The Clinical Problem of Symptomatic Alzheimer Disease and Mild Cognitive Impairment

Tarawneh, Rawan; Holtzman, David M.

doi:10.1101/cshperspect.a006148

Cited by 329 publications

(223 citation statements)

References 99 publications

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“…The distinction between memory decline due to the normal course of aging and early stage AD dementia is so ambiguous that the category of mild cognitive impairment (MCI) has been developed to better characterize the earliest signs of AD 5. The MCI category was initially created to identify the early stages of AD and was primarily based on impairment in memory, but with the advances in research made over time, it was noticeable that some patients with MCI remain stable while others progress to AD 6, 7. Identifying biomarkers at the preclinical stage of AD is essential in properly diagnosing and determining the probability of developing AD.…”

Section: Introductionmentioning

confidence: 99%

Tau oligomers in cerebrospinal fluid in Alzheimer's disease

Sengupta

Portelius

Hansson

et al. 2017

Ann Clin Transl Neurol

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ObjectiveWith an increasing incidence of Alzheimer's disease (AD) and neurodegenerative tauopathies, there is an urgent need to develop reliable biomarkers for the diagnosis and monitoring of the disease, such as the recently discovered toxic tau oligomers. Here, we aimed to demonstrate the presence of tau oligomers in the cerebrospinal fluid (CSF) of patients with cognitive deficits, and to determine whether tau oligomers could serve as a potential biomarker for AD.MethodsA multicentric collaborative study involving a double‐blinded analysis with a total of 98 subjects with moderate to severe AD (N = 41), mild AD (N = 31), and nondemented control subjects (N = 26), and two pilot studies of 33 total patients with AD (N = 19) and control (N = 14) subjects were performed. We carried out biochemical assays to measure oligomeric tau from CSF of these patients with various degrees of cognitive impairment as well as cognitively normal controls.ResultsUsing a highly reproducible indirect ELISA method, we found elevated levels of tau oligomers in AD patients compared to age‐matched controls. Western blot analysis confirmed the presence of oligomeric forms of tau in CSF. In addition, the ratio of oligomeric to total tau increased in the order: moderate to severe AD, mild AD, and controls.ConclusionThese assays are suitable for the analysis of human CSF samples. These results here suggest that CSF tau oligomer measurements could be optimized and added to the panel of CSF biomarkers for the accurate and early detection of AD.

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Section: Introductionmentioning

confidence: 99%

Tau oligomers in cerebrospinal fluid in Alzheimer's disease

Sengupta

Portelius

Hansson

et al. 2017

Ann Clin Transl Neurol

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“…But with progression of the disease, the language difficulties evolve into an inability to communicate as the patient struggles with a markedly limited vocabulary, nominal aphasia, and defects in verbal comprehension. 37 Other cortical signs and symptoms such as apraxia, acalculia, and visio-spatial dysfunction may become apparent over the course of the disease. With the development of apraxia, patients lose the ability to carry out such simple tasks as combing their hair or turning on a water faucet.…”

Section: Signs and Symptomsmentioning

confidence: 99%

“…Visio-spatial abnormalities can be seen as patients become disoriented with their body position in space. 37 Behavioral problems emerge throughout the various stages of the disease. Mood disturbances such as depression, anxiety, or apathy may be present early on in AD, whereas delusions, hallucinations, and psychosis can be prominent in later stages.…”

Section: Signs and Symptomsmentioning

confidence: 99%

Medical Depressive Disorder, Alzheimer’s, Epilepsy and Their Current Treatments Available in India

Al-Ghamdi¹,

Yusuf²

2016

IRJPS

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Brain disorders are not confined to the western countries and their rate is increasing frequently in the Indian subcontinents, ranging from adolescents to adults. The key diseases i.e. Depression, Alzheimer's and Epilepsy are common and are predicted to upsurge in the future. Media and entertainment technologies may be the causative factors but still needs a lot of research. Conventional treatment is effective but with complementary ineligible side effects, which need an effective regimen guidelines for their use. The alternative therapeutic system is also an option to be augmented with the present therapeutic system but still needs a lot of regulation clearance. The present review deals with the current system and the best guidelines to be followed for the particular diseases.

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“…Without intentional stimulation, persons with dementia can remain inactive for prolonged periods of time, resulting in the lowering of physical and cognitive functions. In addition to the primary symptoms of memory disorder and disorientation [10] [11], patients with Alzheimer's dementia, also show behavioral and psychological symptoms of dementia (BPSD) [12] [13] such as daytime drowsiness, nighttime delirium, and irritability [14] [15].…”

Section: Introductionmentioning

confidence: 99%

Characteristic Autonomic Nervous Activity of Institutionalized Elders with Dementia

Fuji¹,

Tanioka²,

Yasuhara³

et al. 2016

OJPsych

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This study clarified the characteristic autonomic nervous activity of institutionalized elders diagnosed with dementia using Hasegawa's Dementia Scale-Revised. Twenty-six healthy adult persons (HPs) in their 20 s -40 s met the inclusion criteria, and 16 persons (27.6 ± 8.2 years old) completed the research procedure. Of 70 persons with dementia (PDs) residing at the one geriatric health services facilities, only 24 persons met the inclusion criteria, and only nine (N = 9, 83.44 ± 9.45 years old) completed the procedure. Actigraph and ambulatory electrocardiographic instruments measuring autonomic nervous activity were attached to the subjects for 24 hours. Activities and behaviors of PDs and HPs were observed by clinically experienced staff nurses and care workers. High frequency (HF) power indicating parasympathetic activity and LF/HF ratio indicating sympathetic activity were calculated. When awake, PDs' LF/HF ratio was significantly lower than HP's (Z = −2.60, p < 0.01), showing significant differences in the LF/HF ratios between waking and sleeping, more than those of the PDs (p < 0.001). Similarly, when awake, significant positive correlations were observed in the LF/HF ratio and actigraph activity count (AC) in 11 HPs and 3 PDs (range r = 0.17 to 0.49, p < 0.05); however, significant negative correlation was found in HF and AC of 12 HPs and 3 PDs (range r = −0.55 to −0.18, p < 0.05). While sleeping, significant positive correlations were observed in LF/HF and AC of 3 HPs and 1 PD (range r = 0.35 to 0.42, p < 0.05) and significant negative correlation was found in the HF and AC of 1 HP (r= −0.32, p < 0.001) and 1 PD (r = −0.32, p < 0.05). The mean value of LF/HF in a wakeful state was significantly lower for PDs than HPs. Combined results of behavioral observation, actigrapy and heart rate variability (HRV) analyses suggested that PDs showed positive correlations between LF/HF and AC in a wakeful state. Compared to those who showed no positive correlation, they did not require much nursing care.

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The Clinical Problem of Symptomatic Alzheimer Disease and Mild Cognitive Impairment

Cited by 329 publications

References 99 publications

Tau oligomers in cerebrospinal fluid in Alzheimer's disease

Tau oligomers in cerebrospinal fluid in Alzheimer's disease

Medical Depressive Disorder, Alzheimer’s, Epilepsy and Their Current Treatments Available in India

Characteristic Autonomic Nervous Activity of Institutionalized Elders with Dementia

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