Epidemiology of Alzheimer’s disease: a relevant challenge for long-term follow-up of a population-based cohort

Author(s):  
Jean François Dartigues ◽  
Leslie Grasset ◽  
Tabue Teguo Maturin ◽  
Alexandra Foubert ◽  
Karine Pérès ◽  
...  

The epidemiology of Alzheimer’s disease (AD) is difficult for several reasons: lack of operational criteria for AD; majority of incident cases occurring in very old people with multiple comorbidities; long prodromal phase before the dementia phase; large proportion of undiagnosed cases; and strong competition with death. There is no clear operational definition of cognitive decline and of impairment in social function related to this decline, and these clinical manifestations are the core of the clinical diagnosis of AD. Diagnosis is left to the the clinician’s subjectivity, which is influenced by the cultural context, the social context, and the expected efficacy of the treatment at the early phase of dementia. Several published papers are presented and conclusions discussed, including the protective effect of playing board games, the effect of changes in leisure activities with age, natural history of cognitive decline before AD according to education, and predictive score for dementia.

2021 ◽  
Vol 33 (S1) ◽  
pp. 90-91
Author(s):  
Alena Sidenkova

IntroductionThe aging processes are accelerating in all regions of the world. The involvement of older people in production and social processes determines the need to maintain a high level of social and psychological adaptation, despite the progressive pathology of the brain caused by its aging. This increases the relevance of research related to the study of biological reserves of the brain and psychological and social mechanisms of human adaptation in late adulthood. The risk of developing cognitive disorders is not fatal. According to some observations, even in the hippocampal type of UKR, despite the content of amyloid in the brain, the functional and social activity of the elderly remains high. Prospective studies show that people with high cognitive reserve have a lower risk of developing dementia. Cognitive reserve is the brain’s resistance to damage. Cognitive reserve is the ability of the brain to cope with the consequences of damage caused by external influences, brain stroke, chronic brain ischemia, neurodegenerative diseases, and age-related changes. Cognitive reserve is the brain’s ability to functionally compensate for and minimize clinical manifestations of cognitive impairment. The mechanisms of cognitive reserve in normal and Alzheimer’s disease are different. In healthy older adults, a higher cognitive reserve correlates with larger brain sizes and effective strategies for performing cognitive tasks. In the early stages of Alzheimer’s disease and Alzheimer’s disease, the size of the brain decreases. But high brain activity helps preserve cognitive resources. Excessive brain activity in dementia is a compensatory mechanism. This is confirmed by the results of functional magnetic resonance imaging of the brain. Of course, the degree of brain atrophy is a predisposing factor for dementia, but it is not a mandatory factor for cognitive decline. So, the symptoms of dementia do not appear until you have crossed the critical border of damage to the brain substance. Progressive brain atrophy underlies the clinical manifestations of dementia in neurodegenerative diseases, but the correlation between the degree of brain damage and cognitive impairment is not linear.Research materials and methodsAn observational 10-year longitudinal study was conducted. In 2006, moderate cognitive impairment was found in 66 patients. The group of patients included 49 women and 49 men. Their average age in 2006 was 59.3±5.2 years. In 2006, the severity of cognitive decline was 26.2±1.9 points on the MMSE scale. This corresponds to indicators of moderate cognitive impairment. Research methods: clinical and psychopathological, psychometric, statistical. Questionnaire “Loss and acquisition of personal resources” (N. Vodopyanova, M. Stein), MMSE scale.Research resultIn 2006, amyloid was detected in the spinal fluid of all patients selected for the study group. If a patient developed dementia, they were given specific therapy. The dynamics of cognitive functions in patients was different. Mild dementia was formed in 53% of patients. Moderate dementia was formed in 10.6% of patients. Moderate cognitive impairment (pre-dementia) persisted in 36.4% of patients. Hereditary burden of dementia in patients with moderate dementia was detected 2 times more often. Back in 2006, we identified the leading sensory systems of patients. The master sensor system determines the modality of the main information flow. This is the most important part of the information that a person interacts with. This is the basis of interaction with reality. This is the basis of cognitive functions. Correlations of age-specific lesions of the corresponding sensory systems with the severity of cognitive decline were found in patients with the corresponding sensory modality (Spearman’s Correlation Coefficient-r, p<0.05): presbyacoussis – auditory r=0.667, presbyopia-visual r=0.705. The influence of psychosocial factors on the condition of patients was studied. In dementia, significant history of psychotrauma was found in 35.7%. Moderate stress was detected in the group of patients with moderate cognitive impairment in 33.3%. Moderate stress was detected in the group of patients with dementia in 83.3%. Stress of loss of life meaning was detected more often in patients with dementia 76.7%. It is important not only what stresses a person endures, but how they can cope with them. Dementia patients were statistically more likely to have unproductive coping strategies that did not help them cope adequately with stress.ConclusionsThe concept of cognitive reserve suggests possible causes of heterogeneity in the dynamics of cognitive decline in the initial stages of atrophic-degenerative brain diseases: biological causes and psychosocial causes. The concept of cognitive reserve helps to study and develop individual programs for the prevention of severe cognitive disorders.


2021 ◽  
Vol 13 ◽  
Author(s):  
Rebecca Langhough Koscik ◽  
Bruce P. Hermann ◽  
Samantha Allison ◽  
Lindsay R. Clark ◽  
Erin M. Jonaitis ◽  
...  

While clinically significant cognitive impairment is the key feature of the symptomatic stages of the Alzheimer’s disease (AD) continuum, subtle cognitive decline is now known to occur years before a clinical diagnosis of mild cognitive impairment (MCI) or dementia due to AD is made. The primary aim of this study was to examine criterion validity evidence for an operational definition of “cognitively unimpaired-declining” (CU-D) in the Wisconsin Registry for Alzheimer’s Prevention (WRAP), a longitudinal cohort study following cognition and risk factors from mid-life and on. Cognitive status was determined for each visit using a consensus review process that incorporated internal norms and published norms; a multi-disciplinary panel reviewed cases first to determine whether MCI or dementia was present, and subsequently whether CU-D was present, The CU-D group differed from CU-stable (CU-S) and MCI on concurrent measures of cognition, demonstrating concurrent validity. Participants who changed from CU-S to CU-D at the next study visit demonstrated greater declines than those who stayed CU-S. In addition, those who were CU-D were more likely to progress to MCI or dementia than those who were CU-S (predictive validity). In a subsample with positron emission tomography (PET) imaging, the CU-D group also differed from the CU-S and MCI/Dementia groups on measures of amyloid and tau burden, indicating that biomarker evidence of AD was elevated in those showing sub-clinical (CU-D) decline. Together, the results corroborate other studies showing that cognitive decline begins long before a dementia diagnosis and indicate that operational criteria can detect subclinical decline that may signal AD or other dementia risk.


Aging ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 10099-10116
Author(s):  
Stephanny Lizarraga ◽  
Etienne W. Daadi ◽  
Gourav Roy-Choudhury ◽  
Marcel M. Daadi

2021 ◽  
Author(s):  
Cassandra Morrison ◽  
Mahsa Dadar ◽  
Neda Shafiee ◽  
Sylvia Villeneuve ◽  
D. Louis Collins ◽  
...  

AbstractBackgroundPeople with subjective cognitive decline (SCD) may be at increased risk for Alzheimer’s disease (AD). However, not all studies have observed this increased risk. Inconsistencies may be related to different methods used to define SCD. The current project examined whether four methods of defining SCD (applied to the same sample) results in different patterns of atrophy and future cognitive decline between cognitively normal older adults with (SCD+) and without SCD (SCD-).MethodsMRI scans and questionnaire data for 273 cognitively normal older adults from Alzheimer’s Disease Neuroimaging Initiative were examined. To operationalize SCD we used four common methods: Cognitive Change Index (CCI), Everyday Cognition Scale (ECog), ECog + Worry, and Worry only. A previously validated MRI analysis method (SNIPE) was used to measure hippocampal volume and grading. Deformation-based morphometry was performed to examine volume at regions known to be vulnerable to AD. Logistic regressions were completed to determine whether diagnostic method was associated with volume differences between SCD- and SCD+. Linear mixed effects models were performed to examine the relationship between the definitions of SCD and future cognitive decline.ResultsResults varied between the four methods of defining SCD. Left hippocampal grading was lower in SCD+ than SCD-when using the CCI (p=.041) and Worry (p=.021) definitions. The right (p=.008) and left (p=.003) superior temporal regions were smaller in SCD+ than SCD-, but only with the ECog. SCD+ was associated with greater future cognitive decline measured by Alzheimer’s Disease Assessment Scale, but only with the CCI definition. In contrast, only the ECog definition of SCD was associated with future decline on the Montreal Cognitive Assessment.ConclusionThe current findings suggest that the various methods used to differentiate between SCD- and SCD+ influence whether volume differences and findings of cognitive decline are observed between groups in this retrospective analysis.


Author(s):  
Marco Bucci ◽  
Konstantinos Chiotis ◽  
Agneta Nordberg ◽  

AbstractFor early detection of Alzheimer’s disease, it is important to find biomarkers with predictive value for disease progression and clinical manifestations, such as cognitive decline. Individuals can now be profiled based on their biomarker status for Aβ42 (A) or tau (T) deposition and neurodegeneration (N). The aim of this study was to compare the cerebrospinal fluid (CSF) and imaging (PET/MR) biomarkers in each ATN category and to assess their ability to predict longitudinal cognitive decline. A subset of 282 patients, who had had at the same time PET investigations with amyloid-β and tau tracers, CSF sampling, and structural MRI (18% within 13 months), was selected from the ADNI dataset. The participants were grouped by clinical diagnosis at that time: cognitively normal, subjective memory concern, early or late mild cognitive impairment, or AD. Agreement between CSF (amyloid-β-1-42(A), phosphorylated-Tau181(T), total-Tau(N)), and imaging (amyloid-β PET (florbetaben and florbetapir)(A), tau PET (flortaucipir)(T), hippocampal volume (MRI)(N)) positivity in ATN was assessed with Cohen’s Kappa. Linear mixed-effects models were used to predict decline in the episodic memory. There was moderate agreement between PET and CSF for A biomarkers (Kappa = 0.39–0.71), while only fair agreement for T biomarkers (Kappa ≤ 0.40, except AD) and discordance for N biomarkers across all groups (Kappa ≤ 0.14) was found. Baseline PET tau predicted longitudinal decline in episodic memory irrespective of CSF p-Tau181 positivity (p ≤ 0.02). Baseline PET tau and amyloid-β predicted decline in episodic memory (p ≤ 0.0001), but isolated PET amyloid-β did not. Isolated PET Tau positivity was only observed in 2 participants (0.71% of the sample). While results for amyloid-β were similar using CSF or imaging, CSF and imaging results for tau and neurodegeneration were not interchangeable. PET tau positivity was superior to CSF p-Tau181 and PET amyloid-β in predicting cognitive decline in the AD continuum within 3 years of follow-up.


2002 ◽  
Vol 14 (4) ◽  
pp. 347-363 ◽  
Author(s):  
Thomas Fritsch ◽  
Mckee J. McClendon ◽  
Kathleen A. Smyth ◽  
Paula K. Ogrocki

Researchers have suggested that educational attainment and occupational status—indicators of cognitive and/or neurologic “reserve”—can help persons compensate for clinical manifestations of Alzheimer's disease (AD), such as the rates of cognitive and functional decline. The effects of educational attainment on rates of decline could be “direct” (independent of occupational status), “indirect” (working through occupational status), or both. We used multilevel analysis for repeated measures to study the effects of educational attainment and occupational status on rates of decline in cognition (Mini-Mental State Examination, MMSE) and function (Cleveland Scale for Activities of Daily Living). Subject included persons with “probable” or “possible” AD, drawn from our Alzheimer's Disease Research Center registry (N = 482 in the analysis of cognitive decline, and N = 450 in the analysis of functional decline). When controlling for year of birth, gender, ethinicity, and duration of illness, we found that there was an inverse relationship between number of years of education and rate of decline in MMSE, but effects of occupational status were not significant. This implies a “direct” effect of education on decline in MMSE, but no “indirect” effect through occupational status. Neither educational attainment nor occupational status affected rate of decline in functional ability. We conclude that education slows the rate of cognitive decline in persons with AD, but not through its impact on occupational status. Thus the protective effects of reserve may be established early in life, before people enter the workforce.


2021 ◽  
pp. 1-7
Author(s):  
Halle J. Kincaid ◽  
Ravinder Nagpal ◽  
Hariom Yadav

<b><i>Background:</i></b> Alzheimer’s disease (AD) is the most common form of dementia, particularly in older adults, with clinical manifestations of progressive cognitive decline and functional impairment. The prevalence of AD and related dementia is mounting worldwide, but its etiology remains unresolved, with no available preventative or ameliorative therapy. Emerging evidence suggests that the gut microbiota of patients with AD is different from cognitively normal counterparts. <b><i>Summary:</i></b> Communication between gut and brain (gut-brain axis) plays a crucial role in AD pathology. Bacteria inhabiting the gut strongly influence this gut-brain axis and thus may participate in AD pathology. Diet, one of the strongest modulators of gut microbiota, also strongly influences brain health and AD pathology. Gut microbiota metabolites including short-chain fatty acids, pro-inflammatory factors, and neurotransmitters may also affect AD pathogenesis and associated cognitive decline. Therefore, investigation of diet-microbiota-brain axis is important to better understand its contribution in AD pathology and its potential use as a target to prevent and treat AD. Herein, we discuss the link between AD and gut microbiota and ponder how microbiota modulation through nutritional approaches may offer avenues for discovering novel preventive and therapeutic strategies against AD. <b><i>Key Message:</i></b> A strong association exists between lifestyle factors and AD prevalence wherein unhealthy dietary factors have been linked to neurodegeneration. Specific prudent dietary patterns might help in preventing or delaying AD progression by affecting β-amyloid production and tau processing and regulating AD-associated inflammation, metabolism and oxidative stress, plausibly via modulating gut microbiota.


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