**8. Cognitive function impairment in motor neuron disease**

Cognitive impairment is increasingly being recognized in MND. Subtle subclinical cognitive defects and frontal lobe dysfunction may be demonstrated in up to half of MND patients with detailed neuropsychological testing (Ringholz, et al. 2005). Several genetic mutations of MND have been identified in association with frontotemporal dementia and/or parkinsonism (Valdmanis and Rouleau. 2008). It is well recognized that MND is a multisystem disorder (Geser, et al, 2008) with compromise of regions beyond the motor

Motor Neuron Disease 209

neuropsychological status of ALS patients a framework was based on four different axes. Axis I is based on the EL Escorial criteria proposed in 1998, that includes possible, probable, and definite ALS clinical subtypes. This multidimensional approach incorporates several criteria (Brooks et al, 2000). The novelty of the classification lies primarily in Axis II with the proposal of five categories which classify ALS patients along a continuum: (1) ALS patients cognitively and behaviorally intact: (2) ALS patients with mild cognitive impairments; (3) ALS patients with mild behavioral impairment; (4) ALS with a full-fledged fronto-temporal

Axis III indicates the presence, in addition to frontotemporal impairments, of additional non-motoneuronal disease manifestations such as extrapyramidal signs, cerebellar degenerations, autonomic dysfunctions, sensory impairments, and ocular motility abnormalities. The absence of the above indicates a "pure form," while their presence defines "complicated forms" with additional pathological motor aspects. Axis IV, instead, provides the search for factors which could modify the course of the disease. Several disease modifiers have been reported in literature associated with longer survival, age at symptom

Language deficits are occasionally found in the early stages of the disease. (Abrahams, et al.

The spectrum of language impairment in MND is wider than simply a problem in speech production due to dysarthria, but it is yet to be fully characterized. Reduced verbal output (adynamism) evolving into mutism has been reported, as well as echolalia. Perseverations, stereotypical expressions, (Bak and Hodges. 2004), true non-fluent aphasia with phonological and/or syntactic deficits and comprehension impairment have been reported

MND has also been associated with apraxia of speech, in which there is breakdown in articulatroy planning, producing slowed, effortful and dysprosodic speech with problems repeating multisyllabic words. Apraxia of speech is often accompanied by orobuccal apraxia

It has been difficult to categorize the pattern of memory impairment, but current evidence suggests that memory problems are related to abnormalities in retrieval of the information secondary to frontal dysfunction. (Neary, et al. 2000). Memory problems involve primarily immediate recall, (Phukan. et al. 2007) but impairment of visual memory also has been

Frontal, temporal and thalamic hypoperfusion on SPECT has been shown to correlate with

Most strikingly, learning and memory were found to be significantly improved in patients

onset (< 45 years), gender (male/sex), and site of the disease onset (bulbar or limb).

dementia; (5) ALS with other non FTD-forms of dementia.

**9. Language** 

**10. Memory** 

implicated,(Kew, et al.1993)

in isolated cases. (Tsuchiya, et al. 2000)

but not necessarily with aphasia.(Duffy, et al ,2007).

the severity of memory impairment. (Montovan, et al. 2003).

in the later stages of the disease, (Lakerveld et al, 2008).

2004).

system, including cortical areas which are consistently involved in FTD. It comes as no surprise, therefore, that a proportion of patients presenting with MND manifest cognitive and/or behavioural changes which may be severe enough in some instances to reach criteria for frank FTD.(Irwin, et al, 2007).
