high purpose of life requires self-reflection,  goals and priority establishment, and focus.

The Health and Retirement Study on a sample of 8,788 middle-aged and older adults in the US found that those with higher adherence to moral standards and ethical behaviors reported a higher sense of purpose in life after the 4-year follow-up period. This association trend remained the same after the adjustment of demographics, socioeconomic status, health conditions, and psychological predispositions such as dispositional optimism and life satisfaction.

Data analysis from two observational studies collected in 1,209 U.S. and 495 Mexican workers found that orientation to promote good, i.e. having thoughts and taking actions that contribute to the good of oneself and others, was positively associated with subsequently higher levels of purpose in life.

Furthermore, the predisposition to act according to ethical standards and rules of good and honest contributes to the good of oneself and others, and better health.

In particular, moral standards and ethical behaviors are associated with lower risks of incidence of cognitive impairment, depression, unfavorable health-related behaviors, immobility and difficulty in activities of daily living, which will eventually reduce the incidence of Alzheimer’s disease.

Maintaining a Sense of Purpose in Life Is Important

Having a purpose also helps to bring lifelong benefits, including increased optimism, resilience, and hope, greater physical health, and a lower risk of death. It helps us to stay emotionally even-keeled in both positive and negative situations, and can be accessed by everyone, regardless of age.

Particularly in old age, maintaining a purpose in life is essential when losses, such as widowhood, retirement, and other age-related deficits and losses, become more common. It is vital for older individuals to prepare in middle adulthood for living longer and prevent Alzheimer’s disease, as this will help to ensure their physical and mental well being in later life.

Promote good consistently with a mindset beneficial to oneself and others help to build up morally valued personality traits, which is fundamental to one’s identity can lead to positive outcomes for oneself and/or others, and also contribute to the greater good.

For some people, this notion might contrast to the rule of “survival of the fittest”, which is a self-oriented, self-preservation concept, and has been flourishing in our individualistic culture. The main difference is that the behavior of living beings is not just self-oriented; rather it is a balance of self-interest and altruism. By promoting kindness using an automatic or mimicry approach, other than scolding or moral persuasion, people can intuitively reconnect with innate desires to help others and shift that balance.

Promoting cooperation and mutual aid, can also better ensure the survival of the species.

Even though promotion of kindness alone will not directly solve problems, it does enable people to feel less stressed and more connected to one another.  The opportunities to find compromises and solutions may flow from the supportive society change other than lonely struggling individuals.

In summary,  purpose in life is associated with cognitive outcomes  and Alzheimer’s disease. It is modifiable, and offers a new treatment focus to reduce the increasing burden of Alzheimer’s disease in old age.

Epoch Health articles are for informational purposes and are not a substitute for individualized medical advice. Please consult a trusted professional for personal medical advice, diagnoses, and treatment. Have a question? Email us at [email protected]

Stephanie Zhang

Stephanie Zhang, PhD, has over 20 years’ research experience in neuroscience and toxicity. She is a former research scientist in The Memory Impairment and Neurodegenerative Dementia (MIND) Center at The University of Mississippi Medical Center.


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