|Year : 2016 | Volume
| Issue : 1 | Page : 10-20
Mild cognitive decline: Concept, types, presentation, and management
Alka A Subramanyam, Shipra Singh
Department of Psychiatry, Topiwala National Medical College (TNMC) and BYL Nair Hospital, Mumbai, Maharashtra, India
|Date of Web Publication||6-May-2016|
Alka A Subramanyam
Department of Psychiatry, OPD-13, First Floor, OPD Building, Topiwala National Medical College (TNMC) and BYL Nair Hospital, Mumbai - 400 008, Maharashtra
Source of Support: None, Conflict of Interest: None
As advancements are being made in the medical field, the average life span is increasing and more complaints related to the elderly are coming into notice. Of these, mild cognitive decline (MCD) or mild cognitive impairment (MCI) is recently becoming an increasingly recognized entity that is often considered a precursor of dementia but is found to have other outcomes as well. It also has variations in presentations; it does not present only as memory complaint but also in the form of other cognitive or behavioral manifestations and has always been a point of controversy regarding the objectivity of the diagnosis. It is considered as the appropriate stage for intervention to prevent its progression to dementia and therefore, requires early identification for which various diagnostic modalities such as neuroimaging, neuropsychological tests, and biological markers are considered. Currently, there are no specific treatment guidelines for MCD. Drugs used in Alzheimer's disease (AD), lifestyle modifications, and other nonpharmacological approaches have shown some benefit in MCI but the results are variable; hence, the need for further research is warranted for effective preventive therapy. In this article, we will be discussing MCD as a clinical construct, evaluation of a person suspected of having MCD, and management of the same.
Keywords: Diagnosis, mild cognitive impairment (MCI), treatment
|How to cite this article:|
Subramanyam AA, Singh S. Mild cognitive decline: Concept, types, presentation, and management. J Geriatr Ment Health 2016;3:10-20
|How to cite this URL:|
Subramanyam AA, Singh S. Mild cognitive decline: Concept, types, presentation, and management. J Geriatr Ment Health [serial online] 2016 [cited 2020 Aug 10];3:10-20. Available from: http://www.jgmh.org/text.asp?2016/3/1/10/181910
| Introduction MCI as a clinical construct|| |
Mild cognitive decline (MCD) or mild cognitive impairment (MCI) refers to a transitional state between the cognition of normal aging and mild dementia. It is a clinical construct that describes individuals with mildly impaired performance on objective neuropsychological tests but relatively intact global cognition and daily functioning.  MCI has been validated as qualitatively different from both normal aging and dementia and has been a matter of debate regarding whether or not it is a risk factor for the development of dementia.  The overall prevalence of MCI in the general elderly population has a range of 2-20% and is lower in the amnestic subtype, i.e., 2-4% as compared to the broader group. , In one Indian study, the prevalence of MCI was found to be 14.89%. 
| History|| |
It was observed that some elderly became mildly forgetful who did not fit clearly either in "cognitively normal" or "demented."  Several terms emerged to describe this group such as "benign senescent forgetfulness" and "age-associated memory impairment" that were soon recognized as inadequate. Clinicians noted that dementia patients and their families retrospectively report cognitive deficits that started several years before evaluation. This in-between group, whose impairment is sometimes called "cognitive impairment not dementia,"  might be subdivided into individuals with memory loss that is age-related and those whose cognitive symptoms are the first clinical manifestations of dementia. The group initially thought to be in the prodromal stages of Alzheimer's disease (AD) is now said to have "mild cognitive impairment."  The term "vascular cognitive impairment" has been proposed to refer to the prodrome of vascular dementia.  A similar term, "subjective cognitive impairment (SCI)," came into existence where cognitive issues were reported by apparently normal-functioning elderly. Reisberg first described this entity in terms of the Global Deterioration Scale that measures cognitive and functional decline on a scale of 1 (cognitively normal) to 7 (severe dementia) with MCI defined as a Global Deterioration Scale (GDS) score of 3. , However, it was Peterson who first coined the term MCI that is now used worldwide. 
| Presentation and subtypes|| |
MCI identifies a spectrum of diseases that includes impairment in both memory and nonmemory cognitive domains. Peterson first gave the concept of MCI as having memory complaint, in the absence of other cognitive disorders or dementia or repercussions on daily life. However, this criterion has been under extensive debate that led to the formulation of various diagnostic guidelines. 
1. National Institute on Ageing and Alzheimer's Association (2010) revised the criteria of MCI as: 1) concern regarding change in cognition, 2) impairment in one or more cognitive domains, 3) preservation of independence in functional abilities, and 4) not demented. 
2. "Diagnostic and Statistical Manual of Mental Disorders" (DSM)-5 includes MCI under the category of mild neurocognitive disorders. 
3. MCI is classified into two subtypes: Amnestic and nonamnestic, based on the involvement of memory and single domain or multiple domain, based on involvement of the number of cognitive domains affected. Amnestic MCI is a clinically significant memory impairment that does not meet the criteria for dementia. It has been stated that mini-mental state examination (MMSE) scores of less than 26 in uneducated individuals and less than 28 in educated individuals warrant assessment for MCI.
Typically, patients and their families are aware of the increasing forgetfulness. However, other cognitive capacities are relatively preserved and functional activities are intact, except for some mild inefficiency. Nonamnestic MCI is characterized by a subtle decline in functions not related to memory, affecting attention, language, problem-solving, word-finding, or visuospatial skills. 
The criteria for subtypes were operationalized using the results of neuropsychological testing in a study  as: (1) MCI amnestic type: Participants with isolated progressive or static memory deficits (delayed recall verbal memory, nonverbal memory, or both) who had a score on a standardized test that was 1.5 standard deviation (SD) below the mean compared with individuals of the same age and level of education (other tests were healthy) and (2) MCI multiple cognitive deficits type: Participants with a progressive or static deterioration in at least one cognitive domain (not including memory) or one abnormal test (1.5 SD below the mean adjusted for age and education) in at least two other domains but who had not crossed the threshold for dementia.
4. In studying the prodromal phase of dementia, another group was observed, known as "mild behavioral impairment" (MBI) that presented only with behavioral symptoms and yet progressed toward dementia. Thus, Taragano et al. proposed another classification: 1) MCI with neuropsychiatric symptoms, 2) MCI without neuropsychiatric symptoms, 3) MBI with cognitive symptoms, and 4) MBI without cognitive symptoms. 
5. Based on etiopathology, it can be neurodegenerative (pre-Alzheimer's, Lewy body, frontotemporal) or vascular. The nonamnestic type is probably less common than the amnestic type and may be the forerunner of non-Alzheimer's Disease in the text such as frontotemporal or dementia with Lewy bodies.  To understand this simplistically, [Figure 1] may be of help.
| Neuropsychiatric manifestations|| |
MCI frequently presents with neuropsychiatric symptoms. The most comprehensive studies of behavioral manifestations have been documented as at least one neuropsychiatric symptom in 35-75% of MCI patients, which was probably why Terragano et al. thought of MBI as a separate entity.  Depression, apathy, and anxiety are consistently among the most common behavioral abnormalities in MCI despite different study designs, behavioral instruments, or MCI diagnostic criteria used. 
Of the neuropsychiatric manifestations of MCI, depression is the most widely studied. In the Cardiovascular Health Study Cognition Study, prevalence of depression was 20% in MCI.  However, figures varied from 11%  to 45%  in various studies. Depression has also been extensively studied as a risk factor for further cognitive decline. ,,,,
Apathy is the most prevalent neuropsychiatric symptom in AD.  It commonly starts during the MCI stage and progressively increases as AD progresses,  and is related to worsening on tests of memory and executive control.
The results for prevalence of anxiety in MCI are varied. , Psychotic symptoms such as delusions and hallucinations were reported to be less than 5%. , However, an association between lower MMSE scores and the onset of psychotic symptoms was reported in one study. Subjects with misidentification symptoms tended to have longer disease duration and lower MMSE scores.  The rates of disinhibition ranged from 3% to 10% and of agitation from 4% to 18% that is not significantly different from those observed in the normal elderly. , Varied results are found for euphoria, aberrant motor behavior, and irritability in MCI. ,
| Stability of diagnosis and outcome|| |
MCI may not always convert to dementia. Around 20-40% cases appear to improve over time on retesting. , After diagnosis, the subtype may change on follow-up. Single domain particularly seems to be at risk of this shift. ,,, However, some have found that all MCI subtypes either convert to dementia or retain their MCI status. ,
MCI may have different outcomes. Multidomain amnestic MCI appear to be at the greatest risk of dementia. , Amnestic MCI has the highest risk for conversion to Alzheimer's dementia, , whereas multidomain presentation to vascular dementia. ,, Nonamnestic subtype with multiple domain involvement more likely converts to non-AD,  with single domain at particular risk of progressing to fronto-temporal dementia. 
Rates of progression from MCI to dementia vary in the range of 20-40% (10-15% per year) with a few outliers at the lower and higher ends of the spectrum. Data from Mayo Alzheimer's Disease Research Center demonstrated a conversion to AD in 80% cases in approximately 10 years  that keeps on increasing exponentially each year.
| Risk factors for progression of mci|| |
Progression of MCI may be determined by the following factors: ,
- Older age.
- Fewer years of education.
- Multidomain amnestic MCI.
- High fat diet.
- Medical comorbidities: Metabolic syndrome, chronic inflammatory diseases, vascular disease, thyroid disorders, and elevated homocysteine levels.
- Excessive alcohol intake.
- Stressful lifestyle.
- Untreated depression.
- Presence of apolipoprotein E (ApoE) E4 allele.
- Magnetic resonance imaging (MRI), with volumetric measurements of the hippocampus at or below the 25th percentile for matched age and sex.
[TAG:2]EVALUATION OF A PATIENT SUSPECTED OF MCI [/TAG:2]
Any patient suspected of having MCI should undergo detailed clinical and investigatory evaluations. A thorough history and physical examination focusing on the status of cognitive functions, status of activities of daily routine, medications, neuropsychiatric evaluation, and laboratory testing are important components of this assessment.
1. HISTORY TAKING
- Details about the onset, duration, nature, and progression of cognitive symptoms.
- Functional status: Information from family members, wherever available, is essential, especially in knowing the previous level of functioning, both personal as well as instrumental, in order to differentiate MCI from dementia. Subtle deficits in instrumental activities of daily living (IADL) are noticed in MCI. IADL requiring higher neuropsychological functioning seem to be most severely affected in patients with MCI.  The Functional Activities Questionnaire is used for assessing these, using data from an informant. Score of 6 or more has >85% accuracy in differentiating MCI from dementia. 
- Information to rule out potentially reversible causes of MCI (depression, vitamin B 12 /folate deficiency, thyroid diseases, and medication). 
- Presence of neurological or psychiatric symptoms (to rule out Parkinson's disease, normal pressure hydrocephalus, stroke, or neuropathy). 
- History of substance use disorders, family history of cognitive disorders, and psychosocial history.
- Thorough Neurological and Psychiatric Evaluation: A complete psychiatric evaluation and neurological examination including orthostatic hypotension, extraocular movements, vision, hearing, speech, focal weakness, ability to stand from a chair, and gait are useful for identifying potential contributors to cognitive decline including stroke, Parkinson disease, normal-pressure hydrocephalus, or neuropathy due to toxins or vitamin deficiency. 
- Depression associated with cognitive impairment in the elderly can be assessed using Geriatric Depression Scale (GDS), on which a score of 6 or more suggests depression. 
a. Laboratory Testing: Testing complete blood count, electrolytes, glucose, calcium, thyroid function, vitamin B 12 , and folate is recommended to identify potentially reversible forms of MCI including infection, renal failure, hypomagnesaemia or hypermagnesemia, hyperglycemia, hypocalcaemia or hypercalcemia, hypothyroidism or hyperthyroidism, and vitamin B 12 or folate deficiency. Laboratory testing for liver function, syphilis, and human immunodeficiency virus (HIV) may reveal rarer causes.  About 9% of the causes of dementia seem to be reversible.  While studies have suggested that levels of biomarkers in the cerebrospinal fluid (e.g., Aί 42 and tau protein) may help identify patients with MCI who are more likely to progress to AD,  routine lumbar puncture is not generally recommended for clinical evaluation. 
i. Structural: The National Institute of Aging-Alzheimer's Association (NIA-AA) diagnostic guidelines do not recommend routine neuroimaging in the assessment of MCI but suggest that it may help in determining MCI etiology and prognosis.  Structural MRI may be useful for identifying MCI and those at greater risk for progression from MCI to dementia. ,
Decreased size of the hippocampus on volumetric measures is suggestive of MCI and correlated with the likelihood of progression to dementia.  MRI in nonamnestic MCI revealed a significant reduction in the dorsolateral and dorsomedial prefrontal cortices and reduction in volume of caudate nucleus; meanwhile, in amnestic MCI, atrophy in bilateral posterior temporoparietal cortices, medial temporal cortices, posterior cingulate gyrus, and right inferior parietal cortex were noted. However, the lack of standardization and validation for these measures limit their usefulness in clinical practice,  and they are not currently recommended for informing prognosis. Nevertheless, they may rule out other potential causes for cognitive decline such as subdural hematoma, stroke, normal pressure hydrocephalus (NPH), or tumor, if suggested by history and physical or laboratory studies. 
ii. Functional and amyloid imaging: Fludeoxyglucose (FDG) positron emission tomography (PET) can detect regions of hypometabolism in the brain that may be suggestive of MCI such as hypoperfusion in bilateral temporoparietal cortices and posterior cingulate cortices, with relative sparing of sensorimotor and occipital cortices. , Most recently, PET imaging of the extent of Aί plaques in the brain is being done with radiotracer florbetapir  and it has been useful in identifying individuals with AD or at high risk for developing the same.  Assessment with 18-FDG Pittsburgh Compound B (PiB) PET was found sensitive in differentiating amnestic and nonamnestic MCI. It shows a good correlation with cognitive measures in patients with MCI, with a sensitivity of 92% and specificity of 89% to predict conversion to AD. A recent review, however, suggested that there is no sufficient evidence yet that will improve health outcomes in cases of suspected MCI. Hence, its use is limited to research purposes. 
c. Neuropathology: Most patients with amnestic MCI demonstrate the deposition of tau proteins in neurofibrillary tangles in the medial temporal lobe and neuronal plaques due to deposition of beta amyloid. Cerebral spinal fluid (CSF) studies have revealed low Aβ42 and elevated tau or phosphorylated tau in cases of Alzheimer's dementia as compared to age-matched cognitively healthy controls. These biomarkers, thus, seem to be useful in a multistep approach in the diagnosis and intervention of MCI or dementia. But this hypothesis still remains questionable as certain studies have reported variable results and there has been no therapeutic breakthrough yet. 
Ongoing research is also targeted toward the process of inflammation and oxidative stress such as cytokines and isoprostanes, using a variety of markers. However, it would be too early to predict the significance of these markers in clinical practice.
d. Genetic testing: The presence of mutations in A4 precursor protein (APP) and PS1 and PS2 genes are likely predictors of the conversion of MCI to early Alzheimer's dementia. In addition, there is increased risk for the development of dementia in an individual with MCI, in the presence of apolipoprotein (Apo) E4 allele. On the other hand, E2 allele is associated with decreased risk.  In an Indian study, frequencies for ApoE2, ApoE3, and ApoE4 alleles were found to be 0.25, 0.35, and 0.4 in Alzheimer's patients and their first-degree relatives. ApoE4 was present in 71% of the patients with Alzheimer's and their relatives that was 2.7 times higher than the controls. However, the cost and availability of the testing have limited its use in the Indian context. 
4. NEUROPSYCHOLOGICAL TESTING
Assessment of cognition in the elderly can be a challenging task. There are a variety of tests that can be used for the assessment of MCI; however, tests such as MMSE, clinical dementia rating (CDR) scale, repetition, fluency, and digit span are the ones that are handy, easy, and quick to administer and can be readily used by the clinicians. The commonly used tests are as follows:
a. Brief cognitive tests:
A comprehensive set of tests is applied when there is suspicion of having MCI. Though there are no clear-cut guidelines, the following tests are commonly used for screening:
- MMSE: It is probably the most widely used test for bedside memory testing. It has sensitivity and specificity of 70% with a cutoff score of 26. The scores of 26 (in noneducated individuals) and 28 (in educated individuals) warrant further assessment, follow up and surveillance for MCI.  Addition of a recall after a longer delay improves the sensitivity and specificity to >80%. 
- Montreal Cognitive Assessment (MoCA): This was developed specifically for the detection of MCI and takes approximately 10 min to administer.  It has a high sensitivity as well as specificity. , Its assesses orientation, attention, immediate and delayed recall, executive function and language, etc. 
- DemTect: This evaluates immediate and delayed recall of word list, number transcoding, verbal fluency and reverse digit span. It has sensitivity of 80% and specificity of 92% in differentiating MCI from normal controls. 
- Clinical Dementia Rating (CDR) Scale: It considers six domains - memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. Score of 0.5 on this scale is of diagnostic importance for MCI, according to Peterson's modified criteria. American Academy of Neurology (AAN) accepts this score as equivalent to the presence of MCI.  It has a high inter-rater reliability and appears to be a reliable and valid tool for assessing and staging dementia.
- Global deterioration scale: A score of 3 is considered to be indicative of MCI. 
- Neuropsychological tests: These are helpful but not definitive for the diagnosis of MCI. Various cognitive domains can be tested and tests used include tests for recall (Hopkins verbal learning test, Wechsler's memory delayed recall), verbal category and semantic fluency, attention (digit span forward and backward), processing speed (trail making test A), visuoconstructional function (clock drawing test and Rey-Osterrieth complex figure test), and executive functioning (trail making test B and symbol digit substitution).
b. A typical battery assessing these domains is more sensitive than routine office tests and can provide a thorough profile of deficits, differentiating between amnestic from nonamnestic and single domain from multiple domain MCI. 
- Neuropsychiatric inventory (NPI) and short questionnaire form of the NPI (NPI-Q): The presence of psychiatric symptoms and caregiver distress can be assessed. 
- Addenbrooke's cognitive assessment: It assesses five domains - orientation/attention, memory, verbal fluency, language and visuospatial. At the cutoff of 82, the likelihood of dementia is 100:1. It has high sensitivity of 0.94 and specificity of 1, and correlates well with CDR.
- AD assessment scale - cognitive subscale (ADAS-Cog): It assesses 11 domains in cognition, along with 10 clinician-rated items for psychosis, depression, agitation, etc. Its results can range from MCI to severe impairment, and is a good tool for longitudinal assessment; however, it takes a long time to administer.
- Informant questionnaire on cognitive decline in the elderly (IQCODE) addresses the objective reporting by the caretaker on the day-to-day behavior of the person. It requires a very well-informed caregiver for the same. 
A simple approach to a patient with MCI for clinicians is outlined in [Figure 2].
| Management of mci|| |
There have been no specific recommendations for the treatment of MCI but the management can be divided into pharmacological and nonpharmacological (that are mostly the preventive factors for MCI) for the sake of simplicity.
1. PHARMACOLOGICAL: Although no drug is approved for treating MCI, the following have been the focus of interest:
- Acetylcholinesterase Inhibitors: The Alzheimer's Disease Cooperative Study favored donepezil at 1 year but not at 3 years follow-up. Its effect was greater in Apoù4-positive individuals that seemed to be an important predictor for progression.  Based on these studies, the screening of patients with amnestic MCI for ApoE4 allele is recommended and only if ApoE4 allele is present the patients should be given AChEIs. ,,
- Memantine: Memantine has not been reported to benefit patients with MCI. 
- Piribedil: It is a dopamine receptor agonist, having acetylcholine release in the hippocampus and the frontal cortex as a putative mechanism of action. Pirbidel improved cognition over 3 months on the primary outcome in placebo-controlled study by Nagraj et al. in National Institute of Mental Health and Neurosciences (NIMHANS). 
- Nicotine: Brain nicotinic receptors are important for cognitive function. Nicotine patches improved attention, but not global functioning, over 6 months. 
- Cyclooxygenase (COX)-2 inhibitors: Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce brain neurotoxic inflammatory responses and so was assumed to improve cognition. Rofecoxib increased incident cases of Alzheimers dementia in the study and has a fair evidence against its use.  Trifusal (COX-1 and COX-2 inhibitors) had no effect on cognition but was associated with a reduced risk of conversion to AD. 
- Gingko biloba: The proposed mechanisms of action include increasing brain the blood supply, modifying neurotransmitter systems, and reducing oxygen-free radical density.  But the results of its use have been inconsistent. ,
- Vitamin B: Higher homocysteine plasma concentrations are associated with cognitive impairment, the levels of which are decreased by B vitamins. Immediate memory did not improve;  however, attention and executive functioning had varying results. 
- Antioxidants such as vitamin E, vitamin C, and curcumin (from turmeric) are hypothesized to reduce oxidative stress and ageing, yet work in this field is largely in the incipient stages. 
- Omega-3 polyunsaturated fatty acids (PUFAs): With PUFAs, cognition, in terms of verbal fluency and depressive symptoms improved at 6 months follow-up. ,
- Antiamyloid therapies: Secretase inhibitors reduce amyloid production by inhibiting the secretase activity. Similarly, fibrillogenesis inhibitors (alzhmed and cliniquinol) are also under research, along with the vaccines that would prevent amyloid plaque formation. 
- Neurotonics: The use of piracetam has not met with any evidence. 
- Estrogens: These have been found to actually increase the risk for MCI and AD. ,
- Others: Huannao Yicong responded on a cognition and social functioning measure but the result was not significant. CDP choline, calcium channel blocker nimodipine and testosterone supplementation seem partially effective. 
- Drugs on trial for MCI include vasoactive intestinal peptide (AL-208), a selective metabotropic glutamate receptor antagonist (C-105), a novel L-type calcium channel blocker (MEM- 1003), a phosphodiesterase inhibitor (MEM-1414), a gamma-aminobutyric acid B receptor antagonist (SGS-742), and a selective serotonin receptor (5HT6) antagonist (SGS-518). 
Intervention in MCI remains a matter of debate owing to its varied course. Though till date there are no particular guidelines for treating MCI, the amnestic type is widely viewed as being an optimal stage to intervene with preventative therapies due to its greater risk of progressing to dementia. Studies have typically aimed to identify treatments that can stabilize symptoms or delay the onset of dementia. Recognition of MCI itself is in the early stage. Thus, further research is required with clinical trials that are designed to select more homogeneous samples at entry with optimal treatment durations and more sensitive cognitive and global outcome measures that reflect subtle impairments in complex activities.
2. NONPHARMACOLOGICAL: Although the outcome of MCI is still a matter of debate, efforts are made to prevent progression of the disorder and much emphasis is given for its prevention at the first place. The following are some nonpharmacological measures that have been discussed, which have a role in preventing MCI and reducing the risk of its progression.
- Treatment of vascular and other comorbidities such as hypertension, diabetes, atrial fibrillation, obesity, vitamin deficiency, hypothyroidism, depression, and sleep disturbances. ,
- Abstention from heavy alcohol, smoking, and other substances of abuse. ,
- Establishment of a fixed and disciplined routine.
- Diet: A Mediterranean diet (with high intake of cereals, fruits, fish, legumes, and vegetables) reduces risk of cardiovascular disease, increases concentration of plasma neutrophins, limits proinflammatory cascades, thereby helping in preventing cognitive decline.  Second dietary factor that has been implicated is curcumin (a pharmacologically active ingredient in the Indian spice "haldi") that was a probable contributory factor mentioned for the lower prevalence of MCI in India than in developed countries. 
- Socialization with people, apart from one's immediate family members, e.g., friends, being part of a senior citizen's group, etc. 
- Spiritual activity of some form is also of importance in maintaining cognition. 
- Physical exercise/activity: It has favorable effects on neuronal survivability and function, neuroinflammation, vascularization, neuroendocrine response to stress, and brain amyloid burden. , Inconsistent results of improvement in fluency, memory, and trail-making were found. , It has been claimed that any frequency of moderate exercise reduced odds of having MCI. 
- Computer-assisted cognitive training: It involves teaching individuals empirically-supported strategies and skills in order to optimize current cognitive functioning and independence in daily life. Its effect was seen on objective and subjective measures of memory, quality of life, and mood. 
- Cognitive stimulation: It involves activities designed to increase cognitive and social functioning in a nonspecific manner (e.g., reading, board games, group discussions). Engagement in such activities is associated with a decreased risk of cognitive decline, amnestic MCI  and AD. ,
- Family psychological intervention: Kinsella et al. found prospective memory improvement up to 4 months later in a trial that was not placebo-controlled. 
REGULAR FOLLOW-UP: Given the uncertainty of prognosis in this population, it has been recommended that MCI patients should be seen every 6-12 months for follow-up. This would consist of repeat cognitive screening, functional inquiry, and careful history taking (including family collateral) to assess for conversion to dementia.  It is also important to educate patients and families about the kinds of warning signs that would suggest the possibility of progression and warrant the need for follow-up. Neuropsychological testing should be repeated every 1-2 years or when conversion is suspected.
| Conclusion and future directions|| |
The hopelessness that a treating geriatric specialist feels while treating a patient with dementia and the realization that it may be too late to intervene at the dementia stage has given MCI an increasing importance as a recognized clinical entity. Older adults fear cognitive decline and many prefer getting evaluated that can have its own financial, social, and emotional bearings.
But owing to its potential importance for early identification and intervention in those at risk for the development of dementia, the concept of MCI has received considerable research attention. It seems that in the near future, we would get a better insight into the illness, its standard clinical criteria, and diagnostic modalities. In addition, options for newer targeted drugs and therapies would be possible that might give hope to many and would cause cognitive decline to be seen as somewhat modifiable instead of an unchangeable reality.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Petersen RC, Smith GE, Waring SC, Ivnik RJ, Tangalos EG, Kokmen E. Mild cognitive impairment: Clinical characterization and outcome. Arch Neurol 1999;56:303-8.
Petersen RC. Mild cognitive impairment as a diagnostic entity. J Intern Med 2004;256:183-94.
Lopez OL, Jagust WJ, DeKosky ST, Becker JT, Fitzpatrick A, Dulberg C, et al
. Prevalence and classification of mild cognitive impairment in the Cardiovascular Health Study Cognitive Study: Part 1. Arch Neurol 2003;60:1385-9.
Ganguli M, Dodge HH, Shen C, DeKosky ST. Mild cognitive impairment, amnestic type: An epidemiologic study. Neurology 2004;63:115-21.
Das SK, Bose P, Biswas A, Dutt A, Banerjee TK, Hazra AM, et al
. An epidemiologic study of mild cognitive impairment in Kolkata, India. Neurology 2007;68:2019-26.
Kay DW, Beamish P, Roth M. Old age mental disorders in Newcastle upon Tyne. I: A study of prevalence. Br J Psychiatry 1964;110:146-58.
Graham JE, Rockwood K, Beattie BL, Eastwood R, Gauthier S, Tuokko H, et al
. Prevalence and severity of cognitive impairment with and without dementia in an elderly population. Lancet 1997;349:1793-6.
Gauthier S, Reisberg B, Zaudig M, Petersen RC, Ritchie K, Broich K, et al
.; International Psychogeriatric Association Expert Conference on mild cognitive impairment. Mild Cognitive Impairment. Lancet 2006;367:1262-70.
Rosenberg PB, Johnston D, Lyketsos CG. A clinical approach to mild cognitive impairment. Am J Psychiatry 2006;163:1884-90.
Reisberg B, Ferris SH, de Leon MJ, Crook T. Global Deterioration Scale (GDS). Psychopharmacol Bull 1988;24:661-3.
Flicker C, Ferris SH, Reisberg B. Mild cognitive impairment in the elderly: Predictors of dementia. Neurology 1991;41:1006-9.
Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, et al
. The diagnosis of mild cognitive impairment due to Alzheimer′s disease: Recommendations from the National Institute on Ageing-Alzheimer′s Association workgroups on diagnostic guidelines for Alzheimer′s Disease. Alzheimers Dement 2011;7:270-9.
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders: DSM-5. Washington D.C.: American Psychiatric Association; 2013. p. 605-6.
Peterson RC. Clinical practice. Mild cognitive impairment. N Engl J Med 2011;364:2227-34.
Taragano FE, Allegri RF, Lyketsos C. Mild behavioral impairment: A prodromal stage of dementia. Dement Neuropsychol 2008;2:265-60.
Roberts R, Knopman DS. Classification and epidemiology of MCI. Clin Geriatr Med 2013;29:753-72.
Apostolova LG, Cummings JL. Neuropsychiatric manifestations in mild cognitive impairment: A systematic review of the literature. Dement Geriatr Cogn Disord 2007;25:115-26.
Lyketsos CG, Lopez O, Jones B, Fitzpatrick AL, Breitner J, DeKosky S. Prevalence of neuropsychiatric symptoms in dementia and mild cognitive impairment: Results from the cardiovascular health study. JAMA 2002;288:1475-83.
Forsell Y, Palmer K, Fratiglioni L. Psychiatric symptoms/syndromes in elderly persons with mild cognitive impairment: Data from a cross-sectional study. Acta Neurol Scand Suppl 2003;179:25-8.
Feldman H, Scheltens P, Scarpini E, Hermann N, Mesenbrink P, Mancione L, et al
. Behavioral symptoms in mild cognitive impairment. Neurology 2004;62:1199-201.
Barnes DE, Alexopoulos GS, Lopez OL, Williamson JD, Yaffe K. Depressive symptoms, vascular disease, and mild cognitive impairment: Findings from the Cardiovascular Health Study. Arch Gen Psychiatry 2006;63:273-9.
Gabryelewicz T, Styczynska M, Luczywek E, Barczak A, Pfeffer A, Androsiuk W, et al
. The rate of conversion of mild cognitive impairment to dementia: Predictive role of depression. Int J Geriatr Psychiatry 2007;22:563-7.
Gabryelewicz T, Styczynska M, Pfeffer A, Wasiak B, Barczak A, Luczywek E, et al
. Prevalence of major and minor depression in elderly persons with mild cognitive impairment--MADRS factor analysis. Int J Geriatr Psychiatry 2004;19:1168-72.
Modrego PJ, Ferrández J. Depression in patients with mild cognitive impairment increases the risk of developing dementia of Alzheimer type: A prospective cohort study. Arch Neurol 2004;61:1290-3.
Geda YE, Knopman DS, Mrazek DA, Jicha GA, Smith GE, Negash S, et al
. Depression, apolipoprotein E genotype, and the incidence of mild cognitive impairment: A prospective cohort study. Arch Neurol 2006;63:435-40.
Winbald B, Portis N. Memantine in severe dementia: results of the 9M-Best Study (Benefit and efficacy in severely demented patients during treatment with memantine). Int J Ger Psych 1999;14:135-46.
Apostolova LG, Cummings JL. Psychiatric manifestation in dementia. Continuum Lifelong Learning Neurology 2007;13:165-79.
Kumar R, Jorm AF, Parslow RA, Sachdev PS. Depression in mild cognitive impairment in a community sample of individuals 60-64 years old. Int Psychogeriatr 2006;18:471-80.
Steinberg M, Corcoran C, Tschanz JT, Huber C, Welsh-Bohmer K, Norton MC, et al
. Risk factors for neuropsychiatric symptoms in dementia: The Cache County Study. Int J Geriatr Psychiatry 2006;21:824-30.
Geda YE, Smith GE, Knopman DS, Boeve BF, Tangalos EG, Ivnik RJ, et al
. De novo
genesis of neuropsychiatric symptoms in mild cognitive impairment (MCI). Int Psychogeriatr 2004;16:51-60.
Hwang TJ, Masterman DL, Ortiz F, Fairbanks LA, Cummings JL. Mild cognitive impairment is associated with characteristic neuropsychiatric symptoms. Alzheimer Dis Assoc Disord 2004;18:17-21.
Fischer P, Jungwirth S, Zehetmayer S, Weissgram S, Hoenigschnabl S, Gelpi E, et al
. Conversion from subtypes of mild cognitive impairment to Alzheimer dementia. Neurology 2007;68:288-91.
Bickel H, Mösch E, Seigerschmidt E, Siemen M, Forstl H. Prevalence and persistence of mild cognitive impairment among elderly patients in general hospitals. Dement Geriatr Cogn Disord 2006;21:242-50.
Busse A, Bischkopf J, Riedel-Heller SG, Angermeyer MC. Sub-classifications for mild cognitive impairment: Prevalence and predictive validity. Psychol Med 2003;33:1029-38.
Jak AJ, Corey-Bloom J, Bondi MW. Diagnostic characterization of MCI subtypes in a naturalistic sample. J Int Neuropscyhol Assoc 2007;13:4.
Zanetti M, Ballabio C, Abbate C, Cutaia C, Vergani C, Bergamaschini L. Mild cognitive impairment subtypes and vascular dementia in community-dwelling elderly people: A 3-year follow-up study. J Am Geriatr Soc 2006;54:580-6.
Jak AJ, Bangen KJ, Wierenga CE, Delano-Wood L, Corey-Bloom J, Bondi MW. Contributions of neuropsychology and neuroimaging to understanding clinical subtypes of mild cognitive impairment. Int Rev Neurobiol 2009;84:81-103.
Di Carlo A, Lamassa M, Baldereschi M, Inzitari M, Scafato E, Farchi G, et al
. CIND and MCI in the Italian elderly: Frequency, vascular risk factors, progression to dementia. Neurology 2007;68:1909-16.
Palmer K, Bäckman L, Winblad B, Fratiglioni L. Mild cognitive impairment in the general population: Occurrence and progression to Alzheimer disease. Am J Geriatr Psychiatry 2008;16:603-11.
Ravaglia G, Forti P, Maioli F, Martelli M, Servadei L, Brunetti N, et al
. Conversion of mild cognitive impairment to dementia: Predictive role of mild cognitive impairment subtypes and vascular risk factors. Dement Geriatr Cogn Disord 2006;21:51-8.
Yaffe K, Petersen RC, Lindquist K, Kramer J, Miller B. Subtype of mild cognitive impairment and progression to dementia and death. Dement Geriatr Cogn Disord 2006;22:312-9.
Petersen RC, Doody R, Kurz A, Mohs RC, Morris JC, Rabins PV, et al
. Current concepts in mild cognitive impairment. Arch neurol 2001;58:1985-92.
Pinto C, Subramanyam AA. Mild Cognitive Impairment: The Emerging Frontier in Elder Cognition. Dementia Decoded. New Delhi: Kontentworx Publishing Ltd; 2014. p. 18-37.
Jekel K, Damian M, Wattmo C, Hausner L, Bullock R, Connelly PJ, et al
. Mild cognitive impairment and deficits in instrumental activities of daily living: A systematic review. Alzheimer′s Res Ther 2015;7:17.
Lenga KM, Levine DA. The diagnosis and management of mild cognitive impairment: A clinical review. JAMA 2014;312:2551-61.
McCarten JR. Clinical evaluation of early cognitive symptoms. Clin Geriatr Med 2013;29:791-807.
Yesavage JA, Brink TL, Rose TL, Lum O, Huang V, Adey M, et al
. Development and validation of a geriatric depression screening scale: A preliminary report. J Psychiatr Res 1983;17:37-49.
Clarfield AM. The decreasing prevalence of reversible dementias: An updated meta-analysis. Arch Intern Med 2003;163:2219-29.
Mattsson N, Zetterberg H, Hansson O, Andreasen N, Parnetti L, Jonsson M, et al
. CSF biomarkers and incipient Alzheimer disease in patients with mild cognitive impairment. JAMA 2009;302:385-93.
Petersen RC, Trojanowski JQ. Use of Alzheimer disease biomarkers: Potentially yes for clinical trials but not yet for clinical practice. JAMA 2009;302:436-7.
Jack CJ, Wiste HJ, Vemuri P, Weigand SD, Senjem ML, Zeng G, et al
.; Alzheimer′s Disease Neuroimaging Initiative. Brain beta-amyloid measures and magnetic resonance imaging atrophy both predict time-to-progression from mild cognitive impairment to Alzheimer′s disease. Brain 2010;133:3336-48.
Jack CR, Lowe VJ, Weigand SD, Wiste HJ, Senjem ML, Knopman DS, et al
.; Alzheimer′s Disease Neuroimaging Initiative. Serial PIB and MRI in normal, mild cognitive impairment and Alzheimer′s disease: Implications for sequence of pathological events in Alzheimer′s disease. Brain 2009;132:1355-65.
Jack CR Jr, Barkhof F, Bernstein MA, Cantillon M, Cole PE, Decarli C, et al
. Steps to standardization and validation of hippocampal volumetry as a biomarker in clinical trials and diagnostic criterion for Alzheimer′s disease. Alzheimers Dement 2011;7:474-85.e4.
Ries ML, Carlsson CM, Rowley HA, Sager MA, Gleason CE, Asthana S, et al
. Magnetic resonance imaging characterization of brain structure and function in mild cognitive impairment. J Am Geriatr Soc 2008;56: 920-34.
Institute for Clinical and Economic Review. Diagnostic Tests for Alzheimer′s Disease: Defining Evidence Standards for Insurance Coverage of Diagnostic Tests for Alzheimer′s Disease. 2012. Available from: http://www.icer-review.org/alzheimers/
. [Last accessed on 2015 Feb 8].
Small GW, Bookheimer SY, Thompson PM, Cole GM, Huang SC, Keep V, et al
. Current and future uses of neuroimaging for cognitively impaired patients. Lancet Neurol 2008;7:161-72.
Clark CM, Schneider JA, Bedell BJ, Beach TG, Bilker WB, Mintun MA, et al
.; AV45-A07 Study Group. Use of florbetapir-PET for imaging beta-amyloid pathology. JAMA 2011;305:275-83.
Johnson KA, Sperling RA, Gidicsin CM, Carmasin JS, Maye JE, Coleman RE, et al
.; AV45-A11 Study Group. Florbetapir (F18-AV-45) PET to assess amyloid burden in Alzheimer′s disease dementia, mild cognitive impairment, and normal aging. Alzheimers Dement 2013;9 (Suppl):S72-83.
Pinto C, Subramanyam AA. Mild cognitive impairment: The dilemma. Indian J Psychiatry 2009;51(Suppl 1):S44-51.
Kapur S, Sharad S, Kapoor M, Bala K. ApoE genotypes: Risk factor for Alzheimer′s disease. J Indian Acad Clin Med 2006;7:118-22.
Teng EL, Chui HC. The modified Mini-Mental State (3MS) examination. Can J Psychiatry 1987;48:314-8.
Nasreddine ZS, Philips NA, Bédirian V, Charbonneau S, Whitehead V, Collin I, et al
. The Montreal Cognitive Assessment, MoCA: A brief screening tool for mild cognitive impairment. J Am Geriatr Soc 2005;53:695-9.
Lin JS, O′Connor E, Rossom RC, Perdue LA, Burda BU, Thompson M, et al
. Screening for cognitive impairment in older adults: A evidence update for the U.S. Preventive Services Task Force. Ann Intern Med 2013;159:601-12.
Roalf DR, Moberg PJ, Xie SX, Wolk DA, Moelter ST, Arnold SE. Comparative accuracies of two common screening instruments for classification of Alzheimer′s disease, mild cognitive impairment, and healthy aging. Alzheimers Dement 2013;9:529-37.
Calabrese P, Kalbe E, Kessler J, Fischer L, Smith B, Passmore P, et al
. A neuropsychological screening test to diagnose mild cognitive impairment and early dementia: DemTect. Psychogeriatria Polska 2004;1:205-14.
Cummings JL, Mega M, Gray K, Rosenberg-Thompson S, Carusi DA, Gornbein J. The neuropsychiatric inventory: Comprehensive assessment of psychopathology in dementia. Neurology 1994;44: 2308-14.
Jorm AF, Jacomb PA. The informant questionnaire on cognitive decline in the elderly (IQCODE): Socio-demographic correlates, reliability, validity and some norms. Psychol Med 1989;19:1015-22.
Petersen RC, Thomas RG, Grundman M, Bennett D, Doody R, Ferris S, et al
.; Alzheimer′s Disease Cooperative Study Group. Vitamin E and donepezil for the treatment of mild cognitive impairment. N Engl J Med 2005;352:2379-88.
Doody RS, Ferris SH, Salloway S, Sun Y, Goldman R, Watkins WE, et al
. Donepezil treatment of patients with MCI: A 48-week randomized, placebo-controlled trial. Neurology 2009;72:1555-61.
Gauthier S. Pharmacotherapy of mild cognitive impairment. Dialogues Clin Neurosci 2004;6:391-5.
Feldman HH, Ferris S, Winblad B, Sfikas N, Mancione L, He Y, et al
. Effect of rivastigmine on delay to diagnosis of Alzheimer′s disease from mild cognitive impairment: The InDDEx study. Lancet Neurol 2007;6:501-12.
Winblad B, Gauthier S, Scinto L, Feldman H, Wilcock GK, Truyen L, et al
. Safety and efficacy of galantamine in subjects with mild cognitive impairment. Neurology 2008;70:2024-35.
Nagaraja D, Jayashree S. Randomized study of dopamine receptor agonist piribedil in the treatment of mild cognitive impairment. Am J Psychiatry 2001;158:1517-9.
Newhouse P, Kellar K, Aisen P, White H, Wesnes K, Coderre E, et al
. Nicotine treatment of mild cognitive impairment: A 6-month double-blind pilot clinical trial. Neurology 2012;78:91-101.
Thal LJ, Ferris SH, Kirby L, Block GA, Lines CR, Yuen E, et al
. A randomized, double-blind, study of rofecoxib in patients with mild cognitive impairment. Neuropsychopharmacology 2005;30:1204-15.
Gomez-Isla T, Blesa R, Boada M, Clarimon J, Del Ser T, Domenech G, et al
.; TRIMCI Study Group. A randomized, double-blind, placebo controlled-trial of triflusal in mild cognitive impairment: The TRIMCI study. Alzheimer Dis Assoc Disord 2008;22:21-9.
Birks J, Grimley Evans J. Ginkgo biloba for cognitive impairment and dementia. Cochrane Database Syst Rev 2009;CD003120.
Snitz BE, O′Meara ES, Carlson MC, Arnold AM, Ives DG, Rapp SR, et al
. Ginkgo biloba for preventing cognitive decline in older adults: A randomized trial. JAMA 2009;302:2663-70.
Zhao MX, Dong ZH, Yu ZH, Xiao SY, Li YM. Effects of Ginkgo biloba extract in improving episodic memory of patients with mild cognitive impairment: A randomized controlled trial. Zhong Xi Yi Jie He Xue Bao 2012;10:628-34.
van Uffelen JG, Chinapaw MJ, van Mechelen W, Hopman-Rock M. Walking or vitamin B for cognition in older adults with mild cognitive impairment? A randomised controlled trial. Br J Sports Med 2008;42:344-51.
de Jager CA, Oulhaj A, Jacoby R, Refsum H, Smith AD. Cognitive and clinical outcomes of homocysteine-lowering B-vitamin treatment in mild cognitive impairment: A randomized controlled trial. Int J Geriatr Psychiatry 2012;27:592-600.
Chiu CC, Su KP, Cheng TC, Liu HC, Chang CJ, Dewey ME, et al
. The effects of omega-3 fatty acids monotherapy in Alzheimer′s disease and mild cognitive impairment: A preliminary randomized double-blind placebo-controlled study. Prog Neuropsychopharmacol Biol Psychiatry 2008;32:1538-44.
Sinn N, Milte CM, Street SJ, Buckley JD, Coates AM, Petkov J, et al
. Effects of n-3 fatty acids, EPA v. DHA, on depressive symptoms, quality of life, memory and executive function in older adults with mild cognitive impairment: A 6-month randomised controlled trial. Br J Nutr 2012;107:1682-93.
Oddo S, Billings L, Kesslak JP, Cribbs DH, LaFerla FM. A beta immunotherapy leads to early, but not late, hyperphosphorylated tau aggregates via the proteasome. Neurology 2004;43:321-32.
Waring SC, Rocca WA, Peterson RC, O′Brien PC, Tanglos EG, Kokmen E. Postmenopausal estrogen replacement therapy and risk of AD: A population-based study. Neurology 1999;52:965-70.
Shumaker SA, Legault C, Kuller L, Rapp SR, Thal L, Lane DS, et al
.; Women′s Health Initiative Memory Study. Conjugated equine estrogen and incidence of probable dementia and mild cognitive impairment in postmenopausal women: Women′s health initiative memory study. JAMA 2004;291:2947-58.
Cooper C, Li R, Lyketsos C, Livingston G. Treatment for mild cognitive impairment: Systematic review. Br J Psychiatry 2013;203:255-64.
Lourida I, Soni M, Thompson-Coon J, Purandare N, Lang IA, Ukoumunne OC, et al
. Mediterranean diet, cognitive function, and dementia: A systematic review. Epidemiology 2013;24:479-89.
Lim GP, Chu T, Yang F, Beech W, Frautschy SA, Cole GM. The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse. J Neurosci 2001;21:8370-7.
Baker LD, Frank LL, Foster-Schubert K, Green PS, Wilkinson CW, McTiernan A, et al
. Effects of aerobic exercise on mild cognitive impairment: A controlled trial. Arch Neurol 2010;67:71-9.
Scherder EJ, Van Paasschen J, Deijen JB, Van Der Knokke S, Orlebeke JF, Burgers I, et al
. Physical activity and executive functions in the elderly with mild cognitive impairment. Aging Ment Health 2005;9:272-80.
Suzuki T, Shimada H, Makizako H, Doi T, Yoshida D, Tsutsumimoto K, et al
. Effects of multicomponent exercise on cognitive function in older adults with amnestic mild cognitive impairment: A randomized controlled trial. BMC Neurol 2012;12:128.
Jean L, Bergeron ME, Thivierge S, Simard M. Cognitive intervention programs for individuals with mild cognitive impairment: Systematic review of the literature. Am J Geriatr Psychiatry 2010;18:281-96.
Verghese J, LeValley A, Derby C, Kuslansky G, Katz M, Hall C, et al
. Leisure activities and the risk of amnestic mild cognitive impairment in the elderly. Neurology 2006;66:821-7.
Wilson RS, Mendes De Leon CF, Barnes LL, Schneider JA, Bienias JL, Evans DA, et al
. Participation in cognitively stimulating activities and risk of incident Alzheimer disease. JAMA 2002;287: 742-8.
Buschert VC, Friese U, Teipel SJ, Schneider P, Merensky W, Rujescu D, et al
. Effects of a newly developed cognitive intervention in amnestic mild cognitive impairment and mild Alzheimer′s disease: A pilot study. J Alzheimers Dis 2011;25:679-94.
[Figure 1], [Figure 2]