**4. Some information about Parkinson's disease**

In the past decade, we applied the term "mild cognitive impairment (MCI) due to AD" to refer to the symptomatic predementia phase of AD; in other words, patients with cognitive decline whose primary underlying pathophysiologic was AD but no evidence of a remarkable impairment in social or occupational activities; currently, we separate those patients in two groups.

Typically, amnestic MCI is the type of prodromal stage of dementia due to AD, but other phenotypes can also mimic to this kind of dementia, such as posterior cortical atrophy (also known as the visual variant), logopenic aphasia, or a frontal lobe-dysexecutive presentation of AD. Therefore, as a general agreement, not all MCI is early AD. The Key Symposium characterization of MCI helps to differentiate between the amnestic form of MCI and the nonamnestic one. These clinical syndromes appeared to be aligned with causes in a differential fashion and may have variable outcomes [60]. The Alzheimer's Disease Neuroimaging Initiative (ADNI) criteria are useful in prediction of amnestic MCI progression to AD, including medial temporal lobe atrophy and hypometabolism in MRI and FDG-PET, respectively [10, 61, 62].

Recently, some researchers reported that plasma total tau and pTau181 levels were higher in AD dementia patients than those in cognitively unimpaired. Plasma pTau181 was more strongly associated with both Aβ and tau PET. Plasma pTau181 was a more sensitive and specific predictor of elevated brain Aβ than total tau and better than the combination of age and apolipoprotein E, and they concluded that plasma pTau181 may have utility as a biomarker of

Few weeks ago, some authors have found that [18F]AV-1451 uptake showed the strongest regional correlation with hypometabolism. Correlations between [18F]AV-1451 uptake and both hypometabolism and cortical thickness were stronger in participants with greater cortical tau severity. In addition, age, tau asymmetry, and clinical diagnosis influenced the strength of the correlation between [18F]AV-1451 uptake and cortical thickness. Therefore, all these findings support a close relationship between tau and hypometabolism in Alzheimer's disease but show that correlations between neuroimaging modalities vary across participants [64].

Some investigations have confirmed that people with MCI and a positive amyloid PET scan are more liable to progress rapidly and, again, ADNI data confirmed this. Nevertheless, it is well known that carriers of the apolipoprotein E4 (*APOE4*) genotype are more susceptible to progress rapidly; however, in clinical practice, *APOE* testing did not contribute remarkable to

The study done by Hansson and colleagues relieved more information with regard to these data and corroborates the suspicion that those individuals, particularly with amnestic MCI presenting low CSF levels of Aβ42 and elevated total tau and phosphorylated tau, are at the higher risk for progressing faster than those patients with the same clinical phenotype but

All people presenting a mild cognitive impairment in our series did not present an early

The criteria for MCI due to AD developed by the National Institute on Aging and the Alzheimer's Association essentially adopted the Key Symposium criteria and explained more explicit some of the diagnostic features. These criteria also considered biomarkers for underlying AD's pathophysiology trying to define the underlying cause and, hence, predict outcome.

AD pathophysiology and as a noninvasive screener for elevated brain Aβ [63].

the diagnostic assessment [65].

198 Cognitive Disorders

Alzheimer's disease later.

normal biomarkers on the CSF [66, 67].

Parkinson's disease (PD) is an idiopathic type of parkinsonism, which progresses gradually in spite of the medical or surgical treatment implemented and it is characterized by bradykinesia, tremor at rest, gait disturbance, postural problems, rigidity, dysarthria, dysfunction of the judgment, reasoning, memory, depression, anxiety, insomnia, and cognitive decline due to loss of midbrain dopaminergic neurons in the pars compacta of the substantia nigra and consequent loss of dopamine input to the caudate nucleus and putamen (striatum), and it is more prevalent in men, whereas rigidity, difficulties pertaining to daytime sleepiness, dribbling saliva, interest in sex, and problems having sex are more common among men with PD [71].

Dementia affected almost 50% of our patients with PD within the first decade after diagnosis is made, but the intensity of their manifestations varied considerably among them. Prospective investigations reveal patient differences in the progression of cognitive deficits and in risk factors for developing PD dementia (PDD) [72].

*Identifying patients at risk of dementia and those at the earliest stages of cognitive involvement is important for three important reasons:*


The concept of MCI is introduced in the 1980s, and it is characterized mild cognitive deficits that did not qualify to a diagnosis of dementia in patients with AD, and more recently, it was also introduced for patients with PD [5].

As far as we remember, the concept of "mild cognitive impairment" as a transitional or predementia state in Parkinson's disease was delivered before 2014, and we also believe that PD-MCI is a transitory stage between normal cognition and dementia.

infections, and other disorders that cause an accumulation of the cerebrospinal fluids (CSF) in the ventricular system of the brain mainly associated to its impaired drainage [80]. Approximately 700,000 persons may have iNPH in the United States. Neuroimaging with either CT or MRI is

Updated Information on Some Cognitive Disorders http://dx.doi.org/10.5772/intechopen.81826 201

The iNPH, the most common form of hydrocephalus in adult's population, affects the brain parenchymal on the cerebral hemisphere causing cognitive dysfunction, lack of balance, urinary urgency with or without incontinence, problem-solving disabilities, dysarthria, and apraxia of gait apart from spasticity, hyperreflexia, and other upper motor neuron signs.

Gait apraxia is typically the first and worst disturbance in patients with iNPH. The overall prevalence of iNPH ranges from 0.02% to up to 5.9%, depending upon age and specific population studied [82, 83]. Another author reported a prevalence about 0.51–2.9% in the elderly population [84]. Some authors found that the male-to-female ratio for those with idiopathic NPH (iNPH) is 1.39:1 (*P* < 0.0001), and the corresponding incidence rate ratio between males and females with iNPH is 1.838 (*P* < 0.0001), indicating that iNPH is almost twice as likely to

In patients presenting Huntington disease with an associated inability to walk or rapid progression of their symptoms, a diagnosis of iNPH should be considered, and they are going to improve the cognitive disorder, gait, and chorea after the lumbar puncture and surgical

Mild apathy is the more common neuropsychiatric symptom in patients with iNPH, and the frontal lobe pathology is the main cause of increased correlation between neuropsychiatric

MCI is quite common presentation in patients with iNPH, and their neuropathological findings are generally consistent with white matter damage, regardless of the underlying, yet

Diffusion tensor imaging (DTI) is a useful MRI technique that can reflect the structural integrity and interstitial space of the white matter by detecting the directionality of extracellular water diffusion [fractional anisotropy (FA)] and of free water diffusion [mean diffusivity (MD)] and has been applied to evaluate white matter damage in iNPH [93–96]. Some authors have confirmed that after shunt surgery in patients presenting iNPH, the fractional anisotropy (FA) in the corona radiata decreases, and the regions involved were located between the enlarged lateral ventricles and Sylvian fissures. The plasticity of the brain for mechanical pressure from the CSF system is also confirmed by their findings [97]. An interesting excep-

Treatment outcome can be predicted by quantitative image biomarker from diffusion MRI, which also serves to distinguish between reversible and irreversible changes in iNPH [103]. Alzheimer's disease can be differentiated from iNPH by cerebral retention of Pittsburgh compound B (PIB: *N*-methyl-[11C]2-(4-methylaminophenyl)-6-hydroxyben-zothiazole) in positron emission tomography (PET) because in iNPH it was limited to the high-convexity parasagittal regions, whereas in AD it spreads over the frontal and temporoparietal lobes. Therefore, the

tion found in iNPH is the increased FA within the corticospinal tract [98–102].

required for the diagnosis of iNPH [81].

occur in older males than older females [85].

symptoms and cognitive impairment [87].

unknown, pathophysiological mechanisms [88–92].

treatment [86].

A recent study showed a strong correlation between the extent of neurofibrillary tangles and alpha synuclein [74]. It seems to be that the insula lobe is one of the vulnerable regions by alpha-synuclein deposition.

The treatment of cognitive symptoms has shown some good results with the introduction of cholinesterase inhibitors (ChEIs) that is more effective in PDD, compared to AD, because of their early, prominent CNS cholinergic disturbance [75].

Rivastigmine has been approved by the United States and European Union for the treatment of PDD with promissory results, while levodopa and other dopaminergic medications are still effective for tremor and parkinsonian motor symptoms of PDD. For the treatment of psychotic manifestations, atypical antipsychotics (e.g., quetiapine, clozapine) have been used in PDD. There is current evidence-based medicine favoring clozapine in PDD [76].

Novel information about imagenological assessment of PDD is positron emission tomography (PET) scan using C-labeled radiotracer Pittsburgh compound B that has been widely applied for the in vivo assessment of amyloid-β (Aβ) deposition in patients with AD, with successful results [77, 78].

Progressive supranuclear palsy is included in the classification of Parkinsonism and is also a form of dementia that is characterized by vertical gaze palsy, falling backward, hypokinesia, rigidity, irritability, dysphagia, dysarthria, apathy, depression, and cognitive decline, which is sometimes misdiagnosed as PD. Based on clinical observations from our series of patients with Parkinsonism, neuropsychologically assessed at the early to moderate stages, cognitive decline was a common problem found and some of those patients developed dementia with reduction of quality of life and functional disability. However, an important number of patients presenting mild cognitive impairment (MCI) did not develop dementia up to date. Because we have not resting-state functional MRI (rs-fMRI) facilities in our setting, we could not document the expected structural and functional connectivity alterations of the brain. Recently, some author confirmed that the temporal connectivity alterations found in patients with PD and PD-MCI could be related to the presence of cognitive impairment in PD [79].
