Smell identification function in early-onset Alzheimer’s disease and mild cognitive impairment

ABSTRACTLittle is known about olfactory identification (OI) function in early-onset Alzheimer’s disease (EOAD) and early-onset mild cognitive impairment (eoMCI) with age of onset <65 years. We aimed to study OI in EOAD compared with eoMCI and age-matched healthy controls (HC). Nineteen EOAD subjects with mild to moderate dementia, 17 with eoMCI, and 21 HC recruited as a convenience sample from memory services were assessed for cognition, behavioral symptoms, and activities for daily living. The OI was tested using the University of Pennsylvania smell identification test (UPSIT). EOAD participants performed worse compared with eoMCI and HC on cognitive tests and OI (p < 0.001). Although eoMCI had poorer cognitive scores compared to HC, they were similar in their OI function. OI correlated with attention (r = 0.494, p = 0.031), executive functions (r = 0.508, p = 0.026), and praxis (r = 0.455, p = 0.05) within the EOAD group. OI impairment was significantly associated with the diagnosis of EOAD versus eoMCI, but not with eoMCI when compared with HC. OI could potentially be useful in differentiating EOAD from eoMCI. Studies with late-life MCI patients showing OI impairment relative to HC may be attributed to a different disease process. Independent replication in a larger sample is needed to validate these findings.

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A Family with Multiple Instances of Definite, Probable and Possible Early-Onset Alzheimer's Disease

The British Journal of Psychiatry ◽

10.1192/bjp.159.4.524 ◽

1991 ◽

Vol 159 (4) ◽

pp. 524-530 ◽

Cited By ~ 9

Author(s):

H. Karlinsky ◽

E. Madrick ◽

J. Ridgley ◽

J. M. Berg ◽

R. Becker ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Early Onset ◽

Age Of Onset ◽

Diagnostic Difficulties ◽

History Of ◽

Early Onset Alzheimer’S Disease ◽

The Mean ◽

Age Of Death

A family with a multigenerational history of proven or suspected early-onset Alzheimer's disease (AD) consistent with autosomal-dominant inheritance is described. To date, the pedigree comprises five generations in which there are 13 known affected individuals. The mean age of onset of cognitive deficits in those for whom data are available (n = 11) is 47.6 (s.d. 3.0) years and the mean age of death (n = 10) is 58.8 (s.d. 4.0) years. The variability in the extent and quality of available data illustrates the diagnostic difficulties encountered in ascertaining such an extended pedigree, and the need for caution in interpreting the evidence.

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Evidence for Allelic Heterogeneity in Familial Early-Onset Alzheimer's Disease

The British Journal of Psychiatry ◽

10.1192/bjp.158.4.471 ◽

1991 ◽

Vol 158 (4) ◽

pp. 471-474 ◽

Cited By ~ 18

Author(s):

Cornelia M. Van Duijn ◽

Christine Van Broeckhoven ◽

John A. Hardy ◽

Alison M. Goate ◽

Martin N. Rossor ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Epidemiological Study ◽

Genetic Counselling ◽

Early Onset ◽

Age Of Onset ◽

Population Based ◽

Chromosome 21 ◽

Allelic Heterogeneity ◽

Early Onset Alzheimer’S Disease

Age of onset was examined for 139 members of 30 families affected by early-onset AD. Most (77%) of the variance of age of onset derived from differences between rather than within families. The constancy of age of onset within families was also observed in an analysis restricted to families derived from a population-based epidemiological study with complete ascertainment of early-onset AD. Furthermore, we observed clustering of age of onset within those families that support linkage to the predisposing locus on chromosome 21. Our data are compatible with the view that allelic heterogeneity at the AD locus may account for the similarity in age of onset within families. This finding may be of value for scientific studies of AD as well as for genetic counselling.

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Detection of prospective memory deficits in mild cognitive impairment of suspected Alzheimer’s disease etiology using a novel event-based prospective memory task

Journal of the International Neuropsychological Society ◽

10.1017/s1355617708090127 ◽

2009 ◽

Vol 15 (1) ◽

pp. 154-159 ◽

Cited By ~ 50

Author(s):

ALBERTO BLANCO-CAMPAL ◽

ROBERT F. COEN ◽

BRIAN A. LAWLOR ◽

JOSEPH B. WALSH ◽

TERESA E. BURKE

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Prospective Memory ◽

Small Sample ◽

Cutoff Score ◽

Convenience Sample ◽

Disease Etiology ◽

Event Based

AbstractWe investigated the relative discriminatory efficacy of an event-based prospective memory (PM) task, in which specificity of the instructions and perceptual salience of the PM cue were manipulated, compared with two widely used retrospective memory (RM) tests (Rivermead Paragraph Recall Test and CERAD-Word List Test), when detecting mild cognitive impairment of suspected Alzheimer’s disease etiology (MCI-AD) (N = 19) from normal controls (NC) (N = 21). Statistical analyses showed high discriminatory capacity of the PM task for detecting MCI-AD. The Non-Specific-Non-Salient condition proved particularly useful in detecting MCI-AD, possibly reflecting the difficulty of the task, requiring more strategic attentional resources to monitor for the PM cue. With a cutoff score of <4/10, the Non-Specific-Non-Salient condition achieved a sensitivity = 84%, and a specificity = 95%, superior to the most discriminative RM test used (CERAD-Total Learning: sensitivity = 83%; specificity = 76%). Results suggest that PM is an early sign of memory failure in MCI-AD and may be a more pronounced deficit than retrospective failure, probably reflecting the greater self-initiated retrieval demands involved in the PM task used. Limitations include the relatively small sample size, and the use of a convenience sample (i.e. memory clinic attenders and healthy active volunteers), reducing the generalizability of the results, which should be regarded as preliminary. (JINS, 2009, 15, 154–159.)

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The Use Of The Hungarian Test Your Memory (Tym-Hun), Mmse And Adas-Cog Tests For Patients With Mild Cognitive Impairment (Mci) In A Hungarian Population: A Cross-Sectional Study

10.21203/rs.3.rs-16948/v1 ◽

2020 ◽

Author(s):

Szabolcs Garbóczy ◽

Éva Magócs ◽

Gergő Szőllősi ◽

Szilvia Harsányi ◽

Égerházi Anikó ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Early Recognition ◽

Early Stage ◽

Disease Process ◽

Disease Assessment ◽

Cross Sectional ◽

Hungarian Population

Abstract BACKGROUND Alzheimer's Disease (AD) is a growing disease process with aging. If we could recognize the disease at an early stage and increase the number of years spent in a better condition through preventive and treatment measures, we could reduce the pressure both directly on families and indirectly on society. There is a need for testing methods that are easy to perform even in general practitioner’s office, inexpensive and non-invasive, which could help early recognition of mental decline. We have selected Test Your Memory (TYM), which has proven to be reliable for detecting AD and mild cognitive impairment (MCI) in several countries. Our study was designed to test the usability of the TYM-HUN comparing with the ADAS-Cog (Alzheimer's Disease Assessment Scale-Cognitive Subscale) in MCI recognition in the Hungarian population. METHODS TYM test was translated and validated into Hungarian (TYM-HUN). The TYM-HUN test was used in conjunction with and compared with the Mini-Mental State Examination (MMSE) and the ADAS-Cog. For our study, 50 subjects were selected, 25 MCI patients and 25 healthy controls. Spearman’s rank correlation was used to analyze the correlation between the scores of MMSE and ADAS-Cog with TYM-HUN. RESULTS MCI can be distinguished from AD and normal aging using ADAS-Cog and MMSE is a useful tool to detect dementia. We established a 'cut-off' point of TYM-HUN (44/45points) where optimal sensitivity and specificity values were obtained to screen MCI. The total TYM-HUN scores significantly correlated with the MMSE scores (ρ=0.626; p<0.001) and ADAS-Cog scores (ρ=-0.723; p<0.001). CONCLUSIONS Our results showed that the Hungarian version of TYM (TYM-HUN) is an easy, fast, self-administered questionnaire with the right low threshold regarding MCI and can be used for the early diagnosis of cognitive impairment.

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Detection and Prediction of Mild Cognitive Impairment in Alzheimer’s Disease Mice

Journal of Alzheimer s Disease ◽

10.3233/jad-200675 ◽

2020 ◽

Vol 77 (3) ◽

pp. 1209-1221

Author(s):

Surya Prakash Rai ◽

Pablo Bascuñana ◽

Mirjam Brackhan ◽

Markus Krohn ◽

Luisa Möhle ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Cognitive Dysfunction ◽

Age Of Onset ◽

Amyloid Β ◽

Current Approach ◽

Classification Algorithm ◽

Wild Type

Background: The recent failure of clinical trials to treat Alzheimer’s disease (AD) indicates that the current approach of modifying disease is either wrong or is too late to be efficient. Mild cognitive impairment (MCI) denotes the phase between the preclinical phase and clinical overt dementia. AD mouse models that overexpress human amyloid-β (Aβ) are used to study disease pathogenesis and to conduct drug development/testing. However, there is no direct correlation between the Aβ deposition, the age of onset, and the severity of cognitive dysfunction. Objective: To detect and predict MCI when Aβ plaques start to appear in the hippocampus of an AD mouse. Methods: We trained wild-type and AD mice in a Morris water maze (WM) task with different inter-trial intervals (ITI) at 3 months of age and assessed their WM performance. Additionally, we used a classification algorithm to predict the genotype (APPtg versus wild-type) of an individual mouse from their respective WM data. Results: MCI can be empirically detected using a short-ITI protocol. We show that the ITI modulates the spatial learning of AD mice without affecting the formation of spatial memory. Finally, a simple classification algorithm such as logistic regression on WM data can give an accurate prediction of the cognitive dysfunction of a specific mouse. Conclusion: MCI can be detected as well as predicted simultaneously with the onset of Aβ deposition in the hippocampus in AD mouse model. The mild cognitive impairment prediction can be used for assessing the efficacy of a treatment.

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Early onset Alzheimer’s disease

Oxford Textbook of Neurologic and Neuropsychiatric Epidemiology ◽

10.1093/med/9780198749493.003.0009 ◽

2020 ◽

pp. 75-82

Author(s):

Ratnavalli Ellajosyula

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Early Onset ◽

Age Of Onset ◽

Late Onset ◽

Geographical Location ◽

Epidemiological Studies ◽

Incidence Rates ◽

Prevalence Rates ◽

Early Onset Alzheimer’S Disease

The term ‘early onset Alzheimer’s disease’ (EOAD) is used when symptoms of Alzheimer’s disease (AD) occur in patients younger than 65 years. EOAD is an uncommon condition and data on epidemiology is limited. Prevalence rates range from 15 to 200 and incidence rates 2.4–22.6 per 100,000 population. Prevalence rates increase with age similar to that for late onset AD. The prevalence of autosomal dominant EOAD is 5.2 per 100,000. Half of these patients have an underlying mutation in amyloid precursor protein, presenilin 1 or 2 genes. Apolipoprotein E genotype is a risk factor for EOAD and homozygotes have an earlier age of onset. Methodological issues and geographical location make comparisons across epidemiological studies difficult. Further cross-national and cross-cultural studies with standardized methodology are necessary to understand the role of risk and protective factors, as well as to estimate the burden of the disease.

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β-Amyloid is Associated with Aberrant Metabolic Connectivity in Subjects with Mild Cognitive Impairment

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.2014.66 ◽

2014 ◽

Vol 34 (7) ◽

pp. 1169-1179 ◽

Cited By ~ 17

Author(s):

Felix Carbonell ◽

Arnaud Charil ◽

Alex P Zijdenbos ◽

Alan C Evans ◽

Barry J Bedell ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Disease Process ◽

Brain Regions ◽

Apoe Ε4 ◽

Positron Emission ◽

Β Amyloid ◽

Glucose Hypometabolism

Positron emission tomography (PET) studies using [18F]2-fluoro-2-deoxyglucose (FDG) have identified a well-defined pattern of glucose hypometabolism in Alzheimer's disease (AD). The assessment of the metabolic relationship among brain regions has the potential to provide unique information regarding the disease process. Previous studies of metabolic correlation patterns have demonstrated alterations in AD subjects relative to age-matched, healthy control subjects. The objective of this study was to examine the associations between β-amyloid, apolipoprotein ε4 (APOE ε4) genotype, and metabolic correlations patterns in subjects diagnosed with mild cognitive impairment (MCI). Mild cognitive impairment subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study were categorized into β-amyloid-low and β-amyloid-high groups, based on quantitative analysis of [18F]florbetapir PET scans, and APOE ε4 non-carriers and carriers based on genotyping. We generated voxel-wise metabolic correlation strength maps across the entire cerebral cortex for each group, and, subsequently, performed a seed-based analysis. We found that the APOE ε4 genotype was closely related to regional glucose hypometabolism, while elevated, fibrillar β-amyloid burden was associated with specific derangements of the metabolic correlation patterns.

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