Mood, memory and movement: an age-related neurodegenerative complex?

Abstract

The following review was constructed as a concept paper based on a recent workshop on neurodegenerative disease sponsored by the National Institute on Aging (NIA), the American Geriatric Society (AGS), and the John A. Hartford Foundation. The meeting was entitled "Thinking, moving and feeling: Common underlying mechanisms? 4(th) Annual Bedside-to-Bench Conference" and had the purpose to connect current basic and clinical findings on common brain-related alterations occurring with aging such as depression, movement disorders, and cognitive decline. Many prominent researchers expressed their opinion on aging and it was revealed that age-related brain dysfunction of any kind seems to share several risk factors and/or pathways. But can something be done to actively achieve "successful aging"? In this review, based largely on the workshop and current literature, we have summarized some of the current theories for depression, movement and cognitive impairment with aging, as well as potential preventive measures. We have also summarized the emerging need for relevant animal models and how these could be developed and utilized.

Fig. (1)

Age-related neurodegenerative complex can be caused by a number of different factors, isolated or in combination. While aging itself is the most common denominator, oxidative stress, inflammation and protein aggregation, for example, are all part of the common pathology seen in PD and AD patients. Studies on movement disorders or memory loss with aging should include at least minimal studies on the other modalities described as well (and listed above in this figure), to reach further understanding of this common co-morbidity in the aged population. For example, most animal models for PD are not tested for cognitive loss or loss of motivation or attention, studies that would definitely add to the validity for future clinical treatment and for more successful drug development.

Fig. (2)

Aging leads to a series of parallel processes, which all affect behavior to different extents. Inflammation, oxidative stress and reduced neuronal function can all have detrimental outcomes on “thinking, moving, feeling”. As the oxidative stress and inflammation increase and neuronal function decreases with age, eventually the individual will develop clinical symptoms. It is important to note, though, that symptoms do not occur (“asymptomatic”) until significant damage has already occurred and the individual crosses the threshold (green bar). It is not known why certain individuals are prone to AD rather than PD, or why certain individuals have PD earlier in life than others. Better animal models are needed to explore these processes.