History and Physical
The common complaints that bring attention to cognitive decline are memory loss, a decline in daily functioning, confusion, deteriorating language skills, and changes in behavior.[2] Clinicians need to understand age-related changes in the patient before considering cognitive decline. Normal age-related changes in the brain include a decrease in the number of neurons, an increase in cranial space from brain atrophy, decline in nerve fibers.[14]
As a result, the patient might have one or more of the following on physical examination: decreased hearing, decreased vision, psychomotor slowing, and decreased Achilles reflex. In normal aging, attention span, simple copy, procedural memory as well as remote memory stay intact while multitasking capability, learning of new information, time of reaction, cognitive processing speed, and language fluency decline.[2][14]
Patients with MCI tend to be aware of their impaired memory and are commonly troubled by it. This awareness is lost in patients with dementia, particularly in AD.[15][16] A good history is often important in gathering data about the patient focusing on reversible causes of their presentation. One such example is depression, where cognitive impairment is a presenting symptom along with personality changes.
Close friends and family members must be interviewed separately from the patient to gather collateral information. The progression from MCI to dementia is also considered when the number of family member and friend-reported symptoms is greater than the patient-reported symptoms.[17]
The patient or family members might explain that the patient quickly forgets things, has trouble putting objects in the correct places at home, repeats stories and questions, has wording finding difficulty, others fill in missing words while the patient is speaking, has difficulty learning new routines, hyperorality, behavioral changes, and may have some delusions.[16]
Evaluation
The evaluation of age-related cognitive decline is limited by the lack of specific diagnostic tests, non-pathological changes in the brain, and difficulty in differentiating signs and symptoms from normal aging.[2]
The diagnosis of MCI is based on subjective complaints, as mentioned earlier. At the initial visit, certain conditions must be investigated, such as polypharmacy, hypothyroidism, Vitamin B12 deficiency, hypo/hyperglycemia, sensory loss (hearing/vision), obstructive sleep apnea, and underlying infection.[11]
After common medical conditions that could alter the mentation are ruled out, the proceeding step is to interview the patient, followed by an interview of family members and, if possible close friends.
A comprehensive geriatric assessment (CGA) is a multidisciplinary and multimodal approach to evaluating a geriatric patient.[18] The initial evaluation should include the following:
- History of presenting illness
- Medical history
- Current and previous medications
- Family history with an emphasis on cognitive issues
- Social history, including occupation, education level, living situation, substance use, and advanced care planning
- Physical examination
- Cognitive assessment
- Laboratory studies
- Review of imaging
- Interview family members
- Identifying other professionals involved in the patient’s care
Subsequently, the following core components must be investigated:
Cognition - The United States Preventive Services Task Force (USPSTF) does not recommend screening for cognitive impairment in older patients due to a lack of evidence for harm and benefit.[19]
There are many screening tests available, and they generally test 1 or more domains of cognition. The most commonly used screening tests are the Mini-Mental State Examination (MMSE) and the Mini-Cognitive Assessment (Mini-Cog).[18][19]
Other tests are the Montreal Cognitive Assessment (MoCA), the clock drawing test (CDT), and the St. Louis University Mental Status Examination (SLUMS). One meta-analysis reveals that the sensitivity of MMSE, MoCA, and other screening tools is 75 to 92%, and the specificity is 81 to 91%.[20]
Depending on the screening test used, the domains tested are language, executive function, abstract reasoning, attention and concentration, memory, and visuospatial skills.
Office staff can also be trained to administer these screening tests. It is important to note that not one test can diagnose dementia or MCI. A positive screen must be followed by a thorough investigation that must include screening for mental health, especially depression.
Mood and altered thought content can also negatively impact cognitive and memory performance. These tests can also keep track of cognitive impairment over time. The caregiver completes certain screening tests, such as the Informant Questionnaire on Cognitive Decline in The Elderly (IQCODE) and Alzheimer Disease Caregiver Questionnaire (ADCQ).[21][22]
Interviewing family members and close friends also increase the amount of data that can be used to assess the patient’s cognitive abilities, especially memory and personality changes.
Functional ability - There are two key allotments of functional ability. The first is activities of daily living (ADL) which includes self-care activities, such as dressing, ambulation and transfers, bathing, toileting, feeding, grooming, and controlling bladder function. The second allotment is instrumental activities of daily living (IADL) which includes activities that a patient performs for independent living, such as managing finances, taking medication, driving, cooking, shopping, housework, and answering the phone.[18]
It is common to see dependency in IADLs than ADLs, and further loss of IADLs can impact independent living. However, impairment in ADLs can lead to a reduced quality of life and functional decline. It is no surprise that early intervention can reduce negative future outcomes. The standard screening tool for functional ability is the Katz ADL scale for ADLs and the Lawton IADL scale for IADLs.
Falls, gait, and mobility assessment - Falls are underreported to the clinicians by the elderly patients.[23] The assessment usually begins with a simple question of whether the patient had a fall in the last year. Falls are associated with worse functional outcomes and increased mortality and are a common cause of hospitalization.[18]
Gait should also be observed when the patient walks into the examination room by direct observation. The get-up and go-test evaluate a patient’s mobility and postural stability in addition to the gait. If the patient takes more than 12 seconds to complete the test, there is an increased risk of falls and functional decline. The office staff can also help the physician by administering this test. Direct observation is beneficial for identifying patients who might require assistive devices for ambulation and physical therapy for improving strength.
Polypharmacy - Certain medications can cause functional impairment in the elderly owing to their side effect profiles. The American Geriatrics Society (AGS) Beers Criteria lists certain medications that should be potentially avoided in older patients unless there is a specific indication for use.[24]
Physicians should take the time to review the medication list of their patients, especially when there are multiple specialists involved in medical management. The use of anticholinergic medications, opiates, benzodiazepines, muscle relaxants, sleep medications, and tricyclic anti-depressants must be reevaluated regularly to prevent polypharmacy and avoid adverse outcomes.
Antihypertensive medications can also cause hypotension leading to falls. Other tools to address the appropriateness of prescriptions are the Screening Tool To Alert Doctors To The Right Treatment (START) and Screening Tool of Older Persons' Prescriptions (STOPP). It is important to consider the time to achieve the medical benefit, the patient’s ability to manage and take the medication, and overall treatment goals when addressing the relevance of a medication.[4]
Diet and nutrition - It is vital to assess the patient's capacity to prepare their food, swallow, digest, and appetite level. Some objective measurements of nutrition include body mass index, height, and weight. Older individuals have reduced physiologic reserves, which puts them at increased risk for malnutrition, especially during an acute illness or hospitalization. One study showed that the body mass index under 23 kg/m² was associated with increased mortality.[25]
Cognition, social, and financial factors must be taken into account for a patient who reports significant weight loss. It is equally important to assess for underlying medical issues and psychological causes. After a thorough investigation, a plan of care can be devised for the patient to address their nutrition status, and if needed, appetite stimulants can be considered if appropriate.
Hearing - Age-related hearing loss, also called presbycusis, is an important consideration when assessing an elderly patient as it can lead to poor performance on cognitive assessments, social isolation, misunderstanding, anxiety or depression, and cognitive fatigue from an assessment, increased effort from listening, and frailty.[26] Common causes of hearing loss must also be investigated, such as cerumen impaction, head trauma, ototoxic medications, and any pathology involving inflammation of the auditory system, cranial nerves, or meninges.[26]
The finger rub test whispered voice test, or an audiometric test can be used to assess for hearing impairment.[27] Due to insufficient data regarding the benefits and harms of screening for hearing loss in adults greater than 50 years of age, the USPSTF and the American Academy of Family Physicians (AAFP) do not recommend its screening.[27]
Vision - Age-related visual changes are expected in the geriatric population. Reduced vision can impact the quality of life and activities of daily living, which can further reduce the chances of independent living. With aging, the visual acuity under low illumination is reduced, leading to low spatial contrast sensitivity, reduced color discrimination, and poor adaptation to the dark.[28][29] Common conditions for age-related visual impairment causes include macular degeneration, cataract, diabetic retinopathy, and glaucoma.[28]
Even though there is a lack of evidence for screening of vision loss by USPSTF and AAFP, vision testing can be done using a Snellen chart in the office. Some key aspects of visual assessment include testing the visual field, acuity, color and contrast discrimination, use of visual and non-visual cues, and patient’s assessment of lighting.[28]
It is also essential to observe the patient for their ability to perform the ADLs and IADLs for comfort level, stressors, and safety. Adverse consequences of visual deficits include increased risk of falls, reduced accessibility, postural instability, and increased risk of an automobile collision.[29]
Screening for depression - Normal aging does not include depression, and patients with depression have reduced function, poor appetite, sleep, and quality of life. They may also have multiple vague complaints, anxiety, preoccupation with finances, bodily function, and difficulty making decisions. Many studies have shown that depression affects cognitive impairment and memory, which is why any evaluation for them must have a screen for depression.[30]
Depression is seen in almost 40% of elderly patients residing in nursing home settings, whereas it is seen between 4% and 9% of elderly patients living in a community.[31][32] The geriatric depression scale (GDS) is a screening tool that is widely used. Patient Health Questionnaire-9 (PHQ-9) is another screening tool. The USPSTF recommends that all individuals over the age of 18 should be screened for depression if the screening tests are implemented with a system to support the diagnosis, treatment, and follow-up.
Urinary incontinence - The incidence of urinary incontinence increase with age, and it does not come without repercussions. Some of them are urinary tract infections, decubitus ulcers, sepsis, and increased mortality.[18] It also causes embarrassment and emotional stress to the patient that can lead to self-restriction of sexual and social activities and may also cause depression.[18]
A review of medications must also be performed to rule out any reversible causes. A screening questionnaire asking if the patient has lost control of their bladder in the last year and got wet, as well as asking if it has happened on more than six different days, is effective in identifying incontinence. It is also important to ask if the incontinence occurs with sneezing, coughing, or lifting. Other components of assessment include inquiry into previous urologic surgeries, fluid intake, and mobility.[18]
Socioenvironmental circumstances - Understanding the social health of elderly patients is tied to their overall well-being. Social history involves assessing the informal needs of the patient at their place of residence, eligibility of care resources, support structure, community involvement, caregiver needs, exercise, and financial assessment.[5][33]
Determining the most appropriate living arrangement is an important shared decision that usually occurs after home safety, injury risk, financial security, and caregiver support are well analyzed.[5]
Caregivers should be screened for burnout, and if needed, alternative living arrangements and support group referrals should be made. Sexually transmitted infections and sexual activity are commonly missed on CGA. Similarly, sexual dysfunction and impotence also need to be discussed for potential treatment options.[5]
Another important topic of inquiry is mistreatment. Elder abuse prevalence is about 10%, and women are more likely to be the victims of abuse than men. A shared living space with a spouse or adult children (the two most common abusers) is a risk factor, along with low income, isolation, and poor physical health.[34]
Types of abuse include financial exploitation, physical, verbal, sexual, and neglect. There are many manifestations of abuse, such as the presence of abrasions, lacerations, fractures, subtle signs of intimidation by the caregiver, frequent urinary tract infections while in a living facility, failure to pay for medications or renew prescriptions, worsening of chronic medical conditions, presence of decubitus ulcers, signs of malnutrition, dehydration, and poor hygiene.[34]
When abuse is suspected, the physician should seek support from law enforcement, social work, and protective services to report and intervene.
Frailty - Frailty is described as a state of reduced physiologic reserve that leads to a state of vulnerability to external stressors.[35] Frailty is a confounder in a patient who is extremely old (>90 years) and has a sudden near-complete loss of functionality in addition to a rapidly progressing dementia. This is rarely a presentation of MCI or Alzheimer disease alone.
Frailty encompasses the physical, social, and cognitive aspects of the patient. The two common measures of frailty include frailty index and frailty phenotype. The five areas of assessment for frailty phenotype are weakness (grip strength lower than 20% at baseline), unintentional weight loss (>10 pounds in the prior year), poor endurance and energy (self-reported), slowness, and low physical activity.[36] The combination of 3 or more characteristics constitutes frailty, whereas those with 1 or 2 characteristics are considered prefrail.
The frailty index, which is a continuous scale based on the effect of functional, psychosocial, medical, and age-related deficits, can predict mortality better than the frailty phenotype.[35] Evidence shows that there is a correlation between physical frailty and cognitive impairment.[37]
Frailty can predict cognitive decline, and conversely, cognitive impairment can predict frailty.[16] Patients with poor balance, altered gait, falls, and poor get up and go performance are at risk of cognitive impairment.[37] Treatment for frailty includes regular exercise, nutritional support, and avoidance of polypharmacy.[35]
Advanced care planning (ACP) - ACP is the process of identifying the patient’s goals and the extent of medical care in the future when the patient is unable to make a decision due to a serious illness. The key steps in the process are assessing the willingness of the patient, appointing surrogate decision-makers, articulating and documenting the patient’s values on medical care and quality of life, and translating those values and preferences into clinical management and treatment plans.[38]
Treatment / Management
Identifying and controlling the risk factors associated with cognitive impairment and dementia is key to planning a treatment plan for the patient.[11] There is no single pharmacologic agent that can reverse cognitive impairment and dementia. There is very limited evidence for nutritional intervention in patients with cognitive deficits for a statistically significant change in cognition.[39] Similarly, unless there is a clear deficiency, the use of antioxidants, vitamins, and herbal supplements has not shown a clear benefit.[11]
Lifestyle modification has been shown to positively impact the risk of cognitive decline. Regular physical activity, engaging in cognitively stimulating activities, social activity, cessation of smoking, and healthy dietary habits have been linked to a reduced risk.[8] The exact mechanism between physical activity and reduction of MCI risk is not well known.
The Lifestyle Interventions and Independence for Elders (LIFE) study showed no significant difference in cognitive outcomes in the moderate-intensity exercise group and the health education control group. However, patients over 80 years and those with poor baseline physical activity had better cognition scores.[40]
The Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) study revealed no difference in the incidence of dementia with the training of memory, reasoning, and speed of processing compared to the control group.[41] But there was a retention of the speed of processing and reasoning after ten years, but no such effect was seen for memory training.[42] Since the etiology of MCI and dementia is multifactorial, the interventions must also be aimed at multiple domains of cognition for effective prevention.
Cholinesterase inhibitors (AChEIs), such as donepezil, galantamine, and rivastigmine, are approved by the Food and Drug Administration (FDA) to treat mild to severe AD.[43] These drugs increase the amount of acetylcholine (a neurotransmitter) at the synapse and aid in improving memory, mood, attention, and behavior. Significant side effects include loss of appetite, loose stools, weight loss, vivid dreams, increased salivation, bradycardia, and muscle cramps.[44]
These medications should be cautiously used in patients with peptic ulcer disease, cardiac conduction disorders, and seizures. The risk of heart block must be assessed in all patients before initiating AChEIs with an electrocardiogram. Setting expectations with the patient at the beginning of the treatment prevents disappointment and establish realistic goals. The efficacy of the medication is determined 2 to 3 months after starting the medication with a reevaluation of cognition and function. These medications are not shown to delay the onset of dementia in patients with MCI.
Antagonists to N-methyl d-aspartate (NMDA), such as memantine, are another class of FDA-approved medication to treat moderate to severe AD. These medications prevent activation of the NMDAR (NMDA receptor) glutamate receptor to prevent cell death from calcium influx. The most common side effect of memantine is confusion and drowsiness.
It is important to note that even though AChEIs and NMDAs have therapeutic effects, they only help treat the symptoms and do not prevent or cure AD.[44]
Disease-modifying therapies (DMTs) target underlying mechanisms that damage a nerve cell. There are a few ongoing clinical trials that allow DMT (aducanumab, gantenerumab, and solanezumab) to be add-on therapies to either cholinesterase inhibitors or memantine.[44][45]
Despite innovation, many new drugs fail phase III trials upon failure to meet the endpoint targets. Continued investigations into combination therapies, repurposing existing drugs, and DMTs add-on to standard-of-care are needed to meet the challenge of treating AD.
Modifying other risk factors - On cessation of smoking, oxidative stress and neuroinflammation are reduced. Similarly, on stopping alcohol, there is a reduced risk of nutritional deficiency and alcohol-related neuron damage. Avoid ototoxic medications, clear out tympanic canal sediment in the clinic, assistive hearing devices, and audit rehabilitation can address hearing loss.[27] Corrective lenses for visual disturbance can increase performance functionally.
Treatment of depression can significantly improve the quality of life and function in the elderly population. Treatment options for depression are multimodal and not limited to psychosocial therapy, cognitive behavioral therapy, medications, and electroconvulsive therapy.[30] It is important to note that depression can be resistant in some elderly patients despite treatment. Extra caution must be used for dozing and monitoring of side effects of antidepressant medications.
Reducing the risk factors of MCI can slow the progression of AD-related dementia and delay mortality.[46] Periodic physician follow-up (3 to 6 months) is encouraged to monitor and delay the progression of cognitive impairment to dementia.
Geriatric Evaluation and Treatment of Age-Related Cognitive Decline