We aimed to compare cerebral beta-amyloid protein (Aβ) positivity rate and amyloid accumulation pattern on amyloid positron emission tomography (PET) between mild cognitive impairment (MCI) subtypes, i.e. amnestic mild cognitive impairment (aMCI) and non-amnestic mild cognitive impairment (naMCI).
The study participants were 34 naMCI patients and age-, sex- and education-matched 68 aMCI patients (1:2 ratio) who visited the Dementia and Age-Associated Cognitive Decline Clinic of the Seoul National University Hospital. All participants received comprehensive clinical and neuropsychological assessments and [18F] florbetaben PET.
Aβ positivity rate of naMCI group (26.5%) was significantly lower than that of aMCI group (64.7%). Among Aβ positive individuals, there was no difference in Aβ accumulation pattern between naMCI and aMCI.
The findings suggest that MCI subtypes based on impaired cognitive domains have a differential association with brain Aβ deposition, a core pathology of AD. Amnestic subtype of MCI are more closely associated with cerebral Aβ deposition compared to non-amnestic subtype. In contrast, the pattern of amyloid deposition does not appear to have any difference between the subtypes.
Mild cognitive impairment (MCI) is a clinical condition between cognitively normal aging and dementia [
In regard of in vivo neuropathological substrates underlying each MCI subtypes, however, sufficient information is still not available. Although several amyloid PET studies indicated that the positivity rate of beta-amyloid protein (Aβ) deposition, a core neuropathology of AD, is higher in aMCI than in naMCI [
Therefore, we aimed to examine the differences of amyloid positivity rate and accumulation pattern between aMCI and naMCI subtypes in MCI subjects including more naMCI individuals compared to previous studies.
A total of 102 MCI (34 naMCI and age-, sex-, and education matched 68 aMCI) patients were recruited from the pool of older adults who visited the Dementia and Age-Associated Cognitive Decline Clinic of the Seoul National University Hospital (SNUH) to get outpatient clinical services. All participants met the current consensus criteria for MCI: 1) cognitive impairment confirmed by an informant, 2) objective cognitive impairment, 3) preserved global cognitive function, 4) independence in functional activities, and 5) not demented [
All participants underwent comprehensive clinical and neuropsychological evaluation based on the CERAD-K assessment packet [
All participant received [18F] florbetaben positron emission tomography (PET) scan. PET scans were performed using the ECAT EXACT47scanner (Siemens-CTI; Knoxville, TN, USA). The participants were classified as either Aβ positive or negative according to the Brain Amyloid Plaque Load (BAPL) score [
All statistical analyses were conducted using SPSS (version 24, IBM Corp., Armonk, NY, USA). For the comparison between aMCI and naMCI, Student’s t-test or chi-square test was used depending on the type of variables. The threshold for statistical significance was p<0.05 for all the analyses.
The Aβ positivity rate of aMCI and naMCI was 64.7% and 26.5%, respectively (
There was no significant difference in the proportion of amyloid accumulation patterns between Aβ positive aMCI and Aβ positive naMCI (
In the present study, cerebral Aβ positivity rate was significantly higher in aMCI compared with naMCI. There was no difference in the proportion of Aβ accumulation patterns between aMCI and naMCI cases with amyloid positivity.
The Aβ positivity rate for aMCI (64.7%) observed in this study was very similar to the rates reported in previous studies, which ranged from 57.9% to 67.9% [
We also compared the proportion of Aβ accumulation patterns between aMCI and naMCI and did not find any significant difference. This observation indicates that regional distribution pattern of cerebral Aβ accumulation is not associated with the difference of impaired cognitive domain in MCI. A previous study also reported similar result although the study included only three Aβ positive naMCI subjects [
Although previous clinical studies suggested that naMCI individuals are more related with vascular dementia than aMCI ones [
Although the present study has a strength in that relatively large number of naMCI patients were included, a couple of limitations should also be mentioned. First, as the MCI subjects were recruited from a dementia clinic in tertiary hospital, there may be some limitation to generalize the results to community population. Second, this study did not evaluate other pathologies frequently found in brain of older adults, such as cerebral tau, alpha synuclein, TDP-43, and vascular pathologies. To get more understandings for the causative neuropathologies underlying MCI subtypes, future studies using other brain imaging modalities or post-mortem brains are necessary.
In conclusion, the current findings suggest that MCI subtypes based on impaired cognitive domains have a differential association with brain Aβ deposition, a core pathology of AD. Amnestic subtype of MCI are more closely associated with cerebral Aβ deposition compared to non-amnestic subtype. In contrast, the pattern of amyloid deposition does not appear to have any difference between the subtypes.
This study was supported by a grant from Ministry of Science and ICT, Republic of Korea (Grant No. NRF-2014M3C7A1046042) and a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (Grant No: HI18C0630 & HI19C0149).
The authors have no potential conflicts of interest to disclose.
Conceptualization: Dong Young Lee, Jun Ho Lee, Sun Hyung Lee. Data curation: Jun Ho Lee, Sun Hyung Lee. Formal analysis: Sun Hyung Lee, Jun Ho Lee. Funding acquisition: Dong Young Lee. Investigation: Dong Young Lee, Jun Ho Lee, Min Soo Byun, Dahyun Yi, Gijung Jung, Jee Eun Park. Methodology: Dong Young Lee, Jun Ho Lee, Min Soo Byun, Dahyun Yi. Project administration: Dong Young Lee, Jun Ho Lee, Min Soo Byun, Dahyun Yi, Gijung Jung, Jee Eun Park. Resources: Dong Young Lee, Jun Ho Lee, Min Soo Byun. Supervision: Dong Young Lee, Jun Ho Lee. Validation: Dong Young Lee, Jun Ho Lee. Visualization: Sun Hyung Lee. Writing—original draft: Sun Hyung Lee. Writing—review & editing: Dong Young Lee, Jun Ho Lee, Min Soo Byun, Dahyun Yi, Gijung Jung, Jee Eun Park.
Cerebral beta-amyloid protein (Aβ) accumulation patterns of [18F] florbetaben PET image. A: Aβ negative. B: Predominant Aβ retention in frontal, anterior cingulate, lateral temporal, and basal ganglia (A-pattern). C: Generalized Aβ retention (B-pattern).
Distribution of cerebral beta-amyloid protein (Aβ) positive and negative cases in amnestic mild cognitive impairment (aMCI) and non-amnestic mild cognitive impairment (naMCI), and distribution of A-Pattern and B-Pattern accumulation in Aβ positive aMCI and naMCI.
Demographic, clinical and neuropsychological characteristics of mild cognitive impairment subtypes
Variables | aMCI (N=68) | naMCI (N=34) | p-value |
---|---|---|---|
Demographic and clinical characteristics | |||
Age (y) | 74.6±6.5 | 74.3±6.9 | 0.801 |
Female, N (%) | 58 (85.3) | 29 (85.3) | 1.000 |
Education (y) | 9.37±4.97 | 8.8±4.71 | 0.597 |
Age of onset (y) | 71.7±7.5 | 71.5±7.2 | 0.910 |
Duration of illness (y) | 2.99±2.31 | 2.76±1.58 | 0.617 |
APOE4 carrier, N (%) |
22 (40.0) | 7 (26.9) | 0.252 |
CDR SOB | 1.71±0.66 | 1.43±0.64 | 0.044 |
VRS total | 1.31±1.08 | 1.65±1.10 | 0.142 |
Neuropsychological tests (z-score) | |||
MMSE | -1.12±0.98 | -0.42±0.85 | 0.001 |
Semantic fluency | -0.69±0.96 | -0.76±0.84 | 0.721 |
Boston naming | -0.11±1.34 | -0.26±1.23 | 0.574 |
Word list memory | -1.09±0.94 | -0.25±0.57 | <0.001 |
Word list recall | -1.70±0.92 | -0.23±0.76 | <0.001 |
Word list recognition | -1.36±1.82 | -0.15±0.76 | <0.001 |
Constructional praxis | -0.24±1.14 | -0.25±1.05 | 0.971 |
Constructional recall | -1.25±0.84 | -0.32±0.76 | <0.001 |
Stroop color-word | -0.92±1.09 | -1.26±0.95 | 0.115 |
Data are presented as means±SD for continuous variables and as N (%) for categorical variables with p-values for comparison between aMCI and naMCI. Continuous variables were analyzed through Student’s t-test and categorical variables were analyzed through chi-square test.
number of participants who underwent APOE genotyping were 81 (aMCI 55, naMCI 26).
aMCI: amnestic mild cognitive impairment, naMCI: non-amnestic mild cognitive impairment, APOE4: apolipoprotein E ε4, CDR-SOB: Clinical Dementia Rating sum of box, VRS: vascular risk score, MMSE: Mini-Mental State Examination
Comparison of Aβ positivity rate between mild cognitive impairment subtypes
aMCI (N=68) | naMCI (N=34) | p-value | |
---|---|---|---|
Aβ positive | 44 (64.7) | 9 (26.5) | <0.001 |
Aβ negative | 24 (35.3) | 25 (73.5) |
Data are presented as N (%). P-value for comparison of aMCI and naMCI with chi-square test. Aβ: beta-amyloid protein, aMCI: amnestic mild cognitive impairment, naMCI: non-amnestic mild cognitive impairment
Comparison of the proportion of Aβ accumulation patterns between Aβ positive aMCI and naMCI
aMCI (N=44) | naMCI (N=9) | p-value | |
---|---|---|---|
A-pattern | 20 (45.5) | 3 (33.3) | 0.504 |
B-pattern | 24 (54.5) | 6 (66.7) |
Data are presented as N (%). P-value for comparison of aMCI and naMCI with chi-square test. Aβ: beta-amyloid protein, aMCI: amnestic mild cognitive impairment, naMCI: non-amnestic mild cognitive impairment