scholarly journals Stages of Objective Memory Impairment Predict Alzheimer’s Disease Neuropathology: Comparison with the Clinical Dementia Rating Scale–Sum of Boxes

2021 ◽  
pp. 1-11
Author(s):  
Ellen Grober ◽  
Qi Qi ◽  
Lynn Kuo ◽  
Jason Hassenstab ◽  
Richard J. Perrin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Logistic Regression ◽  
Memory Impairment ◽  
Rating Scale ◽  
Neurofibrillary Tangle ◽  
Staging System ◽  
Braak Stage ◽  
Operating Characteristics ◽  
Clinical Dementia Rating

Background: The ultimate validation of a clinical marker for Alzheimer’s disease (AD) is its association with AD neuropathology. Objective: To examine how well the Stages of Objective Memory Impairment (SOMI) system predicts intermediate/high AD neuropathologic change and extent of neurofibrillary tangle (NFT) pathology defined by Braak stage, in comparison to the Clinical Dementia Rating (CDR) Scale sum of boxes (CDR-SB). Methods: 251 well-characterized participants from the Knight ADRC clinicopathologic series were classified into SOMI stage at their last assessment prior to death using the free recall and total recall scores from the picture version of the Free and Cued Selective Reminding Test with Immediate Recall (pFCSRT + IR). Logistic regression models assessed the predictive validity of SOMI and CDR-SB for intermediate/high AD neuropathologic change. Receiver operating characteristics (ROC) analysis evaluated the discriminative validity of SOMI and CDR-SB for AD pathology. Ordinal logistic regression was used to predict Braak stage using SOMI and CDR-SB in separate and joint models. Results: The diagnostic accuracy of SOMI for AD diagnosis was similar to that of the CDR-SB (AUC: 85%versus 83%). In separate models, both SOMI and CDR-SB predicted Braak stage. In a joint model SOMI remained a significant predictor of Braak stage but CDR-SB did not. Conclusion: SOMI provides a neuropathologically validated staging system for episodic memory impairment in the AD continuum and should be useful in predicting tau positivity based on its association with Braak stage.

scholarly journals Clinicopathological correlates of Alzheimer's disease in a general autopsy series from Brazil

2007 ◽  
Vol 1 (4) ◽  
pp. 356-360
Author(s):  
Lea Tenenholz Grinberg ◽  
Renata Eloah de Lucena Ferretti ◽  
Renata E.P. Leite ◽  
Jose Marcelo Farfel ◽  
Silmara P. Pacheco ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Rating Scale ◽  
Normal Subjects ◽  
European Ancestry ◽  
Aging Brain ◽  
Braak Stage ◽  
Clinical Dementia Rating ◽  
Score Distribution ◽  
Cognitively Normal Subjects

Abstract The current neuropathological staging models of Alzheimer's disease (AD) have been developed within the last 20 years. Nevertheless, they were mostly tested on Caucasians of Northern European ancestry or on Asians. Objective: To verify which of the accepted neuropathologic criteria best discriminates AD from normal aging in a well characterized Brazilian clinicopathological series. Methods: A random sample consisting of 89 subjects belonging to the Brazilian Brain Bank of the Aging Brain Study were clinically and neuropathologically fully assessed using immunohistochemistry. Clinical and functional statuses were assessed by interviewing a reliable informant. The Clinical dementia rating scale (CDR) was compared to Braak and Braak stage, the consortium to establish a registry for Alzheimer's disease (CERAD) score and NIA-Reagan (National Institute of Aging - Reagan Institute) score. Subjects with a neuropathologic diagnosis other then AD were excluded (n=27). Results: The CDR score distribution for the 62 selected subjects was as follows: CDR0=39, CDR0.5=9, CDR³1=14. There were no differences regarding age, gender and education among the groups. CDR score correlated best with the CERAD score (r=0.5303; p<0.001) . Braak and Braak stage was significantly higher in subjects with higher CDR. Correlation of the NIA-Reagan criteria was partially disrupted because a large proportion of subjects did not fit any of its categories. Conclusions: In this series, CERAD criteria better correlated with the CDR groups. Consistent with earlier studies, some cognitively normal subjects have AD neuropathological diagnosis.

scholarly journals The Free and Cued Selective Reminding Test Predicts Braak Stage

2021 ◽  
pp. 1-9
Author(s):  
Ellen Grober ◽  
Qi Qi ◽  
Lynn Kuo ◽  
Jason Hassenstab ◽  
Richard J. Perrin ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Free Recall ◽  
Rating Scale ◽  
Stage Iv ◽  
Braak Stage ◽  
Clinical Dementia Rating ◽  
Selective Reminding ◽  
Selective Reminding Test ◽  
Clinical Measures

Background: The ultimate validation of a clinical marker for Alzheimer’s disease (AD) is its association with AD neuropathology. Objective: To identify clinical measures that predict pathology, we evaluated the relationships of the picture version of the Free and Cued Selective Reminding Test (pFCSRT + IR), the Mini-Mental State Exam (MMSE), and the Clinical Dementia Rating scale Sum of Boxes (CDR-SB) to Braak stage. Methods: 315 cases from the clinicopathologic series at the Knight Alzheimer’s Disease Research Center were classified according to Braak stage. Boxplots of each predictor were compared to identify the earliest stage at which decline was observed and ordinal logistic regression was used to predict Braak stage. Results: Looking at the assessment closest to death, free recall scores were lower in individuals at Braak stage III versus Braak stages 0 and I (combined) while MMSE and CDR scores for individuals did not differ from Braak stages 0/I until Braak stage IV. The sum of free recall and total recall scores independently predicted Braak stage and had higher predictive validity than MMSE and CDR-SB in models including all three. Conclusion: pFCSRT + IR + IR scores may be more sensitive to early pathological changes than either the CDR-SB or the MMSE.

Alzheimer’s Disease-Related Neuropathology Among Patients with Medication Treated Type 2 Diabetes in a Community-Based Autopsy Cohort

2021 ◽  
pp. 1-10
Author(s):  
Douglas Barthold ◽  
Laura E. Gibbons ◽  
Zachary A. Marcum ◽  
Shelly L. Gray ◽  
C. Dirk Keene ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Sex Education ◽  
Descriptive Analysis ◽  
Neurofibrillary Tangle ◽  
Apoe Genotype ◽  
Severity Index ◽  
Neuritic Plaque ◽  
Braak Stage ◽  
Total N

Background: Diabetes is a risk factor for Alzheimer’s disease and related dementias (ADRD). Epidemiologic evidence shows an association between diabetes medications and ADRD risk; cell and mouse models show diabetes medication association with AD-related neuropathologic change (ADNC). Objective: This hypothesis-generating analysis aimed to describe autopsy-measured ADNC for individuals who used diabetes medications. Methods: Descriptive analysis of ADNC for Adult Changes in Thought (ACT) Study autopsy cohort who used diabetes medications, including sulfonylureas, insulin, and biguanides; total N = 118. ADNC included amyloid plaque distribution (Thal phasing), neurofibrillary tangle (NFT) distribution (Braak stage), and cortical neuritic plaque density (CERAD score). We also examined quantitative measures of ADNC using the means of standardized Histelide measures of cortical PHF-tau and Aβ 1–42. Adjusted analyses control for age at death, sex, education, APOE genotype, and diabetes complication severity index. Results: Adjusted analyses showed no significant association between any drug class and traditional neuropathologic measures compared to nonusers of that class. In adjusted Histelide analyses, any insulin use was associated with lower mean levels of Aβ 1–42 (–0.57 (CI: –1.12, –0.02)) compared to nonusers. Five years of sulfonylureas and of biguanides use was associated with lower levels of Aβ 1–42 compared to nonusers (–0.15 (CI: –0.28, –0.02), –0.31 (CI: –0.54, –0.07), respectively). Conclusion: Some evidence exists that diabetes medications are associated with lower levels of Aβ 1–42, but not traditional measures of neuropathology. Future studies are needed in larger samples to build understanding of the mechanisms between diabetes, its medications, and ADRD, and to potentially repurpose existing medications for prevention or delay of ADRD.

scholarly journals Early detection of Alzheimer’s disease with a total score of the German CERAD

2010 ◽  
Vol 16 (5) ◽  
pp. 910-920 ◽  
Author(s):  
MICHAEL M. EHRENSPERGER ◽  
MANFRED BERRES ◽  
KIRSTEN I. TAYLOR ◽  
ANDREAS U. MONSCH
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Logistic Regression ◽  
Correct Classification ◽  
Operating Characteristics ◽  
Healthy Control ◽  
Neuropsychological Assessment Battery ◽  
State Examination

AbstractThe goal of the present study was to evaluate the diagnostic discriminability of three different global scores for the German version of the Consortium to Establish a Registry on Alzheimer’s Disease-Neuropsychological Assessment Battery (CERAD-NAB). The CERAD-NAB was administered to 1100 healthy control participants [NC; Mini-Mental State Examination (MMSE) mean = 28.9] and 352 patients with very mild Alzheimer’s disease (AD; MMSE mean = 26.1) at baseline and subsets of participants at follow-up an average of 2.4 (NC) and 1.2 (AD) years later. We calculated the following global scores: Chandler et al.’s (2005) score (summed raw scores), logistic regression on principal components analysis scores (PCA-LR), and logistic regression on demographically corrected CERAD-NAB variables (LR). Correct classification rates (CCR) were compared with areas under the receiver operating characteristics curves (AUC). The CCR of the LR score (AUC = .976) exceeded that of the PCA-LR, while the PCA-LR (AUC = .968) and Chandler (AUC = .968) scores performed comparably. Retest data improved the CCR of the PCA-LR and Chandler (trend) scores. Thus, for the German CERAD-NAB, Chandler et al.’s total score provided an effective global measure of cognitive functioning, whereby the inclusion of retest data tended to improve correct classification of individual cases. (JINS, 2010, 16, 910–920.)

scholarly journals Efficacy and Limitations of rCBF-SPECT in the Diagnosis of Alzheimer’s Disease With Amyloid-PET

2019 ◽  
Vol 34 (5) ◽  
pp. 314-321
Author(s):  
Miwako Takahashi ◽  
Tomoko Tada ◽  
Tomomi Nakamura ◽  
Keitaro Koyama ◽  
Toshimitsu Momose
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Rating Scale ◽  
Single Photon ◽  
Photon Emission ◽  
Emission Computed Tomography ◽  
Amyloid Pet ◽  
Clinical Dementia Rating ◽  
Positron Emission ◽  
Rcbf Spect

This study aimed to assess efficacy and limitations of regional cerebral blood flow imaging using single-photon emission computed tomography (rCBF-SPECT) in the diagnosis of Alzheimer’s disease (AD) with amyloid-positron emission tomography (amyloid-PET). Thirteen patients, who underwent both rCBF-SPECT and amyloid-PET after clinical diagnosis of AD or mild cognitive impairment, were retrospectively identified. The rCBF-SPECTs were classified into 4 grades, from typical AD pattern to no AD pattern of hypoperfusion; amyloid-beta (Aβ) positivity was assessed by amyloid-PET. Four patients were categorized into a typical AD pattern on rCBF-SPECT, and all were Aβ+. The other 9 patients did not exhibit a typical AD pattern; however, 4 were Aβ+. The Mini-Mental State Examination score and Clinical Dementia Rating scale were not significantly different between Aβ+ and Aβ– patients. A typical AD pattern on rCBF-SPECT can reflect Aβ+; however, if not, rCBF-SPECT has a limitation to predict amyloid pathology.

scholarly journals Epidemiological pathology of Aβ deposition in the ageing brain in CFAS: addition of multiple Aβ-derived measures does not improve dementia assessment using logistic regression and machine learning approaches

2019 ◽  
Vol 7 (1) ◽  
Author(s):  
S. B. Wharton ◽  
◽  
D. Wang ◽  
C. Parikh ◽  
F. E. Matthews ◽  
...  
Keyword(s):  
Machine Learning ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Logistic Regression ◽  
Neuritic Plaque ◽  
Type I ◽  
Ageing Population ◽  
Braak Stage ◽  
Age Related ◽  
Highly Correlated

AbstractAβ-amyloid deposition is a key feature of Alzheimer’s disease, but Consortium to Establish a Registry for Alzheimer's Disease (CERAD) assessment, based on neuritic plaque density, shows a limited relationships to dementia. Thal phase is based on a neuroanatomical hierarchy of Aβ-deposition, and in combination with Braak neurofibrillary tangle staging also allows derivation of primary age-related tauopathy (PART). We sought to determine whether Thal Aβ phase predicts dementia better than CERAD in a population-representative cohort (n = 186) derived from the Cognitive Function and Ageing Study (CFAS). Cerebral amyloid angiopathy (CAA) was quantitied as the number of neuroanatomical areas involved and cases meeting criteria for PART were defined to determine if they are a distinct pathological group within the ageing population. Agreement with the Thal scheme was excellent. In univariate analysis Thal phase performed less well as a predictor of dementia than CERAD, Braak or CAA. Logistic regression, decision tree and linear discriminant analysis were performed for multivariable analysis, with similar results. Thal phase did not provide a better explanation of dementia than CERAD, and there was no additional benefit to including more than one assessment of Aβ in the model. Number of areas involved by CAA was highly correlated with assessment based on a severity score (p < 0.001). The presence of capillary involvement (CAA type I) was associated with higher Thal phase and Braak stage (p < 0.001). CAA was not associated with microinfarcts (p = 0.1). Cases satisfying pathological criteria for PART were present at a frequency of 10.2% but were not older and did not have a higher likelihood of dementia than a comparison group of individuals with similar Braak stage but with more Aβ. They also did not have higher hippocampal-tau stage, although PART was weakly associated with increased presence of thorn-shaped astrocytes (p = 0.048), suggesting common age-related mechanisms. Thal phase is highly applicable in a population-representative setting and allows definition of pathological subgroups, such as PART. Thal phase, plaque density, and extent and type of CAA measure different aspects of Aβ pathology, but addition of more than one Aβ measure does not improve dementia prediction, probably because these variables are highly correlated. Machine learning predictions reveal the importance of combining neuropathological measurements for the assessment of dementia.

scholarly journals Predictors of rapid cognitive decline in Alzheimer's disease: results from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of ageing

2011 ◽  
Vol 24 (2) ◽  
pp. 197-204 ◽  
Author(s):  
Alessandro Sona ◽  
Ping Zhang ◽  
David Ames ◽  
Ashley I. Bush ◽  
Nicola T. Lautenschlager ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Rating Scale ◽  
Cognitive Status ◽  
Imaging Biomarkers ◽  
Clinical Dementia Rating ◽  
Factors Associated ◽  
Biological Variables ◽  
Rapid Cognitive Decline

ABSTRACTBackground: The AIBL study, which commenced in November 2006, is a two-center prospective study of a cohort of 1112 volunteers aged 60+. The cohort includes 211 patients meeting NINCDS-ADRDA criteria for Alzheimer's disease (AD) (180 probable and 31 possible). We aimed to identify factors associated with rapid cognitive decline over 18 months in this cohort of AD patients.Methods: We defined rapid cognitive decline as a drop of 6 points or more on the Mini-Mental State Examination (MMSE) between baseline and 18-month follow-up. Analyses were also conducted with a threshold of 4, 5, 7 and 8 points, as well as with and without subjects who had died or were too severely affected to be interviewed at 18 months and after, both including and excluding subjects whose AD diagnosis was “possible” AD. We sought correlations between rapid cognitive decline and demographic, clinical and biological variables.Results: Of the 211 AD patients recruited at baseline, we had available data for 156 (73.9%) patients at 18 months. Fifty-one patients were considered rapid cognitive decliners (32.7%). A higher Clinical Dementia Rating scale (CDR) and higher CDR “sum of boxes” score at baseline were the major predictors of rapid cognitive decline in this population. Furthermore, using logistic regression model analysis, patients treated with a cholinesterase inhibitor (CheI) had a higher risk of being rapid cognitive decliners, as did males and those of younger age.Conclusions: Almost one third of patients satisfying established research criteria for AD experienced rapid cognitive decline. Worse baseline functional and cognitive status and treatment with a CheI were the major factors associated with rapid cognitive decline over 18 months in this population.

Associations of Blood Pressure with Functional and Cognitive Changes in Patients with Alzheimer's Disease

2016 ◽  
Vol 41 (5-6) ◽  
pp. 314-323 ◽  
Author(s):  
Fabricio Ferreira de Oliveira ◽  
Elizabeth Suchi Chen ◽  
Marilia Cardoso Smith ◽  
Paulo Henrique Ferreira Bertolucci
Keyword(s):  
Alzheimer’S Disease ◽  
Blood Pressure ◽  
Alzheimer's Disease ◽  
Rating Scale ◽  
Late Onset ◽  
Angiotensin Receptor Blockers ◽  
Channel Blockers ◽  
Clinical Dementia Rating ◽  
Cognitive Changes ◽  
Converting Enzyme Inhibitors

Background: Midlife hypertension followed by late life hypotension resulting from neurodegeneration increases amyloidogenesis and tauopathy. Methods: Consecutive outpatients with late-onset Alzheimer's disease (AD) at various stages and their respective caregivers were assessed for score variations in 1 year of tests assessing caregiver burden, functionality and cognition according to blood pressure (BP) variations and APOE haplotypes, while also taking into account differential effects of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β-blockers, calcium channel blockers, diuretics, or no antihypertensive medication on score changes. The diagnosis and treatment of arterial hypertension followed the JNC 7 report. Results: Variations in systolic BP (-11.76 ± 17.1 mm Hg), diastolic BP (-4.92 ± 10.3 mm Hg) and pulse pressure (-6.84 ± 12.6 mm Hg) were significant after 1 year (n = 191; ρ < 0.01). For APOE4+ carriers, rises in systolic or diastolic BP improved Clinical Dementia Rating Scale Sum of Boxes scores (ρ < 0.04), with marginally significant improvements in Mini-Mental State Examination scores resulting from risen systolic (ρ = 0.069) or diastolic BP (ρ = 0.079), and in basic independence only regarding risen diastolic BP (ρ = 0.055). APOE4- carriers resisted any functional or cognitive effects of BP variations. No differences were found regarding any antihypertensive class for variations in BP or any test scores, regardless of APOE haplotypes. Conclusions: Targeting mild BP elevations brings better functional and cognitive results for APOE4+ carriers with AD.

scholarly journals Education, leisure activities and cognitive and functional ability of Alzheimer's disease patients: A follow-up study

2013 ◽  
Vol 7 (2) ◽  
pp. 181-189 ◽  
Author(s):  
Margarida Sobral ◽  
Constança Paúl
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Disease Progression ◽  
Functional Ability ◽  
Rating Scale ◽  
Leisure Activities ◽  
Functional Decline ◽  
Clinical Dementia Rating ◽  
High Participation ◽  
Relevant Variables

ABSTRACT Education and participation in leisure activities appear to be highly relevant variables in Alzheimer's disease (AD) and usually form the basis of the Cognitive Reserve construct. Objective: [A] To determine the association between education, cognitive and functional ability of AD patients; [B] To determine the association between participation in leisure activities and cognitive and functional ability of AD patients; [C] To evaluate the association of education and participation in leisure activities in the course of AD. Methods: Functional and neuropsychological abilities of 120 outpatients with probable AD were evaluated at baseline, at 36 and 54 months. Data collected at baseline included socio-demographics, clinical variables, education and frequency of participation in leisure activities throughout life. All participants and/or caregivers answered the questionnaire, "Participation in leisure activities throughout life" while patients completed the MMSE, the Clinical Dementia Rating scale, neuropsychological tests from the Lisbon Screening for Dementia Assessment, Barthel Index and Lawton and Brody's Index. Results: AD patients with higher levels of education achieved better results on cognitive tests. The participants with higher participation in leisure activities exhibited better results on cognitive and functional tests than those with lower participation. The disease progression was linear and progressed similarly regardless of the level of education of participants. However, the results suggest a slower disease progression in patients with a higher level of participation in leisure activities throughout their lives. Conclusion: AD patients with high education and high participation in leisure activities may benefit from a slower cognitive and functional decline after diagnosis of AD.

scholarly journals 97 Potentially Inappropriate Medications in Patients with Alzheimer’s Disease: Data from NILVAD

2019 ◽  
Vol 48 (Supplement_3) ◽  
pp. iii1-iii16
Author(s):  
Claire Murphy ◽  
Adam H Dyer ◽  
Brian Lawlor ◽  
Sean P Kennelly
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Adverse Drug Events ◽  
Rating Scale ◽  
Secondary Analysis ◽  
Median Number ◽  
Potentially Inappropriate Medications ◽  
Clinical Dementia Rating ◽  
Start Criteria ◽  
Inappropriate Medications

Abstract Background Prescription of Potentially Inappropriate Medications (PIMs) is common in older adults and is associated with adverse drug events, hospitalisation and mortality. Less well described are the patterns and predictors of PIM usage in patients with Alzheimer’s Disease (AD), a patient group who may be particularly vulnerable to polypharmacy and medication associated adverse events. Methods Secondary analysis of the NILVAD trial, an international phase three trial of Nilvadipine in mild/moderate AD. The v2 STOPP/START criteria were individually applied by a physician to each participant’s medication list and cross-reference with their medical history to identify PIM usage. Predictors of PIM usage were modelled using binary logistic regression. Results Five-hundred and ten patients with AD were included (mean age 72.8 +/-8.3 years; 62% female). The median number of prescribed medications was 5 (IQR 3-7). Over half (55.5%) were prescribed at least one PIM, whilst a minority of patients (14.8%) were prescribed three or more PIMs. The most frequent PIMs were benzodiazepines >4 weeks without indication (n = 55), long-term Proton-Pump Inhibitor (PPI) use without appropriate indication (n = 49), use of non-steroidal analgesics without use of PPI (n=19) and antimuscarinic use in dementia (n= 18). On multivariate analysis, significant predictors of PIM use were higher total number of medications (p=0.001; OR 1.52; 1.36-1.59) in addition to greater AD severity, as rated using the Clinical Dementia Rating Scale Sum-of-Boxes (CDR-sb) (p=0.024; OR 1.18; 1.02-1.35). Conclusion The majority of older patients with AD were prescribed at least one PIM. Usage of PIMs was associated with greater number of medications and increased dementia severity. Particularly concerning is the potentially inappropriate use of benzodiazepines and anti-muscarinic agents in this population, given recent evidence for the adverse cognitive profile associated with these medications. De-prescribing and medication review interventions aimed particularly at patients with AD are warranted.

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