**2. Novel information on mild cognitive impairment**

The estimated prevalence of dementia varies from 4.7% in Central Europe to 8.7% in North Africa/Middle East, and 6.4% at North America. Currently, the number of patients with

Apart from some neuropsychological test that we will describe at the end of this chapter, there are some radiological investigations that can help in increasing the certainty of dementia diagnosis. A positron emission tomography (PET) scan and a special form of MRI can more

dementia is projected to increase to 131.5 million by 2050 [4].

192 Cognitive Disorders

**Figure 2.** Alois Alzheimer 1864–1915 from Bavaria.

**Figure 1.** Pythagoras of Samos (c 570 BC–c 495 BC).

The concept of MCI is described in the nineteenth century when loss of recent memories was documented as the first sign of dementia [5]. Some degree of cognitive disturbance was thought to be part of normal aging, and then various names were used to define it such as (1) age-associated memory impairment, (2) age-associated cognitive decline, and (3) benign senescent forgetfulness [6, 7].

In 1980, with the arrival of new neuropsychological test to measure subjective and objective cognition, an intermediate phase between normal aging and dementia became more widely accepted [8]. At that time, it was defined as the presence of subtle deficits in cognition with some impairment in executive function. Following an expert international conference, all previous definitions and the way of diagnosis and management of MCI were better performed [9, 10].

Historically, the term MCI has been in the literature for almost four decades, with the initial use coming from investigators at the New York University who referred to stage 3 on the Global Deterioration Scale as being MCI [11].

In 1999, some authors at the Mayo Clinic reported subjects in their community aging study presenting a memory problem beyond what was expected for age and who demonstrated a MCI (by neuropsychological test) yet did not meet criteria for dementia [12].

The prevalence of MCI is estimated around 3–19% in the elderly people. However, in a community setting, 44% of people with MCI returned to normal after 1 year [13].

Conversion rates to dementia vary according to the setting, with 11–33% conversion over 2 years [14].

In 2015, other authors demonstrate that females with MCI have greater longitudinal rates of cognitive and functional progression than males [15].

Plasma α-synuclein level was not associated with the presence or type of cognitive impairment, but the *ApoEe4* allele carrier status was significantly associated with executive dysfunction in PD, and both depression and diabetes mellitus are well known as risk factors for

Updated Information on Some Cognitive Disorders http://dx.doi.org/10.5772/intechopen.81826 195

The biomarkers of cognitive disorder in patients with diabetes can be grouped according to

In diabetic patients with cognitive disorder such as specific factors related to associated depression, inflammation, poor glucose metabolism, insulin resistance, micro/macrovascular complications, neurotrophic molecules, adipokines, and Tau protein presented remarkable changes. In diabetic patients, some neuroimaging studies provide more information on functional, structural, and metabolic changes during the cognitive decline progression [23].

Publications from several authors suggest that greater degrees of atherosclerosis of the carotid

In another study, the authors demonstrated that alterations in the intima media thickness (IMT) of the common carotid artery and the number of plaque (confirmed by ultrasound) are associated with an increased risk of MCI and dementia. In MCI, the IMT was more frequently observed, whereas in patients with dementia, the most common finding was increased numbers of carotid plaques. These researchers suggest that their findings may aid in identifying elderly people at higher risk for the progression of MCI when morphological impairment of cerebrovascular structures has been identified. In other words, the presence of atherosclerotic changes and modifications in blood factors such as p-selectin glycoprotein ligand, platelet-leukocyte aggregates, and platelet-monocyte aggregation can be used to predict MCI and dementia [26].

Some authors introduced a novel methodology to get an accurate classification of patients with AD or MCI from cognitively unimpaired (CU) people for clinical diagnosis and adequate intervention, respectively. These researchers focused on differentiating AD or MCI from CU based on the multifeature kernel supervised within-class-similar discriminative dictionary learning algorithm confirmed that methodology had superior performance in face recognition. They also included structural MRI, fluorodeoxyglucose PET, and florbetapir-PET data from the Alzheimer's Disease Neuroimaging Initiative database for classification of AD ver-

Tai Chi is a type of mind-body exercise that combines physical and cognitive-stimulating activity that provides good benefits on general cognition and instrumental activities of daily

Mueller et al. [29] have documented spoken language as a noninvasive, multidimensional, and informative biological sample for the early diagnosis of AD, primary progressive aphasia, and other cognitive disorders. They also confirmed that connected language analysis is one of

artery are associated with the progression from MCI to dementia [24, 25].

sus CU, MCI versus CU, as well as AD versus MCI, successfully [27].

living in patients with MCI [28].

cognitive impairment [5].

the following three aspects:

**3.** Genetic types

**1.** Functional or metabolic changes by neuroimaging tools

**2.** Serum molecules or relevant complications

Gauthier et al. [9] also defined MCI as a syndrome of cognitive decline, which is greater than would be expected for an individual's age and level of education but does not impede the individual's ability to perform daily activities of normal life.

Most of our patients presenting MCI had behavioral changes, depression, anxiety, and apathy, and most of them were full aware on their condition and personal frustrations, and their daily skills and activities necessary for independent daily living within the home and their communities such as dressing, grooming, ambulating, feeding, bathing, continence, transferring, and toileting were not affected. However, some authors have report that MCI patients may have difficulties in performing instrumental activities such as cooking, shopping, cleaning, laundry, driving, self-medication, and making call telephonically, among others, comparing to age-matched normal cognitively people [16, 17].

The Mayo Clinic criteria previously cited have been focused on a memory disorder and were delivered to clarify the earliest symptomatic stages of AD. However, soon later, it was well established that not all intermittent cognitive states were due to incipient AD and not all patients have just a memory impairment. To solve this dilemma, the Key Symposium was held in Stockholm, Sweden, in 2003, and in 2004, broad scope and other goal were delivered [18, 19].

Including a broad classification scheme beyond memory, the recognition of MCI could result from multiple causes and not just AD.

The Key Symposium characterization has been very useful in our practice and allowed us to distinguish the amnestic form of MCI from the nonamnestic ones, among other benefits.

Recently, Su et al. demonstrated that CA1 atrophy and subiculum thinning is significantly greater in AD and MCI patients than their control group, but similar between MCI and AD, as have been reported in previous investigations. It is proved that CA1 and subiculum changes at the hippocampus occur early on these pathologies [20].

Numerous international studies have been completed involving several thousand subjects, and these studies tend to estimate the overall prevalence of MCI in the range of 12–18% in persons above the age of 60 years. Lifestyle modifications and other nonpharmacologic therapies have been investigated by Petersen who found that aerobic exercise may be effective at reducing the rate of progression from MCI to dementia. Criticism has been raised regarding the boundaries of the condition of MCI with respect to differentiating it from changes of cognitive aging and also differentiating it from dementia [21].

Biomarkers provide a path toward the early detection of people at high risk for cognitive disorder and thereby its early prevention and/or management. *Nevertheless, these advances, whether for PD or AD, came with some risks and limitations that should to reconcile the potentially negative aspects of early diagnosis, the risk-benefit ratios of various treatments, and accessibility of biomarker testing and clinical resources, counseling, and ways of therapies once available* [22].

MCI is well represented in our series PD, and in our opinion, Parkinson's disease-cognitive rating scale seems to be more selective in detecting MCI and PDD than Montreal Cognitive Assessment.

Plasma α-synuclein level was not associated with the presence or type of cognitive impairment, but the *ApoEe4* allele carrier status was significantly associated with executive dysfunction in PD, and both depression and diabetes mellitus are well known as risk factors for cognitive impairment [5].

The biomarkers of cognitive disorder in patients with diabetes can be grouped according to the following three aspects:


In 2015, other authors demonstrate that females with MCI have greater longitudinal rates of

Gauthier et al. [9] also defined MCI as a syndrome of cognitive decline, which is greater than would be expected for an individual's age and level of education but does not impede the

Most of our patients presenting MCI had behavioral changes, depression, anxiety, and apathy, and most of them were full aware on their condition and personal frustrations, and their daily skills and activities necessary for independent daily living within the home and their communities such as dressing, grooming, ambulating, feeding, bathing, continence, transferring, and toileting were not affected. However, some authors have report that MCI patients may have difficulties in performing instrumental activities such as cooking, shopping, cleaning, laundry, driving, self-medication, and making call telephonically, among others, comparing

The Mayo Clinic criteria previously cited have been focused on a memory disorder and were delivered to clarify the earliest symptomatic stages of AD. However, soon later, it was well established that not all intermittent cognitive states were due to incipient AD and not all patients have just a memory impairment. To solve this dilemma, the Key Symposium was held in Stockholm, Sweden, in 2003, and in 2004, broad scope and other goal were delivered [18, 19]. Including a broad classification scheme beyond memory, the recognition of MCI could result

The Key Symposium characterization has been very useful in our practice and allowed us to distinguish the amnestic form of MCI from the nonamnestic ones, among other benefits.

Recently, Su et al. demonstrated that CA1 atrophy and subiculum thinning is significantly greater in AD and MCI patients than their control group, but similar between MCI and AD, as have been reported in previous investigations. It is proved that CA1 and subiculum changes

Numerous international studies have been completed involving several thousand subjects, and these studies tend to estimate the overall prevalence of MCI in the range of 12–18% in persons above the age of 60 years. Lifestyle modifications and other nonpharmacologic therapies have been investigated by Petersen who found that aerobic exercise may be effective at reducing the rate of progression from MCI to dementia. Criticism has been raised regarding the boundaries of the condition of MCI with respect to differentiating it from changes of

Biomarkers provide a path toward the early detection of people at high risk for cognitive disorder and thereby its early prevention and/or management. *Nevertheless, these advances, whether for PD or AD, came with some risks and limitations that should to reconcile the potentially negative aspects of early diagnosis, the risk-benefit ratios of various treatments, and accessibility of* 

MCI is well represented in our series PD, and in our opinion, Parkinson's disease-cognitive rating scale seems to be more selective in detecting MCI and PDD than Montreal Cognitive

*biomarker testing and clinical resources, counseling, and ways of therapies once available* [22].

cognitive and functional progression than males [15].

194 Cognitive Disorders

to age-matched normal cognitively people [16, 17].

at the hippocampus occur early on these pathologies [20].

cognitive aging and also differentiating it from dementia [21].

from multiple causes and not just AD.

Assessment.

individual's ability to perform daily activities of normal life.

In diabetic patients with cognitive disorder such as specific factors related to associated depression, inflammation, poor glucose metabolism, insulin resistance, micro/macrovascular complications, neurotrophic molecules, adipokines, and Tau protein presented remarkable changes. In diabetic patients, some neuroimaging studies provide more information on functional, structural, and metabolic changes during the cognitive decline progression [23].

Publications from several authors suggest that greater degrees of atherosclerosis of the carotid artery are associated with the progression from MCI to dementia [24, 25].

In another study, the authors demonstrated that alterations in the intima media thickness (IMT) of the common carotid artery and the number of plaque (confirmed by ultrasound) are associated with an increased risk of MCI and dementia. In MCI, the IMT was more frequently observed, whereas in patients with dementia, the most common finding was increased numbers of carotid plaques. These researchers suggest that their findings may aid in identifying elderly people at higher risk for the progression of MCI when morphological impairment of cerebrovascular structures has been identified. In other words, the presence of atherosclerotic changes and modifications in blood factors such as p-selectin glycoprotein ligand, platelet-leukocyte aggregates, and platelet-monocyte aggregation can be used to predict MCI and dementia [26].

Some authors introduced a novel methodology to get an accurate classification of patients with AD or MCI from cognitively unimpaired (CU) people for clinical diagnosis and adequate intervention, respectively. These researchers focused on differentiating AD or MCI from CU based on the multifeature kernel supervised within-class-similar discriminative dictionary learning algorithm confirmed that methodology had superior performance in face recognition. They also included structural MRI, fluorodeoxyglucose PET, and florbetapir-PET data from the Alzheimer's Disease Neuroimaging Initiative database for classification of AD versus CU, MCI versus CU, as well as AD versus MCI, successfully [27].

Tai Chi is a type of mind-body exercise that combines physical and cognitive-stimulating activity that provides good benefits on general cognition and instrumental activities of daily living in patients with MCI [28].

Mueller et al. [29] have documented spoken language as a noninvasive, multidimensional, and informative biological sample for the early diagnosis of AD, primary progressive aphasia, and other cognitive disorders. They also confirmed that connected language analysis is one of the most promising state-of-the-art diagnostic tools for MCI. Their results provide evidence that features of connected language are associated with very early, subclinical memory loss in late-middle age. This study helped toward a better comprehension of early language dysfunction associated with a cognitive decline.

skills impairment, including dysfunction of the autonomic nervous system and desynchronization of circadian rhythms. According to Picard et al. [41], early-onset Alzheimer's disease (EOAD) and behavioral variant frontotemporal dementia (bvFTD) are the most common types of presenile neurodegenerative dementia (i.e., age at onset around 65 years old). Compared to the typical episodic memory dysfunction of late-onset AD, EOAD patients show a constellation of multidomain deficits at presentation, which can include not only memory, but also language, executive, visuospatial abnormalities, and behavioral disturbances like bvFTD cases [42].

Updated Information on Some Cognitive Disorders http://dx.doi.org/10.5772/intechopen.81826 197

Volumetric and cortical thickness studies have shown a prevalent involvement of posterior parietal regions in EOAD and of anterior fronto-insular-striatal areas in bvFTD [43, 44]. Some studies reported a greater white matter (WM) involvement in bvFTD compared to EOAD [45–50]. Filippi et al. and Zhou et al. [51, 52] found a divergent pattern of altered functional connectivity in the default mode network (DMN) and salience network comparing EOAD

Some specialists from Alzheimer's Association consider that AD is the underlying cause of all types of dementia, and it is characterized by β-amyloid plaques, neurofibrillary tangles, and neurodegeneration in areas of the brain associated with cognition, such as the cortex and hippocampus. AD is also characterized by disturbances of the daily activities involving memory,

The Framingham Study, which followed up 2611 cognitively intact participants (1550 women and 1061 men) on many for 20 years, indicated that risk factor for AD in 65-year-old woman was almost twice that of men [1] because it seems to be that life expectancy is longer in ladies. Other epidemiologic investigations also confirmed that neurodegeneration develops more rapidly in females who are often diagnosed earlier than males [54, 55]. And they are often diagnosed earlier in the course of illness than men. In many cases, inflammation is another risk factor for AD that dysregulated neuroinflammatory reaction is another possible AD etiol-

Some research suggests the important of sex differences in microglia development and in response to fluctuating gonadal steroids during the life and there are more microglia in female

Apart from the previous statements, some authors suggest that particular aspects of music perception such as pitch pattern analysis may open a channel on the processing of information streams in major dementia syndromes. Therefore, the potential selectivity of musical deficits for particular dementia syndromes and particular dimensions of processing warrants

Between classical thiamine deficiency and Alzheimer's disease (AD), many similarities exist and in both are associated reductions in brain glucose metabolism with cognitive deficits. Vitamin B1-dependent enzymes are critical components of glucose metabolism that are reduced in the brains of AD patients and by thiamine deficiency, and their decline could account for the reduction in glucose metabolism [59]. Nevertheless, many other conditions not related with AD can cause dementia as well, and it should be taken into account in the process of diagnosis and management. As the reader can see below, apart from AD, other

than males [58]. Females have been shown to have more microglia than males [1].

speech and language, reasoning, planning, and other cognitive abilities [53].

ogy, which is more pronounced in females [56, 57].

types of dementia and their etiology are also listed.

further systematic investigation [59].

and bvFTD patients.

Recently, Shang et al. [30] investigated differences in plasma fatty acids, adiponectin, reptin, plasma markers of inflammation, serum amyloid A, plasma lipids, and low-density lipoprotein in patients with AD, MCI, vascular dementia, and ischemic stroke in comparison to normal controls. They found different levels in almost all patients, indicating that these diseases have diverse pathological mechanisms.

The evaluation of inner retinal layers as a biomarker of MCI has brought more novel information about the possibility to predict cognitive decline, which can be used as prognostic information for patients who need to take financial and family decisions, advanced directives, afford care/residence decisions, etc. This reliable prognostic information and planification of the future will serve as significant societal benefit, taking into account the high societal cost of cognitive disorder care all over the world [31].

The level of relationship between cognition and functional outcomes in the MCI population is affected mainly by cognitive domains and a little bit by age and educational level. Early identification of subtle functional disturbance in MCI and comprehension of its cognitive and noncognitive correlates are determinant in the diagnostic process because of its prediction for dementia progression [32].

A recent meta-analysis investigation showed that hearing impairment is associated with a higher risk of MCI and dementia in elderly people [33].

Recently, a group of Korean researches have confirmed that a dietary pattern based on seafood and vegetables in older Korean adults can reduce MCI remarkably [34].

Recent study made by Correa-Jaraba and colleagues confirmed that the event-related potential technique is useful for evaluating changes in brain electrical activity and increased amplitude of the P3a component is a novel neurocognitive marker for differentiating amnestic MCI [35].

On the other hand, it seems to be that telerehabilitation by videoconference can improve cognitive function in patients with MCI, but this procedure needs more investigation to confirm its feasibility [36].

Three months ago, some investigators documented the association between the presence of hallucinations, delusions, anxiety, depression, and abnormal motor behavior, with the risk of developing incident dementia*, independent of other known risk factors, including MCI in the future, a simple, low-cost strategy for screening population groups at dementia risk, particularly in environments with limited access to specialized services and very sophisticated resources* [37–40]*.*
