Pattern Recognition to Objectively Differentiate the Etiology of Cognitive Decline: Analysis of the Impact of Stroke and Alzheimer’s Disease

Clouston, Sean; Richmond, Lauren L.; Scott, Stacey B.; Luhmann, Christian C.; Natale, Ginny; Hanes, David A.; Zhang, Yun; Smith, Dylan M.

doi:10.1159/000510133

Cited by 4 publications

(2 citation statements)

References 42 publications

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“…Ageing is the strongest risk factor for dementia [1,2] . Episodic memory and many cognitive functions are known to decline progressively with ageing.…”

Section: Introductionmentioning

confidence: 99%

Re-energising the brain: glucose metabolism, Tau protein and memory in ageing and dementia

Robbins

2024

Ageing Neur Dis

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Memory naturally declines as we age, but the rapid loss of memory can be distressing for people living with Alzheimer’s disease (AD). How memories are formed and retrieved in the brain is not fully understood; it is thought to require plasticity to the synapses connecting neurons in a network of engram cells. Plasticity may occur either through changes to the volume and location of molecules and organelles within the synapse, or gross structural changes of synapses. Memory naturally declines as we age, as do many of the mechanisms required for learning and memory, such as changes in concentrations of the cytoskeletal structural protein Microtubule-Associated Protein Tau, reduced brain glucose metabolism, and sensitivities to insulin. The biggest risk factor for developing AD is ageing, yet only few studies try to reconcile the natural decline in functions we see with ageing with the dramatic impairment of these pathways in AD, such as Tau protein and energy homeostasis by neurons. This review will therefore explain the changes to metabolism, Tau protein, and memory impairment during ageing, and explore the latest research that links these processes to neurodegeneration seen in AD, and other Tauopathies. Understanding how ageing and dementia diverge may offer an important and underutilised avenue for therapeutic interventions to target metabolism in both “healthy” ageing and disease.

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“…Ageing is the strongest risk factor for dementia [1,2] . Episodic memory and many cognitive functions are known to decline progressively with ageing.…”

Section: Introductionmentioning

confidence: 99%

Re-energising the brain: glucose metabolism, Tau protein and memory in ageing and dementia

Robbins

2024

Ageing Neur Dis

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“…1 The onset of MCI and dementia emerge from cognitive decline processes that are complex and dynamic, with a large amount of within-individual and between-individual differences. 2 As adults age, many people experience subtle changes in cognitive abilities that do not affect their independence in daily living activities, but some experience a level of cognitive impairment that may be more severe than expected and indicate onset of possible mild cognitive impairment (MCI). 3 A person experiencing MCI may remain mildly impaired, progress to severe dementia, or even revert to normal cognition.…”

Section: Introductionmentioning

confidence: 99%

Incidence of Mild Cognitive Impairment, Conversion to Probable Dementia, and Mortality

Zhang

Natale

Clouston

2021

Am J Alzheimers Dis Other Demen

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Background: Few studies have jointly estimated incidence of MCI, conversion to probable dementia, and mortality in a nationally representatie sample. Methods: We used data from six waves of the National Health and Aging Trends Study (2011-2016). Multivariable-adjusted multi-state survival models (MSMs) were used to model incidence upon accounting for misclassification. Results: A total of 6,078 eligible NHATS participants were included (average age: 77.49 ± 7.79 years; 58.42% females; 68.99% non-Hispanic white). The incidence of MCI was estimated to be 41.0 [35.5, 47.3]/1,000 person-years (PY). Participants converted to probable dementia at a high rate of 241.3 [189.6, 307.0]/1,000 PY, though a small number also reverted from MCI to cognitively normal. Education was associated with lower incidence of MCI and conversion to probable dementia, but increased mortality in those with MCI. There were also substantial racial and ethnic disparities in the incidence of MCI and dementia. Conclusions: Our results underscore the relatively common incidence of and conversions between MCI and dementia in community-dwelling older Americans and uncover the beneficial impact of education to withstand cognitive impairment before death.

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Inequalities in accelerated cognitive decline: Resolving observational window bias using nested non‐linear regression

Clouston,

Hanes,

Smith

et al. 2024

Alzheimer's & Dementia

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INTRODUCTIONLimited observational windows lead to conflicting results in studies examining educational differences in Alzheimer's disease and related dementias (ADRD) risk, due to observational window bias relative to onset of accelerated cognitive decline. This study tested a novel model to address observational window bias and tested for the presence and sources of disparities in accelerated cognitive declines due to ADRD.METHODSThe sample examined 167,314 cognitive assessments from 32,441 Health and Retirement Study participants. We implemented a parametric non‐linear nested longitudinal regression and reported multivariable‐adjusted nodal incidence ratios (aNIR).RESULTSUniversity degrees were associated with lower incidence (aNIR = 0.253, 95% confidence interval [CI] = [0.221 to 0.289], p < 0.001), while black participants had a higher incidence (aNIR = 1.995, [1.858 to 2.141], p < 0.001) of accelerated cognitive decline, adjusting for demographic, sociobehavioral, and medical risk factors. Sex‐stratified analyses identified diminished educational returns for women and increased incidence among minoritized women.DISCUSSIONAddressing observational window bias reveals large social inequalities in the onset of accelerated cognitive declines indicative of ADRD.Highlights This study identifies observational window bias as a source of conflicting results among previous studies of educational achievement in Alzheimer's disease and related dementias (ADRD) disparities. The study locates preclinical accelerated cognitive decline, which is indicative of ADRD while occurring 10+ years prior to symptom onset, as a site to study ADRD disparities that mitigates observational window bias. A novel method, nested non‐linear regression, is developed to test for differences in the onset of accelerated cognitive decline. Educational and racial/ethnic disparities are demonstrated in the onset of accelerated cognitive decline, as are their intersecting differences with sex/gender.

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Pattern Recognition to Objectively Differentiate the Etiology of Cognitive Decline: Analysis of the Impact of Stroke and Alzheimer’s Disease

Cited by 4 publications

References 42 publications

Re-energising the brain: glucose metabolism, Tau protein and memory in ageing and dementia

Re-energising the brain: glucose metabolism, Tau protein and memory in ageing and dementia

Incidence of Mild Cognitive Impairment, Conversion to Probable Dementia, and Mortality

Inequalities in accelerated cognitive decline: Resolving observational window bias using nested non‐linear regression

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