ADAS-COG and mental deterioration battery: different instruments for different aspects of cognitive decline in Alzheimer's disease

Background: Great effort has been put into developing simple and feasible tools capable to detect Alzheimer's disease (AD) in its early clinical stage. Spatial navigation impairment occurs very early in AD and is detectable even in the stage of mild cognitive impairment (MCI). Objective: The aim was to describe the frequency of self-reported spatial navigation complaints in patients with subjective cognitive decline (SCD), amnestic and non-amnestic MCI (aMCI, naMCI) and AD dementia and to assess whether a simple questionnaire based on these complaints may be used to detect early AD. Method: In total 184 subjects: patients with aMCI (n=61), naMCI (n=27), SCD (n=63), dementia due to AD (n=20) and normal controls (n=13) were recruited. The subjects underwent neuropsychological examination and were administered a questionnaire addressing spatial navigation complaints. Responses to the 15 items questionnaire were scaled into four categories (no, minor, moderate and major complaints). Results: 55% of patients with aMCI, 64% with naMCI, 68% with SCD and 72% with AD complained about their spatial navigation. 38-61% of these complaints were moderate or major. Only 33% normal controls expressed complaints and none was ranked as moderate or major. The SCD, aMCI and AD dementia patients were more likely to express complaints than normal controls (p's<0.050) after adjusting for age, education, sex, depressive symptoms (OR for SCD=4.00, aMCI=3.90, AD dementia=7.02) or anxiety (OR for SCD=3.59, aMCI=3.64, AD dementia=6.41). Conclusion: Spatial navigation complaints are a frequent symptom not only in AD, but also in SCD and aMCI and can potentially be detected by a simple and inexpensive questionnaire.

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Pharmacogenetics of Angiotensin-Converting Enzyme Inhibitors in Patients with Alzheimer's Disease Dementia

Current Alzheimer Research ◽

10.2174/1567205014666171016101816 ◽

2018 ◽

Vol 15 (4) ◽

pp. 386-398 ◽

Cited By ~ 22

Author(s):

Fabricio Ferreira de Oliveira ◽

Elizabeth Suchi Chen ◽

Marilia Cardoso Smith ◽

Paulo Henrique Ferreira Bertolucci

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Angiotensin Converting Enzyme ◽

Cognitive Decline ◽

Enzyme Inhibitors ◽

Late Onset ◽

Amyloid Β ◽

Converting Enzyme ◽

Converting Enzyme Inhibitors ◽

Alzheimer’S Disease Dementia

Background: While the angiotensin-converting enzyme degrades amyloid-β, angiotensinconverting enzyme inhibitors (ACEis) may slow cognitive decline by way of cholinergic effects, by increasing brain substance P and boosting the activity of neprilysin, and by modulating glucose homeostasis and augmenting the secretion of adipokines to enhance insulin sensitivity in patients with Alzheimer’s disease dementia (AD). We aimed to investigate whether ACE gene polymorphisms rs1800764 and rs4291 are associated with cognitive and functional change in patients with AD, while also taking APOE haplotypes and anti-hypertensive treatment with ACEis into account for stratification. Methods: Consecutive late-onset AD patients were screened with cognitive tests, while their caregivers were queried for functional and caregiver burden scores. Prospective pharmacogenetic correlations were estimated for one year, considering APOE and ACE genotypes and haplotypes, and treatment with ACEis. Results: For 193 patients, minor allele frequencies were 0.497 for rs1800764 – C (44.6% heterozygotes) and 0.345 for rs4291 – T (38.9% heterozygotes), both in Hardy-Weinberg equilibrium. Almost 94% of all patients used cholinesterase inhibitors, while 155 (80.3%) had arterial hypertension, and 124 used ACEis. No functional impacts were found regarding any genotypes or pharmacological treatment. Either for carriers of ACE haplotypes that included rs1800764 – T and rs4291 – A, or for APOE4- carriers of rs1800764 – T or rs4291 – T, ACEis slowed cognitive decline independently of blood pressure variations. APOE4+ carriers were not responsive to treatment with ACEis. Conclusion: ACEis may slow cognitive decline for patients with AD, more remarkably for APOE4- carriers of specific ACE genotypes.

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Young adult-onset, very slowly progressive cognitive decline with spastic paraparesis in Alzheimer’s disease with cotton wool plaques due to a novel presenilin1 G417S mutation

Acta Neuropathologica Communications ◽

10.1186/s40478-019-0672-z ◽

2019 ◽

Vol 7 (1) ◽

Author(s):

Tomoko Miki ◽

Osamu Yokota ◽

Takashi Haraguchi ◽

Takeshi Ikeuchi ◽

Bin Zhu ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Young Adult ◽

Cognitive Decline ◽

Spastic Paraparesis ◽

Cotton Wool ◽

Adult Onset

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24(S)-Saringosterol Prevents Cognitive Decline in a Mouse Model for Alzheimer’s Disease

Marine Drugs ◽

10.3390/md19040190 ◽

2021 ◽

Vol 19 (4) ◽

pp. 190

Author(s):

Nikita Martens ◽

Melissa Schepers ◽

Na Zhan ◽

Frank Leijten ◽

Gardi Voortman ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Mouse Model ◽

Cognitive Decline ◽

Inflammatory Marker ◽

Amyloid Β ◽

Liver Fat ◽

Gas Chromatography Mass Spectrometry ◽

Memory Decline ◽

Plaque Load

We recently found that dietary supplementation with the seaweed Sargassum fusiforme, containing the preferential LXRβ-agonist 24(S)-saringosterol, prevented memory decline and reduced amyloid-β (Aβ) deposition in an Alzheimer’s disease (AD) mouse model without inducing hepatic steatosis. Here, we examined the effects of 24(S)-saringosterol as a food additive on cognition and neuropathology in AD mice. Six-month-old male APPswePS1ΔE9 mice and wildtype C57BL/6J littermates received 24(S)-saringosterol (0.5 mg/25 g body weight/day) (APPswePS1ΔE9 n = 20; C57BL/6J n = 19) or vehicle (APPswePS1ΔE9 n = 17; C57BL/6J n = 19) for 10 weeks. Cognition was assessed using object recognition and object location tasks. Sterols were analyzed by gas chromatography/mass spectrometry, Aβ and inflammatory markers by immunohistochemistry, and gene expression by quantitative real-time PCR. Hepatic lipids were quantified after Oil-Red-O staining. Administration of 24(S)-saringosterol prevented cognitive decline in APPswePS1ΔE9 mice without affecting the Aβ plaque load. Moreover, 24(S)-saringosterol prevented the increase in the inflammatory marker Iba1 in the cortex of APPswePS1ΔE9 mice (p < 0.001). Furthermore, 24(S)-saringosterol did not affect the expression of lipid metabolism-related LXR-response genes in the hippocampus nor the hepatic neutral lipid content. Thus, administration of 24(S)-saringosterol prevented cognitive decline in APPswePS1ΔE9 mice independent of effects on Aβ load and without adverse effects on liver fat content. The anti-inflammatory effects of 24(S)-saringosterol may contribute to the prevention of cognitive decline.

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Assessing visuo-constructive functions in patients with subjective cognitive decline, mild cognitive impairment and Alzheimer’s disease with the Vienna Visuo-Constructional Test 3.0 (VVT 3.0)

Neuropsychiatrie ◽

10.1007/s40211-021-00385-x ◽

2021 ◽

Author(s):

Noel Valencia ◽

Johann Lehrner

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Cognitive Decline ◽

Multinomial Logistic Regression ◽

Subjective Cognitive Decline ◽

Healthy Controls ◽

Considerable Potential ◽

Multinomial Logistic Regression Analysis

Summary Background Visuo-Constructive functions have considerable potential for the early diagnosis and monitoring of disease progression in Alzheimer’s disease. Objectives Using the Vienna Visuo-Constructional Test 3.0 (VVT 3.0), we measured visuo-constructive functions in subjective cognitive decline (SCD), mild cognitive impairment (MCI), Alzheimer’s disease (AD), and healthy controls to determine whether VVT performance can be used to distinguish these groups. Materials and methods Data of 671 participants was analyzed comparing scores across diagnostic groups and exploring associations with relevant clinical variables. Predictive validity was assessed using Receiver Operator Characteristic curves and multinomial logistic regression analysis. Results We found significant differences between AD and the other groups. Identification of cases suffering from visuo-constructive impairment was possible using VVT scores, but these did not permit classification into diagnostic subgroups. Conclusions In summary, VVT scores are useful indicators for visuo-constructive impairment but face challenges when attempting to discriminate between several diagnostic groups.

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Subjective Cognitive Decline and its Relation to Verbal Memory and Sex in Cognitively Unimpaired Individuals from a Colombian Cohort with Autosomal-Dominant Alzheimer’s Disease

Journal of the International Neuropsychological Society ◽

10.1017/s1355617721000801 ◽

2021 ◽

pp. 1-9

Author(s):

Jairo E. Martinez ◽

Enmanuelle Pardilla-Delgado ◽

Edmarie Guzmán-Vélez ◽

Clara Vila-Castelar ◽

Rebecca Amariglio ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Sex Differences ◽

Cognitive Decline ◽

Verbal Memory ◽

Autosomal Dominant ◽

Memory Performance ◽

Subjective Cognitive Decline ◽

Mutation Carriers ◽

Study Partner

Abstract Objective: Subjective Cognitive Decline (SCD) may be an early indicator of risk for Alzheimer’s disease (AD). Findings regarding sex differences in SCD are inconsistent. Studying sex differences in SCD within cognitively unimpaired individuals with autosomal-dominant AD (ADAD), who will develop dementia, may inform sex-related SCD variations in preclinical AD. We examined sex differences in SCD within cognitively unimpaired mutation carriers from the world’s largest ADAD kindred and sex differences in the relationship between SCD and memory performance. Methods: We included 310 cognitively unimpaired Presenilin-1 (PSEN-1) E280A mutation carriers (51% females) and 1998 noncarrier family members (56% females) in the study. Subjects and their study partners completed SCD questionnaires and the CERAD word list delayed recall test. ANCOVAs were conducted to examine group differences in SCD, sex, and memory performance. In carriers, partial correlations were used to examine associations between SCD and memory performance covarying for education. Results: Females in both groups had greater self-reported and study partner-reported SCD than males (all p < 0.001). In female mutation carriers, greater self-reported (p = 0.02) and study partner-reported SCD (p < 0.001) were associated with worse verbal memory. In male mutation carriers, greater self-reported (p = 0.03), but not study partner-reported SCD (p = 0.11) was associated with worse verbal memory. Conclusions: Study partner-reported SCD may be a stronger indicator of memory decline in females versus males in individuals at risk for developing dementia. Future studies with independent samples and preclinical trials should consider sex differences when recruiting based on SCD criteria.

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