Neuropsychological Criteria for Mild Cognitive Impairment in the Framingham Heart Study’s Old-Old

Background/Aims: Mild cognitive impairment (MCI) lacks a “gold standard” operational definition. The Jak/Bondi actuarial neuropsychological criteria for MCI are associated with improved diagnostic stability and prediction of progression to dementia compared to conventional MCI diagnostic approaches, although its utility in diagnosing MCI in old-old individuals (age 75+) is unknown. Therefore, we investigated the applicability of neuropsychological MCI criteria among old-old from the Framingham Heart Study. Methods: A total of 347 adults (ages 79–102) were classified as cognitively normal or MCI via Jak/Bondi and conventional Petersen/Winblad criteria, which differ on cutoffs for cognitive impairment and number of impaired scores required for a diagnosis. Cox models examined MCI status in predicting risk of progression to dementia. Results: MCI diagnosed by both the Jak/Bondi and Petersen/Winblad criteria was associated with incident dementia; however, when both criteria were included in the regression model together, only the Jak/Bondi criteria remained statistically significant. At follow-up, the Jak/Bondi criteria had a lower MCI-to-normal reversion rate than the Petersen/Winblad criteria. Conclusions: Our findings are consistent with previous research on the Jak/Bondi criteria and support the use of a comprehensive neuropsychological diagnostic approach for MCI among old-old individuals.

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Association of amyloid-β CSF/PET discordance and tau load 5 years later

Neurology ◽

10.1212/wnl.0000000000010739 ◽

2020 ◽

Vol 95 (19) ◽

pp. e2648-e2657 ◽

Cited By ~ 1

Author(s):

Juhan Reimand ◽

Lyduine Collij ◽

Philip Scheltens ◽

Femke Bouwman ◽

Rik Ossenkoppele ◽

...

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Amyloid Β ◽

Csf Biomarkers ◽

Tau Pathology ◽

Cognitively Normal ◽

Amyloid Aβ ◽

Β Amyloid ◽

Tau Pet

ObjectiveTo investigate the association between discordant β-amyloid (Aβ) PET and CSF biomarkers at baseline and the emergence of tau pathology 5 years later.MethodsWe included 730 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants without dementia (282 cognitively normal, 448 mild cognitive impairment) with baseline [18F]florbetapir PET and CSF Aβ42 available. Aβ CSF/PET status was determined at baseline using established cutoffs. Longitudinal data were available for [18F]florbetapir (Aβ) PET (baseline to 4.3 ± 1.9 years), CSF (p)tau (baseline to 2.0 ± 0.1 years), cognition (baseline to 4.3 ± 2.0 years), and [18F]flortaucipir (tau) PET (measured 5.2 ± 1.2 years after baseline to 1.6 ± 0.7 years later). We used linear mixed modeling to study the association between Aβ CSF/PET status and tau pathology measured in CSF or using PET. We calculated the proportion of CSF+/PET− participants who during follow-up (1) progressed to Aβ CSF+/PET+ or (2) became tau-positive based on [18F]flortaucipir PET.ResultsAβ CSF+/PET+ (n = 318) participants had elevated CSF (p)tau levels and worse cognitive performance at baseline, while CSF+/PET− (n = 80) participants were overall similar to the CSF−/PET− (N = 306) group. Five years after baseline, [18F]flortaucipir PET uptake in the CSF+/PET− group (1.20 ± 0.13) did not differ from CSF−/PET− (1.18 ± 0.08, p = 0.69), but was substantially lower than CSF+/PET+ (1.48 ± 0.44, p < 0.001). Of the CSF+/PET− participants, 21/64 (33%) progressed to Aβ CSF+/PET+, whereas only one (3%, difference p < 0.05) became tau-positive based on [18F]flortaucipir PET.ConclusionsAβ load detectable by both CSF and PET seems to precede substantial tau deposition. Compared to participants with abnormal Aβ levels on both PET and CSF, the CSF+/PET− group has a distinctly better prognosis.

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Mild Cognitive Impairment and Alzheimer Disease

10.1093/med/9780197512166.003.0077 ◽

2021 ◽

pp. 662-671

Author(s):

Philip W. Tipton ◽

Nilüfer Ertekin-Taner

Keyword(s):

Clinical Trials ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Alzheimer Disease ◽

Activities Of Daily Living ◽

Cognitive Decline ◽

Increased Risk ◽

Intervention Point ◽

Risk Of Progression

Many patients who have Alzheimer disease (AD) present initially with mild cognitive impairment (MCI). This chapter reviews the clinical features of MCI and AD, the clinical evaluation of patients with these entities, and the approaches to management. MCI is defined by cognitive decline that is more than expected by aging alone but does not meet criteria for dementia because the person has the ability to perform activities of daily living. MCI is considered to be a prodrome to dementia, especially AD, given the increased risk of progression to dementia. MCI, which probably represents the earliest stages of dementia in many patients, requires clinical follow-up and is expected to become an important intervention point in future clinical trials of novel preventive therapies.

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Neuropsychological Criteria for Mild Cognitive Impairment and Dementia Risk in the Framingham Heart Study

Journal of the International Neuropsychological Society ◽

10.1017/s1355617716000199 ◽

2016 ◽

Vol 22 (9) ◽

pp. 937-943 ◽

Cited By ~ 41

Author(s):

Amy J. Jak ◽

Sarah R. Preis ◽

Alexa S. Beiser ◽

Sudha Seshadri ◽

Philip A. Wolf ◽

...

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Diagnostic Criteria ◽

Framingham Heart Study ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Alternative Methods ◽

Cognitive Test ◽

Incident Dementia ◽

Heart Study

AbstractObjectives: To refine mild cognitive impairment (MCI) diagnostic criteria, we examined progression to dementia using two approaches to identifying MCI. Methods: A total of 1203 Framingham Heart Study participants were classified at baseline as cognitively normal or MCI (overall and four MCI subtypes) via conventional Petersen/Winblad criteria (single cognitive test impaired per domain, >1.5 SD below expectations) or Jak/Bondi criteria (two tests impaired per domain, >1 SD below norms). Cox proportional hazards models were constructed to examine the association between each MCI definition and incident dementia. Results: The Petersen/Winblad criteria classified 34% of participants as having MCI while the Jak/Bondi criteria classified 24% as MCI. Over a mean follow-up of 9.7 years, 58 participants (5%) developed incident dementia. Both MCI criteria were associated with incident dementia [Petersen/Winblad: hazards ratio (HR) = 2.64; p-value=.0002; Jak/Bondi: HR=3.30; p-value <.0001]. When both MCI definitions were included in the same model, only the Jak/Bondi definition remained statistically significantly associated with incident dementia (HR=2.47; p-value=.008). Multi-domain amnestic and single domain non-amnestic MCI subtypes were significantly associated with incident dementia for both diagnostic approaches (all p-values <.01). Conclusions: The Jak/Bondi MCI criteria had a similar association with dementia as the conventional Petersen/Winblad MCI criteria, despite classifying ~30% fewer participants as having MCI. Further exploration of alternative methods to conventional MCI diagnostic criteria is warranted. (JINS, 2016, 22, 937–943)

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DEFINITIONS MATTER WHEN DIAGNOSING MILD COGNITIVE IMPAIRMENT

Innovation in Aging ◽

10.1093/geroni/igz038.424 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S115-S115

Author(s):

Carol Derby ◽

Charles B Hall ◽

Mindy Katz

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Incidence Rate ◽

Population Based ◽

Study Cohort ◽

Dramatic Reduction ◽

Cognitively Normal ◽

Aging Study ◽

Normal Cognition

Abstract Prior studies have shown that when standard diagnostic criteria are applied, the majority of individuals diagnosed with aMCI do not progress to clinical dementia, with a much larger proportion reverting to normal cognition. This suggests that a prospective confirmation of aMCI diagnosis may improve the specificity of the classification. We examined the rates of aMCI reversion using two definitions: one based on a single annual assessment, and one requiring a diagnosis over two consecutive annual assessments within the population based Einstein Aging Study Cohort. Using the definition that used a single annual assessment resulted in 224 incident aMCI cases in 5,321 person years of follow-up, for an incidence rate of 4.21 cases per 100 person years. Requiring the confirmatory diagnosis resulted in only 94 incident aMCI cases in 5736 person years of follow-up, for an incidence rate of 1.64 cases per 100 person years. 41% of the persons diagnosed with aMCI using the single annual assessment were cognitively normal at the next follow-up. Only 14% of the persons diagnosed with incident aMCI using the definition requiring later confirmation ever returned to being cognitively normal. When the aMCI definition that required confirmation was used, a dramatic reduction in the incidence rate of aMCI was observed in persons born after 1930, similar to what has been reported in the same cohort for dementia, but there was no such difference for the definition based on a single annual assessment.

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Clinical and demographic parameters predict the progression from mild cognitive impairment to dementia in elderly patients

Aging Clinical and Experimental Research ◽

10.1007/s40520-020-01697-8 ◽

2020 ◽

Author(s):

Giovanni Zuliani ◽

Michele Polastri ◽

Tommaso Romagnoli ◽

Lisa Marabini ◽

Davide Seripa ◽

...

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Elderly Patients ◽

Predictive Value ◽

Clinical Chemistry ◽

Area Under The Curve ◽

Demographic Parameters ◽

Roc Curve Analysis ◽

Risk Of Progression

Abstract Objectives To evaluate the possibility of predicting the risk of progression from mild cognitive impairment (MCI) to dementia using a combination of clinical/demographic parameters. Methods A total of 462 MCI elderly patients (follow-up: 33 months). Variable measured included cognitive functions, age, gender, MCI type, education, comorbidities, clinical chemistry, and functional status. Results Amnestic type (aMCI) represented 63% of the sample, non-amnestic (naMCI) 37%; 190 subjects progressed to dementia, 49% among aMCI, and 28% among naMCI. At Cox multivariate regression analysis, only MMSE (one point increase HR 0.84; 95% CI 0.79–0.90), aMCI (HR 2.35; 95% CI 1.39–3.98), and age (1 year increase HR 1.05; 95% CI 1.01–1.10) were independently associated with progression to dementia. A score was created based on these dichotomized variables (score 0–3): age (≥ or < 78 years), MMSE score (≥ or < 25/30) and aMCI type. The conversion rate progressed from 6% in subjects with score 0 (negative predictive value: 0.94), to 31% in individuals with score 1, to 53% in subjects with score 2, to 72% in individuals with score 3 (positive predictive value: 0.72). ROC curve analysis showed an area under the curve of 0.72 (95% CI 0.66–0.75, p 0.0001). Conclusions We have described a simple score, based on previously recognized predictors such as age, MMSE, and MCI type, which may be useful for an initial stratification of the risk of progression to dementia in patients affected by MCI. The score might help the clinicians to evaluate the need for more expansive/invasive examinations and for a closer follow-up in MCI patients.

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P1-307: PIB retention changes in cognitively normal, mild cognitive impairment and Alzheimer's disease: One year follow-up study

Alzheimer s & Dementia ◽

10.1016/j.jalz.2011.05.586 ◽

2011 ◽

Vol 7 ◽

pp. S208-S209 ◽

Cited By ~ 1

Author(s):

Il Han Choo ◽

Dong Young Lee ◽

Eun Hyun Seo ◽

Yu Kyeong Kim ◽

Eun Jin Yoon ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Cognitively Normal ◽

Follow Up Study ◽

One Year

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Predictors of Incident Mild Cognitive Impairment and Its Course in a Diverse Community-Based Population

Neurology ◽

10.1212/wnl.0000000000013017 ◽

2021 ◽

pp. 10.1212/WNL.0000000000013017

Author(s):

Milou J Angevaare ◽

Jet M.J. Vonk ◽

Laiss Bertola ◽

Laura Zahodne ◽

Caitlin Wei-Ming Watson ◽

...

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Leisure Activities ◽

Community Based ◽

Cognitively Normal ◽

Clinical Criteria ◽

Apoe Ε4 ◽

Increased Risk ◽

Antidepressant Use

Objective:To investigate socio-demographic and medical predictors of incident mild cognitive impairment (MCI) and subsequent course of MCI at follow-up, including sustained MCI diagnosis, classification as cognitively normal, and progression to dementia.Methods:Within a community-based cohort, diagnoses of MCI were made using a published algorithm. Diagnosis of dementia was based on clinical consensus. Cox regressions estimated hazard ratios of incident MCI associated with several predictors. Modified Poisson regressions estimated relative risks associated with predictors of diagnostic status at follow-up after incidence.Results:Among 2903 cognitively normal participants at baseline, 752 developed MCI over an average of 6.3 (SD=4.5) years (incidence rate: 56/1,000 person-years). Presence of APOE ε4 and higher medical burden increased risk of incident MCI, while more years of education, more leisure activities, and higher income decreased this risk. Of the incident MCI cases, after an average of 2.4 years follow-up, 12.9% progressed to dementia, 9.6% declined in functioning and did not meet the algorithmic criteria for MCI but did not meet the clinical criteria for dementia either, 29.6% continued to meet MCI criteria, and 47.9% no longer met MCI criteria. Multi-domain MCI, presence of APOE ε4, depressive symptoms and antidepressant use increased the risk of progression to dementia.Conclusions:This community-based study showed that almost half of the individuals with incident MCI diagnoses were classified as cognitively normal at follow-up. Predictors of incident MCI demonstrably differed from those of subsequent MCI course; these findings can refine expectations for cognitive and functional course of those presenting with MCI.

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Slowing on quantitative EEG is associated with transition to dementia in mild cognitive impairment

International Psychogeriatrics ◽

10.1017/s1041610221001083 ◽

2021 ◽

pp. 1-5

Author(s):

Calum A. Hamilton ◽

Julia Schumacher ◽

Fiona Matthews ◽

John-Paul Taylor ◽

Louise Allan ◽

...

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Lewy Bodies ◽

Quantitative Eeg ◽

Clinical Progression ◽

Consensus Panel ◽

Functional Changes ◽

Incident Dementia ◽

Eeg Abnormalities

ABSTRACT Electroencephalographic (EEG) abnormalities are greater in mild cognitive impairment (MCI) with Lewy bodies (MCI-LB) than in MCI due to Alzheimer’s disease (MCI-AD) and may anticipate the onset of dementia. We aimed to assess whether quantitative EEG (qEEG) slowing would predict a higher annual hazard of dementia in MCI across these etiologies. MCI patients (n = 92) and healthy comparators (n = 31) provided qEEG recording and underwent longitudinal clinical and cognitive follow-up. Associations between qEEG slowing, measured by increased theta/alpha ratio, and clinical progression from MCI to dementia were estimated with a multistate transition model to account for death as a competing risk, while controlling for age, cognitive function, and etiology classified by an expert consensus panel. Over a mean follow-up of 1.5 years (SD = 0.5), 14 cases of incident dementia and 5 deaths were observed. Increased theta/alpha ratio on qEEG was associated with increased annual hazard of dementia (hazard ratio = 1.84, 95% CI: 1.01–3.35). This extends previous findings that MCI-LB features early functional changes, showing that qEEG slowing may anticipate the onset of dementia in prospectively identified MCI.

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Social Participation and the Risk for Developing Mild Cognitive Impairment and Dementia Among Older Adults

Innovation in Aging ◽

10.1093/geroni/igab046.049 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. 13-13

Author(s):

Hrafnhildur Eymundsdottir ◽

Sigurveig Sigurdardottir ◽

Alfons Ramel ◽

Palmi Jonsson ◽

Vilmundur Gudnason ◽

...

Keyword(s):

Older Adults ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Social Participation ◽

Community Dwelling ◽

Cognitively Normal ◽

Frequency Of Contact ◽

Gene Environment ◽

Vitamin D Levels

Abstract Introduction We aim to investigate the longitudinal associations between social participation and the risk of developing mild cognitive impairment (MCI|) and dementia over 5 years of follow-up among cognitively normal older adults. Methods A total of 2802 participants had complete follow-up data from Age-Gene/Environment-Susceptibility-Reykjavik-Study. Social participation was assessed by a questionnaire asking the frequency of contact with children, relatives, friends and neighbors. MCI and dementia were diagnosed according to international guidelines and by a team composed of a geriatrician, neurologist, neuropsychologist, and neuroradiologist. Logistic regression analysis was used to assess the associations. Results At baseline 8% (n=225) reported no social participation. Among cognitively normal participants at baseline, 5.6% (n=243) developed mild cognitive impairment and 2.4% (n= 103) developed dementia during a mean follow-up time of 5.2 years. After full adjustment with covariates including age, gender, education, marital status, vitamin D levels, depression and APOE ε4, those with no social participation at baseline were significantly more likely to develop MCI at follow-up (OR=1.953, P=0.001). However, social participation at baseline was not associated with higher dementia diagnosis at follow-up (OR= 1.490, P=0.194). Conclusions Community-dwelling old adults who are socially inactive are more likely to develop MCI than those who are socially active. Social participation might independently indicate impending changes in cognitive function among older adults.

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