**5. Updated information on idiopathic normal pressure hydrocephalus**

Idiopathic normal pressure hydrocephalus (iNPH) is an important geriatric disease, a treatable cognitive disorder, which can be reliably diagnosed with an organized approach, and its prevalence is expected to increase gradually. This type of hydrocephalus is characterized by late-onset, surgically treated progressive neurodegenerative disease caused by inadequate cerebrospinal fluid (CSF) dynamics and ventriculomegaly, while other types (including lowpressure hydrocephalus) are usually secondary to head injury, subarachnoid hemorrhage, 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 required for the diagnosis of iNPH [81].

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

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

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

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

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

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 impair-

**5. Updated information on idiopathic normal pressure hydrocephalus**

Idiopathic normal pressure hydrocephalus (iNPH) is an important geriatric disease, a treatable cognitive disorder, which can be reliably diagnosed with an organized approach, and its prevalence is expected to increase gradually. This type of hydrocephalus is characterized by late-onset, surgically treated progressive neurodegenerative disease caused by inadequate cerebrospinal fluid (CSF) dynamics and ventriculomegaly, while other types (including lowpressure hydrocephalus) are usually secondary to head injury, subarachnoid hemorrhage,

in PDD. There is current evidence-based medicine favoring clozapine in PDD [76].

PD-MCI is a transitory stage between normal cognition and dementia.

their early, prominent CNS cholinergic disturbance [75].

alpha-synuclein deposition.

200 Cognitive Disorders

successful results [77, 78].

ment in PD [79].

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 occur in older males than older females [85].

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 treatment [86].

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 symptoms and cognitive impairment [87].

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 unknown, pathophysiological mechanisms [88–92].

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

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 PIB-PET is very useful in the differential diagnosis between iNPH and AD. Kondo et al. have demonstrated that 3 of 10 (30%) patients with iNPH without any clinical signs of AD had obvious cortical retention in PIB-PET, indicating that iNPH is one of the PIB-positive diseases [104].

The CSF tap test shows good results for diagnosis of iNPH, but its accuracy is not certain,

Updated Information on Some Cognitive Disorders http://dx.doi.org/10.5772/intechopen.81826 203

The relationship between radiological markers and mortality rate in iNPH is unknown.

A possible comorbidity between FTD and iNPH is suspected because the prevalence of the

The genetic and pathophysiological mechanism in AD and iNPH are completely independent. Sometimes, the best selection of iNPH patients for VPS can be very difficult, but the CSF tap test by removing 30–50 ml of CSF can be used as prognostic test for shunt surgery outcome, but its negative predictive value is not certain. The most common interval between the LP and the formal follow-up examination is between 2 and 4 hours, and nauseous vomiting and headache are less frequent in iNPH patients than the other ones. Shunt surgery is not contraindicated in patients under antithrombotic therapy, and neurotoxic proteins in CSF can be removed from the brain and also improve learning, retention, and delayed recall of verbal

After shunt surgery, some patients do not get the proper regular follow-up by their attending neurosurgeons apart from the first checkout surgical wound and are seen again when the shunt mechanism has failure (i.e., overdrainage due to shunt setting that is too low); patients develop some complication or neurological manifestations (headache that worsens with sitting and standing and improves when lying down) and pain or discomfort from the shunt components, including abdominal pain that requires surgical approach or risk of shunt infection. Longitudinal care can be provided by neurologists if they are well trained. Some adjust-

Apart from iNPH patients with depression, the associated presence of delirium, hallucinations, visual or auditory agnosia, impaired naming, anosognosia, failure to recognize close relatives, families, and friends suggest a comorbidity with other types of dementia or neuro-

Obviously, in patients presenting dilatation of the ventricular system with an associated cognitive decline only or even only urinary incontinence, the attending doctor should search for another neurological disorder before considering iNPH mainly in those patients without gait disturbances. In cases presenting delirium and ventriculomegaly, the underlying cause of the delirium should be found, treatment initiated, and the patient must recover and return to a stable baseline before looking for iNPH [81]. Currently, the iNPH is the only type of dementia

Frontotemporal dementia (FTD) is a common neurodegenerative disease associated with progressive atrophy of the frontal and temporal lobes, leading to changes in personality,

that has an effective treatment for slowing its progression or for curative purposes.

However, in AD and VaD, the radiological findings are related with high mortality.

memory. The vast majority of patients improve some memory functions [108].

able shunts can be affected by strong external magnetic fields [81].

even for bedridden patients, indicated.

C9ORF72 is greater than expected.

logical disorder [109].

**6. Frontotemporal dementia**

In 2016, several studies on iNPH were published in the medical literature [105]. Below, interested readers can find a summary from the most relevant conclusions.

There is no standardization of care or differentiation between various types of hydrocephalus among the confirmed cases of hydrocephalus in the Middle East.

The most common complication seen in postshunting surgery is subdural hematoma, and it shows reduced and even worsening of gait in iNPH.

Remarkable improvements in gait and clinical outcome are seen in patients presenting iNPH after shunting surgical procedures.

After 6 months of shunt surgery in patients presenting iNPH, the best test for identifying clinical improvements is the European-iNPH scale.

Some authors have demonstrated that the vascular brain expansion (during cardiac cycle) is quickly compensated by CSF volume flush, toward the spinal compartment due to a decreased spinal canal compliance, a decreased vascular brain expansion, or an increase of subarachnoid space resistance to CSF flow.

Based on the knowledge that venous drainage helps to control intracranial pressure, some authors have highlighted the potential role of the right side of the heart and the jugular vein valves in the physiopathology of the intracranial pressure.

In iNPH, the main goal of shunt therapy is to improve the patient's mobility and a mean improvement of 0.4 mph has been confirmed.

Dr. Hakim described the iNPH for the first time in 1964, but its physiopathology was not satisfactorily elucidated as yet. Although changes seen on the brain parenchymal after shunt surgery have not been documented, it seems to be that a number of patients with cerebral atrophy could be presenting a reversible subarachnoid augmentation.

At the present moment, reliable biomarkers for selection of iNPH patients for shunt therapy and T-tau or Aβ-42 for predicting shunt responsiveness are not available and need to be identified. Nevertheless, some potential microRNA biomarkers in the CSF are useful to differentiate iNPH patients from other presenting overlapping symptoms of other disorders such as AD, PD, and progressive supranuclear palsy.

A possible genetic component involved in the pathogenesis of iNPH may be present.

In iNPH patients, the endoscopy third ventriculostomy is also a choice of treatment although some authors have found that it is not effective in treatment of iNPH [106, 107].

Ventriculoatrial shunt (VAS) is another choice of treatment of iNPH, and some authors recommend it as a first choice because it is more physiological, no cardiopulmonary complications have been reported, and less shunt malfunction in the follow-up is found.

The CSF tap test shows good results for diagnosis of iNPH, but its accuracy is not certain, even for bedridden patients, indicated.

The relationship between radiological markers and mortality rate in iNPH is unknown. However, in AD and VaD, the radiological findings are related with high mortality.

A possible comorbidity between FTD and iNPH is suspected because the prevalence of the C9ORF72 is greater than expected.

The genetic and pathophysiological mechanism in AD and iNPH are completely independent.

Sometimes, the best selection of iNPH patients for VPS can be very difficult, but the CSF tap test by removing 30–50 ml of CSF can be used as prognostic test for shunt surgery outcome, but its negative predictive value is not certain. The most common interval between the LP and the formal follow-up examination is between 2 and 4 hours, and nauseous vomiting and headache are less frequent in iNPH patients than the other ones. Shunt surgery is not contraindicated in patients under antithrombotic therapy, and neurotoxic proteins in CSF can be removed from the brain and also improve learning, retention, and delayed recall of verbal memory. The vast majority of patients improve some memory functions [108].

After shunt surgery, some patients do not get the proper regular follow-up by their attending neurosurgeons apart from the first checkout surgical wound and are seen again when the shunt mechanism has failure (i.e., overdrainage due to shunt setting that is too low); patients develop some complication or neurological manifestations (headache that worsens with sitting and standing and improves when lying down) and pain or discomfort from the shunt components, including abdominal pain that requires surgical approach or risk of shunt infection. Longitudinal care can be provided by neurologists if they are well trained. Some adjustable shunts can be affected by strong external magnetic fields [81].

Apart from iNPH patients with depression, the associated presence of delirium, hallucinations, visual or auditory agnosia, impaired naming, anosognosia, failure to recognize close relatives, families, and friends suggest a comorbidity with other types of dementia or neurological disorder [109].

Obviously, in patients presenting dilatation of the ventricular system with an associated cognitive decline only or even only urinary incontinence, the attending doctor should search for another neurological disorder before considering iNPH mainly in those patients without gait disturbances. In cases presenting delirium and ventriculomegaly, the underlying cause of the delirium should be found, treatment initiated, and the patient must recover and return to a stable baseline before looking for iNPH [81]. Currently, the iNPH is the only type of dementia that has an effective treatment for slowing its progression or for curative purposes.
