The Top 10 Hot Topics in Aging

I enjoy talking with very old people. They have gone before us on a road by which we, too, may have to travel, and I think we do well to learn from them what it is like. —Socrates, in Plato's The Republic EACH year in January, I have tried to review the cutting edge of geriatrics over the previous 2 years (1,2). This review is based to some extent on the high impact articles in the literature (3,4), but also on emerging areas. The Journals of Gerontology Series A also continue to welcome articles from some of our distinguished colleagues who have gone before us on the exploration of the wonders of aging and remain active contributors to the field of gerontology (5–8). This year, being my last year as editor of the Journal of Gerontology: Medical Sciences, I have decided to list what I believe are the top 10 hot areas in geriatrics. There is no question that finding solutions to cognitive decline and the behavioral problems associated with it is a central area in geriatrics (9–11). Our knowledge of the pathophysiology of Alzheimer's disease is moving forward rapidly. While beta-amyloid has taken center stage, both as a neurotransmitter that produces learning and memory disturbances (12,13) as well as an initiator of tissue destruction, possibly through free radical activation (14,15), there is also increasing understanding of the tauopathies (16). A recent article showed that measuring tau protein in lip epithelial tissue could possibly be used to diagnose Alzheimer's disease (17). There is an increasing awareness of the importance in early recognition of mild cognitive impairment (18,19). Acute illness causes not only short-term but also long-term functional decline in persons with preexisting cognitive impairment (20). In particular, it is now becoming clear that cognitive decline is associated with a decline in physical performance (19,21–27). This is in part due to the decrease in reaction time associated with central nervous system damage (22). Cognitive dysfunction, whatever the cause, is associated with a high rate of medical comorbidity (23,28) and earlier mortality (24,29). The effects on mortality are worsened when cognitive dysfunction coexists with depression (29). Over the last decade, there has been much enthusiasm for the possibility that hormone replacement therapy may improve cognition and slow progression of Alzheimer's disease (30–33). However, the Women's Health Initiative (WHI) in older women showed that hormone replacement therapy resulted in both a greater degree of cognitive dysfunction and an increase in the incidence of Alzheimer's disease (34,35). At the same time, as these results have become known, there is an increasing belief that testosterone in males may improve cognitive function (36–38). A relationship between elevated homocysteine and vitamin B12 and folate deficiency with Alzheimer's disease has been found (30,39). Other studies have suggested that hypercholesterolemia may play a key role in the development of Alzheimer's disease and worsening cognitive function (40,41). Centenarians with high HDL (high-density lipoprotein) levels have better cognitive function and exceptional longevity (42). It is possible that cholesterol-lowering, especially in mid-life, results in a decline in atherothrombotic brain infarction, which may, in itself, be a causative agent for Alzheimer's disease (43–46). In the arena of treatment for Alzheimer's disease, data continue to emerge that cholinesterase inhibitors slow the progression of the disease (9). Memantine, a drug that modulates the glutamate/NMDA system, can now be added to our therapeutic armamentarium and may prove useful either alone or in combination with cholinesterase inhibitors (47). Studies continue to appear that gingko biloba is a useful therapeutic adjuvant for persons with Alzheimer's disease (48). The effects of gingko appear to be equivalent to some of the more mainstream therapeutic agents (49). There is an urgent need for high-quality, large (i.e., sufficiently well powered) studies utilizing this agent. An exciting recent study has shown that aerobic fitness reduces brain tissue loss in humans (50). Resistance exercise has recently been shown to improve function in people with dementia (51). These findings strongly reinforce the calls in the Journals to continue to exercise throughout life and maintain healthy lifestyle habits in order to compress morbidity (52–55). While antibodies to beta-amyloid can reverse cognitive dysfunction in mice (48,49), the human immunization studies led to disastrous consequences, with some of the patients developing an inflammatory disease of the central nervous system (56). Thus, while we await the potential of antisense to beta-amyloid that can switch off its production or drugs that can inhibit the function of the amyloid precursor protein cleavage enzymes (secretases) (10,57,58), most of the care of patients with Alzheimer's disease still need to focus on end-of-life care (59). As has been demonstrated by Simmons and colleagues (60), feeding the older demented patient takes an inordinately long time. New methods need to be developed to accurately quantify the amount of food consumed by older patients (61). Protein energy malnutrition can cause a marked decline in quality of life in nursing homes (62). Small changes in the emotional status of institutionalized elders can markedly alter food intake (63,64). Innovative programs such as the “Eden” alternative or even mechanical pet therapy need to be put in place to improve quality of care in nursing homes (65–68). As so eloquently suggested by John Schnelle (69), we need to “capture the voice of cognitively impaired elders” to improve their quality of life. Kane and colleagues (70) have provided one approach to doing this. Kane (71) has also called for professionals who have the experience of having loved ones cared for in long-term care facilities to band together in an attempt to find new solutions that will impro