Neuropathological comparisons of amnestic and nonamnestic mild cognitive impairment

Brittany Dugger, Kathryn Davis, Michael Malek-Ahmadi, Joseph G. Hentz, Shawn Sandhu, Thomas G. Beach, Charles H. Adler, Richard J. Caselli, Travis A. Johnson, Geidy E. Serrano, Holly A. Shill, Christine Belden, Erika Driver-Dunckley, John N. Caviness, Lucia I. Sue, Sandra Jacobson, Jessica Powell, Marwan N. Sabbagh

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Background: Although there are studies investigating the pathologic origins of mild cognitive impairment (MCI), they have revolved around comparisons to normal elderly individuals or those with Alzheimer's disease (AD) or other dementias. There are few studies directly comparing the comprehensive neuropathology of amnestic (aMCI) and nonamnestic (naMCI) MCI. Methods: The database of the Brain and Body Donation Program (www.brainandbodydonationprogram.org), a longitudinal clinicopathological study of normal aging and neurodegenerative disorders, was queried for subjects who were carrying a diagnosis of aMCI or naMCI at the time of autopsy. Neuropathological lesions, including neuritic plaques, neurofibrillary tangles (NFTs), Lewy bodies (LBs), infarcts, cerebral white matter rarefaction (CWMR), cerebral amyloid angiopathy (CAA), and concurrent major clinicopathological diagnoses, including Parkinson's disease (PD) were analyzed. Results: Thirty four subjects with aMCI and 15 naMCI met study criteria. Subjects with aMCI were older at death (88 vs. 83 years of age, p = 0.03). Individuals with naMCI had higher densities of LBs within the temporal lobe (p = 0.04) while subjects with aMCI had a propensity for increased NFTs in parietal and temporal lobes (p values = 0.07). After adjusting for age at death, the only significant difference was greater densities of temporal lobe NFTs within the aMCI group. Other regional pathology scores for plaques, NFTs, and LBs were similar between groups. Subjects met clinico-pathological criteria for co-existent PD in 24 % aMCI and 47 % naMCI while neuropathological criteria for AD were met in equal percentages of aMCI and of naMCI cases (53 %); these proportional differences were not significant (p values > 0.35). Furthermore, regardless of amnestic status, there was a greater presence of CAA (71 % of MCI with executive dysfunction vs. 39 % without p = 0.03) and a greater presence of CWMR (81 % of MCI with executive dysfunction and 54 % without p = 0.046) in MCI cases with executive dysfunction. Conclusions: No single pathologic entity strongly dichotomized MCI groups, perhaps due to the pathologic heterogeneity found within both entities. However, these data suggest the possibility for naMCI to have a propensity for increased LBs and aMCI for increased NFTs in select anatomic regions.

Original languageEnglish (US)
Article number146
JournalBMC Neurology
Volume15
Issue number1
DOIs
StatePublished - Aug 20 2015
Externally publishedYes

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Neurofibrillary Tangles
Lewy Bodies
Temporal Lobe
Cerebral Amyloid Angiopathy
Parkinson Disease
Alzheimer Disease
Parietal Lobe
Amyloid Plaques
Neurodegenerative Diseases
Longitudinal Studies
Dementia
Cognitive Dysfunction
Autopsy
Databases
Pathology
Brain

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Dugger, B., Davis, K., Malek-Ahmadi, M., Hentz, J. G., Sandhu, S., Beach, T. G., ... Sabbagh, M. N. (2015). Neuropathological comparisons of amnestic and nonamnestic mild cognitive impairment. BMC Neurology, 15(1), [146]. https://doi.org/10.1186/s12883-015-0403-4

Neuropathological comparisons of amnestic and nonamnestic mild cognitive impairment. / Dugger, Brittany; Davis, Kathryn; Malek-Ahmadi, Michael; Hentz, Joseph G.; Sandhu, Shawn; Beach, Thomas G.; Adler, Charles H.; Caselli, Richard J.; Johnson, Travis A.; Serrano, Geidy E.; Shill, Holly A.; Belden, Christine; Driver-Dunckley, Erika; Caviness, John N.; Sue, Lucia I.; Jacobson, Sandra; Powell, Jessica; Sabbagh, Marwan N.

In: BMC Neurology, Vol. 15, No. 1, 146, 20.08.2015.

Research output: Contribution to journalArticle

Dugger, B, Davis, K, Malek-Ahmadi, M, Hentz, JG, Sandhu, S, Beach, TG, Adler, CH, Caselli, RJ, Johnson, TA, Serrano, GE, Shill, HA, Belden, C, Driver-Dunckley, E, Caviness, JN, Sue, LI, Jacobson, S, Powell, J & Sabbagh, MN 2015, 'Neuropathological comparisons of amnestic and nonamnestic mild cognitive impairment', BMC Neurology, vol. 15, no. 1, 146. https://doi.org/10.1186/s12883-015-0403-4
Dugger, Brittany ; Davis, Kathryn ; Malek-Ahmadi, Michael ; Hentz, Joseph G. ; Sandhu, Shawn ; Beach, Thomas G. ; Adler, Charles H. ; Caselli, Richard J. ; Johnson, Travis A. ; Serrano, Geidy E. ; Shill, Holly A. ; Belden, Christine ; Driver-Dunckley, Erika ; Caviness, John N. ; Sue, Lucia I. ; Jacobson, Sandra ; Powell, Jessica ; Sabbagh, Marwan N. / Neuropathological comparisons of amnestic and nonamnestic mild cognitive impairment. In: BMC Neurology. 2015 ; Vol. 15, No. 1.
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abstract = "Background: Although there are studies investigating the pathologic origins of mild cognitive impairment (MCI), they have revolved around comparisons to normal elderly individuals or those with Alzheimer's disease (AD) or other dementias. There are few studies directly comparing the comprehensive neuropathology of amnestic (aMCI) and nonamnestic (naMCI) MCI. Methods: The database of the Brain and Body Donation Program (www.brainandbodydonationprogram.org), a longitudinal clinicopathological study of normal aging and neurodegenerative disorders, was queried for subjects who were carrying a diagnosis of aMCI or naMCI at the time of autopsy. Neuropathological lesions, including neuritic plaques, neurofibrillary tangles (NFTs), Lewy bodies (LBs), infarcts, cerebral white matter rarefaction (CWMR), cerebral amyloid angiopathy (CAA), and concurrent major clinicopathological diagnoses, including Parkinson's disease (PD) were analyzed. Results: Thirty four subjects with aMCI and 15 naMCI met study criteria. Subjects with aMCI were older at death (88 vs. 83 years of age, p = 0.03). Individuals with naMCI had higher densities of LBs within the temporal lobe (p = 0.04) while subjects with aMCI had a propensity for increased NFTs in parietal and temporal lobes (p values = 0.07). After adjusting for age at death, the only significant difference was greater densities of temporal lobe NFTs within the aMCI group. Other regional pathology scores for plaques, NFTs, and LBs were similar between groups. Subjects met clinico-pathological criteria for co-existent PD in 24 {\%} aMCI and 47 {\%} naMCI while neuropathological criteria for AD were met in equal percentages of aMCI and of naMCI cases (53 {\%}); these proportional differences were not significant (p values > 0.35). Furthermore, regardless of amnestic status, there was a greater presence of CAA (71 {\%} of MCI with executive dysfunction vs. 39 {\%} without p = 0.03) and a greater presence of CWMR (81 {\%} of MCI with executive dysfunction and 54 {\%} without p = 0.046) in MCI cases with executive dysfunction. Conclusions: No single pathologic entity strongly dichotomized MCI groups, perhaps due to the pathologic heterogeneity found within both entities. However, these data suggest the possibility for naMCI to have a propensity for increased LBs and aMCI for increased NFTs in select anatomic regions.",
author = "Brittany Dugger and Kathryn Davis and Michael Malek-Ahmadi and Hentz, {Joseph G.} and Shawn Sandhu and Beach, {Thomas G.} and Adler, {Charles H.} and Caselli, {Richard J.} and Johnson, {Travis A.} and Serrano, {Geidy E.} and Shill, {Holly A.} and Christine Belden and Erika Driver-Dunckley and Caviness, {John N.} and Sue, {Lucia I.} and Sandra Jacobson and Jessica Powell and Sabbagh, {Marwan N.}",
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T1 - Neuropathological comparisons of amnestic and nonamnestic mild cognitive impairment

AU - Dugger, Brittany

AU - Davis, Kathryn

AU - Malek-Ahmadi, Michael

AU - Hentz, Joseph G.

AU - Sandhu, Shawn

AU - Beach, Thomas G.

AU - Adler, Charles H.

AU - Caselli, Richard J.

AU - Johnson, Travis A.

AU - Serrano, Geidy E.

AU - Shill, Holly A.

AU - Belden, Christine

AU - Driver-Dunckley, Erika

AU - Caviness, John N.

AU - Sue, Lucia I.

AU - Jacobson, Sandra

AU - Powell, Jessica

AU - Sabbagh, Marwan N.

PY - 2015/8/20

Y1 - 2015/8/20

N2 - Background: Although there are studies investigating the pathologic origins of mild cognitive impairment (MCI), they have revolved around comparisons to normal elderly individuals or those with Alzheimer's disease (AD) or other dementias. There are few studies directly comparing the comprehensive neuropathology of amnestic (aMCI) and nonamnestic (naMCI) MCI. Methods: The database of the Brain and Body Donation Program (www.brainandbodydonationprogram.org), a longitudinal clinicopathological study of normal aging and neurodegenerative disorders, was queried for subjects who were carrying a diagnosis of aMCI or naMCI at the time of autopsy. Neuropathological lesions, including neuritic plaques, neurofibrillary tangles (NFTs), Lewy bodies (LBs), infarcts, cerebral white matter rarefaction (CWMR), cerebral amyloid angiopathy (CAA), and concurrent major clinicopathological diagnoses, including Parkinson's disease (PD) were analyzed. Results: Thirty four subjects with aMCI and 15 naMCI met study criteria. Subjects with aMCI were older at death (88 vs. 83 years of age, p = 0.03). Individuals with naMCI had higher densities of LBs within the temporal lobe (p = 0.04) while subjects with aMCI had a propensity for increased NFTs in parietal and temporal lobes (p values = 0.07). After adjusting for age at death, the only significant difference was greater densities of temporal lobe NFTs within the aMCI group. Other regional pathology scores for plaques, NFTs, and LBs were similar between groups. Subjects met clinico-pathological criteria for co-existent PD in 24 % aMCI and 47 % naMCI while neuropathological criteria for AD were met in equal percentages of aMCI and of naMCI cases (53 %); these proportional differences were not significant (p values > 0.35). Furthermore, regardless of amnestic status, there was a greater presence of CAA (71 % of MCI with executive dysfunction vs. 39 % without p = 0.03) and a greater presence of CWMR (81 % of MCI with executive dysfunction and 54 % without p = 0.046) in MCI cases with executive dysfunction. Conclusions: No single pathologic entity strongly dichotomized MCI groups, perhaps due to the pathologic heterogeneity found within both entities. However, these data suggest the possibility for naMCI to have a propensity for increased LBs and aMCI for increased NFTs in select anatomic regions.

AB - Background: Although there are studies investigating the pathologic origins of mild cognitive impairment (MCI), they have revolved around comparisons to normal elderly individuals or those with Alzheimer's disease (AD) or other dementias. There are few studies directly comparing the comprehensive neuropathology of amnestic (aMCI) and nonamnestic (naMCI) MCI. Methods: The database of the Brain and Body Donation Program (www.brainandbodydonationprogram.org), a longitudinal clinicopathological study of normal aging and neurodegenerative disorders, was queried for subjects who were carrying a diagnosis of aMCI or naMCI at the time of autopsy. Neuropathological lesions, including neuritic plaques, neurofibrillary tangles (NFTs), Lewy bodies (LBs), infarcts, cerebral white matter rarefaction (CWMR), cerebral amyloid angiopathy (CAA), and concurrent major clinicopathological diagnoses, including Parkinson's disease (PD) were analyzed. Results: Thirty four subjects with aMCI and 15 naMCI met study criteria. Subjects with aMCI were older at death (88 vs. 83 years of age, p = 0.03). Individuals with naMCI had higher densities of LBs within the temporal lobe (p = 0.04) while subjects with aMCI had a propensity for increased NFTs in parietal and temporal lobes (p values = 0.07). After adjusting for age at death, the only significant difference was greater densities of temporal lobe NFTs within the aMCI group. Other regional pathology scores for plaques, NFTs, and LBs were similar between groups. Subjects met clinico-pathological criteria for co-existent PD in 24 % aMCI and 47 % naMCI while neuropathological criteria for AD were met in equal percentages of aMCI and of naMCI cases (53 %); these proportional differences were not significant (p values > 0.35). Furthermore, regardless of amnestic status, there was a greater presence of CAA (71 % of MCI with executive dysfunction vs. 39 % without p = 0.03) and a greater presence of CWMR (81 % of MCI with executive dysfunction and 54 % without p = 0.046) in MCI cases with executive dysfunction. Conclusions: No single pathologic entity strongly dichotomized MCI groups, perhaps due to the pathologic heterogeneity found within both entities. However, these data suggest the possibility for naMCI to have a propensity for increased LBs and aMCI for increased NFTs in select anatomic regions.

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