Geriatric Evaluation and Treatment of Age-Related Cognitive Decline

Etiology

Although genetics can contribute to approximately 60% of our cognitive abilities, aging remains the primary cause of cognitive decline. From age 20 to 80, individuals encounter a consistent decline in their abilities to use current circumstances and information to solve problems and make decisions.[3][6] In addition, as auditory acuity diminishes after age 30, an individual's processing speed and sensory perception also exhibit ongoing decline. 

Chronic medical illnesses, hearing or vision loss, cerebral ischemia, head trauma, toxins such as alcohol, and excessive stress hormone levels can collectively interact with the aging process, leading to cumulative damage to the brain and accelerating the natural cognitive decline. A hallmark feature in patients with MCI who progress to Alzheimer disease is an increase in tau protein in the temporal lobe.[7][8]

Epidemiology

The prevalence of cognitive decline, particularly dementia, rises exponentially with advancing age. Therefore, the geriatric patient population will increase by 21% over the next 50 years. Approximately two-thirds of Americans experience some form of cognitive impairment by age 70.[9] Globally, among adults 60 and older, the prevalence of MCI ranges from approximately 7% to 25%. MCI is about 3 to 4 times more common than dementia.[3] 

The incidence of dementia increases exponentially until the age of 90, with a similar occurrence rate between the genders.[10] Alzheimer dementia is slightly more prevalent in women at advanced ages, primarily because of their longer life expectancy. In contrast, men tend to experience vascular dementia at a younger age.

Patients with lower socioeconomic status and less education are at higher risk for cognitive decline.[2][6] Medical risk factors associated with cognitive impairment include cardiovascular disease, high cholesterol, hypertension, diabetes, atrial fibrillation, stroke, and depression.[7][11] In addition, an elevated risk is linked to smoking, excessive alcohol consumption, and a sedentary lifestyle. 

Pathophysiology

With normal aging, the brain usually experiences a size reduction, which is a commonly observed phenomenon. This reduction of the brain's size affects both the gray and white matter and is primarily attributed to a decrease in the development of dendrites, dendritic spines, axons, and synapses.[12] Moreover, there is an increase in segmental demyelination among axons. Gray matter reduction is notably most pronounced in the prefrontal cortex and temporal lobes, whereas the frontal lobe and corpus callosum show the most substantial white matter loss. 

MCI is on a continuum, and patients with amnestic forms often progress to Alzheimer disease. This condition arises from years of excessive production and reduced clearance of amyloid-β peptides, which form neuritic plaques, and hyperphosphorylated tau proteins, which form neurofibrillary tangles.[13] Frontotemporal dementia is characterized by abnormal protein deposits, including tau, TDP-43, and FUS, with hyperphosphorylated tau proteins being the most prevalent. Lewy body dementia and Parkinson disease reveal alpha-synuclein accumulation. Ultimately, these protein changes alter cellular function, leading to biochemical dysfunction, which causes a decline in acetylcholine and dopamine, structural alterations, and the loss of synapses in some cases.[2][14]

History and Physical

Normal age-related cognitive decline does not usually affect daily activities except for driving. However, when functional impairments emerge, it is advisable to conduct an assessment. Common complaints that raise concerns about cognitive decline include memory loss, a decrease in daily functioning, confusion, declining language skills, and alterations in behavior.[2] 

Individuals experiencing genuine age-related cognitive decline may encounter reduced hearing, diminished visual acuity, slower learning of new information, decreased multitasking abilities, longer reaction times, slower cognitive processing speed, and reduced language fluency.[2][15] However, simple copying skills, procedural memory, and remote memory typically remain unaffected. 

Patients with MCI are often aware of their memory impairment, which can frequently lead to distress. In contrast, patients with dementia eventually lose this awareness.[16][17] Healthcare providers must conduct separate interviews with the patient's close friends and family to gather collateral information.[18] In the interview, patients or their family members might describe situations where they rapidly forget things, struggle with placing objects in their proper locations at home, and repeat stories and questions. In addition, they might mention instances where the patient becomes disoriented or lost, discovers unexplained dents in the car, or experiences difficulty finding words. Sometimes, families may speak for the patient and report signs of hyperorality, difficulty learning new routines, behavioral changes, and delusions.[17]

Evaluation

The assessment of age-related cognitive decline is hindered by the lack of specific diagnostic tests, non-pathological brain changes, and challenges in distinguishing pathological signs and symptoms from normal aging.[2]

Identifying and addressing the underlying causes of reversible cognitive decline is a crucial initial step. For example, cognitive impairment may be linked to underlying psychological conditions such as depression or anxiety, which can significantly improve with proper treatment. Additional potential factors that are reversible or treatable include hypo- and hyperthyroidism, polypharmacy, obstructive sleep apnea, delirium, vitamin B12 deficiency, electrolyte imbalances, and sensory deficits.[19] Gathering collateral information from family members, friends, or caregivers is essential alongside patient interviews.

A CGA is a multidisciplinary and multimodal approach to evaluating geriatric patients with cognitive impairment.[19] The CGA can be conducted during hospital admission, office visit, or home visit. The initial evaluation should include the following criteria:

• History of presenting illness
• Medical history from the patient, family members, friends, and caregivers
• Current and previous medications
• Family history with an emphasis on cognitive issues
• Social history, including occupation, education level, living situation, support system, substance use, and advanced care planning
• A comprehensive physical examination 
• Laboratory studies and medical imaging, as necessary
• Review of imaging and laboratory results
• Identification of all professionals involved in patient care

Functional Status

Frailty is characterized by diminished physiological reserve, making individuals more susceptible to external stressors.[20] Frailty encompasses various aspects, including the patient's physical, social, and cognitive abilities. Frailty comprises 2 central components—the frailty index and the frailty phenotype.

The 5 areas of assessment for frailty phenotype include:

• Weakness or grip strength less than 20% at baseline
• Unintentional weight loss exceeding 10 lbs in the previous year
• Self-reported poor endurance and energy levels
• Self-reported slow gait speed
• Self-reported low levels of physical activity [21] 

Frailty is the combination of 3 or more characteristics, whereas individuals with 1 or 2 features are considered prefrail. The frailty index is a continuous scale that considers the impact of functional, psychosocial, medical, and age-related deficits, and it has been shown to predict mortality more effectively than the frailty phenotype.[20] Evidence exists indicating a correlation between physical frailty and cognitive impairment.[22]

Frailty can be predictive of cognitive decline, and conversely, cognitive impairment can be predictive of frailty.[17] Patients with poor balance, altered gait, frequent falls, and impaired "get-up-and-go" performance are at an increased risk of developing cognitive impairment.[22] 

ADLs encompass dressing, ambulation and transfers, bathing, toileting, feeding, grooming, and controlling bladder function. Instrumental ADLs (IADLs) include tasks that individuals perform to maintain independent living, such as managing finances, taking medication, driving, cooking, shopping, housework, and answering the phone. Assessing both ADLs and IADLs provides a measure of functional ability.[19] 

Patients experiencing cognitive decline typically exhibit a decline in proficiency in IADLs before ADLs. Screening for functional loss offers valuable insights into the risks and vulnerabilities of these patients. Patients who lose the ability to manage medication, finances, or drive are at risk for adverse outcomes, abuse, and eventual loss of their independence. A performance-based road test is a valuable tool for assessing driving skills. Early intervention based on the results of this test can help mitigate adverse future outcomes. The standard screening tools for assessing functional abilities include the Katz index for ADLs and the Lawton IADL scale.

Gait Speed and Falls

In general, it is common for older individuals to minimize or fail to report instances of falls.[23] The assessment begins by inquiring whether the patient has experienced a fall within the past year. Falls are associated with poorer functional outcomes and elevated mortality rates and frequently cause hospitalization.[19] Gait should be observed when the patient walks into the examination room by direct observation. The get-up-and-go test can evaluate a patient's mobility, postural stability, and gait. If the patient takes more than 12 seconds to complete the test, it indicates an elevated risk of falls and functional decline. Multiple members of the interprofessional team can administer this test. Direct observation is beneficial for identifying patients who require assistive devices for ambulation and physical therapy to improve their strength.

Cognition

Numerous screening tests are available for assessing cognition, with varying levels of detail and sensitivity. The most frequently used screening tests include the Montreal Cognitive Assessment (MoCA), the Mini-Mental State Examination (MMSE), and the Mini-Cognitive Assessment (Mini-Cog).[19][24]

Additional tests include the clock drawing test (CDT) and the Saint Louis University Mental Status Examination (SLUMS). A meta-analysis indicates that the sensitivity of screening tools, such as MMSE and MoCA, ranges from 75% to 92%, whereas the specificity falls between 81% and 91%.[25]

Depending on the specific screening test utilized, the assessed domains include language, executive function, abstract reasoning, attention and concentration, memory, and visuospatial skills.

Dementia or MCI cannot be diagnosed with a single test alone. A comprehensive assessment, including screening for depression, should be conducted following a positive screening result. As the scores of these tests can vary over time, it is advisable to repeat the test at regular intervals or following significant medical changes or events for a more accurate assessment.  

Mood Disorders

Depression is not a normal part of aging. People with depression may experience decreased cognitive function, loss of appetite and sleep, and a decreased overall quality of life. Individuals with depression may also exhibit numerous vague complaints, heightened anxiety, preoccupation with financial matters, bodily functions, and difficulty making decisions. Numerous studies have demonstrated that depression can have a negative impact on cognitive function and memory. Notably, depression is found in nearly 40% of older individuals residing in nursing homes. In contrast, its prevalence is generally between 4% and 9% among older adults living in the community.[26][27] Commonly utilized screening tools for depression include the geriatric depression scale (GDS) and the Patient Health Questionnaire-9 (PHQ-9). The United States Preventive Services Task Force (USPSTF) recommends that all individuals 18 and older undergo depression screening, provided that a system is in place to support the diagnosis, treatment, and follow-up based on the screening results.

Polypharmacy

Medications can potentially lead to functional and cognitive impairment in the geriatric population. The American Geriatrics Society (AGS) Beers Criteria provides a comprehensive list of medications that should be avoided in older patients unless the benefits outweigh the risks.[28] The Beers criteria are available on the AGS website.

Healthcare professionals should dedicate time to reviewing their patients' medication lists, particularly when multiple specialties are involved. An effective strategy is encouraging patients to bring their medications in their original bottles to each appointment. Healthcare providers should consider reevaluating the use of anticholinergic drugs, opiates, benzodiazepines, muscle relaxants, sleep medications, and tricyclic antidepressants to prevent polypharmacy and minimize the risk of adverse outcomes. Antihypertensive medications can also potentially induce hypotension, increasing the risk of falls. 

Additional tools for assessing the appropriateness of prescriptions include the Screening Tool to Alert Doctors to the Right Treatment (START) and the Screening Tool of Older Persons' Prescriptions (STOPP). When evaluating the appropriateness of a medication, factors to consider include the time required to achieve medical benefits, the patient's capacity to manage and adhere to the medication regimen, and the overarching treatment objectives.[5] Notably, regularly revisiting the process of selectively discontinuing medications for older patients is crucial. 

Diet and Nutrition 

A nutritional assessment involves assessing a patient's capacity to prepare, swallow, and digest food, as well as their overall appetite level. Objective measurements used to determine nutrition include body mass index (BMI), height, and weight. As older individuals have reduced physiological reserves, they are at an increased risk of malnutrition, particularly during acute illnesses or hospitalization. A study demonstrated that a BMI below 23 kg/m² is correlated with a higher mortality rate.[29]

When a patient reports significant weight loss, healthcare professionals should consider cognitive, social, dental, medical, and financial factors. 

Social and Financial Support

Social health is a vital aspect of an individual for their overall well-being. A comprehensive social history assessment evaluates the patient's living conditions, eligibility for care resources, support network, community engagement, caregiver requirements, physical activity routines, and financial situation.[4][30]

Making a well-informed decision about the most suitable living arrangement for the geriatric population after assessing home safety, injury risk, financial stability, and caregiver support is essential. Shared decision-making should also be involved.[4] Healthcare professionals should screen for caregiver burnout and, if necessary, offer alternatives for living arrangements and provide referrals to support groups. 

Sexual health constitutes a significant component of a CGA. An open discussion about sexually transmitted infections, sexual dysfunction, and impotence creates a safe environment for considering potential treatment options.[4]

Approximately 10% of the geriatric population experiences abuse, with women being more likely to be victims than men. Typically, the most common abusers in elder abuse cases are spouses or adult children. Risk factors for elder abuse include poor socioeconomic status, social isolation, and compromised physical health.[31]

Abuse can take various forms, including neglect, financial exploitation, or physical, verbal, and sexual abuse. Indications of abuse may include the presence of abrasions, lacerations, fractures, decubitus ulcers, subtle signs of caregiver intimidation, frequent urinary tract infections while in a living facility, an inability to afford medications or renew prescriptions, deterioration of chronic medical conditions,  signs of malnutrition and dehydration, and inadequate hygiene.[31]

Healthcare professionals are obligated to report suspected cases of elder abuse. Therefore, seeking support from law enforcement and social work or adult protective services is essential when abuse is suspected.

Hearing

While assessing older patients, it is crucial to consider age-related hearing loss, also referred to as presbycusis. This condition can lead to suboptimal performance on cognitive assessments, increased risk of social isolation, misunderstandings in communication, heightened anxiety or depression, and cognitive fatigue during the assessment process.[32] Furthermore, it is essential to investigate alternative causes of hearing loss, including factors such as cerumen impaction, head trauma, ototoxic medications, and any pathological conditions involving inflammation of the auditory system, cranial nerves, or meninges.[32]

Hearing impairment can be assessed using techniques such as finger rub, whispered voice, or audiometric tests.[33] As hearing loss is associated with cognitive decline, therefore, treating hearing loss may contribute to preventing and slowing cognitive decline.[34] The USPSTF and the American Academy of Family Physicians (AAFP) do not recommend hearing screening for adults older than 50 due to limited data on the potential benefits and harm caused by such screening.[33] 

Vision 

Visual acuity in low-light settings decreases with age. This can manifest as reduced spatial contrast sensitivity, diminished color discrimination, and difficulty adapting to darkness.[35][36] Diminished vision can significantly affect the quality of life and ADLs in the geriatric population, potentially leading to decreased ability to live independently. Common conditions contributing to age-related visual impairment include macular degeneration, cataracts, diabetic retinopathy, and glaucoma.[35]

Although the USPSTF and AAFP do not recommend routine vision screening for asymptomatic older adults, assessing vision in the office using a Snellen chart is possible. Critical elements of a comprehensive visual assessment of patients include evaluating the visual field, acuity, color and contrast discrimination, the utilization of visual and non-visual cues, and the subjective assessment of lighting conditions.[35] Visual deficits can lead to adverse consequences such as an elevated risk of falls, decreased accessibility, postural instability, and an increased likelihood of automobile collisions.[36]

Urinary Incontinence

The prevalence of urinary incontinence rises with age, which can lead to consequences such as urinary tract infections, decubitus ulcers, sepsis, and an elevated mortality risk.[19] Feelings of embarrassment and emotional stress can result in self-imposed limitations on sexual and social activities in patients, which may contribute to depression.[19] Screening questions should inquire whether the patient has experienced loss of bladder control within the past year and if this has occurred on more than 6 distinct days. Furthermore, a comprehensive assessment should encompass the patient's prior urological surgeries, fluid intake patterns, and mobility assessment.[19]

Advanced Care Planning

Advanced care planning involves determining the patient's treatment goals and specifying the level of medical care they desire if they cannot make decisions due to a severe illness. The essential stages in this process include evaluating the patient's willingness, designating surrogate decision-makers, articulating and recording the patient's views on medical care and quality of life, and translating these values and preferences into a clinical management and treatment plan.[37]

Laboratory Testing

Suggested lab tests for this condition include vitamin B12, complete blood count, and serum thyroid-stimulating hormone. In addition, depending on clinical suspicion, further laboratory tests may be ordered. 

Neuroimaging

Patients with acute or rapidly progressive cognitive changes or concerns about a structural lesion should undergo a magnetic resonance imaging (MRI) or computed tomography (CT) scan of the brain. Although some guidelines suggest an MRI for all dementia patients, others recommend it for younger patients with focal findings and symptoms lasting less than 2 years.

Treatment / Management

Identifying and managing risk factors linked to cognitive impairment and dementia are crucial components of developing a treatment plan for the patient.[12] No pharmacological agent is capable of reversing cognitive impairment associated with normal aging. Besides ensuring adequate baseline nutrition, minimal evidence supports nutritional interventions in patients with cognitive deficits.[38] Without a clear deficiency, antioxidants, vitamins, and herbal supplements offer no discernible benefit.[12] Treating vitamin B12 deficiency and hypothyroidism can improve cognitive function.

Lifestyle modifications have a positive impact on the risk of cognitive decline. Engaging in regular physical activity, participating in cognitively stimulating activities, maintaining an active social life, quitting smoking, and adopting healthy dietary habits all contribute to a reduced risk of cognitive decline.[11] The precise mechanism of linking physical activity to reducing MCI risk remains poorly understood. The management of fragility entails regular exercise, nutritional support, and the avoidance of polypharmacy.[20]

Quitting smoking leads to a reduction in oxidative stress and neuroinflammation. Similarly, when alcohol consumption is discontinued, there is a decreased risk of nutritional deficiency and the potential for alcohol-related neuronal damage. Addressing hearing loss can involve avoiding ototoxic medications, in-office cleaning of the external auditory canal, using assistive hearing devices, and engaging in audiological rehabilitation.[33] For visual disturbances, the use of corrective lenses can enhance functional performance. 

Treating depression can significantly improve the quality of life and functioning among the geriatric population. Treatment options for depression are multimodal and encompass various approaches, including medications and psychosocial, cognitive behavioral, and electroconvulsive therapies.[39] Depression can be resistant to treatment in certain older patients. Therefore, it is essential to exercise extra caution when determining dosages and monitoring the adverse effects of antidepressant medications.(B3)

Differential Diagnosis

Aging changes processing speed, sensory perception, concept formation, abstraction, and mental flexibility. A comprehensive CGA enables healthcare professionals to distinguish between normal cognitive decline associated with aging and common conditions that can mimic or contribute to cognitive decline. The common conditions that may add to cognitive decline include:

• Infections of the urinary tract, pneumonia, sepsis, and abscesses
• Vitamin B12 and folic acid deficiencies
• Hypo- or hyperthyroidism
• Hypo- or hyperglycemia
• Hypoxemia
• Hypo- or hypernatremia
• Delirium
• Depression 
• Pathological grief reaction
• Medications such as benzodiazepines, anticholinergics, and antihypertensives
• MCI 
• Alzheimer disease 
• Pick disease
• Lewy body disease 
• Vascular and multi-infarct dementia 
• Frontotemporal dementia 
• Parkinson dementia
• Alcohol-related dementia 
• Creutzfeldt-Jakob disease  

Prognosis

A total of 67% of the geriatric population will experience some form of cognitive decline by age 70. Worldwide, each year, 15% of this population will develop MCI. The average annual transition rate from MCI to any form of dementia is 12% in the general population and increases to 20% in patients at higher risk. Patients with MCI, particularly those with late-life onset of persistent neuropsychiatric symptoms, are more likely to progress to dementia.[40] According to some estimates, 12% of patients with MCI return to normal cognitive function within 3 years of their initial presentation.[3][12][40] 

The APOE ε4 allele is the most consistently identified genetic risk factor for the progression of MCI to Alzheimer-type dementia (MCI-AD). Individuals with amyloid pathology have a 40.8% probability of transitioning from asymptomatic to MCI due to MCI-AD, with a 5.3% annual probability of reverting to the asymptomatic stage.[41] The annual transition probability from MCI-AD to mild AD is 21.8%, from mild-to-moderate AD is 35.9%, and from moderate-to-severe AD is 28.6%. The rates of reverting to a less severe category are 3%, 1.8%, and 1.5%, respectively.[41]

The risk of Alzheimer disease is increased by various factors, including the presence of deep white matter lesions combined with Hachinski ischemic scores greater than 4, the APOE ε4 allele, the clusterin (CLU) risk variant genotype, and having more than 6 genetic markers associated with Alzheimer-type dementia. Other contributing factors include the amnestic subtype of MCI, psychiatric symptoms such as anxiety, depression, or apathy, and diabetes or prediabetes. Clusterin plays a role in regulating apoptosis. Risk factors that increase the likelihood of mixed or vascular dementias include prediabetes, diabetes, carotid stenosis, depression, hypotension, and atrial fibrillation.[42] Vascular disease is the most common comorbidity associated with a more rapid progression of cognitive impairment.

Some favorable factors encouraging the possible return to normal cognition include those using medications to control for vascular risk factors, successful treatment of depression, lack of APOE ε4 allele, higher scores on cognitive testing, and greater hippocampal volume observed on imaging.[12]

Complications

Individuals may experience a decline in decision-making, problem-solving, planning, response sequencing, and multitasking abilities as they age. This cognitive change is anticipated and should not significantly impact most ADLs. However, patients having driving difficulties should undergo a road test to evaluate their abilities.

Patients who develop MCI can usually independently manage their ADLs, but there is a risk of progression to dementia as a potential complication. Complications of cognitive decline and dementia include:

• Inability to perform ADLs
• Increased risk for infection
• Behavioral disturbances
• Hallucinations and psychosis
• Frequent falls
• Increased mortality
• Personality changes and agitation
• Poor nutrition
• Depression
• Unrecognized pain
• Caregiver fatigue and burnout
• Abuse
• Fractures due to falls
• Death
• Incontinence
• Dysphagia
• Disinhibition [43][44][43]