Chronic Conditions Affect Brain Function
As care improves, cognitive impairment is likely to be seen earlier in patients with coronary artery disease, diabetes, and HIV.
Community pharmacies are uniquely positioned to provide added value to both patients and the providers who refer them.
The renewed role of the pharmacist as an educational resource for patients can be invaluable in identifying patients who are at risk of or are beginning to suffer from cognitive decline. In this age of polypharmacy, pharmacists often have weekly or monthly interactions with these patients. Thus, pharmacists often have more data points from which to observe the cognition of these patients. Screening tools such as Cognivue Thrive, the first device that uses computer-assisted technology cleared by the FDA to identify cognitive decline before it progresses to mild cognitive impairment, allow pharmacists to identify cognitive challenges earlier than a provider who may see a patient less frequently.
Virtually all adults will experience some degree of cognitive decline as they age, but a subset of those, about 5% to 20%, will progress to a level that exceeds normal aging called mild cognitive impairment (MCI).¹ MCI is distinguished from dementia by the degree of impairment involved. In patients with MCI, cognitive decline typically occurs in memory and executive functions (complex reasoning) but preserves functioning ability. ² Dementia, by contrast, involves impairment to a degree that compromises occupational or social functioning, as outlined in the DSM-5 diagnostic criteria.
The significance is that many common chronic illnesses carry with them an increased risk of cognitive impairment, which increases with age. Diabetes, hyperlipidemia, and hypertension are associated with vascular dementia through impairment of circulation to the brain. Strokes cause infarctions that destroy focal areas of the brain that may or may not affect cognition, but microvascular damage associated with these conditions, sometimes called multiinfarct dementia, causes a gradual and often more global decline in cognitive function.3-6
Cardiovascular disease (CVD) is associated with both degenerative and vascular dementia. Atherosclerosis-induced hypoperfusion of the brain, inflammation, and oxidative stress contribute to the neuropathology of Alzheimer disease (AD).7
Broadly, disease states that involve systemic inflammation are associated with dementia. Inflammation and inflammatory markers have been linked to both AD and vascular dementia. Inflammation may be viewed as a measure of the receptivity of vulnerable tissues to mechanical injury. This is particularly important for autoimmune diseases such as lupus, psoriasis, and rheumatoid arthritis for which inflammation is a cardinal feature.8 Patients often think of these diseases in terms of symptom control, but clearly there are long-term effects of systemic inflammation beyond the damage to joints and muscles, including an increased incidence of both macrovascular and microvascular disease leading to dementia.
Inflammatory markers associated with dementia include C-reactive protein (CRP), cytokines (specifically tumor necrosis factor-ɑ [TNF-ɑ]), and interleukins. In research, interleukin 6 and TNF-ɑ are most commonly present when looking at different types of dementia. CRP is more associated with CVD but plays a role in brain metabolism and neuronal function. Therefore, it often is seen in later-life dementia.9
Type 2 diabetes (T2D) also is known to increase the risk of cognitive impairment, primarily through the acceleration of microvascular disease of the brain.5 Uncontrolled T2D causes damage to blood vessels that in turn can reduce blood flow to the brain. The results of a study completed by Cholerton et al suggest that individuals with T2D double their risk of dementia compared with individuals who do not have the disease.10
HIV is associated with non—HIV-associated neurocognitive disorders. In individuals with HIV, there is an alteration of biomarkers amyloid-β peptide β amyloid and tau implicated in plaque formation that is the hallmark of AD dementia.11 HIV-positive individuals who carry ApoE ε4, a risk-factor allele 1 are at an especially high risk of neurocognitive disorders when amyloid β plaques are present.11 ApoE ε4 is associated with CVD, decreased longevity, and higher cholesterol levels.11 The results of a study by Sheppard et al show that individuals with HIV aged 60 to 70 years were 7.43 times greater than those not living with HIV to have a mild cognitive impairment designation, which was noted as statistically significant.11
As the care for patients with chronic diseases improves, patients with coronary artery disease, diabetes, and HIV are living to advanced ages. This is expected to lead to a significant increase in the prevalence of cognitive disorders. Identifying individuals who are experiencing MCI beyond what is associated with normal aging also will help predict those who are likely to develop more aggressive disease and dementia over time.
In terms of AD dementia, there are 3 recognized phases. The first is preclinical AD in which there are declines in cognitive function from the patient’s baseline level of function but not severe enough to be called a deficit, because function is normal. An example is when a salesperson realizes that he or she can no longer recall from memory part numbers or the shipping schedule without prompting. The second phase is mild cognitive impairment in which there is a functional deficit in 1 or more areas of cognition but that are mild enough to allow independent function, with some support. An example is a patient who recognizes that he or she has problems with driving directions and becomes dependent on a global positioning system for commutes. AD dementia is the third stage and involves much more pervasive deficits in executive function, language, learning, memory, and spatial awareness to the point that custodial attention is necessary. There is no consensus on the percentage of patients with MCI who will progress to dementia. The Alzheimer’s Association reports on an analysis that showed that among individuals with MCI, 15% of those aged older than 65 developed dementia after 2 years of follow- up. The results of .another study showed that 32% of individuals with MCI developed AD dementia within 5 years of follow-up. The results of a third study showed that among individuals with MCI who were tracked for 5 years or longer, 38% developed dementia.12-14
Pharmacists and technicians in the community may notice when patients require multiple visits for the same prescription because of forgotten doses or misunderstood instructions. Medications that are either inadvertently omitted from a regimen or physically misplaced may provide clues. A patient may ask a pharmacist if a medication will affect their memory or interact with their other medications, which can lead to recognition that a patient is starting to experience cognitive challenges. When a longtime patient starts depending on family members or neighbors to pick up and keep track of prescriptions, asking the caregiver how the patient is doing may reveal a concern. Various tools can be used to solicit information related to concerns about cognitive changes. One method is to use a simple questionnaire, tailored to pharmacists’ priorities, as shown in the FIGURE. Identifying concerns with memory loss can lead to screening for cognitive decline to obtain a baseline measurement and can promote discussion about the modifiable risk factors that preserve cognitive health.
It is important to be sensitive to the complexity of patient adherence. Awareness of a patient’s understanding of their prescriptions, the consequences of not taking them, and frustrations about adverse effects are important. An early feature of many kinds of dementia is an anxious paranoia about medications and people. Patients may be very worried about why the pills change in appearance and unwilling to accept an explanation. Patients with AD dementia are rarely aware of the onset but may apply faulty and sometimes bizarre reasoning to explain incidents. Episodic lapses in balance, changes in personality, or changes in memory may suggest more aggressive types of dementia, such as dementia with Lewy bodies, Pick disease, normal pressure hydrocephalus, or Wernicke encephalopathy.
It is helpful to diplomatically communicate concerns to the patient’s prescriber, but it is also useful to have the means to provide cognitive screenings as part of routine pharmacy counseling. In addition to Cognivue, the Montreal Cognitive Assessment and the Quick Mild Cognitive Impairment screen are validated brief cognitive screening tools that pharmacists can provide. Offering brochures and posting signage that point to the service are helpful prompts for beginning the conversation with caregivers and patients. Baseline screenings provide data points that can be tracked over time as patients act upon modifiable risk factors to assess changes in cognitive health.15
Cognitive function is a moving target. Recognizing the onset of cognitive challenges as they appear is key to managing the condition before it progresses to dementia, which is often modifiable but rarely reversible.16 Modifications as simple as changing medications to alternatives that have less anticholinergic activity; enrolling patients in diabetes education programs, hypertension management, nutrition, or weight loss programs; moving sedating medications to bedtime as appropriate; or providing other clinical services to help patients manage their modifiable risk factors may have a dramatic effect on their cognitive health and quality of life.
Depending on the outcomes, the results may suggest further cognitive evaluation by a primary-care provider. Sharing concerns and the patient’s screening results, with permission, with the primary-care provider should help facilitate 2-way communication between the pharmacy and the physician in a way that benefits multiple patients.
RICHARD WYNN, MD, is cofounder of Amity Medical Group in Charlotte, North Carolina, and is an adjunct professor in the Department of Family Medicine at the University of North Carolina at Chapel Hill.MANDY IRVIN, PHARMD, CPP, AAHIVP, is a clinical pharmacist practitioner for Amity Medical Group.
- Erkinjuntti T. Cognitive decline and treatment options for patients with vascular dementia. Acta Neurol Scand Suppl. 2002;178:15-18. doi:10.1034/j.1600-0404.106.s178.4.x
- Hugo J, Ganguli M. Dementia and cognitive impairment: epidemiology, diagnosis, and treatment. Clin Geriatr Med. 2014;30(3):421-442. doi:10.1016/j. cger.2014.04.001
- Justin BN, Turek M, Hakim AM. Heart disease as a risk factor for dementia. Clin Epidemiol. 2013;5:135-145. doi:10.2147/CLEP.S30621
- Kivipelto M, Ngandu T, Fratiglioni L, et al. Obesity and vascular risk factors at midlife and the risk of dementia and Alzheimer disease. Arch Neurol. 2005;62(10):1556-1560. doi:10.1001/archneur.62.10.1556
- Beeri MS, Goldbourt U, Silverman JM, et al. Diabetes mellitus in midlife and the risk of dementia three decades later. Neurology. 2004;63(10):1902- 1907. doi:10.1212/01.wnl.0000144278.79488.dd
- de la Torre JC. Cardiovascular risk factors promote brain hypoperfusion leading to cognitive decline and dementia. Cardiovasc Psychiatry Neurol. 2012;2012:367516. doi:10.1155/2012/367516
- Eriksson UK, Bennet AM, Gatz M, Dickman PW, Pedersen NL. Nonstroke cardiovascular disease and risk of Alzheimer disease and dementia. Alzheimer Dis Assoc Disord. 2010;24(3):213-219. doi:10.1097/WAD.0b013e3181d1b99b
- Wotton CJ, Goldacre MJ. Associations between specific autoimmune diseases and subsequent dementia: retrospective record-linkage cohort study, UK. J Epidemiol Community Health. 2017;71(6):576-583. doi:10.1136/ jech-2016-207809
- Metti AL, Cauley JA. How predictive of dementia are peripheral inflammatory markers in the elderly? Neurodegener Dis Manag. 2012;2(6):609-622. doi:10.2217/NMT.12.68
- Cholerton B, Baker LD, Montine TJ, Craft S. Type 2 diabetes, cognition, and dementia in older adults: toward a precision health approach. Diabetes Spectr. 2016;29(4):210-219. doi:10.2337/ds16-0041
- Sheppard DP, Iudicello JE, Bondi MW, et al. Elevated rates of mild cognitive impairment in HIV disease. J Neurovirol. 2015;21(5):576-584. doi:10.1007/ s13365-015-0366-7
- Petersen RC, Lopez O, Armstrong MJ, et al. Practice guideline update summary: mild cognitive impairment: report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2018;90(3):126-135. doi:10.1212/ WNL.0000000000004826
- Ward A, Tardiff S, Dye C, Arrighi HM. Rate of conversion from prodromal Alzheimer’s disease to Alzheimer’s dementia: a systematic review of the literature. Dement Geriatr Cogn Dis Extra. 2013;3(1):320-332. doi:10.1159/000354370
- 2020 Alzheimer’s disease facts and figures. Alzheimer’s Association. Accessed December 21, 2010. https://www.alz.org/media/Documents/ alzheimers-facts-and-figures.pdf
- Clarnette R, O’Caoimh R, Antony DN, Svendroski A, Molloy DW. Comparison of the quick mild cognitive impairment (Qmci) screen to the Montreal Cognitive Assessment (MoCA) in an Australian geriatrics clinic. Int J Geriatr Psychiatry. 2017;32(6):643-649. doi:10.1002/gps.4505
- Santacruz KS, Swagerty D. Early diagnosis of dementia. Am Fam Physician. 2001;63(4):703-714.