Neuropsychology. 2014 Nov;28(6):959-72. doi: 10.1037/neu0000117.

Retrograde Memory for Public Events in Mild Cognitive Impairment and its Relationship to Anterograde Memory and Neuroanatomy.

Christine N. Smith, Ph.D.

University of California, San Diego, and Veterans Affairs San Diego Healthcare System, San Diego, California

 

Abstract

OBJECTIVE: The study characterized the status of retrograde amnesia (RA) in amnestic mild cognitive impairment (MCI).

METHOD: We measured RA, anterograde amnesia (AA), brain measures, apolipoprotein-E status (ApoE), and conversion to probable Alzheimer’s disease (AD) across 3 years in 15 individuals with MCI. We compared the severity of amnesia and brain atrophy in MCI to a group of patients with limited damage to the hippocampus (H) or more extensive damage to the medial temporal lobe (MTL).

RESULTS: The MCI group exhibited modest AA, together with severe RA, covering nearly 4 decades before their diagnosis. Compared with H-MTL patients, the temporal extent of RA was disproportionate to the severity of AA. The MCI group exhibited more modest AA and MTL atrophy than H-MTL patients, together with more severe RA and neocortical atrophy than H-MTL patients. The severity of AA corresponded to the integrity of MTL structures, whereas the severity of RA corresponded to the integrity of both MTL and neocortical structures. RA (but not AA, nor measures of cognitive status) was related to ApoE status and subsequent diagnosis of probable AD. RA was predicted by heritable risk for AD, in addition to the integrity of MTL and neocortical structures.

CONCLUSIONS: Compared with H-MTL patients, the MCI group exhibited RA that was disproportionate to their AA and that was more severe than would be expected if their atrophy were limited primarily to the MTL. Heritable risk for AD, as well as the integrity of brain regions within and beyond the MTL, are important for understanding RA in MCI.

PMID: 25068664

 

Supplements:

When memory is impaired after brain damage or head injury both anterograde amnesia and retrograde amnesia tend to occur together. Anterograde amnesia refers to an impaired capacity for new learning. Retrograde amnesia refers to the loss of information that was acquired before the onset of amnesia. When brain damage is limited to the medial temporal lobe (MTL; i.e., the hippocampus and the cortices that make up parahippocampal gyrus: entorhinal cortex, perirhinal cortex, and parahippocampal cortex), the severity of anterograde amnesia is related to the severity of retrograde amnesia (Smith, Frascino, Hopkins, and Squire, 2013). But, it is also true that retrograde amnesia can sometimes appear disproportionately severe in comparison to anterograde amnesia.

Mild Cognitive Impairment (MCI) is considered a transitional stage between healthy aging and Alzheimer’s disease. Indeed, individuals diagnosed with MCI have an increased risk of developing Alzheimer’s disease. Previous studies have shown that anterograde memory impairment exhibited by MCI patients is related to the integrity of structures in the medial temporal lobe, specifically the hippocampus and entorhinal cortex. Yet, the status of retrograde amnesia in MCI patients is less well characterized. Retrograde amnesia has been described as absent, mild and temporally-limited to information learned just prior to the onset of amnesia, or severe and encompassing all time periods tested. We tested the severity of anterograde and retrograde amnesia in MCI patients and asked whether the severity of retrograde amnesia in MCI patients was related to the volumes of medial temporal lobe and cortical structures.

 

Figure 1

Figure 1. Patients with bilateral lesions of the hippocampal (H) and larger medial temporal lobe (MTL) lesions as the result of anoxia or encephalitis exhibited severe anterograde amnesia (lower red bar) and limited retrograde amnesia (lower yellow bar). By contrast, patients diagnosed with mild cognitive impairment exhibited limited anterograde amnesia (upper red bar) and severe retrograde amnesia (upper yellow bar). The dissociation between group and type of amnesia was significant (p < 0.01), indicating that the severity of retrograde amnesia in the MCI patients was out of proportion to the severity of their anterograde amnesia .The anterograde amnesia score was derived from four tests of new learning ability: Paired-associate learning, delayed recall of a complex diagram, delayed recall of a prose passage, and the memory subscale from the Dementia Rating Scale (Mattis, 1976). The retrograde amnesia score represents the severity of retrograde amnesia (duration in years) based on a test of 314 notable news events that occurred between 1931 and 2005. Retrograde amnesia was calculated from the number of 5-year time periods in which recall performance of an individual with memory impairment was significantly below control performance. For anterograde scores, lower scores represent more severe impairment, whereas for retrograde scores, higher scores indicate more severe impairment.

 

MCI patients (N=15) exhibited significant anterograde amnesia relative to controls (N=21). Yet, the severity of amnesia was relatively modest (see Figure 1) compared to a different group of memory-impaired patients (N=11) who developed amnesia as the result of brief oxygen loss (anoxia) or viral encephalitis and who have brain damage limited to the hippocampus (H patients) or larger lesions of the medial temporal lobe (MTL patients). The modest anterograde amnesia exhibited by the MCI patients corresponded to their modest hippocampal volume reduction (19% reduction relative to controls) relative to the H and MTL patients (56% reduction). Volume loss in the parahippocampal gyrus was similar for both groups of patients.

Compared to the relatively modest anterograde memory impairment exhibited by the MCI patients, they exhibited severe retrograde memory loss (see Figure 1) affecting information learned nearly 40 years prior to the onset of amnesia (i.e., the year they were diagnosed with MCI). By contrast, the H and MTL group exhibited very severe AA together with moderate RA. Thus, the MCI group exhibited retrograde amnesia that was disproportionate to the severity of their anterograde amnesia. Furthermore, since the modest MTL damage in the MCI group corresponded their modest anterograde amnesia, damage likely exists outside of the MTL to account for their severe retrograde amnesia. Damage likely exists in neocortex where the memories themselves are stored.

 

Figure 2

Figure 2. A coronal magnetic resonance image showing brain regions where the severity of retrograde amnesia in MCI patients corresponded to smaller neocortical volumes in right lateral temporal cortex (blue), left posterior cingulate cortex (yellow), and paracentral lobule bilaterally (magenta). Smaller volumes in the medial temporal lobe (in the hippocampus bilaterally [red] and in left parahippocampal cortex [green]) were also associated with more severe retrograde amnesia. The left side of the brain is shown on the left side of the figure.

 

Next, we asked where did integrity of brain regions correspond to the severity of retrograde amnesia. Based on quantitative measurement of structural magnetic resonance imaging scans, we carried out an analysis of neocortical volumes in the MCI group. We observed three regions in the neocortex where volumes were related to the severity of retrograde amnesia. The regions were the right lateral temporal cortex, left posterior cingulate cortex, and the immediately adjacent paracentral lobule bilaterally (see Figure 2). In addition, the severity of retrograde amnesia was also related to the volumes of MTL regions, specifically, the volume of the hippocampus bilaterally and left parahippocampal cortex. For all of these regions, more severe retrograde amnesia corresponded to smaller brain volumes. By comparison, the severity of anterograde amnesia (see Figure 3) was related only to the volumes of MTL structures (the hippocampus bilaterally and left parahippocampal cortex).

The findings for lateral temporal cortex may be particularly important because damage to this region has previously been associated with difficulty remembering the past. For example, patients diagnosed with semantic dementia primarily have damage to this region, but relatively less damage to the MTL. These individuals exhibit severe retrograde amnesia together with relatively mild anterograde amnesia. They also have difficulty with semantic memory in general and are impaired at naming objects, for example. The MCI group did not exhibit these types of difficulties with semantic information.

The main conclusion is that regions in the neocortex (including lateral temporal cortex and medial parietal cortex) are likely the regions where the memories themselves are stored. Thus, retrograde amnesia can be caused by MTL damage (in the case of the H and MTL patients), neocortical damage (in the case of semantic dementia patients), or both (in the case of the MCI patients).

 

Figure 3

Figure 3. A coronal magnetic resonance image showing brain regions where the severity of anterograde amnesia in MCI patients corresponded to smaller volumes in the medial temporal lobe (hippocampus, red; left parahippocampal cortex, green). The left side of the brain is shown on the left side of the figure.

 

References

Mattis, S. (1976). Dementia Rating Scale. In R. Bellack & B. Keraso (Eds.), Geriatric Psychiatry (pp. 77–121). New York, NY: Grune and Stratton.

Smith, C. N., Frascino, J. C., Hopkins, R. O., & Squire, L. R. (2013). The nature of anterograde and retrograde memory impairment after damage to the medial temporal lobe. Neuropsychologia, 51, 2709–2714.

 

 

 

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