Clinical Implications of Amyloid-Beta Accumulation in Occipital Lobes in Alzheimer’s Continuum

A substantial amount of amyloid-beta (Aβ) accumulates in the occipital cortices; however, it draws less attention. We investigated the clinical implications of Aβ accumulation in the occipital lobes in the Alzheimer’s disease (AD) continuum. [18F]-Florbetaben amyloid PET scans were performed in a total of 121 AD or amnestic mild cognitive impairment (aMCI) patients. Of the 121 patients, 74 Aβ positive patients were divided into occipital Aβ positive (OCC+) and occipital Aβ negative (OCC−) groups based on Aβ accumulation in the bilateral occipital lobes. The OCC+ group (41/74, 55.4%) was younger and had a younger age at onset than the OCC− group. The OCC+ group also had an increased standard uptake value ratio in the occipital lobes and greater cortical thinning in relevant areas. The OCC+ group had a higher global deterioration scale, lower performance for the copy, immediate recall, delayed recall, and recognition in Rey–Osterrieth Complex Figure tests than the OCC- group, although both groups had similar disease durations. AD or aMCI patients in the OCC+ group exhibited features noted in early onset AD with relevant neuropsychological and image findings. Occipital Aβ positivity in amyloid PET scans need to be considered as an underestimated marker of early onset AD continuum.

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Gender and Schizophrenia: Association of Age at Onset with Antecedent, Clinical and Outcome Features

Australian & New Zealand Journal of Psychiatry ◽

10.3109/00048679809065536 ◽

1998 ◽

Vol 32 (3) ◽

pp. 415-423 ◽

Cited By ~ 13

Author(s):

Oye Gureje ◽

Rotimi W. Bamidele

Keyword(s):

Functional Outcome ◽

Early Onset ◽

Late Onset ◽

Age At Onset ◽

Early Age ◽

Illness Onset ◽

Gender And Age ◽

Males And Females ◽

Clear Method ◽

Illness Outcome

Objective: There is evidence that gender and age at onset may have a bearing on schizophrenia. The extent to which this differential age at onset influences the clinical features of schizophrenia and its outcome in males and females is not clear. Method: One hundred and twenty outpatients with DSM-III-R schizophrenia were studied to determine the association of antecedent, historical, clinical and 13–year outcome features with age at onset in females (n = 64) and in males (n = 56). Results: Males were significantly younger at illness onset but were not otherwise different from females in antecedent features of illness. For males, age at onset bore little relationship to outcome after 13 years. Females with early onset of illness were more likely to have experienced obstetric complications, to evidence poorer premor-bid functioning, and to have a worse clinical, social and functional outcome than females with late onset. Conclusions: Even though females may have a more benign illness than males, among females, those with early age at onset may be characterised by neurodevel-opmental deviance and worse illness outcome.

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Early and Late Onset Bipolar Disorders in Older Adults

European Psychiatry ◽

10.1016/j.eurpsy.2017.01.2179 ◽

2017 ◽

Vol 41 (S1) ◽

pp. S211-S211

Author(s):

N. Smaoui ◽

L. Zouari ◽

N. Charfi ◽

M. Maâlej-Bouali ◽

N. Zouari ◽

...

Keyword(s):

Older Adults ◽

Bipolar Disorder ◽

Early Onset ◽

Age Of Onset ◽

Late Onset ◽

Age At Onset ◽

Bipolar Disorders ◽

Medical Diagnoses ◽

The Mean ◽

Bipolar Patients

IntroductionAge of onset of illness may be useful in explaining the heterogeneity among older bipolar patients.ObjectiveTo examine the relationship of age of onset with clinical, demographic and behavioral variables, in older patients with bipolar disorder.MethodsThis was a cross-sectional, descriptive and analytical study, including 24 patients suffering from bipolar disorders, aged 65 years or more and followed-up in outpatient psychiatry unit at Hedi Chaker university hospital in Sfax in Tunisia. We used a standardized questionnaire including socio-demographic, behavioral and clinical data. Age of onset was split at age 40 years into early-onset (< 40 years; n = 12) and late-onset (≥ 40 years; n = 12) groups.ResultsThe mean age for the entire sample was 68.95 years. The mean age of onset was 39.95 years. The majority (60%) of patients were diagnosed with bipolar I. Few meaningful differences emerged between early-onset and late-onset groups, except that tobacco use was significantly higher in the late-onset group (66.6% vs. 16.6%; P = 0.027). No significant differences between the early-onset and late-onset groups were seen on demographic variables, family history and number of medical diagnoses or presence of psychotic features.ConclusionOur study found few meaningful behavioral differences between early versus late age at onset in older adults with bipolar disorder.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Early-Onset Parkinson Disease Screening in Patients From Nigeria

Frontiers in Neurology ◽

10.3389/fneur.2020.594927 ◽

2021 ◽

Vol 11 ◽

Author(s):

Lukasz M. Milanowski ◽

Olajumoke Oshinaike ◽

Benjamin J. Broadway ◽

Jennifer A. Lindemann ◽

Alexandra I. Soto-Beasley ◽

...

Keyword(s):

Functional Analysis ◽

Parkinson Disease ◽

Neurodegenerative Diseases ◽

Early Onset ◽

Local Population ◽

Age At Onset ◽

Compound Heterozygous ◽

Loss Of Function ◽

African Countries ◽

Age Related

Introduction: Nigeria is one of the most populated countries in the world; however, there is a scarcity of studies in patients with age-related neurodegenerative diseases, such as Parkinson disease (PD). The aim of this study was to screen patients with PD including a small cohort of early-onset PD (EOPD) cases from Nigeria for PRKN, PINK1, DJ1, SNCA multiplication, and LRRK2 p.G2019S.Methods: We assembled a cohort of 109 Nigerian patients with PD from the four main Nigerian tribes: Yoruba, Igbo, Edo, and Hausa. Fifteen cases [14 from the Yoruba tribe (93.3%)] had EOPD (defined as age-at-onset <50 years). All patients with EOPD were sequenced for the coding regions of PRKN, PINK1, and DJ1. Exon dosage analysis was performed with a multiplex ligation-dependent probe amplification assay, which also included a SNCA probe and LRRK2 p.G2019S. We screened for LRRK2 p.G2019S in the entire PD cohort using a genotyping assay. The PINK1 p.R501Q functional analysis was conducted.Results: In 15 patients with EOPD, 22 variants were observed [PRKN, 9 (40.9%); PINK1, 10 (45.5%); and DJ1, 3 (13.6%)]. Three (13.6%) rare, nonsynonymous variants were identified, but no homozygous or compound heterozygous carriers were found. No exonic rearrangements were present in the three genes, and no carriers of SNCA genomic multiplications or LRRK2 p.G2019S were identified. The PINK1 p.R501Q functional analysis revealed pathogenic loss of function.Conclusion: More studies on age-related neurodegenerative diseases are needed in sub-Saharan African countries, including Nigeria. Population-specific variation may provide insight into the genes involved in PD in the local population but may also contribute to larger studiesperformed in White and Asian populations.

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Is asthma associated with COVID-19 infection? A UK Biobank analysis

ERJ Open Research ◽

10.1183/23120541.00309-2021 ◽

2021 ◽

pp. 00309-2021

Author(s):

Caroline J. Lodge ◽

Alice Doherty ◽

Dinh Bui ◽

Raisa Cassim ◽

Adrian J. Lowe ◽

...

Keyword(s):

Lung Function ◽

Early Onset ◽

Age At Onset ◽

Forced Expiratory Volume ◽

Normal Weight ◽

Asthma Medication ◽

Positive Test ◽

Uk Biobank ◽

Increased Risk ◽

Health Related

BackgroundThe relationship between asthma and COVID-19 risk is not clear and may be influenced by level of airway obstruction, asthma medication, and known COVID risk factors. We aimed to investigate COVID-19 risk in people with asthma.MethodsWe used UK Biobank data from all participants tested for SARS-CoV-2 (n=107 412 (17 979 test positive)). Baseline questions at baseline defined ever asthma and asthma medications. Baseline Forced Expiratory Volume in the first second (FEV1) was categorized into quartiles. Logistic regression modelled relationships between asthma, and asthma categories (age at onset, medications, FEV1 quartiles), and risk of SARS-CoV-2 positive test. We investigated modification by sex, ethnic group, smoking, and BMI.ResultsThere was a reduced risk of a positive test associated with with early-onset asthma (<13 years), (OR 0.91(95% CI 0.84, 0.99). This was found for early-onset asthmatics in males (OR 0·87 [95% CI: 0·78, 0·98]), non-smokers (0·87 [0·78, 0·98]), overweight/obese (0.85 [0.77, 0.93]), and non-Black participants (0·90 [0·82, 0.98]). There was increased risk amongst early onset asthmatics in the highest compared to lowest quartile of lung function (1.44 [1.05, 1.72]).ConclusionAmongst males, non-smokers, overweight/obese, and non-Black participants, having early-onset asthma was associated with lower risk of a SARS-CoV-2 positive test. We found no evidence of a protective effect from asthma medication. Early-onset asthmatics of normal weight and with better lung function may have lifestyle differences placing them at higher risk. Further research is needed to elucidate the contribution of asthma pathophysiology and different health-related behaviour, across population groups, to the observed risks.

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Obstetric complications, treatment response and brain morphology in adult-onset and early-onset males with schizophrenia

Psychological Medicine ◽

10.1017/s0033291797006405 ◽

1998 ◽

Vol 28 (3) ◽

pp. 645-653 ◽

Cited By ~ 12

Author(s):

G. N. SMITH ◽

L. C. KOPALA ◽

J. S. LAPOINTE ◽

G. W. MacEWAN ◽

S. ALTMAN ◽

...

Keyword(s):

Treatment Response ◽

Early Onset ◽

Age At Onset ◽

Obstetric Complications ◽

Brain Morphology ◽

Brain Anatomy ◽

Adult Onset ◽

Course Of Illness ◽

Illness Onset ◽

Duration Of Illness

Background. Substantial variability in age at onset of illness and course of illness exists between patients with schizophrenia. Recent studies suggest that age at illness onset may be useful in defining biologically and clinically distinct subgroups of patients.Methods. Two hundred and ten males with schizophrenia were classified as early-onset or adult-onset according to their age at first hospitalization. Birth history, clinical functioning and treatment response was assessed in a subgroup of patients. Brain anatomy was assessed from CT scans in all patients and in 32 non-psychiatric control subjects.Results. Patients with an early-onset were likely to have a history of obstetric complications, a poor response to neuroleptic treatment, and showed no relationship between ventricle size and duration of illness. Adult-onset patients were less likely to have obstetric complications, more likely to respond to treatment in the first years of illness, and showed an association between brain structure and duration of illness.Conclusions. The distinction between early- and adult-onset patients may have important aetiological and treatment implications.

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A multinational study on motor function in early-onset FSHD

Neurology ◽

10.1212/wnl.0000000000005297 ◽

2018 ◽

Vol 90 (15) ◽

pp. e1333-e1338 ◽

Cited By ~ 8

Author(s):

Jean K. Mah ◽

Jia Feng ◽

Marni B. Jacobs ◽

Tina Duong ◽

Kate Carroll ◽

...

Keyword(s):

Motor Function ◽

Early Onset ◽

Age At Onset ◽

Facioscapulohumeral Muscular Dystrophy ◽

Clinical Severity ◽

Manual Muscle Testing ◽

Linear Regression Models ◽

Facial Weakness ◽

Muscle Testing ◽

Severity Scores

ObjectivesTo investigate motor function associations with age, sex, and D4Z4 repeats among participants with early-onset facioscapulohumeral muscular dystrophy (FSHD) type 1 as defined by weakness onset before 10 years of age.MethodsWe collected standardized motor assessments, including manual muscle testing (MMT), quantitative muscle testing, functional motor evaluations, and clinical severity scores (CSSs), at 12 Cooperative International Neuromuscular Research Group centers. To measure associations, we used linear regression models adjusted for sex, evaluation age, age at onset of weakness, and D4Z4 repeats.ResultsAmong 52 participants (60% female, mean age 22.9 ± 14.7 years), weakness was most pronounced in the shoulder and abdominal musculature. Older enrollment age was associated with greater CSSs (p = 0.003). When adjusted for enrollment age, sex, and D4Z4 repeats, younger age at onset of facial weakness was associated with greater CSSs, slower velocities in timed function tests, and lower MMT scores (p < 0.05).ConclusionSignificant clinical variability was observed in early-onset FSHD. Earlier age at onset of facial weakness was associated with greater disease severity. Longitudinal assessments are needed to determine the rate of disease progression in this population.

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The Evolution of Dementia in Idiopathic Parkinson's Disease: Neuropsychological and Clinical Evidence in Support of Subtypes

International Psychogeriatrics ◽

10.1017/s1041610292001248 ◽

1992 ◽

Vol 4 (4) ◽

pp. 147-160 ◽

Cited By ~ 13

Author(s):

Wayne G. J. Reid

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Early Onset ◽

Late Onset ◽

Age At Onset ◽

Critical Determinant ◽

Drug Study ◽

Baseline Phase ◽

Onset Group ◽

Early Onset Group

One hundred and seven newly diagnosed, untreated patients with Parkinson's disease (PD) were divided into two groups according to their age at reported onset of symptoms. Of these, 79 patients were under age 70 (early-onset) and 28 patients were age 70 and over (late-onset). The group of 50 control subjects comprised spouses, friends of the PD patients, and community volunteers. The patients were participants in a multicenter drug study of Parkinson's disease. Each had received a detailed neurological and neuropsychological assessment in the baseline placebo phases of the study. Thirty-4 patients with early-onset and 12 patients with late-onset were reassessed 3 years after treatment with low-dose levodopa, with bromocriptine, or with a combination of the two drugs. The results of the baseline phase of the study revealed that 8% of the early-onset group and 32% of the late-onset group were classified as demented. The 3-year follow-up revealed that the prevalence of dementia had increased to 17% in the early-onset group and to 83% in the late-onset group. This study confirms that at least two distinct subtypes of Parkinson's disease exist. The subtypes differ both clinically and neuropsychologically. The age at onset of symptoms is a critical determinant of the rate and type of cognitive decline in Parkinson's disease.

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VANUTIDE CRIDIFICAR (ACC-001) AND QS-21 ADJUVANT IN INDIVIDUALS WITH EARLY ALZHEIMER’S DISEASE: AMYLOID IMAGING POSITRON EMISSION TOMOGRAPHY AND SAFETY RESULTS FROM A PHASE 2 STUDY

Journal of Prevention of Alzheimer's Disease ◽

10.14283/jpad.2016.91 ◽

2016 ◽

pp. 1-10

Author(s):

C.H. van Dyck ◽

C. Sadowsky ◽

G. Le Prince Leterme ◽

K. Booth ◽

Y. Peng ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Positron Emission Tomography ◽

Amyloid Beta ◽

Standard Uptake Value ◽

Emission Tomography ◽

Amyloid Burden ◽

Treatment Groups ◽

Positron Emission ◽

Early Alzheimer’S Disease

BACKGROUNDd: ACC-001 is an investigational therapeutic vaccine designed to elicit antibodies against the N-terminal peptide 1-7 of the amyloid-beta peptide, believed to be important in the pathogenesis of Alzheimer’s disease. OBJECTIVES: To evaluate safety, immunogenicity, impact on brain amyloid, and other exploratory endpoints in participants receiving ACC-001. DESIGN: Randomized, phase 2, interventional study. Trial registration: Clinicaltrials.gov ID NCT01227564. PARTICIPANTS: Individuals with early Alzheimer’s disease (Mini-Mental State Examination scores ≥25, a global Clinical Dementia Rating of 0.5, and evidence of elevated baseline brain amyloid burden). Intervention: Participants were randomized to ACC-001 3 µg or 10 µg with QS-21 adjuvant (50 µg), or placebo. MEASUREMENTS: The primary endpoint was change in brain amyloid burden by 18F-florbetapir positron emission tomography in composite cortical standard uptake value ratio. RESULTS: A total of 63 participants were randomized and 51 completed the study. At week 104, no significant differences were observed in 18F-florbetapir positron emission tomography composite cortical standard uptake value ratio between either ACC-001 dose compared with placebo. In both ACC-001 + QS-21 treatment groups, following the initial immunization, the anti-amyloid-beta geometric mean titers increased after each subsequent vaccination and then declined, with less apparent decline after the later compared with earlier immunizations. The majority of treatment-emergent adverse events in the ACC-001 + QS-21 groups were injection site reactions, which occurred at a greater rate in active treatment groups than in the placebo group. No amyloid-related imaging abnormalities of edema or effusion were reported. CONCLUSION: No statistically significant differences were observed between groups in the change from baseline brain amyloid burden despite apparently robust systemically measured anti-amyloid-beta antibody response at both dose levels. Insufficient antibody titers, poor quality immune response, short duration of treatment, or small sample size may have resulted in these findings. The safety and tolerability profile was acceptable.

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The Impact of Amyloid-Beta Positivity with 18F-Florbetaben PET on Neuropsychological Aspects in Parkinson’s Disease Dementia

Metabolites ◽

10.3390/metabo10100380 ◽

2020 ◽

Vol 10 (10) ◽

pp. 380

Author(s):

Seunghee Na ◽

Hyeonseok Jeong ◽

Jong-Sik Park ◽

Yong-An Chung ◽

In-Uk Song

Keyword(s):

Alzheimer’S Disease ◽

Parkinson’S Disease ◽

Alzheimer's Disease ◽

Parkinson's Disease ◽

Amyloid Beta ◽

Neuropsychiatric Symptoms ◽

Amyloid Pet ◽

Motor Symptoms ◽

Parkinson’S Disease Dementia ◽

The Impact

The neuropathology of Parkinson’s disease dementia (PDD) is heterogenous, and the impacts of each pathophysiology and their synergistic effects are not fully understood. The aim of this study was to evaluate the frequency and impacts of co-existence with Alzheimer’s disease in patients with PDD by using 18F-florbetaben PET imaging. A total of 23 patients with PDD participated in the study. All participants underwent 18F-florbetaben PET and completed a standardized neuropsychological battery and assessment of motor symptoms. The results of cognitive tests, neuropsychiatric symptoms, and motor symptoms were analyzed between the positive and negative 18F-florbetaben PET groups. Four patients (17.4%) showed significant amyloid burden. Patients with amyloid-beta showed poorer performance in executive function and more severe neuropsychiatric symptoms than those without amyloid-beta. Motor symptoms assessed by UPDRS part III and the modified H&Y Scale were not different between the two groups. The amyloid PET scan of a patient with PDD can effectively reflect a co-existing Alzheimer’s disease pathology. Amyloid PET scans might be able to help physicians of PDD patients showing rapid progression or severe cognitive/behavioral features.

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Optimisation and usefulness of quantitative analysis of18F-florbetapir PET

British Journal of Radiology ◽

10.1259/bjr.20181020 ◽

2019 ◽

Vol 92 (1101) ◽

pp. 20181020 ◽

Cited By ~ 4

Author(s):

Daniel Fakhry-Darian ◽

Neva Hiten Patel ◽

Sairah Khan ◽

Tara Barwick ◽

William Svensson ◽

...

Keyword(s):

Classification Accuracy ◽

Type A ◽

Data Type ◽

Control Group ◽

Amyloid Pet ◽

Quantitative Classification ◽

Typical Type ◽

Healthy Control ◽

Atypical Presentations ◽

Pet Scans

Objectives:This study investigates the usefulness of quantitative SUVR thresholds on sub types of typical (type A) and atypical (non-type A) positive (Aβ+) and negative (Aβ-)18F-florbetapir scans and aims to optimise the thresholds.Methods:Clinical18F-florbetapir scans (n = 100) were categorised by sub type and visual reads were performed independently by three trained readers. Inter-reader agreement and reader-to-reference agreement were measured. Optimal SUVR thresholds were derived by ROC analysis and were compared with thresholds derived from a healthy control group and values from published literature.Results:Sub type division of18F-florbetapir PET scans improves accuracy and agreement of visual reads for type A: accuracy 90%, 96% and 70% and agreement κ > 0.7, κ ≥ 0.85 and −0.1 < κ < 0.9 for all data, type A and non-type A respectively. Sub type division also improves quantitative classification accuracy of type A: optimum mcSUVR thresholds were found to be 1.32, 1.18 and 1.48 with accuracy 86%, 92% and 76% for all data, type A and non-type A respectively.Conclusions:Aβ+/Aβ- mcSUVR threshold of 1.18 is suitable for classification of type A studies (sensitivity = 97%, specificity = 88%). Region-wise SUVR thresholds may improve classification accuracy in non-type A studies. Amyloid PET scans should be divided by sub type before quantification.Advances in knowledge:We have derived and validated mcSUVR thresholds for Aβ+/Aβ-18F-florbetapir studies. This work demonstrates that division into sub types improves reader accuracy and agreement and quantification accuracy in scans with typical presentation and highlights the atypical presentations not suited to global SUVR quantification.

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