To investigate the prevalence and nature of cognitive changes associated with sporadic amyotrophic lateral sclerosis (ALS) using a large scale study.
Consecutive patients with sporadic ALS (n = 279) underwent comprehensive neurologic evaluation and neuropsychological testing. Testing data from normal controls (n = 129) were used for classification and comparison purposes.
On non-motor, non-speed-dependent tasks, 51% of patients with ALS had evidence of cognitive impairment compared to 5% of controls. Cluster analysis suggested four patient subgroups: 49% intact, 32% with mild impairment, 13% with moderate impairment, and 6% with severe impairment. Forty-one patients (15%) met criteria for frontotemporal dementia (FTD). ALS patient subgroups, excluding the intact group, performed significantly lower on tests of executive function and memory than normal controls. Patients with more severe disease also had deficits in confrontation naming. Although memory function declined with increasing severity of overall cognitive impairment, only two patients had the severe memory loss typical of Alzheimer disease. Cognitive impairment was correlated with clinical measures of word-finding, phrase length, and motor programming. Cognitive impairment was not correlated with depression scores or severity or duration of motor or bulbar symptoms. Patients with bulbar vs limb-onset ALS were not different in either level of impairment or pattern of performance.
These data confirm the presence of cognitive impairment in 50% of patients with ALS and particularly implicate executive dysfunction and mild memory decline in the disease process. More severe impairment occurs in a subset of patients with ALS and has features consistent with FTD.
"Using knowledge obtained through research into antisense oligonucleotides (ASOs) therapies for diseases such as Duchenne muscular dystrophy (DMD) and myotonic dystrophy type 1, we propose that using such therapy may be a promising approach for treating C9orf72 repeat expansion in c9FTD/ALS. it is now known that up to 50% of ALS patients have some impairment of frontotemporal function and ∼15% of ALS patients can specifically be said to have FTD     . In addition, significant corticospinal and lower motor neuron dysfunction have been observed across most FTD subtypes , with 10–15% of FTD patients having coexisting motor neuron disease (MND)  . "
"From a clinical perspective, 10–15% of patients with behavioural variant frontotemporal dementia (bvFTD) demonstrate motor impairment that meet criteria for a diagnosis of ALS –, but subtle motor system dysfunction is present in a significant proportion of patients who do not reach diagnostic criteria . Similarly, while 15% of patients with ALS manifest cognitive and neuropsychiatric changes characteristic of bvFTD , , cognitive impairment is also present in a further 35% of ALS patients that do not meet bvFTD criteria , . Neuropsychiatric features (disinhibition, apathy, loss of sympathy, stereotypical behaviour, dietary changes and executive deficits)  are also observed, particularly in patients who develop ALS-bvFTD  and have the C9ORF72 mutation , . "
[Show abstract][Hide abstract] ABSTRACT: Amyotrophic lateral sclerosis (ALS) and behavioural variant frontotemporal dementia (bvFTD) are multisystem neurodegenerative disorders that manifest overlapping cognitive, neuropsychiatric and motor features. The cerebellum has long been known to be crucial for intact motor function although emerging evidence over the past decade has attributed cognitive and neuropsychiatric processes to this structure. The current study set out i) to establish the integrity of cerebellar subregions in the amyotrophic lateral sclerosis-behavioural variant frontotemporal dementia spectrum (ALS-bvFTD) and ii) determine whether specific cerebellar atrophy regions are associated with cognitive, neuropsychiatric and motor symptoms in the patients. Seventy-eight patients diagnosed with ALS, ALS-bvFTD, behavioural variant frontotemporal dementia (bvFTD), most without C9ORF72 gene abnormalities, and healthy controls were investigated. Participants underwent cognitive, neuropsychiatric and functional evaluation as well as structural imaging using voxel-based morphometry (VBM) to examine the grey matter subregions of the cerebellar lobules, vermis and crus. VBM analyses revealed: i) significant grey matter atrophy in the cerebellum across the whole ALS-bvFTD continuum; ii) atrophy predominantly of the superior cerebellum and crus in bvFTD patients, atrophy of the inferior cerebellum and vermis in ALS patients, while ALS-bvFTD patients had both patterns of atrophy. Post-hoc covariance analyses revealed that cognitive and neuropsychiatric symptoms were particularly associated with atrophy of the crus and superior lobule, while motor symptoms were more associated with atrophy of the inferior lobules. Taken together, these findings indicate an important role of the cerebellum in the ALS-bvFTD disease spectrum, with all three clinical phenotypes demonstrating specific patterns of subregional atrophy that associated with different symptomology.
PLoS ONE 08/2014; 9(8):e105632. DOI:10.1371/journal.pone.0105632 · 3.23 Impact Factor
"In accordance with the revised El Escorial criteria , both the upper motor neurons and the lower motor neurons degenerate or die in ALS, and, as a consequence, the communication between the neuron and muscle is lost, prompting progressive muscle weakening and the appearance of fasciculations. In the later disease stages, the patients become paralyzed and up to 50% of ALS patients can show cognitive impairment, particularly implicating more severe executive dysfunction and mild memory decline   . ALS, which is one of the most common motor neuron degenerative diseases, typically strikes adults during midlife. "
[Show abstract][Hide abstract] ABSTRACT: Since amyotrophic lateral sclerosis (ALS) was discovered and described in 1869 as a neurodegenerative disease in which motor neuron death is induced, a wide range of biomarkers have been selected to identify therapeutic targets. ALS shares altered molecular pathways with other neurodegenerative diseases, such as Alzheimer's, Huntington's, and Parkinson's diseases. However, the molecular targets that directly influence its aggressive nature remain unknown. What is the first link in the neurodegenerative chain of ALS that makes this disease so peculiar? In this review, we will discuss the progression of the disease from the viewpoint of the potential biomarkers described to date in human and animal model samples. Finally, we will consider potential therapeutic strategies for ALS treatment and future, innovative perspectives.
BioMed Research International 08/2014; 2014:925101. DOI:10.1155/2014/925101 · 3.17 Impact Factor
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