Aging is associated with cognitive decline, and older subjects can have demonstrable cognitive impairment without crossing the threshold for dementia. This condition has been termed “mild cognitive impairment” (MCI), and these patients have an increased risk of developing dementia, especially Alzheimer disease (AD). Studies conducted in referral clinics have shown that patients with MCI progress to AD at a rate of 10% to 15% per year, and 80% of these patients have converted to AD after approximately 6 years of follow-up. The identification and classification of MCI can be a major challenge.

1. MILD COGNITIVE IMPAIRMENT
(MCI)
Mohammad-Sajjad Lotfi
Ph.D student in Gerontology
In the name of God 1

2. THE PATIENT'S STORY
• Mrs. J, age 81 years, with hypertension and hyperlipidemia, requested a referral to a
neurologist, stating: “I am forgetting things I just heard.”
• Mrs. J and her husband began noticing mild memory problems 1.5 years earlier, and report
slow progression since.
• Her husband noticed changes in problem solving and time management.
• Mrs J was easily distracted and had difficulty remembering recent conversations.
• She misplaced objects and spent time looking for them.
• she read and wrote less than before.
• She repeatedly asked how to do things on her computer and cell phone.
2

3. THE PATIENT'S STORY
• Her husband reported that she exhibited no initiative, and that their home seemed more
disorganized.
• She had difficulty planning dinner and her cooking was simpler.
• Both denied changes in language or speech.
• She continued to drive locally without accidents but had difficulty remembering directions
to familiar places.
• Mrs J had no hallucinations or delusions.
• She slept well, her mood was fine, and she exhibited no behavioral problems or personality
changes.
3

4. THE PATIENT'S STORY
• Functionally, she remained independent in all activities of daily living (ADLs).
• She had urinary frequency and over the past couple of months she had a few incidents of
incontinence, especially when awakening from a nap.
• In instrumental activities of daily living (IADLs), Mr J had recently taken over paying bills.
• Finally, even with a compartmentalized pill-box, she occasionally forgot to take her
medications (amlodipine 5 mg daily; losartan 50 mg twice daily; and ergocalciferol 1,000
units daily.)
4

5. MILD COGNITIVE IMPAIRMENT
(MCI)
• Aging is associated with cognitive decline, and older subjects can have demonstrable
cognitive impairment without crossing the threshold for dementia.
• This condition has been termed “mild cognitive impairment” (MCI), and these patients have
an increased risk of developing dementia, especially Alzheimer disease (AD).
• Studies conducted in referral clinics have shown that patients with MCI progress to AD at a
rate of 10% to 15% per year, and 80% of these patients have converted to AD after
approximately 6 years of follow-up.
• The identification and classification of MCI can be a major challenge.
5

6. MILD COGNITIVE IMPAIRMENT
(MCI)
• The MCI syndrome, as an expression of an incipient neurodegenerative disorder that may
lead to dementia, is extremely heterogeneous and may coexist with systemic, neurologic, or
psychiatric disorders that can cause cognitive deficits.
• Data from community-based studies have shown a greater variability in the clinical course
of the syndromes than that observed in referral clinics:
• some patients with MCI progress to dementia
• some remain stable
• some improve over time
• some who return to normal can go back to MCI eventually develop to dementia.
6

7. PERSPECTIVES
• Mrs J: Asked when her memory first became a concern .
• …. Would you believe I'm about to say: “I forget? ”… It's just been gradual
• Mild Cognitive Impairment (MCI) is a clinical stage on the continuum of cognitive decline between
“normal aging ”and dementia.
• It is characterized by impairment in cognition that is not severe enough to require help with
ADLs / IADLs .
• MrsJ's declining memory has clearly affected daily life in ways that both she and her husband
have noticed, but she has remained generally independent, and therefore has MCI.
7

8. MILD COGNITIVE IMPAIRMENT
CRITERIA
• Initially, the criteria for MCI followed two conceptual models:
1. one associated only with memory deficits
2. other with a broader range of deficits (memory and other areas of cognition).
• Because memory deficits are the clinical hallmark of AD, most of the criteria developed to
characterize MCI required the presence of memory deficits.
• However, other clinicians felt that the memory-centered definition of MCI was too
restrictive because it did not capture other cognitive problems that often occur in the elderly.
8

9. MILD COGNITIVE IMPAIRMENT
CRITERIA
• Longitudinal studies showed that patients with MCI with or without memory deficits can
progress to AD.
• Epidemiologic studies showed that the prevalence of the MCI syndrome with isolated
memory deficits was lower than that observed in subjects who presented with a wider range
of cognitive problems
9

10. • The most recent criteria for MCI encompassed all possible cognitive manifestations of the
syndrome and four subgroups have been proposed:
• deficits only in memory functions
• memory deficits plus deficits in another cognitive domain
• deficits in a single non-memory domain
• deficits in more than one non-memory domain.
• This has expanded the knowledge of the MCI syndrome and allowed examination of the
relationship between MCI syndromes and other dementias that do not have memory deficits.
• For example, the MCI with isolated executive deficits has been reported to be associated
with cerebrovascular disease and a predictor of vascular dementia.
10

11. DEFINITIONS AND DIAGNOSTIC
CRITERIA
• In 2011, the NIA and the AA convened workgroups to revise the 1984 diagnostic criteria for
dementia, as well as dementia due to AD.
• Diagnostic criteria for MCI, the “symptomatic, pre-dementia phase” of the trajectory of
cognitive decline, were established(Box 1).
• The key criteria that distinguish MCI from dementia are
• preservation of independence in functional abilities (i.e., ADLs and IADLs)
• lack of significant impairment in social or occupational functioning.
• MCI sub-types are sometimes defined based on presence or absence of memory difficulties
(amnestic vs. non-amnestic MCI) and the number of affected cognitive domains
11

12. CRITERIA FOR THE DIAGNOSIS OF MILD
COGNITIVE IMPAIRMENT (MCI)
• Box1
• Concern regarding a change in cognition from the patient, knowledgeable informant, or from
a skilled clinician observing the patient
• Objective evidence of impairment (from cognitive testing) in one or more cognitive
domains, including memory, executive function, attention, language, or visuospatial skills
• Preservation of independence in functional abilities (although individuals may be less
efficient and make more errors at performing ADLs / IADLs than in the past)
• No evidence of a significant impairment in social or occupational functioning (i.e., “not
demented”)
12

13. OTHER CRITERIA
• Two other recently-developed clinical classification systems identify a symptomatic but non-
demented stage of cognitive decline, but use different terminology than the NIA-AA criteria.
The International Working Group (IWG) criteria use the terms:
• “prodromal AD”
• “predementia AD”
• to refer to individuals with cognitive impairment that is not severe enough to significantly
affect activities of daily living.
• while the new DSM-5 refers to this stage as “mild neurocognitive disorder.”
13

14. • The National Institute on Aging and Alzheimer’s Association (NIA-AA) criteria for MCI
were created to characterize a syndrome that is most likely associated with AD pathology.
• The purpose of these criteria was to identify subjects in the pre-AD state, and they require
that patients with MCI must have impairments in one or more cognitive domains.
• Although the criteria emphasized the presence of memory deficits as the central
characteristic of the syndrome that can progress to AD, they recognized that there are forms
of AD (eg, visual or language variants) that do not have memory deficits in their early
stages.
• In addition, the syndrome should not be present in the context of vascular, traumatic, or
other causes of mild CNS dysfunction.
14

15. • The use of the criteria in clinical practice is difficult.
• MCI subjects with multiple disease processes that can:
1. affect cognition can progress to AD
2. not all AD patients have memory loss at initial presentation.
• usually, mild non-memory function deficits are difficult to detect with brief cognitive
evaluations (Case 7-1).
15

16. CASE-1
• A 65-year-old man with 16 years of education presented with a 2-year history of progressive
memory problems that affected his job performance.
• His colleagues had not noticed these problems, nor had his wife reported him having any
cognitive problems at home.
• He had recently been diagnosed with hypertension, but his vital signs were normal.
• He denied any symptoms of major depression.
• The results of his neurologic examination were normal, and his Mini-Mental State
Examination (MMSE) score was 29/30 (he forgot the floor on which the doctor’s office was
located in the orientation subtest).
• His clock-drawing test results were normal
• His verbal fluency for animals was 11.
• Laboratory tests and brain MRI showed no abnormalities.
16

17. CASE-1
• Because of the patient’s concerns about his progressive memory problems, he was referred
for a comprehensive neuropsychological assessment.
• The test showed that his memory functions were 1.5 standard deviations (SD) below the
mean adjusted for people of his age and education level, and his executive functions were
between 1.0 and 1.5 SD below the mean.
• He had normal language, visuospatial, and visuo-constructional functions.
• Two years later, the patient retired from his job due to the worsening in his cognition, and his
wife noticed problems in his instrumental activities of daily living (eg, the patient forgot to
pay bills and got lost while driving).
• His MMSE score dropped to 25/30, and his comprehensive cognitive evaluation showed
deficits in memory, language, and executive functions, consistent with a dementia syndrome,
most likely Alzheimer disease.
17

18. COMMENT
• This is a highly educated man who noticed that his cognitive functions were severe enough
to interfere with his occupational affairs. Initially, his wife and colleagues did not detect
these problems, and the brief neuropsychological evaluation conducted at the neurologist’s
office was within normal limits. However, detailed cognitive assessment by a
neuropsychologist revealed the presence of memory and executive function deficits. This
patient presented with the memory plus other cognitive domain subtype of mild cognitive
impairment (MCI), which later progressed to dementia.
• This case illustrates two important aspects of the clinical diagnosis of MCI:
(1) it is difficult to detect the syndrome with bedside cognitive instruments, especially in
highly educated people.
(2) additional cognitive evaluations are an important tool to detect not only impaired cognitive
domains during the MCI stage, but also during the early stages of Alzheimer disease.
18

19. EPIDEMIOLOGY AND RISK
FACTORS
• Recent clinical and population-based samples suggest an MCI prevalence of 10-20% for
adults aged ≥65 years, although lack of standardized diagnostic criteria and differences in
sample characteristics across studies have led to significant uncertainty around these
estimates.
• Prevalence of MCI increases with age, and men appear to be at higher risk.
• Additional risk factors identified in some studies include
• lower educational level, vascular risk factors (e.g., diabetes and hypertension), Apo-
lipoprotein E (APOE) e4 genotype, Vitamin D deficiency, sleep-disordered breathing, and
prior critical illness (eg, sepsis)
19

20. EVALUATION OF THE PATIENT WITH
SUSPECTED MCI
• All patients with suspected MCI should undergo a comprehensive history and physical
examination focusing on:
• cognitive function
• functional status
• Medications
• neurological or psychiatric abnormalities
• laboratory testing.
• The main goals are to distinguish MCI from normal aging or dementia and to identify
potentially reversible forms of MCI due to other conditions (e.g., depression, medication
effects, thyroid disease, and B12 / folate deficiency)
20

21. COGNITIVE FUNCTION
• A history of cognitive changes over time, verified by knowledgeable informants, if available,
is important for identifying the first diagnostic criterion, decline i.
• Critical features that may elucidate a cause are onset, trajectory, time-course, and nature of
the cognitive symptoms.
• Very rapid cognitive decline (e.g., weeks to months) is not typical of MCI due to AD, and
should raise concerns for other causes, such as neoplasm, metabolic disorders, or prion
disease n cognitive function.
• Patients and informants (such as family members) may report conflicting views regarding
the presence and severity of cognitive symptoms, either from lack of insight, or because
cognitive decline can be emotionally-charged and symptom report may be minimized to
avoid difficult or “disrespectful” discussions
21

22. COGNITIVE FUNCTION
• The review concluded that brief cognitive assessments can successfully detect dementia in primary
care, but the sensitivity of those instruments for detecting MCI is generally lower, and it is still
unclear whether early diagnosis of cognitive impairment improves important patient or caregiver
outcomes.
• The Montreal Cognitive Assessment (MoCA) is a screening tool that was developed specifically for
detection of MCI and takes about 10 minutes to administer.
• Using a cut-point of 25/26, the MoCA has a sensitivity of 80 to 100% and specificity of 50 to 76%
for detecting MCI.
• The Mini-Mental State Exam (MMSE) has a sensitivity of45 to 60% and specificity of 65 to 90% for
detecting MCI using cut-points of 27 or 28.
• A recent study directly comparing the MoCA and MMSE found the MoCA to be more sensitive for
accurately differentiating individuals with MCI from those with normal cognition.
22

23. • Clinicians may also consider the Mini-cog test (which combines the Clock Drawing Test
with a 3-word recall test), as it also has acceptable test performance characteristics, and can
be performed in ≤3 minutes.
• Referral for formal neuropsychological testing may help diagnose MCI in patients with
subtle cognitive decline.
• Although Mrs. J scored in the normal range on the MMSE (29 out of 30), her formal
neuropsychological testing showed objective deficits in memory function
23

24. • Clinicians can collect standardized information on cognitive function from informants using
the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE)
• the Dementia Severity Rating Scale (DSRS),and the AD8.
• The NIA-AA MCI criteria note that scores on cognitive tests for individuals with MCI are
typically 1 to 1.5 standard deviations below age- and education- adjusted normative means.
• However, it is emphasized that these score ranges should be considered guidelines, rather
than firm cutoffs, for making an MCI diagnosis.
24

25. FUNCTIONAL STATUS
• Activities of daily living.
• Patients with MCI should have normal ADLs, although they can have mild deficits in IADLs
(eg, problems in job performance, forgetting to pay a bill).
• However, the determination of abnormal IADLs can be difficult in an older population.
• For example, subjects who remain active in their careers (eg, physicians) may report mild
changes affecting their professional activities. By contrast, subjects with sedentary lifestyles
after retirement (or with lower-skill jobs that they have practiced throughout their lives),
who perform activities that do not require significant intellectual challenge, may not report
IADL problems.
• These examples represent the two extremes generally encountered in clinical practice: high-
functioning patients may be overly sensitive in reporting IADL deficits, whereas less
challenged subjects may be unaware of changes.
25

26. FUNCTIONAL STATUS
• Assessment of functional status determines whether a patient is independent (MCI), or
whether cognitive decline is severe enough to require consistent help with daily activities
(dementia).
• The Functional Activities Questionnaire is a brief standardized instrument for clinicians to
obtain IADL information from an informant.
• When using the FAQ, patients with MCI have more IADLs that “require assistance”
compared to those with normal cognition .
• Using a cut-point of ≥6 points on the FAQ was found to have an 85% accuracy for
distinguishing patients with MCI from those with dementia.
• Mrs. J was still generally independent, but had become slower and less efficient with
customary activities (e.g., cooking and driving);
• increasing difficulties with finances may be another sensitive indicator of early cognitive
decline
26

27. CASE-2
• Case 7-2
• A 78-year-old woman with 12 years of education presented for evaluation with a 3-year
history of cognitive decline associated with symptoms of major depression. According to her
family, she had depression associated with cognitive problems, which had worsened over the
past 6 months.
• She had depressed mood, apathy, anxiety, crying spells, suicidal ideation, insomnia, and lack
of appetite; she had lost 15 pounds in 1 year. She also had short-term memory problems and
difficulty managing her finances and using the pillbox for her daily medication.
• However, the effects of her cognitive problems on her activities of daily living were difficult
to determine, since she did not do much at home because of her depressed mood and lack of
motivation. She had a history of breast cancer (treated with mastectomy), coronary artery
disease, glaucoma, and arthritis, but no history of depression or other psychiatric illness. The
patient was medicated with sertraline 25 mg/d for her symptoms of depression 3 months ago.
27

28. CASE-2
• Her laboratory test results were normal and MRI of her brain showed mild atrophy. No
infarcts or white matter lesions were noted.
• On examination, the patient looked tearful and had minimal bradykinesia. Her Mini-Mental
State Examination (MMSE) score was 24 (1/3 recall and 1/5 in attention subtests). Her
clock-drawing test results were normal, and verbal fluency for animals was 7. Her Hamilton
Depression Rating Scale score was 20; she met criteria for major depression.
• Because of the severity of the patient’s depression, sertraline was gradually increased to 150
mg/d. She was re-examined 6 months after her initial examination, after she had remained
stable on sertraline 150 mg/d for a month. Her MMSE score was 30, her clock-drawing test
results were normal, and her verbal fluency for animals was 14. Her Hamilton Depression
Rating Scale score was 5; she met criteria for major depression in full remission.
28

29. CASE-2
• Comment. This patient developed late-life major depression that was severe enough to
affect her cognition and instrumental activities of daily living. She initially presented with
the memory plus other cognitive domain subtype of mild cognitive impairment (MCI).
• After treatment with antidepressant medication, her cognition and depression improved, and
she returned to normal. This case illustrates that late-life mood disorders can cause an MCI
syndrome, and with proper treatment these patients can return to normal.
• However, close follow-up of the symptoms of depression and its treatment is recommended,
since they may return; repeat cognitive evaluations on an annual basis are also
recommended, since depressed mood has been identified as a risk factor for incident
Alzheimer disease.
29

30. COMORBID CONDITIONS
• There are several neurologic, systemic, and psychiatric syndromes that can cause cognitive
impairment (eg, depression, vascular disease).
• The distinction of MCI groups based on the possible etiology of the cognitive deficits is
essential to identify a syndrome that has increased likelihood of progression to AD.
• However, the reality is that patients with MCI with multiple comorbidities are the most
common in clinical practice and progress to AD at the same rate as those without
comorbidities.
• Consequently, even in the presence of a disease process that could explain the MCI
syndrome, it could be an underlying neurodegenerative process that will eventually lead to
the dementia symptoms.
• In addition, other neurodegenerative disorders that cause dementia either in isolation or in
combination with AD pathology can develop an MCI syndrome before progressing to
dementia (eg, Parkinson disease).
30

31. MEDICATION REVIEW
• Certain classes and combinations of medications can contribute to cognitive impairment, so
all current prescription and over-the-counter medications should be reviewed.
• Classes most likely to contribute to cognitive impairment include:
1) Anticholinergics 2) opiates 3) Benzodiazepines Non-benzodiazepine
hypnotics (e.g., zolpidem)
4) Digoxin 5)antihistamines 6) tricyclic anti-depressants
7) skeletal muscle relaxants 8) antiepileptic.
9) Hormonal therapy (estrogen alone or estrogen plus progestin) for menopause has been
shown to increase risk for the combined endpoint of MCI or dementia.
10) hypotension related to intensive treatment of hypertension and hypoglycemia related to
intensive treatment of diabetes may also contribute to cognitive decline.
31

32. NEUROLOGICAL AND PSYCHIATRIC
EVALUATION
• Clinicians should perform a focused review of neurologic and psychiatric symptoms, a
complete neurological exam, and a depression assessment in patients with suspected MCI.
• Review of symptoms should probe: vision and hearing problems, sleep-disordered breathing,
behavioral or personality changes (which may suggest depression, thyroid disease, or
frontotemporal dementia), visual hallucinations (Lewy-Body dementia, depression with
psychotic features) neuropathy, dizziness, orthostatic hypotension, changes in speech
(stroke, Parkinson's disease), and changes in gait (stroke, normal pressure hydrocephalus,
PD).
• Depression is associated with cognitive impairment in older adults, and the relationship is
likely bi-directional. Depression can be screened in older adults using assessment tools such
as the Geriatric Depression Scale, on which a score of ≥6 is suggestive of depression.
Clinicians can query the informant about a patient's depressive and behavioral symptoms
using the neuropsychiatric inventory.
32

33. 33

34. STRUCTURAL NEUROIMAGING
• The NIA-AA diagnostic guidelines do not recommend routine neuroimaging in the typical
clinical assessment of MCI, but do propose research criteria in which neuroimaging may
help in determining MCI etiology and prognosis.
• Some studies suggest that structural magnetic resonance imaging (MRI) may be useful for
identifying MCI and those at greater risk for progression from MCI to dementia.
• Volumetric measures of the hippocampus that show atrophy, for instance, are suggestive of
MCI and have been shown to correlate with likelihood of progression to dementia.
• However, lack of standardization and validation for these measures limits their usefulness in
clinical practice, and they are not currently recommended for informing prognosis.
• Structural brain MRI may rule out other potential causes for cognitive decline, such as
subdural hematoma, stroke, NPH, or tumor, so should be considered if the history, physical,
or laboratory studies suggest one of these causes.
34

35. FUNCTIONAL AND AMYLOID IMAGING
NEUROIMAGING
• Fluorodeoxyglucose positron emission tomography (FDG-PET) can detect regions of hypo
metabolism in the brain which may be characteristic of MCI due to AD, AD dementia, or
other causes for cognitive impairment.
• Most recently, PET imaging of the extent of Aβ plaques in the brain has become more
feasible with the radiopharmaceutical tracer florbetapir, and has been studied for its utility in
identifying individuals with, or at high-risk for developing, AD.
• PET amyloid imaging noted that this technology accurately identifies the presence of
amyloid, but there is not yet sufficient evidence that the imaging results will affect medical
decision-making or improve health outcomes for older adults with suspected MCI or AD.
• Use of the technology is therefore currently only recommended and covered by Medicare
when used in the context of a research study
35

36. LABORATORY TESTING
• Laboratory testing of complete blood count, electrolytes, glucose, calcium, thyroid function,
vitamin B12, and folate is recommended to identify potentially reversible forms of MCI
including infection, renal failure, hypo- or hypermagna, hyperglycemia, hypo- or
hypercalcemia, hypo- or hyperthyroidism, and B12 / folate deficiency.
• Laboratory testing for liver function, syphilis, Lyme titers (Borrelia), and HIV may reveal
rarer causes for cognitive impairment.
• The proportion of dementia cases thought to be due to potentially reversible causes is about
9%.
• It is also critical to understand that the presence of the APOE*E4 allele is not diagnostic but
should be considered a risk factor for AD.
36

37. LABORATORY TESTING
• The use of CSF and neuroimaging biomarkers can improve the identification of AD
pathology in patients with MCI and predict the likelihood of progression to dementia,
especially within a relatively short period.
• The altered pattern of CSF protein levels usually seen in patients with AD can also be seen
in those with MCI (especially in those who will convert to AD):
• high levels of tau or phosphorylated tau (P-tau)
• decreased amyloid-β42 (Aβ42) protein levels.
• However, because there is a great variability in the tau and Aβ42 levels in patients with AD,
negative CSF studies may not completely exclude the presence of AD pathology in patients
with MCI. In addition, CSF studies are an important tool to exclude other disease processes
that can cause cognitive problems (eg, infections).
37

38. MEDICAL THERAPY
• We summarize potential interventions for MCI from recent clinical trials, systematic
reviews, meta-analyses, and observational studies.
38

39. PHARMACOLOGIC TREATMENT OF
MCI
• Currently, no drug has proven effective in treatment of MCI.
• Cholinesterase inhibitors have not been shown to decrease risk of progression from MCI to
dementia at 1 and 3 years, they have limited to no significant effects on cognitive function
over the short-term (<12 months), and may substantially increase adverse effects, based on a
meta-analysis of 4 trials (n=1,960) and another of 9 trials (n=5,149)
• Consequently, cholinesterase inhibitors and memantineare not recommended for MCI
treatment and there are currently no FDA-approved medications for MCI.
• Ginkgo biloba, a widely-used herbal supplement to improve cognition and memory, has not
been shown in randomized trials to prevent cognitive decline in those with MCI or normal
cognition.
• Similarly, testosterone supplementation in older men showed no benefit for cognitive
function in a randomized controlled trial.
39

40. VASCULAR RISK FACTOR
CONTROL
• Stroke prevention and vascular risk factor control may reduce risk of progression from MCI
to dementia, regardless of radiographic evidence of cerebrovascular injury.
• An acute stroke and subclinical infarcts can accelerate cognitive decline and precipitate
dementia in patients with MCI.
• Vascular contributions to cognitive impairment are common, and many MCI patients have
pathological evidence of neurodegenerative and cerebrovascular disease.
• Strategies for primary or secondary stroke prevention include blood pressure control,
smoking cessation, statin therapy, anti-platelet therapy, and anticoagulation or
antithrombotic therapy for atrial fibrillation
40

41. 41

42. 42

43. 43

44. 44

45. TREATMENT OF THE PATIENT
• Although there are no drugs proven or approved to treat MCI, optimizing patients' general
medical and functional status, and providing counseling regarding issues such as driving and
home safety, can maximize patient and caregiver well-being, and reduce risk for negative
outcomes.
• Individuals with MCI are at increased risk for gait dysfunction, mobility decline, and falls.
Gait assessment while performing an attention-demanding task (dual-task testing) may
identify motor control and performance problems that could benefit from tailored
interventions
• Optimizing visual and auditory acuity may enhance functioning as untreated vision and
hearing problems are associated with cognitive decline.
45

46. TREATMENT OF THE PATIENT
• While depressive and vegetative symptoms may cause or contribute to MCI, there is mixed
evidence as to whether treatment of depression improves cognitive impairment, or decreases
risk for incident MCI or dementia.
• Given increasing evidence of the negative impact of anti-cholinergic medications on
cognitive function in older adults, treatment with anti-depressants that have significant anti-
cholinergic properties (e.g., amitriptyline, nortriptyline, and paroxetine) should be avoided.
• A trial of withdrawing and simplifying medication regimens in older adults may lead to
improvements in cognitive function.
46

47. COUNSELING ON BEHAVIORS
• There is modest evidence from RCTs and clinical studies that various behavioral interventions,
particularly aerobic exercise and mental activity, may have small, but beneficial effects on cognitive
function in older adults with MCI.
• Several RCTs of community-dwelling adults with or at risk for MCI have shown that home-based or
professionally-supervised programs of aerobic exercise or resistance training modestly improve
cognition, particularly executive function, over 18-months of follow-up.
• The combination of aerobic exercise and mental activity may benefit MCI patients.
• The Mental Activity and eXercise (MAX) RCT of126 inactive, older adults with memory complaints
demonstrated that a 12-week program of combined physical plus mental activity was associated with
small, significant improvements in global cognitive function regardless of the types of physical
activity (aerobic vs. stretching/toning) and mental activity (intensive vs. educational videos).
• Observational studies suggest that the Mediterranean diet also may reduce the risk of converting
from MCI to dementia.
47

48. COUNSELING ON BEHAVIORS
• Observational studies suggest that social engagement may reduce the risk of cognitive
decline and preserve memory, particularly in adults with <12 years of education or those
with vascular disease.
• Little is known about the effectiveness of multidisciplinary care programs or supportive care
interventions (e.g., counseling, education, support groups) for patients with MCI or their
families because well-designed RCTs are lacking and one RCT that included many patients
with dementia was negative (Table).
• A few, small RCTs found that psychotherapy may modestly increase patients' acceptance of
an MCI diagnosis and also provide knowledge, insight, acceptance, and coping skills for
significant others, but larger RCTs are needed.
48

49. COUNSELING ON BEHAVIORS
• Small RCTs and clinical studies suggest that cognitive interventions may improve cognitive
function moderately over 6 to 12 months for persons with MCI or mild dementia.
• however, improvements are often specific to targeted cognitive domains, may not be greater
than active controls, and may not improve daily functioning.
• Moreover, it is difficult to recommend specific components of cognitive interventions
because of heterogeneity across studies.
49

50. • An issue that often arises in patients with MCI is driving safety.
• While there is general consensus among medical and transportation societies that those with
moderate to severe dementia should not drive due to significantly increased risk for
accidents, evidence of driving impairment for patients with MCI is less clear.
• The clinician should probe patient and family for indicators of driving impairment, including
recent motor vehicle accidents or “near misses,” changes in the patient's driving behaviors
(e.g., speed, ability to stay in lane, road sign comprehension), or episodes of getting lost in
familiar areas.
DRIVING
50

51. • Testing for deficits in visuospatial and executive function (Clock Drawing Task and Trail-
making tests),cognitive domains thought to be important for driving safely, or formal
driving evaluation may provide useful information.
• Patients are often reluctant to stop driving even on physician and/or family recommendation,
so early and repeated discussions suggesting that driving cessation may be necessary, and
referral to public transportation or other options may be useful in early counseling sessions.
• There is no legal requirement for physicians to report a patient with MCI to a Department of
Motor Vehicles, but some states have mandatory reporting for patients with diagnosed
dementia
DRIVING
51

52. FALLOW-UP
• Serial assessments of cognition are recommended because “progressive cognitive decline
provides additional evidence that the individual has ‘MCI due to AD'.”
• Longitudinal follow-up and serial cognitive assessments are also useful since they allow a
clearer assessment of a patient's true baseline and trajectory of cognitive function over time,
and decrease the risk that poor performance on a single assessment due to anxiety, fatigue, or
acute illness leads to a false positive diagnosis of MCI.
• However, the optimal timing, choice, and cost-effectiveness of longitudinal cognitive
assessments are unclear.
• Tests of episodic memory identify MCI patients with high likelihood of progressing to AD
within a few years.
• General cognitive screening instruments (e.g., MoCA) are recommended for detecting
dementia in individuals with suspected MCI.
• Serial assessments of daily functioning may identify MCI patients who are more likely to
develop dementia, may indicate incident dementia, and may identify need for additional
resources.
52

53. FALLOW-UP
• No neuroimaging or laboratory test is currently recommended for predicting MCI
progression to dementia in clinical practice.
• Although specific brain imaging findings (e.g., Aβ deposition, medial temporal lobe atrophy,
hippocampal atrophy, or hypo-perfusion or hypo-metabolism in the temporoparietal cortex)
are associated with an increased risk of progression, these findings currently lack specificity.
• Cerebrospinal fluid tests showing low levels of Aβ42, elevated levels of tau, or a low Aβ42
to tau ratio confer an increased likelihood of progressing to dementia; however, results may
be ambiguous or contradictory for a given patient, may vary across sites, and diagnostic
accuracy and positive predictive value are sub-optimal.
• It is not recommended to perform routine genetic testing for mutations in amyloid precursor
protein, presenilin 1, or presenilin2 in adults with cognitive changes presenting before age
65 or in the APOE e4 allelein older adults.
53

54. PROGNOSIS
• Prognosis is uncertain for patients with MCI and, as articulated by Mr. J, uncertainty about
the future is a major source of worry.
• Although patients with MCI have a greater risk of developing dementia compared with the
general population, studies report substantial variability.
• Reported annual rates of MCI conversion to dementia span<5% to 12-20%, depending on
the country and population studied.
• Patients can be counseled that a minority will progress to dementia annually, however many
patients with MCI (40-70%) may not progress to dementia even after 10 years.
• Importantly, some MCI patients (15-20%) will have improved cognition1-2 years later,
although the latter group likely remains at increased risk of future cognitive decline.
54

55. KEY POINTS
• Patients with mild cognitive impairment can present with mild deficits in instrumental activities of
daily living.
• Increased CSF phosphorylated tau and decreased Aβ-42 protein levels increase the short-term risk of
conversion to Alzheimer disease in mild cognitive impairment patients.
• Decreased metabolism in temporal-parietal regions, including the precuneus (detected with
fluorodeoxyglucose-PET), and increased amyloid deposition (detected with amyloid ligands) increase
the risk of conversion to Alzheimer disease.
• Biomarker studies should be interpreted with caution. Although they indicate that Alzheimer disease
pathology is present, they do not provide information about when the patient will progress to an
Alzheimer disease clinical dementia.
• There are no therapies that can prevent the conversion from mild cognitive impairment to Alzheimer
disease. However, studies conducted with cholinesterase inhibitors have shown a modest cognitive
improvement in subjects with mild cognitive impairment treated with these medications compared to
placebo
55

56. KEY POINTS
• Patients with mild cognitive impairment are at risk of developing dementia, especially Alzheimer
disease.
• The mild cognitive impairment syndrome is not restricted to memory deficits, and these patients can
present with a much broader cognitive syndrome, which may not include memory impairments.
• The prevalence of mild cognitive impairment in the general elderly population ranges from 2% to
more than 20%.
• The mild cognitive impairment syndrome with memory-only deficits is less prevalent than mild
cognitive impairment with a much broader cognitive syndrome in the general population.
• The mild cognitive impairment syndrome, as an expression of an incipient neurodegenerative disorder
that may lead to dementia, is extremely heterogeneous and may coexist with systemic, neurologic, or
psychiatric disorders that can cause cognitive deficits.
• Approximately 20% of patients with diagnosis of mild cognitive impairment return to normal
cognition on follow-up examination.
56

57. WEB RESOURCES
• Alzheimer's Association – http://www.alz.org
• The Alzheimer's Association is a national advocacy organization that supports care and research
related to Alzheimer's disease and other dementias. Their website provides information and links that
can be useful for patients, caregivers, health care providers, and researchers who have questions
regarding Mild Cognitive Impairment (MCI) and cognitive decline, including a telephone helpline
(800-272-3900) and how to contact local Alzheimer's Association chapters.
• Alzheimer's Disease Education and Referral Center -- http://www.nia.nih.gov/alzheimers
• The Alzheimer's Disease Education and Referral Center (ADEAR) is an information clearinghouse
sponsored by the National Institute on Aging (NIA), one of the institutes of the National Institutes of
Health (NIH). ADEAR provides a wide range of free information on causes for cognitive decline,
MCI, and dementia. The information is geared to patients, caregivers, and health care providers. There
is information on ongoing research studies related to cognitive decline and dementia, including how to
explore enrolling in NIH-sponsored research studies.
57

58. WEB RESOURCES
• American Bar Association Commission on Law and Aging –
http://www.americanbar.org/groups/law_aging.html
• The American Bar Association Commission on Law and Aging provides extensive information on a
wide range of legal issues that older adults, in general, and older adults with MCI, in particular, may
need to face. These legal issues include: advance care planning, capacity assessment, health care
decision-making, durable power of attorney, guardianship, and elder abuse. The website includes
helpful charts on how relevant laws may differ by state.
• Caring Connections – http://www.caringinfo.org
• Caring Connections is a program and website run by the National Hospice and Palliative Care
Organization (NHPCO) which aims to provide resources to improve care at the end of life. The
website provides a wide range of information for people living with illness and their caregivers. State-
specific information on advance directives and locating a hospice provider is available at the website,
and there is also a telephone helpline (800-658-8898).
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59. WEB RESOURCES
• Administration on Aging – http://www.aoa.gov
• The Administration on Aging (AoA) is a program run by the federal Department of Health and
Human Services that provides home and community-based services for older adults. The AoA website
has information and web links on government benefits, health and wellness programs, and long-term
care services. An “eldercare locator” at the website can help identify local resources related to
Alzheimer's disease, caregiver programs, food and nutrition, and transportation.
• National Highway Traffic Safety Administration –http://www.nhtsa.gov
• The National Highway Traffic Safety Administration maintains educational resources for older
drivers, their families, and physicians, including the Physician's Guide to Assessing and Counseling
Older Drivers (http://www.nhtsa.gov/people/injury/olddrive/olderdriversbook/pages/contents.html)
which details individual state laws regarding mandatory physician reporting requirements for patients
with a dementia diagnosis.
59

60. RESOURCES
• The Diagnosis and Management of Mild Cognitive Impairment: A Clinical Review.
Kenneth M. Langa, Deborah A. Levine JAMA. Author manuscript; available in PMC 2015
Dec 17. Published in final edited form as: JAMA. 2014 Dec 17; 312(23): 2551–2561.
doi: 10.1001/jama.2014.13806, PMCID: PMC4269302
• Mild Cognitive Impairment. Oscar L. Lopez. Continuum (Minneap Minn) 2013 Apr; 19(2
Dementia): 411–424. doi: 10.1212/01.CON.0000429175.29601.97, PMCID:
PMC3915547
60

61. THANKS A
LOT
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