Alzheimer’s Disease and Long-Term Memory
Written by: Scott D. Slotnick
Cognitive Neuroscience of Memory
Scott D. Slotnick author of Cognitive Neuroscience of Memory discusses the link between Alzheimer's and long term memory.
Alzheimer’s disease (AD) is the most common cause of cognitive deficits in older adults. The first cognitive problem in early AD patients is impaired long-term memory. Long-term memory is a type of explicit/conscious memory in which information that was learned minutes, days, or years ago is retrieved (in contrast to short-term/working memory, where information that was presented seconds ago is actively kept in mind).
As AD progresses from earlier to later stages, atrophy starts in the medial temporal lobe, then it extends to the parietal lobe, and finally it includes the frontal lobe. The long-term memory impairment in early AD patients can be attributed to the disrupted processing in the hippocampus (within the medial temporal lobe) and the parietal cortex, two regions that have been associated with this cognitive process. As the disease progresses, other cognitive functions are disrupted such as attention and language, which both depend on the dorsolateral prefrontal cortex. AD patients also have abnormally high levels of proteins in different brain regions. In the medial temporal lobe, the accumulation of tau protein leads to neurofibrillary tangles. In cortical regions, such as the parietal cortex in early AD, the accumulation of amyloid-β protein leads to amyloid plaques. The neurofibrillary tangles in the medial temporal lobe and amyloid plaques in cortical regions can be assumed to disrupt neural processing in these regions.
There is an influential hypothesis that there is a causal relationship between default network activity that leads to deposition of amyloid that results in atrophy and disrupted metabolic activity, which impairs long-term memory in AD patients (Buckner et al., 2005). Regions in the default network are active when participants are not engaged in a task and include the dorsolateral prefrontal cortex, the medial prefrontal cortex, the inferior parietal cortex, and the medial parietal cortex. In AD patients, amyloid deposition occurs in the same regions, which suggests default network activity may lead to amyloid deposition. However, the link between amyloid deposition and atrophy is tenuous, as AD patients initially have atrophy in the medial temporal lobe and the parietal cortex. Thus, in early AD patients, there is no correlation between amyloid deposition and atrophy in either the medial temporal lobe (where there is low amyloid deposition but significant atrophy) or the frontal cortex (where there is high amyloid deposition but little atrophy). This questions the hypothesis that a high level of amyloid deposition causes atrophy in AD patients. However, it is still possible that a high level of amyloid deposition causes atrophy in susceptible brain regions, such as the parietal cortex. Perhaps a higher level of amyloid deposition, which occurs in late AD patients, is necessary to produce atrophy in the frontal cortex. These are topics for future investigations.
Interestingly, there is considerable variation in the level of amyloid deposition in the brains of healthy older adults. If high amyloid deposition is a causal factor in developing AD, older adults with low levels of amyloid should be at decreased risk for developing this disease. There is some evidence that cognitive engagement and exercise engagement throughout life may reduce the amyloid level in the brains of healthy older adults. In one study, cortical amyloid level was measured in older adults as a function of cognitive engagement and compared to the cortical amyloid levels in AD patients and young adults (Landau et al., 2012). Amyloid level was measured using positron emission tomography (PET) with a radioactive substance that binds to this protein. Participants rated the frequency in which they engaged in cognitively demanding tasks such as reading, writing, going to the library, or playing games at five different ages (6, 12, 18, 40, and their current age). Healthy older adults with greater cognitive engagement throughout their lifetime had lower levels of amyloid in default network regions. Moreover, healthy older adults in the lowest one-third of lifetime cognitive engagement had amyloid levels that were equivalent to AD patients, and the healthy older adults in the highest one-third of lifetime cognitive engagement had amyloid levels that were equivalent to young adults. Another study measured the level of AD biomarkers in healthy older adults as a function of exercise (Liang et al., 2010). Cortical amyloid level was measured using PET and tau protein level was measured in the cerebrospinal fluid using a spinal tap. Participants rated the frequency and duration that they engaged in walking, running, and jogging for the previous 10 years. Exercise engagement was the average metabolic equivalent hours per week during that period. As a reference value, the American Heart Association recommends about 30 minutes of moderate exercise 5 days per week. Older adults with higher level of exercise engagement had lower levels of amyloid and lower levels of tau. It is particularly striking that none of the older adults who exercised more than the recommended hours per week had abnormal levels of amyloid or tau.
The results of the previous two studies suggest that cognitive engagement and exercise engagement throughout life reduce the levels of amyloid protein and tau protein in the brain. As these are the primary biomarkers in AD, mental processing and physical activity may reduce the risk of contracting this disease.
Part 3: The Brain Basis of Forgetting
Part 4: Episodic Memory in Mammals