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Evidence-Based Reviews

Subjective cognitive impairment: When to be concerned about ‘senior moments’

Thorough evaluation can differentiate benign memory problems from dementia

Vol. 10, No. 04 / April 2011

MS. F, age 66, requests genetic testing because she is concerned about mild memory difficulties, such as forgetting names and where she puts her keys or checkbook, and fears she may be developing Alzheimer’s disease (AD). Her mother and sister were diagnosed with AD in their early 60s. Ms. F has 20 years of education and reports no problems with driving, managing her finances, remembering to take her medications, or maintaining social activities, which her husband confirms.

Detailed questioning about anxiety and depressive symptoms reveals substantial worries about future cognitive decline and some concerns about her finances and her husband’s health. Ms. F says she occasionally feels down and has low energy but denies other depressive symptoms. She reports no sleep disturbances—including snoring and daytime sleepiness, which could indicate obstructive sleep apnea—which her husband confirms. Ms. F takes levothyroxine for hypothyroidism, atenolol for hypertension, aspirin and clopidogrel for coronary artery disease, and atorvastatin for hyperlipidemia. In addition, she provides a long list of over-the-counter (OTC) supplements—ginkgo, huperzine, ginseng, phosphatidylserine, B1, B12, folate, vitamin D, alpha-lipoic acid, and vinpocetine—that she takes to “protect” her brain from AD.

Subjective cognitive impairment (SCI) in older persons is a common condition with a largely unclear prognosis. Many older adults (age ≥65) express concern about mild cognitive problems—“senior moments”—such as word-finding difficulties and forgetfulness.1 Individuals may wonder if walking into a room only to forget why might be the first sign of dementia. Some older adults try to counteract these memory problems by engaging in brain exercises—including costly computer games—and taking OTC “brain-enhancing” vitamins, herbal remedies, and other supplements.

Although some clinicians may view SCI as benign, that is not always true (Table l).2-5 This article discusses the clinical significance of these mild cognitive complaints by examining:

  • age-related cognitive decline (ARCD)
  • SCI
  • how SCI can be differentiated from more serious conditions, such as mild cognitive impairment (MCI) and early stages of AD and other dementias.

We also will discuss assessing and treating cognitive complaints. Although distinctions between SCI and ARCD may be controversial, evidence suggests clinicians need to adopt a more nuanced clinical approach.

Table 1

Why SCI should be taken seriously

SCI may create emotional distress because patients are aware of decline in their ‘mental sharpness’

SCI patients might consume unnecessary and potentially harmful OTC supplements touted to promote memory

Patients might limit their driving and financial management to avoid making mistakes

SCI might impair medication adherence2

SCI may be an early sign of dementia3

Patients’ worry about their self-perceived memory loss might predict dementia4

SCI may predict nursing home placement5

Addressing SCI gives health care providers an opportunity to address anxiety or depression that often accompany SCI

Evaluation of potential causes of SCI may uncover reversible conditions that can be treated

OTC: over-the-counter; SCI: subjective cognitive impairment

‘Normal’ cognitive decline

ARCD is subtle decline in cognitive abilities, such as episodic memory, attention, and time needed to complete complex activities.6,7 Individuals with ARCD might not have subjective memory complaints or objective cognitive deficits, and their ability to live independently may not be compromised.7 The degree of decline in ARCD may be smaller than previously thought.8 Park9 summarizes 4 main mechanisms thought to underlie age-related declines in cognition:

  • reduced speed of processing
  • decreased working memory capabilities
  • declining inhibitory control (eg, impaired complex attentional capabilities)
  • sensory changes (eg, visual and auditory deficits).

ARCD traditionally is thought to result from predictable changes in the brain associated with aging, such as reduced brain volume in the hippocampus and frontal lobes, loss of myelin, loss of synapses, and cytoskeletal changes.7 However, not all older adults experience ARCD. Some remain highly functional in their later years and continue to actively engage in life well into very old age.6,9

Subjective cognitive impairment

One-quarter to one-half of community-dwelling older adults report subjective cognitive complaints, such as forgetfulness and word-finding difficulties.10 Patients with SCI do not show objective evidence of cognitive impairment on neuropsychological tests and their cognitive problems cause no functional decline.10

Preliminary evidence indicates that SCI may be a harbinger of further cognitive decline. Reisberg et al3 found that compared with patients without SCI, patients with SCI were 4.5 times more likely to develop MCI—cognitive difficulties that can be detected by cognitive tests, but do not cause functional decline—or dementia within 7 years.3 Studies also have suggested that SCI may be a pre-MCI stage of subsequent dementia.11-13 AD generally has a long (10 to 12 years) and progressive prodromal phase before dementia onset and is characterized by successive emergence of cognitive deficits, memory complaints, depressive symptoms, and functional impairment.14

In light of this research, we believe patients with SCI and other risk factors for AD, such as a family history of AD, may be at higher risk of further cognitive and functional decline compared with individuals with ARCD and no AD risk factors. Therefore, patients with SCI and other risk factors for AD (Table 2)15-19 may benefit from annual follow-up to determine if cognitive problems have progressed to MCI or AD.

SCI may be a response to subclinical alterations in neurobiology—a phenomenon known as reverse causality.20 Biomarkers, such as cerebrospinal fluid levels of ß-amyloid and phosphorylated tau, and amyloid imaging using positron emission tomography may help identify AD in SCI patients.21 In these patients, SCI is a misnomer because the cognitive impairment is real—not “subjective”—but current tests are not sensitive enough to detect the cognitive decline the patient has recognized. This group of patients should be differentiated from individuals who may perceive typical cognitive aging (ARCD) as pathologic and complain about it. In the future, biomarkers may help differentiate these 2 groups.

Table 2

Factors that increase SCI patients’ risk for dementia

Family history of Alzheimer’s disease

Mild behavioral impairment

Slow gait


Rapid weight loss

Multiple subtle neurologic abnormalities

Vascular disease (eg, peripheral vascular disease, coronary artery disease, cerebrovascular disease)

SCI: subjective cognitive impairment
Source: References 15-19

Mild cognitive impairment

MCI is similar to SCI because MCI patients may present with complaints of memory decline and other cognitive difficulties22 but neither condition is associated with significant impairment of daily activities.23 The key difference is that patients with MCI demonstrate impaired performance on objective cognitive tests whereas SCI patients do not.24 In our experience, office-based tests do not reliably differentiate the 2 conditions because many patients with SCI may show mild impairment in tests such as the Mini-Mental State Exam (MMSE)25 but comprehensive neuropsychological testing reveals no objective cognitive deficits. Neuropsychological testing is essential to reliably differentiate SCI from MCI.

The distinction between SCI and MCI is clinically relevant because evidence suggests that MCI patients have a near-term risk of developing dementia, particularly AD.22,23 In a longitudinal study of 76 individuals with MCI, 12% of patients progressed to AD each year compared with 1% to 2% of healthy older adults.26 Patients with MCI are at increased risk of delirium (especially during hospitalization), falls, medication errors, and difficulty managing their finances.24 Older adults with MCI also have increased mortality compared with older adults with normal cognitive functioning.22 Both SCI and MCI should be differentiated from mild dementia. Common dementias in older adults include:

  • AD dementia
  • Vascular dementia (may occur with or without AD)
  • Lewy body dementia
  • Frontotemporal dementia
  • Parkinson’s disease dementia.

By definition, all dementia types are associated with impaired ability to perform daily activities and cognitive decline.27

Assessing cognitive complaints

Evaluation of older adults’ cognitive complaints should begin with a thorough history to elicit symptoms of anxiety, depression, physical complaints, and any associated functional decline; a physical exam; and a comprehensive mental status examination. This initial evaluation should be followed by routine and specific investigations as indicated (Table 3).22,24,28,29

In a 6-year study of 100 older adults with and without objective evidence of memory decline, both groups showed similar rates of cognitive complaints.30 Also, researchers found no relationship between individuals’ perception of their cognitive functioning and performance on neuropsychological testing. Mood, education level, and apolipoprotein E epsilon 4 genotype status also did not correlate with participants’ subjective cognitive complaints. These findings highlight the need for objective test data to determine whether older adults’ memory complaints reflect pathologic changes in cognition. After a thorough diagnostic workup, some patients complaining of memory decline will have no detectable evidence of cognitive dysfunction or an identifiable cause. However, others may have identifiable causes of memory impairment (Table 4)28,29,31,32—which could be treated—some will have MCI, and others may be in an early stage of dementia.

Table 3

Investigation of older adults with SCI




Neuropsychological testing

Delineation of cognitive syndromes (SCI vs MCI vs AD*)

Hematology (full blood count)

Screen for anemia

Biochemistry (electrolytes, renal function, liver function, thyroid function, B12, and folate)

Screen for treatable causes of cognitive complaints

For specific indication suggested by history, physical exam, or neuropsychological testing


Generalized and regional imaging (eg, hippocampal atrophy, space occupying lesions)


Epilepsy/seizures (especially absence and complex partial)

Cardiac (eg, echocardiography)

May reveal cardiac arrhythmia or sources of emboli

Inflammatory markers (eg, ESR)

Screen for inflammatory processes

Treponemal serology

Tertiary syphilis

*Alzheimer’s disease and other dementias
AD: Alzheimer’s disease; ESR: erythrocyte sedimentation rate; MCI: mild cognitive impairment; SCI: subjective cognitive impairment
Source: References 22,24,28,29

Table 4

Differential diagnosis of SCI

Cause of cognitive impairment

Potential mechanism


Allostatic load, ‘wear and tear’ from a lifetime of physiological or psychological stresses and adaptations


Neuronal hypoxia

Alzheimer’s disease

Amyloid and/or tau-mediated neurotoxicity, neuroinflammation

Cerebrovascular disease

Neuronal ischemia and hypoxia, neuroinflammation

Vitamin deficiencies (eg, B1, B12, folate, D)

Impaired neuronal and neurotransmitter function

Inadequate protein intake

Impaired neuronal function

Anticholinergic drug use

Decreased cholinergic neurotransmission

Alcohol use

Direct neurotoxicity and indirect causes such as malnutrition or head injury

Depression, anxiety

Hippocampal dysfunction with or without atrophy

Obstructive sleep apnea

Neuronal hypoxia, neuroinflammation

Head injury

Neuronal and synaptic loss

ARCD: age-related cognitive decline; SCI: subjective cognitive impairment
Source: References 28,29,31,32

CASE CONTINUED: No measurable deficits

Ms. F’s medical history is remarkable for coronary artery disease, hypothyroidism, hypertension, hyperlipidemia, cataracts, arthritis, back surgery (secondary to spondylosis), and foot surgery. Ms. F denies a history of alcohol or illicit substance abuse. She smoked tobacco for 30 years (2 packs per day), but quit 5 years ago after her heart attack. Physical exam is unremarkable except for mild obesity (body mass index = 31 kg/m2).

Ms. F’s mental status exam reveals anxious mood and affect. Her recall is 2 out of 3 items. Her MMSE score is 29/30 (1 point lost on recall) and her Geriatric Depression Scale33 score is 2/15, indicating minimal depressive symptoms. On neuropsychological testing, Ms. F demonstrates high average intellectual abilities; compared with others her age, she performs within expectations on all measures. That is, she performs within the above-average to low-average range on measures of attention, working memory, speed of processing, expressive language, learning, memory, visual spatial abilities, executive functioning, and knowledge of basic health and safety information.

Enhancing neuroplasticity

We recommend neuroplasticity-based interventions to treat SCI and promote healthy brain aging.20,29 For a checklist clinicians can use to promote healthy brain aging and thus improve patients’ cognitive health see this article at CurrentPsychiatry. com. Table 51,29 lists cognitive strategies to improve memory and maintain cognitive vitality.

Enhancing brain plasticity and neurogenesis requires engaging older adults in demanding sensory, cognitive, and motor activities on an intensive basis.34 Therapeutic stimulation of neuroplasticity and neurogenesis might contribute to functional “repair” of the diseased adult brain before damage to whole neuronal networks has ensued.29 An important treatment component is reassuring patients with SCI that they do not have AD or MCI. Treating comorbid anxiety and depression and reversible causes of cognitive complaints is key to successful outcomes.

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