Chapter 25

Frankly, This Subject Is Depressing Me…
How other medical issues contribute to – and often accelerate – functional and neurological decline

I’m not going to go all the way down the list of risk factors contributing to an earlier than otherwise-expected onset of Alzheimer’s. I’ll just cite references for a few of these clinical indications to get you started. It’s easy enough for you to find risk-factor studies for the rest of the things I’ve identified here at PubMed or elsewhere on the Internet.

For DEPRESSION, see, for example, Green RC et al (2003) Depression as a risk factor for Alzheimer’s Disease: The MIRAGE study. rch Neurol 60:753. I cite this study because it showed that even if treated and overcome at a young age, depression occurring any time in your life steals months-to-years of time in life before AD onset can be expected. More recent studies (including several that we have conducted in animal models) indicate that anti-depressant drugs have impacts in the brain that should also, all by themselves, confer significant added risk for earlier AD onset.

Damned if you do. Double-damned if you don’t.

With TRAUMATIC BRAIN INJURY, many studies have demonstrated risk for earlier AD onset. For an early example, see Nemetz PN et al (1997) Traumatic brain injury and the timing of onset of Alzheimer’s disease: A population-based study. Amer J Epidemiol 149:32. A more recent emphasis has been on individuals who have suffered head injuries in sports. For one of a number of examples, see Guskiewicz KM et al (2005) Association between recurrent concussion and late-life cognitive impairment in retired football players. Neurosurg 57:719. Other studies indicate that the same risks apply for kids playing at the high school or college level, and in the other contact sports (esp. hockey and boxing).

A recent study from my scientific colleagues at UCSF illustrated the increased risks of AD following TBI in a compelling way by analyzing the records of about 281,000 veterans 55 years and older who did not have any recognized prior known risk of dementia. These individuals were tracked over a period of 7 years, and some incurred TBIs over that period. For that sub-population,15% developed AD—vs only 7% of vets in the non-head-injured cohort. See

If you’re OBESE, you’re going downhill fast, even before that diabetes sets in. For example, see Sing-Manoux A et al (2012) Obesity phenotypes in midlife and cognition in early old age. The Whitehall II cohort study. Neurology 79:755.

Perhaps your just HEARING IMPAIRED. If so, your risk for an earlier onset of AD is a function of the severity of that hearing loss. For example, see Lin FR et al (2011) Hearing loss and incident dementia. Arch Neurol 68:214.

Hearing loss is an endemic problem in older individualsbut so, too, is HIGH BLOOD PRESSURE and HIGH CHOLESTEROL. In our catch-as-catch-can medical health delivery system, less than half of we Americans who have one of these conditions gets or takes medicine for it—which leads to a significantly increased risk of earlier AD onset for them. See, e.g., Kivipelto M et al (2002) Hypertension and hypercholesterolaemia as risk factors for Alzheimer’s disease. Potential for pharmacological intervention. CNS Drugs 16:435; or Launer LJ et al (200) Midlife blood pressure and dementia: The Honolulu-Asia aging study. Neurobiol Aging 21:49.

ALCOHOLISM impacts millions of our fellow citizens. They get AD and other dementias earlier than they should. For example, see Anstey KJ et al (2009) Alcohol consumption as a risk factor for dementia and cognitive decline: Meta-analysis of prospective studies. Am J Geriat Psychiat 17:542.

I could continue down the list of factors (I noted another 20, but the list could have been quite a bit longer), but you get the point. Alzheimer’s Disease onset is contributed to by MANY things that are no one’s fault that can happen in a life, and there is a more than an even-money chance that one or more of them have been a feature of YOUR life. The big question that I try to begin to answer in this Chapter: WHAT DO ALL OF THESE FACTORS HAVE IN COMMON? How do they gang up on your brain, to lead to an earlier onset of cognitive difficulties? My answer: At least most of them increase the noisiness (“chatter”) in brain processes, which directly contributes to plastic changes that underlie cognitive decline and a slow reversion of your brain machinery to a more child-like status.