Memory deficits in amyotrophic lateral sclerosis patients with dementia and degeneration of the perforant pathway

Takeda, Takahiro; Uchihara, Toshiki; Mochizuki, Yoko; Mizutani, Toshio; Iwata, Makoto

doi:10.1016/j.jns.2007.05.010

Cited by 32 publications

(29 citation statements)

References 22 publications

(30 reference statements)

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“…In the present research, the ALS patients exhibited significant reduced GM volumes only in the bilateral precentral gyrus, whose atrophy produced the motor function deficit in ALS (Takeda et al 2007). This discrepancy could be because of differences in a variety of factors, such as the sample size, disease stage, clinical phenotypes of the ALS patients enrolled in the research, and software and statistical analyses used in the VBM studies.…”

Section: Discussionsupporting

confidence: 45%

“…Thus, we should consider the alterations we identified to represent temporal lobe dysfunction. Recent postmortem and in vivo studies on hippocampal pathology (Braak et al 2013) and volume (Takeda et al 2007) also support the involvement of the temporal lobe in ALS. Therefore, the current results support the notion that memory deficits in sporadic ALS are not exclusively caused by frontal lobe dysfunction; rather, they can also result from temporal lobe dysfunction.…”

Section: Discussionmentioning

confidence: 87%

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ALFF Value in Right Parahippocampal Gyrus Acts as a Potential Marker Monitoring Amyotrophic Lateral Sclerosis Progression: a Neuropsychological, Voxel-Based Morphometry, and Resting-State Functional MRI Study

Zhu

Cui

et al. 2015

J Mol Neurosci

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The aim of this study is to analyze cognitive impairment in amyotrophic lateral sclerosis (ALS). Forty-four participants matched for age, sex, and educational background were enrolled as the sporadic ALS group (n = 22) and the control group (n = 22). All participants completed comprehensive neuropsychological tests, including the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), the Stroop Color-Word Interference Test (SCWT), the Wisconsin Card Sorting Test (WCST), and the Frontal Assessment Battery. The participants underwent a series of 3.0 Tesla magnetic resonance imaging (MRI) scans. Resting-state functional MRI (Rs-fMRI) using the amplitude of low-frequency fluctuation (ALFF) was performed. Three-dimensional T1-weighted anatomical images obtained by voxel-based morphometry (VBM) were used to conduct correlation analyses and group comparisons with the demographic and neuropsychological characteristics. The results indicated that the decreased gray matter (GM) volume in the bilateral precentral gyri and increased ALFF values in the right parahippocampal gyrus, left inferior temporal gyrus, left anterior cingulate gyrus, right superior frontal gyrus, and left middle occipital gyrus were identified in the sporadic ALS group. The increased ALFF value in the right parahippocampal gyrus was positively correlated with ALS progression rate. The ALS patients exhibited poor performances on cognitive and executive tests, which were significantly or marginally significantly correlated with the ALFF values in the anterior cingulate gyrus and the frontal, temporal, and parahippocampal cortices. In conclusion, these findings provide evidence of an extramotor involvement and suggest that the ALFF value in the right parahippocampal gyrus could represent a potential marker to monitor disease progression.

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Section: Discussionsupporting

confidence: 45%

Section: Discussionmentioning

confidence: 87%

ALFF Value in Right Parahippocampal Gyrus Acts as a Potential Marker Monitoring Amyotrophic Lateral Sclerosis Progression: a Neuropsychological, Voxel-Based Morphometry, and Resting-State Functional MRI Study

Zhu

Cui

et al. 2015

J Mol Neurosci

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“…Given that the uncinate fasciculus connects temporal lobe structures such as the hippocampus with frontal lobe areas, its involvement highlights the contribution of structures other than the frontal lobe in memory performance in ALS. Hippocampal and parahippocampal pathology in ALS are well-described in post mortem studies [32,34,35], and lesions have been related to memory deficits. Interestingly, those lesions were different from those found in Alzheimer's Disease [34], which underlines the distinct neuropsychological profiles between patients with ALS and aMCI in the present study.…”

Section: Discussionmentioning

confidence: 99%

“…Most of them support an encoding or short recall deficit with relatively sparing of consolidation performance but the findings are inconsistent and have not been related to temporal lobe dysfunction. Recently, there has been growing postmortem and in vivo evidence of temporal lobe involvement in ALS, based on hippocampal TDP-43 pathology [31,32] and volume loss [33-35]. Temporal lobe pathology is also a key feature of Alzheimer's Disease (AD) with hippocampal atrophy even in early stages [36].…”

Section: Introductionmentioning

confidence: 99%

Memory deficits in amyotrophic lateral sclerosis are not exclusively caused by executive dysfunction: a comparative neuropsychological study of amnestic mild cognitive impairment

et al. 2014

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BackgroundRecent work suggests that ALS and frontotemporal dementia can occur together and share at least in part the same underlying pathophysiology. However, it is unclear at present whether memory deficits in ALS stem from a temporal lobe dysfunction, or are rather driven by frontal executive dysfunction. In this study we sought to investigate the nature of memory deficits by analyzing the neuropsychological performance of 40 ALS patients in comparison to 39 amnestic mild cognitive impairment (aMCI) patients and 40 healthy controls (HC). The neuropsychological battery tested for impairment in executive functions, as well as memory and visuo-spatial skills, the results of which were compared across study groups. In addition, we calculated composite scores for memory (learning, recall, recognition) and executive functions (verbal fluency, cognitive flexibility, working memory). We hypothesized that the nature of memory impairment in ALS will be different from those exhibited by aMCI patients.ResultsPatient groups exhibited significant differences in their type of memory deficit, with the ALS group showing impairment only in recognition, whereas aMCI patients showed short and delayed recall performance deficits as well as reduced short-term capacity. Regression analysis revealed a significant impact of executive function on memory performance exclusively for the ALS group, accounting for one fifth of their memory performance. Interestingly, merging all sub scores into a single memory and an executive function score obscured these differences.ConclusionThe presented results indicate that the interpretation of neuropsychological scores needs to take the distinct cognitive profiles in ALS and aMCI into consideration. Importantly, the observed memory deficits in ALS were distinctly different from those observed in aMCI and can be explained only to some extent in the context of comorbid (coexisting) executive dysfunction. These findings highlight the qualitative differences in temporal lobe dysfunction between ALS and aMCI patients, and support temporal lobe dysfunction as a mechanism underlying the distinct cognitive impairments observed in ALS.

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“…The EC receives and processes information from wide-spread polysensory and limbic cortical areas and sends its major outputs to hippocampus via the “perforant path” (PP, Van Hoesen, 1982; Witter, 2007). The PP degeneration was found to be associated with memory impairment in preclinical and clinical Alzheimer’s disease (AD) and other disorders with dementia (Hyman et al, 1986, 1988, Thal et al, 2000; Takeda et al, 2007). Generally the PP comprises entorhinal layer II projections to the DG, CA2 and CA3, and entorhinal layer III projections to CA1 and subiculum (Witter, 2007).…”

mentioning

confidence: 99%

Stratum radiatum of CA2 is an additional target of the perforant path in humans and monkeys

Ding¹,

Haber²,

Hoesen³

2010

NeuroReport

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The perforant path connects two key components of the medial temporal memory system, the entorhinal cortex and hippocampus. Entorhinal layer II projects densely to the outer portion of the molecular layer of the dentate gyrus and the stratum lacunosum-moleculare of CA2 and CA3 of the hippocampus. The present study for the first time reports that the stratum radiatum of CA2 but not of CA3 in the human brains receives “extra”, unique and dense projections from the layer II using an antibody against an abnormally phosphorylated tau (AT8), which stains both degenerating neurons and their processes including axon terminals in aging and early Alzheimer’s disease. This finding is also confirmed in CA2 of monkey hippocampus by means of anterograde tracer injections in the entorhinal cortex. Thus the present results indicate that CA2 in human and nonhuman primates receives stronger activation from the PP than CA3 does. Our finding also suggests that the SR of CA2 is a major converging zone of the projections from the perforant path and Schaffer collaterals. Thus, CA2 may play a unique role in hippocampal memory networks.

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Memory deficits in amyotrophic lateral sclerosis patients with dementia and degeneration of the perforant pathway

Cited by 32 publications

References 22 publications

ALFF Value in Right Parahippocampal Gyrus Acts as a Potential Marker Monitoring Amyotrophic Lateral Sclerosis Progression: a Neuropsychological, Voxel-Based Morphometry, and Resting-State Functional MRI Study

ALFF Value in Right Parahippocampal Gyrus Acts as a Potential Marker Monitoring Amyotrophic Lateral Sclerosis Progression: a Neuropsychological, Voxel-Based Morphometry, and Resting-State Functional MRI Study

Memory deficits in amyotrophic lateral sclerosis are not exclusively caused by executive dysfunction: a comparative neuropsychological study of amnestic mild cognitive impairment

Stratum radiatum of CA2 is an additional target of the perforant path in humans and monkeys

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