Association of APOE4 and clinical variability in Alzheimer disease with the pattern of tau- and amyloid-PET

ObjectiveTo assess whether Alzheimer disease (AD) clinical presentation and APOE4 relate to the burden and topography of β-amyloid and tau pathologies using in vivo PET imaging.MethodsWe studied 119 β-amyloid-positive symptomatic patients aged 48–95 years, including 29 patients with logopenic variant primary progressive aphasia (lvPPA) and 21 with Posterior Cortical Atrophy (PCA). PIB- (β-amyloid) and Flortaucipir (tau)-PET standardized uptake value ratio (SUVR) images were created. General linear models assessed relationships between demographic/clinical variables (phenotype, age), APOE4, and PET (including global cortical and voxelwise SUVR values) while controlling for disease severity using the clinical dementia rating scale sum of boxes.ResultsPIB-PET binding showed a widespread cortical distribution with subtle differences across phenotypes and was unrelated to demographic/clinical variables or APOE4. Flortaucipir-PET was commonly elevated in temporo-parietal regions, but showed marked phenotype-associated differences, with higher binding observed in occipito-parietal areas for PCA, in left temporal and inferior frontal for lvPPA, and in medial temporal areas for other patients with AD. Cortical Flortaucipir-PET binding was higher in younger patients across phenotypes (r = −0.63, 95%CI [−0.72, −0.50)]), especially in parietal and dorsal prefrontal cortices. The presence of APOE4 was associated with a focal medial temporal Flortaucipir-SUVR increase, controlling for all other variables (entorhinal: + 0.310 SUVR 95%CI [0.091, 0.530]).ConclusionsClinical phenotypes are associated with differential patterns of tau but not amyloid pathology. Older age and APOE4 are not only risk factors for AD but also seem to affect disease expression by promoting a more MTL-predominant pattern of tau pathology.

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β-Amyloid PET and 123I-FP-CIT SPECT in Mild Cognitive Impairment at Risk for Lewy Body Dementia

Neurology ◽

10.1212/wnl.0000000000011454 ◽

2021 ◽

Vol 96 (8) ◽

pp. e1180-e1189

Author(s):

Qin Chen ◽

Val J. Lowe ◽

Bradley F. Boeve ◽

Scott A. Przybelski ◽

Toji Miyagawa ◽

...

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Rating Scale ◽

Rem Sleep Behavior Disorder ◽

Standardized Uptake Value ◽

Clinical Feature ◽

Amyloid Pet ◽

Clinical Phenotypes ◽

Amyloid A ◽

Β Amyloid

ObjectiveTo determine the clinical phenotypes associated with the β-amyloid PET and dopamine transporter imaging (123I-FP-CIT SPECT) findings in mild cognitive impairment (MCI) with the core clinical features of dementia with Lewy bodies (DLB; MCI-LB).MethodsPatients with MCI who had at least 1 core clinical feature of DLB (n = 34) were grouped into β-amyloid A+ or A− and 123I-FP-CIT SPECT D+ or D− groups based on previously established abnormality cut points for A+ with Pittsburgh compound B PET standardized uptake value ratio (PiB SUVR) ≥1.48 and D+ with putamen z score with DaTQUANT <−0.82 on 123I-FP-CIT SPECT. Individual patients with MCI-LB fell into 1 of 4 groups: A+D+, A+D−, A−D+, or A−D−. Log-transformed PiB SUVR and putamen z score were tested for associations with patient characteristics.ResultsThe A−D+ biomarker profile was most common (38.2%), followed by A+D+ (26.5%) and A−D− (26.5%). The least common was the A+D- biomarker profile (8.8%). The A+ group was older, had a higher frequency of APOE ε4 carriers, and had a lower Mini-Mental State Examination score than the A− group. The D+ group was more likely to have probable REM sleep behavior disorder. Lower putamen DaTQUANT z scores and lower PiB SUVRs were independently associated with higher Unified Parkinson’s Disease Rating Scale-III scores.ConclusionsA majority of patients with MCI-LB are characterized by low β-amyloid deposition and reduced dopaminergic activity. β-Amyloid PET and 123I-FP-CIT SPECT are complementary in characterizing clinical phenotypes of patients with MCI-LB.

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Effect of the Interaction Between Hypertension and Cerebral White Matter Changes on the Progression of Alzheimer Disease

Current Alzheimer Research ◽

10.2174/1567205015666181002141013 ◽

2018 ◽

Vol 15 (14) ◽

pp. 1354-1360 ◽

Cited By ~ 4

Author(s):

Ping-Song Chou ◽

Yi-Hui Kao ◽

Meng-Ni Wu ◽

Mei-Chuan Chou ◽

Chun-Hung Chen ◽

...

Keyword(s):

White Matter ◽

Alzheimer Disease ◽

Rating Scale ◽

Vital Role ◽

Independent Effect ◽

Cerebral White Matter ◽

Clinical Dementia Rating ◽

White Matter Changes ◽

Age Related ◽

The Mean

Background: Cerebrovascular pathologies and hypertension could play a vital role in Alzheimer disease (AD) progression. However, whether cerebrovascular pathologies and hypertension accelerate the AD progression through an independent or interaction effect is unknown. Objective: To investigate the effect of the interactions of cerebrovascular pathologies and hypertension on AD progression. Method: A retrospective longitudinal study was conducted to compare AD courses in patients with different severities of cerebral White Matter Changes (WMCs) in relation to hypertension. Annual comprehensive psychometrics were performed. WMCs were rated using a rating scale for Age-related WMCs (ARWMC). Results: In total, 278 patients with sporadic AD were enrolled in this study. The mean age of the patients was 76.6 ± 7.4 years, and 166 patients had hypertension. Among AD patients with hypertension, those with deterioration in clinical dementia rating-sum of box (CDR-SB) and CDR had significantly severe baseline ARWMC scales in total (CDR-SB: 5.8 vs. 3.6, adjusted P = 0.04; CDR: 6.4 vs. 4.4, adjusted P = 0.04) and frontal area (CDR-SB: 2.4 vs. 1.2, adjusted P = 0.01; CDR: 2.4 vs. 1.7, adjusted P < 0.01) compared with those with no deterioration in psychometrics after adjustment for confounders. By contrast, among AD patients without hypertension, no significant differences in ARWMC scales were observed between patients with and without deterioration. Conclusion: The effect of cerebrovascular pathologies on AD progression between those with and without hypertension might differ. An interaction but not independent effect of hypertension and WMCs on the progression of AD is possible.

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Adaptation of the Clinical Dementia Rating Scale for adults with Down syndrome

Journal of Neurodevelopmental Disorders ◽

10.1186/s11689-019-9300-2 ◽

2019 ◽

Vol 11 (1) ◽

Author(s):

Christina N. Lessov-Schlaggar ◽

Olga L. del Rosario ◽

John C. Morris ◽

Beau M. Ances ◽

Bradley L. Schlaggar ◽

...

Keyword(s):

Down Syndrome ◽

Alzheimer Disease ◽

Rating Scale ◽

Assessment Instruments ◽

Clinical Dementia Rating ◽

Data Set ◽

Cognitive Domains ◽

Increased Risk ◽

Caregiver Questionnaire ◽

Raven's Progressive Matrices

Abstract Background Adults with Down syndrome (DS) are at increased risk for Alzheimer disease dementia, and there is a pressing need for the development of assessment instruments that differentiate chronic cognitive impairment, acute neuropsychiatric symptomatology, and dementia in this population of patients. Methods We adapted a widely used instrument, the Clinical Dementia Rating (CDR) Scale, which is a component of the Uniform Data Set used by all federally funded Alzheimer Disease Centers for use in adults with DS, and tested the instrument among 34 DS patients recruited from the community. The participants were assessed using two versions of the modified CDR—a caregiver questionnaire and an in-person interview involving both the caregiver and the DS adult. Assessment also included the Dementia Scale for Down Syndrome (DSDS) and the Raven’s Progressive Matrices to estimate IQ. Results Both modified questionnaire and interview instruments captured a range of cognitive impairments, a majority of which were found to be chronic when accounting for premorbid function. Two individuals in the sample were strongly suspected to have early dementia, both of whom had elevated scores on the modified CDR instruments. Among individuals rated as having no dementia based on the DSDS, about half showed subthreshold impairments on the modified CDR instruments; there was substantial agreement between caregiver questionnaire screening and in-person interview of caregivers and DS adults. Conclusions The modified questionnaire and interview instruments capture a range of impairment in DS adults, including subthreshold symptomatology, and the instruments provide complementary information relevant to the ascertainment of dementia in DS. Decline was seen across all cognitive domains and was generally positively related to age and negatively related to IQ. Most importantly, adjusting instrument scores for chronic, premorbid impairment drastically shifted the distribution toward lower (no impairment) scores.

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Disease Progression in Frontotemporal Dementia and Alzheimer Disease: The Contribution of Staging Scales

Journal of Geriatric Psychiatry and Neurology ◽

10.1177/0891988720944239 ◽

2020 ◽

pp. 089198872094423

Author(s):

Thaís Bento Lima-Silva ◽

Eneida Mioshi ◽

Valéria Santoro Bahia ◽

Mário Amore Cecchini ◽

Luciana Cassimiro ◽

...

Keyword(s):

Alzheimer Disease ◽

Disease Progression ◽

Frontotemporal Dementia ◽

Rating Scale ◽

Severe Disease ◽

Primary Progressive Aphasia ◽

Behavioral Changes ◽

Clinical Dementia Rating ◽

Dementia Rating Scale ◽

Disease Stages

Introduction: There is a shortage of validated instruments to estimate disease progression in frontotemporal dementia (FTD). Objectives: To evaluate the ability of the FTD Rating Scale (FTD-FRS) to detect functional and behavioral changes in patients diagnosed with the behavioral variant of FTD (bvFTD), primary progressive aphasia (PPA), and Alzheimer disease (AD) after 12 months of the initial evaluation, compared to the Clinical Dementia Rating scale−frontotemporal lobar degeneration (CDR-FTLD) and the original Clinical Dementia Rating scale (CDR). Methods: The sample consisted of 70 individuals, aged 40+ years, with at least 2 years of schooling, 31 with the diagnosis of bvFTD, 12 with PPA (8 with semantic variant and 4 with non-fluent variant), and 27 with AD. The FTD-FRS, the CDR, and the 2 additional CDR-FTLD items were completed by a clinician, based on the information provided by the caregiver with frequent contact with the patient. The Addenbrooke Cognitive Examination-Revised was completed by patients. After 12 months, the same protocol was applied. Results: The FTD-FRS, CDR-FTLD, and CDR detected significant decline after 12 months in the 3 clinical groups (exception: FTD-FRS for PPA). The CDR was less sensitive to severe disease stages. Conclusions: The FTD-FRS and the CDR-FTLD are especially useful tools for dementia staging in AD and in the FTD spectrum.

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Prospective longitudinal atrophy in Alzheimer’s disease correlates with the intensity and topography of baseline tau-PET

Science Translational Medicine ◽

10.1126/scitranslmed.aau5732 ◽

2020 ◽

Vol 12 (524) ◽

pp. eaau5732 ◽

Cited By ~ 49

Author(s):

Renaud La Joie ◽

Adrienne V. Visani ◽

Suzanne L. Baker ◽

Jesse A. Brown ◽

Viktoriya Bourakova ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Amyloid Pet ◽

Specific Distribution ◽

Positron Emission ◽

Pet Radiotracers ◽

Β Amyloid ◽

Tau Pet ◽

Prospective Longitudinal

β-Amyloid plaques and tau-containing neurofibrillary tangles are the two neuropathological hallmarks of Alzheimer’s disease (AD) and are thought to play crucial roles in a neurodegenerative cascade leading to dementia. Both lesions can now be visualized in vivo using positron emission tomography (PET) radiotracers, opening new opportunities to study disease mechanisms and improve patients’ diagnostic and prognostic evaluation. In a group of 32 patients at early symptomatic AD stages, we tested whether β-amyloid and tau-PET could predict subsequent brain atrophy measured using longitudinal magnetic resonance imaging acquired at the time of PET and 15 months later. Quantitative analyses showed that the global intensity of tau-PET, but not β-amyloid–PET, signal predicted the rate of subsequent atrophy, independent of baseline cortical thickness. Additional investigations demonstrated that the specific distribution of tau-PET signal was a strong indicator of the topography of future atrophy at the single patient level and that the relationship between baseline tau-PET and subsequent atrophy was particularly strong in younger patients. These data support disease models in which tau pathology is a major driver of local neurodegeneration and highlight the relevance of tau-PET as a precision medicine tool to help predict individual patient’s progression and design future clinical trials.

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Efficacy and Limitations of rCBF-SPECT in the Diagnosis of Alzheimer’s Disease With Amyloid-PET

American Journal of Alzheimer s Disease & Other Dementias® ◽

10.1177/1533317519841192 ◽

2019 ◽

Vol 34 (5) ◽

pp. 314-321

Author(s):

Miwako Takahashi ◽

Tomoko Tada ◽

Tomomi Nakamura ◽

Keitaro Koyama ◽

Toshimitsu Momose

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Rating Scale ◽

Single Photon ◽

Photon Emission ◽

Emission Computed Tomography ◽

Amyloid Pet ◽

Clinical Dementia Rating ◽

Positron Emission ◽

Rcbf Spect

This study aimed to assess efficacy and limitations of regional cerebral blood flow imaging using single-photon emission computed tomography (rCBF-SPECT) in the diagnosis of Alzheimer’s disease (AD) with amyloid-positron emission tomography (amyloid-PET). Thirteen patients, who underwent both rCBF-SPECT and amyloid-PET after clinical diagnosis of AD or mild cognitive impairment, were retrospectively identified. The rCBF-SPECTs were classified into 4 grades, from typical AD pattern to no AD pattern of hypoperfusion; amyloid-beta (Aβ) positivity was assessed by amyloid-PET. Four patients were categorized into a typical AD pattern on rCBF-SPECT, and all were Aβ+. The other 9 patients did not exhibit a typical AD pattern; however, 4 were Aβ+. The Mini-Mental State Examination score and Clinical Dementia Rating scale were not significantly different between Aβ+ and Aβ– patients. A typical AD pattern on rCBF-SPECT can reflect Aβ+; however, if not, rCBF-SPECT has a limitation to predict amyloid pathology.

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Effects of Inappropriate Sexual Behaviors and Neuropsychiatric Symptoms of Patients With Alzheimer Disease and Caregivers’ Depression on Caregiver Burden

Journal of Geriatric Psychiatry and Neurology ◽

10.1177/0891988719874123 ◽

2019 ◽

Vol 33 (5) ◽

pp. 243-249 ◽

Cited By ~ 1

Author(s):

Faik Ilik ◽

Hüseyin Büyükgöl ◽

Fatih Kayhan ◽

Devrimsel Harika Ertem ◽

Timur Ekiz

Keyword(s):

Alzheimer Disease ◽

Caregiver Burden ◽

Sexual Behaviors ◽

Rating Scale ◽

Neuropsychiatric Symptoms ◽

Clinical Dementia Rating ◽

Statistical Manual ◽

Diagnostic And Statistical Manual ◽

Prevalence Of Depression ◽

State Examination

Objective: We investigated the effects of inappropriate sexual behaviors (ISBs) and neuropsychiatric symptoms (NPSs) of patients with Alzheimer disease (AD), and of caregivers’ depression, on the caregiver burden. Method: One hundred forty three patients with AD and their caregivers were included in the study. Sixty-five patients without AD who needed care due to their disability and their caregivers were enrolled for the comparison. Depression in caregivers was diagnosed using The Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (SCID-I). The Mini-Mental State Examination (MMSE) and Clinical Dementia Rating Scale were used to evaluate the severity of AD. The Neuropsychiatric Inventory (NPI) was used to assess the NPSs of patients. Caregiver burden was evaluated using the Zarit Burden Interview (ZBI). Results: Inappropriate sexual behaviors were found in 13 (9.1%) of the AD group. Inappropriate sexual behaviors were more common in moderate or severe AD ( P = .009, χ2 = 9.396). The prevalence of depression (n = 38, 26.6%) was higher in caregivers of AD group with ISBs ( P = .000, χ2 = 24.69). The ZBI scores of caregivers of patients with AD were higher than the comparison group. In addition, the ZBI scores of caregivers of patients with AD were significantly higher in the AD group with ISB, a high total score of NPI, and a low score of MMSE. The caregivers of AD group with depression had higher ZBI scores ( P < .05). Conclusions: The severity of AD, the presence of NPSs in patients, and major depression in caregivers were risk factors for an increased caregiver burden.

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INECO Frontal Screening (IFS): A brief, sensitive, and specific tool to assess executive functions in dementia–CORRECTED VERSION

Journal of the International Neuropsychological Society ◽

10.1017/s1355617709990415 ◽

2009 ◽

Vol 15 (5) ◽

pp. 777-786 ◽

Cited By ~ 118

Author(s):

TERESA TORRALVA ◽

MARÍA ROCA ◽

EZEQUIEL GLEICHGERRCHT ◽

PABLO LÓPEZ ◽

FACUNDO MANES

Keyword(s):

Differential Diagnosis ◽

Alzheimer Disease ◽

Executive Functioning ◽

Neurodegenerative Diseases ◽

Rating Scale ◽

Executive Dysfunction ◽

Screening Tools ◽

Cognitive Screening ◽

Clinical Dementia Rating ◽

Per Se

AbstractAlthough several brief sensitive screening tools are available to detect cognitive dysfunction, few have been developed to quickly assess executive functioning (EF) per se. We designed a new brief tool to evaluate EF in neurodegenerative diseases. Patients with an established diagnosis of behavioral variant frontotemporal dementia (bvFTD; n = 22), Alzheimer disease (AD; n = 25), and controls (n = 26) were assessed with a cognitive screening test, the INECO Frontal Screening (IFS), and EF tests. Clinical Dementia Rating Scale (CDR) scores were obtained for all patients. Internal consistency of the IFS was very good (Cronbach’s alpha = .80). IFS total (out of 30 points) was 27.4 (SD = 1.6) for controls, 15.6 (SD = 4.2) for bvFTD, and 20.1 (SD = 4.7) for AD. Using a cutoff of 25 points, sensitivity of the IFS was 96.2%, and specificity 91.5% in differentiating controls from patients with dementia. The IFS correlated significantly with the CDR and executive tasks. The IFS total discriminated controls from demented patients, and bvFTD from AD. IFS is a brief, sensitive, and specific tool for the detection of executive dysfunction associated with neurodegenerative diseases. The IFS may be helpful in the differential diagnosis of FTD and AD. (JINS, 2009, 15, 777–786.)

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