Aging-Alzheimer's Association Research Articles

Association between cooking fuels and mild cognitive impairment among older adults from six low- and middle-income countries

There is a small body of evidence suggesting that unclean cooking fuel use may be associated with cognitive decline. However, to date, no study has investigated the association between unclean cooking fuel and mild cognitive impairment (MCI). Thus, we investigated the association between cooking fuel type or ventilation type and MCI among adults aged ≥ 65 years using nationally representative datasets from six low- and middle-income countries. Cross-sectional, community-based data from the World Health Organization (WHO) Study on global Ageing and adult health (SAGE) were analyzed. MCI was defined using the National Institute on Aging-Alzheimer's Association criteria. Unclean cooking fuel referred to kerosene/paraffin, coal/charcoal, wood, agriculture/crop, animal dung, and shrubs/grass. Multivariable logistic regression analysis was conducted to assess associations. Data on 13,623 individuals were analyzed [mean (SD) age 72.8 (11.0) years; 45.5% males]. Unclean cooking fuel (vs. clean cooking fuel) was associated with a significant 1.48 (95% CI = 1.08–2.03) times higher odds for MCI. Having no chimney or hood for cooking ventilation was also associated with significantly higher odds for MCI (OR = 1.88; 95% CI = 1.25–2.84). Unclean cooking fuel use and lack of chimney or hood for cooking ventilation were associated with higher odds for MCI. Findings support the implementation of the United Nations Sustainable Goal 7, which advocates affordable, reliable, sustainable, and modern energy for all, as this may also help reduce MCI and ultimately dementia.

Semi-quantitative Assessment of Alzheimer's-like Pathology in Two Aged Polar Bears (Ursus maritimus).

Age-associated neurodegenerative changes, including amyloid β (Aβ) plaques, neurofibrillary tangles (NFTs), and amyloid angiopathy comparable to those seen in the brains of human patients with Alzheimer's disease (AD), have been reported in the brains of aged bears. However, the significance of these findings in bears is unclear due to the difficulty in assessing cognitive impairment and the lack of standardized approaches for the semiquantitative evaluation of Aβ plaques and NFTs. In this study, we evaluate the neuropathologic changes in archival brain tissue of 2 aged polar bears (Ursus maritimus, ages 28 and 37) using the National Institute of Aging-Alzheimer Association (NIA-AA) consensus guidelines for the neuropathologic assessment of Alzheimer's Disease (AD). Both bears had an Aβ (A) score of 3 of 3, Braak stage (B score) of 2 of 3, and neuritic plaque (C) score of 3 of 3. These findings are consistent with the neurodegenerative changes observed in brains of patients with AD. The application of NIA-AA consensus guidelines, as applied to the neuropathologic assessment of the aged bears in this report, demonstrates the use of standardized semiquantitative assessment systems for comparative, translational studies of aging in a vulnerable wildlife species.

Genetic Risk, Midlife Life's Simple 7, and Incident Dementia in the Atherosclerosis Risk in Communities Study.

Higher scores in Life's Simple 7 (LS7), a metric for cardiovascular and brain health, have been associated with lower risk of dementia. It is uncertain whether this association holds among those with high genetic risk of dementia. Our objective is to evaluate the extent that LS7 may offset dementia risk across the range of genetic risk. Participants in the Atherosclerosis Risk in Communities (ARIC) Study were followed from 1987-1989 to 2019. We derived midlife LS7 scores and generated genetic risk scores (GRS) using genome-wide summary statistics of Alzheimer disease, which have been used to study the genetic risk for dementia. Incident dementia was ascertained based on the criteria of the National Institute on Aging-Alzheimer's Association workgroups and Diagnostic and Statistical Manual of Mental Disorders. The associations of the GRS and LS7 with incident dementia were evaluated using Cox regression. This study included 8,823 European American (EA) and 2,738 African American (AA) participants (mean age at baseline 54 years). We observed 1,603 cases of dementia among EA participants and 631 among AA participants (median follow-up 26.2 years). Higher GRS were associated with higher risk of dementia (EA, hazard ratio [HR] per SD 1.44, 95% CI 1.37, 1.51; AA, HR 1.26, 95% CI 1.16, 1.36). Among EA participants, higher LS7 scores were consistently associated with lower risk of dementia across quintiles of GRS, including the highest quintile (HR per point 0.91, 95% CI 0.87, 0.96). Among AA participants, the associations between LS7 and incident dementia within stratum of GRS had the same direction as among EA participants, although wide CIs and smaller sample sizes limited reliable inferences. Across strata of GRS, higher midlife LS7 scores were associated with lower risk of dementia. Larger sample sizes from diverse populations are needed to obtain more reliable estimates of the effects of modifiable health factors on dementia risk within genetic risk strata in each ancestry group.

Brainstem auditory evoked potential in cognitive impairment in patients with type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) can cause mild cognitive impairment (MCI) which threatens the health of patients. So the diagnosis of MCI is particularly important. It is reported that brainstem auditory evoked potential (BAEP) is a sensitive tool to detect the brainstem function in patients with T2DM. This study aimed to investigate the relationship between BAEP and MCI in patients with T2DM. A total of 244 T2DM patients with normal hearing, including 117 normal cognition patients and 127 MCI patients, were recruited in this cross-sectional study. Each subject underwent the BAEP examination. The diagnosis of MCI was based on the diagnostic guideline developed by the National Institute on Aging-Alzheimer's Association workgroups. The Montreal Cognitive Assessment (MoCA) was used to assess the cognitive function of the subjects. Compared with the normal cognition group, the patients in the MCI group had longer latencies of waves III and V and interpeak latencies (IPL) I-V in both ears (P<0.05). The significant negative correlations were found between the latencies of waves III, V, IPL I-V, and MoCA score in both ears (P<0.05). Logistic regression showed that the prolongations of latunits of waves III and V and IPL I-V in both ears were still associated with MCI after adjustment for mixed factors (P<0.05). These results indicate abnormal auditory pathway in brainstem of T2DM patients with MCI. BAEP may contribute to the clinical diagnosis of MCI in patients with T2DM.

Body Mass Index and Mild Cognitive Impairment Among Middle-Aged and Older Adults from Low- and Middle-Income Countries.

The effect of weight modification on future dementia risk is currently a subject of debate and may be modified by age. The aim of the present study was to investigate the association between body mass index (BMI) status with mild cognitive impairment (MCI) (a preclinical stage of dementia) in middle-aged and older adults residing in six low- and middle-income countries using nationally representative data. Cross-sectional data from the Study on Global Ageing and Adult Health (SAGE) were analyzed. MCI was defined using the National Institute on Aging-Alzheimer's Association criteria. BMI (kg/m2) was based on measured weight and height and categorized as: underweight (<18.5), normal (18.5-24.9), overweight (25.0-29.9), and obese (≥30.0). Multivariable logistic regression analysis and meta-analysis were conducted to assess associations. Data on 32,715 individuals aged ≥50 years with preservation in functional abilities were analyzed [mean (SD) age 62.1 (15.6) years; 51.7% females]. Among those aged 50-64 years, compared to normal weight, underweight (OR = 1.44; 95% CI = 1.14-1.81), overweight (OR = 1.17; 95% CI = 1.002-1.37), and obesity (OR = 1.46; 95% CI = 1.09-1.94) were all significantly associated with higher odds for MCI. In those aged ≥65 years, underweight (OR = 0.71; 95% CI = 0.54-0.95) and overweight (OR = 0.72; 95% CI = 0.55-0.94) were associated with significantly lower odds for MCI, while obesity was not significantly associated with MCI. The results of the study suggest that the association between BMI and MCI is likely moderated by age. Future longitudinal studies are required to confirm or refute the present findings before recommendations for policy and practice can be made.

Forecasting the prevalence of dementia

Forecasting the prevalence of dementia

Alzheimer's disease biomarkers in Black and non-Hispanic White cohorts: A contextualized review of the evidence.

Black Americans are disproportionately affected by dementia. To expand our understanding of mechanisms of this disparity, we look to Alzheimer's disease (AD) biomarkers. In this review, we summarize current data, comparing the few studies presenting these findings. Further, we contextualize the data using two influential frameworks: the National Institute on Aging–Alzheimer's Association (NIA‐AA) Research Framework and NIA's Health Disparities Research Framework. The NIA‐AA Research Framework provides a biological definition of AD that can be measured in vivo. However, current cut‐points for determining pathological versus non‐pathological status were developed using predominantly White cohorts—a serious limitation. The NIA's Health Disparities Research Framework is used to contextualize findings from studies identifying racial differences in biomarker levels, because studying biomakers in isolation cannot explain or reduce inequities. We offer recommendations to expand study beyond initial reports of racial differences. Specifically, life course experiences associated with racialization and commonly used study enrollment practices may better account for observations than exclusively biological explanations.

Is cerebral vascular pathology a bystander of Alzheimer’s disease? Evidence from a genetic perspective

Alzheimer's disease (AD) is a multifactorial caused neurodegenerative disorder. The latest AD research framework proposed by the National Institute on aging-Alzheimer's Association described a biomarker-based pathological definition of AD, focusing on amyloid-β (Aβ), tau and neurodegeneration. This proposal separated the role of vascular involvement in the pathophysiology of AD, indicating vascular event is a bystander in AD. To testify this concept, we explored the common genetic evidences for the shared common initiative molecular pathways in AD and ischemic stroke.The common Single Nucleotide Polymorphisms (SNPs) susceptible to AD and ischemic stroke and their mapped genes were identified using GWAS Catalog database. Signaling pathways associated with these genes were obtained from the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Genecards database. The Gene Radar online tool in Gene-cloud of biotechnology information (GCBI) was used to identify the transcription factors involved in these genes.Up to December 15, 2020, 54 AD and 14 ischemic stroke Genome-wide association study(GWAS) datasets were chosen. In AD, 1009 susceptibility SNPs and its 1019 mapped genes were identified; while 138 susceptibility SNPs and its 162 mapped genes were identified in ischemic stroke. No any common AD and ischemic stroke susceptibility SNP was found, but ten common risk genes, accounting for 0.98% AD susceptibility genes and 6.17% ischemic stroke susceptibility genes, were identified. They are AC008125.1, AC011029.1, AGBL1, F13A1, FARP1, HDAC9, HNF4G, MMP12, MMP3 and PTPRG. The common signaling pathways with at least two of these gene products involved are G protein-coupled receptors (GPCR) (HDAC9, MMP12, MMP3), immune response (F13A1 and MMP3) and extracellular matrix (F13A1, MMP12 and MMP3). C-Ets-1 is the common transcription factor for F13A1 and MMP3. For the most AD risk gene apolipoprotein E(ApoE), there is no evidence of its direct association with ischemic stroke, but its putative homologs SERPRINA 1 and FGB associate with ischemic stroke in GWAS studies.There are some evidences of common molecular pathways involved in AD and ischemic stroke, which require further investigations to evaluate cerebral vascular impacts on the pathogenesis of AD.

Neuropathology of late life depression: Clinical predictors of amyloid and tau neuropathology in non-demented older adults with depression.

Previous studies regarding the relationship between depression and amyloid and tau neuropathology have reported conflicting findings. We examined whether depression is associated with higher Alzheimer's disease neuropathologic changes and whether sex moderates their relationships. Using the National Alzheimer's Coordinating Center database (2005-2020), we conducted a cross-sectional study of non-demented older adults (age 50+; CDR ≤ 0.5) who had autopsy within 1 year of their last clinic visit. Multivariable cumulative logit models were fitted to determine if recent and/or remote depression were associated with Thal phase score (a measure of spread of amyloid plaques) modified according to National Institute on Aging-Alzheimer's Association (NIA-AA) guidelines, modified Braak stage for neurofibrillary degeneration according to NIA-AA guidelines, density of neuritic plaques [CERAD score] and if any of their associations were moderated by sex. All regression models were adjusted for covariates associated with both depression and Alzheimer's disease, including selective serotonin or serotonin norepinephrine reuptake inhibitor use, sex, age, years of education, the presence of apolipoprotein E e4 allele, and history of diabetes, hypertension, hypercholesteremia, and traumatic brain injury. We included 395 participants (94 Thal, 393 Braak, and 394 CERAD). Those who had recent (within previous 2 years) but not remote depression were more likely to have higher Thal phase compared to those without a history of depression (Odds Ratio = 13.3; 95% CI, 1.5-116.3, p = 0.019). Sex did not moderate the association between recent depression and Thal phase. No significant associations between depression and Braak or CERAD scores were observed. Our findings suggest that recently active late-life depression is associated with spread of amyloid pathology beyond cortical regions to include subcortical regions but not with density of neuritic plaques or neurofibrillary tangles.

Neuropsychological Impairments and Their Cognitive Architecture in Mild Cognitive Impairment (MCI) with Lewy Bodies and MCI-Alzheimer's Disease.

The present study aimed to clarify the neuropsychological profile of the emergent diagnostic category of Mild Cognitive Impairment with Lewy bodies (MCI-LB) and determine whether domain-specific impairments such as in memory were related to deficits in domain-general cognitive processes (executive function or processing speed). Patients (n = 83) and healthy age- and sex-matched controls (n = 34) underwent clinical and imaging assessments. Probable MCI-LB (n = 44) and MCI-Alzheimer's disease (AD) (n = 39) were diagnosed following National Institute on Aging-Alzheimer's Association (NIA-AA) and dementia with Lewy bodies (DLB) consortium criteria. Neuropsychological measures included cognitive and psychomotor speed, executive function, working memory, and verbal and visuospatial recall. MCI-LB scored significantly lower than MCI-AD on processing speed [Trail Making Test B: p = .03, g = .45; Digit Symbol Substitution Test (DSST): p = .04, g = .47; DSST Error Check: p < .001, g = .68] and executive function [Trail Making Test Ratio (A/B): p = .04, g = .52] tasks. MCI-AD performed worse than MCI-LB on memory tasks, specifically visuospatial (Modified Taylor Complex Figure: p = .01, g = .46) and verbal (Rey Auditory Verbal Learning Test: p = .04, g = .42) delayed recall measures. Stepwise discriminant analysis correctly classified the subtype in 65.1% of MCI patients (72.7% specificity, 56.4% sensitivity). Processing speed accounted for more group-associated variance in visuospatial and verbal memory in both MCI subtypes than executive function, while no significant relationships between measures were observed in controls (all ps > .05). MCI-LB was characterized by executive dysfunction and slowed processing speed but did not show the visuospatial dysfunction expected, while MCI-AD displayed an amnestic profile. However, there was considerable neuropsychological profile overlap and processing speed mediated performance in both MCI subtypes.

Distinct conformers of amyloid beta accumulate in the neocortex of patients with rapidly progressive Alzheimer's disease

Amyloid beta (Aβ) deposition in the neocortex is a major hallmark of Alzheimer's disease (AD), but the extent of deposition does not readily explain phenotypic diversity and rate of disease progression. The prion strain–like model of disease heterogeneity suggests the existence of different conformers of Aβ. We explored this paradigm using conformation-dependent immunoassay (CDI) for Aβ and conformation-sensitive luminescent conjugated oligothiophenes (LCOs) in AD cases with variable progression rates. Mapping the Aβ conformations in the frontal, occipital, and temporal regions in 20 AD patients with CDI revealed extensive interindividual and anatomical diversity in the structural organization of Aβ with the most significant differences in the temporal cortex of rapidly progressive AD. The fluorescence emission spectra collected in situ from Aβ plaques in the same regions demonstrated considerable diversity of spectral characteristics of two LCOs—quatroformylthiophene acetic acid and heptaformylthiophene acetic acid. Heptaformylthiophene acetic acid detected a wider range of Aβ deposits, and both LCOs revealed distinct spectral attributes of diffuse and cored plaques in the temporal cortex of rapidly and slowly progressive AD and less frequent and discernible differences in the frontal and occipital cortex. These and CDI findings indicate a major conformational diversity of Aβ accumulating in the neocortex, with the most notable differences in temporal cortex of cases with shorter disease duration, and implicate distinct Aβ conformers (strains) in the rapid progression of AD.

Longitudinal association of sarcopenia and mild cognitive impairment among older Mexican adults.

BackgroundRecent evidence from cross‐sectional and longitudinal studies supports the hypothesis that sarcopenia is associated with worsening cognitive function. However, primary evidence largely comes from high‐income countries, whereas in low‐ and middle‐income countries, this association has been underexplored. This study aimed to estimate the longitudinal association between sarcopenia and mild cognitive impairment in a sample of older Mexican adults.MethodsData come from the three waves of the World Health Organization (WHO) Study on Global AGEing and Adult Health (SAGE) in Mexico (2009, 2014, 2017). Four hundred ninety‐six older adults, aged ≥50, were included. Sarcopenia was defined as having low muscle quantity and either/both slow gait speed and weak handgrip strength. Mild cognitive impairment was determined based on the recommendations of the National Institute on Aging‐Alzheimer's Association. Cognitive function was evaluated by a composite cognitive score of five different cognitive tests: immediate and delayed recall, forward and backward digit span and semantic verbal fluency. Three‐level mixed‐effects models (logistic and linear) were used to estimate the longitudinal associations between sarcopenia, mild cognitive impairment and cognitive function.ResultsThe prevalence of mild cognitive impairment (8.9%, 12.9%, 16.0%) and sarcopenia (10.5%, 20.7%, 23.3%) showed a significant temporal increase for Waves 1, 2 and 3 (P‐value < 0.01, respectively). The presence of sarcopenia was significantly associated with mild cognitive impairment (OR = 1.74; CI95% 1.02, 2.96; P = 0.04) and worse cognitive function (β = −0.57; CI95% ‐0.93, −0.21; P < 0.01). We observed significant associations between sarcopenia and immediate verbal recall (β = −0.14; CI95% −0.28, −0.01; P = 0.04), delayed verbal recall (β = −0.12; CI95% −0.23, −0.01; P = 0.03) and semantic verbal fluency (β = −0.17; CI95% −0.28, −0.05; P = 0.01). The prevalence of mild cognitive impairment increased at an annual rate of 0.8% for non‐sarcopenic older adults, but nearly 1.5% for sarcopenic adults.ConclusionsSignificant longitudinal associations were observed between sarcopenia, mild cognitive impairment and cognitive function among older Mexican adults. Public health strategies, including policy research and clinical interventions, must be implemented in low‐ and middle‐income countries in order to reduce or delay the onset of sarcopenia and thus improve population‐level cognitive health among older adults.

Sarcopenia and Mild Cognitive Impairment in Older Adults from Six Low- and Middle-Income Countries.

Little is known about the relationship between sarcopenia and mild cognitive impairment (MCI) in low- and middle-income countries (LMICs). This study aimed to investigate this association among community-dwelling adults aged≥65 years from six LMICs. Cross-sectional, nationally representative data from the Study on Global Ageing and Adult Health (SAGE) were analyzed. These data were obtained in China, Ghana, India, Mexico, Russia, and South Africa in 2007-2010. Participants were considered to have sarcopenia if they had low skeletal muscle mass (i.e., lower skeletal mass index) and a weak handgrip strength. MCI was defined using the National Institute on Aging-Alzheimer's Association criteria. Multivariable logistic regression analysis was conducted to assess associations. The final analytical sample consisted of 12,912 individuals aged≥65 years with preservation in functional abilities without stroke (mean [standard deviation] age 72.2 [10.8] years; 45.2% males). The overall prevalence of sarcopenia and MCI were 11.3% and 18.1%, respectively. After adjusting for potential confounders, there was a positive association between sarcopenia and MCI in all countries (i.e., odds ratio [OR] > 1) with the exception of South Africa, and the overall estimate was OR = 1.60 (95% confidence interval [CI] = 1.32-1.93) with a low level of between-country heterogeneity (I2 = 0.0%). There was a positive association between sarcopenia and MCI in this sample of older adults living in LMICs. Causality should be assessed in future longitudinal research, while the utility of sarcopenia as a marker of MCI should also be investigated.

Sleep problems and mild cognitive impairment among adults aged ≥50 years from low- and middle-income countries

BackgroundThe limited available literature suggests that sleep problems are linked to an increased risk of mild cognitive impairment (MCI). However, this association has been little studied to date in low-income settings. ObjectiveTo investigate the association between sleep problems and MCI in a large sample of adults from six low-and middle-income countries (LMICs). DesignCross-sectional. SettingStudy on Global Ageing and Adult Health (SAGE). Subjects32,715 individuals aged ≥50 years with preservation in functional abilities [age range 50–114 years; 51.7% females]. MethodsMCI was defined using the National Institute on Aging-Alzheimer's Association criteria. Sleep problems were assessed by the question “Overall in the last 30 days, how much of a problem did you have with sleeping, such as falling asleep, waking up frequently during the night or waking up too early in the morning?” and categorized as “None”, “Mild”, “Moderate”, “Severe/Extreme”. Multivariable logistic regression analysis and meta-analysis were conducted. ResultsCompared to no sleep problems, mild, moderate, and severe/extreme sleep problems were associated with significant 1.40, 1.83, and 2.69 times higher odds for MCI with similar associations being observed between age groups and sex. Severe/extreme sleep problems were positively associated with MCI (i.e., OR > 1) in the six countries studied with the overall estimate being OR = 1.80 (95% CI = 1.50–2.16), and a low level of between-country heterogeneity was observed (I2 = 28.2%). ConclusionsSleep problems were associated with higher odds for MCI. Interventions to improve sleep quality among middle-aged and older adults in LMICs may be an effective strategy in reducing risk of MCI and dementia.

Optimal Combinations of AT(N) Biomarkers to Determine Longitudinal Cognition in the Alzheimer's Disease.

Background: National Institute on Aging—Alzheimer's Association (NIA-AA) proposed the AT(N) system based on β-amyloid deposition, pathologic tau, and neurodegeneration, which considered the definition of Alzheimer's disease (AD) as a biological construct. However, the associations between different AT(N) combinations and cognitive progression have been poorly explored systematically. The aim of this study is to compare different AT(N) combinations using recognized biomarkers within the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort.Methods: A total of 341 participants were classified into cognitively unimpaired (CU; n = 200) and cognitively impaired (CI; n = 141) groups according to the clinical manifestations and neuropsychological tests. Cerebrospinal fluid (CSF) Aβ42 and amyloid-PET ([18F]flutemetamol) were used as biomarkers for A; CSF phosphorylated tau (p-tau) and tau-PET ([18F]flortaucipir) were used as biomarkers for T; CSF total tau (t-tau), hippocampal volume, temporal cortical thickness, [18F]fluorodeoxyglucose (FDG) PET, and plasma neurofilament light (NfL) were used as biomarkers for (N). Binary biomarkers were obtained from the Youden index and publicly available cutoffs. Prevalence of AT(N) categories was compared between different biomarkers within the group using related independent sample non-parametric test. The relationship between AT(N) combinations and 12-year longitudinal cognition was assessed using linear mixed-effects modeling.Results: Among the CU participants, A–T–(N)– was most common. More T+ were detected using p-tau than tau PET (p < 0.05), and more (N)+ were observed using fluid biomarkers (p < 0.001). A+T+(N)+ was more common in the CI group. Tau PET combined with cortical thickness best predicted cognitive changes in the CI group and MRI predicted changes in the CU group.Conclusions: These findings suggest that optimal AT(N) combinations to determine longitudinal cognition differ by cognitive status. Different biomarkers within a specific component for defining AT(N) cannot be used identically. Furthermore, different strategies for discontinuous biomarkers will be an important area for future studies.

The Longitudinal Early-onset Alzheimer's Disease Study (LEADS): Framework and methodology.

Patients with early‐onset Alzheimer's disease (EOAD) are commonly excluded from large‐scale observational and therapeutic studies due to their young age, atypical presentation, or absence of pathogenic mutations. The goals of the Longitudinal EOAD Study (LEADS) are to (1) define the clinical, imaging, and fluid biomarker characteristics of EOAD; (2) develop sensitive cognitive and biomarker measures for future clinical and research use; and (3) establish a trial‐ready network. LEADS will follow 400 amyloid beta (Aβ)‐positive EOAD, 200 Aβ‐negative EOnonAD that meet National Institute on Aging–Alzheimer's Association (NIA‐AA) criteria for mild cognitive impairment (MCI) or AD dementia, and 100 age‐matched controls. Participants will undergo clinical and cognitive assessments, magnetic resonance imaging (MRI), [18F]Florbetaben and [18F]Flortaucipir positron emission tomography (PET), lumbar puncture, and blood draw for DNA, RNA, plasma, serum and peripheral blood mononuclear cells, and post‐mortem assessment. To develop more effective AD treatments, scientists need to understand the genetic, biological, and clinical processes involved in EOAD. LEADS will develop a public resource that will enable future planning and implementation of EOAD clinical trials.

Early-Stage Alzheimer Primer

Alzheimer disease (AD) is the most common cause of dementia; in the United States alone, approximately 5.8 million people are living with the disease. This slide presentation offers education about AD pathogenesis, trajectory, and diagnostic criteria from the Diagnostic and Statistical Manual of Disorders, Fifth Edition, and from the National Institute on Aging-Alzheimer's Association. To diagnose mild cognitive impairment and early-stage AD, clinicians should employ a stepwise process that includes the following: cognitive screening, laboratory assessments, structural imaging of the brain, full neuropsychologic assessment (if warranted), and biomarker confirmation.

Anxiety symptoms and mild cognitive impairment among community-dwelling older adults from low- and middle-income countries

AimAnxiety may be a risk factor for mild cognitive impairment (MCI) but there is a scarcity of data on this association especially from low- and middle-income countries (LMICs). Thus, we investigated the association between anxiety and MCI among older adults residing in six LMICs (China, Ghana, India, Mexico, Russia, South Africa), and the mediational effect of sleep problems in this association. MethodsCross-sectional, community-based, nationally representative data from the WHO Study on global AGEing and adult health (SAGE) were analyzed. The definition of MCI was based on the National Institute on Ageing-Alzheimer's Association criteria. Multivariable logistic regression analysis, meta-analysis, and mediation analysis were conducted to assess associations. ResultsThe final sample included 32,715 individuals aged ≥50 years with preservation in functional abilities [mean (standard deviation) age 62.1 (15.6) years; 48.3% males]. Country-wise analysis showed a positive association between anxiety and MCI in all countries (OR 1.35–14.33). The pooled estimate based on meta-analysis with random effects was OR=2.27 (95%CI=1.35–3.83). Sleep problems explained 41.1% of this association. ConclusionsOlder adults with anxiety had higher odds for MCI in LMICs. Future studies should examine whether preventing anxiety or addressing anxiety among individuals with MCI can lead to lower risk for dementia onset in LMICs, while the role of sleep problems in this association should be investigated in detail.

The changing definition of Alzheimer's disease

Widely used criteria for the diagnosis of Alzheimer's disease were established in 1984. These criteria outlined a typical clinical picture, recommended laboratory testing to exclude other causes of dementia, required neuropathological examination for a definitive diagnosis, and categorised individuals without pathological verification as having probable or possible Alzheimer's disease. 1 McKhann G Drachman D Folstein M Katzman R Price D Stadlan EM Clinical diagnosis of Alzheimer's disease: report of the NINCDS–ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology. 1984; 34: 939-944 Crossref PubMed Google Scholar For more than 20 years, Alzheimer's disease remained a probabilistic clinical-pathological syndrome; syndromes are notoriously non-specific and the Alzheimer's disease syndrome was no exception. 2 Knopman DS DeKosky ST Cummings JL et al. Practice parameter: diagnosis of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2001; 56: 1143-1153 Crossref PubMed Scopus (1318) Google Scholar The gradual appearance of biomarkers (initially non-specific MRI measures of brain atrophy and PET measures of glucose hypometabolism; later CSF and PET measures of amyloid β and pathological tau) resulted in new criteria, proposed by an International Working Group (IWG), for incorporation of biomarkers into the diagnostic assessment. 3 Dubois B Feldman HH Jacova C et al. Research criteria for the diagnosis of Alzheimer's disease: revising the NINCDS–ADRDA criteria. Lancet Neurol. 2007; 6: 734-746 Summary Full Text Full Text PDF PubMed Scopus (3090) Google Scholar , 4 Dubois B Feldman HH Jacova C et al. Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria. Lancet Neurol. 2014; 13: 614-629 Summary Full Text Full Text PDF PubMed Scopus (1745) Google Scholar Continued evolution of these criteria resulted in the term preclinical dementia, introduced by a US National Institute on Aging–Alzheimer's Association (NIA–AA) workgroup and the IWG. 5 Dubois B Hampel H Feldman HH et al. Preclinical Alzheimer's disease: definition, natural history, and diagnostic criteria. Alzheimers Dement. 2016; 12: 292-323 Summary Full Text Full Text PDF PubMed Scopus (696) Google Scholar , 6 Sperling RA Aisen PS Beckett LA et al. Toward defining the preclinical stages of Alzheimer's disease: recommendations from the National Institute on Aging–Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011; 7: 280-292 Summary Full Text Full Text PDF PubMed Scopus (3999) Google Scholar This term was meant to describe individuals with no symptoms but who expressed biomarkers indicating the presence of amyloid β and tau pathology, with the goal of identifying those in the very earliest stages of Alzheimer's disease who might benefit from therapeutic trials and, eventually, therapy. This description of asymptomatic individuals was controversial enough, but in 2018, the NIA–AA group introduced a research framework in which people with biomarkers indicating pathological accumulation of amyloid β and tau were categorised as having Alzheimer's disease (no longer modified by the term preclinical or probable), regardless of the presence of symptoms. 7 Jack Jr, CR Bennett DA Blennow K et al. NIA–AA Research Framework: toward a biological definition of Alzheimer's disease. Alzheimers Dement. 2018; 14: 535-562 Summary Full Text Full Text PDF PubMed Scopus (2228) Google Scholar Removing clinical criteria eliminated the syndromic aspect of Alzheimer's disease and its inherent non-specificity. However, this shift to an entirely biological or biomarker-based entity also raised questions and objections. In The Lancet Neurology, Bruno Dubois and colleagues from the IWG 8 Dubois B Villain N Frisoni G et al. Clinical diagnosis of Alzheimer's disease: recommendations of the International Working Group. Lancet Neurol. 2021; (publishing online April 29.)https://doi.org/10.1016/S1474-4422(21)00066-1 Summary Full Text Full Text PDF PubMed Scopus (10) Google Scholar critique the shortcomings of this approach, and propose updated criteria for the use of biomarkers in a clinical setting. Clinical diagnosis of Alzheimer's disease: recommendations of the International Working GroupIn 2018, the US National Institute on Aging and the Alzheimer's Association proposed a purely biological definition of Alzheimer's disease that relies on biomarkers. Although the intended use of this framework was for research purposes, it has engendered debate and challenges regarding its use in everyday clinical practice. For instance, cognitively unimpaired individuals can have biomarker evidence of both amyloid β and tau pathology but will often not develop clinical manifestations in their lifetime. Full-Text PDF

Diagnostic Precision in the Detection of Mild Cognitive Impairment: A Comparison of Two Approaches

OBJECTIVEThis study compared diagnostic rates and clinical predictors of discrepancies between diagnoses conferred via: 1) a comprehensive neuropsychological evaluation and National Institute on Aging–Alzheimer's Association (NIA-AA) criteria versus 2) a cognitive screener and Diagnostic Statistical Manual of Mental Disorders (DSM-5) criteria. DESIGNCross-sectional examination of baseline data from the Prevention of Alzheimer's dementia (AD) using Cognitive remediation and transcranial direct current stimulation in Mild Cognitive Impairment (MCI) and Depression (PACt-MD; ClinicalTrials.gov Identifier: NCT02386670) trial. SETTINGFive geriatric psychiatry and memory clinics located at academic hospitals affiliated with the Department of Psychiatry, University of Toronto. PARTICIPANTSOlder adults (N = 431) with a history of major depressive disorder (MDD) in remission, MCI, or both. MEASUREMENTSMain outcome was a comparison of NIA-AA diagnostic rates of MCI or dementia versus DSM-5 rates of mild or major neurocognitive disorder. Secondary analyses examined demographic, race, gender, premorbid intellectual ability, psychosocial, health-related, and genetic predictors of discrepancy between DSM-5 and NIA-AA diagnoses. RESULTSThere were 103 (23.8%) discrepant cases, with most (91; 88.3%) of these discrepant cases reflecting more impairment with the detailed neuropsychological testing and NIA-AA criteria. Discrepancies were more likely in individuals with a history of MDD or who had at least one ApoE4 allele. CONCLUSIONThe NIA-AA criteria, in conjunction with comprehensive neuropsychological testing, identified a greater prevalence of cognitive impairment than DSM-5 criteria, in conjunction with the Montreal Cognitive Assessment. Detailed neuropsychological evaluations are recommended for older adults who have a history of MDD or a genetic vulnerability to dementia.