**4. Clinical diagnosis of mild cognitive impairment**

**Study Country Years N Age Prevalence** Purser et al. US 1981–1991 3673 74 24.7 Lopez et al. US 1991–1999 3608 ≥65 18.8 Solfrizzi et al. Italy 1992–1995 4521 73.4 3.2 Ravaglia et al. Italy 1994–1996 34 ≥ 65 7.7 Pioggiosi et al. Italy 1999–2004 ≥ 90 32.4 Huang et al. China 2005 920 ≥ 55 3.0 Choi et al. Korea 2005–2006 1215 ≥ 65 32.9 Choi et al. Korea 2005–2006 1215 ≥ 65 32.9 Artero et al. France 2008 6892 ≥ 65 42.0 Manly et al. US 2008 1313 ≥ 65 28.3

**Study Country Years N Age Incidence** Larrieu et al. France 2002 1265 ≥ 65 9.9/1000 Busse et al. Germany 2003 684 ≥ 75 8.5/1000 Trevo et al. Finland 2004 550 60–76 25.9/1000 Trevo et al. Finland 2004 550 60–76 25.9/1000 Solfrizzi et al. Italy 2004 2963 ≥75 56.5/1000 Palmer et al. Sweden 2004 379 ≥75 34–168/1000 Carraciolo et al. Sweden 2008 1070 ≥75 13.7/1000 a MCI

Manly et al. US 2008 1800 ≥65 2.3–5.1% Luck et al. Germany 2010 2331 ≥65 18.8

and education [25, 26]. According to Einstein aging study, prevalence of MCI in the same geographical zone is higher in Negroid population compared with Caucasians. According to Mayo clinic study of aging, MCI prevalence was 16%, among them 11.1% was amnestic MCI and 4.9% non-amnestic MCI [5]. Single domain amnestic MCI was the most frequent type, based on Mayo clinic study of aging. MCI prevalence is increasing with age, is more frequent in males and *APOE e3e4* or *e4e4* allele carriers. The estimated prevalence of mild cognitive impairment in non-demented cohort of 65 years old or older in the Cardiovascular Health

Recently an international consortium—Cohort Studies of Memory in an International Consortium (COSMIC) harmonized data from 11 studies from USA, Europe, Asia and Australia and applied

**Table 2.** Selected epidemiological studies in MCI.

96 Alzheimer's Disease - The 21st Century Challenge

Study was 19% and it increased with age [27].

**Table 3.** Selected epidemiological studies in MCI.

All patients with suspected MCI should undergo detailed physical, neurological, cognitive, psychological and functional status evaluation. It is important to identify potentially reversible causes of MCI, such as depression, thyroid diseases, vitamin B12 and foliate deficiency. Special attention should be given to the prescription history. Some medications, including sedatives, narcotic pain medications, anticonvulsants or anticholinergics have potential to affect cognitive function. An accurate *neurological* assessment is essential to determine potential etiology of cognitive impairment [13, 30].

For the accurate diagnosis it is highly important to interview patient's family member or close acquaintance, which is familiar with their functioning in daily activities, requiring planning, organization and communication skills. Ideally, an informant should know the patient for years to adequately recognize deterioration from a baseline of functioning. Information received from different sources should be integrated properly [13].

Clinician should be aware, that cognitive impairment is often accompanied by anxiety, which interferes with cognitive performance; therefore, interview should be held in relaxed and conversational manner.

Examiner should inquire about patient's ability to handle technical devices. For example, patients with MCI can drive cars normally, but they might experience episodes of disorientation when they are driving in an unknown environment, or have a tendency to make wrong turns. Patients with MCI can have particular difficulties while planning a trip or social activities and they might need more time to perform complex activities that require planning and organization [13].

Information should be collected about patient's ability to manage financial operations. Individuals with MCI may require more time to perform monetary transaction, or periodically make careless mistakes.

Cognitive assessment should be performed at the end of the interview, preferably without an accompanying person. Objective demonstration of cognitive dysfunction is obligatory to diagnose MCI. Therefore, examiner should conduct one or more cognitive batteries. Cognitive assessment should incorporate memory, attention, executive function, language and visuospatial function evaluation in order to precisely differentiate MCI subtypes. There is no consensus on the type and number of neuropsychological tests that should be used to assess individuals with MCI. Various cut-off points are used to define abnormal cognitive performance (1.0, 1.5 and 2.0 SD). Commonly a deterioration cut-off point of 1.5 SD is adopted. There is no single recommended "gold standard" battery, but rather a set of valid cognitive tests [31]. Commonly used tests are represented in the **Table 4**.

Cognitive screening tests are helpful in clinical practice as a first step to evaluate patients with MCI, followed by formal neuropsychological assessment in selected cases. Andrew J Larner has reviewed data from several diagnostic test accuracy studies [32]. Summarized data on diagnostic validity are shown in the **Table 5**.

> other neurodegenerative disease can't be fully excluded. Positive amyloid PET scan results in patients with MCI are associated with an increased risk for developing AD dementia. It is important to discuss the risk for cognitive and functional decline and the need for additional monitoring and planning in these patients. Volumetric brain imaging and detailed neuropsychological examination in combination with PET scan results help clinician to determine

**Cognitive screening tests Cut-off Sensitivity Specificity** Mini Mental State Examination (MMSE) ≤22/30 1.00 0.28 Mini Mental Parkinson (MMP) ≤20/32 0.92 0.61 Montreal Cognitive Assessment (MoCA) ≥26/30 0.93 0.60 Test your memory (TYM) ≤42/50 0.79 0.54 Mini-Addenbrooke's cognitive examination (M-ACE) ≤25/30 1.00 0.43 Mini-Addenbrooke's cognitive examination (M-ACE) ≤21/30 0.77 0.82 Six item cognitive impairment test (6CIT) ≤9/28 0.66 0.70

Mild Cognitive Impairment

99

http://dx.doi.org/10.5772/intechopen.75509

Early radiological studies in MCI were focused on the assessment of the entorhinal cortex (ERC) and hippocampus. Volume of the ERC and the hippocampus in MCI patients tends to be smaller and is either intermediate between normal controls and patients with AD, or similar to AD. Some studies demonstrated higher sensitivity of the entorhinal cortex compared with hippocampal volume. The annualized rate of the hippocampal and entorhinal cortex atrophy has been shown to be more prominent in the MCI patients relative to normal

Apart from medial temporal lobe atrophy, decrease in gray matter volume was reported in the lateral temporal, parietal, and frontal lobes, amygdala, fusiform gyrus, cingulate, parietal and occipital lobes and insula. Several studies have documented that the whole brain volume

Apostolova et al. followed a cohort of MCI subjects clinically and neuropsychologically for 3 years. They found that smaller hippocampal volumes predict conversion of MCI to AD and patients with MCI who convert to AD have greater atrophy in the CA1 and subiculum

Several studies reported significant alterations on diffusion weighted MR imaging (DWI) measures in the hippocampus, thalamus, posterior cingulum (PC) and several regions in posterior white matter in MCI patients. Kantarci et al. found that on the follow up, elevated hippocampal diffusivity predicts MCI progression to AD better than hippocampal

MCI prognosis and outcome [33].

**Table 5.** Selected screening tools in MCI [32].

regions of the hippocampus [35].

controls [5, 34].

volumetry [5, 36].

**5. Neuroimaging of mild cognitive impairment**

loss rate is associated with objective cognitive decline over time.

In 2016, a workgroup meeting was held at the Institute of Memory Impairments and Neurological Disorders of the University of California, Irvine, USA with the aim to provide recommendations for the diagnosis of mild cognitive impairments. According to the recommendations, workup with standard laboratory tests, neuropsychological assessment, and structural brain imaging is required to diagnose MCI. Assessment of cognitive performance with specific cognitive tests should be considered by the clinicians when delivering the MCI diagnosis. patients should be provided with a written summary of the diagnosis and treatment recommendations that include referral to appropriate supportive services and other local resources; Amyloid imaging may allow a physician to give the patient additional information about potential causes of MCI, improve prognostic information, and reduce the ambiguity and uncertainty associated with the diagnosis. Communication of negative scan results should include that patients with MCI who have a negative scan results remain at risk for dementia and that negative scans, while informative, do not indicate a specific diagnosis or unambiguously signify the absence of disease. Negative amyloid imaging result reduces the possibility that MCI is due to Alzheimer's disease. It also reduces the risk of MCI progression to dementia. Although the likelihood of underlying Alzheimer's disease or any


**Table 4.** Selected cognitive instruments.


**Table 5.** Selected screening tools in MCI [32].

**Cognitive domains Tests**

**Table 4.** Selected cognitive instruments.

Memory and learning Rey Auditory Verbal Learning Test

Language Semantic and phonemic fluency

Praxis The Rey-Osterreith complex figure

Executive function Trial-Making test

Commonly used tests are represented in the **Table 4**.

diagnostic validity are shown in the **Table 5**.

98 Alzheimer's Disease - The 21st Century Challenge

Logical Memory Subset of WSM-R

diagnose MCI. Therefore, examiner should conduct one or more cognitive batteries. Cognitive assessment should incorporate memory, attention, executive function, language and visuospatial function evaluation in order to precisely differentiate MCI subtypes. There is no consensus on the type and number of neuropsychological tests that should be used to assess individuals with MCI. Various cut-off points are used to define abnormal cognitive performance (1.0, 1.5 and 2.0 SD). Commonly a deterioration cut-off point of 1.5 SD is adopted. There is no single recommended "gold standard" battery, but rather a set of valid cognitive tests [31].

Cognitive screening tests are helpful in clinical practice as a first step to evaluate patients with MCI, followed by formal neuropsychological assessment in selected cases. Andrew J Larner has reviewed data from several diagnostic test accuracy studies [32]. Summarized data on

In 2016, a workgroup meeting was held at the Institute of Memory Impairments and Neurological Disorders of the University of California, Irvine, USA with the aim to provide recommendations for the diagnosis of mild cognitive impairments. According to the recommendations, workup with standard laboratory tests, neuropsychological assessment, and structural brain imaging is required to diagnose MCI. Assessment of cognitive performance with specific cognitive tests should be considered by the clinicians when delivering the MCI diagnosis. patients should be provided with a written summary of the diagnosis and treatment recommendations that include referral to appropriate supportive services and other local resources; Amyloid imaging may allow a physician to give the patient additional information about potential causes of MCI, improve prognostic information, and reduce the ambiguity and uncertainty associated with the diagnosis. Communication of negative scan results should include that patients with MCI who have a negative scan results remain at risk for dementia and that negative scans, while informative, do not indicate a specific diagnosis or unambiguously signify the absence of disease. Negative amyloid imaging result reduces the possibility that MCI is due to Alzheimer's disease. It also reduces the risk of MCI progression to dementia. Although the likelihood of underlying Alzheimer's disease or any

a pair of scissors; and brushing teeth)

The New York University Paragraph Recall Test Buschke Cued Recall Selective Reminding Test

Mimicking the use of objects and Symbol gestures of communication (e.g. inserting a sheet of paper into an envelope; the correct one hand movements designed to wave "goodbye"; cutting a sheet of paper with other neurodegenerative disease can't be fully excluded. Positive amyloid PET scan results in patients with MCI are associated with an increased risk for developing AD dementia. It is important to discuss the risk for cognitive and functional decline and the need for additional monitoring and planning in these patients. Volumetric brain imaging and detailed neuropsychological examination in combination with PET scan results help clinician to determine MCI prognosis and outcome [33].
