Memory loss is a common complaint in the primary care setting. It is particularly common among the elderly but also may be reported by younger people. Sometimes family members rather than the patient report the memory loss (typically in an elderly person, often one with dementia). Clinicians and patients are often concerned that the memory loss indicates impending dementia. Such concern is based on the common knowledge that the first sign of dementia typically is memory loss. However, most memory loss does not represent the onset of dementia.

The most common and earliest complaints of memory loss usually involve difficulty remembering names and the location of car keys or other commonly used items. As memory loss becomes more severe, people may not remember to pay bills or keep appointments. People with severe memory loss may have dangerous lapses, such as forgetting to turn off a stove, to lock the house when leaving, or to keep track of an infant or child they are supposed to watch. Other symptoms (eg, depression, confusion, personality change, difficulty with activities of daily living) may be present depending on the cause of memory loss.

Etiology

The most common causes of memory loss (see Approach to the Neurologic Patient: Characteristics of Common Causes of Memory Loss) are

• Age-related changes in memory (most common)
• Mild cognitive impairment
• Dementia
• Depression

Most people experience some worsening of memory with aging. It takes longer to form new memories (eg, a new neighbor's name, a new computer password) and to learn new complex information and tasks (eg, work procedures, computer programs). Age-related changes lead to occasional forgetfulness (eg, misplacing car keys) or embarrassment. However, cognition is not impaired. Given sufficient time to think and answer questions, patients with age-related memory changes can usually do so, indicating intact memory and cognitive functions.

Patients with mild cognitive impairment have actual memory loss, rather than the sometimes slow memory retrieval from relatively preserved memory storage in age-matched controls. Mild cognitive impairment tends to first affect short-term (also called episodic) memory first. Patients have trouble remembering recent conversations, the location of commonly used items, and appointments. However, memory for remote events is typically intact, as is attention (also called working memory—patients can repeat lists of items and do simple calculations). The definition of mild cognitive impairment is evolving; mild cognitive impairment is now sometimes defined as impairment in memory and/or other cognitive functions that is not severe enough to affect daily function. Mild cognitive impairment often progresses to dementia.

Patients with dementia (see Delirium and Dementia: Dementia) have memory loss plus evidence of cognitive and behavioral dysfunction. For example, they may have difficulty with finding words and/or naming objects (aphasia), doing previously learned motor activities (apraxia), or planning and organizing everyday tasks, such as meals, shopping, and bill paying (impaired executive function—see Approach to the Neurologic Patient: Characteristics of Common Causes of Memory Loss). Their personality may change; for example, they may become uncharacteristically irritable, anxious, agitated, and/or inflexible.

Depression is common among patients with dementia. However, depression itself can cause memory loss that simulates dementia (pseudodementia). However, such patients usually have other features of depression.

Delirium (see Delirium and Dementia: Delirium) is an acute confusional state, which may be caused by a severe infection, a drug (adverse effect), or drug withdrawal. Patients with delirium have impaired memory, but the main reason they present is usually severe global changes in mental status and cognitive dysfunction, not memory loss.

Table 2
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Characteristics of Common Causes of Memory Loss Cause Suggestive Findings Diagnostic Approach Age-related memory changes Occasional forgetfulness (eg, of names or location of car keys) but no other impairment of memory Normal cognitive function Clinical evaluation Mild cognitive impairment Memory impaired Daily function not affected Other aspects of cognition intact Clinical evaluation Sometimes neuropsychiatric testing Dementia Memory impaired Daily function affected (eg, difficulty balancing a checkbook, finding their way around the neighborhood, or doing usual tasks at work) Impairment of at least 1 other aspect of cognition: Aphasia (language dysfunction), causing difficulty finding words and/or naming objects Apraxia, causing difficulty doing previously learned motor activities despite intact motor function Agnosia, causing difficulty identifying objects despite intact sensory nerve function Impaired executive function, causing difficulty planning and organizing everyday tasks (eg, meals, shopping, bill paying) Abstract thinking and judgment impaired Often personality and behavioral changes (eg, suspicion, anxiety, agitation) Clinical evaluation Sometimes neuropsychiatric testing Depression Memory loss often correlated with severity of mood disturbance Sometimes sleep disturbance, loss of appetite, psychomotor slowing Often present in patients with dementia, mild cognitive impairment, or age-related memory changes Clinical evaluation Drug use (eg, of anticholinergic drugs, antidepressants, opioids, psychoactive drugs, or sedatives) Use of causative drug Often recent initiation of drug therapy, an increase in drug dose, or slowing of drug clearance (eg, caused by decrease in renal or liver function) Typically a trial of stopping or changing the suspected causative drug

Evaluation

The highest priority is to identify delirium, which requires rapid treatment. The evaluation then focuses on distinguishing the few cases of mild cognitive impairment and early dementia from the greater number with age-related memory changes or simply normal forgetfulness. Full evaluation for dementia usually requires more time than the 20 to 30 min that is commonly allotted for an office visit.

History: History should, when possible, be taken from the patient and family members separately. Cognitively impaired patients may not be able to provide a detailed, accurate history, and family members may not feel free to give a candid history with the patient listening.

History of present illness should include a description of the specific types of memory loss (eg, forgetting words or names, getting lost) and their onset, severity, and progression. The clinician should determine how much symptoms affect day-to-day function at work and at home. Important associated findings involve changes in language use, eating, sleeping, and mood.

Review of systems should identify neurologic symptoms that may suggest a specific type of dementia (eg, parkinsonian symptoms in Lewy body dementia, focal deficits in vascular dementia, inability to look upward and falling in progressive supranuclear palsy, choreiform movements in Huntington disease, gait disturbance in normal-pressure hydrocephalus, balance problems and difficulty with fine motor movements in vitamin B₁₂ deficiency).

Past medical history should include known disorders and complete prescription and OTC drug use history.

Family and social histories should include the patient's baseline levels of intelligence, education, employment, and social functioning. Previous and current substance abuse is noted. Family history of dementia or early mild cognitive impairment is queried.

Physical examination: In addition to a general examination, a complete neurologic examination is done, with detailed mental status testing.

Mental status testing assesses the following by asking the patient to do certain tasks:

• Orientation (give their name, the date, and their location)
• Attention and concentration (eg, repeat a list of words, do simple calculations, spell "world" backwards)
• Short-term memory (eg, repeat a list of 3 or 4 items after 5, 10, and 30 min)
• Language (eg, name common objects)
• Praxis and executive function (eg, follow a multiple-stage command)
• Constructional praxis (eg, copy a design or draw a clock face)

Various scales can be used to test these components. The most common way to test these components is with the Mini-Mental Status Examination (see Approach to the Neurologic Patient: Examination of Mental Status), which requires about 7 min to administer.

Red flags: The following findings are of particular concern:

• Impaired daily function
• Loss of attention or altered level of consciousness
• Symptoms of depression (eg, loss of appetite, psychomotor slowing, suicidal ideation)

Interpretation of findings: Presence of actual memory loss and impairment of daily function and other cognitive functions help differentiate age-related memory changes, mild cognitive impairment, and dementia. Mood disturbance is present in patients with depression but is also common in patients with dementia or mild cognitive impairment. Thus, differentiating depression from dementia can be difficult until memory loss becomes more severe or unless other neurologic deficits (eg, aphasia, agnosia, apraxia) are evident.

Inattention helps differentiate delirium from early dementia. In most patients with delirium, memory loss is not the presenting symptom. Nonetheless, delirium must be excluded before a diagnosis of dementia is made.

One particularly helpful clue is how the patient came to medical attention. If the patient initiates the medical evaluation because of worries about becoming forgetful, age-related memory change is the likely cause. If a family member initiates a medical evaluation for a patient who is less worried about memory loss than the family, dementia is much more likely than when the patient initiates the evaluation.

Testing: Diagnosis is primary clinical. However, any brief mental status examination (see Approach to the Neurologic Patient: Examination of Mental Status) is affected by the patient's intelligence and educational level and has limited accuracy. For example, patients with high educational levels can score falsely high, and those with low levels can score falsely low. If the diagnosis is unclear, more accurate, formal neuropsychologic testing can be done; results have higher diagnostic accuracy.

If a drug is the suspected cause, the drug can be stopped or another drug substituted as a diagnostic trial.

Treating apparently depressed patients may facilitate differentiation between depression and mild cognitive impairment.

If patients have neurologic abnormalities (eg, weakness, altered gait, involuntary movements), MRI or CT is required.

For most patients, serum vitamin B₁₂ measurement and thyroid functions tests are needed to exclude vitamin B₁₂ deficiency and thyroid disorders, which are reversible causes of impaired memory.

If patients have delirium or dementia, further testing should be done to determine the cause.

Treatment

Patients with age-related memory changes should be reassured. Patients with depression are treated with drugs and/or psychotherapy. Patients with memory loss and signs of depression should be treated with nonanticholinergic antidepressants, preferably SSRIs. Memory loss tends to resolve as depression does. Delirium is treated by correcting the underlying condition. Rarely, dementia is reversible with a specific treatment (eg, supplementary vitamin B₁₂, thyroid hormone replacement, shunting for normal-pressure hydrocephalus). Other patients with memory loss are treated supportively.

Patient safety: Occupational and physical therapists can evaluate the home of impaired patients for safety with the goal of preventing falls and other accidents. Protective measures (eg, hiding knives, unplugging the stove, removing the car, confiscating car keys) may be required. Some states require physicians to notify the Department of Motor Vehicles of patients with dementia. If patients wander, signal monitoring systems can be installed, or patients can be registered in the Safe Return program. Information is available from the Alzheimer's Association (http://www.alz.org/care/dementia-medic-alert-safe-return.asp).

Ultimately, assistance (eg, housekeepers, home health aides) or a change of environment (eg, living facility without stairs, assisted-living facility, skilled nursing facility) may be indicated.

Environmental measures: Patients with dementia usually function best in familiar surroundings, with frequent reinforcement of orientation (including large calendars and clocks), a bright, cheerful environment, and a regular routine. The room should contain sensory stimuli (eg, radio, television, night-light).

In institutions, staff members can wear large name tags and repeatedly introduce themselves. Changes in surroundings, routines, or people should be explained to patients precisely and simply, omitting nonessential procedures. Frequent visits by staff members and familiar people encourage patients to remain social. Activities can help; they should be enjoyable and provide some stimulation but not involve too many choices or challenges. Exercises to improve balance and maintain cardiovascular tone can also help reduce restlessness, improve sleep, and manage behavior. Occupational therapy and music therapy help maintain fine motor control and provide nonverbal stimulation. Group therapy (eg, reminiscence therapy, socialization activities) may help maintain conversational and interpersonal skills.

Drugs: Eliminating or limiting drugs with CNS activity often improves function. Sedating and anticholinergic drugs, which tend to worsen dementia, should be avoided. DonepezilSome Trade Names
ARICEPT
Click for Drug Monograph
may provide temporary improvement in memory for patients with mild cognitive impairment, but the benefit appears to be modest. No other drug is recommended to enhance cognition or memory in patients with mild cognitive impairment.

The cholinesterase inhibitors donepezilSome Trade Names
ARICEPT
Click for Drug Monograph
, rivastigmineSome Trade Names
EXELON
Click for Drug Monograph
, and galantamineSome Trade Names
REMINYL
Click for Drug Monograph
are somewhat effective in improving cognitive function in patients with Alzheimer disease or Lewy body dementia and may be useful in other forms of dementia. MemantineSome Trade Names
NAMENDA
Click for Drug Monograph
, an NMDA (N-methyl-d-aspartate) antagonist, can be used in moderate to severe dementia.

Table 3
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Drugs Used to Treat Alzheimer Disease and Sometimes Other Forms of Dementia Drug Name Starting Dose Maximum Dose Comments DonepezilSome Trade Names ARICEPT Click for Drug Monograph 5 mg once/day 10 mg once/day Generally well-tolerated but can cause nausea or diarrhea GalantamineSome Trade Names REMINYL Click for Drug Monograph 4 mg bid Extended-release: 8 mg once/day in the am 12 mg bid Extended-release: 24 mg once/day in the am Possibly more beneficial for behavioral symptoms than other drugs Modulates nicotinic receptors and appears to stimulate release of acetylcholine and enhances its effect MemantineSome Trade Names NAMENDA Click for Drug Monograph 5 mg bid 10 mg bid Appears to slow disease progression RivastigmineSome Trade Names EXELON Click for Drug Monograph 1.5 mg bid 6 mg bid Available in liquid solution

Geriatric Essentials

Mild cognitive impairment is common with aging. Prevalence is between 14 and 18% after age 70. Dementia is one of the most common causes of institutionalization, morbidity, and mortality among the elderly. Aging itself accounts for most of the risk of dementia. Prevalence of dementia increases from about 1% at age 60 to 64 to 30 to 50% at age > 85. Prevalence among elderly nursing home residents is about 60 to 80%.

Key Points

• Memory loss and dementia are common, and common sources of worry in the elderly.
• Age-related memory change is common, causing slowing, but not deterioration, of memory and cognition.
• Diagnosis is primarily by clinical criteria, particularly mood, attention, presence of true memory loss, and effect on daily function.
• Self-reported memory loss is usually not due to dementia.
• Delirium must be ruled out before diagnosing dementia.

Last full review/revision August 2012 by Michael C. Levin, MD

Content last modified November 2012