Menstrually-related migraine shapes the structural similarity network integration of brain.

Menstrually-related migraine (MM) is a primary migraine in women of reproductive age. The underlying neural mechanism of MM was still unclear. In this study, we aimed to reveal the case-control differences in network integration and segregation for the morphometric similarity network of MM. Thirty-six patients with MM and 29 healthy females were recruited and underwent MRI scanning. The morphometric features were extracted in each region to construct the single-subject interareal cortical connection using morphometric similarity. The network topology characteristics, in terms of integration and segregation, were analyzed. Our results revealed that, in the absence of morphology differences, disrupted cortical network integration was found in MM patients compared to controls. The patients with MM showed a decreased global efficiency and increased characteristic path length compared to healthy controls. Regional efficiency analysis revealed the decreased efficiency in the left precentral gyrus and bilateral superior temporal gyrus contributed to the decreased network integration. The increased nodal degree centrality in the right pars triangularis was positively associated with the attack frequency in MM. Our results suggested MM would reorganize the morphology in the pain-related brain regions and reduce the parallel information processing capacity of the brain.

Comparing machine learning-derived MRI-based and blood-based neurodegeneration biomarkers in predicting syndromal conversion in early AD.

INTRODUCTION: We compared the machine learning-derived, MRI-based Alzheimer's disease (AD) resemblance atrophy index (AD-RAI) with plasma neurofilament light chain (NfL) level in predicting conversion of early AD among cognitively unimpaired (CU) and mild cognitive impairment (MCI) subjects. METHODS: We recruited participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) who had the following data: clinical features (age, gender, education, Montreal Cognitive Assessment [MoCA]), structural MRI, plasma biomarkers (p-tau181 , NfL), cerebrospinal fluid biomarkers (CSF) (Aß42, p-tau181 ), and apolipoprotein E (APOE) ε4 genotype. We defined AD using CSF Aß42 (A+) and p-tau181 (T+). We defined conversion (C+) if a subject progressed to the next syndromal stage within 4 years. RESULTS: Of 589 participants, 96 (16.3%) were A+T+C+. AD-RAI performed better than plasma NfL when added on top of clinical features, plasma p-tau181 , and APOE ε4 genotype (area under the curve [AUC] = 0.832 vs. AUC = 0.650 among CU, AUC = 0.853 vs. AUC = 0.805 among MCI) in predicting A+T+C+. DISCUSSION: AD-RAI outperformed plasma NfL in predicting syndromal conversion of early AD. HIGHLIGHTS: AD-RAI outperformed plasma NfL in predicting syndromal conversion among early AD. AD-RAI showed better metrics than volumetric hippocampal measures in predicting syndromal conversion. Combining clinical features, plasma p-tau181 and apolipoprotein E (APOE) with AD-RAI is the best model for predicting syndromal conversion.

Quantitative Susceptibility Mapping of the Hippocampal Fimbria in Alzheimer's Disease.

BACKGROUND: The fimbria is a small white matter bundle that connects the hippocampus to the rest of the brain. Damage to the hippocampal gray matter is established in Alzheimer's disease (AD), but the hippocampal fimbrial status in the pathogenesis of AD is unclear. AD-related demyelination and iron deposition alter the diamagnetic and paramagnetic composition of tissues, which can be measured by quantitative susceptibility mapping (QSM). HYPOTHESIS: AD is associated with microstructural changes in the fimbria that might be detected by QSM. STUDY TYPE: Retrospective cross-sectional study. SUBJECTS: In all, 53 adults comprised of controls (n = 30), subjects with early stage AD (n = 13), and late stage AD (n = 10) who were classified according to their amyloid and tau status and presence of hippocampal atrophy. FIELD STRENGTH / SEQUENCE: 3T; 3D fast-field echo sequence for QSM analysis and 3D T1 -weighted MP-RAGE sequence for anatomical analysis. ASSESSMENT: Segmentation of the left hippocampal fimbria subfield was performed on T1 -weighted images and was applied to the coregistered QSM map for extraction of the mean, median, minimum, and maximum values of QSM. STATISTICAL TESTS: Group comparison of QSM values using analysis of variance (ANOVA) with post-hoc Tukey's test, accuracy of binary differentiation using receiver operating characteristic (ROC), and individual classification using discriminant analysis. RESULTS: QSMmean and QSMmedian values were significantly different among the three groups (P < 0.05) and showed a shifting from negative in the control group to positive in the AD group. The control and early AD subjects, who have normal hippocampal volumes, were differentiated by the QSMmean value (area under the curve [AUC] 0.744, P < 0.05) and the QSMmedian value (AUC 0.782, P < 0.05). Up to 76% of subjects (inclusive of 26 controls and six with early AD) were correctly classified using a model incorporating clinical and radiologic data. DATA CONCLUSION: The fimbria showed higher magnetic susceptibility in AD compared with controls. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 3.

Plaque morphology in acute symptomatic intracranial atherosclerotic disease.

BACKGROUND: Intracranial atherosclerotic disease (ICAD) is globally a major ischaemic stroke subtype with high recurrence. Understanding the morphology of symptomatic ICAD plaques, largely unknown by far, may help identify vulnerable lesions prone to relapse. METHODS: We prospectively recruited patients with acute ischaemic stroke or transient ischaemic attack attributed to high-grade ICAD (60%-99% stenosis). Plaque morphological parameters were assessed in three-dimensional rotational angiography, including surface contour, luminal stenosis, plaque length/thickness, upstream shoulder angulation, axial/longitudinal plaque distribution and presence of adjoining branch atheromatous disease (BAD). We compared morphological features of smooth, irregular and ulcerative plaques and correlated them with cerebral ischaemic lesion load downstream in MRI. RESULTS: Among 180 recruited patients (median age=60 years; 63.3% male; median stenosis=75%), plaque contour was smooth (51 (28.3%)), irregular (101 (56.1%)) or ulcerative (28 (15.6%)). Surface ulcers were mostly at proximal (46.4%) and middle one-third (35.7%) of the lesions. Most (84.4%) plaques were eccentric, and half had their maximum thickness over the distal end. Ulcerative lesions were thicker (medians 1.6 vs 1.3 mm; p=0.003), had steeper upstream shoulder angulation (56.2° vs 31.0°; p<0.001) and more adjoining BAD (83.3% vs 57.0%; p=0.033) than non-ulcerative plaques. Ulcerative plaques were significantly associated with coexisting acute and chronic infarcts downstream (35.7% vs 12.5%; adjusted OR 4.29, 95% CI 1.65 to 11.14, p=0.003). Sensitivity analyses in patients with anterior-circulation ICAD lesions showed similar results in the associations between the plaque types and infarct load. CONCLUSIONS: Ulcerative intracranial atherosclerotic plaques were associated with vulnerable morphological features and had a higher cumulative infarct load downstream.

Tackling challenges in care of Alzheimer's disease and other dementias amid the COVID-19 pandemic, now and in the future.

We have provided an overview on the profound impact of COVID-19 upon older people with Alzheimer's disease and other dementias and the challenges encountered in our management of dementia in different health-care settings, including hospital, out-patient, care homes, and the community during the COVID-19 pandemic. We have also proposed a conceptual framework and practical suggestions for health-care providers in tackling these challenges, which can also apply to the care of older people in general, with or without other neurological diseases, such as stroke or parkinsonism. We believe this review will provide strategic directions and set standards for health-care leaders in dementia, including governmental bodies around the world in coordinating emergency response plans for protecting and caring for older people with dementia amid the COIVD-19 outbreak, which is likely to continue at varying severity in different regions around the world in the medium term.

Physical activities attenuate the negative cognitive impact from white matter hyperintensities in stroke and TIA patients with low education.

BACKGROUND: The objective of this study is to examine the effects of recent regular participation leisure activities upon cognitive functions between 3 and 6 months after stroke or transient ischemic attack (TIA). We also explored whether the cognitive effects interacted with the severity of white matter hyperintensities (WMH), a marker of cerebral white matter disease, in patients with low or high education. METHODS: Two-hundred and ninety-two subjects with mean age of 66.1 (11.0) years were recruited at median 161(131-180) days post index event. WMH volume was evaluated using a semi-automated method on MRI brain. Cognitive functions were measured using the Montreal Cognitive Assessment (MoCA). Multivariable linear regression analysis was conducted to explore the associations between leisure activity participation with WMH and the moderating effects of leisure activities upon relationship between WMH and MoCA. Analyses were further stratified by low (<6 years) or high education (≥6 years). All models were adjusted with age, sex, and years of education. RESULTS: Physical activity (PA), but not intellectual activity (IA), was negatively related to WMH volume (P < .05). IA exerted a main effect on MoCA performance (b = 3.21, P < .001). PA, but not IA, significantly interacted with WMH volume (b = -0.18, P < .01) on MoCA performance, but the interaction was only significant in the lower education group (b = 0.28, P < .01) but not in the higher education group. CONCLUSIONS: In patients with stroke/TIA, IA confers general cognitive benefits. Regular participation in PA negatively correlated with WMH volume. In patients with low education, PA increases resilience against vascular cognitive impairment.

Converting MMSE to MoCA and MoCA 5-minute protocol in an educationally heterogeneous sample with stroke or transient ischemic attack.

BACKGROUND: The Montreal Cognitive Assessment (MoCA) is psychometrically superior over the Mini-mental State Examination (MMSE) for cognitive screening in stroke or transient ischemic attack (TIA). It is free for clinical and research use. The objective of this study is to convert scores from the MMSE to MoCA and MoCA-5-minute protocol (MoCA-5 min) and to examine the ability of the converted scores in detecting cognitive impairment after stroke or TIA. METHODS: A total of 904 patients were randomly divided into training (n = 623) and validation (n = 281) samples matched for demography and cognition. MMSE scores were converted to MoCA and MoCA-5 min using (1) equipercentile method with log-linear smoothing and (2) Poisson regression adjusting for age and education. Receiver operating characteristics curve analysis was used to examine the ability of the converted scores in differentiating patients with cognitive impairment. RESULTS: The mean education was 5.8 (SD = 4.6; ranged 0-20) years. The entire spectrum of MMSE scores was converted to MoCA and MoCA-5 min using equipercentile method. Relationship between MMSE and MoCA scores was confounded by age and education, and a conversion equation with adjustment for age and education was derived. In the validation sample, the converted scores differentiated cognitively impaired patients with area under receiver operating characteristics curve 0.826 to 0.859. CONCLUSION: We provided 2 methods to convert scores from the MMSE to MoCA and MoCA-5 min based on a large sample of patients with stroke or TIA having a wide range of education and cognitive levels. The converted scores differentiated patients with cognitive impairment after stroke or TIA with high accuracy.

Evolution of intracranial atherosclerotic disease under modern medical therapy.

OBJECTIVE: Understanding how symptomatic intracranial atherosclerotic disease (ICAD) evolves with current medical therapy may inform secondary stroke prevention. METHODS: In a prospective academic-initiated study, we recruited 50 patients (mean age = 63.4 ± 9.0 years) with acute strokes attributed to high-grade (≥70%) intracranial atherosclerotic stenosis for 3-dimensional rotational angiograms before and after intensive medical therapy for 12 months. Treatment targets included low-density lipoprotein ≤ 70mg/dl, glycosylated hemoglobin (HbA1c) ≤ 6.5%, and systolic blood pressure ≤ 140 mmHg. We analyzed infarct topography and monitored microembolic signal in recurrent strokes. The reference group was a published cohort of 143 ICAD patients. RESULTS: Overall, the stenoses regressed from 79% at baseline (interquartile range [IQR] = 71-87%) to 63% (IQR = 54-74%) in 1 year (p < 0.001). Specifically, the qualifying lesions (n = 49) regressed (stenosis reduced >10%) in 24 patients (49%), remained quiescent (stenosis same or ±10%) in 21 patients (43%), and progressed (stenosis increased >10%) in 4 patients (8%). There was no difference in intensity of risk factor control between groups of diverging clinical or angiographic outcomes. Higher HbA1c at baseline predicted plaque regression at 1 year (odds ratio = 4.4, 95% confidence interval = 1.4-14.5, p = 0.006). Among the 6 patients with recurrent strokes pertaining to the qualifying stenosis, 5 patients had solitary or rosarylike acute infarcts along the internal or anterior border zones, and 2 patients showed microembolic signals in transcranial Doppler ultrasound. INTERPRETATION: A majority of symptomatic high-grade intracranial plaques had regressed or remained quiescent by 12 months under intensive medical therapy. Artery-to-artery thromboembolism with impaired washout at border zones was a common mechanism in stroke recurrence.

Delayed-onset dementia after stroke or transient ischemic attack.

INTRODUCTION: Patients surviving stroke without immediate dementia are at high risk of delayed-onset dementia. Mechanisms underlying delayed-onset dementia are complex and may involve vascular and/or neurodegenerative diseases. METHODS: Dementia-free patients with stroke and/or transient ischemic attack (TIA; n = 919) were studied for 3 years prospectively, excluding those who developed dementia 3 to 6 months after stroke and/or TIA. RESULTS: Forty subjects (4.4%) developed dementia during the study period. Imaging markers of severe small vessel disease (SVD), namely presence of ≥3 lacunes and confluent white matter changes; history of hypertension and diabetes mellitus independently predicted delayed-onset dementia after adjustment for age, gender, and education. Only 6 of 31 (19.4%) subjects with delayed cognitive decline harbored Alzheimer's disease-like Pittsburg compound B (PiB) retention. Most PiB cases (16/25, 64%) had evidence of severe SVD. DISCUSSION: Severe SVD contributes importantly to delayed-onset dementia after stroke and/or TIA. Future clinical trials aiming to prevent delayed-onset dementia after stroke and/or TIA should target this high-risk group.

Influence of Amyloid-ß on Cognitive Decline After Stroke/Transient Ischemic Attack: Three-Year Longitudinal Study.

BACKGROUND AND PURPOSE: We hypothesized that comorbid amyloid-beta (Aß) deposition played a key role in long-term cognitive decline in subjects with stroke/transient ischemic attack. METHODS: We recruited 72 subjects with cognitive impairment after stroke/transient ischemic attack to receive Carbon-11-labeled Pittsburgh compound B positron emission tomography. We excluded subjects with known clinical Alzheimer's disease. Those with and without Alzheimer's disease-like Aß deposition were classified as mixed vascular cognitive impairment (mVCI, n=14) and pure VCI (pVCI, n=58), respectively. We performed Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment to evaluate global cognition and cognitive domains (memory, visuospatial function, language, attention, and executive function) at 3 to 6 months (baseline) and annually for 3 years after the index event. We compared cognitive changes between mVCI and pVCI using linear mixed models and analysis of covariance adjusted for age and education. RESULTS: Over 3 years, there were significant differences between mVCI and pVCI on change of MMSE score over time (group×time interaction, P=0.007). We observed a significant decline on MMSE score (P=0.020) in the mVCI group but not in the pVCI group (P=0.208). The annual rates of decline on MMSE (P=0.023) and Montreal Cognitive Assessment score (P=0.003) were greater in the mVCI group than in the pVCI group. Memory, visuospatial, and executive function domain scores on the Montreal Cognitive Assessment were related to Aß deposition. CONCLUSIONS: Compared with subjects without Alzheimer's disease-like Aß deposition, those with Aß deposition experienced a more severe and rapid cognitive decline over 3 years after stroke/transient ischemic attack. Aß was associated with changes in multiple cognitive domains.

Montreal Cognitive Assessment 5-minute protocol is a brief, valid, reliable, and feasible cognitive screen for telephone administration.

BACKGROUND AND PURPOSE: The National Institute of Neurological Disorders and Stroke-Canadian Stroke Network Vascular Cognitive Impairment Harmonization working group proposed a brief cognitive protocol for screening of vascular cognitive impairment. We investigated the validity, reliability, and feasibility of the Montreal Cognitive Assessment 5-minute protocol (MoCA 5-minute protocol) administered over the telephone. METHODS: Four items examining attention, verbal learning and memory, executive functions/language, and orientation were extracted from the MoCA to form the MoCA 5-minute protocol. One hundred four patients with stroke or transient ischemic attack, including 53 with normal cognition (Clinical Dementia Rating, 0) and 51 with cognitive impairment (Clinical Dementia Rating, 0.5 or 1), were administered the MoCA in clinic and a month later, the MoCA 5-minute protocol over the telephone. RESULTS: Administration of the MoCA 5-minute protocol took 5 minutes over the telephone. Total score of the MoCA 5-minute protocol correlated negatively with age (r=-0.36; P<0.001) and positively with years of education (r=0.41; P<0.001) but not with sex (ρ=0.03; P=0.773). Total scores of the MoCA and MoCA 5-minute protocol were highly correlated (r=0.87; P<0.001). The MoCA 5-minute protocol performed equally well as the MoCA in differentiating patients with cognitive impairment from those without (areas under receiver operating characteristics curve for MoCA 5-minute protocol, 0.78; MoCA=0.74; P>0.05 for difference; Cohen d for group difference, 0.80-1.13). It differentiated cognitively impaired patients with executive domain impairment from those without (areas under receiver operating characteristics curve, 0.89; P<0.001; Cohen d=1.7 for group difference). Thirty-day test-retest reliability was excellent (intraclass correlation coefficient, 0.89). CONCLUSIONS: The MoCA 5-minute protocol is a free, valid, and reliable cognitive screen for stroke and transient ischemic attack. It is brief and highly feasible for telephone administration.

Cerebral Microbleeds and Cognitive Function in Ischemic Stroke or Transient Ischemic Attack Patients.

BACKGROUND: We explored the association between cerebral microbleeds (CMBs) and cognitive impairment in patients with ischemic stroke/transient ischemic attack (TIA). METHODS: A total of 488 ischemic stroke/TIA patients received magnetic resonance imaging. Montreal Cognitive Assessment (MoCA) was used to evaluate global cognitive function and cognitive domains. The association of CMB quantity with cognitive function and the impact of CMB locations (strictly lobar, strictly deep, and mixed regions) on cognitive impairment were examined in regression models with adjustments for confounders. RESULTS: A total of 113 subjects (23.2%) had ≥1 CMB. Strictly lobar, strictly deep, and mixed CMBs were identified in 36, 40, and 37 patients, respectively. The presence of ≥5 CMBs or strictly deep CMBs was associated with the MoCA total score (p = 0.007 and 0.020, respectively). Of all MoCA domains tested, a lower score in the attention domain was related to the presence of ≥5 CMBs (p = 0.014) and strictly deep CMBs (p = 0.028). CONCLUSION: CMBs were associated with cognitive dysfunction in stroke/TIA patients, especially in the attention domain. This association was mainly driven by CMBs in the deep region, underlining the role of hypertensive microangiopathy in stroke-related cognitive impairment.

Risk factors for incident dementia after stroke and transient ischemic attack.

BACKGROUND: We hypothesized that chronic brain changes are important substrates for incident dementia after stroke and transient ischemic attack (TIA). METHODS: We compared clinical and imaging features between patients with consecutive stroke/TIA with (n = 88) and without (n = 925) incident dementia at 3 to 6 months after a stroke/TIA. Pittsburg compound B (PiB) positron emission tomography was performed in 50 patients, including those with (n = 37) and without (n = 13) incident dementia. RESULTS: Age, history of diabetes mellitus, severity of white matter changes (WMCs), and medial temporal lobe atrophy (MTLA) were associated with incident dementia. Alzheimer's disease (AD)--like PiB retention was found in 29.7% and 7.7% (P = .032) of patients with and without incident dementia, respectively. CONCLUSIONS: Chronic brain changes including WMCs, MTLA, and AD pathology are associated with incident dementia after stroke/TIA. Interventions targeting these chronic brain changes may reduce burden of vascular cognitive impairment.

Machine Learning-Derived MRI-Based Neurodegeneration Biomarker for Alzheimer's Disease: A Multi-Database Validation Study.

BACKGROUND: Pilot study showed that Alzheimer's disease resemblance atrophy index (AD-RAI), a machine learning-derived MRI-based neurodegeneration biomarker of AD, achieved excellent diagnostic performance in diagnosing AD with moderate to severe dementia. OBJECTIVE: The primary objective was to validate and compare the performance of AD-RAI with conventional volumetric hippocampal measures in diagnosing AD with mild dementia. The secondary objectives were 1) to investigate the association between imaging biomarkers with age and gender among cognitively unimpaired (CU) participants; 2) to analyze whether the performance of differentiating AD with mild dementia from CU will improve after adjustment for age/gender. METHODS: AD with mild dementia (n = 218) and CU (n = 1,060) participants from 4 databases were included. We investigated the area under curve (AUC), sensitivity, specificity, and balanced accuracy of AD-RAI, hippocampal volume (HV), and hippocampal fraction (HF) in differentiating between AD and CU participants. Among amyloid-negative CU participants, we further analyzed correlation between the biomarkers with age/gender. We also investigated whether adjustment for age/gender will affect performance. RESULTS: The AUC of AD-RAI (0.93) was significantly higher than that of HV (0.89) and HF (0.89). Subgroup analysis among A + AD and A- CU showed that AUC of AD-RAI (0.97) was also higher than HV (0.94) and HF (0.93). Diagnostic performance of AD-RAI and HF was not affected by age/gender while that of HV improved after age adjustment. CONCLUSIONS: AD-RAI achieves excellent clinical validity and outperforms conventional volumetric hippocampal measures in aiding the diagnosis of AD mild dementia without the need for age adjustment.

Case Report: Taxifolin for neurosurgery-associated early-onset cerebral amyloid angiopathy.

Cases of iatrogenic cerebral amyloid angiopathy (CAA) have been increasingly reported recently, particularly those associated with neurosurgery. Preclinical studies have shown taxifolin to be promising for treating CAA. We describe a young 42-year-old man with a history of childhood traumatic brain injury that required a craniotomy for hematoma evacuation. He later presented with recurrent lobar intracerebral hemorrhage (ICH) decades later, which was histologically confirmed to be CAA. Serial 11C-Pittsburgh compound B positron emission tomography (11C-PiB-PET) imaging showed a 24% decrease in global standardized uptake value ratio (SUVR) at 10 months after taxifolin use. During this period, the patient experienced clinical improvement with improved consciousness and reduced recurrent ICH frequency, which may be partly attributable to the potential amyloid-ß (Aß) clearing the effect of taxifolin. However, this effect seemed to have diminished at 15 months, CAA should be considered in young patients presenting with recurrent lobar ICH with a history of childhood neurosurgery, and serial 11C-PiB-PET scans warrant further validation as a strategy for monitoring treatment response in CAA for candidate Aß-clearing therapeutic agents such as taxifolin.

Effects of Acupuncture upon cerebral hemodynamics in cerebral small vessel disease: A pilot study.

Background and aims: Recent preclinical studies and meta-analysis of clinical trials suggested that acupuncture may improve cognition in cerebral small vessel disease (CSVD). We investigated the cerebral hemodynamics of acupuncture in subjects with CSVD and compared its impact upon the cerebral hemodynamics in normal elderly subjects. Methods: 10 subjects with CSVD (CSVD group) and 10 aged-matched control subjects who had no or insignificant CSVD (control group) were recruited. A single session of acupuncture was applied for 30 min in both groups. We assessed the effect of our acupuncture intervention on cerebral hemodynamics by transcranial Doppler ultrasound (TCD). Peak systolic velocity (PSV) and pulsatility index (PI) of the middle cerebral artery (MCA) were assessed. Results: We observed that PSV increased by a maximum of 39% at 20 min (p<0.05), while there was no significant change in PI in the CSVD group during the acupuncture session. In the control group, although we observed no significant change in PSV during the acupuncture session, there was a significant decrease in PI by a maximum of 22% at 20 min (p<0.05). No adverse events were reported during or after the procedure. Conclusion: This study suggested that our acupuncture prescription was associated with an increase in cerebral blood flow in subjects with established moderate to severe CSVD yet without apparent impact on distal vascular resistance. While, in subjects with no or insignificant CSVD, it may reduce cerebral small vessel distal vascular resistance. A larger study is needed to confirm our findings.

Lower Posterior Cingulate N-Acetylaspartate to Creatine Level in Early Detection of Biologically Defined Alzheimer's Disease.

Alzheimer's disease (AD) was recently defined as a biological construct to reflect neuropathologic status, and both abnormal amyloid and tau are required for a diagnosis of AD. We aimed to determine the proton MR spectroscopic (1H-MRS) patterns of the posterior cingulate in biologically defined AD. A total of 68 participants were included in this study, comprising 37 controls, 16 early AD, and 15 late AD, who were classified according to their amyloid and tau status and presence of hippocampal atrophy. Compared with controls, early AD showed lower N-acetylaspartate (NAA)/creatine (Cr) (p = 0.003), whereas late AD showed lower NAA/Cr and higher myoInositol (mI)/Cr (all with p < 0.05). Lower NAA/Cr correlated with a greater global amyloid load (r = −0.47, p < 0.001) and tau load (r = −0.51, p < 0.001) and allowed a discrimination of early AD from controls (p < 0.001). Subgroup analysis showed that NAA/Cr also allowed a differentiation of early AD from controls in the cognitively unimpaired subjects, with an area under the receiver operating characteristics curve, sensitivity, and specificity of 0.96, 100%, and 83.8%, respectively. Lower posterior cingulate NAA levels may help to inform underlying neuropathologic changes in the early stage of AD.