by Dr Geoffrey Modest
The MMWR recently published the finding that the age-adjusted rates of Alzheimer’s deaths have increased in 41 states and the District of Columbia from 1999 to 2014 (see https://www.cdc.gov/mmwr/volumes/66/wr/mm6620a1.htm ).
Details:
— Alzheimer’s disease is the 6th leading cause of death United States, accounting for 3.6% of all deaths in 2014
— 93,541 Alzheimer’s deaths occurred in the US in 2014, at an age-adjusted rate of 25.4 deaths per 100K population. This represents a 54.5% increase over 1999, when the rate was 16.5 deaths per 100K (44,536 deaths).
— Most deaths occur in nursing home or long-term care facility (though this was a decrease from 67.5% in 1999, to 54.1% in 2014). The number of deaths in a hospital declined from 14.7% in 1999 to 6.6% in 2014,; the percent who died at home increased from 13.9% in 1999 to 24.9% in 2014. In addition, 6.1% died in a hospice facility in 2014.
— the specific Alzheimer’s death rate per 100K population increased among those to age 75 to 84 from 129.5 to 185.6 per 100K population, as well as in those >85 years old, from 601.3 to 1006.8 per 100K population.
— Overall, the death rates were higher among all age groups, both sexes, all races/ethnicities, urban/rural, and in almost every state. But they were particularly high for women and non-Hispanic whites
— age-adjusted rates for the 50 states and DC range from 7.0 to 29.8 per 100K in 1999, and from 10.7 to 43.6 per 100K in 2014
Commentary:
— this MMWR report is based on death certificates, which are not necessarily accurate and may be influenced by the prevailing culture and the US system of reporting. In particular, the death certificate-based data derive from what the patients’ clinicians decide is the major cause of death, which in my experience is often a best-guess after the fact. and this is likely influenced by several nonclinical factors, including the acceptability of Alzheimer’s disease itself as a cause of death (which may have increased in this time period, at least partly explaining the noted increase), or even the influence of the funeral home directors. In addition, there may be very real issues with deciding if Alzheimer’s is truly the responsible condition: the definitive diagnosis is in fact histopathologic, though there are clinical definitions of reasonable accuracy, but many clinicians may be hesitant to use this label (is it truly accurate??) and avoid coding it; also, at what degree of cognitive impairment does it reach the threshold to go on a death certificate? (and that threshold is likely very different from one clinician to another)
— And, this increased incidence of Alzheimer’s also raises the question of potentially modifiable factors in the development of Alzheimer’s, which may have changed over time. For example, obesity, diet, physical activity, perhaps medications, and levels of education have been found to be associated with Alzheimer’s. See blogs
— one profound implication of an increasing incidence of Alzheimer’s disease is the tremendous effects on others, and especially the paid and unpaid caregiver burden. And this stresses the need for additional resources to educate and train caregivers in the care of Alzheimer’s patients, as well as providing respite care and case management
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another article just came out suggesting an association between persistent chronic pain and memory decline/dementia, in a longitudinal cohort of elders (see doi:10.1001/jamainternmed.2017.1622).
Details:
–10,065 community-dwelling older adults in the Health and Retirement Study, who were at least 62 years old in 2000 and answered questionnaires on pain and cognition; they were followed through 2012 with sequential questionnaires
— 60% female, median age 73 at baseline.
— 10.9% had persistent moderate-to-severe pain at baseline (n= 1120), 76% female (versus 58% female in the nonpain group), 86% white/8% black/5% Hispanic, 58% ever-smokers, 45% nonmarried/non-partnered
— comorbidities (all with differences with p<0.001): hypertension (61% in pain group, 48% comparison)/diabetes (20% pain, 14% comparison) lung disease (14% pain, 8% comparison), heart disease (37% pain, 25% comparison), stroke (13% pain, 8% comparison), depression (50% pain, 20% comparison), alcohol use (less in pain group overall, 68% reporting none versus 53% in comparison), difficulty doing more than 1 ADL (46% pain, 12% comparison)
— primary outcomes included memory score (a compilation of several cognitive tests, by the patient or proxy) and dementia probability score (a different cognitive test which estimates the chance that an individual would reach the DSM3 or 4 diagnostic criteria for dementia
–the fully adjusted model controlled for: demographic measures (age, sex, race/ethnicity), education level, current or former tobacco use, medical comorbidities of self-reported hypertension/diabetes/cancer/chronic lung disease/heart disease/stroke, household financial status, marital status, current alcohol use, and depressive symptoms
Results:
— of the elderly who reported pain on the initial intake evaluation, 69% reported pain subsequently (persistent pain)
— after covariate adjustment, persistent pain was associated with a 9.2% (2.8% – 15.0%) more rapid memory decline as compared to those without persistent pain
— after 10 years, there was a 15.9% higher relative risk of inability to manage medications, and 11.8% higher relative risk of inability to manage finances independently
— adjusted dementia probability increased 7.7% faster (0.55%-14.2%) in those with persistent pain, an absolute 2.2% increase in dementia probability
Commentary:
— the prevalence of chronic pain increases with age, affecting 25 to 33% of older adults. Also the recovery from chronic pain is less likely in older people. Older people with chronic pain are also more likely to be consumed by their chronic pain, reporting pain as affecting their subjective health status
— pain in the elderly has been reported to be more likely to be associated with falls, functional impairment, and cognitive decline/dementia in prior studies. But these are largely cross-sectional, observational studies at a point in time, and not a longitudinal study as above.
–although there are some very important advantages of the current longitudinal study, there are some evident limitations in terms of the extent of the data collected: lack of data on the source/site of the persistent pain, or even of the degree of the medical or psychological comorbidities. Also, there were very significant differences in the baseline characteristics of those with and without persistent pain, both medical and psychosocial (especially for depression and impaired ADLs, but also for all of the major medical comorbidities), or even the medications or other therapies prescribed. So, even though they adjusted for many potential confounders, they really did not have the database to control well for them, and there are likely other unknown (and therefore uncontrolled) factors involved.
— there were also no data specifically on the types of pain medications given. There is concern that use of opioids, for example, might affect cognition, perhaps exacerbated by concomitant disability, depression, etc. However, another study of patients with chronic pain getting NSAIDs found about the same amount of cognitive effect as with opioids. I would however add that several of the adjuvant pain medications (gabapentin, pregabalin, tricyclics, etc) may have significant effects on cognition. and SSRIs or SNRIs themselves, if used to treat depression or pain, can also affect cognition (studies are mixed on this)
–there is a plausible mechanism for the association of persistent pain and cognitive decline. Stress, depression, and even sleep deprivation have been found to affect cortisol secretion, and perhaps through that, can lead to neurologic changes, including decreased neuronal density/function in the hippocampus, with decreased ability to form new memories.
–and there may be other associated changes in those with persistent pain which were not accounted for but could affect cognitive health: eg, physical exercise, diet (ability to shop, cook food, etc), limitations in social interactions/increased social isolation
so, though these studies are both significantly flawed, it is clear that dementia is really prevalent, that it is likely increasing overall and especially so as the population ages, that there are very significant medical and social costs (especially on the caregivers), that many lifestyle measures likely provide benefit (as per prior blogs, see below), and that chronic pain by itself may be associated with the increased incidence and progression of dementia. In this latter case, I think it is important, especially in the elderly, to treat pain but preferably with nonsystemic medications, avoiding the multitude of toxic effects of NSAIDs (cardiac, renal, GI, etc, to which the elderly are likely more susceptible), opiates, and the typical adjuvants (gabapentin, tricyclics, etc). Perhaps it is best to treat with physical therapy and psychosocial therapies (cognitive behavioral therapy, mindfulness therapy, stress reduction therapies, etc) and/or with injections or topical medications. and, as I have mentioned many times, injections into joints, trigger points, muscle spasms, etc often really help the pain and improve the function, often for a very long time.
see:
blog on article finding that prescribing opiates to the elderly is associated with subsequent opiate dependence
article on cognitive behavioral therapy for low back pain
study on tai chi and another on mindfulness for chronic pain