Objective: This study aimed to investigate the association with the functioning of instrumental-activities of daily living (I-ADL) and future development of Alzheimer’s disease (AD) in persons with mild cognitive impairment (MCI). Methods: A total of 116 patients with MCI, aged 65 years to 91 years (male: 88, female: 91 at first visit), from a large hospital cen-ter in Korea, were identified. Those who developed at least two consecutive 1-year follow up were diagnosed according to the DSM-5criteria. Results: When the same level of Mini Mental State Examination (MMSE) scores was given, it could be seen that the probability of AD transfer was predicted differently due to complex changes in I-ADL scores. Specifically, it was observed that with an MMSEscore of approximately 23.9 points, as the I-ADL points increase, the odds of transfer also increase approximately 6.1% (I-ADL low: 8.5 points) to 23.5% (I-ADL high: 31.4), therefore odds of transfer are 17.4% higher than I-ADL low condition. Conclusion The study suggested that even though cognitive problems were not observed due to high MMSE scores, severe damage to I-ADL could lead to AD. Applications may be limited, but such cases may require careful monitoring at the site.

Objective: This study aimed to investigate the association with the functioning of instrumental-activities of daily living (I-ADL) and future development of Alzheimer’s disease (AD) in persons with mild cognitive impairment (MCI). Methods: A total of 116 patients with MCI, aged 65 years to 91 years (male: 88, female: 91 at first visit), from a large hospital cen-ter in Korea, were identified. Those who developed at least two consecutive 1-year follow up were diagnosed according to the DSM-5criteria. Results: When the same level of Mini Mental State Examination (MMSE) scores was given, it could be seen that the probability of AD transfer was predicted differently due to complex changes in I-ADL scores. Specifically, it was observed that with an MMSEscore of approximately 23.9 points, as the I-ADL points increase, the odds of transfer also increase approximately 6.1% (I-ADL low: 8.5 points) to 23.5% (I-ADL high: 31.4), therefore odds of transfer are 17.4% higher than I-ADL low condition. Conclusion The study suggested that even though cognitive problems were not observed due to high MMSE scores, severe damage to I-ADL could lead to AD. Applications may be limited, but such cases may require careful monitoring at the site.

BACKGROUND AND PURPOSE: To analyze 18F-THK5351 positron emission tomography (PET) scans of patients with clinically diagnosed nonfluent/agrammatic variant primary progressive aphasia (navPPA). METHODS: Thirty-one participants, including those with Alzheimer's disease (AD, n=13), navPPA (n=3), and those with normal control (NC, n=15) who completed 3 Tesla magnetic resonance imaging, 18F-THK5351 PET scans, and detailed neuropsychological tests, were included. Voxel-based and region of interest (ROI)-based analyses were performed to evaluate retention of 18F-THK5351 in navPPA patients. RESULTS: In ROI-based analysis, patients with navPPA had higher levels of THK retention in the Broca's area, bilateral inferior frontal lobes, bilateral precentral gyri, and bilateral basal ganglia. Patients with navPPA showed higher levels of THK retention in bilateral frontal lobes (mainly left side) compared than NC in voxel-wise analysis. CONCLUSIONS: In our study, THK retention in navPPA patients was mainly distributed at the frontal region which was well correlated with functional-radiological distribution of navPPA. Our results suggest that tau PET imaging could be a supportive tool for diagnosis of navPPA in combination with a clinical history.
Alzheimer Disease ; Aphasia, Primary Progressive* ; Basal Ganglia ; Broca Area ; Diagnosis ; Frontal Lobe ; Humans ; Magnetic Resonance Imaging ; Neurofibrillary Tangles ; Neuropsychological Tests ; Positron-Emission Tomography ; Primary Progressive Nonfluent Aphasia ; tau Proteins

BACKGROUND AND PURPOSE: There are three distinct subtypes of primary progressive aphasia (PPA): the nonfluent/agrammatic variant (nfvPPA), the semantic variant (svPPA), and the logopenic variant (lvPPA). We sought to characterize the pattern of [¹⁸F]-THK5351 retention across all three subtypes and determine the topography of [¹⁸F]-THK5351 retention correlated with each neurolinguistic score. METHODS: We enrolled 50 participants, comprising 13 PPA patients (3 nfvPPA, 5 svPPA, and 5 lvPPA) and 37 subjects with normal cognition (NC) who underwent 3.0-tesla magnetic resonance imaging, [¹⁸F]-THK5351 positron-emission tomography scans, and detailed neuropsychological tests. The PPA patients additionally participated in extensive neurolinguistic tests. Voxel-wise and region-of-interest-based analyses were performed to analyze [¹⁸F]-THK5351 retention. RESULTS: The nfvPPA patients exhibited higher [¹⁸F]-THK5351 retention in the the left inferior frontal and precentral gyri. In svPPA patients, [¹⁸F]-THK5351 retention was elevated in the anteroinferior and lateral temporal cortices compared to the NC group (left>right). The lvPPA patients exhibited predominant [¹⁸F]-THK5351 retention in the inferior parietal, lateral temporal, and dorsolateral prefrontal cortices, and the precuneus (left>right). [¹⁸F]-THK5351 retention in the left inferior frontal area was associated with lower fluency scores. Comprehension was correlated with [¹⁸F]-THK5351 retention in the left temporal cortices. Repetition was associated with [¹⁸F]-THK5351 retention in the left inferior parietal and posterior temporal areas, while naming difficulty was correlated with retention in the left fusiform and temporal cortices. CONCLUSIONS: The pattern of [¹⁸F]-THK5351 retention was well matched with clinical and radiological findings for each PPA subtype, in agreement with the anatomical and functional location of each language domain.
Aphasia, Primary Progressive ; Cognition ; Comprehension ; Humans ; Magnetic Resonance Imaging ; Neurofibrillary Tangles ; Neuropsychological Tests ; Parietal Lobe ; Positron-Emission Tomography ; Prefrontal Cortex ; Rabeprazole ; Semantics ; Temporal Lobe

Background: and PurposeMild cognitive impairment (MCI) is a condition with diverse clinical outcomes and subgroups. Here we investigated the topographic distribution of tau in vivo using the positron emission tomography (PET) tracer [18F]THK5351 in MCI subgroups. Methods: This study included 96 participants comprising 38 with amnestic MCI (aMCI), 21 with nonamnestic MCI (naMCI), and 37 with normal cognition (NC) who underwent 3.0-T MRI, [18F]THK5351 PET, and detailed neuropsychological tests. [18F]flutemetamol PET was also performed in 62 participants. The aMCI patients were further divided into three groups: 1) verbal-aMCI, only verbal memory impairment; 2) visual-aMCI, only visual memory impairment; and 3) both-aMCI, both visual and verbal memory impairment. Voxel-wise statistical analysis and region-of-interest -based analyses were performed to evaluate the retention of [18F]THK5351 in the MCI subgroups. Subgroup analysis of amyloid-positive and -negative MCI patients was also performed. Correlations between [18F]THK5351 retention and different neuropsychological tests were evaluated using statistical parametric mapping analyses. Results: [18F]THK5351 retention in the lateral temporal, mesial temporal, parietal, frontal, posterior cingulate cortices and precuneus was significantly greater in aMCI patients than in NC subjects, whereas it did not differ significantly between naMCI and NC participants. [18F] THK5351 retention was greater in the both-aMCI group than in the verbal-aMCI and visualaMCI groups, and greater in amyloid-positive than amyloid-negative MCI patients. The cognitive function scores were significantly correlated with cortical [18F]THK5351 retention. Conclusions [18F]THK5351 PET might be useful for identifying distinct topographic patterns of [18F]THK5351 retention in subgroups of MCI patients who are at greater risk of the progression to Alzheimer's dementia.