Motor signs during the course of Alzheimer disease

Scarmeas, Nikolaos; Hadjigeorgiou, Georgios M.; Papadimitriou, Alexandros; Dubois, Bruno; Sarazin, M.; Brandt, Jason; Albert, Marilyn; Marder, Karen; Bell, Karen L.; Honig, Lawrence S.; Wegesin, Domonick J.; Stern, Yaakov

doi:10.1212/01.wnl.0000138440.39918.0c

Cited by 224 publications

(190 citation statements)

References 49 publications

Supporting

Mentioning

174

Contrasting

Unclassified

Order By: Relevance

“…Alterations in facial expression, gait and posture, and manifestations of rigidity, bradykinesia, and tremor are found in late AD stages although mounting evidence suggests that motor problems emerge long before any recognizable sign of AD (Wilson et al ., 2000; Scarmeas et al ., 2004; Buchman & Bennett, 2011). Tau abnormal hyperphosphorylation and subsequent malfunction are postulated as crucial mechanisms in AD neuronal dysfunction where hyperphosphorylated and/or aggregated (insoluble) forms of Tau exhibit neurodegenerative action(s) that also interfere with normal Tau, sequestering and reducing soluble Tau forms (Ksiezak‐Reding et al ., 1988; Zhukareva et al ., 2003).…”

Section: Introductionmentioning

confidence: 99%

Absence of Tau triggers age‐dependent sciatic nerve morphofunctional deficits and motor impairment

Lopes

Pinto

et al. 2016

Aging Cell

View full text Add to dashboard Cite

SummaryDementia is the cardinal feature of Alzheimer's disease (AD), yet the clinical symptoms of this disorder also include a marked loss of motor function. Tau abnormal hyperphosphorylation and malfunction are well‐established key events in AD neuropathology but the impact of the loss of normal Tau function in neuronal degeneration and subsequent behavioral deficits is still debated. While Tau reduction has been increasingly suggested as therapeutic strategy against neurodegeneration, particularly in AD, there is controversial evidence about whether loss of Tau progressively impacts on motor function arguing about damage of CNS motor components. Using a variety of motor‐related tests, we herein provide evidence of an age‐dependent motor impairment in Tau−/− animals that is accompanied by ultrastructural and functional impairments of the efferent fibers that convey motor‐related information. Specifically, we show that the sciatic nerve of old (17–22‐months) Tau−/− mice displays increased degenerating myelinated fibers and diminished conduction properties, as compared to age‐matched wild‐type (Tau+/+) littermates and younger (4–6 months) Tau−/− and Tau+/+ mice. In addition, the sciatic nerves of Tau−/− mice exhibit a progressive hypomyelination (assessed by g‐ratio) specifically affecting large‐diameter, motor‐related axons in old animals. These findings suggest that loss of Tau protein may progressively impact on peripheral motor system.

show abstract

Section: Introductionmentioning

confidence: 99%

Absence of Tau triggers age‐dependent sciatic nerve morphofunctional deficits and motor impairment

Lopes

Pinto

et al. 2016

Aging Cell

View full text Add to dashboard Cite

show abstract

“…Extrapyramidal signs (e.g., bradykinesia, rigidity, and reduced facial expression) are seen in 30% of cases; however, rest tremor is rare (Scarmeas et al 2004). Gait disturbances become more prominent with disease progression and are associated with a substantially higher risk for falls.…”

Section: Neurological Examinationmentioning

confidence: 99%

The Clinical Problem of Symptomatic Alzheimer Disease and Mild Cognitive Impairment

Tarawneh

Holtzman

2012

Cold Spring Harbor Perspectives in Medicine

364

218

View full text Add to dashboard Cite

Alzheimer disease (AD) is the most common cause of dementia in the elderly. Clinicopathological studies support the presence of a long preclinical phase of the disease, with the initial deposition of AD pathology estimated to begin approximately 10-15 years prior to the onset of clinical symptoms. The hallmark clinical phenotype of AD is a gradual and progressive decline in two or more cognitive domains, most commonly involving episodic memory and executive functions, that is sufficient to cause social or occupational impairment. Current diagnostic criteria can accurately identify AD in the majority of cases. As disease-modifying therapies are being developed, there is growing interest in the identification of individuals in the earliest symptomatic, as well as presymptomatic, stages of disease, because it is in this population that such therapies may have the greatest chance of success. The use of informant-based methods to establish cognitive and functional decline of an individual from previously attained levels of performance best allows for the identification of individuals in the very mildest stages of cognitive impairment.

show abstract

“…188 Dementia is estimated to occur in 30% of patients with PD, 6 and a large longitudinal study of AD patients found that at least one motor sign of PD was detected in 44% of patients during at least one of their study visits. 189 Because of this overlap, several studies have evaluated whether APOE genotype is a risk factor for PD.…”

Section: Apoementioning

confidence: 99%

Genetics of Parkinson disease

Pankratz

Foroud

2007

Genetics in Medicine

111

View full text Add to dashboard Cite

During the past decade five genes have been identified that are important in autosomal dominant and autosomal recessive forms of Parkinson disease. The identification of these genes has increased our understanding of the likely pathogenic mechanisms resulting in disease. However, mutations in these genes likely contribute to disease in fewer than 5% of all cases of Parkinson disease. Thus, researchers have continued to search for genes that may influence disease susceptibility. Molecular diagnostic testing is currently available for four of the genes mutated in Parkinson disease. Evidence for reduced penetrance, possible effects of haploinsufficiency, and the identification of nondisease causing polymorphisms within several of these genes has made genetic counseling challenging.Current recommendations are to limit molecular testing only to those individuals who are symptomatic. Furthermore, because treatment is unaltered by the presence or absence of mutations in these genes, restraint is recommended when considering the value of screening for mutations in a clinical setting. Genet Med 2007:9(12): 801-811.

show abstract

Motor signs during the course of Alzheimer disease

Abstract: Background-Motor signs (MOSIs) are common in Alzheimer disease (AD) and may be associated with rates of cognitive decline, mortality, and cost of care.

Cited by 224 publications

References 49 publications

Absence of Tau triggers age‐dependent sciatic nerve morphofunctional deficits and motor impairment

Absence of Tau triggers age‐dependent sciatic nerve morphofunctional deficits and motor impairment

The Clinical Problem of Symptomatic Alzheimer Disease and Mild Cognitive Impairment

Genetics of Parkinson disease

Contact Info

Product

Resources

About