PSYC 322 - Higher Order Cognition II

Identify demographic, medical, and modifiable risk factors for cognitive decline.

1. What factors increase the risk of going from primary to secondary aging?

   1. APOE4 presence, age, less years of education associated with transition to amnestic MCI (memory-prominent deficit).

   2. Age, less years of education associated with transition to mixed MCI (these factors have uniform cognitive deficits).

   3. Surprisingly, sex or family history are not predictive of transition to MCI.

   4. APOE4 presence is significantly associated with the transition from normal to dementia diagnosis.

   5. Age remains a significant risk factor of dementia (generally, regardless of prior state) and death.

      1. Age remains the biggest risk factor of cognitive decline.

   6. A lower score on MCI leads to dementia progression (compared to healthy people with stable MCI scores).

   7. Lower scores in visuospatial, naming, attention, and memory domains are risk factors for cognitive decline.

      1. Generally, decreases in cognitive domains are big risk factors for dementia and cognitive decline.

   8. Age is a big factor in the progression of MCI to dementia.

   9. A stronger attention cognitive domain is neuroprotective from the MCI to dementia progression.

      1. Worse attention domain is associated with the MCI to dementia progression.

   10. There is a higher prevalence of AD in women vs. men, especially in older age (after ~75 years).

       1. Mixed results for MCI.

       2. This is because APOE4 effects are more prominent in women; menopause / hormonal changes in women are linked with cognitive decline. Estrogen is linked with neuroprotective effects, so a decline in estrogen in old age is a possible mechanism.

   11. Females have more neuroprotective measures earlier in aging, with sharper decline.

       1. We see a steadier decline in males. This disparity may explain higher prevalence of AD in women, but there is an unclear / even prevalence between males and females in MCI.

       2. Females' better cognitive domains include verbal memory and verbal fluency tasks. This could be related to cognitive reserve theory.

       3. Female verbal memory advantage is related to education level, and accumulation of knowledge over time. These factors may disguise MCI / early AD.

          1. I.e., since females are stronger in these areas, declines may just be written off as normal declines in primary aging since the baseline is already so strong. We need to see a bigger cognitive change in females early on to diagnose, compared to men.

Understand the differences between treatment and prevention approaches to targeting cognitive decline.

1. Treatment Approach.

   1. Addressing issues that are present in an individual.

   2. Focus on disease mechanisms - how the disease works, its pathology, etc.

      1. Trying to slow down these mechanisms.

   3. The “classic model”, which targets symptoms / mechanisms of disease.

2. Prevention Approach.

   1. Proactive measures to stop or slow progression.

   2. Focus on modifiable risk factors - high-risk factors for a disease state that can be changed / modified if addressed early enough.

   3. Holistic; preventing risk factors so disease state does not develop at all or at least does not develop further / is reversed.

Define and describe the common pharmacological treatments that target cognitive decline / AD.

1. Acetylcholinesterase Inhibitors (AChE inhibitors), such as Rivastigmine.

   1. Used to inhibit the role of AChE (enzyme), which breaks down Acetylcholine (ACh). ACh is very important for learning, memory, and cognitive functioning.

      1. Inhibiting the enzyme that breaks down ACh leads to an increase in ACh levels.

   2. Used to slow cognitive decline in AD, PD, dementia, etc.

   3. Donepezil is another AChE inhibitor that, when combined with other components, can target beta amyloid aggregation.

2. Anti Beta Amyloid Immunotherapy.

   1. An antibody treatment that binds to soluble beta amyloid and effectively clears it.

   2. Slower decline of dementia vs. placebo in clinical trials.

   3. Some adverse effects.

Define and describe some preventative interventions / lifestyle factors that help prevent cognitive decline / AD.

1. Modifiable Risk Factors.

   1. Early Life (<45 years).

      1. Less education.

   2. Midlife (45-65 years).

      1. Hearing loss.

      2. TBI.

      3. Hypertension.

      4. Alcohol.

      5. Obesity.

   3. Later Life (>65 years).

      1. Smoking.

      2. Depression.

      3. Social isolation.

      4. Physical inactivity.

      5. Diabetes.

      6. Air pollution.

   4. This does not mean that these factors do not matter in other stages of life, merely stating when these factors are statistically significant impacting risk of getting dementia. 

   5. By treating and minimising these risk factors, and by maintaining health behaviours, we can reduce neuropathological damage and increase and better maintain our cognitive reserve, leading to a prevention of dementia.

2. Cognitive Training.

   1. Intervention / cognitive training helps improve cognition / slow down decline.

   2. Note: not all cognitive training is made the same! (I.e., Lumosity, which was not developed by researchers nor actually effective).

3. Exercise.

   1. One of the most reliable neuroprotective lifestyle interventions against neurodegenerative diseases.

   2. Open-skill exercises (I.e., dynamic, externally paced, and more unpredictable environments) are linked with better cognitive outcomes across all age groups.

      1. I.e., team sports are open skill, unpredictable, and promote a social circle.

         1. For example, basketball is more unpredictable game to game and requires socializing, compared to something like running which is the same each time and can be done alone.

   3. Possible Mechanisms of Exercise’s Positive Benefits.

      1. Improvement in cardiovascular factors (I.e., diabetes, hypertension, hyperlipidemia, and obesity).

      2. Increased amyloid beta turnover.

      3. Increased cerebral blood flow.

4. Diet.

   1. Mediterranean diet associated with a reduced risk of mild cognitive impairment and dementia, including Alzheimer disease (AD).

      1. Delays onset of PD.

   2. Mediterranean diet can lead to improvements in episodic memory, global cognition, and semantic memory (especially global cognition).