Synergistic Effects of APOE and CLU May Increase the Risk of Alzheimer’s Disease: Acceleration of Atrophy in the Volumes and Shapes of the Hippocampus and Amygdala

2021 ◽  
Vol 80 (3) ◽  
pp. 1311-1327
Author(s):  
Na An ◽  
Yu Fu ◽  
Jie Shi ◽  
Han-Ning Guo ◽  
Zheng-Wu Yang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Morphological Changes ◽  
Synergistic Effects ◽  
Combined Effects ◽  
Individual Effects ◽  
The Individual ◽  
Neuroimaging Genetics ◽  
Surface Based Morphometry

Background: The volume loss of the hippocampus and amygdala in non-demented individuals has been reported to increase the risk of developing Alzheimer’s disease (AD). Many neuroimaging genetics studies mainly focused on the individual effects of APOE and CLU on neuroimaging to understand their neural mechanisms, whereas their synergistic effects have been rarely studied. Objective: To assess whether APOE and CLU have synergetic effects, we investigated the epistatic interaction and combined effects of the two genetic variants on morphological degeneration of hippocampus and amygdala in the non-demented elderly at baseline and 2-year follow-up. Methods: Besides the widely-used volume indicator, the surface-based morphometry method was also adopted in this study to evaluate shape alterations. Results: Our results showed a synergistic effect of homozygosity for the CLU risk allele C in rs11136000 and APOE ɛ4 on the hippocampal and amygdalar volumes during a 2-year follow-up. Moreover, the combined effects of APOE ɛ4 and CLU C were stronger than either of the individual effects in the atrophy progress of the amygdala. Conclusion: These findings indicate that brain morphological changes are caused by more than one gene variant, which may help us to better understand the complex endogenous mechanism of AD.

Disclosing the diagnosis of Alzheimer’s disease

2017 ◽  
Author(s):  
Anne A. Fetherston ◽  
Julian C. Hughes
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Good Practice ◽  
Good Care ◽  
Diagnostic Disclosure ◽  
The Family ◽  
Individual Knowledge ◽  
The Individual ◽  
Diagnostic Support

Diagnostic disclosure of Alzheimer’s disease is generally accepted to be good practice; however, there are important factors for clinicians to consider when preparing to impart such a serious diagnosis. In particular, this chapter explores the issues around timing of the disclosure and determining the correct amount of information to give. It highlights the need for good knowledge of the individual—knowledge of the person’s current mental capacity, the person’s own views, as well as those of the family—in order to provide really good care. It also addresses issues of uncertainty such as making a very early diagnosis and giving an accurate prognosis. The chapter suggests that it is the person (rather than the professional) who should control the situation, and that professionals must be attuned to what the person and family require from them. It also highlights the need for sound post-diagnostic support and follow-up.

Longitudinal Cognitive, Electroencephalographic and Morphological Brain Changes in Ageing and Alzheimer's Disease

1996 ◽  
Vol 168 (3) ◽  
pp. 280-286 ◽  
Author(s):  
Hans Förstl ◽  
Herbert Sattel ◽  
Christoph Besthorn ◽  
Sabine Daniel ◽  
Claudia Geiger-Kabisch ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Performance ◽  
Significant Influence ◽  
Brain Atrophy ◽  
Morphological Changes ◽  
Cognitive Test ◽  
Duration Of Symptoms ◽  
Band Power

BackgroundThe natural course of cognitive performance, electrophysiological alterations and brain atrophy in ageing and Alzheimer's disease (AD) has been investigated in numerous studies, but only few attempts have been made to examine the relationship between clinical, electroencephalographic (EEG) and morphological changes with quantitative methods prospectively over longer periods of time.MethodFifty-five patients with clinically diagnosed AD and 66 healthy elderly controls were examined biannually using a cognitive test (CAMCOG), EEG band power and volumetric estimates of brain atrophy.ResultsOn average cognitive performance deteriorated by 28 points on the CAMCOG in the AD group, the alpha/theta ratio decreased by 0.2, and the proportion of intracranial cerebrospinal fluid volume increased by 3.5% during a 2-year period. Similar changes were observed after a second 2-year interval. A multiple regression model demonstrated a significant influence of age on cognition and atrophy and a significant influence of the estimated duration of symptoms on cognition, alpha/theta ratio and brain atrophy at the initial examination. Cognitive performance at the first examination exerted significant effects on the performance and also on brain atrophy at re-examination after 2 or 4 years, whereas the EEG and neuroimaging findings at the previous examination were exclusively related to the corresponding findings at the follow-up examinations. In the control group no significant cognitive, EEG and morphological changes were observed after 2 and 4 years.ConclusionAfter 2 consecutive follow-up periods, we were able to verify significant deteriorations of cognition accompanied by neurophysiological and neuroradiological changes in AD, but not in normal ageing. In clinically diagnosed AD, cognitive performance at the follow-up examination could not be predicted by the previous alpha/theta ratio or by the previous degree of global brain atrophy, whereas the cognitive test score determined not only performance, but also structural findings at follow-up. Performance on cognitive tests appears to be a more sensitive indicator of the degenerative process than EEG band-power and morphological changes in manifest AD. Neuroimaging, neurophysiology and genetic risk markers may be more important for the early differential diagnosis than for the prediction of the course of illness.

scholarly journals Neuropsychological Profiles and Trajectories in Preclinical Alzheimer’s Disease

2018 ◽  
Vol 24 (7) ◽  
pp. 693-702 ◽  
Author(s):  
Jean K. Ho ◽  
Daniel A. Nation ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Older Adults ◽  
Alzheimer's Disease ◽  
Executive Function ◽  
Processing Speed ◽  
Synergistic Effects ◽  
Verbal Learning ◽  
Semantic Fluency ◽  
Cognitively Normal

AbstractObjectives: The present study investigated the independent and synergistic effects of amyloid beta (Aβ1-42) and phosphorylated tau (Ptau) pathologies on neuropsychological profiles and trajectories in cognitively normal older adults. Methods: Alzheimer’s Disease Neuroimaging Initiative participants identified as cognitively normal at baseline underwent longitudinal assessment (N=518; 0, 12, 24, 36 months), baseline lumbar puncture and follow-up cognitive exams. Cerebral spinal fluid (CSF) biomarker profiles (Aβ-Ptau-, Aβ+Ptau-, Aβ-Ptau+, Aβ+Ptau+) were compared on baseline profiles and trajectories for memory (Rey Auditory Verbal Learning Test), attention/executive function (Trail Making Test, A and B), language (Animal Fluency, Vegetable Fluency, Boston Naming Test) and processing speed (Digit Symbol) using multilevel models. Results: The Aβ+Ptau+ group exhibited significantly worse baseline performance on tests of memory and executive function relative to the Aβ-Ptau+ and Aβ-Ptau- groups. The Aβ+Ptau- group fell between the Aβ+Ptau+ participants and the Aβ-Ptau- and Aβ-Ptau+ groups on all three cognitive domains and exhibited worse baseline executive function. The Aβ-Ptau+ group performed worse than Aβ-Ptau- participants on processing speed. Over 36-month follow-up, the Aβ+Ptau+ group exhibited the greatest declines in memory and semantic fluency compared to all other groups. Conclusions: Cognitively normal older adults with both Aβ and Ptau pathology exhibited the weakest profile, marked by the worst memory decline compared to the other groups. Other subtle changes in this group included declines in executive function and semantic fluency. Those with Ptau pathology alone showed slowed processing speed, and those with Aβ pathology alone showed worse attention and executive function compared to biomarker negative participants. (JINS, 2018, 24, 1–10)

Longitudinal Changes in Individual BrainAGE in Healthy Aging, Mild Cognitive Impairment, and Alzheimer’s Disease

GeroPsych ◽  
2012 ◽  
Vol 25 (4) ◽  
pp. 235-245 ◽  
Author(s):  
Katja Franke ◽  
Christian Gaser
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Healthy Aging ◽  
Brain Aging ◽  
Elderly Subjects ◽  
Additional Increase ◽  
Longitudinal Changes ◽  
Novel Method ◽  
The Brain

We recently proposed a novel method that aggregates the multidimensional aging pattern across the brain to a single value. This method proved to provide stable and reliable estimates of brain aging – even across different scanners. While investigating longitudinal changes in BrainAGE in about 400 elderly subjects, we discovered that patients with Alzheimer’s disease and subjects who had converted to AD within 3 years showed accelerated brain atrophy by +6 years at baseline. An additional increase in BrainAGE accumulated to a score of about +9 years during follow-up. Accelerated brain aging was related to prospective cognitive decline and disease severity. In conclusion, the BrainAGE framework indicates discrepancies in brain aging and could thus serve as an indicator for cognitive functioning in the future.

Elucidating the risk factors for progression from amyloid-negative amnestic mild cognitive impairment to dementia

2020 ◽  
Vol 17 ◽  
Author(s):  
Hyung-Ji Kim ◽  
Jae-Hong Lee ◽  
E-nae Cheong ◽  
Sung-Eun Chung ◽  
Sungyang Jo ◽  
...  
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Amnestic Mild Cognitive Impairment ◽  
Amyloid Pet ◽  
Clinical Progression ◽  
Amnestic Mci

Background: Amyloid PET allows for the assessment of amyloid β status in the brain, distinguishing true Alzheimer’s disease from Alzheimer’s disease-mimicking conditions. Around 15–20% of patients with clinically probable Alzheimer’s disease have been found to have no significant Alzheimer’s pathology on amyloid PET. However, a limited number of studies had been conducted this subpopulation in terms of clinical progression. Objective: We investigated the risk factors that could affect the progression to dementia in patients with amyloid-negative amnestic mild cognitive impairment (MCI). Methods: This study was a single-institutional, retrospective cohort study of patients over the age of 50 with amyloidnegative amnestic MCI who visited the memory clinic of Asan Medical Center with a follow-up period of more than 36 months. All participants underwent brain magnetic resonance imaging (MRI), detailed neuropsychological testing, and fluorine-18[F18]-florbetaben amyloid PET. Results: During the follow-up period, 39 of 107 patients progressed to dementia from amnestic MCI. In comparison with the stationary group, the progressed group had a more severe impairment in verbal and visual episodic memory function and hippocampal atrophy, which showed an Alzheimer’s disease-like pattern despite the lack of evidence for significant Alzheimer’s disease pathology. Voxel-based morphometric MRI analysis revealed that the progressed group had a reduced gray matter volume in the bilateral cerebellar cortices, right temporal cortex, and bilateral insular cortices. Conclusion: Considering the lack of evidence of amyloid pathology, clinical progression of these subpopulation may be caused by other neuropathologies such as TDP-43, abnormal tau or alpha synuclein that lead to neurodegeneration independent of amyloid-driven pathway. Further prospective studies incorporating biomarkers of Alzheimer’s diseasemimicking dementia are warranted.

scholarly journals The individual course of neuropsychiatric symptoms in people with Alzheimer's and Lewy body dementia: 12-year longitudinal cohort study

2019 ◽  
Vol 216 (1) ◽  
pp. 43-48 ◽  
Author(s):  
Audun Osland Vik-Mo ◽  
Lasse Melvaer Giil ◽  
Miguel Germán Borda ◽  
Clive Ballard ◽  
Dag Aarsland
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Neuropsychiatric Symptoms ◽  
Personalised Medicine ◽  
Lewy Bodies ◽  
Lewy Body Dementia ◽  
Psychotic Symptoms ◽  
Primary Inclusion ◽  
The Individual

IntroductionUnderstanding the natural course of neuropsychiatric symptoms (NPS) in dementia is important for planning patient care and trial design, but few studies have described the long-term course of NPS in individuals.MethodPrimary inclusion of 223 patients with suspected mild dementia from general practice were followed by annual assessment, including the Neuropsychiatric Inventory (NPI), for up to 12 years. Total and item NPI scores were classified as stable, relapsing, single episodic or not present based on 4.96 (s.d. 2.3) observations (98% completeness of longitudinal data) for 113 patients with Alzheimer's disease and 84 patients with LBD (68 dementia with Lewy bodies and 16 Parkinson's disease dementia).ResultsWe found that 80% had stable NPI total ≥1, 50% had stable modest NPI total ≥12 and 25% had stable NPI total ≥24 scores. Very severe NPS (≥48) were mostly single episodes, but 8% of patients with Alzheimer's disease had stable severe NPS. Patients with Alzheimer's disease and the highest 20% NPI total scores had a more stable or relapsing course of four key symptoms: aberrant motor behaviour, aggression/agitation, delusions and irritability (odds ratio 55, P < 0.001). This was not seen in LBD. Finally, 57% of patients with Alzheimer's disease and 84% of patients with LBD had reoccurring psychotic symptoms.ConclusionsWe observed a highly individual course of NPS, with most presenting as a single episode or relapsing; a stable course was less common, especially in LBD. These findings demonstrate the importance of an individualised approach (i.e. personalised medicine) in dementia care.

A Detailed Phenomenological Comparison of Complex Visual Hallucinations in Dementia With Lewy Bodies and Alzheimer's Disease

1997 ◽  
Vol 9 (4) ◽  
pp. 381-388 ◽  
Author(s):  
Clive Ballard ◽  
Ian McKeith ◽  
Richard Harrison ◽  
John O'Brien ◽  
Peter Thompson ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Dementia With Lewy Bodies ◽  
Lewy Bodies ◽  
Time Of Day ◽  
Visual Hallucinations ◽  
Dementia Patients ◽  
Core Feature ◽  
Definition Of

Visual hallucinations (VH) are a core feature of dementia with Lewy bodies (DLB), but little is known about their phenomenology. A total of 73 dementia patients (42 DLB, 30 Alzheimer's disease [AD], 1 undiagnosed) in contact with clinical services were assessed with a detailed standardized inventory. DLB was diagnosed according to the criteria of McKeith and colleagues, AD was diagnosed using the NINCDS-ADRDA criteria. Autopsy confirmation has been obtained when possible. VH were defined using the definition of Burns and colleagues. Detailed descriptions of hallucinatory experiences were recorded. Annual follow-up interviews were undertaken. The clinical diagnosis has been confirmed in 18 of the 19 cases that have come to autopsy. A total of 93% of DLB patients and 27% of AD patients experienced VH. DLB patients were significantly more likely to experience multiple VH that persisted over follow-up. They were significantly more likely to hear their VH speak but there were no significant differences in the other phenomenological characteristics including whether the hallucinations moved, the time of day that they were experienced, their size, the degree of insight, and whether they were complete. VH may be more likely to be multiple, to speak, and to be persistent in DLB patients. These characteristics could potentially aid accurate diagnosis.

Prospective longitudinal study of depression and anosognosia in Alzheimer's disease

1997 ◽  
Vol 171 (1) ◽  
pp. 47-52 ◽  
Author(s):  
Sergio E. Starkstein ◽  
Erán Chemerinski ◽  
Liliana Sabe ◽  
Gabriela Kuzis ◽  
Gustavo Petracca ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Major Depression ◽  
Cognitive Status ◽  
Initial Evaluation ◽  
Consecutive Series ◽  
Psychiatric Interview ◽  
Prospective Longitudinal Study ◽  
Prospective Longitudinal

BackgroundThe aim was to examine the longitudinal evolution of depression and anosognosia in patients with probable Alzheimer's disease (AD).MethodSixty-two of a consecutive series of 116 AD patients that were examined with a structured psychiatric interview had a follow-up evaluation between one and two years after the initial evaluation.ResultsAt the initial evaluation 19% of the 62 patients had major depression, 34% had dysthymia, and 47% were not depressed. After a mean follow-up of 16 months, 58% of patients with major depression at the initial evaluation were still depressed, whereas only 28% of patients with initial dysthymia and 21% of the non-depressed patients were depressed at follow-up. During the follow-up period, all three groups showed similar declines in cognitive status and activities of daily living. At the initial evaluation, 39% of the patients had anosognosia, and there was a significant increment of anosognosia during the follow-up period.ConclusionsWhile dysthymia in AD is a brief emotional disorder, major depression is a longer-lasting mood change. Anosognosia is another prevalent disorder among AD patients, and increases with the progression of the illness.

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