Motor signs during the course of Alzheimer disease.

Cognitive Neuroscience Division, Taub Institute for Research in Alzheimer's Disease and the Aging Brain, Gertrude H. Sergievsky Center, and Department of Neurology, New York, NY 10032, USA.
Neurology (Impact Factor: 8.3). 10/2004; 63(6):975-82. DOI: 10.1212/01.WNL.0000138440.39918.0C
Source: PubMed

ABSTRACT Motor signs (MOSIs) are common in Alzheimer disease (AD) and may be associated with rates of cognitive decline, mortality, and cost of care.
To describe the progression and identify predictors of individual MOSIs in AD.
A cohort of 474 patients with AD at early stages was followed semiannually for up to 13.1 years (mean 3.6 years) in five centers in Europe and the United States. MOSIs were rated using a standardized portion of the Unified Parkinson's Disease Rating Scale. Overall, 3,030 visits/assessments of MOSIs (average 6.4/patient) were performed. Prevalence and incidence rates were calculated, and cumulative risk graphs were plotted for individual non-drug-induced MOSI domains. Rates of change over time taking into account potential covariates were also estimated. With use of each MOSI domain as outcome in Cox models, predictors of MOSI incidence were identified.
At least one MOSI was detected in 13% of patients at first examination and in 36% for the last evaluation. Total MOSI score increased at an annual rate of 3% of total possible score. Rates of annual change for speech/facial expression (4%), rigidity (2.45%), posture/gait (3.9%), and bradykinesia (3.75%) were of similar magnitude, and their occurrence increased from first (3 to 6%) to last (22 to 29%) evaluation. Tremor was less frequent throughout the course of the disease (4% at first and 7% at last evaluation) and worsened less (0.75% increase/year).
Most motor signs occur frequently and progress rapidly in Alzheimer disease. Tremor is an exception in that it occurs less frequently and advances at slower rates.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: High-dimensional independent component analysis (ICA), compared to low-dimensional ICA, allows to conduct a detailed parcellation of the resting-state networks. The purpose of this study was to give further insight into functional connectivity (FC) in Alzheimer's disease (AD) using high-dimensional ICA. For this reason, we performed both low- and high-dimensional ICA analyses of resting-state fMRI data of 20 healthy controls and 21 patients with AD, focusing on the primarily altered default-mode network (DMN) and exploring the sensory-motor network. As expected, results obtained at low dimensionality were in line with previous literature. Moreover, high-dimensional results allowed us to observe either the presence of within-network disconnections and FC damage confined to some of the resting-state subnetworks. Due to the higher sensitivity of the high-dimensional ICA analysis, our results suggest that high-dimensional decomposition in subnetworks is very promising to better localize FC alterations in AD and that FC damage is not confined to the DMN.
    Frontiers in Human Neuroscience 02/2015; 9. DOI:10.3389/fnhum.2015.00043 · 2.90 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Clinical and neuropathological similarities between Dementia with Lewy Bodies (DLB), ParkinsonÕs and AlzheimerÕs diseases (PD and AD, respectively) suggest that these disorders may share etiology. To test this hypothesis we have performed an association study of 54 genomic regions, previously implicated in PD or AD, in a large cohort of DLB cases and controls. The cohort comprised 788 DLB cases and 2624 controls. To minimize the issue of potential misdiagnosis, we have also performed the analysis including only neuropathologically proven DLB cases (667 cases). Results show that the APOE is a strong genetic risk factor for DLB, confirming previous findings, and that the SNCA and SCARB2 loci are also associated after study-wise Bonferroni correction, although these have a different association profile than the associations reported for the same loci in PD. We have previously shown that the p.N370S variant in GBA is associated with DLB, which, together with the findings at the SCARB2 locus, suggests a role for lysosomal dysfunction in this disease. These results indicate that DLB has a unique genetic risk profile when compared to the two most common neurodegenerative diseases and that the lysosome may play an important role in the etiology of this disorder. We make all these data available.
    Human Molecular Genetics 06/2014; 23(23). DOI:10.1093/hmg/ddu334 · 6.68 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Recent neuroimaging studies in humans support the clinical observations that the motor cortex is affected early in the course of Alzheimer's disease (AD). We measured the silent period (SP) induced by transcranial magnetic stimulation in AD patients in the very early stage of the disease, and we explored whether and in which way the pharmacologic manipulation of the cholinergic system could modify it. An increase in the duration of the SP was observed in AD patients in the early stage in comparison to controls. After 2 months of treatment with donepezil, the duration did not differ significantly from that of normal subjects. The results of our study show a fragmentation and an enlargement of the SP in the presence of multiple late excitatory potentials (LEPs) in early untreated AD patients. These LEPs were also modulated by donepezil. The results suggest an early functional impairment of cholinergic neurotransmission in AD. The disturbance in acetylcholine output in early AD leads to a decrease in excitability of the motor system.
    09/2014; 4(3):457-64. DOI:10.1159/000367841

Full-text (2 Sources)

Available from
May 27, 2014