Cerebral Volumetric Correlates of Apathy in Alzheimer’s Disease and Cognitively Normal Older Adults: Meta-Analysis, Label-Based Review, and Study of an Independent Cohort

2021 ◽  
pp. 1-15
Author(s):  
Shefali Chaudhary ◽  
Simon Zhornitsky ◽  
Herta H. Chao ◽  
Christopher H. van Dyck ◽  
Chiang-Shan R. Li

Background: Affecting nearly half of the patients with Alzheimer’s disease (AD), apathy is associated with higher morbidity and reduced quality of life. Basal ganglia and cortical atrophy have been implicated in apathy. However, the findings have varied across studies and left unclear whether subdomains of apathy may involve distinct neuroanatomical correlates. Objective: To identify neuroanatomical correlates of AD-associated apathy. Methods: We performed a meta-analysis and label-based review of the literature. Further, following published routines of voxel-based morphometry, we aimed to confirm the findings in an independent cohort of 19 patients with AD/mild cognitive impairment and 25 healthy controls evaluated with the Apathy Evaluation Scale. Results: Meta-analysis of 167 AD and 56 healthy controls showed convergence toward smaller basal ganglia gray matter volume (GMV) in apathy. Label-based review showed anterior cingulate, putamen, insula, inferior frontal gyrus (IFG) and middle temporal gyrus (MTG) atrophy in AD apathy. In independent cohort, with small-volume-correction, right putamen and MTG showed GMVs in negative correlation with Apathy Evaluation Scale total, behavioral, and emotional scores, and right IFG with emotional score (p <  0.05 family-wise error (FWE)-corrected), controlling for age, education, intracranial volume, and depression. With the Mini-Mental State Examination scores included as an additional covariate, the correlation of right putamen GMV with behavioral and emotional score, right MTG GMV with total and emotional score, and right IFG GMV with emotional score were significant. Conclusion: The findings implicate putamen, MTG and IFG atrophy in AD associated apathy, potentially independent of cognitive impairment and depression, and suggest potentially distinct volumetric correlates of apathy.

2020 ◽  
Author(s):  
BUHARI IBRAHIM ◽  
Nisha Syed Nasser ◽  
NORMALA IBRAHIM ◽  
Mazlyfarina Mohamed ◽  
Hasyma Abu Hassan ◽  
...  

Resting state fMRI (rs-fMRI) detects functional connectivity (FC) abnormalities that occur in the brains of patients with Alzheimer's disease (AD) and Mild Cognitive Impairment (MCI). FC of the default mode network (DMN), which is involved in memory consolidation, is commonly impaired in AD and MCI. We aimed to determine the diagnostic power of rs-fMRI to identify FC abnormalities in the DMN, which help to distinguish patients with AD or MCI from healthy controls (HCs). We searched articles in PubMed and Scopus databases using the search terms such as AD, MCI, resting-state fMRI, sensitivity and specificity through to 27th March 2020 and removed duplicate papers. We screened 390 published articles, and shortlisted 12 articles for the final analysis. The range of sensitivity of DMN FC at the posterior cingulate cortex (PCC) for diagnosing AD was between 65.7% - 100% and specificity ranged from 66 - 95%. Reduced DMN FC between the PCC and anterior cingulate cortex (ACC) in the frontal lobes was observed in MCI patients. AD patients had impaired FC in most regions of the DMN; particularly the PCC in early AD. This indicates that DMN's rs-fMRI FC can offer moderate to high diagnostic power to distinguish AD and MCI patients. fMRI detected abnormal DMN FC, particularly in the PCC that helps to differentiate AD and MCI patients from healthy controls (HCs). Combining multivariate method of analysis with other MRI parameters such as structural changes improve the diagnostic power of rs-fMRI in distinguishing patients with AD or MCI from HCs.


2021 ◽  
Author(s):  
Noel Valencia ◽  
Johann Lehrner

Summary Background Visuo-Constructive functions have considerable potential for the early diagnosis and monitoring of disease progression in Alzheimer’s disease. Objectives Using the Vienna Visuo-Constructional Test 3.0 (VVT 3.0), we measured visuo-constructive functions in subjective cognitive decline (SCD), mild cognitive impairment (MCI), Alzheimer’s disease (AD), and healthy controls to determine whether VVT performance can be used to distinguish these groups. Materials and methods Data of 671 participants was analyzed comparing scores across diagnostic groups and exploring associations with relevant clinical variables. Predictive validity was assessed using Receiver Operator Characteristic curves and multinomial logistic regression analysis. Results We found significant differences between AD and the other groups. Identification of cases suffering from visuo-constructive impairment was possible using VVT scores, but these did not permit classification into diagnostic subgroups. Conclusions In summary, VVT scores are useful indicators for visuo-constructive impairment but face challenges when attempting to discriminate between several diagnostic groups.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Yaojing Chen ◽  
Mingxi Dang ◽  
Zhanjun Zhang

AbstractNeuropsychiatric symptoms (NPSs) are common in patients with Alzheimer’s disease (AD) and are associated with accelerated cognitive impairment and earlier deaths. This review aims to explore the neural pathogenesis of NPSs in AD and its association with the progression of AD. We first provide a literature overview on the onset times of NPSs. Different NPSs occur in different disease stages of AD, but most symptoms appear in the preclinical AD or mild cognitive impairment stage and develop progressively. Next, we describe symptom-general and -specific patterns of brain lesions. Generally, the anterior cingulate cortex is a commonly damaged region across all symptoms, and the prefrontal cortex, especially the orbitofrontal cortex, is also a critical region associated with most NPSs. In contrast, the anterior cingulate-subcortical circuit is specifically related to apathy in AD, the frontal-limbic circuit is related to depression, and the amygdala circuit is related to anxiety. Finally, we elucidate the associations between the NPSs and AD by combining the onset time with the neural basis of NPSs.


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