**5. Cognitive impairment in iNPH**

The cognitive and behavioral disturbances accompanying iNPH have been commonly described as "fronto- subcortical dementia" [46, 47]. This clinical term is used to refer to a pattern of mental decline, characterized by executive dysfunction, psychomotor slowing and mood symptoms, especially apathy [48, 49], that is often present in patients with iNPH. However, as it will be detailed in this chapter, a wide range of other cognitive disturbances beside frontal involvement can be detected.

Specific criteria and guidelines have been defined for the surgical procedure and the postoperative and long-term care, including the management of complications [7, 9], even if a

Many studies have investigated the benefit of shunt surgery. Only one assessed the benefit of shunting surgery in a randomized manner and showed that, among the 14 patients included, only those with CSF shunts improved at 3 months follow-up. In particular, the patients with effective (open) shunts showed an improvement in motor and psychometric scores (30 and 23% increase, respectively) at 3 months, whereas those with placebo (ligated) shunts were unchanged. Of note, this latter group also improved after opening the shunts, although with less benefit (28 and 18%, respectively) [39].This rate of benefit is in line with the results of a systematic review, which reported a long-term response of 29% [40]. A double-blind randomized trial on the clinical effect of different shunt valve settings was also performed [41]; improvement after shunt surgery was evident within 3 months, irrespective

Recent studies showed higher rates of success (around 80–90%) [42, 43]; all these outcomes must be interpreted with caution, given the lack of standardized method of comparison. Besides the possible benefit, information about the risks of complications should also be pro-

The complication ratio of CSF shunt was found on average of 38%. Potential complications include infection, seizures, abdominal problems (peritonitis, perforation, volvulus, and ascites), shunt failure or blockage, shunt over-drainage and intracranial hemorrhage. The most common complication was the shunt over-drainage occurring in up to one-third of the patients within the first year [40]. Of course, the complication rates differ across centers. The Eu-iNPH study revealed a complication rate of 28% [42], while a recent study over more 230 subjects

In any case, the clinical follow-up of the patients is essential. The follow-up helps the management of the complication, identifying the patients who need adjustments or revision of the shunt. Repeated brain imaging is usually performed after shunting and can support the

As previously reported, the response to levodopa/carbidopa is absent or scarce. In patients who are poor candidates for shunt surgery, repeated lumbar punctures in combination with acetazolamide may be considered [45]. Recent studies on aquaporin-4 channels suggest inter-

The cognitive and behavioral disturbances accompanying iNPH have been commonly described as "fronto- subcortical dementia" [46, 47]. This clinical term is used to refer to a pattern of mental decline, characterized by executive dysfunction, psychomotor slowing and mood symptoms,

consensus measurement of CSF shunting outcome is still lacking [14].

of valve setting.

52 Hydrocephalus: Water on the Brain

vided, since they appear to be very common [44].

found a complication rate of less than 12% [43].

**5. Cognitive impairment in iNPH**

identification and early treatment of subdural hemorrhage [14].

esting perspectives for future pharmacological treatment of iNPH [31].

Boon et al. [26] in a study evaluated global cognitive functioning, memory, and attention in a large sample (101 patients), reported that iNPH patients showed severe impairment of attention and psychomotor speed.

Iddon et al. [50], on the basis of Mini-Mental State Examination (MMSE) score cutoff, divided their sample of 11 patients into two groups: demented and non-demented. By the means of neuropsychological instruments which evaluated different cognitive functions, two cognitive profiles in iNPH have been identified, one observed in patients at a less advanced disease stage, who presented isolated frontal lobe dysfunction, and the other observed in those who have reached a more advanced stage and presented severe global cognitive dysfunction. The non-demented iNPH patients obtained a worse performance on attentional tasks, thus suggesting a deficit in cognitive flexibility, similar to patients with frontal lobe excision and patients with fronto-subcortical dementia such as Parkinson's disease [51, 52], and unlike patients with AD in which frontal functions usually are spared [53].

Ogino et al. [46], in a well-controlled study, analyzed 21 patients with iNPH and 42 patients with AD, using a neuropsychological assessment investigating different cognitive domains. iNPH patients had more severe impairment of attention, psychomotor speed and calculation than those with AD, while memory function and orientation were more preserved. Impairment in frontal functions in iNPH, but not in AD, was reported also by Miyoshi et al. [54], who compared the scores recorded on the Frontal Assessment Battery (FAB), on verbal fluency subtests and on subtests of the MMSE in patients with iNPH and AD, matched for age, sex, and MMSE score.

Tarnaris et al. [47], analyzing cognitive performances of 10 patients with iNPH through a complete neuropsychological assessment (language, memory, executive functions, visuospatial abilities, and attention), confirmed that all the patients had subcortical cognitive impairment, characterized in particular by dysexecutive dysfunction and slowed mental processing.

Therefore, some studies have tried to relate the cognitive impairment in iNPH to damage the frontal lobe The results of single photon emission computed tomography and positron emission tomography (PET) studies showed that iNPH patients mainly presented hypoperfusion of the frontal lobe [55–57].

On the basis of the finding that periventricular white matter cerebral blood flow was reduced in iNPH [56] it has been suggested that the frontal lobe dysfunction might be secondary to a disturbance of the subcortical area connecting with the frontal lobe cortex [50, 57, 58]. The relatively preserved memory and orientation functions may be explained by a lower involvement of memory systems, including the medial temporal lobe, in iNPH than in AD [46]. However, a neuroimaging study [59] demonstrated a reduction in the medial temporal volume in iNPH. Parietal regional cerebral blood flow reduction in iNPH has also been shown in other neuroimaging studies [60, 61].

On the other hand, other studies have demonstrated that patients with iNPH can be impaired in broader cognitive domains; the definition of fronto-subcortical dementia has therefore to be considered reductive, given that the cognitive deficits observed in iNPH can extend beyond executive function, attention, working memory, and episodic memory to visuoperceptual and visuospatial functions [26, 56, 62, 63].

how it has contributed to our understanding of cognition in iNPH; they proposed a clinical assessment protocol in which beside cognitive evaluation a great importance was attached to the evaluation of emotional domains, apathy and depression in particular, and quality

Clinical and Cognitive Features of Idiopathic Normal Pressure Hydrocephalus

http://dx.doi.org/10.5772/intechopen.73273

55

Ogino et al. [46] assessed cognitive functions by administration of the Wechsler Adult Intelligence Scale-Revised, Wechsler Memory Scale-Revised, and Alzheimer Disease Assessment Scale (ADAS) orientation subtest. Saito et al. [64] used an exhaustive and detailed neuropsychological assessment, which included the MMSE for general cognitive function, Digit Span and Spatial Span for attention, Word fluency, Trail Making Test A (TMT A) and FAB for executive function, Object naming subtest for language, the Word recall and Word recognition subtests of ADAS for episodic memory and Visual discrimination, Overlapping figures and

In a recent study by Missori and Currà [67] all the patients underwent a wide neuropsychological assessment: MMSE, FAB, Rey's 15 words immediate and delayed recall, Wisconsin Card Sorting Test, TMT, Attentive Matrices, Analogies test, and Digit Span forward and backward tasks. However, the authors included only the scores from the MMSE in the analysis of the results because the aim of their work was to grossly quantify cognitive impairment in

As we can see, most authors have used large neuropsychological battery, but different measures within the single cognitive domain have been administered in the different studies. Therefore the various studies are not immediately comparable and a standardized protocol

iNPH is considered a potentially reversible dementia and as described above the treatment of choice is ventriculo-peritoneal or atrial shunt device placement. When considering the global outcome, there is a general agreement about the fact that short-term results are more likely to be influenced by shunt-associated risks, while long-term results are more influenced by other factors, such as concomitant neurodegenerative and cerebrovascular diseases; the one-year post-shunt period can be considered a determinant of long-term results of the treatment [68]. Shunt surgery can help to reduce cognitive impairment, especially if it is performed during the early stage of deterioration, as it will be more detailed below; if the pressure is not relieved quickly by a shunt patients with severe iNPH will in fact develop overall cognitive impairment [9, 50]. This deterioration is only partially reversible as reported by Andrèn et al. [69], who described the effects of waiting for at least 6 months before surgery and compared the outcome with that seen in patients who waited for less than 3 months. The patients of the first group significantly deteriorated; both groups ameliorated at the same size after surgery, but since the symptoms of the patients of the first group had worsened while waiting, their final

Visual counting tasks for evaluating visuoperceptual and visuospatial functions.

of life.

patients.

should be needed.

outcome was significantly poorer.

**6. Cognitive impairment after shunt surgery**

Saito et al. [64] evaluated 32 iNPH patients, 32 AD patients and 30 healthy elderly controls, using an extensive and comprehensive neuropsychological battery to investigate all the different cognitive domains: language, memory, executive functions, visuospatial and visuoperceptual abilities, attention, and mental processing speed. Their results suggested that iNPH is associated with impairment in various aspects of cognition involving both frontal-executive and posterior-cortical functions, such as visuoperceptual and visuospatial abilities. In particular, defective performances were found on the visual discrimination and visual counting tasks; visuoperceptual and visuospatial abilities in iNPH patients were more severe than in those with AD, whereas the degree of memory impairment was comparable to that in AD patients.

The main involvement of visuospatial functions was observed also by Bugalho et al. [65]; 17 iNPH patients have been compared with 14 healthy controls and the authors suggested that visuospatial deficits, and not executive dysfunction, could be an early sign of cognitive deterioration in iNPH patients regardless of the severity of global cognitive dysfunctions.

Some studies, instead, focused on the nature of the memory deficit in order to identify a specific pattern. Walchenbach et al. [63] analyzed 51 iNPH patients, administering the MMSE and neuropsychological tests assessing both cortical (language, visuoperceptual skills and praxis, and memory functions) and fronto-subcortical functions (mental speed, concept shifting, and abstract reasoning). They suggested that the pattern of memory deficit in iNPH is of the frontal lobe type, in which recall is disproportionately affected with respect to recognition, while in patients with AD recall and recognition are both impaired. Ogino et al. [46] observed memory impairment in iNPH, but they found that impairment of executive functions was more severe, while impairment of memory and orientation was milder in patients with iNPH than in those with AD. On the contrary, Saito et al. [64] found that both recognition and recall were impaired in a similar fashion both in iNPH and AD groups, thus suggesting that memory impairment in iNPH is not exclusively ascribable to frontal lobe dysfunction.

Therefore the data of the literature seem to confirm a wide range of cognitive decline in iNPH patients and according to Devito et al. [66] we can conclude that: "in some cases it may be qualitatively similar to normal aging, in others it may manifest as progressive dementia with gait disturbance, clinically similar to Alzheimer's or Parkinson's disease".

However, there is no general agreement on the neuropsychological instruments to be used in assessing cognitive deficits. Bugalho et al. [65] employed a cognitive assessment protocol focused on various cognitive domains (global cognitive function, verbal memory, impulse control, verbal fluency, working memory, attention, visuospatial reasoning, and visuoconstructive abilities) and also on mood and hand dexterity. Devito et al. [66] in a not recent but very interesting paper have reviewed possible application of clinical neuropsychology and how it has contributed to our understanding of cognition in iNPH; they proposed a clinical assessment protocol in which beside cognitive evaluation a great importance was attached to the evaluation of emotional domains, apathy and depression in particular, and quality of life.

Ogino et al. [46] assessed cognitive functions by administration of the Wechsler Adult Intelligence Scale-Revised, Wechsler Memory Scale-Revised, and Alzheimer Disease Assessment Scale (ADAS) orientation subtest. Saito et al. [64] used an exhaustive and detailed neuropsychological assessment, which included the MMSE for general cognitive function, Digit Span and Spatial Span for attention, Word fluency, Trail Making Test A (TMT A) and FAB for executive function, Object naming subtest for language, the Word recall and Word recognition subtests of ADAS for episodic memory and Visual discrimination, Overlapping figures and Visual counting tasks for evaluating visuoperceptual and visuospatial functions.

In a recent study by Missori and Currà [67] all the patients underwent a wide neuropsychological assessment: MMSE, FAB, Rey's 15 words immediate and delayed recall, Wisconsin Card Sorting Test, TMT, Attentive Matrices, Analogies test, and Digit Span forward and backward tasks. However, the authors included only the scores from the MMSE in the analysis of the results because the aim of their work was to grossly quantify cognitive impairment in patients.

As we can see, most authors have used large neuropsychological battery, but different measures within the single cognitive domain have been administered in the different studies. Therefore the various studies are not immediately comparable and a standardized protocol should be needed.
